lamivudine (3TC)
Epivir, Epivir-HBV

Available forms
Available by prescription only
Epivir
Oral solution: 10 mg/ml
Tablets: 150 mg, 300 mg
Epivir-HBV
Oral solution: 5 mg/ml
Tablets: 100 mg

Indications and dosages
 Treatment of HIV infection (should be used with other antiretrovirals). Adults and children age 16 and older: 150 mg P.O. b.i.d. Or, 300 mg P.O. once daily.
Children ages 3 months to 16 years: 4 mg/kg P.O. b.i.d. Maximum dose is 150 mg b.i.d.
Neonates 30 days or younger ◇: 2 mg/kg P.O. b.i.d.
≡ Dosage adjustment. For adults and adolescents with renal impairment, see below. For children with renal impairment, consider decreasing the dose or increasing the dosage interval.

Creatinine clearance (ml/min) Recommended dosage 30-49 150 mg once daily 15-29 150 mg first dose; then 100 mg once daily 5-14 150 mg first dose; then 50 mg once daily < 5 50 mg first; then 25 mg once daily

 Treatment of chronic hepatitis B with evidence of hepatitis B viral replication and active liver inflammation. Adults: 100 mg P.O. once daily. Safety and efficacy of treatment beyond 1 year haven’t been established; optimum duration of treatment isn’t known. Formulation and dosage of lamivudine in Epivir-HBV aren’t appropriate for those dually infected with hepatitis B virus (HBV) and HIV; test patients for HIV before starting treatment. If lamivudine is administered to patients with HBV and HIV, use the higher dosage indicated for HIV therapy as part of an appropriate combination regimen.
Children ages 2 to 17: 3 mg/kg P.O. once daily, to maximum daily dose of 100 mg. Safety and efficacy of treatment beyond 1 year haven’t been established; optimum duration of treatment isn’t known.
≡ Dosage adjustment. For patients age 16 and older with renal impairment, if creatinine clearance is 30 to 49 ml/minute, 100 mg P.O. on the first day, then 50 mg P.O. once daily thereafter. If clearance is 15 to 29 ml/minute, 100 mg on the first day, then 25 mg P.O. once daily thereafter. If clearance is 5 to 14 ml/minute, 35 mg on the first day, then 15 mg once daily thereafter. If creatinine clearance is less than 5 ml/minute, 35 mg on the first day, then 10 mg P.O. once daily thereafter.
 Postexposure prophylaxis following occupational exposure to HIV ◇. Adults: 150 mg P.O. b.i.d. with oral zidovudine (600 mg daily); oral indinavir (800 mg q 8 hours) or oral nelfinavir (750 mg P.O. t.i.d.) is added if risk of transmission is likely. Initiate within a few hours and continue for 28 days.

Pharmacodynamics
Antiviral action: Lamivudine inhibits HIV reverse transcription via viral DNA chain termination. RNA- and DNA-dependent DNA polymerase activities also are inhibited.

Pharmacokinetics
Absorption: Rapidly absorbed after oral administration in HIV- and HBV-infected patients.
Distribution: Believed to be distributed into extravascular spaces. Volume of distribution is independent of dose and doesn’t correlate with body weight. Less than 36% is bound to plasma proteins.
Metabolism: Metabolism is minor route of elimination. The only known metabolite is the trans-sulfoxide metabolite.
Excretion: Primarily eliminated unchanged in urine. Mean elimination half-life is 5 to 7 hours.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug. Use drug with extreme caution and only if there’s no satisfactory alternative therapy in children with history of pancreatitis or other significant risk factors for development of pancreatitis. Stop treatment with lamivudine immediately if clinical signs, symptoms, or laboratory abnormalities suggest pancreatitis.
  Use cautiously and reduce dosage in children with a history of prior therapy with nucleoside reverse transcriptase inhibitors and in patients with impaired renal function.

Interactions
Drug-drug. Co-trimoxazole: Decreases clearance of lamivudine, which may increase blood lamivudine levels. Monitor patient closely.

Adverse reactions
Adverse reactions are related to the combination therapy of lamivudine and zidovudine. CNS: malaise, headache, fatigue, neuropathy, dizziness, insomnia and other sleep disorders, fever, depressive disorders.
EENT: nasal symptoms, sore throat.
GI: nausea, diarrhea, vomiting, anorexia, abdominal pain, abdominal cramps, dyspepsia, pancreatitis (in children younger than age 12).
Hematologic: neutropenia, anemia, thrombocytopenia.
Metabolic: lactic acidosis.
Musculoskeletal: musculoskeletal pain, myalgia, arthralgia.
Respiratory: cough.
Skin: rash.
Other: chills.

Effects on lab test results
• May increase ALT and bilirubin levels.
• May decrease hemoglobin and neutrophil and platelet counts.

Overdose and treatment
No information available.

Special considerations
• When used in treatment of HIV infection, drug must be administered with zidovudine. It isn’t intended for use as monotherapy.
• Safety and efficacy of treatment of HBV for periods over 1 year or in patients with decompensated liver disease or organ transplant haven’t been established.
• Monotherapy with lamivudine in patients with HIV-HBV co-infection in HBV dosage is inadequate and may lead to rapid emergence of HIV resistance. Counseling and testing for HIV infection before and periodically during treatment are recommended. Use higher dosage in combination therapy with other appropriate antiretrovirals.
• Monitor CBC, platelet count, and liver function test values throughout therapy.
• Lactic acidosis and severe hepatomegaly with steatosis have been reported in patients receiving lamivudine. Stop treatment if signs of lactic acidosis or hepatotoxicity develop.
Pregnant patients
• An Antiretroviral Pregnancy Registry has been established to monitor maternal-fetal outcomes of pregnant women exposed to lamivudine. Pregnant patients can be registered by calling 1-800-258-4263.
Breast-feeding patients
• To avoid transmitting HIV to the infant, HIV-positive women shouldn’t breast-feed.
Pediatric patients
• Safety and efficacy in treatment of HIV infection haven’t been established in children younger than age 3 months.

Patient education
• Inform patient that long-term effects of drug are unknown.
• Stress importance of taking drug exactly as prescribed.
• Instruct parents of children receiving drug about signs and symptoms of pancreatitis and tell them to report these immediately if they occur.
• If patient is receiving dosage of less than therapeutic levels for HIV treatment, inform him that HIV testing is recommended.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use