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CLINICAL PHARMACOLOGY Mechanism Of Action Endogenous androgens, including testosterone and dihydrotestosterone (DHT) are responsible for the normal growth and development of the male sex organs and for maintenance of secondary sex characteristics. These effects include the growth and maturation of the prostate, seminal vesicles, penis, and scrotum; the development of male hair distribution, such as facial, pubic, chest, and axillary hair; laryngeal enlargement, vocal cord thickening, and alterations in body musculature and fat distribution. Male hypogonadism, a clinical syndrome resulting from insufficient secretion of testosterone, has two main etiologies. Primary hypogonadism is caused by defects of the gonads, such as Klinefelter's syndrome or Leydig cell aplasia, whereas secondary hypogonadism is the failure of the hypothalamus (or pituitary) to produce sufficient gonadotropins (FSH, LH). Pharmacodynamics No specific pharmacodynamic studies were conducted using Vogelxo. Pharmacokinetics In a single-dose, replicate crossover clinical study evaluating 58 hypogonadal males, the serum testosterone exposures (AUC0-24 and AUC0-t) and maximum testosterone concentration (Cmax) following a topical administration of 100 mg testosterone administration as a 2 X 5 g Vogelxo tubes (applied to the shoulders/upper arms) were bioequivalent to those following a topical administration of an approved testosterone gel product. Absorption Testosterone gel delivers physiologic amounts of testosterone, producing circulating testosterone concentrations that approximate normal levels (e.g., 300 – 1000 ng/dL) seen in healthy men. The skin serves as a reservoir for the sustained release of testosterone into the systemic circulation. Approximately 10% of the testosterone applied on the skin surface is absorbed into the systemic circulation during a 24-hour period. Single Dose In a single dose, replicate crossover study, when Vogelxo 100 mg was applied, absorption of testosterone into the blood continued for the entire 24 hour dosing period. The average (± SD) AUC0-24 and AUC0-t and Cmax were 6625 (±3671) ng·hr/dL, 10425 (±5521) ng·hr/dL, and 573 (±284) ng/dL, respectively. Multiple Dose With single daily applications of testosterone gel 50 mg and 100 mg, follow-up measurements at 30 and 90 days after starting treatment have confirmed that serum testosterone and DHT concentrations are generally maintained within the normal range. Figure 1 summarizes the 24-hour pharmacokinetic profile of testosterone for patients maintained on testosterone gel 50 mg or testosterone gel 100 mg for 30 days. Figure 1 : Mean Steady-State Serum Testosterone (±SD) (ng/dL) Concentrations on Day 30 in Patients Applying Testosterone Once Daily The average daily testosterone concentration produced by testosterone gel 100 mg at Day 30 was 612 (± 286) ng/dL and by testosterone gel 50 mg at Day 30 was 365 (± 187) ng/dL. Distribution Circulating testosterone is primarily bound in the serum to sex hormone-binding globulin (SHBG) and albumin. Approximately 40% of testosterone in plasma is bound to SHBG, 2% remains unbound (free) and the rest is loosely bound to albumin and other proteins. Metabolism Testosterone is metabolized to various 17-keto steroids through two different pathways. The major active metabolites of testosterone are estradiol and DHT. The average daily DHT concentration produced by testosterone gel 100 mg at Day 30 was 555 (± 293) pg/mL and by testosterone gel 50 mg at Day 30 was 346 (± 212) pg/mL. Figure 2 summarizes the 24-hour pharmacokinetic profile of DHT for patients maintained on testosterone gel 50 mg or testosterone gel 100 mg for 30 days. Figure 2 : Mean Steady-State Serum Dihydrotestosterone (±SD) (pg/mL) Concentrations on Day 30 in Patients Applying Testosterone Once Daily Excretion There is considerable variation in the half-life of testosterone concentration as reported in the literature, ranging from 10 to 100 minutes. About 90% of a dose of testosterone given intramuscularly is excreted in the urine as glucuronic acid and sulfuric acid conjugates of testosterone and its metabolites. About 6% of a dose is excreted in the feces, mostly in the unconjugated form. Inactivation of testosterone occurs primarily in the liver. Potential for Transfer from Male Patients to Female Partners The potential for dermal testosterone transfer following Vogelxo use was evaluated in a clinical study between males dosed with Vogelxo and their untreated female partners. Two (2) hours after application of 50 mg of testosterone from 5 g of Vogelxo to upper arm and shoulder of one side by the male subjects, the couples (N = 48 couples) engaged in a 15 minute session of skin-to-skin contact. Serum concentrations of testosterone were monitored in the female subjects for 24 hours after the transfer procedure. Under these study conditions, unprotected female partners had a mean testosterone AUC0-24 and Cmax that were 2.8 and 4 times greater than their mean baseline values, respectively. When a shirt covered the application site or the application site was washed, study results showed less than 10% increase in testosterone AUC0-24 and Cmax, compared to baseline in these females. Effect of Hand Washing In a clinical study conducted to evaluate the effect of hand washing on the residual amount of testosterone, 36 healthy male subjects received 50 mg of testosterone from 5 g of Vogelxo on a hand and applied testosterone gel to the upper arm and shoulder of one side. Subjects washed their hands with liquid soap and warm water immediately after drug application. Then the hand was allowed to air dry or patted dry with a cloth towel. A skin swab sample was collected and analyzed for testosterone content. A mean (SD) of 0.16 (0.46) to 0.65(1.03) μg of residual testosterone (i.e., 99% reduction compared to when hands were not washed) was recovered after washing hands with liquid soap and warm water. Effect of Showering The effect of showering (with mild soap) at 1, 2 and 6 hours post application of testosterone gel 100 mg was evaluated in a clinical trial in 12 men. The study demonstrated that the overall effect of washing was to decrease testosterone concentrations; however, when washing occurred two or more hours post drug application, serum testosterone concentrations remained within the normal range. Clinical Studies Clinical Study In Hypogonadal Males Testosterone gel was evaluated in a randomized multicenter, multi-dose, active and placebo controlled 90-day study in 406 adult males with morning testosterone levels ≤ 300 ng/dL. The study was double-blind for the doses of testosterone gel and placebo, but open label for the nonscrotal testosterone transdermal system. During the first 60 days, patients were evenly randomized to testosterone gel 50 mg, testosterone gel 100 mg, placebo gel, or testosterone transdermal system. At Day 60, patients receiving testosterone gel were maintained at the same dose, or were titrated up or down within their treatment group, based on 24-hour averaged serum testosterone concentration levels obtained on Day 30. Of 192 hypogonadal men who were appropriately titrated with testosterone gel and who had sufficient data for analysis, 74% achieved an average serum testosterone level within the normal range (300 to 1,000 ng/dL) on treatment Day 90. Table 4 summarizes the mean testosterone concentrations on Day 30 for patients receiving testosterone gel 50 mg or 100 mg. Table 4: Mean (± SD) Steady-State Serum Testosterone Concentrations on Day 30 Testosterone gel 50 mg n=94 Testosterone gel 100 mg n=95 Placebo gel n=93 Cavg (ng/dL) 365±187 612±286 216 ± 79 Cmax (ng/dL) 538±371 897 ± 565 271± 110 Cmin (ng/dL) 223 ± 126 394 ±189 164 ± 64

CLINICAL PHARMACOLOGY Mechanism Of Action Endogenous androgens, including testosterone and dihydrotestosterone (DHT), are responsible for the normal growth and development of the male sex organs and for maintenance of secondary sex characteristics. These effects include the growth and maturation of prostate, seminal vesicles, penis and scrotum; the development of male hair distribution, such as facial, pubic, chest and axillary hair; laryngeal enlargement; vocal cord thickening; and alterations in body musculature and fat distribution. Testosterone and DHT are necessary for the normal development of secondary sex characteristics. Male hypogonadism, a clinical syndrome resulting from insufficient secretion of testosterone, has two main etiologies. Primary hypogonadism is caused by defects of the gonads, such as Klinefelter's syndrome or Leydig cell aplasia, while secondary hypogonadism (hypogonadotropic hypogonadism) is the failure of the hypothalamus (or pituitary) to produce sufficient gonadotropins (FSH, LH). Pharmacodynamics No specific pharmacodynamic studies were conducted using Testim. Pharmacokinetics Absorption Testim® (testosterone gel) delivers physiologic amounts of testosterone, producing circulating testosterone concentrations that approximate normal concentrations (e.g., 300 - 1000 ng/dL) seen in healthy men. The skin serves as a reservoir for the sustained release of testosterone into the systemic circulation. Approximately 10% of the testosterone applied on the skin surface is absorbed into the systemic circulation during a 24-hour period. Single Dose In single dose studies, when either Testim 50 mg or 100 mg was administered, absorption of testosterone into the blood continued for the entire 24 hour dosing period. Also, mean peak and average serum concentrations within the normal range were achieved within 24 hours. Multiple Dose With single daily applications of Testim 50 mg and 100 mg, follow-up measurements at 30 and 90 days after starting treatment have confirmed that serum testosterone and DHT concentrations are generally maintained within the normal range. Figure 1 summarizes the 24-hour pharmacokinetic profile of testosterone for patients maintained on Testim 50 mg or Testim 100 mg for 30 days. Figure 1 : Mean Steady-State Serum Testosterone (±SD) (ng/dL) Concentrations on Day 30 in Patients Applying Testim Once Daily The average daily testosterone concentration produced by Testim 100 mg at Day 30 was 612 (± 286) ng/dL and by Testim 50 mg at Day 30 was 365 (± 187) ng/dL. Distribution Circulating testosterone is primarily bound in the serum to sex hormone-binding globulin (SHBG) and albumin. Approximately 40% of testosterone in plasma is bound to SHBG, 2% remains unbound (free) and the rest is loosely bound to albumin and other proteins. Metabolism Testosterone is metabolized to various 17-keto steroids through two different pathways. The major active metabolites of testosterone are estradiol and DHT. The average daily DHT concentration produced by Testim 100 mg at Day 30 was 555 (± 293) pg/mL and by Testim 50 mg at Day 30 was 346 (± 212) pg/mL. Figure 2 summarizes the 24-hour pharmacokinetic profile of DHT for patients maintained on Testim 50 mg or Testim 100 mg for 30 days. Figure 2 : Mean Steady-State Serum Dihydrotestosterone (±SD) (pg/mL) Concentrations on Day 30 in Patients Applying Testim Once Daily Excretion There is considerable variation in the half-life of testosterone concentration as reported in the literature, ranging from 10 to 100 minutes. About 90% of a dose of testosterone given intramuscularly is excreted in the urine as glucuronic acid and sulfuric acid conjugates of testosterone and its metabolites. About 6% of a dose is excreted in the feces, mostly in the unconjugated form. Inactivation of testosterone occurs primarily in the liver. Potential For Testosterone Transfer From Male Patients To Female Partners The potential for dermal testosterone transfer following Testim use was evaluated in two clinical trials with males dosed with Testim and their untreated female partners. In the first trial, 30 couples were evenly randomized to five groups. In the first four groups, 100 mg of Testim was applied to the male abdomen and the couples were then asked to rub abdomen-to-abdomen for 15 minutes at 1 hour, 4 hours, 8 hours or 12 hours after dose application, respectively. In these couples, serum testosterone concentrations in female partners increased from baseline by at least 6 times and potential for transfer was seen at all timepoints. When 6 males used a shirt to cover the abdomen at 15 minutes post-application and partners again rubbed abdomens for 15 minutes at the 1 hour timepoint, serum testosterone concentrations in female partners increased from baseline by approximately 3 times. In the second trial, 24 couples were evenly randomized to four groups. Testim 100 mg was applied to the male upper arms and shoulders. In one group, 15 minutes of direct skin-to-skin rubbing began at 4 hours after application. In these six women, all of whom showered immediately after the rubbing activity, mean maximum serum testosterone concentrations increased from baseline by approximately 4 times. When males wore a long-sleeved T-shirt and rubbing was started at 1 and at 4 hours after application, the transfer of testosterone from male to female partners was prevented. Effect Of Showering The effect of showering (with mild soap) at 1, 2 and 6 hours post application of Testim 100 mg was evaluated in a clinical trial in 12 men. The study demonstrated that the overall effect of washing was to decrease testosterone concentrations; however, when washing occurred two or more hours post drug application, serum testosterone concentrations remained within the normal range. Clinical Studies Clinical Trials In Adult Hypogonadal Males Testim® was evaluated in a randomized multicenter, multi-dose, active and placebo controlled 90-day study in 406 adult males with morning testosterone concentrations ≤ 300 ng/dL. The study was double-blind for the doses of Testim and placebo, but open label for the non-scrotal testosterone transdermal system. During the first 60 days, patients were evenly randomized to Testim 50 mg, Testim 100 mg, placebo gel, or testosterone transdermal system. At Day 60, patients receiving Testim were maintained at the same dose, or were titrated up or down within their treatment group, based on 24-hour averaged serum testosterone concentration obtained on Day 30. Of 192 hypogonadal men who were appropriately titrated with Testim and who had sufficient data for analysis, 74% achieved an average serum testosterone concentration within the normal range (300 to 1,000 ng/dL) on treatment Day 90. Table 2 summarizes the mean testosterone concentrations on Day 30 for patients receiving Testim 50 mg or 100 mg. Table 2: Mean (± SD) Steady-State Serum Testosterone Concentrations on Day 30 Testim 50 mg n=94 Testim 100 mg n=95 Placebo n=93 C avg (ng/dL) 365 ±187 612±286 216 ± 79 Cmax (ng/dL) 538 ±371 897±565 271± 110 Cmin (ng/dL) 223 ±126 394 ±189 164 ± 64

CLINICAL PHARMACOLOGY Mechanism Of Action Endogenous androgens, including testosterone and dihydrotestosterone (DHT), are responsible for the normal growth and development of the male sex organs and for the maintenance of secondary sex characteristics. These effects include the growth and maturation of the prostate, seminal vesicles, penis and scrotum; the development of male hair distribution, such as facial, pubic, chest and axillary hair; laryngeal enlargement, vocal cord thickening, alterations in body musculature and fat distribution. Testosterone and DHT are necessary for the normal development of secondary sex characteristics. Male hypogonadism, a clinical syndrome resulting from insufficient secretion of testosterone, has two main etiologies. Primary hypogonadism is caused by defects of the gonads, such as Klinefelter’s main etiologies. Primary hypogonadism is caused by defects of the gonads, such as Klinefelter’s syndrome or Leydig cell aplasia, whereas secondary hypogonadism is the failure of the hypothalamus or pituitary to produce sufficient gonadotropins (FSH, LH). Pharmacodynamics No specific pharmacodynamic studies were conducted using FORTESTA. Pharmacokinetics Absorption FORTESTA delivers physiologic amounts of testosterone, producing serum testosterone concentrations that approximate normal concentrations (> 300 ng/dL) seen in healthy men. FORTESTA provides continuous transdermal delivery of testosterone for 24 hours following a single application to clean, dry, intact skin of the front and inner thighs (Figure 1). Figure 1: Mean (±SD) Serum Total Testosterone Concentrations on Day 7 in Patients Following FORTESTA Once-Daily Application of 40 mg of Testosterone (N=12) Distribution Circulating testosterone is primarily bound in the serum to sex hormone-binding globulin (SHBG) and albumin. Approximately 40% of testosterone in plasma is bound to SHBG, 2% remains unbound (free) and the rest is loosely bound to albumin and other proteins. Metabolism Testosterone is metabolized to various 17-keto steroids through two different pathways. The major active metabolites of testosterone are estradiol and DHT. Excretion There is considerable variation in the half-life of testosterone concentration as reported in the literature, ranging from 10 to 100 minutes. About 90% of a dose of testosterone given intramuscularly is excreted in the urine as glucuronic acid and sulfuric acid conjugates of testosterone and its metabolites. About 6% is excreted in the feces, mostly in the unconjugated form. Inactivation of testosterone occurs primarily in the liver. Potential For Testosterone Transfer The potential for testosterone transfer from healthy males dosed with FORTESTA to healthy females was evaluated in a placebo-controlled, three-way crossover study. The washout period was approximately 29 days. Six males were treated with either FORTESTA (30 mg testosterone) or placebo to one thigh only. At 2 hours after the application of FORTESTA to males, the females rubbed their forearms for 15 minutes on the thigh of the males. Serum concentrations of testosterone were monitored in females for 24 hours after the transfer procedure. When direct skin-to-skin transfer occurred with FORTESTA mean Cavg increased by 134% and mean Cmax increased by 191%, compared to direct skinto- skin transfer with placebo. When transfer occurred with FORTESTA while covering a thigh with boxer shorts, mean Cavg decreased by 3% and mean Cmax increased by 2%, compared to direct skin-toskin transfer with placebo [see DOSAGE AND ADMINISTRATION]. Effect of Showering In a two-way crossover study, the effects of showering on the pharmacokinetics of total testosterone following application of FORTESTA (30 mg testosterone to each thigh; total 60 mg testosterone) were assessed in 7 hypogonadal males. There were two 7-day treatment phases, with showering 2 hours post FORTESTA application, and without showering on Day 7 of each treatment phase. Showering decreased Cavg by 3% and it increased Cmax by 13% [see DOSAGE AND ADMINISTRATION]. Effect Of Hand Washing And Application Site (Inner Thigh) Washing In an open-label, single-dose study, the amount of residual testosterone on the application finger and application site after washing was evaluated in 12 healthy male subjects. Prior to application of FORTESTA, each index finger and each intended application site (left and right front and inner thighs) was wiped using dry sponges to assess baseline skin testosterone. Subjects then used each index finger to rub FORTESTA (40 mg testosterone) onto each inner thigh. On one side, the index finger was immediately wiped using dry sponges to collect residual testosterone. On the other side, each subject washed their hands with liquid soap and warm tap water immediately after drug application, then wiped the index finger using dry sponges to collect residual testosterone. A mean (SD) of 0.002 (0.006) mg of residual testosterone (i.e., 99.8% reduction compared to when hand was not washed) was recovered after washing hands with liquid soap and warm tap water. Two hours after the application of FORTESTA onto each inner thigh, one thigh was wiped using dry sponges. On the other thigh, the application site was washed with liquid soap and warm tap water, dried, and then wiped using dry sponges. The sponges were assayed for testosterone. A mean (SD) of 0.24 (0.009) mg of residual testosterone (i.e., 94.3% reduction compared to when application site was not washed) was recovered after application site washing. Clinical Studies Clinical Study In Hypogonadal Males FORTESTA was evaluated in a multicenter, 90 day open-label, non-comparative trial of 149 hypogonadal males with body mass index (BMI) ≥ 22 kg/m2 and < 35 kg/m2 and 18-75 years of age (mean age 54.5 years). The patients were screened for a single serum total testosterone concentration < 250 ng/dL, or two consecutive serum total testosterone concentrations < 300 ng/dL. Patients were Caucasian (80.5%), Black (10.1%), Hispanic (7.4%) and other (2.0%). FORTESTA was applied once each morning to the thighs at a starting dose of 40 mg of testosterone (4 pump actuations) per day. The dose was adjusted between a minimum of 10 mg and a maximum of 70 mg testosterone on the basis of total serum testosterone concentration obtained 2 hours post FORTESTA application on Days 14, 35, and 60 (± 3 days). The primary endpoint was the percentage of patients with Cavg within the normal range (greater than or equal to 300 ng/dL and less than or equal to 1140 ng/dL) on Day 90. In patients treated with FORTESTA, 77.5% (100/129) had Cavg within the normal range on Day 90. The secondary endpoint was the percentage of patients with Cmax above three pre-determined limits. The percentages of patients with Cmax greater than 1500 ng/dL, and between 1800 and 2499 ng/dL on Day 90 were 5.4% and 1.6%, respectively. No patient had a Cmax greater than or equal to 2500 ng/dL on Day 90. Dose titrations on Days 14, 35 and 60 resulted in mean (SD) Cavg and Cmax for final doses of 10 mg – 70 mg on Day 90 shown in Table 5. Table 5 Mean (±SD) Steady-State Testosterone Concentrations (Cavg and Cmax ) by final dose on Day 90 Final Dose 10mg (n=1) 20mg (n=6) 30mg (n=16) 40mg (n=30) 50mg (n=26) 60mg (n=27) 70mg (n=23) Cavg (ng/dL) Mean 196 464 392 444 483 441 415 SD 205 164 176 156 163 136 Cmax (ng/dL) Mean 503 971 775 855 964 766 724 SD 399 278 417 389 292 313 Figure 2 summarizes the pharmacokinetic profiles of total testosterone in patients completing 90 days of FORTESTA treatment administered as 40 mg of testosterone once-daily for the initial 14 days followed by possible titration according to follow-up testosterone measurements. Figure 2 Mean (±SD) Steady-State Serum Total Testosterone Concentrations on Day 90 (N=129) Additionally, there were no clinically significant changes from baseline for sex hormone binding globulin (SHBG) (slight decrease), E2 (slight increase) and ratio of DHT to total testosterone (slight increase) at Day 90.

CLINICAL PHARMACOLOGY Mechanism Of Action Endogenous androgens, including testosterone and dihydrotestosterone (DHT), are responsible for the normal growth and development of the male sex organs and for maintenance of secondary sex characteristics. These effects include the growth and maturation of prostate, seminal vesicles, penis and scrotum; the development of male hair distribution, such as facial, pubic, chest and axillary hair; laryngeal enlargement; vocal chord thickening; and alterations in body musculature and fat distribution. Testosterone and DHT are necessary for the normal development of secondary sex characteristics. Male hypogonadism, a clinical syndrome resulting from insufficient secretion of testosterone, has two main etiologies. Primary hypogonadism is caused by defects of the gonads, such as Klinefelter's syndrome or Leydig cell aplasia, whereas secondary hypogonadism is the failure of the hypothalamus (or pituitary) to produce sufficient gonadotropins (FSH, LH). Pharmacodynamics No specific pharmacodynamic studies were conducted using AndroGel 1.62%. Pharmacokinetics Absorption AndroGel 1.62% delivers physiologic amounts of testosterone, producing circulating testosterone concentrations that approximate normal levels (300 – 1000 ng/dL) seen in healthy men. AndroGel 1.62% provides continuous transdermal delivery of testosterone for 24 hours following once daily application to clean, dry, intact skin of the shoulders and upper arms. Average serum testosterone concentrations over 24 hours (Cavg) observed when AndroGel 1.62% was applied to the upper arms/shoulders were comparable to average serum testosterone concentrations (Cavg) when AndroGel 1.62% was applied using a rotation method utilizing the abdomen and upper arms/shoulders. The rotation of abdomen and upper arms/shoulders was a method used in the pivotal clinical trial [see Clinical Studies]. Figure 2: Mean (±SD) Serum Total Testosterone Concentrations on Day 7 in Patients Following AndroGel 1.62% Once-Daily Application of 81 mg of Testosterone (N=33) for 7 Days Distribution Circulating testosterone is primarily bound in the serum to sex hormone-binding globulin (SHBG) and albumin. Approximately 40% of testosterone in plasma is bound to SHBG, 2% remains unbound (free) and the rest is loosely bound to albumin and other proteins. Metabolism Testosterone is metabolized to various 17-keto steroids through two different pathways. The major active metabolites of testosterone are estradiol and DHT. Excretion There is considerable variation in the half-life of testosterone concentration as reported in the literature, ranging from 10 to 100 minutes. About 90% of a dose of testosterone given intramuscularly is excreted in the urine as glucuronic acid and sulfuric acid conjugates of testosterone and its metabolites. About 6% of a dose is excreted in the feces, mostly in the unconjugated form. Inactivation of testosterone occurs primarily in the liver. When AndroGel 1.62% treatment is discontinued, serum testosterone concentrations return to approximately baseline concentrations within 48-72 hours after administration of the last dose. Potential for Testosterone Transfer The potential for testosterone transfer following administration of AndroGel 1.62% when it was applied only to upper arms/shoulders was evaluated in two clinical studies of males dosed with AndroGel 1.62% and their untreated female partners. In one study, 8 male subjects applied a single dose of AndroGel 1.62% 81 mg to their shoulders and upper arms. Two (2) hours after application, female subjects rubbed their hands, wrists, arms, and shoulders to the application site of the male subjects for 15 minutes. Serum concentrations of testosterone were monitored in female subjects for 24 hours after contact occurred. After direct skin-to-skin contact with the site of application, mean testosterone Cavg and Cmax in female subjects increased by 280% and 267%, respectively, compared to mean baseline testosterone concentrations. In a second study evaluating transfer of testosterone, 12 male subjects applied a single dose of AndroGel 1.62% 81 mg to their shoulders and upper arms. Two (2) hours after application, female subjects rubbed their hands, wrists, arms, and shoulders to the application site of the male subjects for 15 minutes while the site of application was covered by a t-shirt. When a t-shirt was used to cover the site of application, mean testosterone Cavg and Cmax in female subjects increased by 6% and 11%, respectively, compared to mean baseline testosterone concentrations. A separate study was conducted to evaluate the potential for testosterone transfer from 16 males dosed with AndroGel 1.62% 81 mg when it was applied to abdomen only for 7 days, a site of application not approved for AndroGel 1.62%. Two (2) hours after application to the males on each day, the female subjects rubbed their abdomens for 15 minutes to the abdomen of the males. The males had covered the application area with a T-shirt. The mean testosterone Cavg and Cmax in female subjects on day 1 increased by 43% and 47%, respectively, compared to mean baseline testosterone concentrations. The mean testosterone Cavg and Cmax in female subjects on day 7 increased by 60% and 58%, respectively, compared to mean baseline testosterone concentrations. Effect of Showering In a randomized, 3-way (3 treatment periods without washout period) crossover study in 24 hypogonadal men, the effect of showering on testosterone exposure was assessed after once daily application of AndroGel 1.62% 81 mg to upper arms/shoulders for 7 days in each treatment period. On the 7th day of each treatment period, hypogonadal men took a shower with soap and water at either 2, 6, or 10 hours after drug application. The effect of showering at 2 or 6 hours post-dose on Day 7 resulted in 13% and 12% decreases in mean Cavg, respectively, compared to Day 6 when no shower was taken after drug application. Showering at 10 hours after drug application had no effect on bioavailability. The amount of testosterone remaining in the outer layers of the skin at the application site on the 7th day was assessed using a tape stripping procedure and was reduced by at least 80% after showering 2-10 hours post-dose compared to on the 6th day when no shower was taken after drug application. Effect of Hand Washing In a randomized, open-label, single-dose, 2-way crossover study in 16 healthy male subjects, the effect of hand washing on the amount of residual testosterone on the hands was evaluated. Subjects used their hands to apply the maximum dose (81 mg testosterone) of AndroGel 1.62% to their upper arms and shoulders. Within 1 minute of applying the gel, subjects either washed or did not wash their hands prior to study personnel wiping the subjects' hands with ethanol dampened gauze pads. The gauze pads were then analyzed for residual testosterone content. A mean (SD) of 0.1 (0.04) mg of residual testosterone (0.12% of the actual applied dose of testosterone, and a 96% reduction compared to when hands were not washed) was recovered after washing hands with water and soap. Effect of Sunscreen Or Moisturizing Lotion On Absorption Of Testosterone In a randomized, 3-way (3 treatment periods without washout period) crossover study in 18 hypogonadal males, the effect of applying a moisturizing lotion or a sunscreen on the absorption of testosterone was evaluated with the upper arms/shoulders as application sites. For 7 days, moisturizing lotion or sunscreen (SPF 50) was applied daily to the AndroGel 1.62% application site 1 hour after the application of AndroGel 1.62% 40.5 mg. Application of moisturizing lotion increased mean testosterone Cavg and Cmax by 14% and 17%, respectively, compared to AndroGel 1.62% administered alone. Application of sunscreen increased mean testosterone Cavg and Cmax by 8% and 13%, respectively, compared to AndroGel 1.62% applied alone. Clinical Studies Clinical Trials In Hypogonadal Males AndroGel 1.62% was evaluated in a multi-center, randomized, double-blind, parallel-group, placebo-controlled study (182-day double-blind period) in 274 hypogonadal men with body mass index (BMI) 18-40 kg/m² and 18-80 years of age (mean age 53.8 years). The patients had an average serum testosterone concentration of < 300 ng/dL, as determined by two morning samples collected on the same visit. Patients were Caucasian 83%, Black 13%, Asian or Native American 4%. 7.5% of patients were Hispanic. Patients were randomized to receive active treatment or placebo using a rotation method utilizing the abdomen and upper arms/shoulders for 182 days. All patients were started at a daily dose of 40.5 mg (two pump actuations) AndroGel 1.62% or matching placebo on Day 1 of the study. Patients returned to the clinic on Day 14, Day 28, and Day 42 for predose serum total testosterone assessments. The patient's daily dose was titrated up or down in 20.25 mg increments if the predose serum testosterone value was outside the range of 350-750 ng/dL. The study included four active AndroGel 1.62% doses: 20.25 mg, 40.5 mg, 60.75 mg, and 81 mg daily. The primary endpoint was the percentage of patients with Cavg within the normal range of 300- 1000 ng/dL on Day 112. In patients treated with AndroGel 1.62%, 81.6% (146/179) had Cavg within the normal range at Day 112. The secondary endpoint was the percentage of patients, with Cmax above three pre-determined limits. The percentages of patients with Cmax greater than 1500 ng/dL, and between 1800 and 2499 ng/dL on Day 112 were 11.2% and 5.5%, respectively. Two patients had a Cmax > 2500 ng/dL on Day 112 (2510 ng/dL and 2550 ng/dL, respectively); neither of these 2 patients demonstrated an abnormal Cmax on prior or subsequent assessments at the same dose. Patients could agree to continue in an open-label, active treatment maintenance period of the study for an additional 182 days. Dose titrations on Days 14, 28, and 42 resulted in final doses of 20.25 mg – 81 mg on Day 112 as shown in Table 6. Table 6: Mean (SD) Testosterone Concentrations (Cavg and Cmax) by final dose on Days 112 and 364 Parameter Final Dose on Day 112 All Active (n=179) Placebo (n=27) 20.25 mg (n=12) 40.5 mg (n=34) 60.75 mg (n=54) 81 mg (n=79) Cavg (ng/dL) 303 (135) 457 (275) 524(228) 643 (285) 537 (240) 561 (259) Cmax (ng/dL) 450 (349) 663 (473) 798 (439) 958 (497) 813 (479) 845(480) Final Dose on Day 364 20.25 mg (n=7) 40.5 mg (n=26) 60.75 mg (n=29) 81 mg (n=74) Continuing Active (n=136) Cavg (ng/dL) 386 (130) 474 (176) 513 (222) 432 (186) 455 (192) Cmax (ng/dL) 562(187) 715 (306) 839 (568) 649 (329) 697 (389) Figure 3 summarizes the pharmacokinetic profile of total testosterone in patients completing 112 days of AndroGel 1.62% treatment administered as a starting dose of 40.5 mg of testosterone (2 pump actuations) for the initial 14 days followed by possible titration according to the follow-up testosterone measurements. Figure 3: Mean (±SD) Steady-State Serum Total Testosterone Concentrations on Day 112 Efficacy was maintained in the group of men that received AndroGel 1.62% for one full year. In that group, 78% (106/136) had average serum testosterone concentrations in the normal range at Day 364. Figure 4 summarizes the mean total testosterone profile for these patients on Day 364. Figure 4: Mean (±SD) Steady-State Serum Total Testosterone Concentrations on Day 364 The mean estradiol and DHT concentration profiles paralleled the changes observed in testosterone. The levels of LH and FSH decreased with testosterone treatment. The decreases in levels of LH and FSH are consistent with reports published in the literature of long-term treatment with testosterone.

Find Lowest Prices on VOGELXO ™ (testosterone) Topical Gel WARNING SECONDARY EXPOSURE TO TESTOSTERONE Virilization has been reported in children who were secondarily exposed to testosterone gel [see WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS]. Children should avoid contact with unwashed or unclothed application sites in men using testosterone gel [see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS]. Healthcare providers should advise patients to strictly adhere to recommended instructions for use [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS  and PATIENT INFORMATION]. DESCRIPTION Vogelxo (testosterone) gel, for topical use is a clear to translucent hydroalcoholic topical gel containing testosterone, an androgen. Vogelxo provides continuous transdermal delivery of testosterone for 24 hours, following a single application to intact, clean, dry skin of the shoulders and/or upper arms. Vogelxo is available in unit-dose tubes, unit-dose packets, and a metered-dose pump. One 5-g or two 5-g tubes/packets of Vogelxo contains 50 mg or 100 mg of testosterone, respectively. One pump actuation dispenses 1.25 g of gel, which contains 12.5 mg of testosterone. Four pump actuations or eight pump actuations contain 50 mg or 100 mg of testosterone, respectively. Each metered-dose pump container is capable of dispensing 60 pump actuations. The active pharmacological ingredient in Vogelxo is testosterone. Testosterone USP is a white to practically white crystalline powder chemically described as 17-β hydroxyandrost-4-en-3-one. The structural formula is shown in the following figure: Testosterone (C19H28O2) MW: 288.42 Inactive ingredients in Vogelxo are carbomer copolymer Type B, carbomer homopolymer Type C, diisopropyl adipate, ethyl alcohol, glycerin, methyl laurate, oleyl alcohol, polyethylene glycol, propylene glycol, purified water, and tromethamine.

Find Lowest Prices on TESTIM® (testosterone) Gel WARNING SECONDARY EXPOSURE TO TESTOSTERONE Virilization has been reported in children who were secondarily exposed to testosterone gel [see WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS]. Children should avoid contact with unwashed or unclothed application sites in men using testosterone gel [see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS] Healthcare providers should advise patients to strictly adhere to recommended instructions for use [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS and PATIENT INFORMATION]. DESCRIPTION Testim® (testosterone gel) is a clear to translucent hydroalcoholic topical gel containing testosterone, an androgen. Testim provides continuous transdermal delivery of testosterone for 24 hours, following a single application to intact, clean, dry skin of the shoulders and/or upper arms. One 5-g or two 5-g tubes of Testim contains 50 mg or 100 mg of testosterone, respectively, to be applied daily to the skin's surface. Approximately 10% of the applied testosterone dose is absorbed across skin of average permeability during a 24-hour period. The active pharmacological ingredient in Testim is testosterone. Testosterone USP is a white to practically white crystalline powder chemically described as 17-β hydroxyandrost-4-en-3-one. The structural formula is shown in the following figure: Inactive ingredients in Testim are purified water, pentadecalactone, carbopol, acrylates, propylene glycol, glycerin, polyethylene glycol, ethanol (74%), and tromethamine.

Find Lowest Prices on FORTESTA® (testosterone) Gel, Metered WARNING SECONDARY EXPOSURE TO TESTOSTERONE Virilization has been reported in children who were secondarily exposed to testosteronegel [see WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS]. Children should avoid contact with unwashed or unclothed application sites in men using FORTESTA [see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS]. Healthcare providers should advise patients to strictly adhere to recommended instructions for use [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS and PATIENT INFORMATION]. DESCRIPTION FORTESTA is a clear, colorless, odorless, gel containing testosterone. FORTESTA is available in a metered-dose pump. Each pump actuation provides 10 mg of testosterone and each container is capable of dispensing 120 pump actuations. One pump actuation dispenses 0.5 g of gel. The active pharmacologic ingredient in FORTESTA is testosterone. Testosterone USP is a white to almost white powder described chemically as 17-beta hydroxyandrost-4-en-3-one. Pharmacologically inactive ingredients in FORTESTA are: propylene glycol, purified water, ethanol, 2-propanol, oleic acid, carbomer 1382, triethanolamine and butylated hydroxytoluene.

AndroGel® (testosterone) Gel WARNING SECONDARY EXPOSURE TO TESTOSTERONE Virilization has been reported in children who were secondarily exposed to testosterone gel [see WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS]. Children should avoid contact with unwashed or unclothed application sites in men using testosterone gel [see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS]. Healthcare providers should advise patients to strictly adhere to recommended instructions for use [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS and PATIENT INFORMATION]. DESCRIPTION AndroGel 1.62% for topical use is a clear, colorless gel containing testosterone. Testosterone is an androgen. AndroGel 1.62% is available in a metered-dose pump or unit dose packets. The active pharmacologic ingredient in AndroGel 1.62% is testosterone. Testosterone USP is a white to almost white powder chemically described as 17-beta hydroxyandrost-4-en-3-one. The structural formula is: The inactive ingredients in AndroGel 1.62% are: carbopol 980, ethyl alcohol, isopropyl myristate, purified water, and sodium hydroxide.

INDICATIONS Vogelxo is indicated for replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone: Primary hypogonadism (congenital or acquired): testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter's syndrome, chemotherapy, or toxic damage from alcohol or heavy metals. These men usually have low serum testosterone levels and gonadotropins (follicle-stimulating hormone [FSH], luteinizing hormone [LH]) above the normal range. Hypogonadotropic hypogonadism (congenital or acquired): gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation. These men have low testosterone serum levels but have gonadotropins in the normal or low range. Limitations of use Safety and efficacy of Vogelxo in men with “age-related hypogonadism” (also referred to as “late-onset hypogonadism”) have not been established. Safety and efficacy of Vogelxo in males less than 18 years old have not been established [see Use In Specific Populations]. Topical testosterone products may have different doses, strengths, or application instructions that may result in different systemic exposure [see DOSAGE AND ADMINISTRATION and CLINICAL PHARMACOLOGY]. DOSAGE AND ADMINISTRATION Prior to initiating Vogelxo, confirm the diagnosis of hypogonadism by ensuring that serum testosterone concentrations have been measured in the morning on at least two separate days and that these serum testosterone concentrations are below the normal range. Dosing And Dose Adjustment The recommended starting dose of Vogelxo is 50 mg of testosterone (one tube, one packet, or 4 pump actuations) applied topically once daily at approximately the same time each day to clean, dry intact skin of the shoulders and/or upper arms. Dose Adjustment To ensure proper dosing, serum testosterone concentrations should be measured. Morning, pre-dose serum testosterone concentrations should be measured approximately 14 days after initiation of therapy to ensure proper serum testosterone concentrations are achieved. If the serum testosterone concentration is below the normal range (300 ng/dL to 1,000 ng/dL), the daily Vogelxo dose may be increased from 50 mg testosterone (one tube, one packet, or 4 pump actuations) to 100 mg of testosterone (two tubes, two packets, or 8 pump actuations) once daily. The maximum recommended dose of Vogelxo is 100 mg once daily. Administration Instructions Unit-Dose Tube or Packet Upon opening the tube or packet the entire contents should be squeezed into the palm of the hand and immediately applied to the shoulders and/or upper arms (area of application should be limited to the area that will be covered by the patient's short sleeve t-shirt [see figure below]). Table 1 has specific dosing guidelines for when the unit-dose tubes or packets are used. Table 1: Specific Dosing Guideline for Using the Unit-Dose Tubes or Packets Prescribed Daily Dose Number of Unit-Dose Tubes or Packets Application Method 50 mg testosterone One unit-dose tube or packet (once daily) Apply one unit-dose tube or packet to one upper arm and shoulder. 100 mg testosterone Two unit-dose tubes or packets (once daily) Apply one unit-dose tube or packet to one upper arm and shoulder and then apply one unit-dose tube or packet to the opposite upper arm and shoulder. Multi-Dose Metered Pump Patients should be instructed to prime the pump before using it for the first time by fully depressing the pump mechanism (actuation) 3 times and discard this portion of the product to assure precise dose delivery. After the priming procedure, patients should completely depress the pump one time (actuation) for every 12.5 mg of testosterone required to achieve the daily prescribed dosage. Table 2 has specific dosing guidelines for when the metered pump is used. Table 2: Specific Dosing Guidelines for Using the Multi-Dose Pump Prescribed Daily Dose Number of Pump Actuations Application Method 50 mg testosterone 4 (once daily) Apply 4 pump actuations to one upper arm and shoulder 100 mg testosterone 8 (once daily) Apply 4 pump actuations to one upper arm and shoulder and then apply 4 pump actuations to the opposite upper arm and shoulder The prescribed amount of product should be delivered directly into the palm of the hand and immediately applied to the shoulders and/or upper arms (area of application should be limited to the area that will be covered by the patient's short sleeve t-shirt [see figure below]) Do not apply Vogelxo to the genitals or to the abdomen. Application sites should be allowed to dry completely prior to dressing. Hands should be washed thoroughly with soap and water after Vogelxo has been applied. Avoid fire, flame or smoking during the application of Vogelxo until the Vogelxo has dried [see WARNINGS AND PRECAUTIONS]. In order to prevent transfer to another person, clothing should be worn to cover the application sites. If direct skin-to-skin contact of the application site(s) with another person is anticipated, the application sites must be washed thoroughly with soap and water [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY]. The patient should avoid swimming or showering or washing the administration site for a minimum of 2 hours after application [see CLINICAL PHARMACOLOGY]. Strict adherence to the following precautions is advised in order to minimize the potential for secondary exposure to testosterone from Vogelxo treated skin: Children and women should avoid contact with unwashed or unclothed application site(s) of men using Vogelxo. Vogelxo should only be applied to the upper arms and shoulders. The area of application should be limited to the area that will be covered by a short sleeve t-shirt. Patients should wash their hands with soap and water immediately after applying Vogelxo. Patients should cover the application site(s) with clothing (e.g., a t-shirt) after the gel has dried. Prior to any situation in which direct skin-to-skin contact of the application site(s) with another person is anticipated, patients should wash the application site(s) thoroughly with soap and water to remove any testosterone residue. In the event that unwashed or unclothed skin to which Vogelxo has been applied comes in direct contact with the skin of another person, the general area of contact on the other person should be washed with soap and water as soon as possible. HOW SUPPLIED Dosage Forms And Strengths Vogelxo (testosterone) gel is a clear to translucent hydroalcoholic topical gel for topical use available in unit-dose tubes, unit-dose packets, and multiple-dose metered pumps. Each tube or packet provides 50 mg testosterone in 5 g of gel. One pump actuation delivers 12.5 mg testosterone in 1.25 g of gel (4 actuations = 50 mg testosterone). Storage And Handling Vogelxo is supplied in unit-dose tubes in cartons of 30 and unit-dose packets in cartons of 30. Each tube or packet contains 50 mg testosterone in 5 g of gel. Vogelxo is also supplied in a metered-dose pump that delivers 12.5 mg of testosterone per complete pump actuation. Each 88 g metered-dose pump is capable of dispensing 75 g of gel or 60-metered pump actuations. Each pump actuation delivers 1.25 g of gel. The metered-dose pump is supplied in cartons of 2. Vogelxo is available as follows: NDC Number Strength Package Size 0245-0871-05 50 mg of testosterone 30 tubes (5 g of gel per tube) 0245-0871-65 50 mg of testosterone 1 tube (5 g of gel per tube) 0245-0871-35 50 mg of testosterone 30 packets (5 g of gel per packet) 0245-0871-89 50 mg of testosterone 1 packet (5 g of gel per packet) 0245-0872-42 12.5 mg of testosterone per pump actuation 2 x 75 g pumps (each pump dispenses 60 metered 1.25 g of gel) Storage Store at 20°C to 25°C (68°F to 77°F). Excursions permitted to 15°C to 30°C (59°F to 86°F). [See USP Controlled Room Temperature.] Handling And Disposal Used Vogelxo tubes, packets or pumps should be discarded in household trash in a manner that prevents accidental exposure of women, children, or pets [see BOXED WARNING and WARNINGS AND PRECAUTIONS]. Contents are flammable [see WARNINGS AND PRECAUTIONS]. Distributed by UPSHER-SMITH LABORATORIES, INC. Maple Grove, MN 55369. Revised May 2015

INDICATIONS Testim® is indicated for testosterone replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone: Primary hypogonadism (congenital or acquired): testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter's syndrome, chemotherapy, or toxic damage from alcohol or heavy metals. These men usually have low serum testosterone concentrations and gonadotropins (follicle-stimulating hormone [FSH], luteinizing hormone [LH]) above the normal range. Hypogonadotropic hypogonadism (congenital or acquired): gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation. These men have low testosterone serum concentrations but have gonadotropins in the normal or low range. Limitations Of Use Safety and efficacy of Testim in men with “age-related hypogonadism” (also referred to as “late-onset hypogonadism”) have not been established. Safety and efficacy of Testim in males less than 18 years old have not been established [see Use in Specific Populations]. Topical testosterone products may have different doses, strengths, or application instructions that may result in different systemic exposure [see DOSAGE AND ADMINISTRATION and CLINICAL PHARMACOLOGY]. DOSAGE AND ADMINISTRATION Prior to initiating, Testim confirm the diagnosis of hypogonadism by ensuring that serum testosterone concentrations have been measured in the morning on at least two separate days and that these serum testosterone concentrations are below the normal range. Dosing And Dose Adjustment The recommended starting dose of Testim® is 50 mg of testosterone (one tube) applied once daily (preferably in the morning) to clean, dry intact skin of the shoulders and/or upper arms. Dose Adjustment To ensure proper dosing, serum testosterone concentrations should be measured. Morning, pre-dose serum testosterone concentrations should be measured approximately 14 days after initiation of therapy to ensure proper serum testosterone concentrations are achieved. If the serum testosterone concentration is below the normal range (300 ng/dL to 1,000 ng/dL), the daily Testim dose may be increased from 50 mg testosterone (one tube) to 100 mg testosterone (two tubes) once daily. The maximum recommended dose of Testim is 100 mg once daily. The application site and dose of Testim are not interchangeable with other topical testosterone products. Administration Instructions Upon opening the tube the entire contents should be squeezed into the palm of the hand and immediately applied to the shoulders and/or upper arms (area of application should be limited to the area that will be covered by the patient's short sleeve T-shirt (see figure below). Do not apply Testim to the genitals or to the abdomen. Application sites should be allowed to dry for a few minutes prior to dressing. Hands should be washed thoroughly with soap and water after Testim has been applied. Avoid fire, flame or smoking during the application of Testim until the Testim has dried [see WARNINGS AND PRECAUTIONS]. In order to prevent transfer to another person, wear clothing to cover the application sites. If direct skin-to-skin contact with another person is anticipated, the application sites must be washed thoroughly with soap and water [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY]. The patient should avoid swimming or showering or washing the administration site for a minimum of 2 hours after application [see CLINICAL PHARMACOLOGY]. Strict adherence to the following precautions is advised in order to minimize the potential for secondary exposure to testosterone from Testim-treated skin: Children and women should avoid contact with unwashed or unclothed application site(s) of men using Testim. Testim should only be applied to the upper arms and shoulders. The area of application should be limited to the area that will be covered by a short sleeve T-shirt. Patients should wash their hands with soap and water immediately after applying Testim. Patients should cover the application site(s) with clothing (e.g., a T-shirt) after the gel has dried. Prior to situations in which direct skin-to-skin contact is anticipated, patients should wash the application site(s) thoroughly with soap and water to remove any testosterone residue. In the event that unwashed or unclothed skin to which Testim has been applied comes in direct contact with the skin of another person, the general area of contact on the other person should be washed with soap and water as soon as possible. HOW SUPPLIED Dosage Forms And Strengths Testim® (testosterone gel) for topical use is available in a unit-dose tube. Each tube contains 50 mg testosterone in 5 g of gel. Storage And Handling Testim is supplied in unit-dose tubes in cartons of 30. Each tube contains 50 mg testosterone in 5 g of gel, and is supplied as follows: NDC Number Package Size 66887-001-05 30 tubes: 50 mg testosterone in 5 g of gel per tube Store at 20 to 25°C (68°F to 77°F). Excursions permitted to 15°-30°C (59°-86°F) [See USP Controlled Room Temperature]. Discard used Testim tubes in household trash in a manner that prevents accidental exposure of women, children, or pets [see BOXED WARNING and WARNINGS AND PRECAUTIONS]. Contents are flammable [see WARNINGS AND PRECAUTIONS]. Manufactured for: Auxilium Pharmaceuticals, Inc. Chesterbrook, PA 19087 USA. By: DPT Laboratories, Ltd. San Antonio, TX 78215. Revised: May 2015

INDICATIONS FORTESTA is indicated for replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone: Primary hypogonadism (congenital or acquired) – testicular failure due to conditions such as cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter’s syndrome, chemotherapy, or toxic damage from alcohol, heavy metals. These men usually have low serum testosterone concentrations and gonadotropins (Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH)) above the normal range. Hypogonadotropic hypogonadism (congenital or acquired) – gonadotropin or luteinizing hormonereleasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation. These men have low serum testosterone concentrations but have gonadotropins in the normal or low range. Limitations Of Use Safety and efficacy of FORTESTA in men with “age-related hypogonadism” (also referred to as “late-onset hypogonadism”) have not been established. Safety and efficacy of FORTESTA in males <18 years old have not been established [see Use In Specific Populations]. DOSAGE AND ADMINISTRATION Prior to initiating, FORTESTA confirm the diagnosis of hypogonadism by ensuring that serum testosterone concentrations have been measured in the morning on at least two separate days and that these serum testosterone concentrations are below the normal range. Dosing And Dose Adjustment The recommended starting dose of FORTESTA is 40 mg of testosterone (4 pump actuations) applied once daily to the thighs in the morning. The dose can be adjusted between a minimum of 10 mg of testosterone and a maximum of 70 mg of testosterone. To ensure proper dosing, the dose should be titrated based on the serum testosterone concentration from a single blood draw 2 hours after applying FORTESTA at approximately 14 days and 35 days after starting treatment or following dose adjustment. In addition, serum testosterone concentration should be assessed periodically thereafter. Table 1 describes the dose adjustments required at each titration step. Table 1 - Dose Adjustment Criteria Total Serum Testosterone Concentration 2 hours Post FORTESTA Application Dose Titration Equal to or greater than 2,500 ng/dL Decrease daily dose by 20 mg (2 pump actuations) Equal to or greater than 1,250 and less than 2,500 ng/dL Decrease daily dose by 10 mg (1 pump actuation) Equal to or greater than 500 and less than 1,250 ng/dL No change: continue on current dose Less than 500 ng/dL Increase daily dose by 10 mg (1 pump actuation) The application site and dose of FORTESTA are not interchangeable with other topical testosterone products. Administration Instructions FORTESTA should be applied directly to clean, dry, intact skin of the front and inner thighs. Do not apply FORTESTA to the genitals or other parts of the body. Patients should be instructed to use one finger to gently rub FORTESTA evenly onto the front and inner area of each thigh as directed in Table 2. Table 2 . Application of FORTESTA Total Dose of Testosterone Total Pump Actuations Pump Actuations per Thigh Thigh # 1 Thigh # 2 10 mg 1 1 0 20 mg 2 1 1 30 mg 3 2 1 40 mg 4 2 2 50 mg 5 3 2 60 mg 6 3 3 70 mg 7 4 3 Once the application site is dry, the site should be covered with clothing [see CLINICAL PHARMACOLOGY]. Wash hands thoroughly with soap and water. Avoid applying the gel to the thigh adjacent to the scrotum. Avoid fire, flames or smoking until the gel has dried since alcohol based products, including FORTESTA, are flammable. The patient should avoid swimming or showering or washing the administration site for a minimum of 2 hours after application [see CLINICAL PHARMACOLOGY]. To obtain a full first dose, it is necessary to prime the canister pump. To do so, with the canister in the upright position, slowly and fully depress the actuator eight times. The first three actuations may result in no discharge of gel. Safely discard the gel from the first eight actuations. It is only necessary to prime the pump before the first dose. Strict adherence to the following precautions is advised in order to minimize the potential for secondary exposure to testosterone from FORTESTA-treated skin: Children and women should avoid contact with unwashed or unclothed application site(s) of men using FORTESTA. FORTESTA should only be applied to the front and inner thighs (area of application should be limited to the area that will be covered by the patient’s shorts or pants). Patients should wash their hands immediately with soap and water after applying FORTESTA. Patients should cover the application site(s) with clothing (e.g., shorts of sufficient length or pants) after the gel has dried. Prior to any situation in which skin-to-skin contact with the application site is anticipated, patients should wash the application site(s) thoroughly with soap and water to remove any testosterone residue. In the event that unwashed or unclothed skin to which FORTESTA has been applied comes in direct contact with the skin of another person, the general area of contact on the other person should be washed with soap and water as soon as possible. HOW SUPPLIED Dosage Forms And Strengths FORTESTA (testosterone) Gel for topical use only, is supplied in a metered-dose pump. One pump actuation delivers 10 mg of testosterone. Storage And Handling FORTESTA is supplied in 60 g canisters with a metered dose pump that delivers 10 mg of testosterone per complete pump actuation. The metered dose pump is capable of dispensing 120 metered pump actuations. One pump actuation dispenses 0.5 g of gel. FORTESTA is available in packages of 1, 2 and 3 canisters (NDC 63481-183-16, NDC 63481-183-17 and NDC 63481-183-18, respectively). Store at controlled room temperature 20° -25°C (68° -77° F); excursions permitted to 15° -30° C (59° - 86° F). [See USP]. Do Not Freeze. Used FORTESTA canisters should be discarded in household trash in a manner that prevents accidental application or ingestion by children or pets. Distributed by: Endo Pharmaceuticals Inc. Malvern, PA 19355. Revised: Aug 2017

INDICATIONS AndroGel 1.62% is indicated for replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone: Primary hypogonadism (congenital or acquired): testicular failure due to conditions such as cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter's syndrome, chemotherapy, or toxic damage from alcohol or heavy metals. These men usually have low serum testosterone concentrations and gonadotropins (folliclestimulating hormone [FSH], luteinizing hormone [LH]) above the normal range. Hypogonadotropic hypogonadism (congenital or acquired): gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation. These men have low testosterone serum concentrations, but have gonadotropins in the normal or low range. Limitations of use Safety and efficacy of AndroGel 1.62% in men with “age-related hypogonadism” (also referred to as “late-onset hypogonadism”) have not been established. Safety and efficacy of AndroGel 1.62% in males less than 18 years old have not been established [see Use in Specific Populations]. Topical testosterone products may have different doses, strengths, or application instructions that may result in different systemic exposure [see CLINICAL PHARMACOLOGY]. DOSAGE AND ADMINISTRATION Dosage and Administration for AndroGel 1.62% differs from AndroGel 1%. For dosage and administration of AndroGel 1% refer to its full prescribing information. Prior to initiating AndroGel 1.62%, confirm the diagnosis of hypogonadism by ensuring that serum testosterone concentrations have been measured in the morning on at least two separate days and that these serum testosterone concentrations are below the normal range. Dosing And Dose Adjustment The recommended starting dose of AndroGel 1.62% is 40.5 mg of testosterone (2 pump actuations or a single 40.5 mg packet) applied topically once daily in the morning to the shoulders and upper arms. The dose can be adjusted between a minimum of 20.25 mg of testosterone (1 pump actuation or a single 20.25 mg packet) and a maximum of 81 mg of testosterone (4 pump actuations or two 40.5 mg packets). To ensure proper dosing, the dose should be titrated based on the pre-dose morning serum testosterone concentration from a single blood draw at approximately 14 days and 28 days after starting treatment or following dose adjustment. In addition, serum testosterone concentration should be assessed periodically thereafter. Table 1 describes the dose adjustments required at each titration step. Table 1: Dose Adjustment Criteria Pre-Dose Morning Total Serum Testosterone Concentration Dose Titration Greater than 750 ng/dL Decrease daily dose by 20.25 mg (1 pump actuation or the equivalent of one 20.25 mg packet) Equal to or greater than 350 and equal to or less than 750 ng/dL No change: continue on current dose Less than 350 ng/dL Increase daily dose by 20.25 mg (1 pump actuation or the equivalent of one 20.25 mg packet) The application site and dose of AndroGel 1.62% are not interchangeable with other topical testosterone products. Administration Instructions AndroGel 1.62% should be applied to clean, dry, intact skin of the upper arms and shoulders. Do not apply AndroGel 1.62% to any other parts of the body, including the abdomen, genitals, chest, armpits (axillae), or knees [see CLINICAL PHARMACOLOGY]. Area of application should be limited to the area that will be covered by the patient's short sleeve t-shirt. Patients should be instructed to use the palm of the hand to apply AndroGel 1.62% and spread across the maximum surface area as directed in Table 2 (for pump) and Table 3 (for packets) and in Figure 1. Table 2: Application Sites for AndroGel 1.62%, Pump Total Dose of Testosterone Total Pump Actuations Pump Actuations Per Upper Arm and Shoulder Upper Arm and Shoulder #1 Upper Arm and Shoulder #2 20.25 mg 1 1 0 40.5 mg 2 1 1 60.75 mg 3 2 1 81 mg 4 2 2 Table 3: Application Sites for AndroGel 1.62%, Packets Total Dose of Testosterone Total packets Gel Applications Per Upper Arm and Shoulder Upper Arm and Shoulder #1 Upper Arm and Shoulder #2 20.25 mg One 20.25 mg packet One 20.25 mg packet 0 40.5 mg One 40.5 mg packet Half of contents of One 40.5 mg packet Half of contents of One 40.5 mg packet 60.75 mg One 20.25 mg packet AND One 40.5 mg packet One 40.5 mg packet One 20.25 mg packet 81 mg Two 40.5 mg packets One 40.5 mg packet One 40.5 mg packet The prescribed daily dose of AndroGel 1.62% should be applied to the right and left upper arms and shoulders as shown in the shaded areas in Figure 1. Figure 1: Application Sites for AndroGel 1.62% Once the application site is dry, the site should be covered with clothing [see CLINICAL PHARMACOLOGY]. Wash hands thoroughly with soap and water. Avoid fire, flames or smoking until the gel has dried since alcohol based products, including AndroGel 1.62%, are flammable. The patient should avoid swimming or showering or washing the administration site for a minimum of 2 hours after application [see CLINICAL PHARMACOLOGY]. To obtain a full first dose, it is necessary to prime the canister pump. To do so, with the canister in the upright position, slowly and fully depress the actuator three times. Safely discard the gel from the first three actuations. It is only necessary to prime the pump before the first dose. After the priming procedure, fully depress the actuator once for every 20.25 mg of AndroGel 1.62%. AndroGel 1.62% should be delivered directly into the palm of the hand and then applied to the application sites. When using packets, the entire contents should be squeezed into the palm of the hand and immediately applied to the application sites. When 40.5 mg packets need to be split between the left and right shoulder, patients may squeeze a portion of the gel from the packet into the palm of the hand and apply to application sites. Repeat until entire contents have been applied. Alternatively, AndroGel 1.62% can be applied directly to the application sites from the pump or packets. Strict adherence to the following precautions is advised in order to minimize the potential for secondary exposure to testosterone from AndroGel 1.62%-treated skin: Children and women should avoid contact with unwashed or unclothed application site(s) of men using AndroGel 1.62%. AndroGel 1.62% should only be applied to the upper arms and shoulders. The area of application should be limited to the area that will be covered by a short sleeve t-shirt. Patients should wash their hands with soap and water immediately after applying AndroGel 1.62%. Patients should cover the application site(s) with clothing (e.g., a t-shirt) after the gel has dried. Prior to situations in which direct skin-to-skin contact is anticipated, patients should wash the application site(s) thoroughly with soap and water to remove any testosterone residue. In the event that unwashed or unclothed skin to which AndroGel 1.62% has been applied comes in direct contact with the skin of another person, the general area of contact on the other person should be washed with soap and water as soon as possible. HOW SUPPLIED Dosage Forms And Strengths AndroGel (testosterone gel) 1.62% for topical use only, is available as follows: A metered-dose pump. Each pump actuation delivers 20.25 mg of testosterone in 1.25 g of gel. A unit dose packet containing 20.25 mg of testosterone in 1.25 g of gel. A unit dose packet containing 40.5 mg of testosterone in 2.5 g of gel. Storage And Handling AndroGel 1.62% is supplied in non-aerosol, metered-dose pumps that deliver 20.25 mg of testosterone per complete pump actuation. The pumps are composed of plastic and stainless steel and an LDPE/aluminum foil inner liner encased in rigid plastic with a polypropylene cap. Each 88 g metered-dose pump is capable of dispensing 75 g of gel or 60-metered pump actuations; each pump actuation dispenses 1.25 g of gel. AndroGel 1.62% is also supplied in unit-dose aluminum foil packets in cartons of 30. Each packet of 1.25 g or 2.5 g gel contains 20.25 mg or 40.5 mg testosterone, respectively. NDC Number Package Size 0051-8462- 33 88 g pump (each pump dispenses 60 metered pump actuations with each pump actuation containing 20.25 mg of testosterone in 1.25 g of gel) 0051-8462- 12 Each unit dose packet contains 20.25 mg of testosterone provided in 1.25 g of gel 0051-8462- 31 30 packets (each unit dose packet contains 20.25 mg of testosterone provided in 1.25 g of gel) 0051-8462- 01 Each unit dose packet contains 40.5 mg of testosterone provided in 2.5 g of gel 0051-8462- 30 30 packets (each unit dose packet contains 40.5 mg of testosterone provided in 2.5 g of gel) Store at controlled room temperature 20°-25°C (68°-77°F); excursions permitted to 15°- 30°C (59°- 86°F) [see USP Controlled Room Temperature]. Used AndroGel 1.62% pumps or used AndroGel 1.62% packets should be discarded in household trash in a manner that prevents accidental application or ingestion by children or pets. Marketed by: AbbVie Inc., North Chicago, IL 60064, USA. Revised May, 2015

PATIENT INFORMATION VOGELXO ™ (voh-JELKS-oh) (testosterone) gel Read this Medication Guide that comes with Vogelxo before you start using it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your healthcare provider about your medical condition or your treatment. What is the most important information I should know about Vogelxo? 1. Early signs and symptoms of puberty have happened in young children who were accidentally exposed to testosterone through contact with men using Vogelxo. Signs and symptoms of early puberty in a child may include: enlarged penis or clitoris early development of pubic hair increased erections or sex drive aggressive behavior Vogelxo can transfer from your body to others. 2. Women and children should avoid contact with the unwashed or unclothed area where Vogelxo has been applied to your skin. Stop using Vogelxo and call your healthcare provider right away if you see any signs and symptoms in a child or a woman that may have occurred through accidental exposure to Vogelxo. Signs and symptoms of exposure to Vogelxo in children may include: enlarged penis or clitoris early development of pubic hair increased erections or sex drive aggressive behavior Signs and symptoms of exposure to Vogelxo in women may include: changes in body hair a large increase in acne To lower the risk of transfer of Vogelxo from your body to others, you should follow these important instructions: Apply Vogelxo only to the areas of your shoulders and upper arms that will be covered by a short sleeve T-shirt. Wash your hands right away with soap and water after applying Vogelxo. After the gel has dried, cover the application area with clothing. Keep the area covered until you have washed the application area well or have showered. If you expect to have skin-to-skin contact with another person, first wash the application area well with soap and water. If a woman or child makes contact with the Vogelxo application area, that area on the woman or child should be washed well with soap and water right away. What is Vogelxo? Vogelxo is a prescription medicine that contains testosterone. Vogelxo is used to treat adult males who have low or no testosterone due to certain medical conditions. Your healthcare provider will test your blood before you start and while you use Vogelxo. It is not known if Vogelxo is safe or effective to treat men who have low testosterone due to aging. It is not known if Vogelxo is safe or effective in children younger than 18 years old. Improper use of Vogelxo may affect bone growth in children. Vogelxo is a controlled substance (CIII) because it contains testosterone that can be a target for people who abuse prescription medicines. Keep your Vogelxo in a safe place to protect it. Never give your Vogelxo to anyone else, even if they have the same symptoms you have. Selling or giving away this medicine may harm others and it is against the law. Vogelxo is not meant for use in women. Who should not use Vogelxo? Do not use Vogelxo if you: have breast cancer have or might have prostate cancer are pregnant or may become pregnant or are breastfeeding. Vogelxo may harm your unborn or breastfeeding baby. Women who are pregnant or who may become pregnant should avoid contact with the area of skin where Vogelxo has been applied. Talk to your healthcare provider before using this medicine if you have any of the above conditions. What should I tell my healthcare provider before using Vogelxo? Before you use Vogelxo, tell your healthcare provider if you: have breast cancer have or might have prostate cancer have urinary problems due to an enlarged prostate have heart problems have liver or kidney problems have problems breathing while you sleep (sleep apnea) have any other medical conditions Tell your healthcare provider about all the medicines you take, including prescription and overthe-counter medicines, vitamins, and herbal supplements. Vogelxo and certain other medicines you take can affect each other. Especially, tell your healthcare provider if you take: insulin medicines that decrease blood clotting corticosteroids Know the medicines you take. Ask your healthcare provider or pharmacist for a list of these medicines, if you are not sure. Keep a list of them and show it to your healthcare provider and pharmacist when you get a new medicine. How should I use Vogelxo? It is important that you apply Vogelxo exactly as your healthcare provider tells you to. Your healthcare provider will tell you how much Vogelxo to apply and when to apply it. Your healthcare provider may change your Vogelxo dose. Do not change your Vogelxo dose without talking to your healthcare provider. Vogelxo is to be applied only to the areas of your shoulders and upper arms that will be covered by a short sleeve t-shirt. Do not apply Vogelxo to any other parts of your body such as your penis, scrotum, or stomach area (abdomen). Apply Vogelxo at the same time each day. Vogelxo should be applied after showering or bathing. Wash your hands right away with soap and water after applying Vogelxo. Avoid showering, swimming, or bathing for at least 2 hours after you apply Vogelxo. Vogelxo is flammable until dry. Let Vogelxo dry before smoking or going near an open flame. Let the application areas dry before putting on a t-shirt. Applying Vogelxo: Vogelxo comes in tubes, packets, or in a pump. Before applying Vogelxo, make sure that your shoulders and upper arms are clean, dry, and there is no broken skin. The application sites for Vogelxo are the shoulders and the upper arms that will be covered by a short sleeve t-shirt (See Figure A). Figure A If you are using Vogelxo tubes: Remove the cap from the tube and use the top of the cap to puncture the metal seal on the top of the tube. Squeeze from the bottom of the tube to the top. Squeeze all of the Vogelxo out of the tube into the palm of your hand. Apply Vogelxo to the application site. Rub the gel onto your skin for several seconds. Let the application site dry for a few minutes before putting on a T-shirt. Wash your hands with soap and water right away. Put the cap back on the tube. If you are using Vogelxo packets: Tear open the packet completely at the notch on the top edge. Squeeze from the bottom of the packet to the top. Squeeze all of the Vogelxo out of the packet into the palm of your hand. Apply Vogelxo to the application site. Rub the gel onto your skin for several seconds. Let the application site dry for a few minutes before putting on a T-shirt. Wash your hands with soap and water right away. If you are using the Vogelxo pump: Before using a new bottle of Vogelxo for the first time, you will need to prime the pump. To prime the Vogelxo pump, remove the cap and slowly push the pump all the way down 3 times. Do not use any Vogelxo that came out while priming. Wash it down the sink to avoid accidental exposure to others. Your Vogelxo pump is now ready to use. Remove the cap from the pump. Then position the nozzle over the palm of your hand and slowly push the pump all the way down. Your healthcare provider will tell you the number of times to press the pump for each dose. Apply Vogelxo to the application site. Rub the gel onto your skin for several seconds. Let the application site dry for a few minutes before putting on a T-shirt. Wash your hands with soap and water right away. Put the cap back on the pump. What are the possible side effects of Vogelxo? Vogelxo can cause serious side effects including: See “What is the most important information I should know about Vogelxo?” If you already have enlargement of your prostate gland your signs and symptoms can get worse while using Vogelxo. This can include: increased urination at night trouble starting your urine stream having to pass urine many times during the day having an urge that you have to go to the bathroom right away having a urine accident being unable to pass urine or weak urine flow Possible increased risk of prostate cancer. Your healthcare provider should check you for prostate cancer or any other prostate problems before you start and while you use Vogelxo. Blood clots in your legs or lungs. Signs and symptoms of a blood clot in your legs can include leg pain, swelling or redness. Signs and symptoms of a blood clot in your lungs can include difficulty breathing or chest pain. Possible increased risk of heart attack or stroke. In large doses Vogelxo may lower your sperm count. Swelling of your ankles, feet, or body, with or without heart failure. Enlarged or painful breasts. Having problems breathing while you sleep (sleep apnea). Call your healthcare provider right away if you have any of the serious side effects listed above. The most common side effects of Vogelxo include: skin irritation where Vogelxo is applied increased red blood cell count headache increased blood pressure Other side effects include more erections than are normal for you or erections that last a long time. Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of Vogelxo. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1800-FDA-1088. How should I store Vogelxo? Store Vogelxo between 68°F to 77°F (20°C to 25°C). Safely throw away used Vogelxo containers in household trash. Be careful to prevent accidental exposure of children or pets. Keep Vogelxo away from fire. Keep Vogelxo and all medicines out of the reach of children. General information about the safe and effective use of Vogelxo. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Vogelxo for a condition for which it was not prescribed. Do not give Vogelxo to other people, even if they have the same symptoms that you have. It may harm them. This Medication Guide summarizes the most important information about Vogelxo. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about Vogelxo that is written for health professionals. For more information, go to www.upsher-smith.com or call 1-888-650-3789. What are the ingredients in Vogelxo? Active ingredient: testosterone Inactive ingredients: carbomer copolymer Type B, carbomer homopolymer Type C, diisopropyl adipate, ethyl alcohol, glycerin, methyl laurate, oleyl alcohol, polyethylene glycol, propylene glycol, purified water, and tromethamine This Medication Guide has been approved by the U.S. Food and Drug Administration.

PATIENT INFORMATION Testim® (TES tim) (testosterone) Gel Read this Medication Guide that comes with Testim before you start using it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your healthcare provider about your medical condition or your treatment. What is the most important information I should know about Testim? 1. Early signs and symptoms of puberty have happened in young children who were accidentally exposed to testosterone through contact with men using Testim. Signs and symptoms of early puberty in a child may include: enlarged penis or clitoris early development of pubic hair increased erections or sex drive aggressive behavior Testim can transfer from your body to others. 2. Women and children should avoid contact with the unwashed or unclothed area where Testim has been applied to your skin. Stop using Testim and call your healthcare provider right away if you see any signs and symptoms in a child or a woman that may have occurred through accidental exposure to Testim. Signs and symptoms of exposure to Testim in children may include: enlarged penis or clitoris early development of pubic hair increased erections or sex drive aggressive behavior Signs and symptoms of exposure to Testim in women may include: changes in body hair a large increase in acne To lower the risk of transfer of Testim from your body to others, you should follow these important instructions: Apply Testim only to the areas of your shoulders and upper arms that will be covered by a short sleeve T-shirt. Wash your hands right away with soap and water after applying Testim. After the gel has dried, cover the application area with clothing. Keep the area covered until you have washed the application area well or have showered. If you expect to have skin-to-skin contact with another person, first wash the application area well with soap and water. If a woman or child makes contact with the Testim application area, that area on the woman or child should be washed well with soap and water right away. What is Testim? Testim is a prescription medicine that contains testosterone. Testim is used to treat adult males who have low or no testosterone due to certain medical conditions. Your healthcare provider will test your blood before you start and while you use Testim. It is not known if Testim is safe or effective to treat men who have low testosterone due to aging. It is not known if Testim is safe or effective in children younger than 18 years old. Improper use of testosterone in children may affect bone growth. Testim is a controlled substance (CIII) because it contains testosterone that can be a target for people who abuse prescription medicines. Keep your Testim in a safe place to protect it. Never give your Testim to anyone else, even if they have the same symptoms you have. Selling or giving away this medicine may harm others and it is against the law. Testim is not meant for use in women. Who should not use Testim? Do not use Testim if you: have breast cancer have or might have prostate cancer are pregnant or may become pregnant or are breastfeeding. Testim may harm your unborn or breastfeeding baby. Women who are pregnant or who may become pregnant should avoid contact with the area of skin where Testim has been applied. Talk to your healthcare provider before taking this medicine if you have any of the above conditions. What should I tell my healthcare provider before using Testim? Before you use Testim, tell your healthcare provider if you: have breast cancer have or might have prostate cancer have urinary problems due to an enlarged prostate have heart problems have liver or kidney problems have problems breathing while you sleep (sleep apnea) have any other medical conditions Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Using Testim with certain other medicines can affect each other. Especially, tell your healthcare provider if you take: insulin medicines that decrease blood clotting corticosteroids Know the medicines you take. Ask your healthcare provider or pharmacist for a list of these medicines, if you are not sure. Keep a list of them and show it to your healthcare provider and pharmacist when you get a new medicine. How should I use Testim? It is important that you apply Testim exactly as your healthcare provider tells you to. Your healthcare provider will tell you how much Testim to apply and when to apply it. Your healthcare provider may change your Testim dose. Do not change your Testim dose without talking to your healthcare provider. Testim is to be applied to the areas of your shoulders and upper arms that will be covered by a short sleeve T-shirt. Do not apply Testim to any other parts of your body such as your stomach area (abdomen), penis, or scrotum. Apply Testim at the same time each morning. Testim should be applied after showering or bathing. Wash your hands with soap and water right away after applying Testim. Avoid showering, swimming, or bathing for at least 2 hours after you apply Testim. Testim is flammable until dry. Let the Testim dry before smoking or going near an open flame. Let the application areas dry for a few minutes before putting on a T-shirt. Applying Testim: Before applying Testim, make sure that your shoulders and upper arms are clean, dry, and there is no broken skin. The application sites for Testim are the shoulders and upper arms that will be covered by a short sleeve T-shirt (see Figure A). Figure A Remove the cap from the tube and use the top of the cap to pierce the metal seal on the top of the tube by pushing or screwing the cap in. Squeeze all of the Testim out of the tube into the palm of your hand. Squeeze from the bottom of the tube to the top. Apply all of the Testim to the application sites. Rub the gel onto your skin for several seconds. Let the application site dry for a few minutes before putting on a T-shirt. Wash your hands with soap and water right away after applying Testim. What are the possible side effects of Testim? Testim can cause serious side effects including: See “What is the most important information I should know about Testim?” If you already have enlargement of your prostate gland your signs and symptoms can get worse while using Testim. This can include: increased urination at night trouble starting your urine stream having to pass urine many times during the day having an urge that you have to go to the bathroom right away having a urine accident being unable to pass urine or weak urine flow Possible increased risk of prostate cancer. Your healthcare provider should check you for prostate cancer or any other prostate problems before you start and while you use Testim. Blood clots in the legs or lungs. Signs and symptoms of a blood clot in your leg can include leg pain, swelling or redness. Signs and symptoms of a blood clot in your lungs can include difficulty breathing or chest pain. Possible increased risk of heart attack or stroke. In large doses Testim may lower your sperm count. Swelling of your ankles, feet, or body, with or without heart failure. This may cause serious problems for people who have heart, kidney or liver disease. Enlarged or painful breasts. Having problems breathing while you sleep (sleep apnea) Call your healthcare provider right away if you have any of the serious side effects listed above. The most common side effects of Testim include: skin irritation where Testim is applied increased red blood cell count headache increased blood pressure Other side effects include more erections than are normal for you or erections that last a long time. Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of Testim. For more information, ask your healthcare provider or pharmacist. Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store Testim? Store Testim between 59°F to 86°F (15°C to 30°C). Safely throw away used Testim in household trash. Be careful to prevent accidental exposure of children or pets. Keep Testim away from fire. Keep Testim and all medicines out of the reach of children. General information about the safe and effective use of Testim. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Testim for a condition for which it was not prescribed. Do not give Testim to other people, even if they have the same symptoms that you have. It may harm them. This Medication Guide summarizes the most important information about Testim. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about Testim that is written for health professionals. For more information, go to www.TESTIM.com or call 1-877-663-0412. What are the ingredients in Testim? Active ingredient: testosterone Inactive ingredients: purified water, pentadecalactone, carbopol, acrylates, propylene glycol, glycerin, polyethylene glycol, ethanol (74%), and tromethamine. This Medication Guide has been approved by the US Food and Drug Administration.

PATIENT INFORMATION FORTESTA® (FOR-tes -ta) (testosterone) Gel Read this Medication Guide before you start using FORTESTA and each time you get a refill. There may be new information. This information does not take the place of talking with your healthcare provider about your medical condition or your treatment. What is the most important information I should know about FORTESTA? Early signs and symptoms of puberty have happened in young children who were accidentally exposed to testosterone through contact with men using topical testosterone products like FORTESTA. Signs and symptoms of early puberty in a child may include: enlarged penis or clitoris early development of pubic hair increased erections or sex drive aggressive behavior FORTESTA can transfer from your body to others. Women and children should avoid contact with the unwashed or unclothed area where FORTESTA has been applied to your skin. Stop using FORTESTA and call your healthcare provider right away if you see any signs and symptoms in a child or a woman that may have occurred through accidental exposure to FORTESTA. Signs and symptoms of exposure to FORTESTA in a child may include: enlarged penis or clitoris early development of pubic hair increased erections or sex drive aggressive behavior Signs and symptoms of exposure to FORTESTA in women may include: changes in body hair a large increase in acne To lower the risk of transfer of FORTESTA from your body to others, you should follow these important instructions: Apply FORTESTA only to the front and inside area of your thighs that will be covered by clothing. Wash your hands right away with soap and water after applying FORTESTA. After the FORTESTA gel has dried, cover the application area with clothing. Keep the area covered until you have washed the application area well or have showered. If you expect another person to have skin-to-skin contact with your thighs, first wash the application area well with soap and water. If a woman or child makes contact with the FORTESTA application area, that area on the woman or child should be washed well with soap and water right away. What is FORTESTA? FORTESTA is a prescription medicine that contains testosterone. FORTESTA is used to treat adult males who have low or no testosterone due to certain medical conditions. Your healthcare provider will test your blood before you start taking and while you are taking FORTESTA. It is not known if FORTESTA is safe or effective to treat men who have low testosterone due to aging. It is not known if FORTESTA is safe or effective in children younger than 18 years old. Improper use of FORTESTA may affect bone growth in children. FORTESTA is a controlled substance (CIII) because it contains testosterone that can be a target for people who abuse prescription medicines. Keep your FORTESTA in a safe place to protect it. Never give FORTESTA to anyone else, even if they have the same symptoms you have. Selling or giving away this medicine may harm others and is against the law. FORTESTA is not meant for use in women. Who should not use FORTESTA? Do not use FORTESTA if you: have breast cancer have or might have prostate cancer are pregnant or may become pregnant or breast-feeding. FORTESTA may harm your unborn or breast-feeding baby. Women who are pregnant or who may become pregnant should avoid contact with the area of skin where FORTESTA has been applied. Talk to your healthcare provider before taking this medicine if you have any of the above conditions. What should I tell my healthcare provider before using FORTESTA? Before you use FORTESTA, tell your healthcare provider if you: have breast cancer have or might have prostate cancer have urinary problems due to an enlarged prostate have heart problems have liver or kidney problems have problems breathing while you sleep (sleep apnea) have any other medical conditions Tell your healthcare provider about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements. Using FORTESTA with certain other medicines can affect each other. Especially, tell your healthcare provider if you take: insulin medicines that decrease blood clotting corticosteroids Know the medicines you take. Ask your healthcare provider or pharmacist for a list of these medicines, if you are not sure. Keep a list of them and show it to your healthcare provider and pharmacist when you get a new medicine. How should I use FORTESTA? It is important that you apply FORTESTA exactly as your healthcare provider tells you to. Your healthcare provider will tell you how much FORTESTA to apply and when to apply it. Your healthcare provider may change your FORTESTA dose. Do not change your FORTESTA dose without talking to your healthcare provider. FORTESTA should be applied to the front and inner part of your thighs only. Do not apply FORTESTA to any other parts of your body such as your stomach area (abdomen), penis, scrotum, shoulders or upper arms. Apply FORTESTA in the morning. If you shower or bathe, FORTESTA should be applied afterwards. Avoid swimming, showering, or bathing for at least 2 hours after you apply FORTESTA. FORTESTA is flammable until dry. Let FORTESTA dry before smoking or going near an open flame. Apply FORTESTA only to areas that will be covered by shorts or pants . Wash your hands with soap and water right after you apply FORTESTA. Applying FORTESTA: Before using a new canister of FORTESTA for the first time, you will need to prime the pump. To prime the FORTESTA pump, gently push down on the pump 8 times. Do not use any FORTESTA that comes out while priming. Wash it down the sink or throw it in the trash to avoid accidental exposure to others. Your FORTESTA pump is now ready to use. Use FORTESTA exactly as your healthcare provider tells you to use it. Your healthcare provider will tell you the dose of FORTESTA that is right for you. Depress the pump to apply the medicine directly on clean, dry, intact skin of the front and inner part of your thighs. Use one finger to gently rub FORTESTA evenly onto the front and inner part of each thigh. Let the application site dry completely before putting on shorts or pants. Wash your hands right away with soap and water. What are the possible side effects of FORTESTA? See “What is the most important information I should know about FORTESTA?” FORTESTA can cause serious side effects including: If you already have enlargement of your prostate gland your signs and symptoms can get worse while using FORTESTA. This can include: increased urination at night trouble starting your urine stream having to pass urine many times during the day having an urge that you have to go to the bathroom right away having a urine accident being unable to pass urine or weak urine flow Possible increased risk of prostate cancer. Your healthcare provider should check you for prostate cancer or any other prostate problems before you start and while you use FORTESTA. Blood clots in the legs or lungs. Signs and symptoms of a blood clot in your leg can include leg pain, swelling or redness. Signs and symptoms of a blood clot in your lungs can include difficulty breathing or chest pain. Possible increased risk of heart attack or stroke. In large doses FORTESTA may lower your sperm count. Swelling of your ankles, feet, or body, with or without heart failure. Enlarged or painful breasts . Have problems breathing while you sleep (sleep apnea). Increased red blood cell count Call your healthcare provider right away if you have any of the serious side effects listed above. The most common side effects of FORTESTA include: skin redness or irritation where FORTESTA is applied increased in blood level of Prostate Specific Antigen (a test used to screen for prostate cancer) abnormal dreams Other side effects include more erections than are normal for you or erections that last a long time. Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of FORTESTA. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800- FDA-1088. How should I store FORTESTA? Store FORTESTA at 15°C to 30°C (59°F to 86°F). When it is time to throw away the canister, safely throw away used FORTESTA in household trash. Be careful to prevent accidental exposure of children or pets. Keep FORTESTA away from fire. Do not freeze FORTESTA. Keep FORTESTA and all medicines out of the reach of children. General information about FORTESTA Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use FORTESTA for a condition for which it was not prescribed. Do not give FORTESTA to other people, even if they have the same symptoms you have. It may harm them. This Medication Guide summarizes the most important information about FORTESTA. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about FORTESTA that is written for health professionals. For more information, go to www.fortestagel.com or call 1-800-462-3636. What are the ingredients in FORTESTA? Active ingredient: testosterone Inactive ingredients : propylene glycol, purified water, ethanol, 2-propanol, oleic acid, carbomer 1382, triethanolamine and butylated hydroxytoluene. This Medication Guide has been approved by the U.S. Food and Drug Administration

PATIENT INFORMATION ANDROGEL® (AN DROW JEL) (testosterone gel) 1.62% Read this Medication Guide before you start using ANDROGEL 1.62% and each time you get a refill. There may be new information. This information does not take the place of talking with your healthcare provider about your medical condition or treatment. What is the most important information I should know about ANDROGEL 1.62%? 1. Early signs and symptoms of puberty have happened in young children who were accidentally exposed to testosterone through contact with men using ANDROGEL 1.62%. Signs and symptoms of early puberty in a child may include: enlarged penis or clitoris early development of pubic hair increased erections or sex drive aggressive behavior ANDROGEL 1.62% can transfer from your body to others. 2. Women and children should avoid contact with the unwashed or unclothed area where ANDROGEL 1.62% has been applied to your skin. Stop using ANDROGEL 1.62% and call your healthcare provider right away if you see any signs and symptoms in a child or a woman that may have occurred through accidental exposure to ANDROGEL 1.62%. Signs and symptoms of exposure to ANDROGEL 1.62% in children may include: enlarged penis or clitoris early development of pubic hair increased erections or sex drive aggressive behavior Signs and symptoms of exposure to ANDROGEL 1.62% in women may include: changes in body hair a large increase in acne To lower the risk of transfer of ANDROGEL 1.62% from your body to others, you should follow these important instructions: Apply ANDROGEL 1.62% only to your shoulders and upper arms that will be covered by a short sleeve t-shirt. Wash your hands right away with soap and water after applying ANDROGEL 1.62%. After the gel has dried, cover the application area with clothing. Keep the area covered until you have washed the application area well or have showered. If you expect to have skin-to-skin contact with another person, first wash the application area well with soap and water. If a woman or child makes contact with the ANDROGEL 1.62% application area, that area on the woman or child should be washed well with soap and water right away. What is ANDROGEL 1.62%? ANDROGEL 1.62% is a prescription medicine that contains testosterone. ANDROGEL 1.62% is used to treat adult males who have low or no testosterone due to certain medical conditions. Your healthcare provider will test your blood before you start and while you are taking ANDROGEL 1.62%. It is not known if AndroGel 1.62% is safe or effective to treat men who have low testosterone due to aging. It is not known if ANDROGEL 1.62% is safe or effective in children younger than 18 years old. Improper use of ANDROGEL 1.62% may affect bone growth in children. ANDROGEL 1.62% is a controlled substance (CIII) because it contains testosterone that can be a target for people who abuse prescription medicines. Keep your ANDROGEL 1.62% in a safe place to protect it. Never give your ANDROGEL 1.62% to anyone else, even if they have the same symptoms you have. Selling or giving away this medicine may harm others and is against the law. ANDROGEL 1.62% is not meant for use in women. Who should not use ANDROGEL 1.62%? Do not use ANDROGEL 1.62% if you: have breast cancer have or might have prostate cancer are pregnant or may become pregnant or are breast-feeding. ANDROGEL 1.62% may harm your unborn or breast-feeding baby. Women who are pregnant or who may become pregnant should avoid contact with the area of skin where ANDROGEL 1.62% has been applied. Talk to your healthcare provider before taking this medicine if you have any of the above conditions. What should I tell my healthcare provider before using ANDROGEL 1.62%? Before you use ANDROGEL 1.62%, tell your healthcare provider if you: have breast cancer have or might have prostate cancer have urinary problems due to an enlarged prostate have heart problems have kidney or liver problems have problems breathing while you sleep (sleep apnea) have any other medical conditions Tell your healthcare provider about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements. Using ANDROGEL 1.62% with certain other medicines can affect each other. Especially, tell your healthcare provider if you take: insulin medicines that decrease blood clotting corticosteroids Know the medicines you take. Ask your healthcare provider or pharmacist for a list of all of your medicines, if you are not sure. Keep a list of them and show it to your healthcare provider and pharmacist when you get a new medicine. How should I use ANDROGEL 1.62%? It is important that you apply ANDROGEL 1.62% exactly as your healthcare provider tells you to. Your healthcare provider will tell you how much ANDROGEL 1.62% to apply and when to apply it. Your healthcare provider may change your ANDROGEL 1.62% dose. Do not change your ANDROGEL 1.62% dose without talking to your healthcare provider. ANDROGEL 1.62% is to be applied to the area of your shoulders and upper arms that will be covered by a short sleeve t-shirt. Do not apply ANDROGEL 1.62% to any other parts of your body such as your stomach area (abdomen), penis, scrotum, chest, armpits (axillae), or knees. Apply ANDROGEL 1.62% at the same time each morning. ANDROGEL 1.62% should be applied after showering or bathing. Wash your hands right away with soap and water after applying ANDROGEL 1.62%. Avoid showering, swimming or bathing for at least 2 hours after you apply ANDROGEL 1.62%. ANDROGEL 1.62% is flammable until dry. Let ANDROGEL 1.62% dry before smoking or going near an open flame. Let the application site dry completely before putting on a t-shirt. Applying ANDROGEL 1.62%: ANDROGEL 1.62% comes in a pump or in packets. Before applying ANDROGEL 1.62% make sure that your shoulders and upper arms are clean, dry, and that there is no broken skin. The application sites for ANDROGEL 1.62% are the upper arms and shoulders that will be covered by a short sleeve t-shirt (See Figure A). Figure A If you are using ANDROGEL 1.62% pump: Before using a new bottle of ANDROGEL 1.62 % for the first time, you will need to prime the pump. To prime the ANDROGEL 1.62% pump, slowly push the pump all the way down 3 times. Do not use any ANDROGEL 1.62% that came out while priming. Wash it down the sink to avoid accidental exposure to others. Your ANDROGEL 1.62% pump is now ready to use. Remove the cap from the pump. Then, position the nozzle over the palm of your hand and slowly push the pump all the way down. Apply ANDROGEL 1.62% to the application site. You may also apply ANDROGEL 1.62% directly to the application site. Wash your hands with soap and water right away. Find Your Dose as Prescribed by Your Healthcare Provider Application Method 1 PUMP DEPRESSION 20.25 mg Apply 1 pump depression of ANDROGEL 1.62% to 1 upper arm and shoulder. 2 PUMP DEPRESSIONS 40.5 mg Apply 1 pump depression of ANDROGEL 1.62% to 1 upper arm and shoulder and then apply 1 pump depression of ANDROGEL 1.62% to the opposite upper arm and shoulder. 3 PUMP DEPRESSIONS 60.75 mg Apply 2 pump depressions of ANDROGEL 1.62% to 1 upper arm and shoulder and then apply 1 pump depression of ANDROGEL 1.62% to the opposite upper arm and shoulder. 4 PUMP DEPRESSIONS 81 mg Apply 2 pump depressions of ANDROGEL 1.62% to 1 upper arm and shoulder and then apply 2 pump depressions of ANDROGEL 1.62% to the opposite upper arm and shoulder. If you are using ANDROGEL 1.62% packets: Tear open the packet completely at the dotted line. Squeeze from the bottom of the packet to the top. Squeeze all of the ANDROGEL 1.62% out of the packet into the palm of your hand. Apply ANDROGEL 1.62% to the application site. You may also apply ANDROGEL 1.62% directly to the application site. ANDROGEL 1.62% should be applied right away. Wash your hands with soap and water right away. Find Your Dose as Prescribed by Your Healthcare Provider Application Method One 20.25 mg packet 20.25 mg Apply 1 packet of ANDROGEL 1.62% to 1 upper arm and shoulder. One 40.5 mg packet 40.5 mg Apply half of the 40.5 mg packet of ANDROGEL 1.62% to 1 upper arm and shoulder and then apply the remaining packet contents to the opposite upper arm and shoulder. One 40.5 mg packet and one 20.25 mg packet 60.75 mg Apply one 40.5 mg packet of ANDROGEL 1.62% to 1 upper arm and shoulder and then apply one 20.25 mg packet of ANDROGEL 1.62% to the opposite upper arm and shoulder. Two 40.5 mg packets 81 mg Apply one 40.5 mg packet of ANDROGEL 1.62% to 1 upper arm and shoulder and then apply one 40.5 mg packet of ANDROGEL 1.62% to the opposite upper arm and shoulder. What are the possible side effects of ANDROGEL 1.62%? See “What is the most important information I should know about ANDROGEL 1.62%?” ANDROGEL 1.62% can cause serious side effects including: If you already have enlargement of your prostate gland your signs and symptoms can get worse while using ANDROGEL 1.62%. This can include: increased urination at night trouble starting your urine stream having to pass urine many times during the day having an urge that you have to go to the bathroom right away having a urine accident being unable to pass urine or weak urine flow Possible increased risk of prostate cancer. Your healthcare provider should check you for prostate cancer or any other prostate problems before you start and while you use ANDROGEL 1.62%. Blood clots in the legs or lungs. Signs and symptoms of a blood clot in your leg can include leg pain, swelling, or redness. Signs and symptoms of a blood clot in your lungs can include difficulty breathing or chest pain. Possible increased risk of heart attack or stroke. In large doses ANDROGEL 1.62% may lower your sperm count. Swelling of your ankles, feet, or body, with or without heart failure. Enlarged or painful breasts. Have problems breathing while you sleep (sleep apnea). Call your healthcare provider right away if you have any of the serious side effects listed above. The most common side effects of ANDROGEL 1.62% include: increased prostate specific antigen (a test used to screen for prostate cancer) mood swings hypertension increased red blood cell count skin irritation where ANDROGEL 1.62% is applied Other side effects include more erections than are normal for you or erections that last a long time. Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of ANDROGEL 1.62%. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1- 800-FDA-1088. How should I store ANDROGEL 1.62%? Store ANDROGEL 1.62% at 59°F to 86°F (15°C to 30°C). When it is time to throw away the pump or packets, safely throw away used ANDROGEL 1.62% in household trash. Be careful to prevent accidental exposure of children or pets. Keep ANDROGEL 1.62% away from fire. Keep ANDROGEL 1.62% and all medicines out of the reach of children. General information about the safe and effective use of ANDROGEL 1.62% Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use ANDROGEL 1.62% for a condition for which it was not prescribed. Do not give ANDROGEL 1.62% to other people, even if they have the same symptoms you have. It may harm them. This Medication Guide summarizes the most important information about ANDROGEL 1.62%. If you would like more information, talk to your healthcare provider. You can ask your pharmacist or healthcare provider for information about ANDROGEL 1.62% that is written for health professionals. For more information, go to www.androgel.com or call 1-800-633-9110. What are the ingredients in ANDROGEL 1.62%? Active ingredient: testosterone Inactive ingredients: carbopol 980, ethyl alcohol, isopropyl myristate, purified water and sodium hydroxide.

SIDE EFFECTS Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. In a controlled multicenter, open label, non-comparative 90-day clinical study, 149 hypogonadal patients were treated with FORTESTA [see Clinical Studies]. Adverse reactions occurred in 22.8% (34/149) of patients. The most common adverse reaction reported in this study was skin reactions associated with the site of application (16.1%; 24/149) of which 79% (19/24) were mild, and the remainder were moderate (21%; 5/24) (Table 3). Table 3 – Adverse Reactions Reported in >1% Patients in the US Phase 3 Clinical Trial of FORTESTA Adverse Reaction Number (%) of Patients N = 149 Skin reaction 24 (16.1%) Prostatic specific antigen increased 2 (1.3%) Abnormal dreams 2 (1.3%) During the 90 day trial 5 patients (3.4%) discontinued treatment because of adverse reactions. These reactions were: 1 patient with contact dermatitis (considered probably related to FORTESTA application), 1 with application site reaction (considered probably related to FORTESTA application), 1 with gastrointestinal hypomotility (considered possibly related to FORTESTA application), 1 with severe dyspnea (considered not related to FORTESTA application), and 1 with moderate contusion (considered not related to FORTESTA application). Postmarketing Experience The following adverse reactions have been identified during post approval use of FORTESTA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure (Table 4). Table 4 - Adverse Drug Reactions from Post approval Experience of FORTESTA by System System Organ Class Adverse Reaction Blood and lymphatic system disorders Polycythemia Eye disorders Vitreous detachment Gastrointestinal disorders Abdominal symptoms General disorders and administrative site conditions Application site erythema, irritation, pruritus, and swelling; fatigue, influenza like illness, and malaise. Investigations Decreased serum testosterone, increased hematocrit and hemoglobin Musculoskeletal and connective tissue disorders Pain in extremity Nervous system disorders Dizziness, headache, and migraine Reproductive system and breast disorders Erectile dysfunction, and priapism Skin and subcutaneous tissue disorders Allergic dermatitis, erythema, rash, and papular rash. Vascular disorders Venous thromboembolism Cardiovascular disorders Myocardial infarction, stroke Secondary Exposure To Testosterone In Children Cases of secondary exposure to testosterone resulting in virilization of children have been reported in postmarketing surveillance of testosterone gel products. Signs and symptoms of these reported cases have included enlargement of the clitoris (with surgical intervention) or the penis, development of pubic hair, increased erections and libido, aggressive behavior, and advanced bone age. In most cases with a reported outcome, these signs and symptoms were reported to have regressed with removal of the testosterone gel exposure. In a few cases, however, enlarged genitalia did not fully return to age appropriate normal size, and bone age remained modestly greater than chronological age. In some of the cases, direct contact with the sites of application on the skin of men using testosterone gel was reported. In at least one reported case, the reporter considered the possibility of secondary exposure from items such as the testosterone gel user’s shirts and/or other fabric, such as towels and sheets [see WARNINGS AND PRECAUTIONS]. DRUG INTERACTIONS Insulin Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease insulin requirements. Oral Anticoagulants Changes in anticoagulant activity may be seen with androgens, therefore more frequent monitoring of international normalized ratio (INR) and prothrombin time are recommended in patients taking anticoagulants, especially at the initiation and termination of androgen therapy. Corticosteroids The concurrent administration of testosterone with adrenocorticotropic hormone (ACTH) or corticosteroids may result in increased fluid retention and requires careful monitoring particularly in patients with cardiac, renal or hepatic disease. Drug Abuse And Dependence Controlled Substance FORTESTA contains testosterone, a Schedule III controlled substance in the Controlled Substances Act. Abuse Drug abuse is intentional non-therapeutic use of a drug, even once, for its rewarding psychological and physiological effects. Abuse and misuse of testosterone are seen in male and female adults and adolescents. Testosterone, often in combination with other anabolic androgenic steroids (AAS), and not obtained by prescription through a pharmacy, may be abused by athletes and bodybuilders. There have been reports of misuse of men taking higher doses of legally obtained testosterone than prescribed and continuing testosterone despite adverse events or against medical advice. Abuse-Related Adverse Reactions Serious adverse reactions have been reported in individuals who abuse anabolic androgenic steroids, and include cardiac arrest, myocardial infarction, hypertrophic cardiomyopathy, congestive heart failure, cerebrovascular accident, hepatotoxicity, and serious psychiatric manifestations, including major depression, mania, paranoia, psychosis, delusions, hallucinations, hostility and aggression. The following adverse reactions have also been reported in men: transient ischemic attacks, convulsions, hypomania, irritability, dyslipidemias, testicular atrophy, subfertility, and infertility. The following additional adverse reactions have been reported in women: hirsutism, virilization, deepening of voice, clitoral enlargement, breast atrophy, male-pattern baldness, and menstrual irregularities. The following adverse reactions have been reported in male and female adolescents: premature closure of bony epiphyses with termination of growth, and precocious puberty. Because these reactions are reported voluntarily from a population of uncertain size and may include abuse of other agents, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Dependence Behaviors Associated with Addiction Continued abuse of testosterone and other anabolic steroids, leading to addiction is characterized by the following behaviors: Taking greater dosages than prescribed Continued drug use despite medical and social problems due to drug use Spending significant time to obtain the drug when supplies of the drug are interrupted Giving a higher priority to drug use than other obligations Having difficulty in discontinuing the drug despite desires and attempts to do so Experiencing withdrawal symptoms upon abrupt discontinuation of use Physical dependence is characterized by withdrawal symptoms after abrupt drug discontinuation or a significant dose reduction of a drug. Individuals taking supratherapeutic doses of testosterone may experience withdrawal symptoms lasting for weeks or months which include depressed mood, major depression, fatigue, craving, restlessness, irritability, anorexia, insomnia, decreased libido and hypogonadotropic hypogonadism. Drug dependence in individuals using approved doses of testosterone for approved indications has not been documented.

WARNINGS Included as part of the PRECAUTIONS section. PRECAUTIONS Worsening Of Benign Prostatic Hyperplasia (BPH) And Potential Risk Of Prostate Cancer Men with BPH treated with androgens are at an increased risk for worsening of signs and symptoms of BPH. Monitor patients with BPH for worsening signs and symptoms. Patients treated with androgens may be at increased risk for prostate cancer. Evaluate patients for prostate cancer prior to initiating and during treatment with androgens [see CONTRAINDICATIONS]. Potential For Secondary Exposure To Testosterone Cases of secondary exposure resulting in virilization of children have been reported in postmarketing surveillance. Signs and symptoms have included enlargement of the penis or clitoris, development of pubic hair, increased erections and libido, aggressive behavior, and advanced bone age. In most cases, these signs and symptoms regressed with removal of the exposure to testosterone gel. In a few cases, however, enlarged genitalia did not fully return to age-appropriate normal size, and bone age remained modestly greater than chronological age. The risk of transfer was increased in some of these cases by not adhering to precautions for the appropriate use of the topical testosterone product. Children and women should avoid contact with unwashed or unclothed application sites in men using Vogelxo [see DOSAGE AND ADMINISTRATION, Use In Specific Populations and CLINICAL PHARMACOLOGY]. Inappropriate changes in genital size or development of pubic hair or libido in children, or changes in body hair distribution, significant increase in acne, or other signs of virilization in adult women should be brought to the attention of a physician and the possibility of secondary exposure to testosterone gel should also be brought to the attention of a physician. Testosterone gel should be promptly discontinued until the cause of virilization has been identified. Polycythemia Increases in hematocrit, reflective of increases in red blood cell mass, may require lowering or discontinuation of testosterone. Check hematocrit prior to initiating treatment. It would also be appropriate to re-evaluate the hematocrit 3 to 6 months after starting treatment, and then annually. If hematocrit becomes elevated, stop therapy until hematocrit decreases to an acceptable concentration. An increase in red blood cell mass may increase the risk of thromboembolic events. Venous Thromboembolism There have been postmarketing reports of venous thromboembolic events, including deep vein thrombosis (DVT) and pulmonary embolism (PE), in patients using testosterone products, such as Vogelxo. Evaluate patients who report signs and symptoms of pain, edema, warmth and erythema in the lower extremity for DVT and those who present with acute shortness of breath for PE. If a venous thromboembolic event is suspected, discontinue treatment with Vogelxo and initiate appropriate workup and management [see ADVERSE REACTIONS]. Cardiovascular Risk Long term clinical safety trials have not been conducted to assess the cardiovascular outcomes of testosterone replacement therapy in men. To date, epidemiologic studies and randomized controlled trials have been inconclusive for determining the risk of major adverse cardiovascular events (MACE), such as non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death, with the use of testosterone compared to non-use. Some studies, but not all, have reported an increased risk of MACE in association with use of testosterone replacement therapy in men. Patients should be informed of this possible risk when deciding whether to use or to continue to use Vogelxo. Use In Women Due to lack of controlled evaluations in women and potential virilizing effects, Vogelxo is not indicated for use in women. Potential For Adverse Effects On Spermatogenesis With large doses of exogenous androgens, including Vogelxo, spermatogenesis may be suppressed through feedback inhibition of pituitary follicle-stimulating hormone (FSH) which could possibly lead to adverse effects on semen parameters including sperm count. Hepatic Adverse Effects Prolonged use of high doses of orally active 17-alpha-alkyl androgens (e.g., methyltestosterone) has been associated with serious hepatic adverse effects (peliosis hepatis, hepatic neoplasms, cholestatic hepatitis, and jaundice). Peliosis hepatis can be a life-threatening or fatal complication. Long-term therapy with intramuscular testosterone enanthate, which elevate blood levels for prolonged periods, has produced multiple hepatic adenomas. Vogelxo is not known to produce these adverse effects. Nonetheless, patients should be instructed to report any signs or symptoms of hepatic dysfunction (e.g., jaundice). If these occur, promptly discontinue Vogelxo while the cause is evaluated. Edema Androgens, including Vogelxo, may promote retention of sodium and water. Edema, with or without congestive heart failure, may be a serious complication in patients with preexisting cardiac, renal, or hepatic disease. In addition to discontinuation of the drug, diuretic therapy may be required. Gynecomastia Gynecomastia occasionally develops and occasionally persists in patients being treated for hypogonadism [see ADVERSE REACTIONS]. Sleep Apnea The treatment of hypogonadal men with testosterone may potentiate sleep apnea in some patients, especially those with risk factors such as obesity or chronic lung diseases. Lipids Changes in the serum lipid profile may occur. Monitor the lipid profile periodically, particularly after starting testosterone therapy and after any dose increases. Hypercalcemia Androgens, including Vogelxo, should be used with caution in cancer patients at risk of hypercalcemia (and associated hypercalciuria). Regular monitoring of serum calcium concentrations is recommended in these patients. Decreased Thyroxine-binding Globulin Androgens, including Vogelxo, may decrease concentrations of thyroxine-binding globulins, resulting in decreased total T4 serum concentrations and increased resin uptake of T3 and T4. Free thyroid hormone levels remain unchanged, however, and there is no clinical evidence of thyroid dysfunction. Flammability Alcohol-based products, including Vogelxo, are flammable; therefore, patients should be advised to avoid fire, flame or smoking until the Vogelxo has dried. Patient Counseling Information Advise the patient to read the FDA-approved patient labeling (Medication Guide). Men with Known or Suspected Carcinoma of the Breast or Prostate Men with known or suspected prostate or breast cancer should not use Vogelxo [see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS]. Potential for Secondary Exposure to Testosterone and Steps to Prevent Secondary Exposure Secondary exposure to testosterone in children and women can occur with the use of testosterone gel products in men. Cases of secondary exposure to testosterone have been reported in children. Physicians should advise patients of the reported signs and symptoms of secondary exposure which may include the following: In children; unexpected sexual development including inappropriate enlargement of the penis or clitoris, premature development of pubic hair, increased erections, and aggressive behavior In women; changes in hair distribution, increase in acne, or other signs of testosterone effects The possibility of secondary exposure to Vogelxo should be brought to the attention of a healthcare provider Vogelxo should be promptly discontinued until the cause of virilization is identified Strict adherence to the following precautions is advised to minimize the potential for secondary exposure to testosterone from Vogelxo in men [see Medication Guide] Children and women should avoid contact with unwashed or unclothed application site(s) of men using Vogelxo Patients using Vogelxo should apply the product as directed and strictly adhere to the following: Wash hands with soap and water immediately after application Cover the application site(s) with clothing after the gel has dried Wash the application site(s) thoroughly with soap and water prior to any situation where skin-to-skin contact of the application site with another person is anticipated In the event that unwashed or unclothed skin to which Vogelxo has been applied comes in contact with the skin of another person, the general area of contact on the other person should be washed with soap and water as soon as possible [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY]. Potential Adverse Reactions with Androgens Patients should be informed that treatment with androgens may lead to adverse reactions which include: Changes in urinary habits, such as increased urination at night, trouble starting the urine stream, passing urine many times during the day, having an urge to go the bathroom right away, having a urine accident, or being unable to pass urine or weak urine flow Breathing disturbances, including those associated with sleep or excessive daytime sleepiness. Too frequent or persistent erections of the penis Nausea, vomiting, changes in skin color, or ankle swelling Patients Should Be Advised of the Following Instructions for Use Read the Medication Guide before starting Vogelxo therapy and reread it each time the prescription is renewed. Vogelxo should be applied and used appropriately to maximize the benefits and to minimize the risk of secondary exposure in children and women. Keep Vogelxo out of the reach of children. The package is not child resistant. Vogelxo is an alcohol-based product and is flammable; therefore avoid fire, flame or smoking until the gel has dried. It is important to adhere to all recommended monitoring. Report any changes in their state of health, such as changes in urinary habits, breathing, sleep, and mood. Vogelxo is prescribed to meet the patient's specific needs; therefore, the patient should never share Vogelxo with anyone. Vogelxo should be applied topically once daily at approximately the same time each day to clean dry skin of the shoulders and/or upper arms. Vogelxo should not be applied to the scrotum, penis, or abdomen. Wait 2 hours before washing or swimming following application of Vogelxo. This will ensure that the greatest amount of Vogelxo is absorbed. Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment Of Fertility Carcinogenicity Testosterone has been tested by subcutaneous injection and implantation in mice and rats. In mice, the implant induced cervical-uterine tumors, which metastasized in some cases. There is suggestive evidence that injection of testosterone into some strains of female mice increases their susceptibility to hepatoma. Testosterone is also known to increase the number of tumors and decrease the degree of differentiation of chemically induced carcinomas of the liver in rats. Mutagenesis Testosterone was negative in the in vitro Ames and in the in vivo mouse micronucleus assays. Impairment of Fertility The administration of exogenous testosterone has been reported to suppress spermatogenesis in the rat, dog and non-human primates, which was reversible on cessation of the treatment. Use In Specific Populations Pregnancy Pregnancy Category X Vogelxo is contraindicated in pregnant women or in women who may become pregnant. Testosterone is teratogenic and may cause fetal harm. Exposure of a fetus to androgens, such as testosterone, may result in varying degrees of virilization. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be made aware of the potential hazard to the fetus. Nursing Mothers Although it is not known how much testosterone transfers into human milk, Vogelxo is contraindicated in nursing women because of the potential for serious adverse reactions in nursing infants. Pediatric Use The safety and efficacy of Vogelxo in pediatric patients less than 18 years old have not been established. Improper use may result in acceleration of bone age and premature closure of epiphyses. Geriatric Use There is insufficient long-term safety data in geriatric patients to assess the potentially increased risks of cardiovascular disease and prostate cancer [see WARNINGS AND PRECAUTIONS]. Renal Impairment No studies were conducted in patients with renal impairment. Hepatic Impairment No studies were conducted in patients with hepatic impairment.

WARNINGS Included as part of the PRECAUTIONS section. PRECAUTIONS Worsening Of Benign Prostatic Hyperplasia (BPH) And Potential Risk Of Prostate Cancer Patients with BPH treated with androgens are at an increased risk for worsening of signs and symptoms of BPH. Monitor patients with BPH for worsening signs and symptoms. Patients treated with androgens may be at increased risk for prostate cancer. Evaluate patients for prostate cancer prior to initiating and during treatment with androgens [see CONTRAINDICATIONS]. Potential For Secondary Exposure To Testosterone Cases of secondary exposure resulting in virilization of children have been reported in postmarketing surveillance. Signs and symptoms have included enlargement of the penis or clitoris, development of pubic hair, increased erections and libido, aggressive behavior, and advanced bone age. In most cases, these signs and symptoms regressed with removal of the exposure to testosterone gel. In a few cases, however, enlarged genitalia did not fully return to age-appropriate normal size, and bone age remained modestly greater than chronological age. The risk of transfer was increased in some of these cases by not adhering to precautions for the appropriate use of the topical testosterone product. Children and women should avoid contact with unwashed or unclothed application sites in men using Testim [see DOSAGE AND ADMINISTRATION, Use in Specific Populations and CLINICAL PHARMACOLOGY]. Inappropriate changes in genital size or development of pubic hair or libido in children, or changes in body hair distribution, significant increase in acne, or other signs of virilization in adult women should be brought to the attention of a physician and the possibility of secondary exposure to testosterone gel should also be brought to the attention of a physician. Testosterone gel should be promptly discontinued until the cause of virilization has been identified. Polycythemia Increases in hematocrit, reflective of increases in red blood cell mass, may require lowering or discontinuation of testosterone. Check hematocrit prior to initiating treatment. It would also be appropriate to re-evaluate the hematocrit 3 to 6 months after starting treatment, and then annually. If hematocrit becomes elevated, stop therapy until hematocrit decreases to an acceptable concentration. An increase in red blood cell mass may increase the risk of thromboembolic events. Venous Thromboembolism There have been postmarketing reports of venous thromboembolic events, including deep vein thrombosis (DVT) and pulmonary embolism (PE), in patients using testosterone products, such as Testim. Evaluate patients who report symptoms of pain, edema, warmth and erythema in the lower extremity for DVT and those who present with acute shortness of breath for PE. If a venous thromboembolic event is suspected, discontinue treatment with Testim and initiate appropriate workup and management [see ADVERSE REACTIONS]. Cardiovascular Risk Long term clinical safety trials have not been conducted to assess the cardiovascular outcomes of testosterone replacement therapy in men. To date, epidemiologic studies and randomized controlled trials have been inconclusive for determining the risk of major adverse cardiovascular events (MACE), such as non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death, with the use of testosterone compared to non-use. Some studies, but not all, have reported an increased risk of MACE in association with use of testosterone replacement therapy in men. Patients should be informed of this possible risk when deciding whether to use or to continue to use Testim. Use in Women Due to lack of controlled evaluations in women and potential virilizing effects, Testim is not indicated for use in women [see CONTRAINDICATIONS and Use in Specific Populations]. Potential For Adverse Effects On Spermatogenesis With large doses of exogenous androgens, including Testim, spermatogenesis may be suppressed through feedback inhibition of pituitary follicle-stimulating hormone (FSH) which could possibly lead to adverse effects on semen parameters including sperm count. Hepatic Adverse Effects Prolonged use of high doses of orally active 17-alpha-alkyl androgens (e.g., methyltestosterone) has been associated with serious hepatic adverse effects (peliosis hepatis, hepatic neoplasms, cholestatic hepatitis, and jaundice). Peliosis hepatis can be a life-threatening or fatal complication. Long-term therapy with intramuscular testosterone enanthate, which elevates blood levels for prolonged periods, has produced multiple hepatic adenomas. Testim is not known to cause these adverse effects. Nonetheless, patients should be instructed to report any signs or symptoms of hepatic dysfunction (e.g., jaundice). If these occur, promptly discontinue Testim while the cause is evaluated. Edema Androgens, including Testim, may promote retention of sodium and water. Edema, with or without congestive heart failure, may be a serious complication in patients with preexisting cardiac, renal, or hepatic disease. In addition to discontinuation of the drug, diuretic therapy may be required. Gynecomastia Gynecomastia occasionally develops and occasionally persists in patients being treated for hypogonadism [see ADVERSE REACTIONS]. Sleep Apnea The treatment of hypogonadal men with testosterone may potentiate sleep apnea in some patients, especially those with risk factors such as obesity or chronic lung diseases. Lipids Changes in the serum lipid profile may occur. Monitor the lipid profile periodically, particularly after starting testosterone therapy and after dose increases. Hypercalcemia Androgens, including Testim, should be used with caution in cancer patients at risk of hypercalcemia (and associated hypercalciuria). Regular monitoring of serum calcium concentrations is recommended in these patients. Decreased Thyroxine-binding Globulin Androgens, including Testim, may decrease concentrations of thyroxine-binding globulins, resulting in decreased total T4 serum concentrations and increased resin uptake of T3 and T4. Free thyroid hormone concentrations remain unchanged, however, and there is no clinical evidence of thyroid dysfunction. Flammability Alcohol-based products, including Testim, are flammable; therefore, patients should be advised to avoid fire, flame or smoking until the Testim has dried. Patient Counseling Information See FDA-approved patient labeling (Medication Guide). Advise patients of the following: Men With Known Or Suspected Carcinoma Of The Breast Or Prostate Men with known or suspected prostate or breast cancer should not use Testim® [see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS]. Potential For Secondary Exposure To Testosterone And Steps To Prevent Secondary Exposure Secondary exposure to testosterone in children and women can occur with the use of testosterone gel in men. Cases of secondary exposure to testosterone have been reported in children. Physicians should advise patients of the reported signs and symptoms of secondary exposure which may include the following: In children; unexpected sexual development including inappropriate enlargement of the penis or clitoris, premature development of pubic hair, increased erections, and aggressive behavior In women; changes in hair distribution, increase in acne, or other signs of testosterone effects The possibility of secondary exposure to testosterone gel should be brought to the attention of a healthcare provider Testim should be promptly discontinued until the cause of virilization is identified Strict adherence to the following precautions is advised to minimize the potential for secondary exposure to testosterone from testosterone gel in men [see Medication Guide]: Children and women should avoid contact with unwashed or unclothed application site(s) of men using testosterone gel Patients using Testim should apply the product as directed and strictly adhere to the following: Wash hands with soap and water immediately after application Cover the application site(s) with clothing after the gel has dried Wash the application site(s) thoroughly with soap and water prior to any situation where skin-to-skin contact of the application site with another person is anticipated In the event that unwashed or unclothed skin to which Testim has been applied comes in contact with the skin of another person, the general area of contact on the other person should be washed with soap and water as soon as possible [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY]. Potential Adverse Reactions With Androgens Patients should be informed that treatment with androgens may lead to adverse reactions which include: Changes in urinary habits, such as increased urination at night, trouble starting the urine stream, passing urine many times during the day, having an urge to go the bathroom right away, having a urine accident, or being unable to pass urine or weak urine flow Breathing disturbances, including those associated with sleep or excessive daytime sleepiness. Too frequent or persistent erections of the penis Nausea, vomiting, changes in skin color, or ankle swelling Patients Should Be Advised Of The Following Instructions For Use Read the Medication Guide before starting Testim therapy and reread it each time the prescription is renewed. Testim should be applied and used appropriately to maximize the benefits and to minimize the risk of secondary exposure in children and women Keep Testim out of the reach of children. The package is not child resistant. Testim is an alcohol-based product and is flammable; therefore avoid fire, flame or smoking until the gel has dried It is important to adhere to all recommended monitoring Report any changes in their state of health, such as changes in urinary habits, breathing, sleep, and mood Testim is prescribed to meet the patient’s specific needs; therefore, the patient should never share Testim with anyone. Testim should be applied once daily at approximately the same time each day to clean dry skin of the shoulders and/or upper arms. Testim should not be applied to the scrotum, penis, or abdomen. Wait 2 hours before swimming or washing following application of Testim. This will ensure that the greatest amount of Testim is absorbed into their system. Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment Of Fertility Carcinogenicity Testosterone has been tested by subcutaneous injection and implantation in mice and rats. In mice, the implant induced cervical-uterine tumors, which metastasized in some cases. There is suggestive evidence that injection of testosterone into some strains of female mice increases their susceptibility to hepatoma. Testosterone is also known to increase the number of tumors and decrease the degree of differentiation of chemically induced carcinomas of the liver in rats. Mutagenesis Testosterone was negative in the in vitro Ames and in the in vivo mouse micronucleus assays. Impairment Of Fertility The administration of exogenous testosterone has been reported to suppress spermatogenesis in the rat, dog and non-human primates, which was reversible on cessation of the treatment. Use In Specific Populations Pregnancy Pregnancy Category X [see CONTRAINDICATIONS]: Testim® is contraindicated in pregnant women or in women who may become pregnant. Testosterone is teratogenic and may cause fetal harm. Exposure of a fetus to androgens, such as testosterone, may result in varying degrees of virilization. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be made aware of the potential hazard to the fetus. Nursing Mothers Although it is not known how much testosterone transfers into human milk, Testim is contraindicated in nursing women because of the potential for serious adverse reactions in nursing infants [see CONTRAINDICATIONS]. Pediatric Use The safety and effectiveness of Testim in pediatric patients less than 18 years old have not been established. Improper use may result in acceleration of bone age and premature closure of epiphyses. Geriatric Use There is insufficient long-term safety data in geriatric patients to assess the potentially increased risks of cardiovascular disease and prostate cancer [see WARNINGS AND PRECAUTIONS]. Renal Impairment No studies were conducted in patients with renal impairment. Hepatic Impairment No studies were conducted in patients with hepatic impairment.

WARNINGS Included as part of the "PRECAUTIONS" Section PRECAUTIONS Worsening Of Benign Prostatic Hyperplasia (BPH) And Potential Risk Of Prostate Cancer Patients with BPH treated with androgens are at an increased risk of worsening of signs and symptoms of BPH. Monitor patients with BPH for worsening signs and symptoms. Patients treated with androgens may be at increased risk for prostate cancer. Evaluation of the patients for the presence of prostate cancer prior to initiating and during treatment with androgens is appropriate [see CONTRAINDICATIONS]. Potential For Secondary Exposure To Testosterone Cases of secondary exposure resulting in virilization of children have been reported in postmarketing surveillance of testosterone gel products. Signs and symptoms have included enlargement of the penis or clitoris, development of pubic hair, increased erections and libido, aggressive behavior, and advanced bone age. In most cases, these signs and symptoms regressed with removal of the exposure to testosterone gel. In a few cases, however, enlarged genitalia did not fully return to age-appropriate normal size, and bone age remained modestly greater than chronological age. The risk of transfer was increased in some of these cases by not adhering to precautions for the appropriate use of the topical testosterone product. Children and women should avoid contact with unwashed or unclothed application sites in men using FORTESTA [see DOSAGE AND ADMINISTRATION, Use In Specific Populations and CLINICAL PHARMACOLOGY]. Inappropriate changes in genital size or development of pubic hair or libido in children, or changes in body hair distribution, significant increase in acne, or other signs of virilization in adult women should be brought to the attention of a physician and the possibility of secondary exposure to testosterone gel should also be brought to the attention of a physician. Testosterone gel should be promptly discontinued until the cause of virilization has been identified. Polycythemia Increases in hematocrit, reflective of increases in red blood cell mass, may require lowering or discontinuation of testosterone. Check hematocrit prior to initiating treatment. It would also be appropriate to re-evaluate the hematocrit 3 to 6 months after starting treatment, and then annually. If hematocrit becomes elevated, stop therapy until hematocrit decreases to an acceptable concentration. An increase in red blood cell mass may increase the risk of thromboembolic events. Venous Thromboembolism There have been Postmarketing reports of venous thromboembolic events, including deep vein thrombosis (DVT) and pulmonary embolism (PE), in patients using testosterone products, such as FORTESTA. Evaluate patients who report symptoms of pain, edema, warmth and erythema in the lower extremity for DVT and those who present with acute shortness of breath for PE. If a venous thromboembolic event is suspected, discontinue treatment with FORTESTA and initiate appropriate workup and management. Cardiovascular Risk Long term clinical safety trials have not been conducted to assess the cardiovascular outcomes of testosterone replacement therapy in men. To date, epidemiologic studies and randomized controlled trials have been inconclusive for determining the risk of major adverse cardiovascular events (MACE), such as non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death, with the use of testosterone compared to non-use. Some studies, but not all, have reported an increased risk of MACE in association with use of testosterone replacement therapy in men. Patients should be informed of this possible risk when deciding whether to use or to continue to use FORTESTA. Abuse Of Testosterone And Monitoring Of Serum Testosterone Concentrations Testosterone has been subject to abuse, typically at doses higher than recommended for the approved indication and in combination with other anabolic androgenic steroids. Anabolic androgenic steroid abuse can lead to serious cardiovascular and psychiatric adverse reactions [see Drug Abuse And Dependence]. If testosterone abuse is suspected, check serum testosterone concentrations to ensure they are within therapeutic range. However, testosterone levels may be in the normal or subnormal range in men abusing synthetic testosterone derivatives. Counsel patients concerning the serious adverse reactions associated with abuse of testosterone and anabolic androgenic steroids. Conversely, consider the possibility of testosterone and anabolic androgenic steroid abuse in suspected patients who present with serious cardiovascular or psychiatric adverse events. Use In Women Due to the lack of controlled evaluations in women and potential virilizing effects, FORTESTA is not indicated for use in women [see CONTRAINDICATIONS and Use In Specific Populations]. Potential For Adverse Effects On Spermatogenesis With large doses of exogenous androgens, including FORTESTA, spermatogenesis may be suppressed through feedback inhibition of pituitary FSH which could possibly lead to adverse effects on semen parameters including sperm count. Hepatic Adverse Effects Prolonged use of high doses of orally active 17-alpha-alkyl androgens (e.g. methyltestosterone) has been associated with serious hepatic adverse effects (peliosis hepatis, hepatic neoplasms, cholestatic hepatitis and jaundice). Peliosis hepatis can be a life-threatening or fatal complication. Long-term therapy with testosterone enanthate has produced multiple hepatic adenomas. FORTESTA is not known to cause these adverse effects. Edema Androgens, including FORTESTA, may promote retention of sodium and water. Edema, with or without congestive heart failure, may be a serious complication in patients with pre-existing cardiac, renal, or hepatic disease [see ADVERSE REACTIONS]. Gynecomastia Gynecomastia may develop and persist in patients being treated with androgens, including FORTESTA, for hypogonadism. Sleep Apnea The treatment of hypogonadal men with testosterone may potentiate sleep apnea in some patients, especially those with risk factors such as obesity or chronic lung diseases. Lipids Changes in serum lipid profile may require dose adjustment or discontinuation of testosterone therapy. Hypercalcemia Androgens, including FORTESTA, should be used with caution in cancer patients at risk of hypercalcemia (and associated hypercalciuria). Regular monitoring of serum calcium concentrations is recommended in these patients. Decreased Thyroxine-Binding Globulin Androgens, including FORTESTA, may decrease concentrations of thyroxin-binding globulins, resulting in decreased total T4 serum concentrations and increased resin uptake of T3 and T4. Free thyroid hormone concentrations remain unchanged, however, and there is no clinical evidence of thyroid dysfunction. Flammability Alcohol based products, including FORTESTA, are flammable; therefore, patients should be advised to avoid smoking, fire or flame until the FORTESTA gel has dried. Patient Counseling Information See FDA-approved PATIENT INFORMATION. Patients should be informed of the following information: Use In Men With Known Or Suspected Prostate Or Breast Cancer Men with known or suspected prostate or breast cancer should not use FORTESTA [see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS]. Potential For Secondary Exposure To Testosterone And Steps To Prevent Secondary Exposure Secondary exposure to testosterone in children and women can occur with the use of testosterone gel in men. Cases of secondary exposure to testosterone in children have been reported. Physicians should advise patients of the reported signs and symptoms of secondary exposure which may include the following: In children; unexpected sexual development including inappropriate enlargement of the penis or clitoris, premature development of pubic hair, increased erections, and aggressive behavior. In women; changes in hair distribution, increase in acne, or other signs of testosterone effects. The possibility of secondary exposure to FORTESTA should be brought to the attention of a healthcare provider. FORTESTA should be promptly discontinued until the cause of virilization is identified. Strict adherence to the following precautions is advised to minimize the potential for secondary exposure to testosterone from FORTESTA in men [see PATIENT INFORMATION]: Children and women should avoid contact with unwashed or unclothed application site(s) of men using FORTESTA. Patients using FORTESTA should apply the product as directed and strictly adhere to the following: Wash hands with soap and water after application. Cover the application site(s) with clothing after the gel has dried. Wash the application site(s ) thoroughly with soap and water prior to any situation where skinto- skin contact of the application site with another person is anticipated. In the event that unwashed or unclothed skin to which FORTESTA has been applied comes in contact with the skin of another person, the general area of contact on the other person should be washed with soap and water as soon as possible [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY]. Potential Adverse Reactions With Androgens Patients should be informed that treatment with androgens may lead to adverse reactions which include: Changes in urinary habits such as increased urination at night, trouble starting your urine stream, passing urine many times during the day, having an urge that you have to go to the bathroom right away, having a urine accident, being unable to pass urine and weak urine flow. Breathing disturbances, including those associated with sleep, or excessive daytime sleepiness. Too frequent or persistent erections of the penis. Nausea, vomiting, changes in skin color, or ankle swelling. Patients Should Be Advised Of The Following Instructions For Use Read the Medication Guide before starting FORTESTA therapy and reread it each time the prescription is renewed. FORTESTA should be applied and used appropriately to maximize the benefits and to minimize the risk of secondary exposure in children and women. Keep FORTESTA out of the reach of children. FORTESTA is an alcohol based product and is flammable; therefore avoid fire, flame or smoking until the gel has dried. It is important to adhere to all recommended monitoring. Report any changes in their state of health, such as changes in urinary habits, breathing, sleep, and mood. FORTESTA is prescribed to meet the patient’s specific needs, therefore, the patient should never share FORTESTA with anyone. Wait 2 hours before swimming or washing following application of FORTESTA. This will ensure that the greatest amount of FORTESTA is absorbed into their system. Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment Of Fertility Testosterone has been tested by subcutaneous injection and implantation in mice and rats. In mice, implant induced cervical-uterine tumors metastasized in some cases. There is suggestive evidence that injection of testosterone into some strains of female mice increases their susceptibility to hepatoma. Testosterone is also known to increase the number of tumors and decrease the degree of differentiation of chemically induced carcinomas of the liver in rats. Testosterone was negative in the in vitro Ames and in the in vivo mouse micronucleus assays. The administration of exogenous testosterone has been reported to suppress spermatogenesis in the rat, dog and non-human primates, which was reversible on cessation of the treatment. Use In Specific Populations Pregnancy Pregnancy Category X [see CONTRAINDICATIONS]. – FORTESTA is contraindicated during pregnancy or in women who may become pregnant. Testosterone is teratogenic and may cause fetal harm. Exposure of a female fetus to androgens may result in varying degrees of virilization. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be made aware of the potential hazard to the fetus. Nursing Mothers Although it is not known how much testosterone transfers into human milk, FORTESTA is contraindicated in nursing women because of the potential for serious adverse reactions in nursing infants. Testosterone and other androgens may adversely affect lactation [see CONTRAINDICATIONS]. Pediatric Use The safety and efficacy of FORTESTA in pediatric patients <18 years old has not been established. Improper use may result in acceleration of bone age and premature closure of epiphyses. Geriatric Use There have not been sufficient numbers of geriatric patients involved in controlled clinical studies utilizing FORTESTA to determine whether efficacy in those over 65 years of age differs from younger subjects. Of the 149 patients enrolled in the pivotal clinical study utilizing FORTESTA, 20 were over 65 years of age. Additionally, there are insufficient long-term safety data in geriatric patients to assess the potential risks of cardiovascular disease and prostate cancer. Geriatric patients treated with androgens may also be at risk for worsening of signs and symptoms of BPH. Renal Impairment No studies were conducted in patients with renal impairment. Hepatic Impairment No studies were conducted in patients with hepatic impairment.

WARNINGS Included as part of the PRECAUTIONS section. PRECAUTIONS Worsening Of Benign Prostatic Hyperplasia (BPH) And Potential Risk Of Prostate Cancer Patients with BPH treated with androgens are at an increased risk for worsening of signs and symptoms of BPH. Monitor patients with BPH for worsening signs and symptoms. Patients treated with androgens may be at increased risk for prostate cancer. Evaluation of patients for prostate cancer prior to initiating and during treatment with androgens is appropriate [see CONTRAINDICATIONS]. Potential For Secondary Exposure To Testosterone Cases of secondary exposure resulting in virilization of children have been reported in postmarketing surveillance of testosterone gel products. Signs and symptoms have included enlargement of the penis or clitoris, development of pubic hair, increased erections and libido, aggressive behavior, and advanced bone age. In most cases, these signs and symptoms regressed with removal of the exposure to testosterone gel. In a few cases, however, enlarged genitalia did not fully return to age-appropriate normal size, and bone age remained modestly greater than chronological age. The risk of transfer was increased in some of these cases by not adhering to precautions for the appropriate use of the topical testosterone product. Children and women should avoid contact with unwashed or unclothed application sites in men using AndroGel 1.62% [see DOSAGE AND ADMINISTRATION, Use in Specific Populations and CLINICAL PHARMACOLOGY]. Inappropriate changes in genital size or development of pubic hair or libido in children, or changes in body hair distribution, significant increase in acne, or other signs of virilization in adult women should be brought to the attention of a physician and the possibility of secondary exposure to testosterone gel should also be brought to the attention of a physician. Testosterone gel should be promptly discontinued until the cause of virilization has been identified. Polycythemia Increases in hematocrit, reflective of increases in red blood cell mass, may require lowering or discontinuation of testosterone. Check hematocrit prior to initiating treatment. It would also be appropriate to re-evaluate the hematocrit 3 to 6 months after starting treatment, and then annually. If hematocrit becomes elevated, stop therapy until hematocrit decreases to an acceptable concentration. An increase in red blood cell mass may increase the risk of thromboembolic events. Venous Thromboembolism There have been postmarketing reports of venous thromboembolic events, including deep vein thrombosis (DVT) and pulmonary embolism (PE), in patients using testosterone products such as AndroGel 1.62%. Evaluate patients who report symptoms of pain, edema, warmth and erythema in the lower extremity for DVT and those who present with acute shortness of breath for PE. If a venous thromboembolic event is suspected, discontinue treatment with AndroGel 1.62% and initiate appropriate workup and management [see ADVERSE REACTIONS]. Cardiovascular Risk Long term clinical safety trials have not been conducted to assess the cardiovascular outcomes of testosterone replacement therapy in men. To date, epidemiologic studies and randomized controlled trials have been inconclusive for determining the risk of major adverse cardiovascular events (MACE), such as non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death, with the use of testosterone compared to non-use. Some studies, but not all, have reported an increased risk of MACE in association with use of testosterone replacement therapy in men. Patients should be informed of this possible risk when deciding whether to use or to continue to use AndroGel 1.62%. Use In Women Due to the lack of controlled evaluations in women and potential virilizing effects, AndroGel 1.62% is not indicated for use in women [see CONTRAINDICATIONS and Use in Specific Populations]. Potential For Adverse Effects On Spermatogenesis With large doses of exogenous androgens, including AndroGel 1.62%, spermatogenesis may be suppressed through feedback inhibition of pituitary FSH possibly leading to adverse effects on semen parameters including sperm count. Hepatic Adverse Effects Prolonged use of high doses of orally active 17-alpha-alkyl androgens (e.g., methyltestosterone) has been associated with serious hepatic adverse effects (peliosis hepatis, hepatic neoplasms, cholestatic hepatitis, and jaundice). Peliosis hepatis can be a life-threatening or fatal complication. Long-term therapy with intramuscular testosterone enanthate has produced multiple hepatic adenomas. AndroGel 1.62% is not known to cause these adverse effects. Edema Androgens, including AndroGel 1.62%, may promote retention of sodium and water. Edema, with or without congestive heart failure, may be a serious complication in patients with preexisting cardiac, renal, or hepatic disease [see ADVERSE REACTIONS]. Gynecomastia Gynecomastia may develop and persist in patients being treated with androgens, including AndroGel 1.62%, for hypogonadism. Sleep Apnea The treatment of hypogonadal men with testosterone may potentiate sleep apnea in some patients, especially those with risk factors such as obesity or chronic lung diseases. Lipids Changes in serum lipid profile may require dose adjustment or discontinuation of testosterone therapy. Hypercalcemia Androgens, including AndroGel 1.62 %, should be used with caution in cancer patients at risk of hypercalcemia (and associated hypercalciuria). Regular monitoring of serum calcium concentrations is recommended in these patients. Decreased Thyroxine-binding Globulin Androgens, including AndroGel 1.62%, may decrease concentrations of thyroxin-binding globulins, resulting in decreased total T4 serum concentrations and increased resin uptake of T3 and T4. Free thyroid hormone concentrations remain unchanged, however, and there is no clinical evidence of thyroid dysfunction. Flammability Alcohol based products, including AndroGel 1.62%, are flammable; therefore, patients should be advised to avoid fire, flame or smoking until the AndroGel 1.62% has dried. Patient Counseling Information See FDA-Approved Medication Guide Patients should be informed of the following: Use In Men With Known Or Suspected Prostate Or Breast Cancer Men with known or suspected prostate or breast cancer should not use AndroGel 1.62% [see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS]. Potential For Secondary Exposure To Testosterone And Steps To Prevent Secondary Exposure Secondary exposure to testosterone in children and women can occur with the use of testosterone gel in men. Cases of secondary exposure to testosterone have been reported in children. Physicians should advise patients of the reported signs and symptoms of secondary exposure, which may include the following: In children: unexpected sexual development including inappropriate enlargement of the penis or clitoris, premature development of pubic hair, increased erections, and aggressive behavior. In women: changes in hair distribution, increase in acne, or other signs of testosterone effects. The possibility of secondary exposure to testosterone gel should be brought to the attention of a healthcare provider. AndroGel 1.62% should be promptly discontinued until the cause of virilization is identified. Strict adherence to the following precautions is advised to minimize the potential for secondary exposure to testosterone from AndroGel 1.62% in men [see Medication Guide]: Children and women should avoid contact with unwashed or unclothed application site(s) of men using AndroGel 1.62%. Patients using AndroGel 1.62% should apply the product as directed and strictly adhere to the following: Wash hands with soap and water immediately after application. Cover the application site(s) with clothing after the gel has dried. Wash the application site(s) thoroughly with soap and water prior to any situation where skin-to-skin contact of the application site with another person is anticipated. In the event that unwashed or unclothed skin to which AndroGel 1.62% has been applied comes in contact with the skin of another person, the general area of contact on the other person should be washed with soap and water as soon as possible [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY]. Potential Adverse Reactions With Androgens Patients should be informed that treatment with androgens may lead to adverse reactions which include: Changes in urinary habits such as increased urination at night, trouble starting the urine stream, passing urine many times during the day, having an urge to go to the bathroom right away, having a urine accident, being unable to pass urine and weak urine flow. Breathing disturbances, including those associated with sleep, or excessive daytime sleepiness. Too frequent or persistent erections of the penis. Nausea, vomiting, changes in skin color, or ankle swelling. Patients Should Be Advised Of The Following Instructions For Use Read the Medication Guide before starting AndroGel 1.62% therapy and to reread it each time the prescription is renewed. AndroGel 1.62% should be applied and used appropriately to maximize the benefits and to minimize the risk of secondary exposure in children and women. Keep AndroGel 1.62% out of the reach of children. AndroGel 1.62% is an alcohol based product and is flammable; therefore avoid fire, flame or smoking until the gel has dried. It is important to adhere to all recommended monitoring. Report any changes in their state of health, such as changes in urinary habits, breathing, sleep, and mood. AndroGel 1.62% is prescribed to meet the patient's specific needs; therefore, the patient should never share AndroGel 1.62% with anyone. Wait 2 hours before swimming or washing following application of AndroGel 1.62%. This will ensure that the greatest amount of AndroGel 1.62% is absorbed into their system. Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment Of Fertility Testosterone has been tested by subcutaneous injection and implantation in mice and rats. In mice, the implant induced cervical-uterine tumors which metastasized in some cases. There is suggestive evidence that injection of testosterone into some strains of female mice increases their susceptibility to hepatoma. Testosterone is also known to increase the number of tumors and decrease the degree of differentiation of chemically induced carcinomas of the liver in rats. Testosterone was negative in the in vitro Ames and in the in vivo mouse micronucleus assays. The administration of exogenous testosterone has been reported to suppress spermatogenesis in the rat, dog and non-human primates, which was reversible on cessation of the treatment. Use In Specific Populations Pregnancy Pregnancy Category X [see CONTRAINDICATIONS]: AndroGel 1.62% is contraindicated during pregnancy or in women who may become pregnant. Testosterone is teratogenic and may cause fetal harm. Exposure of a fetus to androgens may result in varying degrees of virilization. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be made aware of the potential hazard to the fetus. Nursing Mothers Although it is not known how much testosterone transfers into human milk, AndroGel 1.62% is contraindicated in nursing women because of the potential for serious adverse reactions in nursing infants. Testosterone and other androgens may adversely affect lactation [see CONTRAINDICATIONS]. Pediatric Use The safety and effectiveness of AndroGel 1.62% in pediatric patients less than 18 years old has not been established. Improper use may result in acceleration of bone age and premature closure of epiphyses. Geriatric Use There have not been sufficient numbers of geriatric patients involved in controlled clinical studies utilizing AndroGel 1.62% to determine whether efficacy in those over 65 years of age differs from younger subjects. Of the 234 patients enrolled in the clinical trial utilizing AndroGel 1.62%, 21 were over 65 years of age. Additionally, there is insufficient long-term safety data in geriatric patients to assess the potentially increased risks of cardiovascular disease and prostate cancer. Geriatric patients treated with androgens may also be at risk for worsening of signs and symptoms of BPH. Renal Impairment No studies were conducted involving patients with renal impairment. Hepatic Impairment No studies were conducted in patients with hepatic impairment.