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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(la MI vyoo deen)
Generic Available (U.S.)
No
Index Terms
U.S. Brand Names
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Epivir®: Treatment of HIV infection when antiretroviral therapy is warranted; should always be used as part of a multidrug regimen (at least three antiretroviral agents)
Epivir-HBV®: Treatment of chronic hepatitis B associated with evidence of hepatitis B viral replication and active liver inflammation. Resistance develops rapidly in hepatitis B; consider use only if other anti-HBV antiviral agents with more favorable resistance patterns cannot be used.
Use: Unlabeled/Investigational
Postexposure prophylaxis for HIV exposure as part of a multidrug regimen
Pregnancy Risk Factor
C
Pregnancy Considerations
Adverse events were observed in some animal reproduction studies. Lamivudine crosses the human placenta. No increased risk of overall birth defects has been observed following first trimester exposure according to data collected by the antiretroviral pregnancy registry. The pharmacokinetics of lamivudine during pregnancy are not significantly altered and dosage adjustment is not required. The Perinatal HIV Guidelines Working Group recommends lamivudine for use during pregnancy; the combination of lamivudine with zidovudine is the recommended dual combination NRTI in pregnancy. Lamivudine plus zidovudine and ritonavir-boosted lopinavir is the preferred regimen in antiretroviral-naive pregnant women (DHHS, 2011). It may also be used in combination with zidovudine in HIV-infected women who are in labor, but have had no prior antiretroviral therapy, in order to reduce the maternal-fetal transmission of HIV. Cases of lactic acidosis/hepatic steatosis syndrome related to mitochondrial toxicity have been reported in pregnant women receiving nucleoside analogues. It is not known if pregnancy itself potentiates this known side effect; however, women may be at increased risk of lactic acidosis and liver damage. In addition, these adverse events are similar to other rare but life-threatening syndromes which occur during pregnancy (eg, HELLP syndrome). Hepatic enzymes and electrolytes should be monitored frequently during the third trimester of pregnancy in women receiving nucleoside analogues and clinicians should watch for early signs of the syndrome. Use caution with hepatitis B coinfection; hepatitis B flare may occur if lamivudine is discontinued postpartum. Healthcare providers are encouraged to enroll pregnant women exposed to antiretroviral medications in the Antiretroviral Pregnancy Registry (1-800-258-4263 or www.APRegistry.com). Healthcare providers caring for HIV-infected women and their infants may contact the National Perinatal HIV Hotline (888-448-8765) for clinical consultation.
Lactation
Enters breast milk/contraindicated
Breast-Feeding Considerations
In infants born to mothers who are HIV positive, HAART while breast-feeding may decrease postnatal infection. However, maternal or infant antiretroviral therapy does not completely eliminate the risk of postnatal HIV transmission. In addition, multiclass-resistant virus has been detected in breast-feeding infants despite maternal therapy.
In the United States where formula is accessible, affordable, safe, and sustainable, complete avoidance of breast-feeding by HIV-infected women is recommended to decrease potential transmission of HIV.
Contraindications
Hypersensitivity to lamivudine or any component of the formulation
Warnings/Precautions
Boxed warnings:
• Chronic hepatitis B: See “Disease-related concerns” below.
• Epivir-HBV®: See “Dosage form specific issues” below.
• Lactic acidosis/hepatomegaly: See “Concerns related to adverse effects” below.
Concerns related to adverse effects:
• Fat redistribution: May cause redistribution of fat (eg, buffalo hump, peripheral wasting with increased abdominal girth, cushingoid appearance).
• Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection; further evaluation and treatment may be required.
• Lactic acidosis/hepatomegaly: [U.S Boxed Warning]: Lactic acidosis and severe hepatomegaly with steatosis have been reported with nucleoside analogues, including fatal cases; use with caution in patients with risk factors for liver disease (risk may be increased with female gender, obesity, pregnancy or prolonged exposure) and suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity (transaminase elevation may/may not accompany hepatomegaly and steatosis).
• Pancreatitis: Has been reported, particularly in HIV-infected children with a history of nucleoside use.
Disease-related concerns:
• Chronic hepatitis B: [U.S. Boxed Warning]: Monitor patients closely for several months following discontinuation of therapy for chronic hepatitis B; clinical exacerbations may occur. Treatment of HBV in patients with unrecognized/untreated HIV may lead to rapid HIV resistance;
• Renal impairment: Use with caution in patients with renal impairment; dosage reduction recommended.
Concurrent drug therapy issues:
• Interferon alfa: Use with caution in combination with interferon alfa with or without ribavirin in HIV/HBV 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:
• Pediatrics: Use with extreme caution in children with history of pancreatitis or risk factors for development of pancreatitis.
Dosage form specific issues:
• Epivir-HBV®: [U.S. Boxed Warning]: Do not use Epivir-HBV® tablets or Epivir-HBV® oral solution for the treatment of HIV.
Other warnings/precautions:
• Appropriate use:
- 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. Lamivudine combined with emtricitabine is not recommended as a dual-NRTI combination due to similar resistance patterns and negligible additive antiviral activity; lamivudine and tenofovir combination is preferred as the NRTIs in a fully suppressive antiretroviral regimen (DHHS, 2011).
- HBV: Not recommended as first line therapy of chronic HBV due to high rate of resistance; consider use only if other anti-HBV antiviral agents with more favorable resistance patterns cannot be used. Use may be appropriate in short-term treatment of acute HBV (Lok, 2009). Potential compliance problems, frequency of administration, and adverse effects should be discussed with patients before initiating therapy to help prevent the emergence of resistance.
- HIV/HBV coinfection: Lamivudine and tenofovir are a preferred NRTI backbone in a fully suppressive antiretroviral regimen to provide activity against both HIV and HBV (DHHS, 2011).
Adverse Reactions
Reported for treatment of HIV or HBV in adults. Incidence data include patients on combination therapy with other antiretroviral agents.
>10%:
Central nervous system: Headache (21% to 35%), fatigue (24% to 27%), insomnia (11%)
Gastrointestinal: Nausea (15% to 33%), diarrhea (14% to 18%), pancreatitis (range: 0.3% to 18%; higher percentage in pediatric patients), abdominal pain (9% to 16%), vomiting (13% to 15%)
Hematologic: Neutropenia (7% to 15%)
Hepatic: Transaminases increased (2% to 11%)
Neuromuscular & skeletal: Myalgia (8% to 14%), neuropathy (12%), musculoskeletal pain (12%)
Respiratory: Nasal signs and symptoms (20%), cough (18%), sore throat (13%)
Miscellaneous: Infections (25%; includes ear, nose, and throat)
1% to 10%:
Central nervous system: Dizziness (10%), depression (9%), fever (7% to 10%), chills (7% to 10%)
Dermatologic: Rash (5% to 9%)
Gastrointestinal: Anorexia (10%), lipase increased (10%), abdominal cramps (6%), dyspepsia (5%), amylase increased (<1% to 4%), heartburn
Hematologic: Thrombocytopenia (1% to 4%), hemoglobinemia (2% to 3%)
Neuromuscular & skeletal: Creatine phosphokinase increased (9%), arthralgia (5% to 7%)
<1%, postmarketing, and/or case reports: Alopecia, anaphylaxis, anemia, body fat redistribution, hepatitis B exacerbation, hepatomegaly, hyperbilirubinemia, hyperglycemia, immune reconstitution syndrome, lactic acidosis, lymphadenopathy, muscle weakness, paresthesia, peripheral neuropathy, pruritus, red cell aplasia, rhabdomyolysis, splenomegaly, steatosis, stomatitis, urticaria, weakness, wheezing
Drug Interactions
Emtricitabine: LamiVUDine may enhance the adverse/toxic effect of Emtricitabine. Risk X: Avoid combination
Ganciclovir-Valganciclovir: May enhance the adverse/toxic effect of Reverse Transcriptase Inhibitors (Nucleoside). Hematologic toxicity is of specific concern. Risk D: Consider therapy modification
Ribavirin: May enhance the hepatotoxic effect of Reverse Transcriptase Inhibitors (Nucleoside). Lactic acidosis may occur. Risk D: Consider therapy modification
Trimethoprim: May decrease the excretion of LamiVUDine. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Food: Food decreases the rate of absorption and Cmax; however, there is no change in the systemic AUC. Therefore, may be taken with or without food.
Storage
Oral solution:
Epivir®: Store at 25°C (77°F) tightly closed.
Epivir-HBV®: Store at 20°C to 25°C (68°F to 77°F) tightly closed.
Tablet: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
Mechanism of Action
Lamivudine is a cytosine analog. 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.
Pharmacodynamics/Kinetics
Absorption: Rapid
Distribution: Vd: 1.3 L/kg
Protein binding, plasma: <36%
Metabolism: 4.2% to trans-sulfoxide metabolite
Bioavailability: Absolute; Cpmax decreased with food although AUC not significantly affected
Children: 66%
Adults: 86% to 87%
Half-life elimination: Children: 2 hours; Adults: 5-7 hours
Time to peak, plasma: Fed: 3.2 hours; Fasted: 0.9 hours
Excretion: Primarily urine (as unchanged drug)
Dosage
Oral: Note: Use with at least two other antiretroviral agents when treating HIV.
HIV:
Neonates <30 days (DHHS [pediatric], 2010): 2 mg/kg/dose twice daily
Infants 1-3 months (DHHS [pediatric], 2010): 4 mg/kg/dose twice daily
Infants and Children 3 months to 16 years: 4 mg/kg/dose twice daily (maximum: 150 mg/dose twice daily)
Alternate weight-based dosing using scored 150 mg tablets (DHHS [pediatric], 2010):
14-21 kg: 75 mg/dose twice daily (150 mg/day)
22-29 kg: 75 mg in the morning, 150 mg in the evening (225 mg/day)
≥30 kg: 150 mg/dose twice daily (300 mg/day)
Adults: 150 mg twice daily or 300 mg once daily
<50 kg (DHHS [pediatric], 2010): 4 mg/kg/dose twice daily (maximum: 150 mg/dose twice daily)
Treatment of hepatitis B (Epivir-HBV®): Note: Not a preferred agent in chronic HBV treatment due to high rates of resistance; consider alternative agents:
Children 2-17 years: 3 mg/kg/dose once daily (maximum: 100 mg/day)
Adults: 100 mg/day
Treatment duration (AASLD practice guidelines):
Hepatitis Be antigen (HBeAg) positive chronic hepatitis: Treat ≥1 year until HBeAg seroconversion and undetectable serum HBV DNA; continue therapy for ≥6 months after HBeAg seroconversion
HBeAg negative chronic hepatitis: Treat >1 year until hepatitis B surface antigen (HBsAg) clearance
Note: Patients achieving <2 log decrease in serum HBV DNA after at least 6 months of therapy should either receive additional treatment or be switched to an alternative therapy (Lok, 2009).
Treatment of hepatitis B/HIV coinfection (in patients with both infections requiring treatment): Note: The formulation and dosage of Epivir-HBV® are not appropriate for patients infected with both HBV and HIV. Tenofovir and lamivudine are a preferred NRTI backbone in a fully suppressive antiretroviral regimen for the treatment of HIV/HBV coinfection (DHHS, 2011).
Infants and Children: 4 mg/kg/dose (maximum: 150 mg/dose) twice daily, in combination with other antiretrovirals in a HAART regimen (CDC, 2009).
Adolescents and Adults: 150 mg/dose twice daily or 300 mg/dose once daily, in combination with other antiretrovirals in a HAART regimen (DHHS, 2011)
Postexposure prophylaxis for HIV exposure (unlabeled use [CDC, 2005]): Adolescents ≥16 years and Adults: 150 mg/dose twice daily or 300 mg/dose once daily, in combination with zidovudine, tenofovir, stavudine, or didanosine, with or without a protease inhibitor depending on risk
Prevention of maternal-fetal HIV transmission (DHHS [perinatal], 2010): Note: Lamivudine may be used in combination with zidovudine and nevirapine in select situations (eg, infants born to mothers with suboptimal viral suppression at delivery, infants born to mothers with only intrapartum therapy or no therapy, or infants born to mothers with known antiretroviral drug-resistant virus). Lamivudine is used in this situation to reduce the development of nevirapine resistant virus:
Mother: 150 mg twice daily starting at onset of labor and continuing through 1 week postpartum
Neonate: 2 mg/kg/dose twice daily given at birth through 1 week of age
Dosing adjustment in renal impairment: HIV:
Patients ≤16 years: Insufficient data; however, dose reduction should be considered.
Patients >16 years:
Clcr 30-49 mL/minute: Administer 150 mg once daily
Clcr 15-29 mL/minute: Administer 150 mg first dose, then 100 mg once daily
Clcr 5-14 mL/minute: Administer 150 mg first dose, then 50 mg once daily
Clcr <5 mL/minute: Administer 50 mg first dose, then 25 mg once daily
Dosing adjustment in renal impairment: Hepatitis B: Adults:
Clcr 30-49: Administer 100 mg first dose then 50 mg once daily
Clcr 15-29: Administer 100 mg first dose then 25 mg once daily
Clcr 5-14: Administer 35 mg first dose then 15 mg once daily
Clcr <5: Administer 35 mg first dose then 10 mg once daily
Dialysis: Negligible amounts are removed by 4-hour hemodialysis or peritoneal dialysis. Supplemental dosing not needed; however, dosing after dialysis is recommended (DHHS, 2011).
Administration: Oral
May be administered without regard to meals. Adjust dosage in renal failure.
Monitoring Parameters
Amylase, bilirubin, liver enzymes (every 3 months during therapy), hematologic parameters, HIV viral load, and CD4 count; signs/symptoms of pancreatitis, HBV DNA (every 3-6 months during therapy), HBeAg and anti-HBe (after 1 year of therapy and every 3-6 months thereafter); signs/symptoms of HBV relapse/exacerbation (every 1-3 months for 6 months after discontinuation and every 3-6 months thereafter)
Dietary Considerations
May be taken without regard to meals. Some products may contain sucrose.
Patient Education
Maintain adequate hydration unless instructed to restrict fluid intake. This medication may be prescribed with a combination of other medications; time these medications as directed by prescriber. Take with or without food. Frequent blood tests may be required. May cause nausea, vomiting, abdominal pain, diarrhea, dizziness, insomnia, headache, fever, or muscle pain. Report persistent lethargy or unusual fatigue, yellowing of eyes, pale stool and dark urine, acute headache, severe nausea or vomiting, respiratory difficulty, loss of sensation, or rash.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Fatigue and insomnia are common; may cause dizziness or depression
Mental Health: Effects on Psychiatric Treatment
May rarely cause neutropenia; use caution with clozapine and carbamazepine
Nursing: Physical Assessment/Monitoring
Use caution in presence of impaired renal function. Monitor for headache, fatigue, and insomnia on a regular basis throughout therapy. Monitor patients closely for several months following discontinuation of therapy for chronic hepatitis B. Teach patient proper timing of multiple medications.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, oral:
Epivir-HBV®: 5 mg/mL [contains propylene glycol, sucrose 200 mg/mL; strawberry-banana flavor]
Epivir®: 10 mg/mL [DSC] [contains propylene glycol, sucrose 200 mg/mL; strawberry-banana flavor]
Epivir®: 10 mg/mL [ethanol free; contains propylene glycol, sucrose 200 mg/mL; strawberry-banana flavor]
Tablet, oral:
Epivir-HBV®: 100 mg
Epivir®: 150 mg [scored]
Epivir®: 300 mg
Pricing: U.S. (www.drugstore.com)
Solution (Epivir)
10 mg/mL (240): $109.99
Tablets (Epivir HBV)
100 mg (60): $748.02
References
Centers for Disease Control and Prevention, “Guidelines for the Prevention and Treatment of Opportunistic Infections Among HIV-Exposed and HIV-Infected Children: Recommendations from CDC, the National Institutes of Health, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics,” MMWR Recomm Rep, 2009, 58(RR-11):1-166. Available at http://aidsinfo.nih.gov/contentfiles/Pediatric_OI.pdf.
Centers for Disease Control and Prevention, “Notice to Readers: Updated Information Regarding Antiretroviral Agents Used as HIV Postexposure Prophylaxis for Occupational HIV Exposures,” MMWR Morb Mortal Wkly Rep, 2007, 56(49):1291-2. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5649a4.htm
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.
Lok AS and McMahon BJ, “Chronic Hepatitis B: Update 2009,” Hepatology, 2009, 50(3):661-2.
Panel on Antiretroviral Guidelines for Adults and Adolescents, “Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents, Department of Health and Human Services (DHHS),” January 10, 2011; 1-166. Available at http://www.aidsinfo.nih.gov
Panlilio AL, Cardo DM, Grohskopf LA, et al, “Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HIV and Recommendations for Postexposure Prophylaxis,” MMWR Recomm Rep, 2005, 54(RR-9):1-17. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5409a1.htm
“Perinatal HIV Guidelines Working Group. Public Health Service Task Force Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States,” May 24, 2010. Available at http://aidsinfo.nih.gov/ContentFiles/PerinatalGL.pdf
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.
Tremoulet AH, Capparelli EV, Patel P, et al, “Population Pharmacokinetics of Lamivudine in Human Immunodeficiency Virus-Exposed and -Infected Infants,” Antimicrob Agents Chemother, 2007, 51(12):4297-302.
Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children, “Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection,” August 16, 2010. Available at http://www.aidsinfo.nih.gov
International Brand Names
Lexi-Comp.com
Last full review/revision May 2011
Content last modified May 2011
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