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

Mavyret (glecaprevir/pibrentasvir) is involved in a significant number of drug interactions—over 230 medications have documented interactions with Mavyret. Many of these are minor, but some are serious or even life-threatening. Before starting Mavyret, your doctor and pharmacist will need a complete list of everything you take. Here's what you need to know.

Why Does Mavyret Have So Many Drug Interactions?

Both glecaprevir and pibrentasvir are processed by and interact with important drug transporters and enzymes in your body, specifically:

P-glycoprotein (P-gp) and BCRP transporters — Mavyret is a substrate AND inhibitor of these; drugs that strongly affect P-gp can raise or lower Mavyret levels significantly

OATP1B1 and OATP1B3 liver transporters — Mavyret inhibits these, which can dramatically raise the levels of drugs that depend on them for clearance (like some statins)

CYP3A4 enzyme — drugs that strongly induce CYP3A4 can dramatically reduce Mavyret blood levels, causing treatment failure

Absolutely Contraindicated Medications (Do NOT Take With Mavyret)

These drug combinations are absolutely contraindicated—meaning you must not take them at the same time as Mavyret:

Atazanavir (Reyataz): HIV protease inhibitor. Dramatically increases glecaprevir blood levels (up to 6.5-fold increase in AUC), causing severe liver enzyme elevations (ALT/AST). CONTRAINDICATED.

Rifampin (Rifadin): Antibiotic used for tuberculosis. A potent inducer of CYP3A4 and P-gp that dramatically REDUCES Mavyret levels, leading to treatment failure. CONTRAINDICATED.

Atorvastatin: Mavyret raises atorvastatin blood levels up to 8.3-fold, dramatically increasing the risk of muscle injury (myopathy/rhabdomyolysis). Concomitant use is NOT recommended.

Drugs to Avoid or Use With Extreme Caution

Simvastatin, lovastatin: Like atorvastatin, these statins have their blood levels significantly raised by Mavyret. Risk of muscle damage. Should generally be avoided during Mavyret treatment.

Darunavir (Prezista): HIV protease inhibitor. Increases Mavyret levels due to CYP3A4/P-gp inhibition. Avoid co-administration.

Ritonavir: HIV protease inhibitor and pharmacokinetic booster. Increases Mavyret levels. Avoid.

Efavirenz (Sustiva): HIV NNRTI. Reduces glecaprevir and pibrentasvir levels, potentially causing Mavyret treatment failure. Not recommended with Mavyret.

Carbamazepine (Tegretol), phenytoin (Dilantin), phenobarbital: Anti-seizure medications. Strong CYP3A4 inducers that significantly reduce Mavyret blood levels. Can cause treatment failure. Avoid.

St. John's Wort (herbal supplement): Strong P-gp/CYP3A4 inducer. Significantly reduces Mavyret levels. Do NOT take during Mavyret treatment.

Cyclosporine (doses over 100 mg/day): Immunosuppressant used after transplant. At high doses, significantly increases Mavyret levels. If cyclosporine is necessary at doses ≤100 mg/day, caution is advised with monitoring.

Drugs That Require Monitoring or Dose Adjustment

Warfarin (Coumadin): As HCV is cleared and liver function improves, warfarin metabolism changes. INR should be monitored more frequently during Mavyret treatment.

Diabetes medications (insulin, sulfonylureas): As HCV is cleared and liver function improves, blood glucose control can change significantly, causing hypoglycemia. Blood sugar monitoring should be increased.

Digoxin: Mavyret increases digoxin levels via P-gp inhibition. Digoxin levels should be monitored.

Tacrolimus, everolimus (transplant drugs): Mavyret can affect levels of these immunosuppressants. Transplant patients should have drug levels carefully monitored.

Drugs That Are Safe With Mavyret

Many commonly used medications have been studied with Mavyret and found to have no clinically significant interactions, including:

Methadone and buprenorphine/naloxone (no dose adjustment required)

Raltegravir, dolutegravir, rilpivirine (HIV integrase inhibitors)

Tenofovir alafenamide (TAF) — commonly used HIV medication

Omeprazole and other PPIs (no interaction — an advantage over Epclusa and Harvoni)

Lamotrigine, losartan, midazolam, amlodipine (no dose adjustment needed)

What to Tell Your Doctor Before Starting Mavyret

Bring a complete, updated medication list to every appointment—including prescriptions, OTC drugs, vitamins, and herbal supplements. Specifically mention any anticonvulsants, statins, HIV medications, immunosuppressants, blood thinners, and herbal supplements. Also see our guides on Mavyret side effects and what Mavyret is and how it's taken for complete prescribing context.