Lamivudine

Lamivudine is an oral cytidine analogue and nucleoside reverse transcriptase inhibitor active against HIV-1 and hepatitis B virus. It is a core backbone drug in first-line HIV regimens and is used for infant prophylaxis and, less often now, hepatitis B. It is well tolerated, but resistance develops fast when it is used alone because a single mutation (M184V) removes its activity. Stopping it in hepatitis B co-infection can cause severe flares.

Class. Nucleoside reverse transcriptase inhibitor; nucleoside analogue antiviral.

Mechanism. Phosphorylated to lamivudine triphosphate, which competes with cytidine triphosphate and terminates viral DNA synthesis. M184V in HIV and YMDD mutations in hepatitis B reduce susceptibility.

Pharmacokinetics. Oral bioavailability about 85%, not affected by food. Plasma half life 5 to 7 hours and intracellular half life 10 to 15 hours. About 70% excreted unchanged by the kidney.

HIV-1 infection (adults and children 35 kg or more). 300 mg orally once daily or 150 mg twice daily, combined with other antiretrovirals. Duration: lifelong.

Children (HIV). Weight-banded dosing, equivalent to 4 mg/kg twice daily (maximum 150 mg twice daily) from 3 months of age; neonates under 4 weeks 2 mg/kg twice daily.

Chronic hepatitis B (adults). 100 mg once daily; not preferred because resistance reaches about 70% after 5 years of use alone.

Dose adjustment for kidney function (adults, 150 mg regimen). - CrCl 30 to 49 mL/min: 150 mg once daily. - CrCl 15 to 29: 150 mg first dose, then 100 mg once daily. - CrCl 5 to 14: 150 mg first dose, then 50 mg once daily. - CrCl under 5: 50 mg first dose, then 25 mg once daily.

Loading dose, maintenance dose and titration. Not applicable beyond the kidney first doses. Maximum: 300 mg daily.

Main alternative. Emtricitabine (interchangeable in HIV regimens; never combine the two).

Contraindications. Hypersensitivity to lamivudine.

Serious adverse effects. Severe acute exacerbation of hepatitis B on stopping, pancreatitis (mainly children with previous exposure), lactic acidosis with hepatic steatosis (rare), and neutropenia or anaemia with zidovudine.

Common adverse effects. Headache, nausea, fatigue, diarrhoea and cough.

Interactions. - Co-trimoxazole in high dose raises lamivudine levels; adjust only in kidney impairment. - Sorbitol-containing liquids lower levels. - Emtricitabine duplicates its action; do not give together. - Cladribine: avoid.

Common prescribing errors. Using it alone or as the only active drug in a regimen, stopping it in hepatitis B co-infection without cover, adding emtricitabine, and full dose in kidney impairment.

Special groups. - Pregnancy: safe and widely used. - Breastfeeding: compatible. - Children: weight-banded dispersible tablets and oral solution; monitor for pancreatitis. - Older adults: adjust for kidney function. - Kidney impairment: 150 mg once daily at CrCl 30 to 49 mL/min, with lower doses at CrCl under 30. - Liver impairment: no adjustment; monitor for hepatitis B flares.

Regional points. In East Africa lamivudine is a component of the first-line fixed-dose combination with tenofovir disoproxil fumarate and dolutegravir, and of the paediatric combination with abacavir and dolutegravir; the M184V mutation is commonly found at first-line failure, but dolutegravir regimens are less affected by it.

Formulations. Tablets 150 mg and 300 mg; oral solution 10 mg/mL; dispersible tablets 30 mg (with abacavir); fixed-dose combinations with tenofovir, zidovudine, abacavir, dolutegravir or efavirenz.

Administration. With or without food.

Baseline. HIV test, hepatitis B surface antigen, creatinine and eGFR, full blood count if zidovudine is also used, pregnancy test.

Monitoring. Viral load at 6 months and then yearly; creatinine yearly; ALT and HBV DNA in hepatitis B; full blood count if with zidovudine.

Stopping thresholds. Stop for pancreatitis, hepatic steatosis or lactic acidosis; if stopped in hepatitis B, monitor ALT for at least 6 months.

Referral and escalation. Specialist review for treatment failure, hepatitis B flare and decompensated liver disease.