Emtricitabine

Emtricitabine is an oral fluorinated cytidine analogue and nucleoside reverse transcriptase inhibitor with activity against HIV-1 and hepatitis B virus. It is used with tenofovir for first-line HIV treatment and for pre-exposure prophylaxis. It is very well tolerated, and skin hyperpigmentation of the palms and soles is the characteristic effect. It shares the M184V resistance pattern and the hepatitis B flare warning with lamivudine.

Class. Nucleoside reverse transcriptase inhibitor.

Mechanism. Phosphorylated to emtricitabine triphosphate, which competes with cytidine triphosphate and terminates viral DNA synthesis. M184V confers resistance and also to lamivudine.

Pharmacokinetics. Oral bioavailability about 93% for capsules and 75% for solution. Plasma half life about 10 hours; intracellular half life over 39 hours. Excreted unchanged by the kidney (about 86%).

HIV-1 infection (adults and adolescents 33 kg or more). 200 mg capsule orally once daily, or 240 mg (24 mL) of the oral solution once daily, combined with other antiretrovirals. Duration: lifelong.

Pre-exposure prophylaxis against HIV. 200 mg with tenofovir disoproxil fumarate 300 mg (or tenofovir alafenamide 25 mg in selected groups) once daily.

Children (HIV). Oral solution 6 mg/kg once daily (maximum 240 mg) from 3 months; 0 to 3 months 3 mg/kg once daily.

Dose adjustment for kidney function (capsule). - CrCl 30 to 49 mL/min: 200 mg every 48 hours. - CrCl 15 to 29: 200 mg every 72 hours. - CrCl under 15, including haemodialysis: 200 mg every 96 hours, given after dialysis.

Loading dose, maintenance dose and titration. Not applicable. Maximum: 200 mg daily (capsule).

Main alternative. Lamivudine.

Contraindications. Hypersensitivity to emtricitabine; use for prophylaxis in people with unknown or positive HIV status.

Serious adverse effects. Severe acute exacerbation of hepatitis B after stopping, lactic acidosis with hepatic steatosis (rare), and immune reconstitution syndrome.

Common adverse effects. Headache, diarrhoea, nausea, rash and skin hyperpigmentation of the palms and soles (mainly in people with darker skin).

Interactions. Few; additive kidney effects with nephrotoxins when given with tenofovir disoproxil fumarate. Do not give with lamivudine.

Common prescribing errors. Giving with lamivudine, full dose in kidney impairment, starting prophylaxis without an HIV test, and stopping in hepatitis B without cover.

Special groups. - Pregnancy: safe and widely used. - Breastfeeding: compatible. - Children: oral solution from birth; capsules from 33 kg. - Older adults: adjust for kidney function. - Kidney impairment: 200 mg every 48 hours at CrCl 30 to 49 mL/min and longer intervals at CrCl under 30. - Liver impairment: no adjustment; monitor for hepatitis B flares.

Formulations. Capsules 200 mg; oral solution 10 mg/mL; fixed-dose tablets with tenofovir disoproxil fumarate or tenofovir alafenamide (with or without a third drug).

Administration. With or without food.

Baseline. HIV test (essential for prophylaxis), hepatitis B surface antigen, creatinine and eGFR, pregnancy test.

Monitoring. HIV test every 3 months in prophylaxis; creatinine every 6 to 12 months; viral load in treatment; ALT and HBV DNA in hepatitis B.

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

Referral and escalation. Specialist review for treatment failure, breakthrough HIV on prophylaxis and hepatitis B flare.