The integrase inhibitor dolutegravir (brand name: Tivicay) was approved by the U.S. Federal Drug Administration in August, for use in treatment-naive and treatment-experienced adults, as well as for children aged ≥12 years (and weight ≥40 kg) who have not previously taken integrase inhibitors.
Recommended dosing depends on whether the patient's HIV virus has known or suspected resistance to integrase inhibitors and on whether interacting ARVs or other medications are coadministered.
|For adults and children (age ≥12 years and weight ≥40 kg) who have not taken integrase inhibitors previously: dolutegravir 50 mg daily|
|For adults with certain integrase inhibitor-associated resistance mutations, or with suspected resistance to integrase inhibitors: dolutegravir 50 mg BID|
|For adults and children who are naive to integrase inhibitors but who are taking efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, rifampin or other UGT1A or CYP3A inducers: dolutegravir 50 mg BID|
Dolutegravir is active against some strains of HIV with resistance to raltegravir and elvitegravir, but the likelihood of virologic response is greatly reduced if the virus has a 148H/R mutation plus ≥2 other integrase inhibitor mutations (eg, L74I/M, E138A/D/K/T, G140A/S, Y143H/R, E157Q, G163E/K/Q/R/S, G193E/R). Interestingly, no significant resistance to dolutegravir has been described in ARV-naive patients who develop virologic failure while taking dolutegravir.
Dolutegravir is metabolized by UGT1A1 and CYP3A--inducers of these (including the NNRTIs efavirenz and etravirine and the PIs fosamprenavir/ritonavir and tipranavir/ritonavir) may cause significant decreases in serum dolutegravir levels. GI absorption of dolutegravir is greatly impaired by concurrent administration with polyvalent cations (eg, aluminum, calcium, iron, or magnesium cations), including those contained in some antacids, laxatives, buffered medications, and vitamin/mineral preparations. Polyvalent cations should be taken ≥2 hours before or ≥6 hours after dolutegravir.
In clinical studies, adverse effects were uncommon but included headache and insomnia, as well as hypersensitivity reactions and, in patients with hepatitis B or C, transaminase elevations.
Dolutegravir is classified as an FDA Pregnancy Category B drug.
The Tivicay label information is available at Drugs@FDA.