Genvoya Drug Interactions: What to Avoid and What to Tell Your Doctor

Genvoya has an unusually large drug interaction profile — over 730 known interactions with other medications, of which 358 are classified as major. This is primarily because cobicistat, one of Genvoya's four components, is a potent inhibitor of CYP3A, an enzyme in the liver that metabolizes a huge number of drugs. If you take Genvoya, your prescriber and pharmacist need to review all of your other medications carefully.

Why Does Genvoya Have So Many Drug Interactions?

The culprit is cobicistat — the pharmacokinetic booster in Genvoya. Cobicistat powerfully inhibits the CYP3A enzyme family in the liver, as well as CYP2D6 and several drug transporters (P-glycoprotein, BCRP, OATP1B1, and OATP1B3). Any drug that is processed by these pathways can be affected when you add Genvoya.

Interactions can go both ways:

Other drugs can increase or decrease Genvoya levels: Drugs that strongly induce CYP3A (speed it up) will reduce elvitegravir blood levels, potentially making Genvoya ineffective.

Genvoya can increase levels of other drugs: Because cobicistat blocks CYP3A, drugs metabolized by CYP3A can build up to toxic or dangerous levels when combined with Genvoya.

Medications That Are CONTRAINDICATED With Genvoya (Do Not Use Together)

The following medications must never be taken with Genvoya due to the risk of serious or life-threatening interactions:

St. John's wort (Hypericum perforatum): This herbal supplement is a strong CYP3A inducer that dramatically reduces elvitegravir blood levels, potentially causing treatment failure and HIV resistance.

Rifampin (rifampicin): A potent antibiotic/CYP3A inducer used for tuberculosis — dramatically reduces Genvoya levels.

Lovastatin and simvastatin: Cholesterol medications that are highly dependent on CYP3A; Genvoya dramatically increases their blood levels, raising the risk of severe muscle damage (rhabdomyolysis).

Triazolam and oral midazolam: Sedative medications — Genvoya can cause life-threatening respiratory depression by increasing their levels.

Lomitapide: Used for rare cholesterol disorders; Genvoya greatly increases its levels.

Sildenafil for pulmonary arterial hypertension (Revatio): Using sildenafil at the doses for PAH treatment (not erectile dysfunction) with Genvoya can cause dangerous drops in blood pressure. (Lower doses for erectile dysfunction may be used with caution and dose adjustment — discuss with your provider.)

Anticonvulsants (carbamazepine, phenobarbital, phenytoin): Strong CYP3A inducers that will reduce Genvoya's effectiveness.

Rifapentine: Another tuberculosis drug and strong CYP3A inducer.

Medications That Require Monitoring or Dose Adjustment With Genvoya

Many other medications can still be used with Genvoya but require careful monitoring or dose adjustments:

Statins (atorvastatin, rosuvastatin): Can be used but at reduced doses with monitoring for muscle symptoms. Start with the lowest effective dose.

Hormonal contraceptives: Genvoya alters blood levels of hormonal contraceptives. Use non-hormonal contraception (condoms, IUD) or a regimen with at least 35 mcg ethinyl estradiol. Discuss with your provider.

Methadone and buprenorphine: Monitor for signs of opioid withdrawal or toxicity; doses may need adjustment.

Antacids (aluminum, calcium, magnesium, iron): Separate from Genvoya by at least 2 hours before or after.

Warfarin: Monitor INR closely when starting or stopping Genvoya; dose adjustments may be needed.

NSAIDs (ibuprofen, naproxen): Regular use may increase risk of kidney toxicity when combined with Genvoya. Use cautiously and only as directed.

Azole antifungals (fluconazole, itraconazole, ketoconazole, voriconazole): These can increase Genvoya components' levels — careful monitoring needed.

What to Tell Your Doctor and Pharmacist Before Starting Genvoya

Before starting Genvoya, give your HIV provider and pharmacist a complete list of everything you take, including:

All prescription medications (including medications prescribed by any other doctor)

Over-the-counter medications (antacids, pain relievers, allergy medications, sleep aids)

Vitamins and supplements (calcium, magnesium, iron, vitamin D)

Herbal products (especially St. John's wort, which is absolutely contraindicated)

Also tell your provider any time you start or stop a medication while on Genvoya, as new interactions can develop at any time.

Key Takeaway

Drug interactions are one of the most important things to manage when taking Genvoya. Always work closely with your HIV provider and a pharmacist who is familiar with HIV medications. See also our guide on Genvoya side effects for more on what to watch for while on treatment.

If you're struggling to find Genvoya in stock, medfinder can help by calling local pharmacies on your behalf.