Victrelis

Boceprevir comes as a capsule to take by mouth. It is usually taken with a meal or light snack three times a day (every 7 to 9 hours). Take boceprevir at around the same times 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 boceprevir exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

You will take peginterferon alfa and ribavirin for 4 weeks before you begin treatment with boceprevir. Then you will take all three medications for 12 to 44 weeks. After this time, you will stop taking boceprevir, but you may continue to take peginterferon alfa and ribavirin for an additional number of weeks. The length of your treatment depends on your condition, how well you respond to the medication, and whether you experience severe side effects. Continue to take boceprevir, peginterferon alfa, and ribavirin as long as they are prescribed by your doctor. Do not stop taking any of these medications without talking to your doctor even if you are feeling well.

Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with boceprevir and each time you refill your prescription. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website (http://www.fda.gov/Drugs/DrugSafety/ucm085729.htm) or the manufacturer's website to obtain the Medication Guide.

Dosage Forms & Strengths

capsule

• 200mg

Chronic Hepatitis C

Discontinued; sale and distribution of boceprevir will be discontinued in the United States by December 2015

Indicated for treatment of chronic hepatitis C (CHC) genotype 1 infection in combination with peginterferon alfa and ribavirin

Indication is specifically for adults with compensated liver disease, including cirrhosis, who are previously untreated or who have failed previous interferon and ribavirin therapy

Initiate therapy with peginterferon alfa and ribavirin for 4 weeks, THEN

Add boceprevir 800 mg PO q8hr (ie, q7-9hr) with food

Treatment Duration

Duration of treatment depends on HCV-RNA levels at treatment weeks 8, 12, and 24

HCV-RNA levels at 8 weeks

• Previously untreated and HCV-RNA levels undetectable: Complete 3-medication regimen at week 28
• Previously untreated and HCV-RNA levels detectable: Continue 3 medication regimen through week 36, then continue peginterferon alfa and ribavirin through week 48
• Partial responders or relapsed and HCV-RNA levels undetectable: Complete 3-medication regimen at week 36
• Partial responders or relapsed and HCV-RNA levels detectable: Continue 3 medication regimen through week 36, then continue peginterferon alfa and ribavirin through week 48

HCV-RNA levels at 12 weeks

• Response-guided therapy was not studied in individuals who had less than a 2-log10 HCV-RNA decline by treatment week 12 during prior therapy with peginterferon alfa and ribavirin
• If considered for treatment, these patients should receive peginterferon alfa and ribavirin x4 weeks followed by boceprevir x44 weeks in combination with peginterferon alfa and ribavirin
• In addition, consideration should be given to treating previously untreated patients who are poorly interferon responsive (as determined at TW 4) with 4 weeks peginterferon alfa and ribavirin followed by boceprevir x44 weeks in combination with peginterferon alfa and ribavirin in order to maximize rates of a sustained virologic response

HCV-RNA levels at 24 weeks

• If HCV-RNA levels are undetectable at treatment week 24, continue with treatment regimen identified at week 8

Treatment futility

• Discontinuation of therapy is recommended in all patients with any of the following circumstances:
• If HCV-RNA levels ≥1000 IU/mL at week 8, discontinue 3-medication regimen, OR
• If HCV-RNA levels ≥100 IU/mL at week 12, discontinue 3-medication regimen, OR
• If confirmed, detectable HCV-RNA levels at week 24, discontinue 3-medication regimen

Compensated cirrhosis

• Peginterferon alfa and ribavirin x 4 weeks followed by boceprevir x44 weeks in combination with peginterferon alfa and ribavirin

Renal or Hepatic Impairment

No dose adjustment for boceprevir is required

See peginterferon alfa and ribavirin monographs for recommended dose adjustments

Administration

Must be administered in combination with peginterferon alfa and ribavirin

Administer with a meal or light snack

<18 years: Safety and efficacy not established

Mechanism of Action

Inhibits HCV NS3/4A protease needed for proteolytic cleavage of the HCV encoded polyprotein into mature forms, which in turn inhibits replication of the hepatitis C virus

Absorption

Peak plasma time: 2 hr peak

Plasma concentration: 1723 ng/mL

AUC: 5408 ng•hr/mL Should be administered with food; food enhanced the exposure of boceprevir by up to 65%

Distribution

Protein bound: 75%

Vd: 772 L (at steady state)

Metabolism

Primarily undergoes metabolism through the aldoketoreductase (AKR)-mediated pathway to ketone-reduced metabolites that are inactive against HCV; also undergoes, to a lesser extent, oxidative metabolism mediated by CYP3A4/5

Metabolized by aldoketoreductase (AKR), CYP3A4/5 (partial)

Enzymes inhibited: Strong CYP3A4/5 inhibitor

Elimination

Half-life: 3.4 hr

Total body clearance: 161 L/hr

Excretion: feces (79%), urine (9%)

Pharmacogenomics

A genetic variant near the gene encoding interferon-lambda-3 (IL28B rs12979860, a C to T change) is a strong predictor of response to peginterferon and ribavirin

Sustained virologic response rates tended to be lower with the C/T and T/T genotypes compared to those with the C/C genotype, particularly among previously untreated subjects receiving 48 weeks of peginterferon and ribavirin

Boceprevir is an antiviral medication that prevents certain virus cells from multiplying in your body.

Boceprevir is used in combination with peginterferon alfa and ribavirin to treat hepatitis C in adults.

Boceprevir may also be used for purposes not listed in this medication guide.

Boceprevir must be used in combination with peginterferon alfa and ribavirin.

Do not use this combination of drugs if you are pregnant, or if you are a man and your sexual partner is pregnant.

Certain other drugs may interact with boceprevir or should not be used at the same time. Tell each of your healthcare providers about all medicines you use now, and any medicine you start or stop using.

You should not use boceprevir if you are allergic to it.

Do not take boceprevir as your only hepatitis medicine. Boceprevir must be used in combination with peginterferon alfa and ribavirin. Read the medication guide or patient instructions provided with each medicine you take. In some cases, you may not be able to use this drug combination.

To make sure you can safely take boceprevir, tell your doctor if you have:

• liver problems other than hepatitis C (including hepatitis B);
• a history of liver or other organ transplant; or
• low white blood cell (WBC) or red blood cell (RBC) counts, or low levels of platelets in in your blood;

Some medicines can cause unwanted or dangerous effects when used with boceprevir. Your doctor may need to change your treatment plan if you use any of the following drugs:

• cisapride;
• drospirenone (Yasmin, Yaz, Angeliq, and others);
• pimozide;
• rifampin;
• St. John's wort;
• alfuzosin, doxazosin, silodosin, tamsulosin;
• lovastatin or simvastatin;
• oral midazolam or triazolam;
• ergonovine, ergotamine, dihydroergotamine, methylergonovine;
• the seizure medications carbamazepine, phenobarbital, or phenytoin; or
• sildenafil (Revatio) or tadalafil (Adcirca) when used to treat pulmonary arterial hypertension.

FDA pregnancy category X. Boceprevir is given together with interferon alfa and ribavirin. Although boceprevir is not expected to harm an unborn baby, ribavirin is known to cause birth defects or death in an unborn baby. Do not use this combination of drugs if you are pregnant, or if you are a man and your sexual partner is pregnant. If you are a woman, you may need to have a negative pregnancy test before using these medications and every month during your treatment.

• Use at least 2 non-hormonal forms of birth control while either sexual partner is using boceprevir with interferon alfa and ribavirin. Keep using 2 forms of birth control for at least 6 months after treatment ends.
• If you are a woman, do not use boceprevir with interferon alfa and ribavirin if you are pregnant.
• If you are a man, do not use boceprevir with interferon alfa and ribavirin if your sexual partner is pregnant. An unborn baby could also be harmed if a man fathers the child while he is taking ribavirin.
• Hormonal contraception (such as birth control pills, injections, implants, skin patches, and vaginal rings) may not be effective enough to prevent pregnancy during your treatment. Ask your doctor about using a non-hormone method of birth control (such as a condom, intrauterine device (IUD), diaphragm with spermicide) to prevent pregnancy while taking boceprevir.
• Tell your doctor right away if a pregnancy occurs while either the mother or the father is using boceprevir with interferon alfa and ribavirin.

It is not known whether boceprevir passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are using boceprevir.

Taking this medicine will not prevent you from passing hepatitis C to other people. Do not have unprotected sex or share razors or toothbrushes. Talk with your doctor about safe ways to prevent transmission during sex. Sharing drug or medicine needles is never safe, even for a healthy person.

Many drugs can interact with boceprevir. Not all possible interactions are listed here. Tell your doctor about all your medications and any you start or stop using during treatment with boceprevir, especially:

• a blood thinner (warfarin, Coumadin, Jantoven);
• hormone replacement therapy, birth control pills, implants, vaginal rings, or injections;
• sildenafil (Viagra) and other erectile dysfunction medicines;
• an antibiotic or antifungal medicine--clarithromycin, itraconazole, ketoconazole, posaconazole, rifabutin, voriconazole; asthma or allergy medicine--budesonide, fluticasone, salmeterol (Advair, Serevent); steroid medicine--dexamethasone, prednisone, prednisolone;
• an antidepressant--desipramine, escitalopram; narcotic medication--buprenorphine, methadone, naloxone; a sedative--alprazolam, trazodone;
• cholesterol-lowering drugs--atorvastatin, pravastatin; heart or blood pressure medicine--amlodipine, amiodarone, digoxin, diltiazem, felodipine, nicardipine, nifedipine, nisoldipine, propafenone, quinidine, verapamil; or
• HIV or AIDS medicines--atazanavir, darunavir, efavirenz, etravirine, lopinavir, raltegravir, ritonavir; medicine to prevent organ transplant rejection--cyclosporine, sirolimus, tacrolimus.

This list is not complete and many other drugs can interact with boceprevir. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Give a list of all your medicines to any healthcare provider who treats you.

Although appropriate studies on the relationship of age to the effects of boceprevir have not been performed in the geriatric population, no geriatric-specific problems have been documented to date. However, elderly patients are more likely to have age-related liver problems, which may require caution in patients receiving boceprevir.

• Merck Sharp & Dohme Corp.

• Take Victrelis exactly as your healthcare provider tells you. Your healthcare provider will tell you how much to take and when to take it.
• Take Victrelis with food (a meal or light snack).
• Victrelis is packaged into single daily-use bottles. Each bottle has your entire day's worth of medicine. Make sure you are taking the correct amount of medicine each time.
• If you miss a dose of Victrelis and it is less than 2 hours before the next dose, the missed dose should be skipped.
• If you miss a dose of Victrelis and it is more than 2 hours before the next dose, take the missed dose with food. Take your next dose at your normal time and continue the normal dosing schedule. Do not double the next dose. If you have questions about what to do, call your healthcare provider.
• Your healthcare provider should do blood tests before you start treatment, at weeks 4, 8, 12, and 24, and at other times as needed during treatment, to see how well the medicines are working and to check for side effects.
• If you take too much Victrelis, call your healthcare provider or go to the nearest hospital emergency room right away.

• It is used to treat hepatitis C infection.

Use this medicine (Victrelis) as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take this medicine with food.
• Keep taking this medicine (Victrelis) 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 this medicine (Victrelis) 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.

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

Read all of your medication guides to learn about possible side effects of other medications you use in combination with Victrelis. Ask your doctor or pharmacist if you have any questions.

Stop using Victrelis 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 Victrelis 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.