Lamivudine

Lamivudine (3TC) is a nucleoside reverse transcriptase inhibitor (NRTI) used in combination with other antiretrovirals for HIV-1 treatment and as a standalone agent for chronic hepatitis B (HBV). It is a cytidine analog functionally interchangeable with emtricitabine (FTC) — the two should never be combined. Lamivudine is found in the widely prescribed fixed-dose combinations Triumeq, Dovato, Epzicom, and Combivir.[1]

Critical dosing distinction: Lamivudine is marketed at two different doses — Epivir (150 mg/300 mg for HIV) and Epivir-HBV (100 mg for hepatitis B). Using the lower HBV dose in an HIV/HBV co-infected patient will provide subtherapeutic HIV coverage and rapidly select for HIV resistance.[1]

Administration

  • Type: Nucleoside reverse transcriptase inhibitor (NRTI); cytidine analog
  • Dosage Forms: 150 mg scored tablets, 300 mg tablets; 10 mg/mL oral solution (Epivir for HIV); 100 mg tablets, 5 mg/mL oral solution (Epivir-HBV)
  • Routes of Administration: Oral
  • Common Trade Names: Epivir (HIV dose), Epivir-HBV (hepatitis B dose); also in fixed-dose combinations: Triumeq (Dolutegravir/abacavir/lamivudine), Dovato (dolutegravir/lamivudine), Epzicom (abacavir/lamivudine), Combivir (zidovudine/lamivudine), Trizivir (abacavir/zidovudine/lamivudine)

Adult Dosing

  • HIV treatment: 300 mg PO once daily, or 150 mg PO twice daily[1]
  • Hepatitis B (Epivir-HBV): 100 mg PO once daily (do not use this dose for HIV)[1]
  • HIV/HBV co-infection: Use the HIV dose (300 mg daily) as part of combination ART[1]
  • May take with or without food
  • Scored tablets preferred over oral solution (solution has lower bioavailability; sorbitol-containing coadministered medications further reduce lamivudine exposure)[1]

Pediatric Dosing

  • Approved for HIV treatment in patients ≥3 months[1]
  • Weight-based: 5 mg/kg PO twice daily or 10 mg/kg PO once daily (max 300 mg/day)
  • Tablets preferred for children ≥14 kg (oral solution associated with lower virologic suppression rates in the ARROW trial)[1]
  • Neonatal dosing available for perinatal prophylaxis regimens

Special Populations

Pregnancy Rating

  • Extensively studied in pregnancy; APR data show no increased birth defect risk compared to background[1]
  • Crosses the placenta; widely used as part of preferred NRTI backbone in pregnancy
  • Antiretroviral Pregnancy Registry: 1-800-258-4263

Lactation risk

  • Excreted in human milk; women with HIV should discuss risks and benefits of breastfeeding with their provider[1]

Renal Dosing

  • Adult (primarily renally eliminated; dose reduction required):[1]
    • CrCl 30–49 mL/min: 150 mg PO once daily
    • CrCl 15–29 mL/min: 150 mg first dose, then 100 mg PO once daily
    • CrCl 5–14 mL/min: 150 mg first dose, then 50 mg PO once daily
    • CrCl <5 mL/min: 50 mg first dose, then 25 mg PO once daily
    • No additional dosing required after routine hemodialysis or peritoneal dialysis
  • Pediatric: Insufficient data; consider proportional reduction

Hepatic Dosing

  • Adult: No dose adjustment needed (pharmacokinetics not significantly altered by hepatic impairment)[1]
  • Pediatric: No specific data

Contraindications

  • Allergy to class/drug
  • Do not coadminister with emtricitabine-containing products (therapeutic duplication — both are cytidine analogs with overlapping resistance profiles)[1]

Adverse Reactions

Serious

  • Hepatitis B flare (Boxed Warning): Severe, acute exacerbations of HBV (including hepatic decompensation and failure) reported in HIV/HBV co-infected patients who discontinue lamivudine-containing regimens. Monitor hepatic function closely for at least several months after stopping[1]
  • Lactic acidosis with hepatic steatosis (NRTI class effect; including fatal cases)[1]
  • Pancreatitis (rare; more common in pediatric patients)[1]
  • Immune reconstitution inflammatory syndrome (IRIS)

Common

  • Headache, nausea, malaise, fatigue, nasal symptoms, diarrhea, cough[1]
  • Insomnia
  • Musculoskeletal pain
  • Elevated transaminases, CPK

Pharmacology

  • Half-life: ~5–7 hours (plasma); intracellular triphosphate half-life ~10–15 hours[1]
  • Bioavailability: ~86%[1]
  • Protein Binding: <36%[1]
  • Metabolism: Minimal hepatic metabolism; not a CYP450 substrate and does not inhibit or induce CYP enzymes[1]
  • Excretion: ~70% unchanged in urine via glomerular filtration and active organic cationic tubular secretion[1]

Mechanism of Action

Lamivudine is a cytidine analog that is intracellularly phosphorylated to its active form, lamivudine triphosphate. This competes with the natural substrate deoxycytidine triphosphate for incorporation by HIV-1 reverse transcriptase. Once incorporated into viral DNA, it acts as a chain terminator due to the absence of a 3'-hydroxyl group. Lamivudine triphosphate also inhibits HBV polymerase, which accounts for its dual HIV/HBV activity.[1]

Comments

  • Epivir vs. Epivir-HBV — the critical dosing trap: If an HIV/HBV co-infected patient is accidentally prescribed Epivir-HBV (100 mg) instead of Epivir (150/300 mg), they are receiving subtherapeutic HIV coverage which will rapidly select for resistant HIV. Always verify the formulation and dose in co-infected patients[1]
  • Hepatitis B flare on discontinuation: Identical to the emtricitabine pearl — lamivudine has anti-HBV activity. Stopping any lamivudine-containing regimen (Triumeq, Dovato, Epzicom, Combivir, etc.) in an HIV/HBV co-infected patient can trigger a severe HBV flare presenting as acute liver failure. Check HBV serologies and LFTs in any HIV patient with jaundice or transaminase elevation after recent ARV discontinuation[1]
  • Emtricitabine duplication: Lamivudine and emtricitabine are functionally interchangeable — never combine them. Check the full medication list when reconciling ARVs (e.g., a patient on Dovato [dolutegravir/lamivudine] should not also receive Descovy [emtricitabine/TAF])
  • Sorbitol interaction: Sorbitol-containing liquid medications significantly reduce lamivudine oral solution exposure. Avoid coadministration when possible; this is relevant in pediatric patients receiving multiple liquid formulations[1]
  • TMP-SMX interaction: Trimethoprim increases lamivudine levels by ~40% via competition for renal organic cationic secretion. No dose adjustment at standard TMP-SMX doses, but avoid high-dose TMP-SMX (PCP treatment doses) with lamivudine when possible[1]
  • Low drug interaction profile: Not CYP450-metabolized; does not affect levels of other drugs. Very safe from an interaction standpoint when prescribing in the ED
  • Low resistance barrier: The M184V/I mutation emerges rapidly with lamivudine monotherapy or subtherapeutic dosing. This is why proper combination therapy and correct dosing (HIV vs. HBV formulation) are essential
  • Overdose: No specific antidote; supportive care. No significant symptoms reported in acute overdoses. No additional dosing needed after dialysis[1]

See Also

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 1.19 1.20 1.21 1.22 1.23 1.24 1.25 1.26 1.27 Epivir (lamivudine) [prescribing information]. Research Triangle Park, NC: ViiV Healthcare; 2017.
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