Treating Chronic Hepatitis C With Mavyret

Mavyret (glecapravir, pibrentasvir) is a fixed dose combination drug used in the treatment of chronic hepatitis C (HCV) infection. The drugs used in Mavyret work by blocking two individual proteins that the virus needs to replicate.

Mavyret was approved on August 3, 2017 by the U.S. Food and Drug Administration for use in adults 18 and over. Research suggests that the drug can achieve cure rates of between 92 percent and 100 percent depending HCV subtype, a figure that is more or less in line with other direct-acting antivirals (DAAs) currently used in hepatitis C treatment.

Pros and Cons

Mavyret is able to treat all six HCV strains (genotypes) and can be used both in persons who have been never exposed to HCV drugs and those who have previously failed treatment. Moreover, the drug can be used in people with compensated cirrhosis (in which the liver is still functional).

Mavyret has one key advantage over similar drugs in that it can treat chronic hepatitis C infection in as little as eight weeks. All other drugs require no less 12 weeks for newly treated patients. This includes the combination HCV drug Epclusa which is also approved for all six genotypes.

However, unlike Epclusa, Mavyret cannot be used in persons with decompensated cirrhosis (whose livers are no longer functioning).

Another key differentiator is the price. Whereas drugs like Epclusa carry a wholesale price tag of around $75,000 for a 12-week course (or $890 per pill), Mavyret is offered at $26,400 for an eight-week course (or $439 per tablet).

The price difference may be enough to convince health insurers to expand treatment to the 3.9 million Americans chronically infected with HCV, most of whom have to wait until there is significant liver impairment before treatment can be approved.

Prescribing Recommendations

The recommended dosage of Mavyret is three tablets taken once daily with food. Each tablet contains 100 milligrams of glecaprevir and 40 milligrams of pibrentasvir. The tablets are pink, oblong-shaped, film-coated, and debossed with "NXT" on one side.

The duration of therapy varies by the HCV genotype, treatment experience, and liver status of the patient, as follows:

• Previously untreated with no cirrhosis: eight weeks
• Previously untreated with compensated cirrhosis: 12 weeks
• Previously treated with HCV genotypes 1, 2, 4, 5, and 6 with no cirrhosis: eight to 16 weeks depending on the previous therapy
• Previously treated with HCV genotypes 1, 2, 4, 5, and 6 with compensated cirrhosis: 12 to 16 weeks depending on the previous therapy
• Previously treated with HCV genotype 3 with or without cirrhosis: 16 weeks

Approximately 75 percent of Americans with hepatitis C have genotype 1, which is the most prevalent but also the most difficult to treat. By contrast, between 20 and 25 percent have genotypes 2 and 3, while only a small handful have genotypes 4, 5, or 6.

Side Effects

Newer generation DAAs like Mavyret have far fewer side effects than earlier generation therapies, many of which included the drug pegylated interferon (peginterferon) and ribavirin. The most common side effects associated with Mavyret (occurring in over five percent of patients) include:

• Headache
• Fatigue
• Nausea
• Diarrhea

Generally speaking, the side effects are manageable and tend to improve over time. In fact, pre-market research concluded that less than one percent of people on Mavyret discontinued treatment as a result of intolerable side effects.

Drug Interactions

The use of rifampin-based medications, commonly used to treat tuberculosis, are contraindicated for use with Mavyret and should be discontinued prior to the start of treatment. These include drugs with the brand names Mycobutin, Rifater, Rifamate, Rimactane, Rifadin, and Priftin.

Other drugs are known to interact with Mavyret and may either increase or decrease the concentration of Mavyret in the blood. The following are not recommended for use with Mavyret:

• Carbamepazine, used to treat seizures and bipolar disorder
• Ethinyl estradiol (estrogen)-containing birth control medications
• Sustiva (efavirenz) used in HIV therapy
• Atorvastatin, lovastatin, and simvastatin used to treat high cholesterol
• St. John’s Wort

Liver Impairment

Mavyret is contraindicated for use in persons with severe liver impairment (as measured by a Child-Pugh score of C) and is not recommended for anyone with even moderate impairment (Child-Pugh B).

Liver function testing is recommended prior the start of therapy to avoid complications. The Child-Pugh score is also useful in determining the severity of the liver disease based on blood tests and a review of the characteristic symptoms.

Hepatitis B Reactivation

Mavyret should be used with caution in persons who have both hepatitis B and hepatitis C. The hepatitis B virus (HBV) has been known to reactive during or soon after treatment. Reactivation may be accompanied by symptoms of jaundice and liver inflammation. If treatment is not stopped immediately, reactivation could lead to liver failure and even death.

While HBV infection does not contraindicate the use of Mavyret, it would require closer monitoring of the liver enzymes to identify the early signs of reactivation.

In Pregnancy

While Mavyret is not contraindicated in pregnancy, there is little human clinical data available to assess the actual risk. With that being said, animal studies have shown that the use of glecaprevir and pibrentasvir during pregnancy is not associated with fetal abnormalities, including exposure during breastfeeding.

Specialist consultation is recommended to not only weigh the benefits and risks of treatment but to help determine whether the treatment is a matter of urgency or something that can be delayed until after the delivery.

To prevent pregnancy during treatment, couples are advised use at least two non-hormonal methods of contraception during and up to six months after the completion of therapy. Since estrogen-based birth control is not recommended, speak with your healthcare provider to see whether a progestin-only oral contraceptive may be a suitable option.