Dolutegravir is a next-generation integrase strand transfer inhibitor, recommended by WHO as first-line therapy for HIV. It has a high genetic barrier to resistance and good tolerability.
Also known as: Tivicay, DTG
Rifampicin reduces dolutegravir levels by ~54% via UGT1A1 induction. The dolutegravir dose must be increased to 50 mg twice daily when coadministered.
Rifampicin is one of the most potent enzyme inducers, acting primarily on UGT1A1 (the glucuronidation enzyme for dolutegravir) and secondarily on CYP3A4. Pharmacokinetic studies demonstrated that coadministration reduces dolutegravir AUC by 54% and Cmax by 36%, significantly compromising viral suppression. WHO and FDA labels recommend increasing dolutegravir dose to 50 mg twice daily when coadministered with rifampicin, maintaining antiretroviral efficacy. This adjustment should be maintained throughout rifampicin treatment and for 2 weeks after discontinuation. Alternative: rifabutin (weaker induction, 150 mg/day with dolutegravir 50 mg once daily).
Dolutegravir + rifampicin: ~54% reduction in dolutegravir levels via UGT1A1 induction. Increase dose to 50 mg twice daily.
Rifampicin is a potent inducer of UGT1A1, the enzyme responsible for dolutegravir glucuronidation. This induction significantly reduces dolutegravir plasma levels, compromising viral suppression.
Monitor viral load 2-4 weeks after starting rifampicin. Consider alternative to rifampicin (e.g. rifabutin with dose adjustment).
Virological failure if dose is not adjusted. Subtherapeutic dolutegravir levels.
Increase dolutegravir dose to 50 mg twice daily (instead of 50 mg once daily). Discontinue rifampicin 2 weeks after last dose and resume normal dolutegravir dose.
DailyMed/FDA (NIH/NLM) — approved Dolutegravir (Tivicay) label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=485bc9db-8665-9f5a-e063-6394a90a7921 ; approved Rifampicin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=04e52489-77af-4b7f-b20b-3c5742e7b75e
Carbamazepine may reduce dolutegravir levels via enzyme induction. Consider dose adjustment or alternative.
Carbamazepine induces UGT1A1 and CYP3A4, enzymes involved in dolutegravir metabolism. Although the induction is less potent than rifampicin, the reduction in levels may be clinically significant, especially in patients with high viral load or pre-existing resistance. The dolutegravir label (Tivicay) recommends increasing the dose to 50 mg twice daily when coadministered with moderate UGT1A1 inducers such as carbamazepine. Alternative: consider switching carbamazepine to an antiepileptic without significant enzyme induction (e.g. levetiracetam, lamotrigine) or use raltegravir (not metabolised by CYP3A4) as an alternative INSTI.
Dolutegravir + carbamazepine: reduced dolutegravir levels via UGT1A1/CYP3A4 induction. Consider dose increase or alternative.
Carbamazepine induces UGT1A1 and CYP3A4, enzymes involved in dolutegravir metabolism, reducing its plasma levels.
Monitor viral load and liver function periodically.
Virological failure if no dose adjustment.
Consider increasing dolutegravir dose to 50 mg twice daily. Monitor viral load. Alternative: switch carbamazepine to another antiepileptic.
DailyMed/FDA (NIH/NLM) — approved Dolutegravir (Tivicay) label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=485bc9db-8665-9f5a-e063-6394a90a7921 ; approved Carbamazepine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a63e2ab0-ddf2-4718-b59c-5a96507151aa
Food does not significantly affect dolutegravir absorption.
Can be taken with or without food.
DailyMed/FDA (NIH/NLM) — approved Dolutegravir (Tivicay) label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=485bc9db-8665-9f5a-e063-6394a90a7921
No documented disease interactions.
WHO recommends dolutegravir as first-line in pregnant women. Initial concern about neural tube defects (2018), but subsequent studies showed safety.
Recommended by WHO as first-line in all stages of pregnancy. Dose may be increased to 50 mg twice daily in the third trimester.
Excreted in breast milk in small amounts. Artificial feeding is recommended for HIV-positive mothers.
Reliable contraceptive methods are recommended.
DailyMed/FDA (NIH/NLM) — approved Dolutegravir (Tivicay) label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=485bc9db-8665-9f5a-e063-6394a90a7921
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Dolutegravir is an integrase inhibitor with a high genetic barrier to resistance. It is effective against HIV-1 strains resistant to other INSTIs (raltegravir, elvitegravir).
Dolutegravir binds to the active site of HIV-1 integrase, blocking strand transfer — an essential step for integration of viral DNA into the host cell genome.
Rapid oral absorption. Bioavailability: ~63%. Tmax: 2-3 hours. Food does not significantly affect absorption. Can be taken with or without food.
Metabolised by UGT1A1 (glucuronidation) and CYP3A4 (oxidation). Induced by rifampicin, carbamazepine, phenytoin, phenobarbital (via UGT1A1). Does not require ritonavir as a booster.
14 hours (33 hours for glucuronide metabolite). Elimination: 53% faeces, 33% urine (metabolites). No dose adjustment required in most cases.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
