Lamivudine

May cause redistribution/accumulation of fat (eg, central obesity, buffalo hump, peripheral wasting, facial wasting, breast enlargement, cushingoid appearance).

Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection during initial HIV treatment or activation of autoimmune disorders (eg, Graves disease, polymyositis, Guillain-Barré syndrome) later in therapy; further evaluation and treatment may be required.

Lactic acidosis and severe hepatomegaly with steatosis have been reported with nucleoside analogues, including fatal cases; suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity; use with caution in patients with risk factors for liver disease (risk may be increased with female gender, obesity, pregnancy, or prolonged exposure); transaminase elevation may/may not accompany hepatomegaly and steatosis.

Has been reported, particularly in HIV-infected children with a history of nucleoside use. Discontinue treatment if signs of symptoms of pancreatitis occur. Disease-related concerns:

Severe acute exacerbations of hepatitis B (some fatal) have been reported in patients with HBV or HIB/HBV coinfection who have discontinued lamivudine; hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months after discontinuation. Initiate antihepatitis B (HBV) medications if clinically appropriate.

Use with caution in patients with renal impairment; dosage reduction recommended.

- HIV: [US Boxed Warning]: HIV-1 resistance may emerge in chronic hepatitis B-infection patients with unrecognized or untreated HIV-1 infection. Counseling and HIV testing should be offered to all patients before beginning treatment with lamivudine for hepatitis B and then periodically during treatment. Lamivudine dosing for hepatitis B is subtherapeutic if used for HIV-1 infection treatment. Lamivudine monotherapy is not appropriate for HIV-1 infection treatment. Lamivudine resistant HIV-1 can develop rapidly and limit treatment options if used in unrecognized or untreated HIV-1 infection or if a patient becomes coinfected during HBV treatment. Lamivudine dosing for hepatitis B is also subtherapeutic if used for HIV-1/HBV coinfection treatment. If lamivudine is chosen as part of a HIV-1 treatment regimen in coinfected patients, the higher lamivudine dosage indicated for HIV-1 therapy should be used, with other drugs, in an appropriate combination regimen. - HBV: Patients treated with lamivudine-HBV with YMDD-mutant HBV showed diminished treatment response (lower rates of HbeAg seroconversion and HbeAg loss, more frequent return of positive HBV DNA, more frequent ALT elevations) compared to patients without evidence of YMDD substitutions. Emergence of lamivudine resistant HBV variants has also been reported in HIV-1/HBV coinfected patients who have received lamivudine-containing antiretroviral regimens. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information

Use with caution in combination with interferon alfa with or without ribavirin in HIV/HCV coinfected patients; monitor closely for hepatic decompensation, anemia, or neutropenia; dose reduction or discontinuation of interferon and/or ribavirin may be required if toxicity evident. Special populations:

Use with caution in pediatric patients with a history of prior antiretroviral nucleoside exposure or pancreatitis, or other significant risk factors for development of pancreatitis. Dosage form specific issues:

Epivir HBV: [US Boxed Warning]: Do not use Epivir HBV tablets or Epivir HBV oral solution for the treatment of HIV.

Use of lamivudine oral solution has been associated with lower rates of virologic suppression, lower plasma lamivudine exposure, and increased rates of resistance when compared to lamivudine tablets in pediatric clinical trials. Lamivudine scored tablet is the preferred formulation for HIV-1 infected pediatric patients weighing ≥14 kg and for whom a solid dosage form is appropriate; consider more frequent monitoring of HIV-1 viral load if oral solution is used.

Lamivudine oral solutions contains 3 g of sucrose/15 mL; advise diabetic patients of sucrose content.

Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated hyperosmolality, lactic acidosis, seizures and respiratory depression; use caution (AAP 1997; Zar 2007). Other warnings/precautions:

-HIV: Do not use as monotherapy in treatment of HIV. Treatment of HIV in patients with unrecognized/untreated HBV may lead to rapid HBV resistance; HIV-infected patients should be screened for hepatitis B prior to starting lamivudine HIV therapy. Lamivudine combined with emtricitabine is not recommended as a dual-nucleoside reverse transcriptase inhibitor (NRTI) combination due to similar resistance patterns and negligible additive antiviral activity. Do not use lamivudine/abacavir (plus efavirenz or plus atazanavir/ritonavir) in adolescent and adult HIV-1 patients with a pre-ART HIV RNA >100,000 copies/mL (HHS [adult] 2017). - HBV: Current clinical hepatitis B practice guidelines do not recommend lamivudine for initial use in the management of chronic HBV due to low barrier to resistance; other antiviral agents with a high genetic barrier to drug resistance are preferred (eg, tenofovir or entecavir) (AASLD [Terrault 2016]). - HIV/HBV coinfection: Lamivudine and tenofovir is a recommended NRTI backbone in a fully suppressive antiretroviral regimen to provide activity against both HIV and HBV (HHS [adult] 2017).