epivir

Important safety information

Co-infected HIV‑1/HBV Patients: Emergence of lamivudine-resistant HBV variants associated with lamivudine‑containing antiretroviral regimens has been reported. ( 5.1 ) • Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues. ( 5.2 ) • Pancreatitis: Use with caution in pediatric patients with a history of pancreatitis or other significant risk factors for pancreatitis. Discontinue treatment as clinically appropriate. ( 5.3 ) • Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy. ( 5.4 ) • Lower virologic suppression rates and increased risk of viral resistance were observed in pediatric subjects who received EPIVIR oral solution concomitantly with other antiretroviral oral solutions compared with those who received tablets. An all-tablet regimen should be used when possible. ( 5.5 ) 5.1 Patients with Hepatitis B Virus Co-Infection Posttreatment Exacerbations of Hepatitis Clinical and laboratory evidence of exacerbations of hepatitis have occurred after discontinuation of lamivudine. These exacerbations have been detected primarily by serum ALT elevations in addition to re‑emergence of HBV DNA. Although most events appear to have been self‑limited, fatalities have been reported in some cases. Similar events have been reported from postmarketing experience after changes from lamivudine‑containing HIV‑1 treatment regimens to non‑lamivudine–containing regimens in patients infected with both HIV‑1 and HBV. The causal relationship to discontinuation of lamivudine treatment is unknown. Patients should be closely monitored with both clinical and laboratory follow‑up for at least several months after stopping treatment. Important Differences among Lamivudine ‑ Containing Products EPIVIR tablets and oral solution contain a higher dose of the same active ingredient (lamivudine) than EPIVIR‑HBV tablets and EPIVIR‑HBV oral solution. EPIVIR‑HBV was developed for patients with chronic hepatitis B. The formulation and dosage of lamivudine in EPIVIR‑HBV are not appropriate for patients co-infected with HIV‑1 and HBV. Safety and efficacy of lamivudine have not been established for treatment of chronic hepatitis B in patients co‑infected with HIV‑1 and HBV. If treatment with EPIVIR‑HBV is prescribed for chronic hepatitis B for a patient with unrecognized or untreated HIV-1 infection, rapid emergence of HIV‑1 resistance is likely to result because of the subtherapeutic dose and the inappropriateness of monotherapy HIV‑1 treatment. If a decision is made to administer lamivudine to patients co‑infected with HIV‑1 and HBV, EPIVIR tablets, EPIVIR oral solution, or another product containing the higher dose of lamivudine should be used as part of an appropriate combination regimen. Emergence of Lamivudine-Resistant HBV Safety and efficacy of lamivudine have not been established for treatment of chronic hepatitis B in subjects dually infected with HIV-1 and HBV (see full prescribing information for EPIVIR-HBV). Emergence of hepatitis B virus variants associated with resistance to lamivudine has also been reported in HIV-1–infected subjects who have received lamivudine-containing antiretroviral regimens in the presence of concurrent infection with hepatitis B virus. 5.2 Lactic Acidosis and Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues, including EPIVIR. A majority of these cases have been in women. Female sex and obesity may be risk factors for the development of lactic acidosis and severe hepatomegaly with steatosis in patients treated with antiretroviral nucleoside analogues. Treatment with EPIVIR should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity, which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations. 5.3 Pancreatitis In pediatric patients with a history of prior antiretroviral nucleoside exposure, a history of pancreatitis, or other significant risk factors for the development of pancreatitis, EPIVIR should be used with caution. Treatment with EPIVIR should be stopped immediately if clinical signs, symptoms, or laboratory abnormalities suggestive of pancreatitis occur [see Adverse Reactions ( 6.1 )] . 5.4 Immune Reconstitution Syndrome Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including EPIVIR. During the initial phase of combination antiretroviral treatment, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment. Autoimmune disorders (such as Graves’ disease, polymyositis, and Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution, however, the time to onset is more variable, and can occur many months after initiation of treatment. 5.5 Lower Virologic Suppression Rates and Increased Risk of Viral Resistance with Oral Solution Pediatric subjects who received EPIVIR oral solution (at weight band-based doses approximating 8 mg per kg per day) concomitantly with other antiretroviral oral solutions at any time in the ARROW trial had lower rates of virologic suppression, lower plasma lamivudine exposure, and developed viral resistance more frequently than those receiving EPIVIR tablets [see Clinical Pharmacology ( 12.3 ), Microbiology ( 12.4 ), Clinical Studies ( 14.2 )] . EPIVIR scored tablet is the preferred formulation for HIV-1‑infected pediatric patients who weigh at least 14 kg and for whom a solid dosage form is appropriate. An all-tablet regimen should be used when possible to avoid a potential interaction with sorbitol [see Clinical Pharmacology ( 12.3 )] . Consider more frequent monitoring of HIV-1 viral load when treating with EPIVIR oral solution.