Dolutegravirinteractions

DOVATO is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral drugs for the treatment of HIV-1 infection is not recommended.

Refer to the full prescribing information for important drug interactions with DOVATO.

7.1 Coadministration with

Other Antiretroviral Drugs DOVATO is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral drugs for the treatment of HIV-1 infection is not recommended. Information regarding potential drug-drug interactions with other antiretroviral drugs is not provided.

7.2 Potential for DOVATO to

Affect Other Drugs Dolutegravir, a component of DOVATO, inhibits the renal organic cation transporters (OCT)2 and multidrug and toxin extrusion transporter (MATE)1; thus, it may increase plasma concentrations of drugs eliminated via OCT2 or MATE1 such as dofetilide, dalfampridine, and metformin.

7.3 Potential for

Other Drugs to Affect the Components of DOVATO Dolutegravir is metabolized by uridine diphosphate (UDP)-glucuronosyl transferase (UGT)1A1 with some contribution from cytochrome P450 (CYP)3A. Dolutegravir is also a substrate of UGT1A3, UGT1A9, breast cancer resistance protein (BCRP), and P-glycoprotein (P-gp) in vitro. Drugs that induce those enzymes and transporters may decrease dolutegravir plasma concentrations and reduce the therapeutic effect of DOVATO. Coadministration of DOVATO and other drugs that inhibit these enzymes may increase dolutegravir plasma concentrations. Coadministration of dolutegravir with polyvalent cation-containing products may lead to decreased absorption of dolutegravir.

7.4 Established and

Other Potentially Significant Drug Interactions No drug interaction studies were conducted with DOVATO. The drug interactions described are based on studies conducted with dolutegravir or lamivudine when administered alone. Information regarding potential drug interactions with DOVATO are provided in Table 5. These recommendations are based on either drug interaction trials or predicted interactions due to the expected magnitude of interaction and potential for serious adverse events or loss of efficacy. Table 5. Established and Other Potentially Significant Drug Interactions for DOVATO: Alterations in Dose May Be Recommended Based on Drug Interaction Trials or Predicted Interactions ↑ = Increase, ↓ = Decrease. a See Clinical Pharmacology Table 8 or Table 9 for magnitude of interaction.

Coadministered Drug Class: Drug Name Effect on Concentration Clinical Comment Antiarrhythmic: Dofetilide ↑Dofetilide Coadministration is contraindicated with DOVATO.

Anticonvulsant: Carbamazepine a ↓Dolutegravir An additional dolutegravir 50-mg dose should be taken, separated by 12 hours from DOVATO.

Anticonvulsants: Oxcarbazepine Phenytoin Phenobarbital ↓Dolutegravir Avoid coadministration with DOVATO because there are insufficient data to make dosing recommendations.

Antidiabetic: Metformin a ↑Metformin Refer to the prescribing information for metformin for assessing the benefit and risk of concomitant use of DOVATO and metformin.

Antimycobacterial: Rifampin a ↓Dolutegravir An additional 50-mg dose of dolutegravir should be taken, separated by 12 hours from DOVATO.

Herbal product: St. John’s wort ( Hypericum perforatum ) ↓Dolutegravir Avoid coadministration with DOVATO because there are insufficient data to make dosing recommendations. Medications containing polyvalent cations (e.g., Mg or Al): Cation-containing antacids a or laxatives Sucralfate Buffered medications ↓Dolutegravir Administer DOVATO 2 hours before or 6 hours after taking medications containing polyvalent cations. Oral calcium and iron supplements, including multivitamins containing calcium or iron a ↓Dolutegravir When taken with food, DOVATO and supplements or multivitamins containing calcium or iron can be taken at the same time. Under fasting conditions, DOVATO should be taken 2 hours before or 6 hours after taking supplements containing calcium or iron.

Potassium channel blocker: Dalfampridine ↑Dalfampridine Elevated levels of dalfampridine increase the risk of seizures. The potential benefits of taking dalfampridine concurrently with DOVATO should be considered against the risk of seizures in these patients. Sorbitol a ↓Lamivudine When possible, avoid use of sorbitol-containing medicines with DOVATO.