Glecaprevir and pibrentasvir

Glecaprevir and pibrentasvir has the following uses:

The fixed combination of glecaprevir and pibrentasvir is indicated for the treatment of patients with chronic HCV genotype (GT) 1, 2, 3, 4, 5 or 6 infection without cirrhosis and with compensated cirrhosis (Child-Pugh A). Glecaprevir and pibrentasvir is also indicated for the treatment of adult patients with HCV genotype 1 infection, who previously have been treated with a regimen containing an HCV NS5A inhibitor or an NS3/4A protease inhibitor, but not both. 1

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Carbamazepine, efavirenz, and St. John’s wort may decrease concentrations of glecaprevir and pibrentasvir. Coadministration of carbamazepine, efavirenz containing regimens, and St. John’s wort with glecaprevir and pibrentasvir is not recommended. 1

Consult the full prescribing information prior to and during treatment for potential drug interactions.1

AHFS First Release. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

• If you have an allergy to glecaprevir and pibrentasvir or any part of this medicine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have liver problems other than hepatitis C.
• If you are taking a drug that contains ethinyl estradiol, like certain birth control pills. Do not take a drug that contains ethinyl estradiol while taking glecaprevir and pibrentasvir.
• If you take any drugs (prescription or OTC, natural products, vitamins) that must not be taken with this medicine, like certain drugs that are used for HIV, infections, or seizures. There are many drugs that must not be taken with glecaprevir and pibrentasvir.
• If you are taking St. John's wort. Do not take St. John's wort with this medicine. This medicine may not work as well.

This is not a list of all drugs or health problems that interact with glecaprevir and pibrentasvir.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

• Tell all of your health care providers that you take glecaprevir and pibrentasvir. This includes your doctors, nurses, pharmacists, and dentists.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• It is not known if this medicine stops the spread of diseases like hepatitis that are passed through blood or having sex. Do not have any kind of sex without using a latex or polyurethane condom. Do not share needles or other things like toothbrushes or razors. Talk with your doctor.
• This medicine may affect how much of some other drugs are in your body. If you are taking other drugs, talk with your doctor. You may need to have your blood work checked more closely while taking glecaprevir and pibrentasvir with your other drugs.
• Call your doctor right away if you have signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
• Drugs that contain ethinyl estradiol, like certain birth control pills, must not be used with this medicine. If you use birth control that contains ethinyl estradiol, you will need to use another type of birth control like condoms. Talk with the doctor.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using glecaprevir and pibrentasvir while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

• Store at room temperature.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take glecaprevir and pibrentasvir or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to glecaprevir and pibrentasvir. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Glecaprevir AUC was 100% higher in Child-Pugh class B patients, and increased to 11-fold in Child-Pugh class C patients. Pibrentasvir AUC was 26% higher in Child-Pugh class B patients, and 114% higher in Child-Pugh class C patients.

Severe hepatic impairment (Child-Pugh class C); coadministration with atazanavir or rifampin

Applies to glecaprevir / pibrentasvir: oral tablet

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache.
• Feeling tired or weak.
• Upset stomach.
• Loose stools (diarrhea).

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Animal studies with glecaprevir have failed to reveal evidence of embryofetal toxicity in rats (exposures up to 53 times the exposure in humans at the recommended human dose [RHD]); in rabbits, maternal toxicity (anorexia, lower body weight, lower body weight gain) with some embryofetal toxicity (increased postimplantation loss, increased number of resorptions, decreased fetal body weight) prevented evaluation of glecaprevir at clinical exposures (highest exposure reached in rabbits was 0.07 times the exposure in humans at RHD). Animal studies with pibrentasvir have failed to reveal evidence of embryofetal toxicity in mice and rabbits (exposures up to 51 and 1.5 times the exposure in humans at RHD, respectively). There are no controlled data in human pregnancy. US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.

According to some authorities: As a precaution, use is not recommended. US FDA pregnancy category: Not assigned. Risk summary: No adequate data available on use of this drug in pregnant women to inform a drug-related risk.

Glecaprevir and pibrentasvir may be found in some form under the following brand names:

• Mavyret

The combination of glecaprevir and pibrentasvir comes as a tablet to take by mouth. It is usually taken with food once daily for 8 to 16 weeks. Take glecaprevir and pibrentasvir at around the same time every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take glecaprevir and pibrentasvir exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Continue to take glecaprevir and pibrentasvir even if you feel well. The length of your treatment depends on your condition, if you have previously taken certain HCV medications, how well you respond to the medication, and whether you experience serious side effects. Do not stop taking glecaprevir and pibrentasvir without talking to your doctor.

Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient.

Before taking glecaprevir and pibrentasvir,

• tell your doctor and pharmacist if you are allergic to glecaprevir, pibrentasvir, any other medications, or any of the ingredients in the glecaprevir and pibrentasvir tablets. Ask your pharmacist for a list of the ingredients.
• tell your doctor if you are taking atazanavir (Reyataz, in Evotaz) or rifampin (Rifadin, Rimactane, in Rifamate, in Rifater). Your doctor will probably tell you not to take glecaprevir and pibrentasvir if you are taking one of these medications.
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: carbamazepine (Carbatrol, Epitol, Equetro, Tegretol), cholesterol-lowering medications (statins) such as atorvastatin (Lipitor, in Caduet), fluvastatin (Lescol), lovastatin (Altoprev), pitavastatin (Livalo), pravastatin (Pravachol), rosuvastatin (Crestor), and simvastatin (Zocor, in Simcor, in Vytorin); cyclosporine (Gengraf, Neoral, Sandimmune); dabigatran (Pradaxa); digoxin (Lanoxin); ethinyl estradiol oral contraceptives such as certain ('birth control pills'), patches, hormonal vaginal rings, and other ethinyl estradiol products; certain hormone replacement therapies (HRT); and certain medications for human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) including darunavir (Prezista, in Prezcobix), efavirenz (Sustiva, in Atripla), or lopinavir (in Kaletra). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor what herbal products you are taking, especially St. John's wort.
• tell your doctor if you have any type of liver disease other than hepatitis C. Your doctor may tell you not to take glecaprevir and pibrentasvir.
• tell your doctor if you have ever had human immunodeficiency virus (HIV).
• tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. If you become pregnant while taking glecaprevir and pibrentasvir, call your doctor.

Unless your doctor tells you otherwise, continue your normal diet.

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom).

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

In the U.S.

• Mavyret

Available Dosage Forms:

• Tablet

Therapeutic Class: Antiviral

Pharmacologic Class: Hepatitis C Virus NS5A Inhibitor