HIV/AIDS Update - Changes to the Trivicay (dolutegravir) product labeling

["U.S. Food & Drug Administration (FDA)" <fda@xxxxxxxxxxxxxxxxxxxxxxx>]

Title: HIV/AIDS Update - Changes to the Trivicay (dolutegravir) product labeling

You are receiving this message as a subscriber to the FDA HIV/AIDS electronic list serve. The purpose of the list serve is to relay important information about HIV/AIDS-related products and issues, including product approvals, significant labeling changes, safety warnings, notices of upcoming public meetings and alerts to proposed regulatory guidances for comment.

Please do not reply to this message.

On May 12, 2014, FDA approved updates to the TIVICAY (dolutegravir) product labeling with information regarding the effect of dolutegravir on renal transporters and drug-drug interaction data between dolutegravir and calcium carbonate or ferrous fumarate.

Section 7.1 Effect of Dolutegravir on the Pharmacokinetics of Other Agents, subsection was updated as follows:

In vitro, dolutegravir inhibited the renal organic cation transporters, OCT2 (IC₅₀ =1.93 µM) and multidrug and toxin extrusion transporter (MATE) 1 (IC₅₀ = 6.34 mM). In vivo, dolutegravir inhibits tubular secretion of creatinine by inhibiting OCT2 and potentially MATE1. Dolutegravir may increase plasma concentrations of drugs eliminated via OCT2 or MATE1 (dofetilide and metformin, Table 5) [see Contraindications (4), Drug Interactions (7.3)].

              

In vitro, dolutegravir inhibited the basolateral renal transporters, organic anion transporter (OAT) 1 (IC₅₀ = 2.12 mM) and OAT3 (IC₅₀ = 1.97 mM). However, in vivo, dolutegravir did not alter the plasma concentrations of tenofovir or paraaminohippurate, substrates of OAT1 and OAT3.

 

In vitro, dolutegravir did not inhibit (IC₅₀ >50 μM) the following: cytochrome P450 (CYP)1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A, UGT1A1, UGT2B7, P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), bile salt export pump (BSEP), organic anion transporter polypeptide (OATP)1B1, OATP1B3, OCT1, multidrug resistance protein (MRP)2 or MRP4. In vitro, dolutegravir did not induce CYP1A2, CYP2B6, or CYP3A4. Based on these data and the results of drug interaction trials, dolutegravir is not expected to affect the pharmacokinetics of drugs that are substrates of these enzymes or transporters.

 

Additionally, in section 7: Drug Interactions, Table 5 – the following was added regarding co administration with oral calcium or iron supplements, including multivitamins containing calcium or iron:

TIVICAY should be administered 2 hours before or 6 hours after taking supplements containing calcium or iron. Alternatively, TIVICAY and supplements containing calcium or iron can be taken together with food.

 

The complete revised label can be viewed at this Drugs@FDA  link.

 

Tivicay is a human immunodeficiency virus type 1 (HIV-1) integrase strand transfer inhibitor (INSTI) indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and children aged 12 years and older and weighing at least 40 kg,marketed by GlaxoSmithKline.

 

Richard Klein
Office of Health and Constituent Affairs
Food and Drug Administration

Kimberly Struble
Division of Antiviral Products
Food and Drug Administration

Steve Morin
Office of Health and Constituent Affairs
Food and Drug Administration

 

If you are interested in receiving information about a broader range of FDA topics, consider subscribing to the FDA Patient Network News, a twice monthly newsletter containing FDA-related information on a variety of topics, including new product approvals, significant labeling changes, safety warnings, notices of upcoming public meetings, proposed regulatory guidances and opportunity to comment, and other information of interest to patients and patient advocates.

---

This email was sent to list-fda@xxxxxxxxxxx using GovDelivery, on behalf of: U.S. Food & Drug Administration (FDA) · 10903 New Hampshire Ave · Silver Spring, MD 20993 · 800-439-1420