Prescription Drugs

Find Lowest Prices on DYLOJECT™ (diclofenac sodium) Injection WARNING RISK OF SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS Cardiovascular Thrombotic Events Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction, and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use [see WARNINGS AND PRECAUTIONS]. DYLOJECT is contraindicated in the setting of coronary artery bypass graft (CABG) surgery [see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS]. Gastrointestinal Bleeding, Ulceration, and Perforation NSAIDs cause an increased risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events [see WARNINGS AND PRECAUTIONS]. DESCRIPTION DYLOJECT (diclofenac sodium) Injection is a nonsteroidal anti-inflammatory drug for intravenous administration. Each mL of aqueous solution contains 37.5 mg of diclofenac sodium (34.8 mg of diclofenac). Diclofenac sodium is a phenylacetic acid derivative that is a white to off-white, virtually odorless, crystalline powder. Diclofenac sodium is freely soluble in methanol, soluble in ethanol, and practically insoluble in chloroform and in dilute acid. Diclofenac sodium is sparingly soluble in water. Its chemical formula and name are: C14H10Cl2NO2Na [M.W. = 318.14] 2-[(2,6-dichlorophenyl) amino] benzeneacetic acid, monosodium salt. DYLOJECT is a clear colorless sterile solution. The inactive ingredients of DYLOJECT include: 333 mg hydroxypropyl betadex (HPβCD), 5 mg monothioglycerol, sodium hydroxide and/or hydrochloric acid for pH adjustment, and water for injection.

INDICATIONS DYLOJECT is indicated in adults for the: management of mild to moderate pain management of moderate to severe pain alone or in combination with opioid analgesics. DOSAGE AND ADMINISTRATION Use for the shortest duration consistent with individual patient treatment goals [see WARNINGS AND PRECAUTIONS]. DYLOJECT is for intravenous administration only. After observing the response to initial therapy with DYLOJECT, the frequency should be adjusted to suit an individual patient's needs. Do not exceed 150 mg total daily dose. For the treatment of acute pain, the recommended dose of DYLOJECT is 37.5 mg administered by intravenous bolus injection over 15 seconds every 6 hours as needed, Maximum daily dose is 150 mg. To reduce the risk of renal adverse reactions, patients must be well hydrated prior to administration of DYLOJECT. Visually inspect parenteral drug products for particulate matter and discoloration prior to administration. If visibly opaque particles, discoloration or other foreign particles are observed, the solution should not be used. HOW SUPPLIED Dosage Forms And Strengths DYLOJECT (diclofenac) Injection: 37.5 mg/mL in a single-dose glass vial. DYLOJECT is a clear, colorless, aqueous, nonpyrogenic sterile solution. Storage And Handling DYLOJECT (diclofenac sodium) Injection, is a clear, colorless solution that is supplied as a 1 mL fill in a clear 2 mL glass vial with an orange tamper-evident top. NDC No. Strength Fill Container Size 0409-1068-01 37.5 mg/mL 1 mL 2 mL Carton of 25 vials Store at Controlled Room Temperature 20 to 25°C (68 to 77°F) [see USP Controlled Room Temperature]. Do not freeze. Protect from light. Keep DYLOJECT out of reach and sight of children. Not made with natural rubber latex. Manufactured for: Hospira, Inc., Lake Forest, IL 60045 USA. Revised: May 2016

PATIENT INFORMATION Inform patients, families, or their caregivers of the following information before initiating therapy with DYLOJECT and periodically during the course of ongoing therapy. Cardiovascular Thrombotic Events Advise patients to be alert for the symptoms of cardiovascular thrombotic events, including chest pain, shortness of breath, weakness, or slurring of speech, and to report any of these symptoms to their health care provider immediately [see WARNINGS AND PRECAUTIONS]. Gastrointestinal Bleeding, Ulceration, And Perforation Advise patients to report symptoms of ulcerations and bleeding, including epigastric pain, dyspepsia, melena, and hematemesis to their health care provider. In the setting of concomitant use of low-dose aspirin for cardiac prophylaxis, inform patients of the increased risk for and the signs and symptoms of GI bleeding [see WARNINGS AND PRECAUTIONS]. Hepatotoxicity Inform patients of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, pruritus, diarrhea, jaundice, right upper quadrant tenderness, and “flu-like” symptoms). If these occur instruct patients to stop DYLOJECT and seek immediate medical therapy [see WARNINGS AND PRECAUTIONS]. Heart Failure And Edema Advise patients to be alert for the symptoms of congestive heart failure including shortness of breath, unexplained weight gain, or edema and to contact their healthcare provider if such symptoms occur [see WARNINGS AND PRECAUTIONS]. Anaphylactic Reactions Inform patients of the signs of an anaphylactic reaction (e.g., difficulty breathing, swelling of the face or throat). Instruct patients to seek immediate emergency help if these occur [see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS]. Serious Skin Reactions Advise patients to stop DYLOJECT immediately if they develop any type of rash, and to contact their healthcare provider as soon as possible [see WARNINGS AND PRECAUTIONS]. Female Fertility Advise females of reproductive potential who desire pregnancy that NSAIDs, including DYLOJECT, may be associated with a reversible delay in ovulation [see Use in Specific Populations]. Fetal Toxicity Inform pregnant women to avoid use of DYLOJECT and other NSAIDs starting at 30 weeks gestation, because of the risk of the premature closing of the fetal ductus arteriosus [see WARNINGS AND PRECAUTIONS and Use In Specific Populations]. Avoid Concomitant Use Of NSAIDs Inform patients that the concomitant use of DYLOJECT with other NSAIDs or salicylates (e.g., diflunisal, salsalate) is not recommended due to the increased risk of gastrointestinal toxicity, and little or no increase in efficacy [see WARNINGS AND PRECAUTIONS and DRUG INTERACTIONS]. Alert patients that NSAIDs may be present in “over the counter” medications for treatment of colds, fever, or insomnia. Use Of NSAIDS And Low-Dose Aspirin Inform patients not to use low-dose aspirin concomitantly with DYLOJECT until they talk to their healthcare provider [see DRUG INTERACTIONS].

WARNINGS Included as part of the PRECAUTIONS section. PRECAUTIONS Cardiovascular Thrombotic Events Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI) and stroke, which can be fatal. Based on available data, it is unclear that the risk for CV thrombotic events is similar for all NSAIDs. The relative increase in serious CV thrombotic events over baseline conferred by NSAID use appears to be similar in those with and without known CV disease or risk factors for CV disease. However, patients with known CV disease or risk factors had a higher absolute incidence of excess serious CV thrombotic events, due to their increased baseline rate. Some observational studies found that this increased risk of serious CV thrombotic events began as early as the first weeks of treatment. The increase in CV thrombotic risk has been observed most consistently at higher doses. To minimize the potential risk for an adverse CV event in NSAID-treated patients, use the lowest effective dose for the shortest duration possible. Physicians and patients should remain alert for the development of such events, throughout the entire treatment course, even in the absence of previous CV symptoms. Patients should be informed about the symptoms of serious CV events and the steps to take if they occur. There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID, such as diclofenac, increases the risk of serious gastrointestinal (GI) events [see Gastrointestinal Bleeding, Ulceration, And Perforation]. Status Post Coronary Artery Bypass Graft (CABG) Surgery Two large, controlled clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10-14 days following CABG surgery found an increased incidence of myocardial infarction and stroke. NSAIDs are contraindicated in the setting of CABG [see CONTRAINDICATIONS]. Post-MI Patients Observational studies conducted in the Danish National Registry have demonstrated that patients treated with NSAIDs in the post-MI period were at increased risk of reinfarction, CV-related death, and all-cause mortality beginning in the first week of treatment. In this same cohort, the incidence of death in the first year post-MI was 20 per 100 person years in NSAID-treated patients compared to 12 per 100 person years in non-NSAID exposed patients. Although the absolute rate of death declined somewhat after the first year post-MI, the increased relative risk of death in NSAID users persisted over at least the next four years of follow-up. Avoid the use of DYLOJECT in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events. If DYLOJECT is used in patients with a recent MI, monitor patients for signs of cardiac ischemia. Gastrointestinal Bleeding, Ulceration, And Perforation NSAIDs, including diclofenac, cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the esophagus, stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients who develop a serious upper GI adverse event on NSAID therapy is symptomatic. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occurred in approximately 1% of patients treated for 3-6 months and in about 2%-4% of patients treated for one year. DYLOJECT is administered by intravenous injection and is intended for acute short term use. However, even short-term NSAID therapy is not without risk. Risk Factors For GI Bleeding, Ulceration, And Perforation Patients with a prior history of peptic ulcer disease and/or GI bleeding who used NSAIDs had a greater than 10-fold increased risk for developing a GI bleed compared to patients without these risk factors. Other factors that increase the risk of GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. Most postmarketing reports of fatal GI events occurred in elderly or debilitated patients. Additionally, patients with advanced liver disease and/or coagulopathy are at increased risk for GI bleeding. Strategies to Minimize the GI Risks in NSAID-treated Patients: Use the lowest effective dosage for the shortest possible duration. Avoid administration of more than one NSAID at a time. Avoid use in patients at higher risk unless benefits are expected to outweigh the increased risk of bleeding. For such patients, as well as those with active GI bleeding, consider alternate therapies other than NSAIDs. Remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy. If a serious GI adverse event is suspected, promptly initiate evaluation and treatment and discontinue DYLOJECT until a serious GI adverse event is ruled out. In the setting of concomitant use of low-dose aspirin for cardiac prophylaxis, monitor patients more closely for evidence of GI bleeding [see DRUG INTERACTIONS]. Hepatotoxicity In clinical trials of oral diclofenac-containing products, meaningful elevations (i.e., more than 3 times the ULN) of AST (SGOT) were observed in about 2% of approximately 5,700 patients at some time during diclofenac treatment (ALT was not measured in all studies). In a large, open-label, controlled trial of 3,700 patients treated with oral diclofenac sodium for 2-6 months, patients were monitored first at 8 weeks and 1,200 patients were monitored again at 24 weeks. Meaningful elevations of ALT and/or AST occurred in about 4% of patients and included marked elevations (greater than 8 times the ULN) in about 1% of the 3,700 patients. In that open-label study, a higher incidence of borderline (less than 3 times the ULN), moderate (3-8 times the ULN), and marked (greater than 8 times the ULN) elevations of ALT or AST was observed in patients receiving diclofenac when compared to other NSAIDs. Elevations in transaminases were seen more frequently in patients with osteoarthritis than in those with rheumatoid arthritis. Almost all meaningful elevations in transaminases were detected before patients became symptomatic. Abnormal tests occurred during the first 2 months of therapy with diclofenac in 42 of the 51 patients in all trials who developed marked transaminase elevations. In postmarketing reports, cases of drug-induced hepatotoxicity have been reported in the first month, and in some cases, the first 2 months of therapy, but can occur at any time during treatment with diclofenac. Postmarketing surveillance has reported cases of severe hepatic reactions, including liver necrosis, jaundice, fulminant hepatitis with and without jaundice, and liver failure. Some of these reported cases resulted in fatalities or liver transplantation. In a European retrospective population-based, case-controlled study, 10 cases of diclofenac associated drug-induced liver injury with current use compared with non-use of diclofenac were associated with a statistically significant 4-fold adjusted odds ratio of liver injury. In this particular study, based on an overall number of 10 cases of liver injury associated with diclofenac, the adjusted odds ratio increased further with female sex, doses of 150 mg or more, and duration of use for more than 90 days. Physicians should measure transaminases at baseline and periodically in patients receiving long-term therapy with diclofenac, because severe hepatotoxicity may develop without a prodrome of distinguishing symptoms. The optimum times for making the first and subsequent transaminase measurements are not known. Based on clinical trial data and postmarketing experiences, transaminases should be monitored within 4 to 8 weeks after initiating treatment with diclofenac. DYLOJECT is not indicated for long-term treatment. However, severe hepatic reactions can occur at any time during treatment with diclofenac. If abnormal liver tests persist or worsen, if clinical signs and/or symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g. eosinophilia, rash, abdominal pain, diarrhea, dark urine, etc.), DYLOJECT should be discontinued immediately. Inform patients of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, diarrhea, pruritus, jaundice, right upper quadrant tenderness, and “flu-like” symptoms). If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), discontinue DYLOJECT immediately, and perform a clinical evaluation of the patient. To minimize the potential risk for an adverse liver-related event in patients treated with diclofenac, use the lowest effective dose for the shortest duration possible. Exercise caution when prescribing DYLOJECT with concomitant drugs that are known to be potentially hepatotoxic (e.g., acetaminophen, antibiotics, anti-epileptics). Hypertension NSAIDs, including DYLOJECT, can lead to new onset of hypertension or worsening of preexisting hypertension, either of which may contribute to the increased incidence of CV events. Patients taking angiotensin converting enzyme (ACE) inhibitors, thiazide diuretics, or loop diuretics may have impaired response to these therapies when taking NSAIDs [see DRUG INTERACTIONS]. Monitor blood pressure (BP) during the initiation of NSAID treatment and throughout the course of therapy. Heart Failure And Edema The Coxib and traditional NSAID Trialists' Collaboration meta-analysis of randomized controlled trials demonstrated an approximately two-fold increase in hospitalizations for heart failure in COX-2 selective-treated patients and nonselective NSAID-treated patients compared to placebo-treated patients. In a Danish National Registry study of patients with heart failure, NSAID use increased the risk of MI, hospitalization for heart failure, and death. Additionally, fluid retention and edema have been observed in some patients treated with NSAIDs. Use of diclofenac may blunt the CV effects of several therapeutic agents used to treat these medical conditions (e.g., diuretics, ACE inhibitors, or angiotensin receptor blockers [ARBs]) [see DRUG INTERACTIONS]. Avoid the use of DYLOJECT in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. If DYLOJECT is used in patients with severe heart failure, monitor patients for signs of worsening heart failure. Renal Toxicity And Hyperkalemia Renal Toxicity Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of an NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors or ARBs, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state. DYLOJECT is not recommended in patients with moderate to severe renal insufficiency and is contraindicated in patients with moderate to severe renal insufficiency in the perioperative period and who are at risk for volume depletion. Acute renal decompensation was observed in 4% out of 68 patients enrolled with renal impairment and treated with DYLOJECT in clinical trials in the perioperative period. Correct volume status in dehydrated or hypovolemic patients prior to initiating DYLOJECT. Monitor renal function in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia during use of DYLOJECT [see DRUG INTERACTIONS]. Avoid the use of DYLOJECT in patients with advanced renal disease unless the benefits are expected to outweigh the risk of worsening renal function. If DYLOJECT is used in patients with advanced renal disease, monitor patients for signs of worsening renal function. Hyperkalemia Increases in serum potassium concentration, including hyperkalemia, have been reported with use of NSAIDs, even in some patients without renal impairment. In patients with normal renal function, these effects have been attributed to a hyporeninemic-hypoaldosteronism state. Anaphylactic Reactions Diclofenac has been associated with anaphylactic reactions in patients with and without known hypersensitivity to diclofenac and in patients with aspirin-sensitive asthma [see CONTRAINDICATIONS and Exacerbation Of Asthma Related To Aspirin Sensitivity]. Seek emergency help if an anaphylactic reaction occurs. Exacerbation Of Asthma Related To Aspirin Sensitivity A subpopulation of patients with asthma may have aspirin-sensitive asthma which may include chronic rhinosinusitis complicated by nasal polyps; severe, potentially fatal bronchospasm; and/or intolerance to aspirin and other NSAIDs. Because cross-reactivity between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients, DYLOJECT is contraindicated in patients with this form of aspirin sensitivity [see CONTRAINDICATIONS]. When DYLOJECT is used in patients with preexisting asthma (without known aspirin sensitivity), monitor patients for changes in the signs and symptoms of asthma. Serious Skin Reactions NSAIDs, including diclofenac, can cause serious skin adverse reactions such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. Inform patients about the signs and symptoms of serious skin reactions, and to discontinue the use of DYLOJECT at the first appearance of skin rash or any other sign of hypersensitivity. DYLOJECT is contraindicated in patients with previous serious skin reactions to NSAIDs [see CONTRAINDICATIONS]. Premature Closure Of Fetal Ductus Arteriosus Diclofenac may cause premature closure of the fetal ductus arteriosus. Avoid use of NSAIDs, including DYLOJECT, in pregnant women starting at 30 weeks of gestation (third trimester) [see Use in Specific Populations]. Hematologic Toxicity Anemia has occurred in NSAID-treated patients. This may be due to occult or gross blood loss, fluid retention, or an incompletely described effect on erythropoiesis. If a patient treated with DYLOJECT has any signs or symptoms of anemia, monitor hemoglobin or hematocrit. NSAIDs, including DYLOJECT, may increase the risk of bleeding events. Co-morbid conditions such as coagulation disorders, concomitant use of warfarin, other anticoagulants, antiplatelet agents (e.g., aspirin), serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) may increase this risk. Monitor these patients for signs of bleeding [see DRUG INTERACTIONS]. Masking Of Inflammation And Fever The pharmacological activity of DYLOJECT in reducing inflammation, and possibly fever, may diminish the utility of diagnostic signs in detecting infections. Laboratory Monitoring Because serious GI bleeding, hepatotoxicity, and renal injury can occur without warning symptoms or signs, consider monitoring patients on long-term NSAID treatment with a CBC and chemistry profile periodically. DYLOJECT is not indicated for long-term treatment. Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment Of Fertility Carcinogenesis Long-term carcinogenicity studies in rats given diclofenac sodium up to 2 mg/kg/day (approximately 0.13 times the maximum recommended human dose [MRHD] of DYLOJECT, 150 mg/day, based on mg/m² body surface area [BSA] comparison) have revealed no significant increase in tumor incidence. A 2-year carcinogenicity study conducted in mice employing diclofenac sodium at doses up to 0.3 mg/kg/day (approximately 0.01 times the MRHD based on BSA comparison) in males and 1 mg/kg/day (approximately 0.04 times the MRHD based on BSA comparison) in females did not reveal any oncogenic potential. Mutagenesis Diclofenac sodium did not show mutagenic activity in in vitro point mutation assays in mammalian (mouse lymphoma) and microbial (yeast, Ames) test systems and was nonmutagenic in several mammalian in vitro and in vivo tests, including dominant lethal and male germinal epithelial chromosomal aberration studies in Chinese hamsters. Impairment Of Fertility Diclofenac sodium administered to male and female rats at 4 mg/kg/day (approximately 0.3 times the MRHD based on BSA comparison) did not affect fertility. Use In Specific Populations Pregnancy Pregnancy Category C prior to 30 weeks gestation; Category D starting at 30 weeks gestation. Risk Summary Use of NSAIDs, including DYLOJECT, during the third trimester of pregnancy increases the risk of premature closure of the fetal ductus arteriosus. Avoid use of NSAIDs, including DYLOJECT, in pregnant women starting at 30 weeks of gestation (third trimester). There are no adequate and well-controlled studies of DYLOJECT in pregnant women. Data from observational studies regarding potential embryofetal risks of NSAID use in women in the first or second trimesters of pregnancy are inconclusive. In the general U.S. population, all clinically recognized pregnancies, regardless of drug exposure, have a background rate of 2-4% for major malformations, and 15-20% for pregnancy loss. In animal reproduction studies, no evidence of teratogenicity was observed in mice, rats, and rabbits given diclofenac during the period of organogenesis at doses up to approximately 0.7, 0.7, and 1.3 times, respectively, the maximum recommended human dose (MRHD) of DYLOJECT despite the presence of maternal and fetal toxicity at these doses [see Data]. Based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. In animal studies, administration of prostaglandin synthesis inhibitors such as diclofenac, resulted in increased pre- and post-implantation loss. Clinical Considerations Labor or Delivery There are no studies on the effects of DYLOJECT during labor or delivery. In animal studies, NSAIDS, including diclofenac, inhibit prostaglandin synthesis, cause delayed parturition, and increase the incidence of stillbirth. Data Animal data Reproductive and developmental studies in animals demonstrated that diclofenac sodium administration during organogenesis did not produce teratogenicity despite the induction of maternal toxicity and fetal toxicity in mice at oral doses up to 20 mg/kg/day (approximately 0.7 times the maximum recommended human dose [MRHD] of DYLOJECT, 150 mg/day, based on body surface area (BSA) comparison), and in rats and rabbits at oral doses up to 10 mg/kg/day (approximately 0.7 and 1.3 times, respectively, the MRHD based on BSA comparison). In rats, maternally toxic doses were associated with dystocia, prolonged gestation, reduced fetal weights and growth, and reduced fetal survival. Diclofenac has been shown to cross the placental barrier in mice, rats, and humans. Lactation Risk Summary Based on available data, diclofenac may be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for DYLOJECT and any potential adverse effects on the breastfed infant from the DYLOJECT or from the underlying maternal condition. Data One woman treated orally with a diclofenac salt, 150 mg/day, had a milk diclofenac level of 100 mcg/L, equivalent to an infant dose of about 0.03 mg/kg/day. Diclofenac was not detectable in breast milk in 12 women using diclofenac (after either 100 mg/day orally for 7 days or a single 50 mg intramuscular dose administered in the immediate postpartum period). Females And Males Of Reproductive Potential Infertility Females Based on the mechanism of action, the use of prostaglandin-mediated NSAIDs, including DYLOJECT, may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women. Published animal studies have shown that administration of prostaglandin synthesis inhibitors has the potential to disrupt prostaglandin-mediated follicular rupture required for ovulation. Small studies in women treated with NSAIDs have also shown a reversible delay in ovulation. Consider withdrawal of NSAIDs, including DYLOJECT, in women who have difficulties conceiving or who are undergoing investigation of infertility. Pediatric Use The safety and efficacy of DYLOJECT has not been established in pediatric patients. Geriatric Use Elderly patients, compared to younger patients, are at greater risk for NSAID-associated serious cardiovascular, gastrointestinal, and/or renal adverse reactions. If the anticipated benefit for the elderly patient outweighs these potential risks, start dosing at the low end of the dosing range, and monitor patients for adverse effects [see WARNINGS AND PRECAUTIONS]. Diclofenac metabolites are known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. The pharmacokinetics of DYLOJECT are similar in elderly compared to young adults [see CLINICAL PHARMACOLOGY]. Hepatic Impairment Orally administered diclofenac sodium is extensively metabolized. The pharmacokinetics of DYLOJECT are similar in patients with mild hepatic impairment compared to healthy subjects [see CLINICAL PHARMACOLOGY]. Dosing adjustments in patients with mild hepatic impairment is not necessary. The pharmacokinetics of DYLOJECT were not studied in patients with moderate to severe hepatic impairment and use in this population is not recommended. Renal Impairment Pharmacokinetics of DYLOJECT in patients with mild to moderate renal impairment is similar compared to healthy subjects. However, acute renal decompensation was observed in 4% out of 68 patients enrolled with renal impairment and treated with DYLOJECT in clinical trials in the perioperative period. DYLOJECT is not recommended in patients with moderate to severe renal insufficiency and is contraindicated in patients with moderate to severe renal insufficiency in the perioperative period and who are at risk for volume depletion [see CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY]. Body Weight Pharmacokinetics of diclofenac following DYLOJECT injection appear to be dependent on body weight. The effect of body weight on clinical efficacy and safety of DYLOJECT has not been fully studied. Therefore, adjusting dose based on body weight is not recommended [see CLINICAL PHARMACOLOGY].