Dolutegravir Approved in the U.S.
The indication for use in adults and children aged 12 years and older weighing at least 40 kg (approx. 88 lbs).Approval is based on results from four phase 3 studies whose results have already been reported in HIV Treatment Bulletin (HTB).3
The indication for children older than 12 years is based on a 24-week open-label label study in integrase-naive patients.
Dolutegravir is dosed 50 mg once-daily for naive and integrase-naive patients and at 50 mg twice-daily for patients who are integrase-experienced. Twice-daily dosing is also required for naive and experienced patients when coadministered with efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, or rifampin to overcome UGT1A/CYP3A inducing by these drugs.
Dolutegravir should be taken 2 hours before or 6 hours after taking cation-containing antacids or laxatives, sucralfate, oral iron supplements, oral calcium supplements, or buffered medications.
Dolutegravir can be taken with or without food.
For prescribing details see the full product information.4
Dolutegravir is marketed by ViiV Healthcare and has the tradename Tivicay.
U.S. approval of this long-awaited new integrase inhibitor is welcomed and it is clearly supported by good efficacy and tolerability results. At a low milligram dose it also has the potential to be coformulated with other ARVs and a Fixed Dose Combination (FDC) with abacavir/3TC is already underway.
Although dolutegravir is active against HIV that is resistant to raltegravir or elvitegravir, even using twice-daily dose it is not able to overcome extensive integrase inhibitor resistance. The prescribing information notes that poor virologic response was observed in subjects treated with 50 mg twice daily with Q148 mutations plus two or more additional integrase-associated mutations including L74I/M, E138A/D/K/T, G140A/S, Y143H/R, E157Q, G163E/K/Q/R/S, or G193E/R.4,5
Also, although indication is to take with or without food, drug levels are increased when taken with a meal, especially if this has a higher fat content (AUC increased by 33%, 41%, and 66% when administered with low-, moderate-, or high-fat meals, respectively, compared with fasting).6
Given the need for a twice daily dose in integrase inhibitor experienced patients to increase drug exposure it would be interesting to know whether taking it with food to maximise the PK levels in patients with existing integrase inhibitor mutations would affect outcomes.
As with all new drugs, how widely dolutegravir will be used, is likely to depend on pricing (see article in this issue of HTB).
Dolutegravir was submitted to the European regulatory agency at the same time as to the FDA and a decision is expected later this year.7
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This article was provided by HIV i-Base. It is a part of the publication HIV Treatment Bulletin. Visit HIV i-Base's website to find out more about their activities, publications and services.
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