Boceprevir

Boceprevir is used to treat chronic hepatitis C. Boceprevir is discontinued.

Boceprevir is available under the following different brand names: Victrelis.

Dosages of Boceprevir:

Dosage Forms and Strengths

Capsule

• 200 mg

Dosage Considerations – Should be Given as Follows:

Chronic Hepatitis C

• Discontinued; sale and distribution of boceprevir will be discontinued in the United States by December 2015
• Indicated for the treatment of chronic hepatitis C (CHC) genotype 1 infection in combination with peginterferon alfa and ribavirin
• The 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 orally every 8 hours (i.e., every 7-9 hours) 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 for 4 weeks followed by boceprevir for 44 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 for 44 weeks in combination with peginterferon alfa and ribavirin 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 the 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 or greater at week 8, discontinue the 3-medication regimen, OR
• If HCV-RNA levels 100 IU/mL or greater at week 12, discontinue the 3-medication regimen, OR
• If confirmed, detectable HCV-RNA levels at week 24, discontinue 3-medication regimen

Compensated cirrhosis

• Peginterferon alfa and ribavirin for 4 weeks followed by boceprevir for 44 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

Side effects of Boceprevir include:

• Fatigue
• Anemia
• Nausea
• Headache
• Changes in taste
• Insomnia
• Chills
• Hair loss
• Diarrhea
• Loss of appetite
• Low white blood cell count (neutropenia)
• Joint pain
• Irritability
• Dry skin
• Weakness/lethargy
• Vomiting
• Dizziness
• Rash
• Dru mouth
• Exertional shortness of breath

Postmarketing side effects of boceprevir reported include:

• Blood and lymphatic system disorders: Agranulocytosis, pancytopenia, thrombocytopenia
• Gastrointestinal disorders: Mouth ulceration, inflammation of the mouth and lips
• Infections and Infestations: Pneumonia, sepsis
• Skin and subcutaneous tissue disorders: Angioedema, hives; drug rash with eosinophilia and systemic symptoms (DRESS) syndrome, exfoliative rash, exfoliative dermatitis, Stevens-Johnson syndrome, toxic skin eruption, toxicoderma

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Boceprevir has no listed severe interactions with other drugs.
• Serious interactions of boceprevir include:
  • atorvastatin
• Moderate interactions of boceprevir include:
  • mometasone, intranasal
• Boceprevir has no listed mild interactions with other drugs.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

Warnings

• This medication contains boceprevir. Do not take Victrelis if you are allergic to boceprevir or any ingredients contained in this drug.
• Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Contraindications

• Coadministration with drugs that are highly dependent on CYP3A4/5 for clearance, and for which elevated plasma concentrations are associated with serious and/or life-threatening events
• Potent CYP3A4/5 inducers were significantly reduced boceprevir plasma concentrations may be associated with reduced efficacy
• Hypersensitivity
• Also, consider contraindications to peginterferon alfa and ribavirin
• Because ribavirin may cause birth defects and fetal death, boceprevir in combination with peginterferon alfa and ribavirin is contraindicated in pregnant women and in men whose female partners are pregnant

Effects of Drug Abuse

• No information is available.

Short-Term Effects

• See "What Are Side Effects Associated with Using Boceprevir?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Boceprevir?"

Cautions

• Ribavirin may cause birth defects and fetal death; avoid pregnancy in female patients and female partners of male patients; patients must have a negative pregnancy test before therapy; use 2 or more forms of contraception, 1 of these forms of contraception can be a combined oral contraceptive product containing at least 1 mg of norethindrone (lower doses of norethindrone and other forms of hormonal contraception have not been studied or are contraindicated)
• Perform monthly pregnancy tests in sexually active women
• Serious acute hypersensitivity reactions (e.g., hives, angioedema) reported
• Anemia: The addition of boceprevir to peginterferon alfa and ribavirin is associated with an additional decrease in hemoglobin concentrations compared with peginterferon alfa and ribavirin alone
• Neutropenia: Addition of boceprevir to peginterferon alfa and ribavirin may result in worsening of neutropenia associated with peginterferon alfa and ribavirin therapy alone
• Pancytopenia reported; obtain complete blood count pretreatment and at treatment weeks 2, 4, 8, and 12, and periodically thereafter as clinically appropriate
• Safety and efficacy not established with decompensated cirrhosis, organ transplant, or coinfection with HIV or HBV
• Potential inhibitor of p-glycoprotein (P-gp) based on in vitro studies; the potential for drug interaction with sensitive substrates of p-glycoprotein (e.g., digoxin) has not been evaluated in a clinical trial

Pregnancy and Lactation

• Do not use boceprevir in pregnancy. The risks involved outweigh the potential benefits. Safer alternatives exist.
• Boceprevir is co-administered with ribavirin. Significant teratogenic and/or embryocidal effects have been demonstrated in all animal species exposed to ribavirin and therefore ribavirin is contraindicated in women who are pregnant and in the male partners of women who are pregnant.
• It is unknown whether boceprevir is distributed in breast milk. Because of the potential for adverse reactions, breastfeeding is not recommended while using boceprevir.