Prescription Drugs

CLINICAL PHARMACOLOGY Pharmacodynamics Mechanism of Action: Dutasteride inhibits the conversion of testosterone to 5α-dihydrotestosterone (DHT). DHT is the androgen primarily responsible for the initial development and subsequent enlargement of the prostate gland. Testosterone is converted to DHT by the enzyme 5α-reductase, which exists as 2 isoforms, type 1 and type 2. The type 2 isoenzyme is primarily active in the reproductive tissues while the type 1 isoenzyme is also responsible for testosterone conversion in the skin and liver. Dutasteride is a competitive and specific inhibitor of both type 1 and type 2 5α-reductase isoenzymes, with which it forms a stable enzyme complex. Dissociation from this complex has been evaluated under in vitro and in vivo conditions and is extremely slow. Dutasteride does not bind to the human androgen receptor. Effect on DHT and Testosterone: The maximum effect of daily doses of dutasteride on the reduction of DHT is dose dependent and is observed within 1 to 2 weeks. After 1 and 2 weeks of daily dosing with dutasteride 0.5 mg, median serum DHT concentrations were reduced by 85% and 90%, respectively. In patients with BPH treated with dutasteride 0.5 ing/day for 1 year, the median decrease in serum DHT was 94%. The median increase in serum testosterone was 19% but remained within the physiologic range. In BPH patients treated with 5 mg/day of dutasteride or placebo for up to 12 weeks prior to transurethral resection of the prostate, mean DHT concentrations in prostatic tissue were significantly lower in the dutasteride group compared with placebo (784 and 5793 pg/g, respectively, p

Find Lowest Prices on Duagen (dutasteride)Soft Gelatin Capsules DESCRIPTION Duagen (dutasteride) is a synthetic 4-azasteroid compound that is a selective inhibitor of both the type 1 and type 2 isoforms of steroid 5α-reductase (5AR), an intracellular enzyme that converts testosterone to 5α-dihydrotestosterone (DHT). Dutasteride is chemically designated as (5α, 17β)-N-{2, 5 bis(trifluoromethyl) phenyl}-3-oxo-4-azaandrost-l-ene-17-carboxamide. The empirical formula of dutasteride is C27H30F6N2O2, representing a molecular weight of 528.5. Dutasteride is a white to pale yellow powder with a melting point of 242 to 250°C. It is soluble in ethanol (44 mg/mL), methanol (64 mg/mL) and polyethylene glycol 400 (3 mg/mL), but it is insoluble in water. Duagen (dutasteride) Soft Gelatin Capsules for oral administration contain 0.5 mg of the active ingredient dutasteride in yellow capsules with red print. Each capsule contains 0.5 mg dutasteride dissolved in a mixture of mono-di-glycerides of caprylic/capric acid and butylated hydroxytoluene. The inactive excipients in the capsule shell are gelatin (from certified BSE-free bovine sources), glycerin, and ferric oxide (yellow). The soft gelatin capsules are printed with edible red ink.

INDICATIONS Duagen (dutasteride) is indicated for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate gland. DOSAGE AND ADMINISTRATION The recommended dose of Duagen (dutasteride) is 1 capsule (0.5 mg) taken orally once a day. The capsules should be swallowed whole. Duagen (dutasteride) may be administered with or without food. No dosage adjustment is necessary for subjects with renal impairment or for the elderly (see CLINICAL PHARMACOLOGY: Pharmacokinetics: Geriatric and Renal Impairment). Due to the absence of data in patients with hepatic impairment, no dosage recommendation can be made (see PRECAUTIONS: General). HOW SUPPLIED Duagen (dutasteride) Soft Gelatin Capsules 0.5 mg are oblong, opaque, dull yellow, gelatin capsules imprinted with "GX CE2" in red ink on one side packaged in bottles of 100 (NDC 0173-0712-00) with child-resistant closures and unit dose blister packs of 70 capsules (NDC 0173-0712-01). Storage and Handling: Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]. Dutasteride is absorbed through the skin. Duagen (dutasteride) Soft Gelatin capsules should not be handled by women who are pregnant or who may become pregnant because of the potential for absorption of dutasteride and the subsequent potential risk to a developing male fetus (see CLINICAL PHARMACOLOGY: Pharmacokinetics, WARNINGS: Exposure of Women†?Risk to Male Fetus, and PRECAUTIONS: Information For Patients and Pregnancy). Manufactured by: RP Scherer Beinheim, France for GlaxoSmithKline GlaxoSmithKline Research Triangle Park, NC 27709 ©2001 ,GlaxoSmithKline All rights reserved. (Updated Sep 05, 2003)

PATIENT INFORMATION Duagen (dutasteride) Soft Gelatin Capsules Duagen (dutasteride) is for use by men only. Read this information carefully before you start taking Duagen (dutasteride) . Read the information you get with Duagen (dutasteride) each time you refill your prescription. There may be new information. This information does not take the place of talking with your doctor. What is Duagen (dutasteride) ? Duagen (dutasteride) is a medication to treat men who have symptoms of benign prostatic hyperplasia. Duagen (dutasteride) is not a treatment for prostate cancer. See the end of this leaflet for information about how Duagen (dutasteride) works. Who should NOT take Duagen (dutasteride) ? • Women and children should not take Duagen (dutasteride) . A woman who is pregnant or capable of becoming pregnant should not handle Duagen (dutasteride) capsules. See "What are the special warnings for women about Duagen (dutasteride) ?" • Do not take Duagen (dutasteride) if you have had an allergic reaction to Duagen (dutasteride) or any of its ingredients. • Tell your doctor if you have liver problems. Duagen (dutasteride) may not be right for you. What are the special warnings for women about Duagen (dutasteride) ? • Women should never take Duagen (dutasteride) , • Women who are pregnant or may become pregnant should not handle Duagen (dutasteride) Capsules. If a woman who is pregnant with a male baby gets enough Duagen (dutasteride) into her body after swallowing it or through her skin after handling it, the male baby may be born with abnormal sex organs. What are the special precautions about Duagen (dutasteride) ? • Men treated with Duagen (dutasteride) should not donate blood until at least 6 months after their final dose to prevent giving Duagen (dutasteride) to a pregnant female through a blood transfusion. How should I take Duagen (dutasteride) ? • Take 1 Duagen (dutasteride) capsule once a day. • Swallow the capsule whole. • You can take Duagen (dutasteride) with or without food. • If you miss a dose, you may take it later that day. Do not make up the missed dose by taking 2 doses the next day. • You may find it helpful to take Duagen (dutasteride) at the same time every day to help you remember to take your dose. What are the possible side effects of Duagen (dutasteride) ? The most common side effects of Duagen (dutasteride) are impotence (trouble getting or keeping an erection), a decrease in libido (sex drive), and enlarged breasts. Also, some men may notice a decrease in the amount of semen they release during sex, Talk with your doctor if you have questions about these and other side effects that you think may be related to taking Duagen (dutasteride) . How should I store Duagen (dutasteride) ? Duagen (dutasteride) is a soft gelatin capsule that may become soft and leak or may stick to other capsules if kept at high temperatures. Store Duagen (dutasteride) capsules at room temperature of 77°F (25°C) or lower. If your capsules are cracked or leaking, don't use them, and contact your pharmacist. General information about Duagen (dutasteride) . • Do not use Duagen (dutasteride) for a condition for which it was not prescribed. • Do not share your Duagen (dutasteride) . • Ask your doctor about how often you should return for a visit to check your BPH. • A blood test called PSA (prostate-specific antigen) is sometimes used to detect prostate cancer. Duagen (dutasteride) will reduce the amount of PSA measured in your blood. Your doctor is aware of this effect and can still use PSA to detect prostate cancer in you. • If you have questions about Duagen (dutasteride) , ask your doctor or pharmacist. They can show you detailed information about Duagen (dutasteride) that was written for healthcare professionals. How does Duagen (dutasteride) work? Prostate growth is caused by a hormone in the blood called dihydrotestosterone (DHT). Duagen (dutasteride) lowers DHT production in the body, leading to shrinkage of the enlarged prostate in most men. Just as your prostate became large over a long period of time, reducing the size of your prostate and improving your symptoms will take time. While some men have fewer problems and symptoms after 3 months of treatment with Duagen (dutasteride) , a treatment period of at least 6 months is usually necessary to see if Duagen (dutasteride) will work for you. Manufactured by: RP Scherer Beinheim, France for GlaxoSmithKline GlaxoSmithKline Research Triangle Park, NC 27709 © 2001, GlaxoSmithKline All rights reserved. Updated Sep 05, 2003

OVERDOSE In volunteer studies, single doses of dutasteride up to 40 mg (80 times the therapeutic dose) for 7 days have been administered without adverse events or significant safety concerns. In clinical studies, doses of 5 mg daily have been administered to subjects for 6 months with no additional adverse effects to those seen at therapeutic doses of 0.5 mg. There is no specific antidote for dutasteride. Therefore, in cases of suspected overdosage symptomatic and supportive treatment should be given as appropriate, taking the long half-life of dutasteride into consideration. CONTRAINDICATIONS Duagen (dutasteride) is contraindicated for use in women and children. Duagen (dutasteride) is contraindicated for patients with known hypersensitivity to dutasteride, other 5α-reductase inhibitors, or any component of the preparation.

SIDE EFFECTS Adverse reactions were generally mild and transient. The most common adverse events leading to withdrawal in both treatment groups were associated with the reproductive system. The data described below reflect exposure to Duagen (dutasteride) in 2166 male subjects, including 1772 exposed for one year. Over 4300 male subjects with BPH were randomly assigned to receive placebo or 0.5-mg daily doses of Duagen (dutasteride) in three identical, placebo-controlled Phase in treatment studies. The population was aged 47 to 94 years (mean age 66 years) and greater than 90% Caucasian. A total of 267 subjects (6% of each treatment group) were withdrawn from the studies due to adverse experiences, usually associated with the reproductive system. Withdrawals due to adverse events considered by the investigator to have a reasonable possibility of being caused by the study medication occurred in 3% of the subjects receiving Duagen (dutasteride) and in 2% of the subjects receiving placebo. Table 1 summarizes clinical adverse reactions that were reported by the investigator as drug-related in at least 1% of subjects receiving Duagen (dutasteride) and at a higher incidence than subjects receiving placebo. Table 1: Drug-related Adverse Events* Reported in >1% Subjects and More Frequently in the Duagen (dutasteride) Group than the Placebo Group Pivotal Studies Pooled Adverse Event Placebo (N = 2158) Duagen (dutasteride) (N = 2l66) Impotence 59 (3%) 117(5%) Decreased libido 40 (2%) 74 (3%) Ejaculation disorders 14(

WARNINGS Exposure of Women-Risk to Male Fetus: Dutasteride is absorbed through the skin. Therefore, women who are pregnant or may be pregnant should not handle Duagen (dutasteride) Soft Gelatin Capsules because of the possibility of absorption of dutasteride and the potential risk of a fetal anomaly to a male fetus (see CONTRAINDICATIONS). In addition, women should use caution whenever handling Duagen (dutasteride) Soft Gelatin Capsules. PRECAUTIONS General: Lower urinary tract symptoms of BPH can be indicative of other urological diseases, including prostate cancer. Patients should be assessed to rule out other urological diseases prior to treatment with Duagen (dutasteride) . Patients with a large residual urinary volume and/or severely diminished urinary flow may not be good candidates for 5α-reductase inhibitor therapy and should be carefully monitored for obstructive uropathy. Blood Donation: Men being treated with dutasteride should not donate blood until at least 6 months have passed following their last dose. The purpose of this deferred period is to prevent administration of dutasteride to a pregnant female transfusion recipient. Use in Hepatic Impairment: The effect of hepatic impairment on dutasteride pharmacokinetics has not been studied. Because dutasteride is extensively metabolized and has a half-life of approximately 5 weeks at steady state, caution should be used in the administration of dutasteride to patients with liver disease. Use with Potent CYP3A4 Inhibitors: Although dutasteride is extensively metabolized, no metabolically-based drug interaction studies have been conducted. The effect of potent CYP3A4 inhibitors has not been studied. Because of the potential for drug-drug interactions, care should be taken when administering dutasteride to patients taking potent, chronic CYP3A4 enzyme inhibitors (e.g., ritonavir). Effects on PSA and Prostate Cancer Detection: Digital rectal examinations, as well as other evaluations for prostate cancer, should be performed on patients with BPH prior to initiating therapy with Duagen and periodically thereafter. Dutasteride reduces total serum PSA concentration by approximately 40% following 3 months of treatment and 50% following 6 and 12 months of treatment. This decrease is predictable over the entire range of PSA values, although it may vary in individual patients. Therefore, for interpretation of serial PSAs in a man taking Duagen (dutasteride) , a new baseline PSA concentration should be established after 3 to 6 months of treatment, and this new value should be used to assess potentially cancer-related changes in PSA. To interpret an isolated PSA value in a man treated with Duagen (dutasteride) for 6 months or more, the PSA value should be doubled for comparison with normal values in untreated men. Information for Patients Physicians should instruct their patients to read the Information for Patient leaflet before starting therapy with Duagen (dutasteride) and to reread it upon prescription renewal for new information regarding the use of Duagen (dutasteride) . Duagen (dutasteride) Soft Gelatin Capsules should not be handled by a woman who is pregnant or who may become pregnant because of the potential for absorption of dutasteride and the subsequent potential risk to a developing male fetus (see CONTRAINDICATIONS, and WARNINGS: Exposure Of Women†?Risk To Male Fetus). Physicians should inform patients that ejaculate volume might be decreased in some patients durine treatment with Duagen (dutasteride) . This decrease does not appear to interfere with normal sexual function. In clinical trials, impotence and decreased libido, considered by the investigator to be drug-related, occurred in a small number of patients treated with Duagen (dutasteride) or placebo (5% and 3%, respectively, see ADVERSE REACTIONS). Men treated with dutasteride should not donate blood until at least 6 months have passed following their last dose to prevent pregnant women from receiving dutasteride through blood transfusion (see PRECAUTIONS: Blood Donation).