FDA label 42677863-38cb-0042-e054-00144ff8d46c

BOXED WARNING LACTIC ACIDOSIS AND SEVERE HEPATOMEGALY WITH STEATOSIS, INCLUDING FATAL CASES, HAVE BEEN REPORTED WITH THE USE OF NUCLEOSIDE ANALOGUES ALONE OR IN COMBINATION, INCLUDING LAMIVUDINE AND OTHER ANTIRETROVIRALS (SEE WARNINGS). HUMAN IMMUNODEFICIENCY VIRUS (HIV) COUNSELING AND TESTING SHOULD BE OFFERED TO ALL PATIENTS BEFORE BEGINNING EPIVIR-HBV AND PERIODICALLY DURING TREATMENT (SEE WARNINGS), BECAUSE EPIVIR-HBV TABLETS AND ORAL SOLUTION CONTAIN A LOWER DOSE OF THE SAME ACTIVE INGREDIENT (LAMIVUDINE) AS EPIVIRTABLETS AND ORAL SOLUTION USED TO TREAT HIV INFECTION. IF TREATMENT WITH EPIVIR-HBV IS PRESCRIBED FOR CHRONIC HEPATITIS B FOR A PATIENT WITH UNRECOGNIZED OR UNTREATED HIV INFECTION, RAPID EMERGENCE OF HIV RESISTANCE IS LIKELY BECAUSE OF SUBTHERAPEUTIC DOSE AND INAPPROPRIATE MONOTHERAPY. SEVERE ACUTE EXACERBATIONS OF HEPATITIS B HAVE BEEN REPORTED IN PATIENTS WHO HAVE DISCONTINUED ANTI-HEPATITIS B THERAPY (INCLUDING EPIVIR-HBV). HEPATIC FUNCTION SHOULD BE MONITORED CLOSELY WITH BOTH CLINICAL AND LABORATORY FOLLOW-UP FOR AT LEAST SEVERAL MONTHS IN PATIENTS WHO DISCONTINUE ANTI-HEPATITIS B THERAPY. IF APPROPRIATE, INITIATION OF ANTI-HEPATITIS B THERAPY MAY BE WARRANTED (SEE WARNINGS).

WARNINGS Lactic Acidosis/Severe Hepatomegaly With Steatosis: Important Differences Between Lamivudine-Containing Products, HIV Testing, and Risk of Emergence of Resistant HIV: EPIVIR-HBV Tablets and Oral Solution contain a lower dose of the same active ingredient (lamivudine) as EPIVIR Tablets and Oral Solution, COMBIVIR(lamivudine/zidovudine) Tablets, EPZICOM(abacavir sulfate and lamivudine) Tablets, and TRIZIVIR(abacavir, lamivudine, and zidovudine) Tablets used to treat HIV infection. The formulation and dosage of lamivudine in EPIVIR-HBV are not appropriate for patients dually infected with HBV and HIV. If a decision is made to administer lamivudine to such patients, the higher dosage indicated for HIV therapy should be used as part of an appropriate combination regimen, and the prescribing information for EPIVIR, COMBIVIR, EPZICOM, or TRIZIVIR as well as for EPIVIR-HBV should be consulted. HIV counseling and testing should be offered to all patients before beginning EPIVIR-HBV and periodically during treatment because of the risk of rapid emergence of resistant HIV and limitation of treatment options if EPIVIR-HBV is prescribed to treat chronic hepatitis B in a patient who has unrecognized or untreated HIV infection or acquires HIV infection during treatment. ; Posttreatment Exacerbations of Hepatitis: Pancreatitis: Pancreatitis has been reported in patients receiving lamivudine, particularly in HIV-infected pediatric patients with prior nucleoside exposure.

ADVERSE REACTIONS Several serious adverse events reported with lamivudine (lactic acidosis and severe hepatomegaly with steatosis, posttreatment exacerbations of hepatitis B, pancreatitis, and emergence of viral mutants associated with reduced drug susceptibility and diminished treatment response) are also described in WARNINGS and PRECAUTIONS. Clinical Trials In Chronic Hepatitis B: Adults: Selected clinical adverse events observed with afrequency during therapy with EPIVIR-HBV compared with placebo are listed in Table 5. Frequencies of specified laboratory abnormalities during therapy with EPIVIR-HBV compared with placebo are listed in Table 6. Table 5. Selected Clinical Adverse Events (Frequency) in 3 Placebo-Controlled Clinical Trials in Adults During Treatmenta (Studies 1-3) EPIVIR-HBVPlaceboAdverse Event(n = 332)(n = 200)Non-site SpecificMalaise and fatigue24%28%Fever or chills7%9%Ear, Nose, and ThroatEar, nose, and throat infections25%21%Sore throat13%8%GastrointestinalNausea and vomiting15%17%Abdominal discomfort and pain16%17%Diarrhea14%12%MusculoskeletalMyalgia14%17%Arthralgia7%5%NeurologicalHeadache21%21%SkinSkin rashes5%5%a Includes patients treated for 52 to 68 weeks. Table 6. Frequencies of Specified Laboratory Abnormalities in 3 Placebo-Controlled Trials in Adults During Treatmenta (Studies 1-3) Test Patients With Abnormality/Patients With Observations (Abnormal Level) EPIVIR-HBV Placebo ALT >3 x baselineb 37/331 (11%) 26/199 (13%) Albumin <2.5 g/dL 0/331 (0%) 2/199 (1%) Amylase >3 x baseline 2/259 (<1%) 4/167 (2%) Serum Lipasex ULNc 19/189 (10%) 9/127 (7%) CPKx baseline 31/329 (9%) 9/198 (5%) Neutrophils <750/mm3 0/331 (0%) 1/199 (<1%) Platelets <50,000/mm3 10/272 (4%) 5/168 (3%) a Includes patients treated for 52 to 68 weeks. b See Table 7 for posttreatment ALT values. c Includes observations during and after treatment in the 2 placebo-controlled trials that collected this information. ULN = Upper limit of normal. In patients followed for up to 16 weeks after discontinuation of treatment, posttreatment ALT elevations were observed more frequently in patients who had received EPIVIR-HBV than in patients who had received placebo. A comparison of ALT elevations between Weeks 52 and 68 in patients who discontinued EPIVIR-HBV at Week 52 and patients in the same studies who received placebo throughout the treatment course is shown in Table 7 Table 7. Posttreatment ALT Elevations in 2 Placebo-Controlled Studies in Adults With No-Active-Treatment Follow-up (Studies 1 and 3) Abnormal Value Patients With ALT Elevation/Patients With Observationsa . EPIVIR-HBV Placebo ALTx baseline value 37/137 (27%) 22/116 (19%) ALTx baseline valueb 29/137 (21%) 9/116 (8%) ALTx baseline value and absolute ALT >500 IU/L 21/137 (15%) 8/116 (7%) ALTx baseline value 1/137 (0.7%) 1/116 (0.9%) a Each patient may be represented in one or more category. b Comparable to a Grade 3 toxicity in accordance with modified WHO criteria. ULN = Upper limit of normal. Lamivudine in Patients With HIV: In HIV-infected patients, safety information reflects a higher dose of lamivudine (150 mg b.i.d.) than the dose used to treat chronic hepatitis B in HIV-negative patients. In clinical trials using lamivudine as part of a combination regimen for treatment of HIV infection, several clinical adverse events occurred more often in lamivudine-containing treatment arms than in comparator arms. These included nasal signs and symptoms (20% vs. 11%), dizziness (10% vs. 4%), and depressive disorders (9% vs. 4%). Pancreatitis was observed in 9 of the 2,613 adult patients (<0.5%) who received EPIVIR in controlled clinical trials. Laboratory abnormalities reported more often in lamivudine-containing arms included neutropenia and elevations of liver function tests (also more frequent in lamivudine-containing arms for a retrospective analysis of HIV/HBV dually infected patients in one study), and amylase elevations. Please see the complete prescribing information for EPIVIR Tablets and Oral Solution for more information. Pediatric Patients With Hepatitis B: Pediatric Patients With HIV Infection: In early open-label studies of lamivudine in children with HIV, peripheral neuropathy and neutropenia were reported, and pancreatitis was observed in 14% to 15% of patients Observed During Clinical Practice: The following events have been identified during post-approval use of lamivudine in clinical practice. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to either their seriousness, frequency of reporting, potential causal connection to lamivudine, or a combination of these factors. Post-marketing experience with lamivudine at this time is largely limited to use in HIV-infected patients. Digestive: Stomatitis. Endocrine and Metabolic: Hyperglycemia. General: Weakness. Hemic and Lymphatic: Anemia (including pure red cell aplasia and severe anemias progressing on therapy), lymphadenopathy, splenomegaly. Hepatic and Pancreatic: Lactic acidosis and steatosis, pancreatitis, posttreatment exacerbation of hepatitis (see WARNINGS and PRECAUTIONS). Hypersensitivity: Anaphylaxis, urticaria. Musculoskeletal: Rhabdomyolysis. Nervous: Paresthesia, peripheral neuropathy. Respiratory: Abnormal breath sounds/wheezing. Skin: Alopecia, pruritus, rash.