Abacavir

Abacavir is an oral guanosine analogue and nucleoside reverse transcriptase inhibitor used for HIV-1 infection, mainly with lamivudine and a third drug, and widely in children. Its defining risk is a multi-organ hypersensitivity reaction, strongly linked to HLA-B*5701, which can be fatal on rechallenge. It has no activity against hepatitis B, so co-infected patients need tenofovir. Some studies link it to myocardial infarction, but the association is disputed.

Class. Nucleoside reverse transcriptase inhibitor.

Mechanism. Converted intracellularly to carbovir triphosphate, which competes with deoxyguanosine triphosphate and terminates viral DNA synthesis.

Pharmacokinetics. Oral bioavailability about 83%, not affected by food. Plasma half life about 1.5 hours; intracellular half life about 12 to 26 hours. Hepatic metabolism by alcohol dehydrogenase and glucuronidation; renal elimination of metabolites.

HIV-1 infection (adults and adolescents 25 kg or more). 600 mg orally once daily or 300 mg twice daily, with lamivudine and a third active drug. Duration: lifelong.

Children (3 months and over). 8 mg/kg twice daily (maximum 300 mg twice daily) or 16 mg/kg once daily (maximum 600 mg), using weight bands with dispersible tablets (60 mg with lamivudine 30 mg).

Dose adjustment for liver function. Child-Pugh A: 200 mg twice daily (oral solution); Child-Pugh B or C: avoid.

Loading dose, maintenance dose and titration. Not applicable. Maximum: 600 mg daily.

Main alternative. Tenofovir disoproxil fumarate or zidovudine with lamivudine.

Contraindications. Positive HLA-B*5701 status where testing is available; previous hypersensitivity reaction to abacavir; moderate or severe liver impairment.

Serious adverse effects. - Hypersensitivity reaction (fever, rash, gastrointestinal upset, cough, breathlessness, malaise), usually within the first 6 weeks; never restart after a reaction. - Lactic acidosis with hepatic steatosis (rare); possible raised cardiovascular risk.

Common adverse effects. Nausea, headache, fatigue, diarrhoea and insomnia.

Interactions. Alcohol raises abacavir levels by about 40%; methadone dose may need to rise; riociguat levels rise.

Common prescribing errors. Restarting after a reaction (including after a gap in treatment that began with symptoms), not warning patients, and giving it without checking hepatitis B status, since it is inactive against hepatitis B.

Special groups. - Pregnancy: acceptable. - Breastfeeding: compatible. - Children: first-line with lamivudine and dolutegravir in many programmes. - Older adults: caution if cardiovascular risk is high. - Kidney impairment: no adjustment for abacavir; combination tablets with lamivudine are used at CrCl 30 mL/min or more. - Liver impairment: 200 mg twice daily in Child-Pugh A; avoid in B and C.

Regional points. HLA-B*5701 is uncommon in African populations, and testing is often not available, so patients and carers are taught the early signs of hypersensitivity. In East Africa abacavir with lamivudine and dolutegravir is the usual first-line regimen for children.

Formulations. Tablets 300 mg; dispersible tablets 60 mg; oral solution 20 mg/mL; fixed-dose combinations with lamivudine and with dolutegravir.

Administration. With or without food; swallow adult tablets whole.

Baseline. HLA-B*5701 where available, hepatitis B surface antigen, liver tests, cardiovascular risk, pregnancy test.

Monitoring. Symptoms of hypersensitivity in the first 6 weeks; viral load; liver tests; cardiovascular risk factors.

Stopping thresholds. Stop at once for any suspected hypersensitivity reaction and do not rechallenge; stop for lactic acidosis or hepatic steatosis.

Referral and escalation. Admission for suspected hypersensitivity with respiratory or circulatory symptoms; specialist review for treatment failure.