Raltegravir

Raltegravir is an oral integrase strand transfer inhibitor, the first in its class, with a low drug-interaction burden. It is used when dolutegravir is unsuitable, in pregnancy and neonates where specialist advice supports it, and in tuberculosis co-treatment. It has a lower resistance barrier than dolutegravir and needs twice daily dosing in most settings.

Class. Integrase strand transfer inhibitor.

Mechanism. Binds the integrase active site and blocks strand transfer. Resistance arises through the N155H or Q148 mutation groups with additional mutations.

Pharmacokinetics. Oral absorption highly variable; food effect is not clinically important for the 400 mg tablet. Half life about 9 hours. Cleared by UGT1A1 glucuronidation, so it is not boosted by ritonavir.

HIV-1 infection (adults). 400 mg orally twice daily, with two nucleosides.

With rifampicin. 800 mg twice daily.

Once daily option (naive or suppressed adults, not pregnant, not on rifampicin). 1200 mg (two 600 mg tablets) once daily.

Children. Weight-banded chewable tablets twice daily from 11 kg; neonatal and granule dosing is specialist-led. Adults and children 40 kg or more: 400 mg twice daily.

Loading dose, maintenance dose and titration. Not applicable. Maximum: 800 mg twice daily with rifampicin.

Main alternative. Dolutegravir.

Contraindications. Hypersensitivity.

Serious adverse effects. Severe skin reactions and hypersensitivity, rhabdomyolysis and myopathy (monitor creatine kinase), hepatotoxicity, depression and suicidal thoughts (uncommon), and immune reconstitution syndrome.

Common adverse effects. Headache, nausea, insomnia, dizziness and raised creatine kinase.

Interactions. - Aluminium and magnesium antacids lower levels; avoid. Calcium carbonate antacids: avoid with the 1200 mg once daily dose. - Rifampicin lowers levels, so the dose is doubled. - Efavirenz and etravirine lower levels modestly. - Chewable tablets are not interchangeable with film-coated tablets.

Common prescribing errors. Using 400 mg twice daily with rifampicin, once daily dosing in pregnancy or with rifampicin, and exchanging tablet forms.

Special groups. - Pregnancy: used widely, though exposure falls in the third trimester; the twice daily dose is used. - Breastfeeding: limited data; avoid unless benefit is clear. - Children: chewable tablets or granules by weight. - Older adults: usual dose. - Kidney impairment: no adjustment. - Liver impairment: no adjustment in mild to moderate disease; not studied in severe.

Regional points. In East Africa it is an alternative for patients who cannot take dolutegravir, and during tuberculosis treatment its dose is doubled to 800 mg twice daily.

Formulations. Tablets 400 mg and 600 mg; chewable tablets 25 mg and 100 mg; granules for suspension 100 mg sachet.

Administration. With or without food; swallow whole; chew the chewable tablets.

Baseline. HIV test, viral load, creatine kinase if muscle symptoms, liver tests, hepatitis B and C status, pregnancy test.

Monitoring. Viral load at 3 and 6 months and then yearly; creatine kinase if myalgia; mood and skin.

Stopping thresholds. Stop for severe rash, hypersensitivity, rhabdomyolysis, or ALT over 3 times the upper limit of normal with symptoms, or over 5 times without.

Referral and escalation. Specialist review for treatment failure, neonatal use and complex interactions.