No

Antiretroviral Agent, Reverse Transcriptase Inhibitor (Non-Nucleoside)

Treatment of HIV infection when antiretroviral therapy is warranted; should always be used as part of a multidrug regimen (at least three antiretroviral agents); indicated for the treatment of chronic hepatitis B associated with evidence of hepatitis B viral replication and active liver inflammation

C

Clinical effects on the fetus: Use only if the potential benefits outweigh the risks. Combination therapy with zidovudine and lamivudine is currently being investigated to decrease the maternal/fetal transmission of HIV.

Breast-feeding/lactation: HIV-infected mothers are discouraged from breast-feeding to decrease postnatal transmission of HIV

Hypersensitivity to lamivudine or any component

A decreased dosage is recommended in patients with renal dysfunction since AUC, C_max, and half-life increased with diminishing renal function; use with extreme caution in children with history of pancreatitis or risk factors for development of pancreatitis. Do not use as monotherapy in treatment of HIV.

>10%:

Central nervous system: Headache, insomnia, malaise, fatigue, pain

Gastrointestinal: Nausea, diarrhea, vomiting

Neuromuscular & skeletal: Peripheral neuropathy, paresthesia

Respiratory: Nasal signs and symptoms, cough

1% to 10%:

Central nervous system: Dizziness, depression, fever, chills

Dermatologic: Rashes

Gastrointestinal: Anorexia, abdominal pain, dyspepsia, increased amylase

Hematologic: Neutropenia, anemia

Hepatic: Elevated AST/ALT

Neuromuscular & skeletal: Myalgia, arthralgia

<1%: Pancreatitis, thrombocytopenia, hyperbilirubinemia

Very limited information is available although there have been no clinical signs or symptoms noted and hematologic tests remained normal in overdose

No antidote is available; unknown dialyzability

Increased effect: Zidovudine concentrations increase (~39%) with coadministration with lamivudine; trimethoprim/sulfamethoxazole increases lamivudine's AUC and decreases its renal clearance by 44% and 29%, respectively; although the AUC was not significantly affected, absorption of lamivudine was slowed and C_max was 40% lower when administered to patients in the fed versus the fasted state

Store solution at 2°C to 25°C tightly closed

After lamivudine is triphosphorylated, the principle mode of action is inhibition of HIV reverse transcription via viral DNA chain termination; inhibits RNA- and DNA-dependent DNA polymerase activities of reverse transcriptase. The monophosphate form of lamivudine is incorporated into the viral DNA by hepatitis B virus polymerase, resulting in DNA chain termination.

Absorption: Oral: Rapid

Distribution: V_d: 1.3 L/kg

Protein binding, plasma: <36%

Metabolism: 5.6% metabolized to trans-sulfoxide metabolite

Bioavailability: Absolute; Cp_max decreased with food although AUC not significantly affected

Children: 66%

Adults: 87%

Half-life: Children: 2 hours; Adults: 5-7 hours

Elimination: Most eliminated unchanged in urine

Oral: Use with at least two other antiretroviral agents when treating HIV

Adolescents 12-16 years and Adults: 150 mg twice daily

Prevention of HIV following needlesticks: 150 mg twice daily (with zidovudine and a protease inhibitor)

Adults <50 kg: 2 mg/kg twice daily

Treatment of hepatitis B: 100 mg/day

Dosing interval in renal impairment in patients >16 years for HIV:

Cl_cr 30-49 mL/minute: Administer 150 mg once daily

Cl_cr 15-29 mL/minute: Administer 150 mg first dose, then 100 mg once daily

Cl_cr 5-14 mL/minute: Administer 150 mg first dose, then 50 mg once daily

Cl_cr <5 mL/minute: Administer 50 mg first dose, then 25 mg once daily

Dosing interval in renal impairment in patients with hepatitis B:

Cl_cr 30-49: Administer 100 mg first dose then 50 mg once daily

Cl_cr 15-29: Administer 100 mg first dose then 25 mg once daily

Cl_cr 5-14: Administer 35 mg first dose then 15 mg once daily

Cl_cr <5: Administer 35 mg first dose then 10 mg once daily

Dialysis: No data available

Amylase, bilirubin, liver enzymes, hematologic parameters, viral load, and CD4 count; signs and symptoms of pancreatitis

Fatigue and insomnia are common; may cause dizziness or depression

May rarely cause neutropenia; use caution with clozapine and carbamazepine

No information available to require special precautions

No effects or complications reported

This is not a cure for AIDS or AIDS complex, nor will it reduce the risk of transmission to others. Long-term effects are unknown. You will need frequent blood tests to adjust dosage for maximum therapeutic effect. Take as directed for full course of therapy; do not discontinue (even if feeling better). You may experience loss of appetite; change in taste (sucking on lozenges, chewing gum, or small frequent meals may help); dizziness or numbness (use caution when driving or engaging in tasks that require alertness until response to drug is known); headache, fever, or muscle pain (an analgesic may be recommended). Report persistent lethargy, acute headache, severe nausea or vomiting, difficulty breathing, loss of sensation, or rash. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Do not breast-feed.

Solution, oral: 5 mg/mL (240 mL); 10 mg/mL (240 mL)

Tablet: 100 mg, 150 mg

CDC and the National Foundation for Infectious Disease, "Update: Provisional Public Health Service Recommendations for Chemoprophylaxis After Occupational Exposure to HIV," MMWR Morb Mortal Wkly Rep, 1996, 45(22):468-80.

Dienstag JL, Perrillo, RP, Schiff, ER, et al, "A Preliminary Trial of Lamivudine for Chronic Hepatitis B Infection," N Engl J Med, 1995, 333(25):1657-61.

Eron JJ, Benoit SL, Jemsek J, et al, "Treatment With Lamivudine, Zidovudine, or Both in HIV-Positive Patients With 200 to 500 CD4⁺ Cells Per Cubic Millimeter," N Engl J Med, 1995, 333(25):1662-9.

Hilts AE and Fish DN, "Dosage Adjustment of Antiretroviral Agents in Patients With Organ Dysfunction," Am J Health Syst Pharm, 1998, 55:2528-33.

Johnson MA, Verpooten GA, Daniel MJ, et al, "Single Dose Pharmacokinetics of Lamivudine in Subjects With Impaired Renal Function and the Effect of Haemodialysis," Br J Clin Pharmacol, 1998, 46(1):21-7.

Lai CL, Chien RN, Leung NW, et al, "A One-Year Trial of Lamivudine for Chronic Hepatitis B," N Engl J Med, 1998, 339(2):61-8.

Lewis LL, Mueller B, Schock R, et al, "A Phase I/II Study to Evaluate the Safety, Toxicity, and Preliminary Efficacy of Combinations of Lamivudine (3TC), Zidovudine (AZT) and Didanosine (ddI) in Children With HIV Infection," Natl Conf Hum Retroviruses Relat Infect (2nd), 1995, Jan 29-Feb 2:103.

Lewis LL, Venzon D, Church J, et al, "Lamivudine in Children With Human Immunodeficiency Virus Infection: A Phase I/II Study," J Infect Dis, 1996, 174(1):16-25.

Perry CM and Faulds D, "Lamivudine. A Review of Its Antiviral Activity, Pharmacokinetic Properties and Therapeutic Efficacy in the Management of HIV Infection," Drugs, 1997, 53(4):657-80.

Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children, "Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection," March 1, 1999, http://www.hivatis.org.