Mavyret

Chronic Hepatitis C Treatment

Mavyret is used to treat chronic hepatitis C, a viral infection that causes inflammation of the liver. It is a combination of two antiviral medications, glecaprevir and pibrentasvir, which work together to stop the virus from multiplying in the body.

Genotypes and Patient Groups

This medication is approved for several specific situations:

• All Genotypes: It is used to treat adults and children (3 years of age and older) who have any of the six major genotypes (1, 2, 3, 4, 5, or 6) of the hepatitis C virus.
• Liver Health: It is suitable for patients who do not have cirrhosis (liver scarring) or those who have compensated cirrhosis (mild scarring where the liver still functions).
• Previous Treatment: It is used in adults with genotype 1 infection who have been previously treated with certain types of antiviral drugs, specifically an NS3/4A protease inhibitor or an NS5A inhibitor.
• Kidney Disease: It can be used in patients with any stage of kidney disease, including those on dialysis.

Important Limitations

Mavyret is not intended for everyone with hepatitis C. It is not recommended for patients with moderate or severe liver disease, also known as decompensated cirrhosis. Healthcare providers will assess liver function before and during treatment to ensure the medication is appropriate.

Mechanism of Action

Mavyret is a direct-acting antiviral (DAA) medication. It is made of two drugs, glecaprevir and pibrentasvir, which interfere with the proteins the hepatitis C virus (HCV) uses to reproduce.

How the Ingredients Work

• Glecaprevir: This is an NS3/4A protease inhibitor. The virus uses the NS3/4A protease enzyme to cut long protein chains into smaller pieces that are necessary for the virus to make copies of itself. Glecaprevir blocks this enzyme, stopping the replication process.
• Pibrentasvir: This is an NS5A inhibitor. It targets the NS5A protein, which is required for the virus to copy its genetic material and assemble new virus particles.

By attacking the virus at these two different stages, Mavyret prevents the virus from multiplying. This reduces the amount of virus in the body, with the goal of clearing the infection completely.

Common Side Effects

The most frequently reported side effects of Mavyret are typically mild. These may include:

• Headache
• Tiredness or fatigue
• Nausea
• Diarrhea
• Itching

Serious Side Effects

While rare, some individuals may experience serious side effects that require immediate medical attention. These include:

• Worsening liver function: In rare cases, Mavyret can cause serious liver injury, especially in patients with pre-existing advanced liver disease. Symptoms may include yellowing of the skin or eyes (jaundice), dark urine, light-colored stools, nausea, vomiting, or swelling in the stomach area.
• Allergic reactions: Signs of a severe allergic reaction include skin rash, hives, swelling of the face, lips, or throat, and difficulty breathing.
• Hepatitis B reactivation: If you have ever had hepatitis B, the virus could become active again during or after treatment with Mavyret, which can lead to serious liver problems.

It is important to report any new or worsening symptoms to a healthcare provider during treatment.

Hepatitis B Virus Reactivation

Mavyret has a boxed warning for the risk of hepatitis B virus (HBV) reactivation. In patients who have both hepatitis C and hepatitis B, the HBV can become active again during or after treatment. This can lead to serious liver problems, including liver failure or death. Testing for HBV infection is required before starting Mavyret.

Liver Function Concerns

This medication is not recommended for patients with moderate liver impairment and is contraindicated in those with severe liver impairment (Child-Pugh C). There have been reports of serious liver injury or liver failure in patients with advanced liver disease who took Mavyret. Monitoring for signs of liver damage is common during treatment. Symptoms that may indicate liver issues include:

• Yellowing of the eyes or skin
• Nausea and vomiting
• Dark urine
• Pain in the upper right stomach area
• Confusion or swelling in the abdomen

Contraindications and Interactions

Mavyret should not be used with certain other medications, as they may decrease its effectiveness or increase the risk of side effects. Contraindicated drugs include atazanavir and rifampin. Additionally, medications containing ethinyl estradiol, such as certain hormonal contraceptives, are not recommended for use with Mavyret due to the risk of increased liver enzyme levels.

Pregnancy

There are no adequate and well-controlled studies on the use of Mavyret in pregnant individuals. Data from animal studies involving glecaprevir and pibrentasvir did not show a risk of birth defects or miscarriage, even at doses much higher than those used in humans. However, animal studies do not always predict how a drug will affect human pregnancy.

If you are pregnant or planning to become pregnant, talk to your doctor about whether Mavyret is appropriate for you. They will help weigh the potential benefits of treating hepatitis C against any unknown risks to the developing fetus.

Breastfeeding

It is unknown if the active ingredients in Mavyret pass into human breast milk, how they might affect milk production, or if they have any impact on a breastfed infant. In animal studies, the components of the medication were found in the milk of lactating rats.

If you are breastfeeding or planning to breastfeed, consult your healthcare provider. They can help you decide whether to continue breastfeeding or start treatment based on your clinical needs and the potential risks to the child.

Available Forms

Mavyret is supplied in the following oral formulations:

• Tablets: These are oral tablets intended to be swallowed whole.
• Oral Pellets: These are small pellets contained in individual packets or sachets. They are designed to be sprinkled on a small amount of soft food, which is particularly useful for children or individuals who have difficulty swallowing tablets.

Both the tablets and the oral pellets must be administered with food to ensure the medication is absorbed correctly.

FDA Approval and Indications

Mavyret was approved by the U.S. Food and Drug Administration (FDA) to treat chronic hepatitis C virus (HCV) genotypes 1 through 6. It is authorized for use in adults and pediatric patients aged 3 years and older who have no cirrhosis or mild cirrhosis. It is also indicated for certain patients with genotype 1 infection who were previously treated with specific antiviral regimens.

Boxed Warning

Mavyret carries a boxed warning concerning the risk of hepatitis B virus (HBV) reactivation. In patients coinfected with HCV and HBV, the hepatitis B virus can become active again during or after treatment, potentially leading to severe liver damage or death. Screening for HBV infection is required before beginning therapy.

Safety Warnings

The FDA has issued safety alerts regarding the use of Mavyret in patients with advanced liver disease. While the drug is safe for those with no or mild liver impairment, it is not recommended for patients with moderate liver impairment and is contraindicated for those with severe liver impairment (Child-Pugh C) due to the risk of serious liver injury or liver failure.

Factors Influencing Cost

The total price of Mavyret can vary significantly based on several factors, including your specific insurance plan, the pharmacy you use, and the duration of your treatment. Most patients require an 8-week course, but some may need longer treatment, which can increase the overall cost.

Insurance and Medicare Coverage

Many private insurance plans, Medicare Part D, and Medicaid cover Mavyret. However, your out-of-pocket expenses will depend on your plan's formulary, your deductible, and your specific co-pay or coinsurance requirements. Because Mavyret is a specialty medication, it is typically dispensed through specialty pharmacies.

Financial Assistance

Because specialty medications can be expensive, there are often programs available to help reduce the cost:

• Co-pay Savings Cards: The manufacturer may offer co-pay cards for patients with commercial insurance that can significantly lower out-of-pocket costs.
• Patient Assistance Programs: For individuals who are uninsured or underinsured, patient assistance programs may provide the medication at a reduced cost or for free, depending on financial eligibility.

Generic Availability

Mavyret is a brand-name drug containing the active ingredients glecaprevir and pibrentasvir. There are currently no generic versions available. Brand-name specialty drugs typically cost more than generic alternatives because they are protected by patents that prevent other companies from making the same medication for a set period.