Mavyret (glecaprevir/pibrentasvir) interacts with a surprisingly long list of medications, supplements, and even some foods. Some combinations are outright dangerous, while others can make the treatment less effective against hepatitis C. Knowing what to steer clear of during your 8- to 16-week course can help you finish treatment safely and get the best chance at a cure.
Medications That Are Strictly Off-Limits
Several drugs are fully contraindicated with Mavyret, meaning they should not be taken together under any circumstances. The FDA’s prescribing information names two in particular: atazanavir (an HIV medication) and rifampin (used for tuberculosis and some other infections). Rifampin drastically lowers the levels of Mavyret’s active ingredients in your blood, which can cause treatment failure. Atazanavir does the opposite, raising drug levels to a potentially toxic range.
A handful of seizure medications also fall into the contraindicated category: carbamazepine, phenytoin, and phenobarbital. Like rifampin, these drugs speed up the breakdown of Mavyret in your body, reducing its concentration below what’s needed to clear the virus. If you take any of these, your provider will need to find alternatives or choose a different hepatitis C regimen entirely.
The blood thinner dabigatran is also contraindicated. Mavyret can significantly increase dabigatran levels, raising the risk of serious bleeding.
Cholesterol Medications That Need Attention
Statins are one of the most commonly prescribed drug classes, and several of them interact dangerously with Mavyret. The combination with atorvastatin is contraindicated because Mavyret increases atorvastatin exposure in the body by roughly 8-fold overall, with peak blood levels jumping by 22-fold. That kind of spike dramatically raises the risk of muscle breakdown, a serious condition called rhabdomyolysis.
Simvastatin is also contraindicated. Even at a low dose, combining it with Mavyret more than doubles simvastatin levels and increases the active form in the blood by about 10-fold.
Lovastatin is not formally contraindicated but is not recommended. If it absolutely must be used, the dose should not exceed 20 mg per day, and you’d need close monitoring for muscle pain or weakness. Other statins like rosuvastatin and pravastatin may also need dose adjustments, so your prescriber should review your specific statin before you start treatment. In many cases, the simplest approach is to pause your statin for the 8 to 12 weeks of Mavyret therapy.
Estrogen-Containing Contraceptives
Birth control products that contain ethinyl estradiol, the synthetic estrogen found in most combination pills, patches, and vaginal rings, pose a real risk during Mavyret treatment. Ethinyl estradiol interferes with the same liver enzymes that process Mavyret, which can increase the concentration of glecaprevir and its toxic byproducts. In Europe, this combination is flatly contraindicated. In the U.S., it’s listed as a significant interaction.
The concern isn’t theoretical. In one published case, a woman without cirrhosis who took both medications developed severe drug-induced liver injury, with liver enzyme levels climbing to more than 17 times the upper limit of normal. If you use hormonal contraception, switch to a progestin-only method or a non-hormonal option like an IUD or condoms for the duration of treatment.
St. John’s Wort and Herbal Supplements
St. John’s Wort is the most important herbal product to avoid. It activates the same enzyme pathways (P-gp and CYP3A) that break down Mavyret, lowering drug levels enough to reduce the treatment’s effectiveness. The FDA prescribing information specifically recommends against combining the two.
Other herbal supplements that stimulate those same pathways could pose similar risks, though St. John’s Wort is the best-studied offender. If you take any herbal or dietary supplements, bring the full list to your provider before starting treatment. Some may be fine to continue, but others may need to be paused.
Alcohol and Liver Health
Mavyret’s prescribing label doesn’t list alcohol as a formal contraindication, but clinical guidelines are clear: there is no known safe level of alcohol use for people with hepatitis C. Alcohol accelerates liver scarring even at modest levels, likely through increased viral replication, greater oxidative stress, and weakened immune responses in the liver. Patients starting hepatitis C treatment are routinely advised to reduce or stop drinking entirely.
Since Mavyret is already processed through the liver, adding alcohol to the mix puts extra strain on an organ that’s already working hard. Treatment courses are short, typically 8 to 12 weeks, making this a manageable window to go without drinking.
Taking Mavyret on an Empty Stomach
This one is easy to overlook but matters for how well the medication works. Mavyret must be taken with food. The FDA labeling specifies taking all three tablets at the same time, once daily, just before or after a snack or meal. Food increases the absorption of both active ingredients. Taking it on an empty stomach can lower drug levels in your blood and reduce your chances of clearing the virus.
You don’t need a large meal. A snack is enough. The key is consistency: take it at roughly the same time each day, with something to eat.
What to Do if You Miss a Dose
Mavyret uses an 18-hour rule for missed doses. If fewer than 18 hours have passed since your usual dosing time, take the missed dose with food as soon as you remember, then resume your normal schedule. If more than 18 hours have passed, skip the missed dose entirely and take the next one at your regular time. Don’t double up.
Consistency matters because maintaining steady drug levels is what keeps the virus from developing resistance. Setting a daily alarm can help you stay on track.
Advanced Liver Disease
Mavyret is not appropriate for everyone with hepatitis C. People with moderate to severe liver impairment, classified as Child-Pugh B or C, or anyone with a history of liver decompensation (when the liver has lost the ability to function adequately) should not take this medication. In these patients, drug exposure rises significantly because the damaged liver can’t process the medication normally, increasing the risk of serious side effects. Alternative hepatitis C treatments exist for people in this situation.