Dolutegravirinteractions

Because JULUCA is a complete regimen, coadministration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended.

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

Drugs that induce or inhibit cytochrome P450 (CYP)3A4 or uridine diphosphate glucuronosyltransferase (UGT)1A1 may affect the plasma concentrations of the components of JULUCA.

Drugs that increase gastric pH or containing polyvalent cations may decrease plasma concentrations of the components of JULUCA.

Consider alternatives to prescribing JULUCA with drugs with a known risk of Torsade de Pointes.

7.1 Concomitant

Use with Other Antiretroviral Medicines Because JULUCA is a complete regimen, coadministration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended. Information regarding potential drug-drug interactions with other antiretroviral medications is not provided.

7.2 Potential for JULUCA to

Affect Other Drugs Dolutegravir, a component of JULUCA, 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 JULUCA Dolutegravir 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 dolutegravir. Coadministration of dolutegravir 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. Rilpivirine Rilpivirine is primarily metabolized by CYP3A, and drugs that induce or inhibit CYP3A may affect the clearance of rilpivirine. Coadministration of JULUCA and drugs that induce CYP3A may result in decreased plasma concentrations of rilpivirine and loss of virologic response and possible resistance to rilpivirine or to the class of NNRTIs. Coadministration of JULUCA and drugs that inhibit CYP3A may result in increased plasma concentrations of rilpivirine. Coadministration of JULUCA with drugs that increase gastric pH may result in decreased plasma concentrations of rilpivirine and loss of virologic response and possible resistance to rilpivirine or to the class of NNRTIs.

QT-Prolonging Drugs: In healthy subjects, 75 mg once daily of rilpivirine (3 times the dose in JULUCA) and 300 mg once daily (12 times the dose in JULUCA) have been shown to prolong the QTc interval of the electrocardiogram. Consider alternatives to JULUCA when coadministered with a drug with a known risk of Torsade de Pointes.

7.4 Established and

Other Potentially Significant Drug Interactions Information regarding potential drug interactions with dolutegravir and rilpivirine are provided in Table 4. These recommendations are based on either drug interaction trials of individual components or predicted interactions due to the expected magnitude of interaction and potential for serious adverse events or loss of efficacy. Table 4. Established and Other Potentially Significant Drug Interactions: Alterations in Dose or Regimen May Be Recommended Based on Drug Interaction Trials or Predicted Interactions a ↑ = Increase, ↓ = Decrease, ↔ = No change. a This table is not all inclusive. b See Clinical Pharmacology for magnitude of interaction.

Concomitant Drug Class: Drug Name Effect on Concentration Clinical Comment Antacids (e.g., aluminum or magnesium hydroxide, calcium carbonate) ↓Rilpivirine Administer JULUCA 4 hours before or 6 hours after taking antacids.

Antiarrhythmic: Dofetilide ↑Dofetilide Coadministration is contraindicated with JULUCA.

Anticonvulsants: Carbamazepine Oxcarbazepine Phenobarbital Phenytoin ↓Dolutegravir ↓Rilpivirine Coadministration is contraindicated with JULUCA due to decreased rilpivirine concentrations.

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

Antimycobacterials: Rifampin Rifapentine ↓Dolutegravir ↓Rilpivirine Coadministration is contraindicated with JULUCA due to decreased rilpivirine concentrations.

Antimycobacterial: Rifabutin b ↔Dolutegravir ↔Rifabutin ↓Rilpivirine An additional rilpivirine 25-mg tablet should be taken with JULUCA once daily with a meal when rifabutin is coadministered. Glucocorticoid (systemic): Dexamethasone (more than a single-dose treatment) ↓Rilpivirine Coadministration is contraindicated with JULUCA due to decreased rilpivirine concentrations.

H 2 -receptor antagonists: Famotidine Cimetidine Nizatidine Ranitidine ↔Dolutegravir ↓Rilpivirine JULUCA should only be administered at least 4 hours before or 12 hours after taking H 2 -receptor antagonists.

Herbal product: St John’s wort ( Hypericum perforatum ) ↓Dolutegravir ↓Rilpivirine Coadministration is contraindicated with JULUCA due to decreased rilpivirine concentrations.

Macrolide or ketolide antibiotics: Clarithromycin Erythromycin Telithromycin ↔Dolutegravir ↑Rilpivirine Where possible, consider alternatives, such as azithromycin. Medications containing polyvalent cations (e.g., Mg or Al): Cation-containing products b or laxatives Sucralfate Buffered medications ↓Dolutegravir Administer JULUCA 4 hours before or 6 hours after taking products containing polyvalent cations.

Narcotic analgesic: Methadone b ↔Dolutegravir ↓Methadone ↔Rilpivirine No dose adjustments are required when starting coadministration of methadone with JULUCA. However, clinical monitoring is recommended as methadone maintenance therapy may need to be adjusted in some patients. Oral calcium and iron supplements, including multivitamins containing calcium or iron b (non-antacid) ↓Dolutegravir Administer JULUCA and supplements containing calcium or iron together with a meal or take JULUCA 4 hours before or 6 hours after taking these supplements.

Potassium channel blocker: Dalfampridine ↑Dalfampridine Elevated levels of dalfampridine increase the risk of seizures. The potential benefits of taking dalfampridine concurrently with JULUCA should be considered against the risk of seizures in these patients.

Proton pump inhibitors: e.g., Esomeprazole Lansoprazole Omeprazole Pantoprazole Rabeprazole ↓Rilpivirine Coadministration is contraindicated with JULUCA due to decreased rilpivirine concentrations.