Lamivudineside effects

The following adverse reactions are discussed in other sections of the labeling: Exacerbations of hepatitis B after discontinuation of treatment. Risk of emergence of resistant HIV-1 infection. Risk of emergence of resistant HBV infection. Lactic acidosis and severe hepatomegaly with steatosis. The most common reported adverse reactions in those receiving lamivudine tablets (HBV) (incidence greater than or equal to 10% and reported at a rate greater than placebo) were ear, nose, and throat infections; sore throat; and diarrhea. To report SUSPECTED ADVERSE REACTIONS, contact Apotex Corp. at 1-800-706-5575 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical

Trials 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 with rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Clinical Trials Experience in Adult Subjects with Chronic HBV Infection Clinical adverse reactions (regardless of investigator’s causality assessment) reported in greater than or equal to 10% of subjects who received lamivudine tablets (HBV) and reported at a rate greater than in subjects who received placebo are listed in Table 2. Table 2. Clinical Adverse Reactions a Reported in Greater than or Equal to 10% of Subjects Who Received Lamivudine Tablets (HBV) for 52 to 68 Weeks and at an Incidence Greater than Placebo (Trials 1 to 3) a Includes adverse events regardless of severity and causality assessment. Adverse Event Lamivudine Tablets (HBV) (n = 332) Placebo (n = 200) Ear, Nose, and Throat Ear, nose, and throat infections 25% 21% Sore throat 13% 8% Gastrointestinal Diarrhea 14% 12% Specified laboratory abnormalities reported in subjects who received lamivudine tablets (HBV) and reported at a rate greater than in subjects who received placebo are listed in Table 3. Table 3. Frequencies of Specified Laboratory Abnormalities Reported during Treatment at a Greater Frequency in Subjects Treated with Lamivudine Tablets (HBV) than with Placebo (Trials 1 to 3) a a Includes subjects treated for 52 to 68 weeks. b Includes observations during and after treatment in the 2 placebo-controlled trials that collected this information. ULN = Upper limit of normal. Test (Abnormal Level) Subjects with Abnormality/Subjects with Observations Lamivudine Tabglets (HBV) Placebo Serum Lipase ≥2.5 x ULN b 10% 7% Creatine Phosphokinase (CPK) ≥7 x baseline 9% 5% Platelets <50,000/mm 3 4% 3% In subjects followed for up to 16 weeks after discontinuation of treatment, posttreatment ALT elevations were observed more frequently in subjects who had received lamivudine tablets (HBV) than in subjects who had received placebo. A comparison of ALT elevations between Weeks 52 and 68 in subjects who discontinued lamivudine tablets (HBV) at Week 52 and subjects in the same trials who received placebo throughout the treatment course is shown in Table 4. Table 4. Posttreatment ALT Elevations with No-Active-Treatment Follow-up (Trials 1 and 3) a Each subject may be represented in one or more category. b During treatment phase. c Comparable to a Grade 3 toxicity in accordance with modified WHO criteria. ULN = Upper limit of normal. Abnormal Value Subjects with ALT Elevation/ Subjects with Observations a Lamivudine Tablets (HBV) b Placebo b ALT ≥2 x baseline value 27% 19% ALT ≥3 x baseline value c 21% 8% ALT ≥2 x baseline value and absolute ALT >500 IU/L 15% 7% ALT ≥2 x baseline value; and bilirubin >2 x ULN and ≥2 x baseline value 0.7% 0.9% Clinical Trials Experience in Pediatric Subjects with Chronic HBV Infection Most commonly observed adverse reactions in the pediatric trials were similar to those in adult trials. Posttreatment transaminase elevations were observed in some subjects followed after cessation of lamivudine tablets (HBV).

6.2 Postmarketing

Experience The following adverse reactions have been identified during post-approval use of lamivudine tablets (HBV). Because these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These reactions have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to lamivudine. Blood and Lymphatic Anemia (including pure red cell aplasia and severe anemias progressing on therapy), lymphadenopathy, splenomegaly, thrombocytopenia. Digestive Stomatitis. Endocrine and Metabolic Hyperglycemia. General Weakness. Hepatic and Pancreatic Lactic acidosis and steatosis, posttreatment exacerbations of hepatitis, pancreatitis. Hypersensitivity Anaphylaxis, urticaria. Musculoskeletal Cramps, rhabdomyolysis. Nervous Paresthesia, peripheral neuropathy. Respiratory Abnormal breath sounds/wheezing. Skin Alopecia, pruritus, rash.