Boceprevir

>10%

Fatigue (55-58%)

Anemia (45-50%)

Nausea (43-46%)

Headache (>35%)

Dysgeusia (35-44%)

Insomnia (30-34%)

Chills (33-34%)

Alopecia (22-27%)

Diarrhea (25%)

Anorexia (25%)

Neutropenia (14-25%)

Arthralgia (19-23%)

Irritability (21-22%)

Dry skin (18-22%)

Asthenia (15-21%)

Vomiting (15-20%)

Dizziness (16-19%)

Rash (16-17%)

Xerostomia (11-15%)

Exertional dyspnea (8-11%)

Postmarketing Reports

Blood and lymphatic system disorders: Agranulocytosis, pancytopenia, thrombocytopenia

Gastrointestinal disorders: Mouth ulceration, stomatitis

Infections and Infestations: Pneumonia, sepsis

Skin and subcutaneous tissue disorders: Angioedema, urticaria; drug rash with eosinophilia and systemic symptoms (DRESS) syndrome, exfoliative rash, exfoliative dermatitis, Stevens-Johnson syndrome, toxic skin eruption, toxicoderma

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Stop using boceprevir and call your doctor at once if you have:

• tired feeling, weakness, confusion;
• easy bruising or bleeding (nosebleed, bleeding gums);
• pale skin, feeling light-headed or short of breath, rapid heart rate, trouble concentrating; or
• fever, chills, body aches, flu symptoms, sores in your mouth and throat.

Common side effects may include:

• headache;
• altered sense of taste; or
• nausea.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Boceprevir is part of the drug class:

• Protease inhibitors

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

This medication falls into category X. Boceprevir, in combination with peginterferon alfa and ribavirin, may cause birth defects or death of your unborn baby. If you are pregnant or your sexual partner is pregnant or plans to become pregnant, do not take these medicines. You or your sexual partner should not become pregnant while taking boceprevir, peginterferon alfa, and ribavirin combination therapy and for 6 months after treatment is over.

See "Drug Precautions."

Boceprevir is used in combination with other medications called peginterferon alfa and ribavirin.

Do not use boceprevir with peginterferon alfa and ribavirin if you are pregnant, or if you are a man and your female sexual partner is pregnant. Ribavirin can cause birth defects or death in an unborn baby.

Some medicines can interact with boceprevir and should not be used at the same time. Tell your doctor about all your current medicines and any you start or stop using.

Chronic Hepatitis C Virus (HCV) Infection

Treatment of chronic HCV genotype 1 infection in adults with compensated liver disease (including cirrhosis) who are treatment naive (previously untreated) or have failed prior treatment with interferon and ribavirin (including those with prior null response, partial response, or relapse).1 3 4

Used in conjunction with peginterferon alfa (alfa-2a, alfa-2b) and ribavirin;1 do not use alone.1

Consider that poor interferon responders subsequently treated with boceprevir in conjunction with peginterferon alfa and ribavirin are less likely to achieve sustained virologic response (SVR) and more likely to have resistance-associated mutations detected on treatment failure compared with those who had a greater response to lead-in therapy with peginterferon alfa and ribavirin.1 3

Efficacy not established in patients who previously failed therapy with a regimen containing boceprevir or other HCV NS3/4A PI.1

Safety and efficacy not established in chronic HCV patients with HBV or HIV coinfection or in recipients of liver or other organ transplantations.1

Treatment of chronic HCV infection is complex and rapidly evolving; consult a specialist to obtain the most up-to-date information.119 Information from the American Association for the Study of Liver Diseases (AASLD), IDSA, and International Antiviral Society–USA (IAS–USA) regarding diagnosis and management of HCV infection, including current recommendations for initial treatment, is available at .119

In the U.S.

• Victrelis

Available Dosage Forms:

• Capsule

Therapeutic Class: Antiviral

Pharmacologic Class: Protease Inhibitor

It is very important that your doctor check your progress at regular visits to make sure boceprevir is working properly. Blood tests may be needed to check for unwanted effects.

Using boceprevir together with peginterferon alfa and ribavirin while you are pregnant can harm your unborn baby. These medicines may also cause birth defects if the father is using it when his sexual partner becomes pregnant. If a pregnancy occurs while you are using these medicines, tell your doctor right away.

To make sure you are not pregnant, your doctor may ask you to have a pregnancy test before you start using boceprevir. You must have a negative pregnancy test before you will be allowed to use boceprevir with ribavirin. Two forms of birth control must be used during treatment and for 6 months after treatment ends. You should test for pregnancy every month while you are using boceprevir, and for 6 months after your treatment ends.

Birth control pills may not work while you are using boceprevir. To keep from getting pregnant, use two other forms of birth control. Other forms of birth control include condoms, a diaphragm, or contraceptive foam or jelly.

Do not use boceprevir together with the following medicines: cisapride (Propulsid®), drospirenone (Yasmin®, Yaz®), lurasidone (Latuda®), oral midazolam (Versed®), pimozide (Orap®), rifampin (Rifadin®, Rimactane®), sildenafil (Revatio®), St. John's wort, tadalafil (Adcirca®), triazolam (Halcion®), medicines to treat an enlarged prostate (such as alfuzosin, doxazosin, silodosin, tamsulosin, Cardura®, Flomax®, Rapaflo®, Uroxatral®), certain medicines to lower cholesterol (such as lovastatin, simvastatin, Mevacor®, Zocor®), medicines to treat seizures (such as carbamazepine, phenobarbital, phenytoin, Dilantin®, Tegretol®), or ergot medicines (such as dihydroergotamine, ergonovine, ergotamine, methylergonovine, DHE 45®, Ergomar®, Ergotrate®, Methergine®). Using boceprevir with any of these medicines can cause very serious medical problems.

Check with your doctor right away if you have back, leg, or stomach pains, bleeding gums, chills, dark urine, difficulty with breathing, fever, general body swelling, headache, loss of appetite, nausea or vomiting, nosebleeds, pale skin, sore throat, unusual tiredness or weakness, or yellowing of the eyes or skin. These could be symptoms of a blood disorder called anemia.

Using boceprevir can temporarily lower the number of white blood cells in your blood, increasing the chance of getting an infection. It can also lower the number of platelets in the blood, which are necessary for proper blood clotting. If this occurs, there are certain precautions you can take, especially when your blood count is low, to reduce the risk of infection or bleeding:

• If you can, avoid people with infections. Check with your doctor immediately if you think you are getting an infection or if you get a fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination.
• Check with your doctor immediately if you notice any unusual bleeding or bruising, black, tarry stools, blood in the urine or stools, or pinpoint red spots on your skin.
• Be careful when using a regular toothbrush, dental floss, or toothpick. Your medical doctor, dentist, or nurse may recommend other ways to clean your teeth and gums. Check with your medical doctor before having any dental work done.
• Do not touch your eyes or the inside of your nose unless you have just washed your hands and have not touched anything else in the meantime.
• Be careful not to cut yourself when you are using sharp objects such as a safety razor or fingernail or toenail cutters.
• Avoid contact sports or other situations where bruising or injury could occur.

Serious allergic reactions can occur with boceprevir. Check with your doctor right away if you have hives, itching, swelling of the face, eyes, lips, tongue, or throat, or trouble breathing or swallowing while you are using boceprevir.

boceprevir will not keep you from giving hepatitis C to other people. Follow your doctor's instructions about how to prevent the spread of this infection.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Use boceprevir as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take this medicine with food.
• Keep taking boceprevir as you have been told by your doctor or other health care provider, even if you feel well.
• It is important that you do not miss or skip a dose of this medicine during treatment.
• If you stop taking any of your other drugs to treat hepatitis C, talk with your doctor. You may need to stop taking boceprevir also.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it, with food.
• If it is less than 2 hours until your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of infection like fever, chills, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or wound that will not heal.
• Signs of bleeding like throwing up blood or throw up that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; vaginal bleeding that is not normal; bruises without a reason or that get bigger; or any bleeding that is very bad or that you cannot stop.
• Feeling very tired or weak.
• Pale skin.
• Very bad dizziness or passing out.
• Shortness of breath.

• Store capsules in a refrigerator.
• You may also store this medicine at room temperature. If stored at room temperature, throw away any part not used after 3 months.
• Store in original container.
• Protect from heat.
• 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.

Mean AUC of the active metabolite was 32% and 45% higher in subjects with moderate and severe hepatic impairment, respectively, relative to subjects with healthy hepatic function. Mean Cmax values were 28% and 62% higher in subjects with moderate and severe hepatic impairment, respectively. Subjects with mild hepatic impairment had similar exposure as subjects with healthy hepatic function.

Concerns related to adverse effects:

• Anemia: Has been reported with peginterferon alfa and ribavirin; addition of boceprevir is associated with further hemoglobin decreases. With anemia management, average hemoglobin decrease in clinical trials was ~1 g/dL with a median time to onset of 71 days. Dose modifications of peginterferon alfa and ribavirin were needed more often in patients also taking boceprevir. Complete blood counts with differential should be obtained pretreatment and at weeks 2, 4, 8, and 12, as well as other times during treatment. Dose reduction of ribavirin therapy is recommended for the initial management of anemia if hemoglobin <10 g/dL; permanent discontinuation of ribavirin treatment is recommended if hemoglobin <8.5 g/dL. If ribavirin is permanently discontinued, boceprevir and peginterferon alfa must also be discontinued. In clinical trials comparing erythropoiesis-stimulating agents (ESAs) to ribavirin dose reduction for initial management of anemia during combination therapy, an increased risk of thromboembolic events were observed in patients receiving an ESA compared to the ribavirin dose reduction group.

• Hypersensitivity: Serious acute hypersensitivity reactions (eg, angioedema, urticaria) have been reported with boceprevir, peginterferon alfa, and ribavirin combination therapy. Discontinuation of combination therapy and institution of supportive measures may be necessary.

• Neutropenia: Has been reported with peginterferon alfa and ribavirin; addition of boceprevir is associated with a higher incidence of neutropenia. Complete blood counts with differential should be obtained pretreatment and at weeks 2, 4, 8, and 12, as well as other times during treatment. May require dose reduction of peginterferon or ribavirin therapy. May be severe or life-threatening (rare); discontinuation of therapy may be necessary. If ribavirin and peginterferon alfa are permanently discontinued, boceprevir must also be discontinued.

• Pancytopenia: Serious cases have been reported in patients receiving boceprevir in combination with peginterferon alfa and ribavirin. Complete blood counts with differential should be obtained at pretreatment, and at weeks 2, 4, 8, and 12, as well as other time points during treatment.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Pregnancy: Combination therapy with ribavirin and interferons may cause birth defects; avoid pregnancy in females and female partners of male patients during therapy and for 6 months following treatment; two forms of effective contraception should be used. Combination therapy with ribavirin and peginterferon alfa-2a is contraindicated in pregnancy.

Commonly reported side effects of boceprevir include: anemia, dizziness, dyspnea on exertion, and neutropenia. See below for a comprehensive list of adverse effects.

Applies to boceprevir: oral capsule

Along with its needed effects, boceprevir may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking boceprevir:

• Black, tarry stools
• chills
• cough
• difficult or labored breathing
• fever
• lower back or side pain
• painful or difficult urination
• pale skin
• sore throat
• tightness in the chest
• troubled breathing with exertion
• ulcers, sores, or white spots in the mouth
• unusual bleeding or bruising
• unusual tiredness or weakness

Some side effects of boceprevir may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Change in taste
• decreased appetite
• diarrhea
• difficulty with moving
• dizziness
• dry mouth
• dry skin
• hair loss or thinning of the hair
• irritability
• lack or loss of strength
• loss of taste
• muscle pain or stiffness
• nausea
• pain in the joints
• rash
• trouble sleeping
• vomiting

No adjustment recommended.

Comments: The manufacturer product information for peginterferon alfa should be consulted regarding use in patients with hepatic decompensation.

No adjustment recommended.

A decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother and the benefit of breastfeeding for the infant; a different drug may be preferred. Excreted into human milk: Unknown Excreted into animal milk: Yes Comments: The effects in the nursing infant are unknown.