boceprevir

These drugs are direct-acting antiviral agents that act on hepatitis C virus by inhibiting protease enzymes used for replication. This reduces viral load in some patients.

Boceprevir was FDA-approved in March 2011 but was discontinued in 2015.

Side effects of boceprevir

Side effects include:

• hair loss
• dry skin
• diarrhea
• loss of appetite
• nausea
• altered taste
• sleeplessness
• irritability
• fatigue
• shivering
• anemia
• low white blood cell count

Serious skin reactions can occur and require discontinuation of boceprevir. These reactions include:

• urticaria
• angioedema
• Stevens Johnson syndrome (SJS)
• drug reaction with eosinophilia and systemic symptoms (DRESS)
• exfoliative dermatitis

Dosage for boceprevir

Dosage Forms and Strengths

Dosage Considerations – Should be Given as Follows:

• Discontinued in the US by December 2015
• Indicated for the treatment of chronic hepatitis C (CHC) genotype 1 infection in combination with peginterferon alfa and ribavirin
• Treatment initiation: peginterferon alfa and ribavirin for 4 weeks, THEN add boceprevir 800 mg orally every 8 hours with food

Treatment Duration

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

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

At 12 weeks:

• Response-guided therapy was not studied in individuals with less than a 2-log10 HCV-RNA decline by treatment week 12 with previous therapy
• 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
• Consideration should be given to treating previously untreated patients who are poorly interferon responsive (as determined at treatment week 4) with 4 weeks of peginterferon alfa and ribavirin followed by boceprevir for 44 weeks in combination with peginterferon alfa and ribavirin to maximize response rates

At 24 weeks:

• If HCV-RNA levels are undetectable, continue with the treatment regimen identified at week 8
• 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 the 3-medication regimen
• 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

Drug interactions with boceprevir

• Do not combine boceprevir with alfuzosin, doxazosin, sildosin, tamsulosin, sildenafil, or tadalafil as it can increase their blood levels, leading to increased side effects
• Do not combine boceprevir with carbamazepine, phenobarbital, phenytoin, rifampin, or St. John’s wort as it can decrease its effectiveness
• Do not combine boceprevir with lovastatin or simvastatin as it increases the risk of muscle aches, including rhabdomyolysis
• Combine boceprevir with midazolam and triazolam with caution due to increased risk of sedation and respiratory depression
• Use boceprevir with caution with HIV medications like atazanavir, ritonavir, darunavir, and lopinavir/ritonavir as it can lead to fluctuating levels of boceprevir and HIV medications, decreasing effectiveness
• Use boceprevir with caution with arrhythmia medications as the combination can increase the risk of irregular heart rate and rhythm
• Use boceprevir with caution with antifungal medications like ketoconazole, itraconazole, and voriconazole; antibiotics like clarithromycin and erythromycin; and immunosuppressant medications like cyclosporine, tacrolimus, and sirolimus. Boceprevir can slow the breakdown of these medications and increase their levels in the body, leading to increased side effects and toxicity
• Use boceprevir with caution with warfarin as it can increase or decrease warfarin breakdown, affecting its effectiveness

QUESTION

Is boceprevir safe during pregnancy or breastfeeding?

• Boceprevir, combined with ribavirin and peginterferon alfa, cause harm to fetuses and birth defects. Effective birth control is required during treatment and for 6 months after
• Monthly pregnancy tests are recommended for female patients during treatment and for 6 months after
• Caution should be exercised before using boceprevir in nursing mothers as it is not known if it enters breast milk

Additional information on boceprevir

Is a prescription needed for boceprevir?

What preparations of boceprevir are available?

• Capsule, 200 mg

How should boceprevir be stored?

• Refrigerate at 2 C to 8 C (36 F to 46 F) until dispensed. Can be stored at room temperature (up to 25 C or 77 F) for 3 months
• Store in tightly closed containers, avoiding excessive heat

Summary

Boceprevir is an antiviral medication used to treat hepatitis C. Side effects may include hair loss, dry skin, diarrhea, loss of appetite, nausea, altered taste, sleeplessness, irritability, fatigue, shivering, anemia, and low white blood cell count. It is not safe for use during pregnancy or breastfeeding as it can cause harm to the fetus or newborn.