lamivudine (Rx)

>10%

Cough

Diarrhea

Fatigue & malaise

Fever (peds)

Headache

Musculoskeletal pain

Nausea

Nervous system neuropathy

Pancreatitis

Peripheral neuropathy

Nasal S/S

Vomiting

1-10%

Abdominal cramps, abdominal pain

Anorexia &/or decr appetite

Arthralgia

Chills

Depression

Dizziness

Dyspepsia

Insomnia

Myalgia

Rash

Thrombocytopenia

Creatine phosphokinase increased

Frequency Not Defined

Body fat redistribution

Elevated amylase

Neutropenia

Hepatitis B exacerbation

Postmarketing reports

Immune reconstitution

Blood and lymphatic system disorders

Anemia (including pure red cell aplasia and severe anemias progressing on therapy), lymphadenopathy, splenomegaly, thrombocytopenia

Contraindications

Hypersensitivity

Cautions

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, reported with use of nucleoside analogues, including lamivudine; a majority of these cases have been in women; female sex and obesity may be risk factors for development of lactic acidosis and severe hepatomegaly with steatosis in patients treated with antiretroviral nucleoside analogues; suspend treatment 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

Exacerbation of hepatitis B in HBV/HIV coinfected patients may occur on discontinuation

Risk of immune reconstitution syndrome if used in combination with other antiretroviral drugs

Discontinue immediately if signs or symptoms of pancreatitis occur in patients with history of pancreatitis

EPIVIR-HBV is not appropriate for patients co-infected with HBV and HIV-1; if patient with unrecognized or untreated HIV-1 infection is prescribed EPIVIR-HBV for treatment of HBV, rapid emergence of HIV-1 resistance is likely to result because of subtherapeutic dose and inappropriate use of monotherapy for HIV-1 treatment

In order to reduce risk of resistance in patients receiving monotherapy, consider a switch to alternative regimen if serum HBV DNA remains detectable after 24 weeks of treatment; optimal therapy should be guided by resistance testing

Patients with HIV-1 infection should receive only dosage forms of lamivudine appropriate for treatment of HIV-1

Emergence of lamivudine-resistant HBV variants associated with lamivudine-containing antiretroviral regimens reported

Concomitant administration of emtricitabine with lamivudine-containing products not recommended

Hepatic decompensation (some fatal) reported in HIV-1/HCV co-infected patients receiving interferon and ribavirin-based regimens; monitor for treatment-associated toxicities; discontinue therapy as medically appropriate and consider dose reduction or discontinuation of interferon alfa, ribavirin, or both

Use with caution in pediatric patients with a history of pancreatitis or other significant risk factors for pancreatitis; discontinue treatment as clinically appropriate

Lower Virologic Suppression Rates and Increased Risk of Viral Resistance with Oral Solution

• Pediatric subjects who received lamivudine (Epivir) oral solution 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 lamivudine (Epivir) tablets; lamivudine (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; consider more frequent monitoring of HIV-1 viral load when treating with lamivudine (EPIVIR) oral solution

Pregnancy

A pregnancy registry has been established to monitor maternal-fetal outcomes of women exposed to lamivudine: 1-800-258-4263

Available data from the APR show no difference in the overall risk of birth defects for lamivudine or zidovudine compared with background rate for birth defects of 2.7% in the Metropolitan Atlanta Congenital Defects Program (MACDP) reference population; APR uses the MACDP as the U.S. reference population for birth defects in the general population; MACDP evaluates women and infants from a limited geographic area and does not include outcomes for births that occurred at less than 20 weeks gestation; rate of miscarriage is not reported in the APR

Lactation

The Centers for Disease Control and Prevention recommend that HIV-1-infected mothers in the United States not breastfeed infants to avoid risking postnatal transmission of HIV-1 infection; lamivudine is present in human milk; there is no information on effects of lamivudine or zidovudine on breastfed infant or effects of drugs on milk production; because of potential for (1) HIV-1 transmission (in HIV-negative infants), (2)developing viral resistance (in HIV-positive infants), and (3) serious adverse reactions in a breastfed infant, instruct mothers not to breastfeed if they are receiving therapy

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Nucleoside Reverse Transcriptase Inhibitor (NRTI); following phosphorylation, inhibits HIV reverse transcriptase by viral DNA chain termination; cytosine analog

Useful in combination with ZDV

ZDV-induced codon mutations result in viral sensitivity to drug

Pharmacokinetics

Absorption: Rapid

Vd: 1.3 L/kg

Protein Bound: <36%

Metabolism: 5.6% to trans-sulfoxide metabolite

Bioavailability: Absolute; Cp max decreased with food although AUC not significantly affected, 66% (children); 87% (adults)

Half-life elimination: 2 hr (children); 5-7 hr (adults)

Excretion: Primarily urine