VICTRELIS

NS3/4A Protease Inhibitor Antivirals for Hepatitis C

 
NOTE: Boceprevir MUST be administered in combination with peginterferon alfa and ribavirin; never administer as monotherapy.

Oral Administration

Administer with food (meal or light snack).

Severe

pancytopenia / Delayed / Incidence not known
agranulocytosis / Delayed / Incidence not known
exfoliative dermatitis / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known

Moderate

anemia / Delayed / 45.0-50.0
neutropenia / Delayed / 14.0-25.0
dyspnea / Early / 8.0-11.0
thrombocytopenia / Delayed / 3.0-4.0
oral ulceration / Delayed / Incidence not known
stomatitis / Delayed / Incidence not known

Mild

fatigue / Early / 55.0-58.0
nausea / Early / 43.0-46.0
dysgeusia / Early / 35.0-44.0
chills / Rapid / 33.0-34.0
insomnia / Early / 30.0-34.0
alopecia / Delayed / 22.0-27.0
diarrhea / Early / 24.0-25.0
arthralgia / Delayed / 19.0-23.0
irritability / Delayed / 21.0-22.0
xerosis / Delayed / 18.0-22.0
asthenia / Delayed / 15.0-21.0
vomiting / Early / 15.0-20.0
dizziness / Early / 16.0-19.0
rash / Early / 16.0-17.0
xerostomia / Early / 11.0-15.0
infection / Delayed / Incidence not known
urticaria / Rapid / Incidence not known

VICTRELIS

Rx

Hepatitis C virus NS3/4A protease inhibitor
For treatment of genotype 1 chronic HCV in adults with compensated hepatic disease, including cirrhosis
Must be used with peginterferon and ribavirin; avoid monotherapy

For the treatment of chronic hepatitis C infection (HCV, genotype 1) in adults with compensated liver disease.
 NOTE: Boceprevir must be administered in combination with peginterferon alfa and ribavirin; never administer as monotherapy.
Oral dosage Adults without cirrhosis who are previously untreated with interferon and ribavirin

Prior to initiating boceprevir, patients must receive 4 weeks of treatment with peginterferon alfa and ribavirin. After the initial 4 weeks of therapy, add boceprevir 800 mg PO 3 times daily (given every 7 to 9 hours). Duration of therapy is determined by the patient's HCV RNA concentrations at treatment weeks 4, 8, 12, and 24. If HCV RNA concentrations are undetectable at weeks 8 and 24, discontinue all 3 medications at week 28. If HCV RNA is detectable at week 8 but undetectable at week 24, continue the 3-drug regimen through week 36, and then administer only peginterferon alfa and ribavirin through treatment week 48. If the response to peginterferon alfa and ribavirin during the initial 4 weeks was poor, continue treatment with all 3 medications for a total of 48 weeks. Discontinue therapy if HCV RNA concentrations are 1,000 International Units/mL or more at week 8, 100 International Units/mL or more at week 12, or detectable at week 24.[44314]

Adults without cirrhosis who are previous partial responders to or who have relapsed on interferon and ribavirin

Prior to initiating boceprevir, patients must receive 4 weeks of treatment with peginterferon alfa and ribavirin. After the initial 4 weeks of therapy, add boceprevir 800 mg PO 3 times daily (given every 7 to 9 hours). Duration of therapy is determined by the patient's HCV RNA concentrations at treatment weeks 4, 8, 12, and 24. If HCV RNA concentrations are undetectable at weeks 8 and 24, discontinue all 3 medications at week 36. If HCV RNA is detectable at week 8 but undetectable at week 24, continue the 3-drug regimen through week 36, and then administer only peginterferon alfa and ribavirin through treatment week 48. Discontinue therapy if HCV RNA concentrations are 1,000 International Units/mL or more at week 8, 100 International Units/mL or more at week 12, or detectable at week 24.[44314]

Adults without cirrhosis who are previous null responders to interferon and ribavirin

Prior to initiating boceprevir, patients must receive 4 weeks of treatment with peginterferon alfa and ribavirin. After the initial 4 weeks of therapy, add boceprevir 800 mg PO 3 times daily (given every 7 to 9 hours) for an additional 44 weeks (48 weeks total). Monitor HCV RNA concentrations at treatment weeks 4, 8, 12, and 24. Discontinue therapy if HCV RNA concentrations are 1,000 International Units/mL or more at week 8, 100 International Units/mL or more at week 12, or detectable at week 24.[44314]

Adults with cirrhosis

Prior to initiating boceprevir, patients must receive 4 weeks of treatment with peginterferon alfa and ribavirin. After the initial 4 weeks of therapy, add boceprevir 800 mg PO 3 times daily (given every 7 to 9 hours) for an additional 44 weeks (48 weeks total). Monitor patient's HCV RNA concentrations at treatment weeks 4, 8, 12, and 24. Discontinue therapy if HCV RNA concentrations are 1,000 International Units/mL or more at week 8, 100 International Units/mL or more at week 12, or detectable at week 24.

Hepatic Impairment

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed. Safety and efficacy have not been established in patients with decompensated cirrhosis.

Renal Impairment

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Acetaminophen: (Moderate) Close clinical monitoring is advised when administering acetaminophen with boceprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Close clinical monitoring is advised when administering acetaminophen with boceprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations.
Acetaminophen; Butalbital: (Moderate) Close clinical monitoring is advised when administering acetaminophen with boceprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations.
Acetaminophen; Butalbital; Caffeine: (Moderate) Close clinical monitoring is advised when administering acetaminophen with boceprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations.
Acetaminophen; Butalbital; Caffeine; Codeine: (Moderate) Close clinical monitoring is advised when administering acetaminophen with boceprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations.
Acetaminophen; Caffeine: (Moderate) Close clinical monitoring is advised when administering acetaminophen with boceprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Close clinical monitoring is advised when administering acetaminophen with boceprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations.
Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Moderate) Close clinical monitoring is advised when administering acetaminophen with boceprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations.
Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Moderate) Close clinical monitoring is advised when administering acetaminophen with boceprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Close clinical monitoring is advised when administering acetaminophen with boceprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations. (Moderate) Close clinical monitoring is advised when administering dextromethorphan with boceprevir due to an increased potential for dextromethorphan-related adverse events. If dextromethorphan dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of dextromethorphan. Dextromethorphan is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated dextromethorphan plasma concentrations.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Close clinical monitoring is advised when administering acetaminophen with boceprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations. (Moderate) Close clinical monitoring is advised when administering dextromethorphan with boceprevir due to an increased potential for dextromethorphan-related adverse events. If dextromethorphan dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of dextromethorphan. Dextromethorphan is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated dextromethorphan plasma concentrations.
Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Moderate) Close clinical monitoring is advised when administering acetaminophen with boceprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations.
Acetaminophen; Codeine: (Moderate) Close clinical monitoring is advised when administering acetaminophen with boceprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations.
Acetaminophen; Dextromethorphan: (Moderate) Close clinical monitoring is advised when administering acetaminophen with boceprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations. (Moderate) Close clinical monitoring is advised when administering dextromethorphan with boceprevir due to an increased potential for dextromethorphan-related adverse events. If dextromethorphan dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of dextromethorphan. Dextromethorphan is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated dextromethorphan plasma concentrations.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Close clinical monitoring is advised when administering acetaminophen with boceprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations. (Moderate) Close clinical monitoring is advised when administering dextromethorphan with boceprevir due to an increased potential for dextromethorphan-related adverse events. If dextromethorphan dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of dextromethorphan. Dextromethorphan is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated dextromethorphan plasma concentrations.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Close clinical monitoring is advised when administering acetaminophen with boceprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations. (Moderate) Close clinical monitoring is advised when administering dextromethorphan with boceprevir due to an increased potential for dextromethorphan-related adverse events. If dextromethorphan dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of dextromethorphan. Dextromethorphan is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated dextromethorphan plasma concentrations.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Close clinical monitoring is advised when administering acetaminophen with boceprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations. (Moderate) Close clinical monitoring is advised when administering dextromethorphan with boceprevir due to an increased potential for dextromethorphan-related adverse events. If dextromethorphan dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of dextromethorphan. Dextromethorphan is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated dextromethorphan plasma concentrations.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Close clinical monitoring is advised when administering acetaminophen with boceprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations. (Moderate) Close clinical monitoring is advised when administering dextromethorphan with boceprevir due to an increased potential for dextromethorphan-related adverse events. If dextromethorphan dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of dextromethorphan. Dextromethorphan is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated dextromethorphan plasma concentrations.
Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Close clinical monitoring is advised when administering acetaminophen with boceprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations.
Acetaminophen; Diphenhydramine: (Moderate) Close clinical monitoring is advised when administering acetaminophen with boceprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations.
Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Close clinical monitoring is advised when administering acetaminophen with boceprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations.
Acetaminophen; Hydrocodone: (Major) Monitor for respiratory depression and sedation if hydrocodone and boceprevir are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as boceprevir, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects. (Moderate) Close clinical monitoring is advised when administering acetaminophen with boceprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations.
Acetaminophen; Oxycodone: (Moderate) Close clinical monitoring is advised when administering acetaminophen with boceprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations. (Moderate) Close clinical monitoring is advised when administering oxycodone with boceprevir due to an increased potential for oxycodone-related adverse events. If oxycodone dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of oxycodone. Oxycodone is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated oxycodone plasma concentrations.
Acetaminophen; Pentazocine: (Moderate) Close clinical monitoring is advised when administering acetaminophen with boceprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations.
Acetaminophen; Propoxyphene: (Moderate) Close clinical monitoring is advised when administering acetaminophen with boceprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations.
Acetaminophen; Pseudoephedrine: (Moderate) Close clinical monitoring is advised when administering acetaminophen with boceprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations.
Acetaminophen; Tramadol: (Moderate) Close clinical monitoring is advised when administering acetaminophen with boceprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations. (Moderate) Close clinical monitoring is advised when administering tramadol with boceprevir due to an increased potential for tramadol-related adverse events. If tramadol dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of tramadol. Tramadol is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated tramadol plasma concentrations.
Ado-Trastuzumab emtansine: (Severe) Boceprevir is contraindicated for use with medications that are highly dependent on CYP3A4 for clearance and are associated with serious and/or life-threatening events; do not use boceprevir concomitantly with ado-trastuzumab emtansine. Boceprevir is a strong CYP3A4 inhibitor. Although formal drug interactions have not been completed, the cytotoxic small molecule of ado-trastuzumab emtansine, DM1, is primarily metabolized by CYP3A4 (and to a lesser extent, CYP3A5) in vitro, and has been associated with hepatotoxicity, interstitial lung disease (ILD) / pneumonitis, and severe bleeding events. Treatment with ado-trastuzumab emtansine should be delayed until boceprevir is cleared from the circulation (approximately 3 elimination half-lives) or an alternate medication with less potential to inhibit CYP3A4 should be considered.
Aldesleukin, IL-2: (Moderate) Close clinical monitoring is advised when administering aldesleukin, IL-2 with boceprevir due to an increased potential for aldesleukin-related adverse events. If aldesleukin dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of aldesleukin and boceprevir. Both aldesleukin and boceprevir are inhibitors of the hepatic isoenzyme CYP3A4. When used in combination, the plasma concentrations of both medications may be elevated.
Alfentanil: (Moderate) Close clinical monitoring is advised when administering alfentanil with boceprevir due to an increased potential for alfentanil-related adverse events. If alfentanil dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of alfentanil. Alfentanil is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated alfentanil plasma concentrations.
Alfuzosin: (Severe) Concurrent use of alfuzosin and boceprevir is contraindicated due to the potential for serious/life-threatening reactions. Boceprevir is a potent inhibitor of CYP3A4, which is responsible for alfuzosin metabolism. Coadministration may result in large increases in alfuzosin serum concentrations, which could cause adverse events such as hypotension.
Aliskiren: (Moderate) Close clinical monitoring is advised when administering aliskiren with boceprevir due to an increased potential for aliskiren-related adverse events. If aliskiren dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of aliskiren. Aliskiren is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated aliskiren plasma concentrations.
Aliskiren; Amlodipine: (Moderate) Close clinical monitoring is advised when administering aliskiren with boceprevir due to an increased potential for aliskiren-related adverse events. If aliskiren dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of aliskiren. Aliskiren is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated aliskiren plasma concentrations. (Moderate) Close clinical monitoring is advised when administering amlodipine with boceprevir due to an increased potential for amlodipine-related adverse events. A reduction in the dose of amlodipine may be considered. If amlodipine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Predictions about the interaction can be made based on the metabolic pathway of amlodipine. Amlodipine is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated amlodipine plasma concentrations.
Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Close clinical monitoring is advised when administering aliskiren with boceprevir due to an increased potential for aliskiren-related adverse events. If aliskiren dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of aliskiren. Aliskiren is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated aliskiren plasma concentrations. (Moderate) Close clinical monitoring is advised when administering amlodipine with boceprevir due to an increased potential for amlodipine-related adverse events. A reduction in the dose of amlodipine may be considered. If amlodipine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Predictions about the interaction can be made based on the metabolic pathway of amlodipine. Amlodipine is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated amlodipine plasma concentrations.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Close clinical monitoring is advised when administering aliskiren with boceprevir due to an increased potential for aliskiren-related adverse events. If aliskiren dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of aliskiren. Aliskiren is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated aliskiren plasma concentrations.
Aliskiren; Valsartan: (Moderate) Close clinical monitoring is advised when administering aliskiren with boceprevir due to an increased potential for aliskiren-related adverse events. If aliskiren dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of aliskiren. Aliskiren is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated aliskiren plasma concentrations.
Almotriptan: (Major) Boceprevir may increase the systemic exposure of almotriptan. If coadministered, the recommended starting dose of almotriptan is 6.25 mg; do not exceed 12.5 mg within a 24-hour period. Avoid coadministration in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and boceprevir is a potent CYP3A4 inhibitor. In a drug interaction study, coadministration of almotriptan and ketoconazole, another potent CYP3A4 inhibitor, resulted in an approximately 60% increase in almotriptan exposure.
Alosetron: (Moderate) Close clinical monitoring is advised when administering alosetron with boceprevir due to an increased potential for alosetron-related adverse events. If alosetron dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of alosetron. Alosetron is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated alosetron plasma concentrations.
Alprazolam: (Major) Coadministration of alprazolam and boceprevir is not recommended. If coadministration cannot be avoided, a dosage reduction of alprazolam should be considered. Boceprevir is a potent CYP3A4 inhibitor. The initial step in alprazolam metabolism is hydroxylation catalyzed by cytochrome CYP3A. Drugs that inhibit this metabolic pathway may profoundly decrease alprazolam clearance, resulting in increased potential for serious alprazolam-related adverse events, such as respiratory depression and prolonged sedation. Consequently, alprazolam should be avoided in patients receiving very potent inhibitors of CYP3A isoenzymes.
Amiodarone: (Moderate) Close clinical monitoring is advised when administering amiodarone with boceprevir due to an increased potential for serious and/or life-threatening amiodarone-related adverse events. If amiodarone dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of amiodarone and boceprevir. Both amiodarone and boceprevir are substrates and inhibitors of the hepatic isoenzyme CYP3A4. Additionally amiodarone is an inhibitor of P-glycoprotein (PGP), an efflux transporter partially responsible for the metabolism of boceprevir. When used in combination, the plasma concentrations of both medications may be elevated.
Amitriptyline: (Moderate) Close clinical monitoring is advised when administering amitriptyline with boceprevir due to an increased potential for amitriptyline-related adverse events. If amitriptyline dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of amitriptyline. Amitriptyline is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; boceprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated amitriptyline plasma concentrations.
Amitriptyline; Chlordiazepoxide: (Moderate) Close clinical monitoring is advised when administering amitriptyline with boceprevir due to an increased potential for amitriptyline-related adverse events. If amitriptyline dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of amitriptyline. Amitriptyline is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; boceprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated amitriptyline plasma concentrations.
Amlodipine: (Moderate) Close clinical monitoring is advised when administering amlodipine with boceprevir due to an increased potential for amlodipine-related adverse events. A reduction in the dose of amlodipine may be considered. If amlodipine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Predictions about the interaction can be made based on the metabolic pathway of amlodipine. Amlodipine is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated amlodipine plasma concentrations.
Amlodipine; Atorvastatin: (Major) Use the lowest effective dose of atorvastatin and do not exceed a total daily dose of 40 mg when coadministered with boceprevir. The AUC and Cmax of atorvastatin were increased by 2.3-fold and 2.66-fold, respectively in a drug interaction study with boceprevir. (Moderate) Close clinical monitoring is advised when administering amlodipine with boceprevir due to an increased potential for amlodipine-related adverse events. A reduction in the dose of amlodipine may be considered. If amlodipine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Predictions about the interaction can be made based on the metabolic pathway of amlodipine. Amlodipine is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated amlodipine plasma concentrations.
Amlodipine; Benazepril: (Moderate) Close clinical monitoring is advised when administering amlodipine with boceprevir due to an increased potential for amlodipine-related adverse events. A reduction in the dose of amlodipine may be considered. If amlodipine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Predictions about the interaction can be made based on the metabolic pathway of amlodipine. Amlodipine is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated amlodipine plasma concentrations.
Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Close clinical monitoring is advised when administering amlodipine with boceprevir due to an increased potential for amlodipine-related adverse events. A reduction in the dose of amlodipine may be considered. If amlodipine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Predictions about the interaction can be made based on the metabolic pathway of amlodipine. Amlodipine is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated amlodipine plasma concentrations.
Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Close clinical monitoring is advised when administering amlodipine with boceprevir due to an increased potential for amlodipine-related adverse events. A reduction in the dose of amlodipine may be considered. If amlodipine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Predictions about the interaction can be made based on the metabolic pathway of amlodipine. Amlodipine is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated amlodipine plasma concentrations.
Amlodipine; Olmesartan: (Moderate) Close clinical monitoring is advised when administering amlodipine with boceprevir due to an increased potential for amlodipine-related adverse events. A reduction in the dose of amlodipine may be considered. If amlodipine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Predictions about the interaction can be made based on the metabolic pathway of amlodipine. Amlodipine is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated amlodipine plasma concentrations.
Amlodipine; Telmisartan: (Moderate) Close clinical monitoring is advised when administering amlodipine with boceprevir due to an increased potential for amlodipine-related adverse events. A reduction in the dose of amlodipine may be considered. If amlodipine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Predictions about the interaction can be made based on the metabolic pathway of amlodipine. Amlodipine is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated amlodipine plasma concentrations.
Amlodipine; Valsartan: (Moderate) Close clinical monitoring is advised when administering amlodipine with boceprevir due to an increased potential for amlodipine-related adverse events. A reduction in the dose of amlodipine may be considered. If amlodipine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Predictions about the interaction can be made based on the metabolic pathway of amlodipine. Amlodipine is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated amlodipine plasma concentrations.
Amoxicillin; Clarithromycin; Lansoprazole: (Major) Close clinical monitoring is advised when administering clarithromycin with boceprevir due to an increased potential for serious clarithromycin-related adverse events, such as QT prolongation and torsade de pointes. No clarithromycin dosage adjustments are required for patients with normal renal function. If clarithromycin dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Predictions about the interaction can be made based on the metabolic pathways of clarithromycin and boceprevir. Both clarithromycin and boceprevir are substrates and inhibitors of the hepatic isoenzyme CYP3A4. Additionally, clarithromycin is an inhibitor of P-glycoprotein (P-gp), and efflux transporter partially responsible for the metabolism of boceprevir. When used in combination, the plasma concentrations of both medications may be elevated. (Moderate) Close clinical monitoring is advised when administering lansoprazole with boceprevir due to an increased potential for lansoprazole-related adverse events. If lansoprazole dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of lansoprazole. Lansoprazole is a CYP3A4 substrate; boceprevir is a CYP3A4 inhibitor. Coadministration may result in elevated lansoprazole plasma concentrations.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Close clinical monitoring is advised when administering clarithromycin with boceprevir due to an increased potential for serious clarithromycin-related adverse events, such as QT prolongation and torsade de pointes. No clarithromycin dosage adjustments are required for patients with normal renal function. If clarithromycin dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Predictions about the interaction can be made based on the metabolic pathways of clarithromycin and boceprevir. Both clarithromycin and boceprevir are substrates and inhibitors of the hepatic isoenzyme CYP3A4. Additionally, clarithromycin is an inhibitor of P-glycoprotein (P-gp), and efflux transporter partially responsible for the metabolism of boceprevir. When used in combination, the plasma concentrations of both medications may be elevated.
Aprepitant, Fosaprepitant: (Major) Avoid the concomitant use of boceprevir with aprepitant, fosaprepitant due to substantially increased exposure of aprepitant; increased boceprevir exposure may also occur for several days after administration of a multi-day aprepitant regimen. Boceprevir is a strong CYP3A4 inhibitor and aprepitant is a CYP3A4 substrate. Coadministration of a single oral dose of aprepitant (125 mg) on day 5 of a 10-day ketoconazole regimen (strong CYP3A4 inhibitor) increased the aprepitant AUC approximately 5-fold, and increased the mean terminal half-life by approximately 3-fold. Boceprevir is also a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of boceprevir. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
Aripiprazole: (Major) Because aripiprazole is partially metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be reduced to one-half of the usual dose in patients receiving strong inhibitors of CYP3A4 such as boceprevir. In adults receiving 300 mg or 400 mg of Abilify Maintena, dose reductions to 200 mg or 300 mg, respectively, are recommended if the CYP3A4 inhibitor is used for more than 14 days. Patients receiving a strong CYP3A4 inhibitor for more than 14 days should have their Aristada dose reduced to the next lower strength. For patients receiving 882 mg of Aristada every 6 weeks or 1,064 mg every 2 months, the next lower strength should be 441 mg administered every 4 weeks. No dosage adjustment is necessary in patients taking 441 mg IM of Aristada, if tolerated. Because aripiprazole is also metabolized by CYP2D6, patients classified as CYP2D6 poor metabolizers (PMs) who are receiving a strong CYP3A4 inhibitor or patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response. Adults receiving Abilify Maintena who are PMs of CYP2D6 and receiving a strong CYP3A4 inhibitor should have a dose reduction to 200 mg/month IM. Patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their Abilify Maintena dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. Adults receiving Aristada injection who are PMs of CYP2D6 and receiving a strong CYP3A4 inhibitor for more than 14 days should have their dose reduced from 662 mg, 882 mg, or 1,064 mg to 441 mg IM; no dose adjustment is needed in patients receiving 441 mg of Aristada, if tolerated. In patients receiving Aristada 662 mg, 882 mg, or 1,064 mg, combined use of a strong CYP2D6 inhibitor and a strong CYP3A4 inhibitor for more than 14 days should be avoided; no dose adjustment is needed in patients taking 441 mg, if tolerated. Avoid concurrent use of Aristada Initio and strong CYP3A4 inhibitors because the dose of Aristada Initio cannot be modified.
Artemether; Lumefantrine: (Moderate) Close clinical monitoring is advised when administering artemether; lumefantrine with boceprevir due to an increased potential for artemether; lumefantrine-related adverse events. If artemether; lumefantrine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of artemether; lumefantrine. Artemether; lumefantrine is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated artemether; lumefantrine plasma concentrations. (Moderate) Close clinical monitoring is advised when administering artemether; lumefantrine with telaprevir due to an increased potential for artemether; lumefantrine-related adverse events. If artemether; lumefantrine dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of artemether; lumefantrine. Artemether; lumefantrine is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated artemether; lumefantrine plasma concentrations.
Aspirin, ASA; Oxycodone: (Moderate) Close clinical monitoring is advised when administering oxycodone with boceprevir due to an increased potential for oxycodone-related adverse events. If oxycodone dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of oxycodone. Oxycodone is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated oxycodone plasma concentrations.
Aspirin, ASA; Pravastatin: (Moderate) Pravastatin systemic exposure is increased when coadministered with boceprevir. According to the manufacturer, dose modifications are not required during concomitant use; however, close clinical monitoring for pravastatin-related adverse events is advised.
Atazanavir: (Major) Concurrent administration of atazanavir and ritonavir with boceprevir is not recommended due to the potential for HIV and hepatitis C treatment failures. This combination has resulted in decreased serum concentrations of all 3 drugs. Predictions about the interaction can be made based on metabolic pathways. The atazanavir/ritonavir combination is an inhibitor, inducer, and substrate of the hepatic isoenzyme CYP3A4; boceprevir is an inhibitor and substrate of this isoenzyme. Additionally, they are all are substrates and inhibitors of the drug efflux transporter P-glycoprotein (P-gp). If used in combination, health care providers are advised to closely monitor for decreased treatment response and virologic rebound. Health care providers are also encouraged to report any drug-related adverse reactions to the FDA MedWatch Program.
Atazanavir; Cobicistat: (Major) Avoid concurrent use of cobicistat with boceprevir, as drug interaction data are not available. Clinically significant drug interactions may occur during coadministration. Boceprevir is a CYP3A4 inhibitor/substrate and P-glycoprotein (P-gp) substrate. Cobicistat is an inhibitor of CYP3A4 and P-gp, and a substrate of CYP3A4. (Major) Concurrent administration of atazanavir and ritonavir with boceprevir is not recommended due to the potential for HIV and hepatitis C treatment failures. This combination has resulted in decreased serum concentrations of all 3 drugs. Predictions about the interaction can be made based on metabolic pathways. The atazanavir/ritonavir combination is an inhibitor, inducer, and substrate of the hepatic isoenzyme CYP3A4; boceprevir is an inhibitor and substrate of this isoenzyme. Additionally, they are all are substrates and inhibitors of the drug efflux transporter P-glycoprotein (P-gp). If used in combination, health care providers are advised to closely monitor for decreased treatment response and virologic rebound. Health care providers are also encouraged to report any drug-related adverse reactions to the FDA MedWatch Program.
Atorvastatin: (Major) Use the lowest effective dose of atorvastatin and do not exceed a total daily dose of 40 mg when coadministered with boceprevir. The AUC and Cmax of atorvastatin were increased by 2.3-fold and 2.66-fold, respectively in a drug interaction study with boceprevir.
Atorvastatin; Ezetimibe: (Major) Use the lowest effective dose of atorvastatin and do not exceed a total daily dose of 40 mg when coadministered with boceprevir. The AUC and Cmax of atorvastatin were increased by 2.3-fold and 2.66-fold, respectively in a drug interaction study with boceprevir.
Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Severe) The potential for boceprevir treatment failure exists when boceprevir is administered with phenobarbital; concurrent use is contraindicated. Phenobarbital is a potent inducer of CYP3A4, which is partially responsible for boceprevir metabolism. Coadministration may result in decreased boceprevir serum concentrations and impaired virologic response.
Avanafil: (Major) Avanafil is a substrate of and primarily metabolized by CYP3A4. Studies have shown that drugs that inhibit CYP3A4 can increase avanafil exposure. Patients taking strong CYP3A4 inhibitors including boceprevir, should not take avanafil.
Bedaquiline: (Major) Concurrent use of bedaquiline and a strong CYP3A4 inhibitor, such as boceprevir, for more than 14 days should be avoided unless the benefits justify the risks. When administered together, boceprevir may inhibit the metabolism of bedaquiline resulting in increased systemic exposure (AUC) and potentially more adverse reactions, such as QT prolongation and hepatotoxicity.
Belladonna Alkaloids; Ergotamine; Phenobarbital: (Severe) Concurrent use of ergot alkaloids and boceprevir is contraindicated due to the potential for serious/life-threatening ergot toxicities, such as peripheral vasospasm and ischemia of the extremities and other tissues. Boceprevir is a potent inhibitor of CYP3A4, which is responsible for the metabolism of ergot alkaloids. Coadministration may result in large increases in ergot alkaloid serum concentrations, which could cause fatal ergot toxicities. (Severe) The potential for boceprevir treatment failure exists when boceprevir is administered with phenobarbital; concurrent use is contraindicated. Phenobarbital is a potent inducer of CYP3A4, which is partially responsible for boceprevir metabolism. Coadministration may result in decreased boceprevir serum concentrations and impaired virologic response.
Benzhydrocodone; Acetaminophen: (Moderate) Close clinical monitoring is advised when administering acetaminophen with boceprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations.
Bepridil: (Moderate) Close clinical monitoring is advised when administering bepridil with boceprevir due to an increased potential for serious and/or life-threatening bepridil-related adverse events. If bepridil dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of bepridil. Bepridil is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Additionally, bepridil is an inhibitor of P-glycoprotein (PGP), an efflux transporter partially responsible for the metabolism of boceprevir. When used in combination, the plasma concentrations of both medications may be elevated.
Bortezomib: (Moderate) Close clinical monitoring is advised when administering bortezomib with boceprevir due to an increased potential for bortezomib-related adverse events. If bortezomib dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of bortezomib. Bortezomib is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated bortezomib plasma concentrations.
Bosentan: (Moderate) Close clinical monitoring is advised when administering bosentan with boceprevir due to an increased potential for bosentan-related adverse events and the potential for decreased boceprevir efficacy. If bosentan dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Predictions about the interaction can be made based on the metabolic pathways of bosentan and boceprevir. Bosentan is an inducer and substrate of the hepatic isoenzyme CYP3A4; boceprevir is an inhibitor and substrate of this isoenzyme. When used in combination, bosentan plasma concentrations may be elevated and boceprevir plasma concentrations may be deceased, resulting in an increased potential for bosentan-related adverse events and boceprevir treatment failure.
Bosutinib: (Major) Avoid concomitant use of bosutinib and boceprevir; bosutinib plasma exposure may be significantly increased resulting in an increased risk of bosutinib adverse events (e.g., myelosuppression, GI toxicity). Bosutinib is a CYP3A4 substrate and boceprevir is a strong CYP3A4 inhibitor. In a cross-over trial in 24 healthy volunteers, the Cmax and AUC values of bosutinib were increased 5.2-fold and 8.6-fold, respectively, when a single oral dose of bosutinib 100 mg PO was administered after 5 days of a strong CYP3A4 inhibitor.
Brentuximab vedotin: (Minor) Concomitant administration of brentuximab vedotin and boceprevir may increase the exposure of monomethyl auristatin E (MMAE), one of the 3 components released from brentuximab vedotin. The manufacturer suggests that potent CYP3A4 inhibitors, such as boceprevir, may alter MMAE exposure as MMAE is a CYP3A4 substrate. Monitor patients for adverse reactions.
Brexpiprazole: (Major) Because brexpiprazole is partially metabolized by CYP3A4, the manufacturer recommends that the brexpiprazole dose be reduced to one-half of the usual dose in patients receiving strong inhibitors of CYP3A4 such as boceprevir. If these agents are used in combination, the patient should be carefully monitored for brexpiprazole-related adverse reactions. Because brexpiprazole is also metabolized by CYP2D6, patients classified as CYP2D6 poor metabolizers (PMs) who are receiving a strong CYP3A4 inhibitor or patients receiving a combination of a moderate to strong CYP3A4 inhibitor and moderate to strong CYP2D6 inhibitor should have their brexpiprazole dose reduced to one-quarter (25%) of the usual dose. If the co-administered CYP inhibitor is discontinued, adjust the brexpiprazole dose to its original level.
Bromocriptine: (Major) When bromocriptine is used for diabetes, avoid coadministration with boceprevir ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; boceprevir is a strong inhibitor of CYP3A4.
Brompheniramine; Dextromethorphan; Guaifenesin: (Moderate) Close clinical monitoring is advised when administering dextromethorphan with boceprevir due to an increased potential for dextromethorphan-related adverse events. If dextromethorphan dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of dextromethorphan. Dextromethorphan is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated dextromethorphan plasma concentrations.
Brompheniramine; Guaifenesin; Hydrocodone: (Major) Monitor for respiratory depression and sedation if hydrocodone and boceprevir are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as boceprevir, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects.
Brompheniramine; Hydrocodone; Pseudoephedrine: (Major) Monitor for respiratory depression and sedation if hydrocodone and boceprevir are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as boceprevir, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects.
Budesonide: (Major) Concurrent administration of budesonide and boceprevir is not recommended unless the benefits outweigh the risks. If they are coadministered, close monitoring for corticosteroid-related adverse events is advised. If budesonide dose adjustments are made, readjust the dose upon completion of boceprevir treatment. Predictions about the interaction can be made based on the metabolic pathway of budesonide. Budesonide is metabolized by the hepatic isoenzyme CYP3A4 and the drug efflux transporter P-glycoprotein (P-gp); boceprevir inhibits both the isoenzyme and the drug efflux pump. Coadministration may result in elevated budesonide plasma concentrations.
Budesonide; Formoterol: (Major) Concurrent administration of budesonide and boceprevir is not recommended unless the benefits outweigh the risks. If they are coadministered, close monitoring for corticosteroid-related adverse events is advised. If budesonide dose adjustments are made, readjust the dose upon completion of boceprevir treatment. Predictions about the interaction can be made based on the metabolic pathway of budesonide. Budesonide is metabolized by the hepatic isoenzyme CYP3A4 and the drug efflux transporter P-glycoprotein (P-gp); boceprevir inhibits both the isoenzyme and the drug efflux pump. Coadministration may result in elevated budesonide plasma concentrations.
Bupivacaine Liposomal: (Moderate) Close clinical monitoring is advised when administering bupivacaine with boceprevir due to an increased potential for bupivacaine-related adverse events. If bupivacaine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of bupivacaine. Bupivacaine is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated bupivacaine plasma concentrations.
Bupivacaine: (Moderate) Close clinical monitoring is advised when administering bupivacaine with boceprevir due to an increased potential for bupivacaine-related adverse events. If bupivacaine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of bupivacaine. Bupivacaine is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated bupivacaine plasma concentrations.
Bupivacaine; Lidocaine: (Major) Close clinical monitoring is advised when administering systemic lidocaine with boceprevir due to an increased potential for serious and/or life-threatening lidocaine-related adverse events. If lidocaine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of lidocaine. Lidocaine is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated lidocaine plasma concentrations. (Moderate) Close clinical monitoring is advised when administering bupivacaine with boceprevir due to an increased potential for bupivacaine-related adverse events. If bupivacaine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of bupivacaine. Bupivacaine is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated bupivacaine plasma concentrations.
Buprenorphine: (Moderate) The plasma concentrations of CYP3A4 substrates such as buprenorphine and its metabolite, norbuprenorphine, may be elevated when administered concurrently with strong CYP3A4 inhibitors such as boceprevir. During co-administration, use the lowest buprenorphine starting dose and slowly titrate to desired effect. Monitoring for adverse effects, such as CNS side effects or respiratory depression, is advisable. The effect of CYP3A4 inhibitors on buprenorphine implants has not been studied.
Buprenorphine; Naloxone:

(Moderate) The plasma concentrations of CYP3A4 substrates such as buprenorphine and its metabolite, norbuprenorphine, may be elevated when administered concurrently with strong CYP3A4 inhibitors such as boceprevir. During co-administration, use the lowest buprenorphine starting dose and slowly titrate to desired effect. Monitoring for adverse effects, such as CNS side effects or respiratory depression, is advisable. The effect of CYP3A4 inhibitors on buprenorphine implants has not been studied.
Buspirone: (Moderate) Close clinical monitoring is advised when administering buspirone with boceprevir due to an increased potential for buspirone-related adverse events. If buspirone dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of buspirone. Buspirone is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated buspirone plasma concentrations.
Caffeine; Ergotamine: (Severe) Concurrent use of ergot alkaloids and boceprevir is contraindicated due to the potential for serious/life-threatening ergot toxicities, such as peripheral vasospasm and ischemia of the extremities and other tissues. Boceprevir is a potent inhibitor of CYP3A4, which is responsible for the metabolism of ergot alkaloids. Coadministration may result in large increases in ergot alkaloid serum concentrations, which could cause fatal ergot toxicities.
Carbamazepine: (Severe) The potential for boceprevir treatment failure exists when boceprevir is administered with carbamazepine; concurrent use is contraindicated. Carbamazepine is a potent inducer of CYP3A4, which is partially responsible for boceprevir metabolism. Coadministration may result in decreased boceprevir serum concentrations and impaired virologic response.
Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Moderate) Close clinical monitoring is advised when administering dextromethorphan with boceprevir due to an increased potential for dextromethorphan-related adverse events. If dextromethorphan dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of dextromethorphan. Dextromethorphan is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated dextromethorphan plasma concentrations.
Carbinoxamine; Hydrocodone; Phenylephrine: (Major) Monitor for respiratory depression and sedation if hydrocodone and boceprevir are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as boceprevir, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects.
Carbinoxamine; Hydrocodone; Pseudoephedrine: (Major) Monitor for respiratory depression and sedation if hydrocodone and boceprevir are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as boceprevir, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects.
Cariprazine: (Major) Cariprazine and its active metabolites are extensively metabolized by CYP3A4. When a strong CYP3A4 inhibitor, such as boceprevir, is initiated in a patient who is on a stable dose of cariprazine, reduce the cariprazine dosage by half. For adult patients taking cariprazine 4.5 mg daily, the dosage should be reduced to 1.5 mg or 3 mg daily. For adult patients taking cariprazine 1.5 mg daily, the dosing frequency should be adjusted to every other day. When the CYP3A4 inhibitor is withdrawn, the cariprazine dosage may need to be increased. When initiating cariprazine in a patient who is stable on a strong CYP3A4 inhibitor, the patient should be administered 1.5 mg of cariprazine on Day 1 and on Day 3 with no dose administered on Day 2. From Day 4 onward, the dose should be administered at 1.5 mg daily, then increased to a maximum dose of 3 mg daily. When the CYP3A4 inhibitor is withdrawn, the cariprazine dosage may need to be increased.
Carvedilol: (Moderate) Close clinical monitoring is advised when administering carvedilol with boceprevir due to an increased potential for carvedilol and or boceprevir-related adverse events. If carvedilol dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of carvedilol. Carvedilol is an inhibitor and substrate of the drug efflux transporter P-glycoprotein (PGP); boceprevir is an inhibitor and substrate of this efflux protein. Coadministration may result in elevated plasma concentrations of either drug.
Cevimeline: (Moderate) Close clinical monitoring is advised when administering cevimeline with boceprevir due to an increased potential for cevimeline-related adverse events. If cevimeline dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of cevimeline. Cevimeline is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated cevimeline plasma concentrations.
Chloramphenicol: (Moderate) Close clinical monitoring is advised when administering chloramphenicol with boceprevir due to an increased potential for boceprevir-related adverse events. If chloramphenicol dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of chloramphenicol and boceprevir. Chloramphenicol is an inhibitor of the hepatic isoenzyme CYP3A4; boceprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of boceprevir may be elevated.
Chlorpheniramine; Dextromethorphan: (Moderate) Close clinical monitoring is advised when administering dextromethorphan with boceprevir due to an increased potential for dextromethorphan-related adverse events. If dextromethorphan dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of dextromethorphan. Dextromethorphan is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated dextromethorphan plasma concentrations.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Close clinical monitoring is advised when administering dextromethorphan with boceprevir due to an increased potential for dextromethorphan-related adverse events. If dextromethorphan dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of dextromethorphan. Dextromethorphan is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated dextromethorphan plasma concentrations.
Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Monitor for respiratory depression and sedation if hydrocodone and boceprevir are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as boceprevir, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects.
Chlorpheniramine; Hydrocodone: (Major) Monitor for respiratory depression and sedation if hydrocodone and boceprevir are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as boceprevir, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects.
Chlorpheniramine; Hydrocodone; Phenylephrine: (Major) Monitor for respiratory depression and sedation if hydrocodone and boceprevir are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as boceprevir, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects.
Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Major) Monitor for respiratory depression and sedation if hydrocodone and boceprevir are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as boceprevir, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects.
Cilostazol: (Moderate) Close clinical monitoring is advised when administering cilostazol with boceprevir due to an increased potential for cilostazol-related adverse events. If cilostazol dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of cilostazol. Cilostazol is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated cilostazol plasma concentrations.
Cimetidine: (Moderate) Close clinical monitoring is advised when administering cimetidine with boceprevir due to an increased potential for boceprevir-related adverse events. If cimetidine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of cimetidine and boceprevir. Cimetidine is an inhibitor of the hepatic isoenzyme CYP3A4; boceprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of boceprevir may be elevated.
Cinacalcet: (Moderate) Close clinical monitoring is advised when administering cinacalcet with boceprevir due to an increased potential for cinacalcet-related adverse events. If cinacalcet dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of cinacalcet. Cinacalcet is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated cinacalcet plasma concentrations.
Ciprofloxacin: (Moderate) Close clinical monitoring is advised when administering ciprofloxacin with boceprevir due to an increased potential for boceprevir-related adverse events. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of ciprofloxacin and boceprevir. Ciprofloxacin is an inhibitor of the hepatic isoenzyme CYP3A4; boceprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of boceprevir may be elevated.
Cisapride: (Severe) The concurrent use of cisapride and boceprevir is contraindicated due to the potential for serious/life-threatening reactions. Boceprevir is a potent inhibitor of CYP3A4, which is responsible cisapride metabolism. Coadministration may result in large increases in cisapride serum concentrations, which could cause adverse events such as cardiac arrhythmias.
Citalopram: (Moderate) Close clinical monitoring is advised when administering citalopram with boceprevir due to an increased potential for citalopram-related adverse events. If citalopram dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of citalopram. Citalopram is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated citalopram plasma concentrations.
Clarithromycin: (Major) Close clinical monitoring is advised when administering clarithromycin with boceprevir due to an increased potential for serious clarithromycin-related adverse events, such as QT prolongation and torsade de pointes. No clarithromycin dosage adjustments are required for patients with normal renal function. If clarithromycin dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Predictions about the interaction can be made based on the metabolic pathways of clarithromycin and boceprevir. Both clarithromycin and boceprevir are substrates and inhibitors of the hepatic isoenzyme CYP3A4. Additionally, clarithromycin is an inhibitor of P-glycoprotein (P-gp), and efflux transporter partially responsible for the metabolism of boceprevir. When used in combination, the plasma concentrations of both medications may be elevated.
Clindamycin: (Moderate) Concomitant use of clindamycin and boceprevir may decrease clindamycin clearance and increase the risk of adverse reactions. Clindamycin is a CYP3A4 substrate; boceprevir is a strong inhibitor of CYP3A4. Caution and close monitoring are advised if these drugs are used together.
Clomipramine: (Moderate) Close clinical monitoring is advised when administering clomipramine with boceprevir due to an increased potential for clomipramine-related adverse events. If clomipramine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of clomipramine. Clomipramine is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated clomipramine plasma concentrations.
Clonazepam: (Moderate) Close clinical monitoring is advised when administering clonazepam with boceprevir due to an increased potential for clonazepam-related adverse events. If clonazepam dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of clonazepam. Clonazepam is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated clonazepam plasma concentrations.
Clozapine: (Moderate) Caution is advisable during concurrent use of boceprevir and clozapine. Boceprevir is an inhibitor of CYP3A4, one of the isoenzymes responsible for the metabolism of clozapine. Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. Elevated plasma concentrations of clozapine occurring through CYP inhibition may potentially increase the risk of life-threatening arrhythmias, sedation, anticholinergic effects, seizures, orthostasis, or other adverse effects. According to the manufacturer, patients receiving clozapine in combination with a CYP3A4 inhibitor should be monitored for adverse reactions. Consideration should be given to reducing the clozapine dose if necessary. If the inhibitor is discontinued after dose adjustments are made, monitor for lack of clozapine effectiveness and consider increasing the clozapine dose if necessary.
Cobicistat: (Major) Avoid concurrent use of cobicistat with boceprevir, as drug interaction data are not available. Clinically significant drug interactions may occur during coadministration. Boceprevir is a CYP3A4 inhibitor/substrate and P-glycoprotein (P-gp) substrate. Cobicistat is an inhibitor of CYP3A4 and P-gp, and a substrate of CYP3A4.
Cobimetinib: (Major) Avoid the concurrent use of cobimetinib with boceprevir due to the risk of cobimetinib toxicity. Cobimetinib is a P-glycoprotein (P-gp) substrate as well as a CYP3A substrate in vitro; boceprevir is a weak P-gp inhibitor and a strong CYP3A inhibitor. In healthy subjects (n = 15), coadministration of a single 10 mg dose of cobimetinib with itraconazole (200 mg once daily for 14 days), another strong CYP3A4 inhibitor, increased the mean cobimetinib AUC by 6.7-fold (90% CI, 5.6 to 8) and the mean Cmax by 3.2-fold (90% CI, 2.7 to 3.7).
Colchicine: (Major) Coadministration of colchicine and boceprevir is not recommended in patients with renal or hepatic impairment due to an increased risk for fatal colchicine toxicity. In patients with normal renal and hepatic function, a reduction in colchicine dose or an interruption of colchicine treatment is recommended. When coadministered with boceprevir and used for treatment of gout flares, patients should be administered 0.6 mg of colchicine for one dose, followed by 0.3 mg one hour later. Wait at least 3 days before repeating colchicine therapy. If colchicine is administered with boceprevir for prophylaxis of gout flare and the original regimen with 0.6 mg twice day, the colchicine regimen should be adjusted to 0.3 mg once daily. If the original regimen was 0.6 mg daily, the adjusted regimen should be 0.3 mg every other day. If colchicine is used for treatment of familial Mediterranean fever and in conjunction with boceprevir, the maximum daily dose should not exceed 0.6 mg daily (may be given as 0.3 mg twice daily).
Colchicine; Probenecid: (Major) Coadministration of colchicine and boceprevir is not recommended in patients with renal or hepatic impairment due to an increased risk for fatal colchicine toxicity. In patients with normal renal and hepatic function, a reduction in colchicine dose or an interruption of colchicine treatment is recommended. When coadministered with boceprevir and used for treatment of gout flares, patients should be administered 0.6 mg of colchicine for one dose, followed by 0.3 mg one hour later. Wait at least 3 days before repeating colchicine therapy. If colchicine is administered with boceprevir for prophylaxis of gout flare and the original regimen with 0.6 mg twice day, the colchicine regimen should be adjusted to 0.3 mg once daily. If the original regimen was 0.6 mg daily, the adjusted regimen should be 0.3 mg every other day. If colchicine is used for treatment of familial Mediterranean fever and in conjunction with boceprevir, the maximum daily dose should not exceed 0.6 mg daily (may be given as 0.3 mg twice daily).
Conivaptan: (Severe) Coadministration of conivaptan with potent CYP3A4 inhibitors like boceprevir is contraindicated. Exposure to both drugs may be elevated during concurrent use, increasing the risk for serious adverse events. Coadministration of conivaptan with another potent CYP3A4 inhibitor resulted in 4- and 11- fold increases in conivaptan Cmax and AUC, respectively; similar pharmacokinetic effects could be seen with the coadministration of conivaptan and boceprevir. In addition, conivaptan inhibits both CYP3A4 and P-glycoprotein; boceprevir is a substrate of both CYP3A4 and P-gp.
Cyclosporine: (Major) Close monitoring of cyclosporine serum concentrations and frequent assessments of renal function are advised when coadministering cyclosporine with boceprevir. Cyclosporine is a substrate of the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Additionally, both cyclosporine and boceprevir are inhibitors and substrates of the drug efflux transporter P-glycoprotein (PGP). After a single 100 mg dose of cyclosporine, the mean AUC and Cmax of cyclosporine are increased approximately 2.7-fold and 2-fold, respectively, when administered in combination with boceprevir; thus, cyclosporine dose reductions and prolongation of the dosing interval are recommended to achieve desired cyclosporine concentrations. If cyclosporine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment.
Dabigatran: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with boceprevir, a mild P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like boceprevir in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with boceprevir, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Dabrafenib: (Major) The concomitant use of dabrafenib, a CYP3A4 substrate and moderate CYP3A4 inducer, and boceprevir, a strong CYP3A4 inhibitor and CYP3A4 substrate, may result in altered levels of either agent; avoid concomitant use if possible. If another agent cannot be substituted and coadministration of these agents is unavoidable, monitor patients closely for dabrafenib adverse reactions including skin toxicity, ocular toxicity, and cardiotoxicity and for loss of boceprevir efficacy.
Daclatasvir: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be reduced to 30 mg PO once daily when administered in combination with strong CYP3A4 inhibitors, such as boceprevir. Taking these drugs together may increase daclatasvir serum concentrations, and potentially increase the risk for adverse effects. In addition, the therapeutic effects of boceprevir, a P-glycoprotein (P-gp) substrate, may be increased by daclatasvir, a P-gp inhibitor.
Danazol: (Moderate) Close clinical monitoring is advised when administering danazol with boceprevir due to an increased potential for boceprevir-related adverse events. If danazol dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of danazol and boceprevir. Danazol is an inhibitor of the hepatic isoenzyme CYP3A4; boceprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of boceprevir may be elevated.
Dapsone: (Moderate) Close clinical monitoring is advised when administering dapsone with boceprevir due to an increased potential for dapsone-related adverse events. If dapsone dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of dapsone. Dapsone is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated dapsone plasma concentrations.
Darifenacin: (Moderate) Close clinical monitoring is advised when administering darifenacin with boceprevir due to an increased potential for darifenacin-related adverse events. If darifenacin dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of darifenacin. Darifenacin is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated darifenacin plasma concentrations.
Darunavir: (Major) Concurrent administration of boceprevir and darunavir is not recommended due to the potential for HIV and hepatitis C treatment failures. Use of boceprevir with darunavir plus a pharmacokinetic enhancer results in decreased serum concentrations of all 3 drugs. Predictions about the interaction can be made based on metabolic pathways. Both boceprevir and darunavir are inhibitors and substrates of the hepatic isoenzyme CYP3A4. If used in combination, health care providers are advised to closely monitor for decreased treatment response and virologic rebound. Health care providers are also encouraged to report any drug-related adverse reactions to the FDA MedWatch Program.
Darunavir; Cobicistat: (Major) Avoid concurrent use of cobicistat with boceprevir, as drug interaction data are not available. Clinically significant drug interactions may occur during coadministration. Boceprevir is a CYP3A4 inhibitor/substrate and P-glycoprotein (P-gp) substrate. Cobicistat is an inhibitor of CYP3A4 and P-gp, and a substrate of CYP3A4. (Major) Concurrent administration of boceprevir and darunavir is not recommended due to the potential for HIV and hepatitis C treatment failures. Use of boceprevir with darunavir plus a pharmacokinetic enhancer results in decreased serum concentrations of all 3 drugs. Predictions about the interaction can be made based on metabolic pathways. Both boceprevir and darunavir are inhibitors and substrates of the hepatic isoenzyme CYP3A4. If used in combination, health care providers are advised to closely monitor for decreased treatment response and virologic rebound. Health care providers are also encouraged to report any drug-related adverse reactions to the FDA MedWatch Program.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Avoid concurrent use of cobicistat with boceprevir, as drug interaction data are not available. Clinically significant drug interactions may occur during coadministration. Boceprevir is a CYP3A4 inhibitor/substrate and P-glycoprotein (P-gp) substrate. Cobicistat is an inhibitor of CYP3A4 and P-gp, and a substrate of CYP3A4. (Major) Concurrent administration of boceprevir and darunavir is not recommended due to the potential for HIV and hepatitis C treatment failures. Use of boceprevir with darunavir plus a pharmacokinetic enhancer results in decreased serum concentrations of all 3 drugs. Predictions about the interaction can be made based on metabolic pathways. Both boceprevir and darunavir are inhibitors and substrates of the hepatic isoenzyme CYP3A4. If used in combination, health care providers are advised to closely monitor for decreased treatment response and virologic rebound. Health care providers are also encouraged to report any drug-related adverse reactions to the FDA MedWatch Program.
Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) Concurrent administration of ritonavir with boceprevir is not recommended due to the potential for HIV and hepatitis C treatment failures. This combination has resulted in decreased serum concentrations of both medications. Ritonavir is an inhibitor, inducer, and substrate of the hepatic isoenzyme CYP3A4; boceprevir is an inhibitor and substrate of this isoenzyme. Additionally, both drugs are substrates and inhibitors of the drug efflux transporter P-glycoprotein (PGP). If these drugs are coadministered, health care providers are advised to closely monitor for decreased treatment response and virologic rebound. Health care providers are also encouraged to report any drug-related adverse reactions to the FDA MedWatch Program.
Deflazacort: (Major) Decrease deflazacort dose to one third of the recommended dosage when coadministered with boceprevir. Concurrent use may significantly increase concentrations of 21-desDFZ, the active metabolite of deflazacort, resulting in an increased risk of toxicity. Deflazacort is a CYP3A4 substrate; boceprevir is a strong inhibitor of CYP3A4. Administration of deflazacort with clarithromycin, a strong CYP3A4 inhibitor, increased total exposure to 21-desDFZ by about 3-fold.
Delavirdine: (Moderate) Close clinical monitoring is advised when administering delavirdine with boceprevir due to an increased potential for delavirdine-related adverse events. If delavirdine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of delavirdine and boceprevir. Both delavirdine and boceprevir are substrates and inhibitors of the hepatic isoenzyme CYP3A4. When used in combination, the plasma concentrations of both medications may be elevated.
Desipramine: (Moderate) Close clinical monitoring is advised when administering desipramine with boceprevir due to an increased potential for desipramine-related adverse event, such as dizziness, hypotension, and syncope. When used in combination, the plasma concentrations of desipramine were increased; thus, consider initiating desipramine at the lowest effective dose. If desipramine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment.
Dexamethasone: (Moderate) Coadministration of dexamethasone and boceprevir is not recommended. If coadministered, close clinical monitoring for increased dexamethasone-related adverse events and for decreased boceprevir efficacy is advised. If dexamethasone dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Predictions about the interaction can be made based on the metabolic pathways of dexamethasone and boceprevir. Dexamethasone is an inducer and substrate of the hepatic isoenzyme CYP3A4; boceprevir is an inhibitor and substrate of this isoenzyme. Additionally, both dexamethasone and boceprevir are substrates for the drug efflux transporter P-glycoprotein (PGP). When used in combination, the plasma concentrations of dexamethasone may be elevated and the plasma concentration of boceprevir may be deceased, resulting in an increased potential for dexamethasone-related adverse events and boceprevir treatment failure.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Close clinical monitoring is advised when administering dextromethorphan with boceprevir due to an increased potential for dextromethorphan-related adverse events. If dextromethorphan dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of dextromethorphan. Dextromethorphan is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated dextromethorphan plasma concentrations.
Dexlansoprazole: (Moderate) Close clinical monitoring is advised when administering dexlansoprazole with boceprevir due to an increased potential for dexlansoprazole-related adverse events. If dexlansoprazole dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of dexlansoprazole. Dexlansoprazole is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated dexlansoprazole plasma concentrations.
Dextromethorphan: (Moderate) Close clinical monitoring is advised when administering dextromethorphan with boceprevir due to an increased potential for dextromethorphan-related adverse events. If dextromethorphan dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of dextromethorphan. Dextromethorphan is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated dextromethorphan plasma concentrations.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Close clinical monitoring is advised when administering dextromethorphan with boceprevir due to an increased potential for dextromethorphan-related adverse events. If dextromethorphan dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of dextromethorphan. Dextromethorphan is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated dextromethorphan plasma concentrations.
Dextromethorphan; Guaifenesin: (Moderate) Close clinical monitoring is advised when administering dextromethorphan with boceprevir due to an increased potential for dextromethorphan-related adverse events. If dextromethorphan dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of dextromethorphan. Dextromethorphan is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated dextromethorphan plasma concentrations.
Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Close clinical monitoring is advised when administering dextromethorphan with boceprevir due to an increased potential for dextromethorphan-related adverse events. If dextromethorphan dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of dextromethorphan. Dextromethorphan is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated dextromethorphan plasma concentrations.
Dextromethorphan; Guaifenesin; Potassium Guaiacolsulfonate: (Moderate) Close clinical monitoring is advised when administering dextromethorphan with boceprevir due to an increased potential for dextromethorphan-related adverse events. If dextromethorphan dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of dextromethorphan. Dextromethorphan is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated dextromethorphan plasma concentrations.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Close clinical monitoring is advised when administering dextromethorphan with boceprevir due to an increased potential for dextromethorphan-related adverse events. If dextromethorphan dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of dextromethorphan. Dextromethorphan is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated dextromethorphan plasma concentrations.
Dextromethorphan; Promethazine: (Moderate) Close clinical monitoring is advised when administering dextromethorphan with boceprevir due to an increased potential for dextromethorphan-related adverse events. If dextromethorphan dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of dextromethorphan. Dextromethorphan is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated dextromethorphan plasma concentrations.
Dextromethorphan; Quinidine: (Major) Close clinical monitoring is advised when administering quinidine with boceprevir due to an increased potential for serious and/or life-threatening quinidine-related adverse events. If quinidine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of quinidine and boceprevir. Quinidine is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Additionally, both quinidine and boceprevir are substrates and inhibitors of P-glycoprotein (PGP) drug efflux transporter. When used in combination, the plasma concentrations of both medications may be elevated. (Moderate) Close clinical monitoring is advised when administering dextromethorphan with boceprevir due to an increased potential for dextromethorphan-related adverse events. If dextromethorphan dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of dextromethorphan. Dextromethorphan is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated dextromethorphan plasma concentrations.
Diazepam: (Moderate) Close clinical monitoring is advised when administering diazepam with boceprevir due to an increased potential for diazepam-related adverse events. If diazepam dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of diazepam. Diazepam is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated diazepam plasma concentrations.
Diclofenac: (Moderate) Close clinical monitoring is advised when administering diclofenac with boceprevir due to an increased potential for diclofenac-related adverse events. If diclofenac dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of diclofenac. Diclofenac is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated diclofenac plasma concentrations.
Diclofenac; Misoprostol: (Moderate) Close clinical monitoring is advised when administering diclofenac with boceprevir due to an increased potential for diclofenac-related adverse events. If diclofenac dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of diclofenac. Diclofenac is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated diclofenac plasma concentrations.
Dienogest; Estradiol valerate: (Major) Boceprevir reduces the Cmax of norethindrone by 17%, which may be sufficient to decrease the effectiveness of combined oral contraceptives containing less than 1 mg of norethindrone (ethinyl estradiol; norethindrone, ethinyl estradiol; norethindrone acetate, mestranol; norethindrone); concurrent use of these products are contraindicated. Instead, the manufacturer recommends use of contraceptives that contain ethinyl estradiol and at least 1 mg of norethindrone. Boceprevir recipients and their partners are also required to use a second, non-hormonal, form of birth control while on therapy and for at least 6 months after treatment.
Digoxin: (Moderate) Monitoring of digoxin serum concentrations is advised when administering digoxin with boceprevir due to an increased potential for digoxin-related adverse events. Digoxin is a substrate for P-glycoprotein (P-gp). Boceprevir is a substrate and inhibitor of P-gp. The lowest dose of digoxin should be initially prescribed with titrations of digoxin based on serum concentrations. If digoxin dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment.
Dihydroergotamine: (Severe) Concurrent use of ergot alkaloids and boceprevir is contraindicated due to the potential for serious/life-threatening ergot toxicities, such as peripheral vasospasm and ischemia of the extremities and other tissues. Boceprevir is a potent inhibitor of CYP3A4, which is responsible for the metabolism of ergot alkaloids. Coadministration may result in large increases in ergot alkaloid serum concentrations, which could cause fatal ergot toxicities.
Diphenhydramine; Hydrocodone; Phenylephrine: (Major) Monitor for respiratory depression and sedation if hydrocodone and boceprevir are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as boceprevir, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects.
Disopyramide: (Moderate) Close clinical monitoring is advised when administering disopyramide with boceprevir due to an increased potential for disopyramide-related adverse events. If disopyramide dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of disopyramide. Disopyramide is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated disopyramide plasma concentrations.
Disulfiram: (Moderate) Close clinical monitoring is advised when administering disulfiram with boceprevir due to an increased potential for disulfiram-related adverse events. If disulfiram dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of disulfiram. Disulfiram is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated disulfiram plasma concentrations.
Docetaxel: (Moderate) Close clinical monitoring is advised when administering docetaxel with boceprevir due to an increased potential for docetaxel-related adverse events. If docetaxel dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of docetaxel. Docetaxel is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; boceprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated docetaxel plasma concentrations.
Dolasetron: (Moderate) Close clinical monitoring is advised when administering dolasetron with boceprevir due to an increased potential for dolasetron-related adverse events. If dolasetron dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of dolasetron. Dolasetron is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated dolasetron plasma concentrations.
Dolutegravir; Rilpivirine: (Moderate) Although dose adjustments are not recommended, close clinical monitoring is advised when administering boceprevir with rilpivirine due to an increased potential for rilpivirine-related adverse events. When these drugs are administered concurrently, the Cmax and AUC of rilpivirine are significantly increased. Predictions about the interaction can be made based on metabolic pathways of boceprevir and rilpivirine. Boceprevir is an inhibitor of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in increased rilpivirine plasma concentrations.
Donepezil: (Moderate) Observe patients for a potential increase in adverse effects during concurrent administration of donepezil and boceprevir. Donepezil is partially metabolized by CYP3A4. Coadministration with CYP3A4 inhibitors, such as boceprevir, may increase donepezil concentrations, potentially resulting in dose-related toxicity. However, the clinical effect of such an interaction on the response to donepezil has not been determined.
Donepezil; Memantine: (Moderate) Observe patients for a potential increase in adverse effects during concurrent administration of donepezil and boceprevir. Donepezil is partially metabolized by CYP3A4. Coadministration with CYP3A4 inhibitors, such as boceprevir, may increase donepezil concentrations, potentially resulting in dose-related toxicity. However, the clinical effect of such an interaction on the response to donepezil has not been determined.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as boceprevir. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Doxazosin: (Severe) The concurrent use of doxazosin and boceprevir is contraindicated due to the potential for serious/life-threatening reactions. Doxzosin is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated doxazosin plasma concentrations, which could cause adverse events such as hypotension and priapism.
Doxorubicin: (Major) Boceprevir is a strong CYP3A4 inhibitor and a mild inhibitor of P-glycoprotein (P-gp); doxorubicin is a major substrate of both CYP3A4 and P-gp. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP3A4 and/or P-gp, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of boceprevir and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
Dronedarone: (Moderate) Close clinical monitoring is advised when administering dronedarone with boceprevir due to an increased potential for dronedarone-related adverse events. If dronedarone dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of dronedarone and boceprevir. Both dronedarone and boceprevir are substrates and inhibitors of the hepatic isoenzyme CYP3A4. Additionally, dronedarone is an inhibitor of the drug efflux transporter P-glycoprotein (PGP); boceprevir is partially metabolized by this efflux protein. When used in combination, the plasma concentrations of both medications may be elevated.
Drospirenone: (Severe) Concurrent use of drosperinone and boceprevir is contraindicated due to the potential for serious reactions. Boceprevir is a potent inhibitor of CYP3A4, which is responsible drospirenone metabolism. Coadministration may result in large increases in drosperinone serum concentrations, which could cause adverse events such as hyperkalemia.
Drospirenone; Estradiol: (Severe) Concurrent use of drosperinone and boceprevir is contraindicated due to the potential for serious reactions. Boceprevir is a potent inhibitor of CYP3A4, which is responsible drospirenone metabolism. Coadministration may result in large increases in drosperinone serum concentrations, which could cause adverse events such as hyperkalemia.
Drospirenone; Ethinyl Estradiol: (Severe) Concurrent use of drosperinone and boceprevir is contraindicated due to the potential for serious reactions. Boceprevir is a potent inhibitor of CYP3A4, which is responsible drospirenone metabolism. Coadministration may result in large increases in drosperinone serum concentrations, which could cause adverse events such as hyperkalemia. (Major) Close clinical monitoring for signs of estrogen deficiency is advised when administering ethinyl estradiol in combination with boceprevir. When used concurrently, ethinyl estradiol plasma concentrations may be decreased, potentially resulting in impaired efficacy. If ethinyl estradiol dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Severe) Concurrent use of drosperinone and boceprevir is contraindicated due to the potential for serious reactions. Boceprevir is a potent inhibitor of CYP3A4, which is responsible drospirenone metabolism. Coadministration may result in large increases in drosperinone serum concentrations, which could cause adverse events such as hyperkalemia. (Major) Close clinical monitoring for signs of estrogen deficiency is advised when administering ethinyl estradiol in combination with boceprevir. When used concurrently, ethinyl estradiol plasma concentrations may be decreased, potentially resulting in impaired efficacy. If ethinyl estradiol dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment.
Dutasteride: (Moderate) Monitor for common side effects of dutasteride, such as libido decrease, breast tenderness, or erectile dysfunction when chronic, potent inhibitors of CYP3A4 like boceprevir are used concomitantly. The effect of potent CYP3A4 inhibitors on the metabolism of dutasteride has not been studied. However, because dutasteride is metabolized by CYP3A4 and CYP3A5 isoenzymes, chronic coadministration with potent CYP3A4 enzyme inhibitors may result in elevated concentrations of dutasteride.
Dutasteride; Tamsulosin: (Severe) The concurrent use of tamsulosin and boceprevir is contraindicated due to the potential for serious/life-threatening reactions. Tamsulosin is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated tamsulosin plasma concentrations, which could cause adverse events such as hypotension and priapism. (Moderate) Monitor for common side effects of dutasteride, such as libido decrease, breast tenderness, or erectile dysfunction when chronic, potent inhibitors of CYP3A4 like boceprevir are used concomitantly. The effect of potent CYP3A4 inhibitors on the metabolism of dutasteride has not been studied. However, because dutasteride is metabolized by CYP3A4 and CYP3A5 isoenzymes, chronic coadministration with potent CYP3A4 enzyme inhibitors may result in elevated concentrations of dutasteride.
Efavirenz: (Moderate) Avoid concurrent administration of efavirenz and boceprevir, as use of these drugs together may result in hepatitis C treatment failures and efavirenz-related adverse events. When administered in combination, the mean plasma concentration (AUC) of boceprevir was deceased by 19%, and the mean AUC of efavirenz was increased by 20%. Predictions about the interaction can be made based on the metabolic pathways of efavirenz and boceprevir. Efavirenz is an inducer and substrate of the hepatic isoenzyme CYP3A4; boceprevir is an inhibitor and substrate of this isoenzyme.
Efavirenz; Emtricitabine; Tenofovir: (Moderate) Avoid concurrent administration of efavirenz and boceprevir, as use of these drugs together may result in hepatitis C treatment failures and efavirenz-related adverse events. When administered in combination, the mean plasma concentration (AUC) of boceprevir was deceased by 19%, and the mean AUC of efavirenz was increased by 20%. Predictions about the interaction can be made based on the metabolic pathways of efavirenz and boceprevir. Efavirenz is an inducer and substrate of the hepatic isoenzyme CYP3A4; boceprevir is an inhibitor and substrate of this isoenzyme. (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as boceprevir. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Avoid concurrent administration of efavirenz and boceprevir, as use of these drugs together may result in hepatitis C treatment failures and efavirenz-related adverse events. When administered in combination, the mean plasma concentration (AUC) of boceprevir was deceased by 19%, and the mean AUC of efavirenz was increased by 20%. Predictions about the interaction can be made based on the metabolic pathways of efavirenz and boceprevir. Efavirenz is an inducer and substrate of the hepatic isoenzyme CYP3A4; boceprevir is an inhibitor and substrate of this isoenzyme. (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as boceprevir. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Elbasvir; Grazoprevir: (Major) Concurrent administration of elbasvir with boceprevir should be avoided if possible. Use of these drugs together is expected to significantly increase the plasma concentrations of elbasvir, and may result in adverse effects (i.e., elevated ALT concentrations and hepatotoxicity). Boceprevir is a strong inhibitor of the hepatic enzyme CYP3A, while elbasvir is metabolized by CYP3A. (Major) Concurrent administration of grazoprevir with boceprevir should be avoided if possible. Use of these drugs together is expected to significantly increase the plasma concentration of grazoprevir, and may result in adverse effects (i.e., elevated ALT concentrations and hepatotoxicity). Boceprevir is a strong inhibitor of the hepatic enzyme CYP3A, while grazoprevir is metabolized by CYP3A. In addition, plasma concentrations of boceprevir (also a CYP3A substrate) may be increased when given with grazoprevir (a weak CYP3A inhibitor).
Eletriptan: (Moderate) Close clinical monitoring is advised when administering eletriptan with boceprevir due to an increased potential for eletriptan-related adverse events. If eletriptan dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of eletriptan. Eletriptan is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; boceprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated eletriptan plasma concentrations.
Elexacaftor; tezacaftor; ivacaftor: (Major) If boceprevir and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to twice weekly (e.g., if the usual dosage is 150 mg twice daily, reduce to 150 mg twice weekly). Ivacaftor is a CYP3A substrate, and boceprevir is a strong CYP3A inhibitor. Coadministration with ketoconazole, another strong CYP3A inhibitor, increased ivacaftor exposure by 8.5-fold. Ivacaftor is also an inhibitor of CYP3A and P-glycoprotein (P-gp); boceprevir is metabolized by CYP3A4 and is a substrate of P-gp. Coadministration may increase boceprevir exposure leading to increased or prolonged therapeutic effects and adverse events.
Eliglustat: (Major) In intermediate or poor CYP2D6 metabolizers (IMs or PMs), coadministration of boceprevir and eliglustat is contraindicated. In extensive CYP2D6 metabolizers (EMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with both boceprevir and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Boceprevir is a strong CYP3A inhibitor and P-gp substrate; eliglustat is a CYP3A and CYP2D6 substrate and P-gp inhibitor. Coadministration of eliglustat with CYP3A inhibitors, such as boceprevir, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. Although boceprevir's product labeling states that coadministration of other drugs that are highly dependent on CYP3A for metabolic clearance and for which elevated plasma concentrations are associated with serious adverse events, the interaction between ketoconazole (a potent CYP3A inhibitor) and eliglustat was studied during clinical trials. The resultant data supports eliglustat dosage reduction in EMs instead of contraindication. In addition, coadministration of eliglustat with P-gp substrates (e.g., boceprevir) may result in increased concentrations of the concomitant drug; monitor patients closely for adverse events.
Elvitegravir: (Major) Avoid concurrent use of elvitegravir containing antiretroviral regimens with boceprevir. If these drugs are used together, there is a potential for reduced boceprevir concentrations and altered concentrations of the coadministered HIV protease inhibitor. This interaction may result in a reduction of antiretroviral efficacy and the potential development of viral resistance.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Avoid concurrent use of cobicistat with boceprevir, as drug interaction data are not available. Clinically significant drug interactions may occur during coadministration. Boceprevir is a CYP3A4 inhibitor/substrate and P-glycoprotein (P-gp) substrate. Cobicistat is an inhibitor of CYP3A4 and P-gp, and a substrate of CYP3A4. (Major) Avoid concurrent use of elvitegravir containing antiretroviral regimens with boceprevir. If these drugs are used together, there is a potential for reduced boceprevir concentrations and altered concentrations of the coadministered HIV protease inhibitor. This interaction may result in a reduction of antiretroviral efficacy and the potential development of viral resistance.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid concurrent use of cobicistat with boceprevir, as drug interaction data are not available. Clinically significant drug interactions may occur during coadministration. Boceprevir is a CYP3A4 inhibitor/substrate and P-glycoprotein (P-gp) substrate. Cobicistat is an inhibitor of CYP3A4 and P-gp, and a substrate of CYP3A4. (Major) Avoid concurrent use of elvitegravir containing antiretroviral regimens with boceprevir. If these drugs are used together, there is a potential for reduced boceprevir concentrations and altered concentrations of the coadministered HIV protease inhibitor. This interaction may result in a reduction of antiretroviral efficacy and the potential development of viral resistance. (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as boceprevir. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Empagliflozin; Linagliptin: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. A possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic therapy, such as linagliptin, should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Although dose adjustments are not recommended, close clinical monitoring is advised when administering boceprevir with rilpivirine due to an increased potential for rilpivirine-related adverse events. When these drugs are administered concurrently, the Cmax and AUC of rilpivirine are significantly increased. Predictions about the interaction can be made based on metabolic pathways of boceprevir and rilpivirine. Boceprevir is an inhibitor of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in increased rilpivirine plasma concentrations.
Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Moderate) Although dose adjustments are not recommended, close clinical monitoring is advised when administering boceprevir with rilpivirine due to an increased potential for rilpivirine-related adverse events. When these drugs are administered concurrently, the Cmax and AUC of rilpivirine are significantly increased. Predictions about the interaction can be made based on metabolic pathways of boceprevir and rilpivirine. Boceprevir is an inhibitor of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in increased rilpivirine plasma concentrations. (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as boceprevir. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Emtricitabine; Tenofovir disoproxil fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as boceprevir. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Enalapril; Felodipine: (Moderate) Close clinical monitoring is advised when administering felodipine with boceprevir due to an increased potential for felodipine-related adverse events. If felodipine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Predictions about the interaction can be made based on the metabolic pathway of felodipine. Felodipine is metabolized by the hep atic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated felodipine plasma concentrations.
Eplerenone: (Severe) Coadministration of boceprevir and eplerenone is contraindicated. Boceprevir potently inhibits the hepatic CYP3A4 isoenzyme and can increase the serum concentrations of eplerenone. Increased eplerenone concentrations may lead to a risk of developing hyperkalemia and hypotension.
Ergoloid Mesylates: (Severe) Concurrent use of ergot alkaloids and boceprevir is contraindicated due to the potential for serious/life-threatening ergot toxicities, such as peripheral vasospasm and ischemia of the extremities and other tissues. Boceprevir is a potent inhibitor of CYP3A4, which is responsible for the metabolism of ergot alkaloids. Coadministration may result in large increases in ergot alkaloid serum concentrations, which could cause fatal ergot toxicities.
Ergonovine: (Severe) Concurrent use of ergot alkaloids and boceprevir is contraindicated due to the potential for serious/life-threatening ergot toxicities, such as peripheral vasospasm and ischemia of the extremities and other tissues. Boceprevir is a potent inhibitor of CYP3A4, which is responsible for the metabolism of ergot alkaloids. Coadministration may result in large increases in ergot alkaloid serum concentrations, which could cause fatal ergot toxicities.
Ergot alkaloids: (Severe) Concurrent use of ergot alkaloids and boceprevir is contraindicated due to the potential for serious/life-threatening ergot toxicities, such as peripheral vasospasm and ischemia of the extremities and other tissues. Boceprevir is a potent inhibitor of CYP3A4, which is responsible for the metabolism of ergot alkaloids. Coadministration may result in large increases in ergot alkaloid serum concentrations, which could cause fatal ergot toxicities.
Ergotamine: (Severe) Concurrent use of ergot alkaloids and boceprevir is contraindicated due to the potential for serious/life-threatening ergot toxicities, such as peripheral vasospasm and ischemia of the extremities and other tissues. Boceprevir is a potent inhibitor of CYP3A4, which is responsible for the metabolism of ergot alkaloids. Coadministration may result in large increases in ergot alkaloid serum concentrations, which could cause fatal ergot toxicities.
Escitalopram: (Moderate) When used in combination with boceprevir, the plasma concentrations of escitalopram are decreased. Escitalopram has a wide therapeutic index; however, dose adjustments may be needed. If dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Close clinical monitoring is advised.
Eslicarbazepine: (Moderate) In vivo studies suggest eslicarbazepine is an inducer of the hepatic isoenzyme CYP3A4; boceprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of boceprevir may decrease, resulting in decreased boceprevir efficacy. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of eslicarbazepine and boceprevir. Close clinical monitoring is advised when administering eslicarbazepine with boceprevir due to the potential for boceprevir treatment failure. If eslicarbazepine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment.
Esomeprazole: (Moderate) Close clinical monitoring is advised when administering esomeprazole with boceprevir due to an increased potential for esomeprazole-related adverse events. If esomeprazole dosage adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of esomeprazole. Esomeprazole is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated esomeprazole plasma concentrations.
Esomeprazole; Naproxen: (Moderate) Close clinical monitoring is advised when administering esomeprazole with boceprevir due to an increased potential for esomeprazole-related adverse events. If esomeprazole dosage adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of esomeprazole. Esomeprazole is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated esomeprazole plasma concentrations.
Estazolam: (Moderate) Close clinical monitoring is advised when administering estazolam with boceprevir due to an increased potential for estazolam-related adverse events. If estazolam dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of estazolam. Estazolam is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated estazolam plasma concentrations.
Estradiol; Levonorgestrel: (Major) Boceprevir reduces the Cmax of norethindrone by 17%, which may be sufficient to decrease the effectiveness of combined oral contraceptives containing less than 1 mg of norethindrone (ethinyl estradiol; norethindrone, ethinyl estradiol; norethindrone acetate, mestranol; norethindrone); concurrent use of these products are contraindicated. Instead, the manufacturer recommends use of contraceptives that contain ethinyl estradiol and at least 1 mg of norethindrone. Boceprevir recipients and their partners are also required to use a second, non-hormonal, form of birth control while on therapy and for at least 6 months after treatment.
Estradiol; Norethindrone: (Major) Boceprevir reduces the Cmax of norethindrone by 17%, which may be sufficient to decrease the effectiveness of combined oral contraceptives containing less than 1 mg of norethindrone (ethinyl estradiol; norethindrone, ethinyl estradiol; norethindrone acetate, mestranol; norethindrone); concurrent use of these products are contraindicated. Instead, the manufacturer recommends use of contraceptives that contain ethinyl estradiol and at least 1 mg of norethindrone. Boceprevir recipients and their partners are also required to use a second, non-hormonal, form of birth control while on therapy and for at least 6 months after treatment.
Estradiol; Norgestimate: (Major) Boceprevir reduces the Cmax of norethindrone by 17%, which may be sufficient to decrease the effectiveness of combined oral contraceptives containing less than 1 mg of norethindrone (ethinyl estradiol; norethindrone, ethinyl estradiol; norethindrone acetate, mestranol; norethindrone); concurrent use of these products are contraindicated. Instead, the manufacturer recommends use of contraceptives that contain ethinyl estradiol and at least 1 mg of norethindrone. Boceprevir recipients and their partners are also required to use a second, non-hormonal, form of birth control while on therapy and for at least 6 months after treatment.
Eszopiclone: (Major) The adult dose of eszopiclone should not exceed 2 mg/day during co-administration of potent CYP3A4 inhibitors, such as boceprevir. CYP3A4 is a primary metabolic pathway for eszopiclone, and increased systemic exposure to eszopiclone increases the risk of next-day psychomotor or memory impairment, which may decrease the ability to perform tasks requiring full mental alertness such as driving. If eszopiclone dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment.
Ethinyl Estradiol: (Major) Close clinical monitoring for signs of estrogen deficiency is advised when administering ethinyl estradiol in combination with boceprevir. When used concurrently, ethinyl estradiol plasma concentrations may be decreased, potentially resulting in impaired efficacy. If ethinyl estradiol dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment.
Ethinyl Estradiol; Desogestrel: (Major) Boceprevir reduces the Cmax of norethindrone by 17%, which may be sufficient to decrease the effectiveness of combined oral contraceptives containing less than 1 mg of norethindrone (ethinyl estradiol; norethindrone, ethinyl estradiol; norethindrone acetate, mestranol; norethindrone); concurrent use of these products are contraindicated. Instead, the manufacturer recommends use of contraceptives that contain ethinyl estradiol and at least 1 mg of norethindrone. Boceprevir recipients and their partners are also required to use a second, non-hormonal, form of birth control while on therapy and for at least 6 months after treatment. (Major) Close clinical monitoring for signs of estrogen deficiency is advised when administering ethinyl estradiol in combination with boceprevir. When used concurrently, ethinyl estradiol plasma concentrations may be decreased, potentially resulting in impaired efficacy. If ethinyl estradiol dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment.
Ethinyl Estradiol; Ethynodiol Diacetate: (Major) Boceprevir reduces the Cmax of norethindrone by 17%, which may be sufficient to decrease the effectiveness of combined oral contraceptives containing less than 1 mg of norethindrone (ethinyl estradiol; norethindrone, ethinyl estradiol; norethindrone acetate, mestranol; norethindrone); concurrent use of these products are contraindicated. Instead, the manufacturer recommends use of contraceptives that contain ethinyl estradiol and at least 1 mg of norethindrone. Boceprevir recipients and their partners are also required to use a second, non-hormonal, form of birth control while on therapy and for at least 6 months after treatment. (Major) Close clinical monitoring for signs of estrogen deficiency is advised when administering ethinyl estradiol in combination with boceprevir. When used concurrently, ethinyl estradiol plasma concentrations may be decreased, potentially resulting in impaired efficacy. If ethinyl estradiol dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment.
Ethinyl Estradiol; Etonogestrel: (Major) Close clinical monitoring for signs of estrogen deficiency is advised when administering ethinyl estradiol in combination with boceprevir. When used concurrently, ethinyl estradiol plasma concentrations may be decreased, potentially resulting in impaired efficacy. If ethinyl estradiol dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. (Major) Use of non-oral combination contraceptives with boceprevir have not been studied and are contraindicated. Patients receiving boceprevir in combination with ribavirin (and their partners) are required to use two reliable forms of contraception, including a non-hormonal form of birth control, while on therapy and for at least 6 months after treatment. The manufacturer states that one of reliable forms of contraception can be combined oral contraceptives containing ethinyl estradiol and at least 1 mg of norethindrone. Bceprevir is a potent inhibitor of CYP3A4, has been shown to reduce the Cmax of norethindrone by 17%, a decrease which may be sufficient to reduce the effectiveness of combined oral contraceptives containing less than 1 mg of norethindrone. Additionally, ethinyl estradiol plasma concentrations may be decreased is administered with boceprevir.
Ethinyl Estradiol; Levonorgestrel: (Major) Boceprevir reduces the Cmax of norethindrone by 17%, which may be sufficient to decrease the effectiveness of combined oral contraceptives containing less than 1 mg of norethindrone (ethinyl estradiol; norethindrone, ethinyl estradiol; norethindrone acetate, mestranol; norethindrone); concurrent use of these products are contraindicated. Instead, the manufacturer recommends use of contraceptives that contain ethinyl estradiol and at least 1 mg of norethindrone. Boceprevir recipients and their partners are also required to use a second, non-hormonal, form of birth control while on therapy and for at least 6 months after treatment. (Major) Close clinical monitoring for signs of estrogen deficiency is advised when administering ethinyl estradiol in combination with boceprevir. When used concurrently, ethinyl estradiol plasma concentrations may be decreased, potentially resulting in impaired efficacy. If ethinyl estradiol dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment.
Ethinyl Estradiol; Levonorgestrel; Ferrous bisglycinate: (Major) Boceprevir reduces the Cmax of norethindrone by 17%, which may be sufficient to decrease the effectiveness of combined oral contraceptives containing less than 1 mg of norethindrone (ethinyl estradiol; norethindrone, ethinyl estradiol; norethindrone acetate, mestranol; norethindrone); concurrent use of these products are contraindicated. Instead, the manufacturer recommends use of contraceptives that contain ethinyl estradiol and at least 1 mg of norethindrone. Boceprevir recipients and their partners are also required to use a second, non-hormonal, form of birth control while on therapy and for at least 6 months after treatment. (Major) Close clinical monitoring for signs of estrogen deficiency is advised when administering ethinyl estradiol in combination with boceprevir. When used concurrently, ethinyl estradiol plasma concentrations may be decreased, potentially resulting in impaired efficacy. If ethinyl estradiol dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment.
Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Major) Boceprevir reduces the Cmax of norethindrone by 17%, which may be sufficient to decrease the effectiveness of combined oral contraceptives containing less than 1 mg of norethindrone (ethinyl estradiol; norethindrone, ethinyl estradiol; norethindrone acetate, mestranol; norethindrone); concurrent use of these products are contraindicated. Instead, the manufacturer recommends use of contraceptives that contain ethinyl estradiol and at least 1 mg of norethindrone. Boceprevir recipients and their partners are also required to use a second, non-hormonal, form of birth control while on therapy and for at least 6 months after treatment. (Major) Close clinical monitoring for signs of estrogen deficiency is advised when administering ethinyl estradiol in combination with boceprevir. When used concurrently, ethinyl estradiol plasma concentrations may be decreased, potentially resulting in impaired efficacy. If ethinyl estradiol dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment.
Ethinyl Estradiol; Norelgestromin: (Major) Close clinical monitoring for signs of estrogen deficiency is advised when administering ethinyl estradiol in combination with boceprevir. When used concurrently, ethinyl estradiol plasma concentrations may be decreased, potentially resulting in impaired efficacy. If ethinyl estradiol dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. (Major) Use of non-oral combination contraceptives with boceprevir have not been studied and are contraindicated. Patients receiving boceprevir in combination with ribavirin (and their partners) are required to use two reliable forms of contraception, including a non-hormonal form of birth control, while on therapy and for at least 6 months after treatment. The manufacturer states that one of reliable forms of contraception can be combined oral contraceptives containing ethinyl estradiol and at least 1 mg of norethindrone. Bceprevir is a potent inhibitor of CYP3A4, has been shown to reduce the Cmax of norethindrone by 17%, a decrease which may be sufficient to reduce the effectiveness of combined oral contraceptives containing less than 1 mg of norethindrone. Additionally, ethinyl estradiol plasma concentrations may be decreased is administered with boceprevir.
Ethinyl Estradiol; Norethindrone Acetate: (Major) Boceprevir reduces the Cmax of norethindrone by 17%, which may be sufficient to decrease the effectiveness of combined oral contraceptives containing less than 1 mg of norethindrone (ethinyl estradiol; norethindrone, ethinyl estradiol; norethindrone acetate, mestranol; norethindrone); concurrent use of these products are contraindicated. Instead, the manufacturer recommends use of contraceptives that contain ethinyl estradiol and at least 1 mg of norethindrone. Boceprevir recipients and their partners are also required to use a second, non-hormonal, form of birth control while on therapy and for at least 6 months after treatment. (Major) Close clinical monitoring for signs of estrogen deficiency is advised when administering ethinyl estradiol in combination with boceprevir. When used concurrently, ethinyl estradiol plasma concentrations may be decreased, potentially resulting in impaired efficacy. If ethinyl estradiol dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment.
Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate: (Major) Boceprevir reduces the Cmax of norethindrone by 17%, which may be sufficient to decrease the effectiveness of combined oral contraceptives containing less than 1 mg of norethindrone (ethinyl estradiol; norethindrone, ethinyl estradiol; norethindrone acetate, mestranol; norethindrone); concurrent use of these products are contraindicated. Instead, the manufacturer recommends use of contraceptives that contain ethinyl estradiol and at least 1 mg of norethindrone. Boceprevir recipients and their partners are also required to use a second, non-hormonal, form of birth control while on therapy and for at least 6 months after treatment. (Major) Close clinical monitoring for signs of estrogen deficiency is advised when administering ethinyl estradiol in combination with boceprevir. When used concurrently, ethinyl estradiol plasma concentrations may be decreased, potentially resulting in impaired efficacy. If ethinyl estradiol dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment.
Ethinyl Estradiol; Norethindrone: (Major) Boceprevir reduces the Cmax of norethindrone by 17%, which may be sufficient to decrease the effectiveness of combined oral contraceptives containing less than 1 mg of norethindrone (ethinyl estradiol; norethindrone, ethinyl estradiol; norethindrone acetate, mestranol; norethindrone); concurrent use of these products are contraindicated. Instead, the manufacturer recommends use of contraceptives that contain ethinyl estradiol and at least 1 mg of norethindrone. Boceprevir recipients and their partners are also required to use a second, non-hormonal, form of birth control while on therapy and for at least 6 months after treatment. (Major) Close clinical monitoring for signs of estrogen deficiency is advised when administering ethinyl estradiol in combination with boceprevir. When used concurrently, ethinyl estradiol plasma concentrations may be decreased, potentially resulting in impaired efficacy. If ethinyl estradiol dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment.
Ethinyl Estradiol; Norethindrone; Ferrous fumarate: (Major) Boceprevir reduces the Cmax of norethindrone by 17%, which may be sufficient to decrease the effectiveness of combined oral contraceptives containing less than 1 mg of norethindrone (ethinyl estradiol; norethindrone, ethinyl estradiol; norethindrone acetate, mestranol; norethindrone); concurrent use of these products are contraindicated. Instead, the manufacturer recommends use of contraceptives that contain ethinyl estradiol and at least 1 mg of norethindrone. Boceprevir recipients and their partners are also required to use a second, non-hormonal, form of birth control while on therapy and for at least 6 months after treatment. (Major) Close clinical monitoring for signs of estrogen deficiency is advised when administering ethinyl estradiol in combination with boceprevir. When used concurrently, ethinyl estradiol plasma concentrations may be decreased, potentially resulting in impaired efficacy. If ethinyl estradiol dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment.
Ethinyl Estradiol; Norgestimate: (Major) Boceprevir reduces the Cmax of norethindrone by 17%, which may be sufficient to decrease the effectiveness of combined oral contraceptives containing less than 1 mg of norethindrone (ethinyl estradiol; norethindrone, ethinyl estradiol; norethindrone acetate, mestranol; norethindrone); concurrent use of these products are contraindicated. Instead, the manufacturer recommends use of contraceptives that contain ethinyl estradiol and at least 1 mg of norethindrone. Boceprevir recipients and their partners are also required to use a second, non-hormonal, form of birth control while on therapy and for at least 6 months after treatment. (Major) Close clinical monitoring for signs of estrogen deficiency is advised when administering ethinyl estradiol in combination with boceprevir. When used concurrently, ethinyl estradiol plasma concentrations may be decreased, potentially resulting in impaired efficacy. If ethinyl estradiol dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment.
Ethinyl Estradiol; Norgestrel: (Major) Boceprevir reduces the Cmax of norethindrone by 17%, which may be sufficient to decrease the effectiveness of combined oral contraceptives containing less than 1 mg of norethindrone (ethinyl estradiol; norethindrone, ethinyl estradiol; norethindrone acetate, mestranol; norethindrone); concurrent use of these products are contraindicated. Instead, the manufacturer recommends use of contraceptives that contain ethinyl estradiol and at least 1 mg of norethindrone. Boceprevir recipients and their partners are also required to use a second, non-hormonal, form of birth control while on therapy and for at least 6 months after treatment. (Major) Close clinical monitoring for signs of estrogen deficiency is advised when administering ethinyl estradiol in combination with boceprevir. When used concurrently, ethinyl estradiol plasma concentrations may be decreased, potentially resulting in impaired efficacy. If ethinyl estradiol dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment.
Ethosuximide: (Moderate) Close clinical monitoring is advised when administering ethosuximide with boceprevir due to an increased potential for ethosuximide-related adverse events. If ethosuximide dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of ethosuximide. Ethosuximide is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated ethosuximide plasma concentrations.
Etonogestrel: (Major) Use of non-oral combination contraceptives with boceprevir have not been studied and are contraindicated. Patients receiving boceprevir in combination with ribavirin (and their partners) are required to use two reliable forms of contraception, including a non-hormonal form of birth control, while on therapy and for at least 6 months after treatment. The manufacturer states that one of reliable forms of contraception can be combined oral contraceptives containing ethinyl estradiol and at least 1 mg of norethindrone. Bceprevir is a potent inhibitor of CYP3A4, has been shown to reduce the Cmax of norethindrone by 17%, a decrease which may be sufficient to reduce the effectiveness of combined oral contraceptives containing less than 1 mg of norethindrone. Additionally, ethinyl estradiol plasma concentrations may be decreased is administered with boceprevir.
Etoposide, VP-16: (Major) Monitor for an increased incidence of etoposide-related adverse effects if used concomitantly with boceprevir. Boceprevir is a strong inhibitor of CYP3A4 and a weak P-glycoprotein (P-gp) inhibitor; etoposide, VP-16 is a CYP3A4 and P-gp substrate. Coadministration may cause accumulation of etoposide and decreased metabolism, resulting in increased etoposide concentrations.
Etravirine: (Moderate) Etravirine and boceprevir may be given together without dosage adjustments; however, coadministration is not recommended if given in the presence of other drugs that may further decrease etravirine exposure (e.g., darunavir/ritonavir, lopinavir/ritonavir, saquinavir/ritonavir, tenofovir, rifabutin). Etravirine is a substrate and inducer of the hepatic isoenzyme CYP3A4; boceprevir is a substrate and an inhibitor of this isoenzyme. Additionally, etravirine is an inhibitor of the drug efflux transporter P-glycoprotein (P-gp); boceprevir is partially metabolized by this efflux protein. When used in combination, the Cmax, AUC and Cmin of etravirine are decreased.
Ezetimibe; Simvastatin: (Severe) The concurrent use of simvastatin and boceprevir is contraindicated due to the potential for serious/life-threatening reactions. Boceprevir is a potent inhibitor of CYP3A4, which is responsible simvastatin metabolism. Coadministration may result in large increases in simvastatin serum concentrations, which could cause adverse events such as myopathy and rhabdomyolysis.
Felodipine: (Moderate) Close clinical monitoring is advised when administering felodipine with boceprevir due to an increased potential for felodipine-related adverse events. If felodipine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Predictions about the interaction can be made based on the metabolic pathway of felodipine. Felodipine is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated felodipine plasma concentrations.
Fexofenadine: (Moderate) Close clinical monitoring is advised when administering fexofenadine with boceprevir due to an increased potential for fexofenadine-related adverse events. If fexofenadine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of fexofenadine. Fexofenadine is a substrate of the drug efflux transporter P-glycoprotein (P-gp); boceprevir is an inhibitor of this efflux protein. Coadministration may result in elevated fexofenadine plasma concentrations.
Fexofenadine; Pseudoephedrine: (Moderate) Close clinical monitoring is advised when administering fexofenadine with boceprevir due to an increased potential for fexofenadine-related adverse events. If fexofenadine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of fexofenadine. Fexofenadine is a substrate of the drug efflux transporter P-glycoprotein (P-gp); boceprevir is an inhibitor of this efflux protein. Coadministration may result in elevated fexofenadine plasma concentrations.
Flecainide: (Major) Close clinical monitoring is advised when administering flecainide with boceprevir due to an increased potential for serious and/or life-threatening flecainide-related adverse events. If flecainide dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment.
Flibanserin: (Severe) The concomitant use of flibanserin and strong CYP3A4 inhibitors, such as boceprevir, is contraindicated. Strong CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a strong CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a strong CYP3A4 inhibitor following flibanserin use, start the strong CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
Fluconazole: (Moderate) Close clinical monitoring is advised when administering fluconazole with boceprevir due to an increased potential for boceprevir-related adverse events. If fluconazole dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of fluconazole and boceprevir. Fluconazole is an inhibitor of the hepatic isoenzyme CYP3A4; boceprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of boceprevir may be elevated.
Fluoxetine: (Moderate) Close clinical monitoring is advised when administering fluoxetine with boceprevir due to an increased potential for boceprevir-related adverse events. If fluoxetine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of fluoxetine and boceprevir. Fluoxetine is an inhibitor of the hepatic isoenzyme CYP3A4; boceprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of boceprevir may be elevated.
Fluoxetine; Olanzapine: (Moderate) Close clinical monitoring is advised when administering fluoxetine with boceprevir due to an increased potential for boceprevir-related adverse events. If fluoxetine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of fluoxetine and boceprevir. Fluoxetine is an inhibitor of the hepatic isoenzyme CYP3A4; boceprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of boceprevir may be elevated.
Flurazepam: (Moderate) Close clinical monitoring is advised when administering flurazepam with boceprevir due to an increased potential for flurazepam-related adverse events. If flurazepam dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of flurazepam. Flurazepam is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated flurazepam plasma concentrations.
Flutamide: (Moderate) Close clinical monitoring is advised when administering flutamide with boceprevir due to an increased potential for flutamide-related adverse events and the potential for boceprevir treatment failure. If flutamide dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of flutamide and boceprevir. Flutamide is a substrate and inducer of the hepatic isoenzyme CYP3A4; boceprevir is a substrate and an inhibitor of this isoenzyme. When used in combination, the plasma concentrations of flutamide may increase and the plasma concentrations of boceprevir may decrease, resulting in an increased risk for flutamide-related adverse events and decreased boceprevir efficacy.
Fluticasone; Salmeterol: (Major) Concurrent administration of salmeterol with boceprevir is not recommended. If salmeterol and boceprevir are coadministered, monitor the patient closely for salmeterol-related cardiovascular adverse events, such as QT interval prolongation, palpitations, and sinus tachycardia.
Fluvoxamine: (Moderate) Close clinical monitoring is advised when administering fluvoxamine with boceprevir due to an increased potential for boceprevir-related adverse events. If fluvoxamine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of fluvoxamine and boceprevir. Fluvoxamine is an inhibitor of the hepatic isoenzyme CYP3A4; boceprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of boceprevir may be elevated.
Formoterol; Mometasone: (Moderate) Concomitant administration of boceprevir and mometasone may increase systemic exposure to mometasone, increasing the risk of corticosteroid-related adverse events. Exercise caution when administering mometasone with boceprevir long-term and monitor closely for hypercorticism and adrenal suppression. Mometasone is a CYP3A4 substrate and boceprevir is a strong CYP3A4 inhibitor.
Fosamprenavir: (Major) Due to the potential for HIV and hepatitis C treatment failures, concurrent administration of fosamprenavir and boceprevir is not recommended. Concurrent administration is predicted to decrease the concentrations of both fosamprenavir and boceprevir. If fosamprenavir/ritonavir and boceprevir are coadministered, monitor the patient closely for HIV and hepatitis C treatment failures.
Fosphenytoin: (Severe) The potential for boceprevir treatment failure exists when boceprevir is administered with fosphenytoin; therefore, the concurrent use of these medications is contraindicated. Fosphenytoin is a potent inducer of CYP3A4, which is partially responsible for boceprevir metabolism. Coadministration may result in decreased boceprevir serum concentrations, which could result in impaired virologic response to boceprevir.
Galantamine: (Moderate) Close clinical monitoring is advised when administering galantamine with boceprevir due to an increased potential for galantamine-related adverse events. If galantamine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of galantamine. Galantamine is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated galantamine plasma concentrations.
Glyburide: (Moderate) Close clinical monitoring is advised when administering glyburide with boceprevir due to an increased potential for glyburide-related adverse events. If glyburide dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of glyburide. Glyburide is a substrate of the drug efflux transporter P-glycoprotein (PGP); boceprevir is an inhibitor of this efflux protein. Coadministration may result in elevated glyburide plasma concentrations.
Glyburide; Metformin: (Moderate) Close clinical monitoring is advised when administering glyburide with boceprevir due to an increased potential for glyburide-related adverse events. If glyburide dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of glyburide. Glyburide is a substrate of the drug efflux transporter P-glycoprotein (PGP); boceprevir is an inhibitor of this efflux protein. Coadministration may result in elevated glyburide plasma concentrations.
Granisetron: (Moderate) Close clinical monitoring is advised when administering granisetron with boceprevir due to an increased potential for granisetron-related adverse events. If granisetron dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of granisetron. Granisetron is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated granisetron plasma concentrations.
Grapefruit juice: (Moderate) Close clinical monitoring is advised when administering grapefruit juice with boceprevir due to an increased potential for boceprevir-related adverse events. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of grapefruit juice and boceprevir. Grapefruit juice is an inhibitor of the hepatic isoenzyme CYP3A4; boceprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of boceprevir may be elevated.
Guaifenesin; Hydrocodone: (Major) Monitor for respiratory depression and sedation if hydrocodone and boceprevir are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as boceprevir, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects.
Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Monitor for respiratory depression and sedation if hydrocodone and boceprevir are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as boceprevir, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects.
Guanfacine: (Major) Boceprevir may significantly increase guanfacine plasma concentrations. FDA-approved labeling for extended-release (ER) guanfacine recommends that, if these agents are taken together, the guanfacine dosage should be decreased to half of the recommended dose. Specific recommendations for immediate-release (IR) guanfacine are not available. Monitor patients closely for alpha-adrenergic effects including hypotension, drowsiness, lethargy, and bradycardia. If boceprevir is discontinued, the guanfacine ER dosage should be increased back to the recommended dose. Guanfacine is primarily metabolized by CYP3A4, and boceprevir is a strong CYP3A4 inhibitor.
Halofantrine: (Moderate) Close clinical monitoring is advised when administering halofantrine with boceprevir due to an increased potential for halofantrine-related adverse events. If halofantrine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of halofantrine. Halofantrine is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated halofantrine plasma concentrations.
Haloperidol: (Moderate) Boceprevir is a substrate and inhibitor of CYP3A4, one of the isoenzymes responsible for the metabolism of haloperidol. Mild to moderate increases in haloperidol plasma concentrations have been reported during concurrent use of haloperidol and substrates or inhibitors of CYP3A4. Elevated haloperidol concentrations occurring through inhibition of CYP3A4 may increase the risk of adverse effects, including QT prolongation. Until more data are available, it is advisable to closely monitor for adverse events when these medications are co-administered.
Homatropine; Hydrocodone: (Major) Monitor for respiratory depression and sedation if hydrocodone and boceprevir are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as boceprevir, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects.
Hydrochlorothiazide, HCTZ; Losartan: (Moderate) Close clinical monitoring is advised when administering losartan with boceprevir due to an increased potential for losartan-related adverse events. If losartan dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of losartan. Losartan is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated losartan plasma concentrations.
Hydrocodone: (Major) Monitor for respiratory depression and sedation if hydrocodone and boceprevir are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as boceprevir, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects.
Hydrocodone; Ibuprofen: (Major) Monitor for respiratory depression and sedation if hydrocodone and boceprevir are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as boceprevir, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects.
Hydrocodone; Phenylephrine: (Major) Monitor for respiratory depression and sedation if hydrocodone and boceprevir are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as boceprevir, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects.
Hydrocodone; Potassium Guaiacolsulfonate: (Major) Monitor for respiratory depression and sedation if hydrocodone and boceprevir are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as boceprevir, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects.
Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Major) Monitor for respiratory depression and sedation if hydrocodone and boceprevir are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as boceprevir, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects.
Hydrocodone; Pseudoephedrine: (Major) Monitor for respiratory depression and sedation if hydrocodone and boceprevir are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as boceprevir, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects.
Ibrutinib: (Severe) Do not use ibrutinib concomitantly with boceprevir; boceprevir is contraindicated for use with medications that are highly dependent on CYP3A4 for clearance and are associated with serious and/or life-threatening events. Significantly increased ibrutinib levels may occur. Consider the use of alternate agents. Ibrutinib is a CYP3A4 substrate; boceprevir is a strong CYP3A inhibitor. When ibrutinib was administered with multiple doses of other strong CYP3A4 inhibitors, the Cmax and AUC values of ibrutinib were increased significantly.
Ibuprofen; Oxycodone: (Moderate) Close clinical monitoring is advised when administering oxycodone with boceprevir due to an increased potential for oxycodone-related adverse events. If oxycodone dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of oxycodone. Oxycodone is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated oxycodone plasma concentrations.
Idelalisib: (Major) Concomitant use of idelalisib, a CYP3A4 substrate, and boceprevir, a strong CYP3A4 inhibitor, may increase the exposure of idelalisib. Additionally, idelalisib is a strong CYP3A inhibitor while boceprevir is a CYP3A substrate. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Avoid concomitant use of idelalisib and boceprevir.
Imatinib: (Moderate) Close clinical monitoring is advised when administering imatinib, STI-571 with boceprevir due to an increased potential for imatinib-related adverse events. If imatinib dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of imatinib and boceprevir. Both imatinib and boceprevir are substrates and inhibitors of the hepatic isoenzyme CYP3A4. When used in combination, the plasma concentrations of both medications may be elevated.
Imipramine: (Moderate) Close clinical monitoring is advised when administering imipramine with boceprevir due to an increased potential for imipramine-related adverse events. If imipramine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of imipramine. Imipramine is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated imipramine plasma concentrations.
Indinavir: (Moderate) Close clinical monitoring is advised when administering indinavir with boceprevir due to an increased potential for indinavir-related adverse events. If indinavir dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of indinavir and boceprevir. Both indinavir and boceprevir are substrates and inhibitors of the hepatic isoenzyme CYP3A4. When used in combination, the plasma concentrations of both medications may be elevated.
Isavuconazonium: (Severe) Concomitant use of isavuconazonium with boceprevir is contraindicated due to the risk for increased isavuconazole serum concentrations and serious adverse reactions, such as hepatic toxicity. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; bocepravir is a strong inhibitor of this enzyme. According to the manufacturer, coadministration of isavuconazole with strong CYP3A4 inhibitors is contraindicated. Isavuconazole serum concentrations were increased 5-fold when coadministered with ketoconazole, another strong CYP3A4 inhibitor. Elevated boceprevir concentrations would also be expected with coadministration, as boceprevir is a substrate of CYP3A4 and the P-glycoprotein (P-gp) drug transporter and isavuconazole is an inhibitor of CYP3A4 and P-gp.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Severe) The potential for boceprevir treatment failure exists when boceprevir is administered with rifampin; concurrent use is contraindicated. Rifampin is a potent inducer of CYP3A4, which is partially responsible for boceprevir metabolism. Coadministration may result in decreased boceprevir serum concentrations and impaired virologic response.
Isoniazid, INH; Rifampin: (Severe) The potential for boceprevir treatment failure exists when boceprevir is administered with rifampin; concurrent use is contraindicated. Rifampin is a potent inducer of CYP3A4, which is partially responsible for boceprevir metabolism. Coadministration may result in decreased boceprevir serum concentrations and impaired virologic response.
Isradipine: (Moderate) Close clinical monitoring is advised when administering isradipine with boceprevir due to an increased potential for isradipine-related adverse events. If isradipine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of isradipine. Isradipine is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated isradipine plasma concentrations.
Itraconazole: (Major) Close clinical monitoring is advised when administering itraconazole with boceprevir due to an increased potential for itraconazole and boceprevir-related adverse events. When concurrent administration is required, high doses of itraconazole (> 200 mg/day) are not recommended. If itraconazole dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Predictions about the interaction can be made based on the metabolic pathways of itraconazole and boceprevir. Both itraconazole and boceprevir are substrates and inhibitors of the drug efflux transporter P-glycoprotein (P-gp) and the hepatic isoenzyme CYP3A4. When used in combination, the plasma concentrations of both medications may be elevated.
Ivabradine: (Severe) Coadministration of ivabradine and boceprevir is contraindicated. Ivabradine is primarily metabolized by CYP3A4; boceprevir is a strong CYP3A4 inhibitor. Coadministration will increase the plasma concentrations of ivabradine. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
Ivacaftor: (Major) If boceprevir and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to twice weekly (e.g., if the usual dosage is 150 mg twice daily, reduce to 150 mg twice weekly). Ivacaftor is a CYP3A substrate, and boceprevir is a strong CYP3A inhibitor. Coadministration with ketoconazole, another strong CYP3A inhibitor, increased ivacaftor exposure by 8.5-fold. Ivacaftor is also an inhibitor of CYP3A and P-glycoprotein (P-gp); boceprevir is metabolized by CYP3A4 and is a substrate of P-gp. Coadministration may increase boceprevir exposure leading to increased or prolonged therapeutic effects and adverse events.
Ivermectin: (Moderate) Close clinical monitoring is advised when administering ivermectin with boceprevir due to an increased potential for ivermectin-related adverse events. If ivermectin dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of ivermectin. Ivermectin is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated ivermectin plasma concentrations.
Ixabepilone: (Moderate) Close clinical monitoring is advised when administering ixabepilone with boceprevir due to an increased potential for ixabepilone-related adverse events. If ixabepilone dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of ixabepilone. Ixabepilone is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated ixabepilone plasma concentrations.
Ketoconazole: (Major) Close clinical monitoring is advised when administering ketoconazole with boceprevir due to an increased potential for serious ketoconazole and boceprevir-related adverse events, such as QT prolongation. When concurrent administration is required, high doses of ketoconazole (> 200 mg/day) are not recommended. If ketoconazole dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Predictions about the interaction can be made based on the metabolic pathways of ketoconazole and boceprevir. Both ketoconazole and boceprevir are substrates and inhibitors of the hepatic isoenzyme CYP3A4. Additionally, ketoconazole is an inhibitor of P-glycoprotein (P-gp), a drug efflux transporter partially responsible for the metabolism of boceprevir. When used in combination, the plasma concentrations of both medications may be elevated.
Lacosamide: (Moderate) Use caution during concurrent use of lacosamide and boceprevir, particularly in patients with renal or hepatic impairment. Lacosamide is a CYP3A4 substrate; boceprevir is a potent inhibitor of CYP3A4. Patients with renal or hepatic impairment may have significantly increased exposure to lacosamide if coadminsitered with a strong CYP3A4 inhibitor. Dosage reduction of lacosamide may be necessary in this population.
Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as boceprevir. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Lansoprazole: (Moderate) Close clinical monitoring is advised when administering lansoprazole with boceprevir due to an increased potential for lansoprazole-related adverse events. If lansoprazole dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of lansoprazole. Lansoprazole is a CYP3A4 substrate; boceprevir is a CYP3A4 inhibitor. Coadministration may result in elevated lansoprazole plasma concentrations.
Lansoprazole; Naproxen: (Moderate) Close clinical monitoring is advised when administering lansoprazole with boceprevir due to an increased potential for lansoprazole-related adverse events. If lansoprazole dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of lansoprazole. Lansoprazole is a CYP3A4 substrate; boceprevir is a CYP3A4 inhibitor. Coadministration may result in elevated lansoprazole plasma concentrations.
Ledipasvir; Sofosbuvir: (Moderate) Caution and close monitoring of adverse reactions is advised with concomitant administration of boceprevir and ledipasvir; sofosbuvir. Both ledipasvir and boceprevir are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp); sofosbuvir is a P-gp substrate. Taking these drugs together may increase plasma concentrations of all three drugs. According to the manufacturer, no dosage adjustments are required when ledipasvir; sofosbuvir is administered concurrently with P-gp inhibitors.
Lesinurad: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of boceprevir; monitor for potential reduction in efficacy. Boceprevir is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Lesinurad; Allopurinol: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of boceprevir; monitor for potential reduction in efficacy. Boceprevir is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Leuprolide; Norethindrone: (Major) Boceprevir reduces the Cmax of norethindrone by 17%, which may be sufficient to decrease the effectiveness of combined oral contraceptives containing less than 1 mg of norethindrone (ethinyl estradiol; norethindrone, ethinyl estradiol; norethindrone acetate, mestranol; norethindrone); concurrent use of these products are contraindicated. Instead, the manufacturer recommends use of contraceptives that contain ethinyl estradiol and at least 1 mg of norethindrone. Boceprevir recipients and their partners are also required to use a second, non-hormonal, form of birth control while on therapy and for at least 6 months after treatment.
Levomilnacipran: (Major) The adult dose of levomilnacipran should not exceed 80 mg/day during concurrent use of strong CYP3A4 inhibitors. Boceprevir is considered a strong inhibitor of CYP3A4. Levomilnacipran is partially metabolized by CYP3A4, and decreased metabolism of the drug can lead to an increased risk of adverse effects such as urinary retention.
Levonorgestrel: (Major) Boceprevir reduces the Cmax of norethindrone by 17%, which may be sufficient to decrease the effectiveness of combined oral contraceptives containing less than 1 mg of norethindrone (ethinyl estradiol; norethindrone, ethinyl estradiol; norethindrone acetate, mestranol; norethindrone); concurrent use of these products are contraindicated. Instead, the manufacturer recommends use of contraceptives that contain ethinyl estradiol and at least 1 mg of norethindrone. Boceprevir recipients and their partners are also required to use a second, non-hormonal, form of birth control while on therapy and for at least 6 months after treatment.
Lidocaine: (Major) Close clinical monitoring is advised when administering systemic lidocaine with boceprevir due to an increased potential for serious and/or life-threatening lidocaine-related adverse events. If lidocaine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of lidocaine. Lidocaine is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated lidocaine plasma concentrations.
Linagliptin: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. A possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic therapy, such as linagliptin, should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
Linagliptin; Metformin: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. A possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic therapy, such as linagliptin, should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
Lomitapide: (Severe) Concomitant use of boceprevir and lomitapide is contraindicated. If treatment with boceprevir is unavoidable, lomitapide should be stopped during the course of treatment. Boceprevir is a strong CYP3A4 inhibitor. The exposure to lomitapide was increased 27-fold in the presence of ketoconazole, a strong CYP3A4 inhibitor.
Loperamide: (Moderate) The plasma concentration of loperamide, a CYP3A4 and P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with boceprevir, a CYP3A4 and P-gp inhibitor. If these drugs are used together, monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest).
Loperamide; Simethicone: (Moderate) The plasma concentration of loperamide, a CYP3A4 and P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with boceprevir, a CYP3A4 and P-gp inhibitor. If these drugs are used together, monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest).
Lopinavir; Ritonavir: (Major) Concurrent administration of lopinavir; ritonavir with boceprevir is not recommended due to the potential for HIV and hepatitis C treatment failures. Use of this combination has resulted in decreased serum concentrations of both drugs. Lopinavir; ritonavir is an inhibitor, inducer, and substrate of CYP3A4; boceprevir is an inhibitor and substrate of this isoenzyme. Additionally, both are substrates and inhibitors of the drug efflux transporter P-glycoprotein (P-gp). If these drugs are coadministered, health care providers are advised to closely monitor for decreased treatment response and virologic rebound. Health care providers are also encouraged to report any drug-related adverse reactions to the FDA MedWatch Program. (Major) Concurrent administration of ritonavir with boceprevir is not recommended due to the potential for HIV and hepatitis C treatment failures. This combination has resulted in decreased serum concentrations of both medications. Ritonavir is an inhibitor, inducer, and substrate of the hepatic isoenzyme CYP3A4; boceprevir is an inhibitor and substrate of this isoenzyme. Additionally, both drugs are substrates and inhibitors of the drug efflux transporter P-glycoprotein (PGP). If these drugs are coadministered, health care providers are advised to closely monitor for decreased treatment response and virologic rebound. Health care providers are also encouraged to report any drug-related adverse reactions to the FDA MedWatch Program.
Losartan: (Moderate) Close clinical monitoring is advised when administering losartan with boceprevir due to an increased potential for losartan-related adverse events. If losartan dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of losartan. Losartan is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated losartan plasma concentrations.
Lovastatin: (Severe) Concurrent use of lovastatin and boceprevir is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with boceprevir. Lovastatin is a substrate of CYP3A4 and boceprevir is a strong inhibitor of CYP3A4; therefore, coadministration may result in substantial increases in plasma concentrations of lovastatin.
Lovastatin; Niacin: (Severe) Concurrent use of lovastatin and bocepre vir is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with boceprevir. Lovastatin is a substrate of CYP3A4 and boceprevir is a strong inhibitor of CYP3A4; therefore, coadministration may result in substantial increases in plasma concentrations of lovastatin.
Lumacaftor; Ivacaftor: (Severe) Concomitant use of lumacaftor; ivacaftor and boceprevir is contraindicated due to the risk for reduced boceprevir efficacy. Boceprevir is a substrate of CYP3A, and lumacaftor is a strong CYP3A inducer. (Major) If boceprevir and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to twice weekly (e.g., if the usual dosage is 150 mg twice daily, reduce to 150 mg twice weekly). Ivacaftor is a CYP3A substrate, and boceprevir is a strong CYP3A inhibitor. Coadministration with ketoconazole, another strong CYP3A inhibitor, increased ivacaftor exposure by 8.5-fold. Ivacaftor is also an inhibitor of CYP3A and P-glycoprotein (P-gp); boceprevir is metabolized by CYP3A4 and is a substrate of P-gp. Coadministration may increase boceprevir exposure leading to increased or prolonged therapeutic effects and adverse events.
Lumacaftor; Ivacaftor: (Severe) Concomitant use of lumacaftor; ivacaftor and boceprevir is contraindicated due to the risk for reduced boceprevir efficacy. Boceprevir is a substrate of CYP3A, and lumacaftor is a strong CYP3A inducer.
Lurasidone: (Severe) Concurrent use of lurasidone with strong CYP3A4 inhibitors, such as boceprevir, is contraindicated. Lurasidone is primarily metabolized by CYP3A4. Increased lurasidone plasma concentrations are expected when the drug is co-administered with inhibitors of CYP3A4.
Macitentan: (Major) Avoid concurrent use of macitentan and boceprevir. Boceprevir is a strong inhibitor of CYP3A4. Coadminsitration of macitentan with another strong CYP3A4 inhibitor (ketoconazole) approximately doubles macitentan exposure. Consider alternative treatment options for pulmonary hypertension if treatment with boceprevir is necessary.
Maraviroc: (Major) Coadministration of maraviroc, a CYP3A/P-gp substrate, with boceprevir, a strong CYP3A4 inhibitor and P-gp inhibitor, may result in increased maraviroc concentrations. Reduce the dose of maraviroc when coadministered with strong CYP3A inhibitors; coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCl less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with boceprevir (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily.
Mefloquine: (Moderate) Close clinical monitoring is advised when administering mefloquine with boceprevir due to an increased potential for mefloquine-related adverse events. If mefloquine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of mefloquine. Mefloquine is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; boceprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated mefloquine plasma concentrations.
Meloxicam: (Moderate) Close clinical monitoring is advised when administering meloxicam with boceprevir due to an increased potential for meloxicam-related adverse events. If meloxicam dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of meloxicam. Meloxicam is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated meloxicam plasma concentrations.
Mestranol; Norethindrone: (Major) Boceprevir reduces the Cmax of norethindrone by 17%, which may be sufficient to decrease the effectiveness of combined oral contraceptives containing less than 1 mg of norethindrone (ethinyl estradiol; norethindrone, ethinyl estradiol; norethindrone acetate, mestranol; norethindrone); concurrent use of these products are contraindicated. Instead, the manufacturer recommends use of contraceptives that contain ethinyl estradiol and at least 1 mg of norethindrone. Boceprevir recipients and their partners are also required to use a second, non-hormonal, form of birth control while on therapy and for at least 6 months after treatment.
Metformin; Repaglinide: (Moderate) Close clinical monitoring is advised when administering repaglinide with boceprevir due to an increased potential for repaglinide-related adverse events. If repaglinide dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of repaglinide. Repaglinide is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated repaglinide plasma concentrations.
Methadone: (Moderate) Close clinical monitoring is advised when administering methadone with boceprevir due to the potential for decreased methadone efficacy. The dose of methadone may need to be adjusted during therapy. If methadone dose adjustments are made, they should be re-adjusted upon completion of boceprevir treatment.
Methylergonovine: (Severe) Concurrent use of ergot alkaloids and boceprevir is contraindicated due to the potential for serious/life-threatening ergot toxicities, such as peripheral vasospasm and ischemia of the extremities and other tissues. Boceprevir is a potent inhibitor of CYP3A4, which is responsible for the metabolism of ergot alkaloids. Coadministration may result in large increases in ergot alkaloid serum concentrations, which could cause fatal ergot toxicities.
Methylprednisolone: (Major) Concomitant use of systemic methylprednisolone with boceprevir may result in increased plasma concentrations of methylprednisolone, resulting in significantly reduced serum cortisol concentrations. Avoid coadministration if possible, particularly for extended durations. Methylprednisolone is a CYP3A4 substrate; boceprevir is a strong inhibitor of CYP3A4. Coadministration may result in elevated methylprednisolone plasma concentrations. For long-term use, consider an alternative corticosteroid, such as beclomethasone or prednisolone, if appropriate. whose concentrations are less affected by strong CYP3A4 inhibitors.
Methysergide: (Severe) Concurrent use of ergot alkaloids and boceprevir is contraindicated due to the potential for serious/life-threatening ergot toxicities, such as peripheral vasospasm and ischemia of the extremities and other tissues. Boceprevir is a potent inhibitor of CYP3A4, which is responsible for the metabolism of ergot alkaloids. Coadministration may result in large increases in ergot alkaloid serum concentrations, which could cause fatal ergot toxicities.
Midazolam: (Severe) Concurrent use of oral midazolam and boceprevir is contraindicated due to the risk of life threatening reactions, such as prolonged or increased sedation or respiratory depression. Boceprevir is a potent inhibitor of CYP3A4, which is responsible for the metabolism orally administered midazolam. Coadministration may result in large increases in midazolam serum concentrations, which could cause fatal toxicities. Increased midazolam serum concentrations resulting from boceprevir CYP3A4 inhibition are higher for oral midazolam than for the intravenous formulation; use of intravenous midazolam is not contraindicated with boceprevir, although dosage adjustments and close monitoring for respiratory depression and/or prolonged sedation is recommended. Lorazepam, oxazepam, or temazepam may be safer alternatives if a benzodiazepine must be administered in combination with boceprevir, as they are not oxidatively metabolized.
Mifepristone: (Major) Medications that are potent CYP3A inhibitors, such as boceprevir, are expected to increase plasma mifepristone concentrations. A dose reduction of the current dose of mifepristone may be required when mifepristone is used chronically to treat hormonal conditions, such as Cushing's disease. Adjust to clinical response. Limit the maximum dose of mifepristone to 600 mg/day PO. In a patient already receiving boceprevir, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 600 mg/day if clinically indicated. If therapy with boceprevir is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with boceprevir is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg/day and titrate to a maximum of 600 mg/day if clinically indicated. If therapy with boceprevir is initiated in a patient already receiving mifepristone 900 mg or 1200 mg, reduce the mifepristone dose to 600 mg/day. Also, CYP3A inhibitors like mifepristone may increase plasma concentrations of boceprevir. Monitor for boceprevir-related adverse effects due to increased boceprevir concentrations. Due to the slow elimination of mifepristone from the body, interactions that occur may be prolonged.
Mirtazapine: (Moderate) Close clinical monitoring is advised when administering mirtazapine with boceprevir due to an increased potential for mirtazapine-related adverse events. If mirtazapine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of mirtazapine. Mirtazapine is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated mirtazapine plasma concentrations.
Mitomycin: (Moderate) Close clinical monitoring is advised when administering mitomycin with boceprevir due to an increased potential for mitomycin-related adverse events. If mitomycin dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of mitomycin. Mitomycin is a substrate of the drug efflux transporter P-glycoprotein (PGP); boceprevir is an inhibitor of this efflux protein. Coadministration may result in elevated mitomycin plasma concentrations.
Mitotane: (Severe) Boceprevir is contraindicated for use with mitotane. Mitotane is a strong CYP3A4 inducer and boceprevir is a CYP3A4 substrate; coadministration significantly reduces plasma concentrations of boceprevir, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance.
Modafinil: (Moderate) Close clinical monitoring is advised when administering modafinil with boceprevir due to an increased potential for modafinil-related adverse events and the potential for boceprevir treatment failure. If modafinil dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of modafinil and boceprevir. Modafinil is a substrate and inducer of the hepatic isoenzyme CYP3A4; boceprevir is a substrate and an inhibitor of this isoenzyme. When used in combination, the plasma concentrations of modafinil may increase and the plasma concentrations of boceprevir may decrease.
Mometasone: (Moderate) Concomitant administration of boceprevir and mometasone may increase systemic exposure to mometasone, increasing the risk of corticosteroid-related adverse events. Exercise caution when administering mometasone with boceprevir long-term and monitor closely for hypercorticism and adrenal suppression. Mometasone is a CYP3A4 substrate and boceprevir is a strong CYP3A4 inhibitor.
Morphine: (Moderate) Close clinical monitoring is advised when administering morphine with boceprevir due to an increased potential for morphine-related adverse events. If morphine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of morphine. Morphine is a substrate of the drug efflux transporter P-glycoprotein (P-gp); boceprevir is an inhibitor of this efflux protein. Coadministration may result in elevated morphine plasma concentrations.
Morphine; Naltrexone: (Moderate) Close clinical monitoring is advised when administering morphine with boceprevir due to an increased potential for morphine-related adverse events. If morphine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of morphine. Morphine is a substrate of the drug efflux transporter P-glycoprotein (P-gp); boceprevir is an inhibitor of this efflux protein. Coadministration may result in elevated morphine plasma concentrations.
Nafcillin: (Moderate) Close clinical monitoring is advised when administering nafcillin with boceprevir due to the potential for boceprevir treatment failure. If nafcillin dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of nafcillin and boceprevir. Nafcillin is an inducer of the hepatic isoenzyme CYP3A4; boceprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of boceprevir may decrease, resulting in decreased boceprevir efficacy.
Nefazodone: (Moderate) Close clinical monitoring is advised when administering nefazodone with boceprevir due to an increased potential for nefazodone-related adverse events. If nefazodone dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of nefazodone and boceprevir. Both nefazodone and boceprevir are substrates and inhibitors of the hepatic isoenzyme CYP3A4. When used in combination, the plasma concentrations of both medications may be elevated.
Nelfinavir: (Moderate) Close clinical monitoring is advised when administering nelfinavir with boceprevir due to an increased potential for nelfinavir-related adverse events. If nelfinavir dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of nelfinavir and boceprevir. Both nelfinavir and boceprevir are substrates and inhibitors of the hepatic isoenzyme CYP3A4 and the drug efflux transporter, P-glycoprotein (PGP). When used in combination, the plasma concentrations of both medications may be elevated.
Neratinib: (Major) Avoid concomitant use of boceprevir with neratinib due to an increased risk of neratinib-related toxicity. Neratinib is a CYP3A4 substrate and boceprevir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased neratinib exposure by 481%; concomitant use with other strong inhibitors of CYP3A4 may also increase neratinib concentrations.
Netupitant, Fosnetupitant; Palonosetron: (Moderate) Netupitant is a moderate inhibitor of CYP3A4 and should be used with caution in patients receiving concomitant medications that are primarily metabolized through CYP3A4 since the plasma concentrations of the primary substrate can increase; the inhibitory effect on CYP3A4 can last for multiple days. Boceprevir is partially metabolized by CYP3A4. In addition, netupitant is mainly metabolized by CYP3A4. Coadministration of netupitant; palonosetron with a strong CYP3A4 inhibitor can significantly increase the systemic exposure to netupitant. Boceprevir is a strong CYP3A4 inhibitor. No dosage adjustment is necessary for single dose administration of netupitant; palonosetron.
Nevirapine: (Major) Nevirapine and boceprevir should not be coadministered due to the potential for boceprevir treatment failure. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of nevirapine and boceprevir. Plasma concentrations of boceprevir may be decreased due to induction of CYP3A4/5 by nevirapine.
Niacin; Simvastatin: (Severe) The concurrent use of simvastatin and boceprevir is contraindicated due to the potential for serious/life-threatening reactions. Boceprevir is a potent inhibitor of CYP3A4, which is responsible simvastatin metabolism. Coadministration may result in large increases in simvastatin serum concentrations, which could cause adverse events such as myopathy and rhabdomyolysis.
Nicardipine: (Moderate) Close clinical monitoring is advised when administering nicardipine with boceprevir due to increased potential for nicardipine-related adverse events. When used in combination, the plasma concentrations of nicardipine were increased. If nicardipine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment.
Nintedanib: (Moderate) Dual inhibitors of P-glycoprotein (P-gp) and CYP3A4, such as boceprevir, are expected to increase the exposure and clinical effect of nintedanib. If use together is necessary, closely monitor for increased nintedanib side effects including gastrointestinal toxicity (nausea, vomiting, diarrhea, abdominal pain, loss of appetite), headache, elevated liver enzymes, and hypertension. A dose reduction, interruption of therapy, or discontinuation of nintedanib therapy may be necessary. Boceprevir is a potent inhibitor of CYP3A4 and a mild P--gp inhibitor; nintedanib is a P-gp substrate, and a minor substrate of CYP3A4. Administration of nintedanib with a dual P-gp and CYP3A4 inhibitor increased nintedanib AUC by 60%.
Nisoldipine: (Moderate) Close clinical monitoring is advised when administering nisoldipine with boceprevir due to an increased potential for nisoldipine-related adverse events. If nisoldipine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Predictions about the interaction can be made based on the metabolic pathway of nisoldipine. Nisoldipine is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated nisoldipine plasma concentrations.
Non-oral combination contraceptives: (Major) Use of non-oral combination contraceptives with boceprevir have not been studied and are contraindicated. Patients receiving boceprevir in combination with ribavirin (and their partners) are required to use two reliable forms of contraception, including a non-hormonal form of birth control, while on therapy and for at least 6 months after treatment. The manufacturer states that one of reliable forms of contraception can be combined oral contraceptives containing ethinyl estradiol and at least 1 mg of norethindrone. Bceprevir is a potent inhibitor of CYP3A4, has been shown to reduce the Cmax of norethindrone by 17%, a decrease which may be sufficient to reduce the effectiveness of combined oral contraceptives containing less than 1 mg of norethindrone. Additionally, ethinyl estradiol plasma concentrations may be decreased is administered with boceprevir.
Norethindrone: (Major) Boceprevir reduces the Cmax of norethindrone by 17%, which may be sufficient to decrease the effectiveness of combined oral contraceptives containing less than 1 mg of norethindrone (ethinyl estradiol; norethindrone, ethinyl estradiol; norethindrone acetate, mestranol; norethindrone); concurrent use of these products are contraindicated. Instead, the manufacturer recommends use of contraceptives that contain ethinyl estradiol and at least 1 mg of norethindrone. Boceprevir recipients and their partners are also required to use a second, non-hormonal, form of birth control while on therapy and for at least 6 months after treatment.
Norgestrel: (Major) Boceprevir reduces the Cmax of norethindrone by 17%, which may be sufficient to decrease the effectiveness of combined oral contraceptives containing less than 1 mg of norethindrone (ethinyl estradiol; norethindrone, ethinyl estradiol; norethindrone acetate, mestranol; norethindrone); concurrent use of these products are contraindicated. Instead, the manufacturer recommends use of contraceptives that contain ethinyl estradiol and at least 1 mg of norethindrone. Boceprevir recipients and their partners are also required to use a second, non-hormonal, form of birth control while on therapy and for at least 6 months after treatment.
Nortriptyline: (Moderate) Close clinical monitoring is advised when administering nortriptyline with boceprevir due to an increased potential for nortriptyline-related adverse events. If nortriptyline dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of nortriptyline. Nortriptyline is a substrate of the drug efflux transporter P-glycoprotein (PGP); boceprevir is an inhibitor of this efflux protein. Coadministration may result in elevated nortriptyline plasma concentrations.
Octreotide: (Moderate) Close clinical monitoring is advised when administering octreotide with boceprevir due to an increased potential for boceprevir-related adverse events. If octreotide dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of octreotide and boceprevir. Octreotide is an inhibitor of the hepatic isoenzyme CYP3A4; boceprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of boceprevir may be elevated.
Ombitasvir; Paritaprevir; Ritonavir: (Major) Concurrent administration of ritonavir with boceprevir is not recommended due to the potential for HIV and hepatitis C treatment failures. This combination has resulted in decreased serum concentrations of both medications. Ritonavir is an inhibitor, inducer, and substrate of the hepatic isoenzyme CYP3A4; boceprevir is an inhibitor and substrate of this isoenzyme. Additionally, both drugs are substrates and inhibitors of the drug efflux transporter P-glycoprotein (PGP). If these drugs are coadministered, health care providers are advised to closely monitor for decreased treatment response and virologic rebound. Health care providers are also encouraged to report any drug-related adverse reactions to the FDA MedWatch Program.
Ondansetron: (Moderate) Close clinical monitoring is advised when administering ondansetron with boceprevir due to an increased potential for ondansetron-related adverse events. If ondansetron dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of ondansetron. Ondansetron is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; boceprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated ondansetron plasma concentrations.
Oritavancin: (Moderate) Boceprevir is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of boceprevir may be reduced if these drugs are administered concurrently.
Ospemifene: (Moderate) Coadministration of boceprevir and ospemifene may increase ospemifene systemic concentrations and, thus, increase the risk of ospemifene-related adverse reactions. Boceprevir is a strong CYP3A4 inhibitor, and ospemifene is a CYP3A4 substrate. Strong CYP3A4 inhibitors increase the systemic exposure of ospemifene by approximately 1.4-fold.
Oxybutynin: (Moderate) Close clinical monitoring is advised when administering oxybutynin with boceprevir due to an increased potential for oxybutynin-related adverse events. If oxybutynin dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of oxybutynin. Oxybutynin is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated oxybutynin plasma concentrations.
Oxycodone: (Moderate) Close clinical monitoring is advised when administering oxycodone with boceprevir due to an increased potential for oxycodone-related adverse events. If oxycodone dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of oxycodone. Oxycodone is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated oxycodone plasma concentrations.
Paclitaxel: (Moderate) Close clinical monitoring is advised when administering paclitaxel with boceprevir due to an increased potential for paclitaxel-related adverse events. If paclitaxel dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of paclitaxel. Paclitaxel is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; boceprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated paclitaxel plasma concentrations.
Panobinostat: (Major) Use caution when administering panobinostat and boceprevir together; reduce the initial panobinostat dose from 20 mg PO to 10 mg PO. Boceprevir is a strong CYP3A4 inhibitor and panobinostat is a CYP3A4 substrate. The panobinostat Cmax and AUC (0-48hr) values were increased by 62% and 73%, respectively, in patients with advanced cancer who received a single 20 mg-dose of panobinostat after taking 14 days of a strong CYP3A4 inhibitor.
Paricalcitol: (Moderate) Close clinical monitoring is advised when administering paricalcitol with boceprevir due to an increased potential for paricalcitol-related adverse events. If paricalcitol dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of paricalcitol. Paricalcitol is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated paricalcitol plasma concentrations.
Pazopanib: (Major) Avoid administering pazopanib with strong CYP3A4 inhibitors, such as boceprevir. If co-administration with a strong CYP3A4 inhibitor is unavoidable, reduce the pazopanib dose to 400 mg PO once daily; further dose adjustments may be necessary if adverse effects occur. The concomitant use of pazopanib, a weak CYP3A4 inhibitor and a CYP3A4 and P-glycoprotein (P-gp) substrate, and boceprevir, a strong CYP3A4 inhibitor and a P-gp inhibitor and substrate, may result in altered pazopanib and/or boceprevir concentrations.
Perampanel: (Moderate) Concurrent use of perampanel with boceprevir, may increase exposure to perampanel and lead to elevated plasma concentrations. Boceprevir is a potent inhibitor of CYP3A4, an enzyme responsible for perampanel metabolism. Monitor patients for increases in adverse effects such as anger, anxiety, irritability, somnolence, dizziness, or nausea. Dose adjustment may be required.
Pergolide: (Severe) Concurrent use of ergot alkaloids and boceprevir is contraindicated due to the potential for serious/life-threatening ergot toxicities, such as peripheral vasospasm and ischemia of the extremities and other tissues. Boceprevir is a potent inhibitor of CYP3A4, which is responsible for the metabolism of ergot alkaloids. Coadministration may result in large increases in ergot alkaloid serum concentrations, which could cause fatal ergot toxicities.
Perindopril; Amlodipine: (Moderate) Close clinical monitoring is advised when administering amlodipine with boceprevir due to an increased potential for amlodipine-related adverse events. A reduction in the dose of amlodipine may be considered. If amlodipine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Predictions about the interaction can be made based on the metabolic pathway of amlodipine. Amlodipine is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated amlodipine plasma concentrations.
Perphenazine; Amitriptyline: (Moderate) Close clinical monitoring is advised when administering amitriptyline with boceprevir due to an increased potential for amitriptyline-related adverse events. If amitriptyline dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of amitriptyline. Amitriptyline is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; boceprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated amitriptyline plasma concentrations.
Phenobarbital: (Severe) The potential for boceprevir treatment failure exists when boceprevir is administered with phenobarbital; concurrent use is contraindicated. Phenobarbital is a potent inducer of CYP3A4, which is partially responsible for boceprevir metabolism. Coadministration may result in decreased boceprevir serum concentrations and impaired virologic response.
Phentermine; Topiramate: (Moderate) Close clinical monitoring is advised when administering topiramate with boceprevir due to the potential for boceprevir treatment failure. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of topiramate and boceprevir. Topiramate is a weak inducer of the hepatic isoenzyme CYP3A4; boceprevir is a substrate of this isoenzyme. When used in combination, the plasma concentrations of boceprevir may decrease.
Phenytoin: (Severe) The potential for boceprevir treatment failure exists when boceprevir is administered with phenytoin; therefore, the concurrent use of these medications is contraindicated. Phenytoin is a potent inducer of CYP3A4, which is partially responsible for boceprevir metabolism. Coadministration may result in decreased boceprevir serum concentrations, which could result in impaired virologic response to boceprevir.
Pimavanserin: (Major) Because pimavanserin is primarily metabolized by CYP3A4 and CYP3A5, the manufacturer recommends that the pimavanserin dose be reduced to 10 mg/day PO in patients receiving strong inhibitors of CYP3A4 such as boceprevir. If these agents are used in combination, the patient should be carefully monitored for pimavanserin-related adverse reactions, including nausea, vomiting, confusion, loss of balance or coordination, and QT prolongation.
Pimozide: (Severe) The concurrent use of pimozide and boceprevir is contraindicated due to the risk of life threatening arrhythmias such as torsades de pointes (TdP). Boceprevir is a potent inhibitor of CYP3A4, which is partially responsible pimozide metabolism. Elevated plasma concentrations of pimozide are expected with coadministration and can lead to QT prolongation, ventricular arrhythmia, and sudden death.
Ponatinib: (Major) Concomitant use of ponatinib, a CYP3A4 substrate, and boceprevir, a strong CYP3A4 inhibitor, may increase the exposure of ponatinib. If the use of both agents is necessary, reduce the starting ponatinib dose to 30 mg/day. Additionally, ponatinib is a P-gp inhibitor and may increase the plasma concentration of a P-gp substrate such as, boceprevir.
Posaconazole: (Major) Close clinical monitoring is advised when administering posaconazole with boceprevir due to an increased potential for posaconazole and boceprevir-related adverse events, such as QT prolongation and Torsade de Pointes. If posaconazole dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Predictions about the interaction can be made based on the metabolic pathways of posaconazole and boceprevir. Both posaconazole and boceprevir are substrates and inhibitors of the drug efflux transporter P-glycoprotein (PGP). Additionally, posaconazole is an inhibitor of the hepatic isoenzyme CYP3A4, an isoenzyme partially responsible for the metabolism of boceprevir. When used in combination, the plasma concentrations of both medications may be elevated.
Pravastatin: (Moderate) Pravastatin systemic exposure is increased when coadministered with boceprevir. According to the manufacturer, dose modifications are not required during concomitant use; however, close clinical monitoring for pravastatin-related adverse events is advised.
Prednisolone: (Major) Close clinical monitoring is advised when administering prednisolone with boceprevir due to an increased potential for corticosteroid-related adverse events. If prednisolone dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of prednisolone. Prednisolone is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated prednisolone plasma concentrations.
Prednisone: (Major) Concurrent administration of systemic corticosteroids, such as prednisone, and boceprevir is not recommended. If prednisone and boceprevir are coadministered, close monitoring for corticosteroid-related adverse events and for decreased boceprevir efficacy is advised. If prednisone dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Predictions about the interaction can be made based on the metabolic pathway of prednisone. Prednisone is metabolized by the hepatic isoenzyme CYP3A4 and the drug efflux transporter P-glycoprotein (P-gp); boceprevir inhibits both the isoenzyme and the drug efflux pump. Coadministration may result in elevated prednisone plasma concentrations.
Primidone: (Moderate) Close clinical monitoring is advised when administering primidone with boceprevir due to the potential for boceprevir treatment failure. If primidone dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of primidone and boceprevir. Primidone is an inducer of the hepatic isoenzyme CYP3A4; boceprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of boceprevir may decrease.
Propafenone: (Major) Close clinical monitoring is advised when administering propafenone with boceprevir due to an increased potential for serious and/or life-threatening propafenone-related adverse events. If propafenone dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of propafenone. Propafenone is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Additionally, propafenone is an inhibitor of P-glycoprotein (P-gp), an efflux transporter partially responsible for the metabolism of boceprevir. When used in combination, the plasma concentrations of both medications may be elevated.
Quazepam: (Moderate) Close clinical monitoring is advised when administering quazepam with boceprevir due to an increased potential for quazepam-related adverse events. If quazepam dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of quazepam. Quazepam is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated quazepam plasma concentrations.
Quetiapine: (Major) Coadministration of boceprevir, a potent CYP3A4 inhibitor, with quetiapine, a CYP3A4 substrate, may result in increased exposure to quetiapine. If administration of boceprevir is required in a patient taking quetiapine, reduce the quetiapine dose to one sixth of the current dose and monitor for quetiapine-related adverse events. If boceprevir is discontinued, increase the quetiapine dose by 6-fold.
Quinidine: (Major) Close clinical monitoring is advised when administering quinidine with boceprevir due to an increased potential for serious and/or life-threatening quinidine-related adverse events. If quinidine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of quinidine and boceprevir. Quinidine is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Additionally, both quinidine and boceprevir are substrates and inhibitors of P-glycoprotein (PGP) drug efflux transporter. When used in combination, the plasma concentrations of both medications may be elevated.
Quinine: (Moderate) Close clinical monitoring is advised when administering quinine with boceprevir due to an increased potential for quinine-related adverse events. If quinine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of quinine and boceprevir. Quinine is a substrate, inducer, and inhibitor of the hepatic isoenzyme CYP3A4; boceprevir is a substrate and an inhibitor of this isoenzyme. When used in combination, the plasma concentrations of both medications may be altered.
Rabeprazole: (Moderate) Close clinical monitoring is advised when administering rabeprazole with boceprevir due to an increased potential for rabeprazole-related adverse events. If rabeprazole dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of rabeprazole. Rabeprazole is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated rabeprazole plasma concentrations.
Ramelteon: (Moderate) Close clinical monitoring is advised when administering ramelteon with boceprevir due to an increased potential for ramelteon-related adverse events. If ramelteon dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of ramelteon. Ramelteon is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated ramelteon plasma concentrations.
Ranolazine: (Moderate) Close clinical monitoring is advised when administering ranolazine with boceprevir due to an increased potential for ranolazine-related adverse events. If ranolazine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of ranolazine and boceprevir. Both ranolazine and boceprevir are substrates and inhibitors of the hepatic isoenzyme CYP3A4 and the drug efflux transporter, P-glycoprotein (PGP). When used in combination, the plasma concentrations of both medications may be elevated.
Repaglinide: (Moderate) Close clinical monitoring is advised when administering repaglinide with boceprevir due to an increased potential for repaglinide-related adverse events. If repaglinide dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of repaglinide. Repaglinide is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated repaglinide plasma concentrations.
Rifabutin: (Major) Coadministration of rifabutin and boceprevir is not recommended. If rifabutin and boceprevir are coadministered, close clinical monitoring is advised due to the increased potential for rifabutin-related adverse events and for the potential of decreased boceprevir efficacy. If rifabutin dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Predictions about the interaction can be made based on the metabolic pathways of rifabutin and boceprevir. Rifabutin is an inducer and substrate of the hepatic isoenzyme CYP3A4; boceprevir is an inhibitor and substrate of this isoenzyme. When used in combination, rifabutin plasma concentrations may be elevated and the plasma concentration of boceprevir may be deceased, resulting in an increased potential for rifabutin-related adverse events and boceprevir treatment failure.
Rifampin: (Severe) The potential for boceprevir treatment failure exists when boceprevir is administered with rifampin; concurrent use is contraindicated. Rifampin is a potent inducer of CYP3A4, which is partially responsible for boceprevir metabolism. Coadministration may result in decreased boceprevir serum concentrations and impaired virologic response.
Rifaximin: (Moderate) Rifaximin is a substrate of P-gp and boceprevir is a P-gp inhibitor. Coadministation may result in increased plasma concentrations of rifaximin; use caution. In patients with hepatic impairment, reduced drug metabolism may increase the effects of P-gp inhibition.
Rilpivirine: (Moderate) Although dose adjustments are not recommended, close clinical monitoring is advised when administering boceprevir with rilpivirine due to an increased potential for rilpivirine-related adverse events. When these drugs are administered concurrently, the Cmax and AUC of rilpivirine are significantly increased. Predictions about the interaction can be made based on metabolic pathways of boceprevir and rilpivirine. Boceprevir is an inhibitor of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in increased rilpivirine plasma concentrations.
Riociguat: (Moderate) Concomitant use of riociguat with strong cytochrome CYP3A inhibitors may result in hypotension. Boceprevir is a potent inhibitor of CYP3A4. Monitor for signs and symptoms of hypotension on initiation and on treatment with strong CYP inhibitors. A dose reduction should be considered in patients who may not tolerate the hypotensive effect of riociguat.
Risperidone: (Moderate) Close clinical monitoring is advised when administering risperidone with boceprevir due to an increased potential for risperidone-related adverse events. If risperidone dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of risperidone. Risperidone is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; boceprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated risperidone plasma concentrations.
Ritonavir: (Major) Concurrent administration of ritonavir with boceprevir is not recommended due to the potential for HIV and hepatitis C treatment failures. This combination has resulted in decreased serum concentrations of both medications. Ritonavir is an inhibitor, inducer, and substrate of the hepatic isoenzyme CYP3A4; boceprevir is an inhibitor and substrate of this isoenzyme. Additionally, both drugs are substrates and inhibitors of the drug efflux transporter P-glycoprotein (PGP). If these drugs are coadministered, health care providers are advised to closely monitor for decreased treatment response and virologic rebound. Health care providers are also encouraged to report any drug-related adverse reactions to the FDA MedWatch Program.
Rivaroxaban: (Major) Avoid concomitant administration of rivaroxaban and boceprevir due to increased rivaroxaban exposure and bleeding risk. Rivaroxaban is a substrate of CYP3A4/5 and the P-glycoprotein (P-gp) transporter. Boceprevir is a combined mild P-gp inhibitor and strong CYP3A4 inhibitor. Concurrent use of a single dose of rivaroxaban and another combined P-gp and strong CYP3A4 inhibitor resulted in significant increases in the steady-state rivaroxaban AUC and Cmax.
Romidepsin: (Moderate) The concomitant use of romidepsin, a CYP3A4 substrate and a P-glycoprotein (P-gp) substrate, and boceprevir, a strong CYP3A4 inhibitor and a P-gp substrate and inhibitor, may increase romidepsin plasma exposure. If these agents are used together, monitor patients for signs and symptoms of romidepsin toxicity including hematologic toxicity, infection, and electrocardiogram changes; therapy interruption or discontinuation or a dosage reduction may be required if toxicity develops.
Ropivacaine: (Moderate) Close clinical monitoring is advised when administering ropivacaine with boceprevir due to an increased potential for ropivacaine-related adverse events. If ropivacaine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of ropivacaine. Ropivacaine is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated ropivacaine plasma concentrations.
Salmeterol: (Major) Concurrent administration of salmeterol with boceprevir is not recommended. If salmeterol and boceprevir are coadministered, monitor the patient closely for salmeterol-related cardiovascular adverse events, such as QT interval prolongation, palpitations, and sinus tachycardia.
Saquinavir: (Major) Close clinical monitoring is advised when administering saquinavir with boceprevir due to an increased potential for adverse events. If saquinavir dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of saquinavir and boceprevir. Both saquinavir and boceprevir are substrates and inhibitors of the hepatic isoenzyme CYP3A4 and the drug efflux transporter, P-glycoprotein (PGP). When used in combination, the plasma concentrations of both medications may be elevated.
Segesterone Acetate; Ethinyl Estradiol: (Major) Close clinical monitoring for signs of estrogen deficiency is advised when administering ethinyl estradiol in combination with boceprevir. When used concurrently, ethinyl estradiol plasma concentrations may be decreased, potentially resulting in impaired efficacy. If ethinyl estradiol dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. (Major) Use of non-oral combination contraceptives with boceprevir have not been studied and are contraindicated. Patients receiving boceprevir in combination with ribavirin (and their partners) are required to use two reliable forms of contraception, including a non-hormonal form of birth control, while on therapy and for at least 6 months after treatment. The manufacturer states that one of reliable forms of contraception can be combined oral contraceptives containing ethinyl estradiol and at least 1 mg of norethindrone. Bceprevir is a potent inhibitor of CYP3A4, has been shown to reduce the Cmax of norethindrone by 17%, a decrease which may be sufficient to reduce the effectiveness of combined oral contraceptives containing less than 1 mg of norethindrone. Additionally, ethinyl estradiol plasma concentrations may be decreased is administered with boceprevir.
Selegiline: (Moderate) Close clinical monitoring is advised when administering selegiline with boceprevir due to an increased potential for selegiline-related adverse events. If selegiline dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of selegiline. Selegiline is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated selegiline plasma concentrations.
Sibutramine: (Moderate) Close clinical monitoring is advised when administering sibutramine with boceprevir due to an increased potential for sibutramine-related adverse events. If sibutramine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of sibutramine. Sibutramine is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated sibutramine plasma concentrations.
Sildenafil: (Major) Sildenafil, when used for pulmonary arterial hypertension (PAH), is contraindicated with boceprevir. Coadministration of boceprevir with phosphodiesterase type 5 (PDE5) inhibitors is expected to substantially increase their plasma concentrations and may result in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Boceprevir can be used with sildenafil for erectile dysfunction; use sildenafil at reduced doses of 25 mg every 48 hours with increased monitoring for adverse reactions.
Silodosin: (Severe) The concurrent use of silodosin and boceprevir is contraindicated due to the potential for serious/life-threatening reactions. Silodosin is a substrate of the drug efflux transporter P-glycoprotein (P-gp) and of the hepatic isoenzyme CYP3A4; boceprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated silodosin plasma concentrations, which could cause adverse events such as hypotension and priapism.
Simeprevir: (Major) Avoid concurrent use of simeprevir and boceprevir. Inhibition of CYP3A4 and P-glycoprotein (P-gp) by boceprivir may increase the plasma concentrations of simeprevir, resulting in adverse effects, such as rash. Additionaly, simeprivir, a P-gp inhibitor and a mild intestinal CYP3A4 inhibitor, may increase the side effects of boceprevir, a Pg-p and CYP3A4 substrate.
Simvastatin: (Severe) The concurrent use of simvastatin and boceprevir is contraindicated due to the potential for serious/life-threatening reactions. Boceprevir is a potent inhibitor of CYP3A4, which is responsible simvastatin metabolism. Coadministration may result in large increases in simvastatin serum concentrations, which could cause adverse events such as myopathy and rhabdomyolysis.
Simvastatin; Sitagliptin: (Severe) The concurrent use of simvastatin and boceprevir is contraindicated due to the potential for serious/life-threatening reactions. Boceprevir is a potent inhibitor of CYP3A4, which is responsible simvastatin metabolism. Coadministration may result in large increases in simvastatin serum concentrations, which could cause adverse events such as myopathy and rhabdomyolysis.
Sirolimus: (Major) Plasma concentrations of sirolimus are significantly increased when administered in combination with boceprevir. If these drugs are used together, closely monitor sirolimus concentrations and make dose reductions as required. If sirolimus dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Closely monitor the patients renal function and for sirolimus-related side effects.. Predictions about the interaction can be made based on the metabolic pathway of sirolimus. Sirolimus is a substrate of the hepatic isoenzyme CYP3A4 and the drug efflux transporter P-glycoprotein (P-gp); boceprevir inhibits both the isoenzyme and the drug efflux protein.
Sofosbuvir; Velpatasvir: (Moderate) Use caution when administering velpatasvir with boceprevir. Taking these medications together may increase the plasma concentrations of both drugs, potentially resulting in adverse events. Both drugs are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp). In addition, boceprevir is a potent inhibitor of the hepatic enzyme CYP3A4. Velpatasvir is a CYP3A4 substrate.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Use caution when administering velpatasvir with boceprevir. Taking these medications together may increase the plasma concentrations of both drugs, potentially resulting in adverse events. Both drugs are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp). In addition, boceprevir is a potent inhibitor of the hepatic enzyme CYP3A4. Velpatasvir is a CYP3A4 substrate.
Solifenacin: (Moderate) Close clinical monitoring is advised when administering solifenacin with boceprevir due to an increased potential for solifenacin-related adverse events. If solifenacin dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of solifenacin. Solifenacin is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated solifenacin plasma concentrations.
Sonidegib: (Major) Avoid the concomitant use of sonidegib and boceprevir; sonidegib levels may be significantly increased resulting in an increased risk of adverse events, particularly musculoskeletal toxicity. Sonidegib is a CYP3A4 substrate and boceprevir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor for 14 days increased the Cmax and AUC of sonidegib by 2.2-fold and 1.5-fold, respectively.
St. John's Wort, Hypericum perforatum: (Severe) The potential for boceprevir treatment failure exists when boceprevir is administered with St. John's wort, Hypericum perforatum; concurrent use is contraindicated. St. John's wort appears to be an inducer of CYP3A4, which is partially responsible boceprevir metabolism. Coadministration may result in decreased boceprevir serum concentrations and impaired virologic response.
Sufentanil: (Moderate) Close clinical monitoring is advised when administering sufentanil with boceprevir due to an increased potential for sufentanil-related adverse events. If sufentanil dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of sufentanil. Sufentanil is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated sufentanil plasma concentrations.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Moderate) Close clinical monitoring is advised when administering sulfamethoxazole with boceprevir due to an increased potential for sulfamethoxazole-related adverse events. If sulfamethoxazole dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of sulfamethoxazole. Sulfamethoxazole is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated sulfamethoxazole plasma concentrations.
Suvorexant: (Major) Coadministration of suvorexant and boceprevir is not recommended due to the potential for significantly increased suvorexant exposure. Suvorexant is a CYP3A4 substrate. Boceprevir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold.
Tacrolimus: (Major) Tacrolimus is a substrate of the hepatic isoenzyme CYP3A4. Coadministration with strong CYP3A4 inhibitors such as boceprevir is not recommended without adjustments in the dosing regimen of tacrolimus and subsequent close monitoring of tacrolimus whole blood trough concentrations and tacrolimus-associated adverse reactions. In addition, frequent assessments of renal function are advised. In a single dose study in 12 subjects, coadministration of tacrolimus (0.5 mg single dose) with boceprevir (800 mg three times daily for 11 days) increased tacrolimus Cmax by 9.9 - fold and AUC by 17 - fold compared to tacrolimus alone.
Tadalafil: (Major) Tadalafil, when used for pulmonary arterial hypertension (PAH), is contraindicated with boceprevir. Coadministration of boceprevir with phosphodiesterase type 5 (PDE5) inhibitors is expected to substantially increase their plasma concentrations and may result in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Boceprevir can be used with tadalafil for erectile dysfunction; use tadalafil at reduced doses of 10 mg every 72 hours with increased monitoring for adverse reactions.
Tamsulosin: (Severe) The concurrent use of tamsulosin and boceprevir is contraindicated due to the potential for serious/life-threatening reactions. Tamsulosin is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated tamsulosin plasma concentrations, which could cause adverse events such as hypotension and priapism.
Tasimelteon: (Major) Concurrent use of tasimelteon and strong inhibitors of CYP3A4, such as boceprevir, should be avoided if possible. Because tasimelteon is partially metabolized via CYP3A4, a large increase in exposure of tasimelteon with the potential for adverse reactions is possible if these drugs are coadministered. During administration of tasimelteon and another potent CYP3A4 inhibitor, tasimelteon exposure increased by about 50%.
Telithromycin: (Major) Close clinical monitoring is advised when administering telithromycin with boceprevir due to an increased potential for serious telithromycin-related adverse events, such as QT prolongation. If telithromycin dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of telithromycin and boceprevir. Telithromycin is an inhibitor of the hepatic isoenzyme CYP3A4 and the drug efflux transporter P-glycoprotein (P-gp); boceprevir is metabolized by CYP3A4 and PGP. When used in combination, the plasma concentrations of both medications may be elevated.
Telotristat Ethyl: (Moderate) Use caution if coadministration of telotristat ethyl and boceprevir is necessary, as the systemic exposure of boceprevir may be decreased resulting in reduced efficacy; exposure to telotristat ethyl may also be increased. If these drugs are used together, monitor patients for suboptimal efficacy of boceprevir as well as a possible increase in adverse reactions related to telotristat ethyl. Consider increasing the dose of boceprevir if necessary. Boceprevir is a CYP3A4 substrate. The mean Cmax and AUC of another sensitive CYP3A4 substrate was decreased by 25% and 48%, respectively, when coadministered with telotristat ethyl; the mechanism of this interaction appears to be that telotristat ethyl increases the glucuronidation of the CYP3A4 substrate. Coadministration with a moderate CYP3A4 inducer decreased the mean Cmax and AUC of boceprevir by 8% and 19%, respectively. Additionally, the active metabolite of telotristat ethyl, telotristat, is a substrate of P-glycoprotein (P-gp) and boceprevir is a P-gp inhibitor in vitro. At clinically relevant concentrations, boceprevir increased the mean Cmax and AUC of another sensitive P-gp substrate by 1.18-fold and 1.19-fold, respectively; exposure to telotristat ethyl may increase.
Teniposide: (Moderate) Close clinical monitoring is advised when administering teniposide with boceprevir due to an increased potential for teniposide-related adverse events. If teniposide dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of teniposide. Teniposide is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; boceprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated teniposide plasma concentrations.
Tenofovir Alafenamide: (Moderate) Close clinical monitoring is advised when administering boceprevir with tenofovir alafenamide due to an increased potential for adverse events. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of these drugs. Boceprevir is an inhibitor of the drug transporter P-glycoprotein (P-gp). Tenofovir alafenamide is a P-gp substrate. Coadministr ation may result in increased tenofovir plasma concentrations. Of note, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor.
Tenofovir, PMPA: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as boceprevir. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Terbinafine: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering boceprevir. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; boceprevir is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
Testosterone: (Moderate) Close clinical monitoring is advised when administering testosterone with boceprevir due to an increased potential for testosterone-related adverse events. If testosterone dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of testosterone. Testosterone is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; boceprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated testosterone plasma concentrations.
Tezacaftor; Ivacaftor: (Major) If boceprevir and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to twice weekly (e.g., if the usual dosage is 150 mg twice daily, reduce to 150 mg twice weekly). Ivacaftor is a CYP3A substrate, and boceprevir is a strong CYP3A inhibitor. Coadministration with ketoconazole, another strong CYP3A inhibitor, increased ivacaftor exposure by 8.5-fold. Ivacaftor is also an inhibitor of CYP3A and P-glycoprotein (P-gp); boceprevir is metabolized by CYP3A4 and is a substrate of P-gp. Coadministration may increase boceprevir exposure leading to increased or prolonged therapeutic effects and adverse events.
Theophylline, Aminophylline: (Moderate) Close clinical monitoring is advised when administering theophylline, aminophylline with boceprevir due to an increased potential for theophylline-related adverse events. If theophylline dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of theophylline. Theophylline is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated theophylline plasma concentrations.
Tiagabine: (Moderate) Close clinical monitoring is advised when administering tiagabine with boceprevir due to an increased potential for tiagabine-related adverse events. If tiagabine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of tiagabine. Tiagabine is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated tiagabine plasma concentrations.
Ticagrelor: (Minor) Coadministration of ticagrelor and boceprevir may result in increased exposure to ticagrelor which may increase the bleeding risk. Ticagrelor is a P-glycoprotein (P-gp) substrate. In vitro data suggests boceprevir is a mild P-gp inhibitor. Based on drug information data with cyclosporine, no dose adjustment is recommended by the manufacturer of ticagrelor. Use combination with caution and monitor for evidence of bleeding.
Tinidazole: (Moderate) Close clinical monitoring is advised when administering tinidazole with boceprevir due to an increased potential for tinidazole-related adverse events. If tinidazole dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of tinidazole. Tinidazole is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated tinidazole plasma concentrations.
Tipranavir: (Major) Close clinical monitoring is advised when administering tipranavir with boceprevir due to an increased potential for adverse events. If tipranavir dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of tipranavir and boceprevir. Both tipranavir and boceprevir are substrates and inhibitors of the hepatic isoenzyme CYP3A4. When used in combination, the plasma concentrations of both medications may be elevated.
Tolterodine: (Moderate) Close clinical monitoring is advised when administering tolterodine with boceprevir due to an increased potential for tolterodine-related adverse events. If tolterodine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of tolterodine. Tolterodine is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated tolterodine plasma concentrations.
Tolvaptan: (Moderate) Close clinical monitoring is advised when administering tolvaptan with boceprevir due to an increased potential for tolvaptan-related adverse events. If tolvaptan dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of tolvaptan. Tolvaptan is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; boceprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated tolvaptan plasma concentrations.
Topiramate: (Moderate) Close clinical monitoring is advised when administering topiramate with boceprevir due to the potential for boceprevir treatment failure. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of topiramate and boceprevir. Topiramate is a weak inducer of the hepatic isoenzyme CYP3A4; boceprevir is a substrate of this isoenzyme. When used in combination, the plasma concentrations of boceprevir may decrease.
Trabectedin: (Major) Avoid the concomitant use of trabectedin with boceprevir due to significantly increased trabectedin exposure. If short-term boceprevir (less than 14 days) cannot be avoided, begin administration 1 week after the trabectedin infusion and discontinue it the day prior to the next trabectedin infusion. Trabectedin is a CYP3A substrate and boceprevir is a strong CYP3A inhibitor. Coadministration with ketoconazole (200 mg twice daily for 7.5 days), another strong CYP3A inhibitor, increased the systemic exposure of a single dose of trabectedin (0.58 mg/m2 IV) by 66% and the Cmax by 22% compared to a single dose of trabectedin (1.3 mg/m2) given alone.
Tramadol: (Moderate) Close clinical monitoring is advised when administering tramadol with boceprevir due to an increased potential for tramadol-related adverse events. If tramadol dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of tramadol. Tramadol is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated tramadol plasma concentrations.
Trandolapril; Verapamil: (Moderate) Close clinical monitoring is advised when administering verapamil with boceprevir due to an increased potential for verapamil-related adverse events. If verapamil dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Predictions about the interaction can be made based on the metabolic pathways of verapamil and boceprevir. Both verapamil and boceprevir are substrates and inhibitors of the hepatic isoenzyme CYP3A4 and the drug efflux transporter, P-glycoprotein (PGP). When used in combination, the plasma concentrations of both medications may be elevated.
Trazodone: (Moderate) Close clinical monitoring is advised when administering trazodone with boceprevir due to an increased potential for trazodone-related adverse event, such as dizziness, hypotension, and syncope. When used in combination, the plasma concentrations of trazodone were increased; thus, consider initiating trazodone at the lowest effective dose. If trazodone dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment.
Triazolam: (Severe) Concurrent use of triazolam and boceprevir is contraindicated due to the risk of life threatening reactions, such as prolonged or increased sedation or respiratory depression. Boceprevir is a potent inhibitor of CYP3A4, which is responsible for the metabolism of triazolam. Coadministration may result in large increases in triazolam serum concentrations, which could cause fatal toxicities. Lorazepam, oxazepam, or temazepam may be safer alternatives if a benzodiazepine must be administered in combination with boceprevir, as they are not oxidatively metabolized.
Ulipristal: (Minor) In vitro data indicate that ulipristal may be an inhibitor of P-glycoprotein (P-gp) at clinically relevant concentrations. Thus, co-administration of ulipristal and P-gp substrates such as boceprevir may increase bocepravir concentrations. With single doses of ulipristal for emergency contraception it is not clear this interaction will have clinical consequence. In the absence of clinical data, co-administration of ulipristal (when given daily) and P-gp substrates is not recommended.
Valbenazine: (Major) The dose of valbenazine should be reduced to 40 mg once daily during co-administration with a strong CYP3A4 inhibitor, such as boceprevir. QT prolongation is not clinically significant at valbenazine concentrations expected with recommended dosing; however, valbenazine concentrations may be higher in patients taking a strong CYP3A4 inhibitor and QT prolongation may become clinically significant.
Vardenafil: (Moderate) Close clinical monitoring is advised when administering vardenafil with boceprevir due to an increased potential for vardenafil-related adverse events, such as hypotension, syncope, visual disturbances, and priapism. During coadministration, do not exceed a maximum vardenafil dosage of 2.5 mg in 24 hours. If vardenafil dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Predictions about the interaction can be made based on the metabolic pathways of vardenafil. Vardenafil is a substrate of the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. When used in combination, the plasma concentrations of vardenafil may be elevated.
Vemurafenib: (Major) The concomitant use of vemurafenib, a CYP3A4 substrate and a P-glycoprotein (P-gp) substrate and inhibitor, and boceprevir, a strong CYP3A4 inhibitor and a P-gp substrate and inhibitor, may result in altered vemurafenib or boceprevir concentrations. Avoid using vemurafenib in combination with potent CYP3A4 inhibitors if possible.
Venetoclax: (Severe) Boceprevir is contraindicated for use with medications that are highly dependent on CYP3A4 for clearance and are associated with serious and/or life-threatening events, such as venetoclax. Significantly increased venetoclax levels may occur. Venetoclax is a sensitive CYP3A4 substrate; boceprevir is a strong CYP3A inhibitor. When venetoclax was administered with multiple doses of other strong CYP3A4 inhibitors, the Cmax and AUC values of venetoclax were increased significantly.
Venlafaxine: (Moderate) Close clinical monitoring is advised when administering venlafaxine with boceprevir due to an increased potential for venlafaxine-related adverse events. If venlafaxine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of venlafaxine. Venlafaxine is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated venlafaxine plasma concentrations.
Verapamil: (Moderate) Close clinical monitoring is advised when administering verapamil with boceprevir due to an increased potential for verapamil-related adverse events. If verapamil dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Predictions about the interaction can be made based on the metabolic pathways of verapamil and boceprevir. Both verapamil and boceprevir are substrates and inhibitors of the hepatic isoenzyme CYP3A4 and the drug efflux transporter, P-glycoprotein (PGP). When used in combination, the plasma concentrations of both medications may be elevated.
Vilazodone: (Major) CYP3A4 is the primary isoenzyme involved in the metabolism of vilazodone and boceprevir is a strong CYP3A4 inhibitor. Concurrent use of vilazodone and boceprevir may lead to an increased risk of vilazodone-related adverse reactions. The manufacturer recommends a reduction in vilazodone dose to 20 mg/day in patients receiving a strong CYP3A4 inhibitor. When the inhibitor is discontinued, resume the previous vilazodone dose.
Vincristine Liposomal: (Moderate) Close clinical monitoring is advised when administering vincristine with boceprevir due to an increased potential for vincristine-related adverse events. If vincristine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of vincristine. Vincristine is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; boceprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated vincristine plasma concentrations.
Vincristine: (Moderate) Close clinical monitoring is advised when administering vincristine with boceprevir due to an increased potential for vincristine-related adverse events. If vincristine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of vincristine. Vincristine is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; boceprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated vincristine plasma concentrations.
Vorapaxar: (Major) Avoid coadministration of vorapaxar and boceprevir. Increased serum concentrations of vorapaxar are possible when vorapaxar, a CYP3A4 substrate, is coadministered with boceprevir, a strong CYP3A inhibitor. Increased exposure to vorapaxar may increase the risk of bleeding complications.
Voriconazole: (Major) Close clinical monitoring is advised when administering voriconazole with boceprevir due to an increased potential for voriconazole and boceprevir-related adverse events, such as QT prolongation and torsade de pointes. If voriconazole dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Predictions about the interaction can be made based on the metabolic pathways of voriconazole and boceprevir. Both voriconazole and boceprevir are substrates and inhibitors of the hepatic isoenzyme CYP3A4. When used in combination, the plasma concentration of both medications may be elevated.
Warfarin: (Moderate) Monitoring of the international normalized ratio (INR) is advised when administering warfarin with boceprevir due to an increased potential for warfarin-related adverse events, such as bleeding or thrombosis. If warfarin dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Predictions about the interaction can be made based on the metabolic pathway of warfarin. Warfarin is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in altered warfarin plasma concentrations.
Yohimbine: (Moderate) Close clinical monitoring is advised when administering yohimbine with boceprevir due to an increased potential for yohimbine-related adverse events. If yohimbine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of yohimbine. Yohimbine is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated yohimbine plasma concentrations.
Zafirlukast: (Moderate) Close clinical monitoring is advised when administering zafirlukast with boceprevir due to an increased potential for boceprevir-related adverse events. If zafirlukast dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of zafirlukast and boceprevir. Zafirlukast is an inhibitor of the hepatic isoenzyme CYP3A4; boceprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of boceprevir may be elevated.
Zileuton: (Moderate) Close clinical monitoring is advised when administering zileuton with boceprevir due to an increased potential for zileuton-related adverse events. If zileuton dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of zileuton. Zileuton is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated zileuton plasma concentrations.
Ziprasidone: (Moderate) Close clinical monitoring is advised when administering ziprasidone with boceprevir due to an increased potential for ziprasidone-related adverse events. If ziprasidone dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of ziprasidone. Ziprasidone is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated ziprasidone plasma concentrations.
Zolpidem: (Major) It is advisable to closely monitor zolpidem tolerability and safety during co-administration of potent CYP3A4 inhibitors, such as boceprevir, and consider using a lower dose of zolpidem to minimize the potential for adverse CNS effects. CYP3A4 is the primary isoenzyme responsible for zolpidem metabolism, and there is evidence of an increase in pharmacodynamics effects and systemic exposure of zolpidem during co-administration with some potent inhibitors of CYP3A4, such as azole antifungals.
Zonisamide: (Moderate) Close clinical monitoring is advised when administering zonisamide with boceprevir due to an increased potential for zonisamide-related adverse events. If zonisamide dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of zonisamide. Zonisamide is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated zonisamide plasma concentrations.

VICTRELIS Oral Cap: 200mg

Adults

2400 mg/day PO.

Geriatric

2400 mg/day PO.

Adolescents

Safety and efficacy have not been established.

Children

Safety and efficacy have not been established.

Infants

Safety and efficacy have not been established.

Neonates

Safety and efficacy have not been established.

Boceprevir prevents hepatitis C viral (HCV) replication by blocking the proteolytic activity of HCV NS3/4A serine protease. Hepatitis C virus NS3/4A serine protease is an enzyme responsible for the conversion of HCV encoded polyproteins to functioning mature viral proteins. These mature proteins, NS4A, NS4B, NS5A, and NS5B, are essential for viral replication.
 
Hepatitis C viral resistance to boceprevir has been demonstrated in both cell cultures and during clinical studies. Analysis of cell cultures found amino acid substitutions in the NS3 protease domain were associated with a 2- to more than 10-fold reduction in boceprevir anti-HCV activity. During clinical studies, these treatment emergent amino acid substitutions were isolated in 53% of patients who failed to achieve a sustained viral response. Boceprevir treatment emergent NS3 amino acid substitutions have resulted in cross-resistance with other NS3/4A protease inhibitors. Cross-resistance between boceprevir and interferons or ribavirin is not expected.[44314]

Boceprevir is administered orally as an equal mixture of 2 diastereomers, SCH534128 (active) and SCH534129 (inactive), which rapidly interconvert in the plasma. Following systemic absorption, approximately 75% of a single 800 mg dose is bound to plasma proteins. Boceprevir is primarily metabolized by the enzyme aldo-keto reductase (AKR) to a ketone-reduced metabolite. It also undergoes oxidative metabolism by the hepatic isoenzyme CYP3A4/5 and is a substrate for the drug efflux transporter, P-glycoprotein (P-gp). Excretion occurs primarily in the feces (79%) with 9% being eliminated in the urine. The mean elimination half-life is approximately 3.4 hours.
 
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, P-glycoprotein (P-gp)
Boceprevir is a substrate and potent inhibitor of CYP3A4 and the drug transporter P-gp.

Oral Route

Following oral administration, the median time to reach maximum serum concentration is 2 hour (Tmax) with steady state concentrations achieved after 3 doses. The absolute bioavailability has not been studied; however, administration with food increases boceprevir exposure by up to 65%, relative to fasting state. Of note, the effect of food on the bioavailability was consistent regardless of the type of meal (low fat vs. high fat) or on the timing of administration (5 minutes before, during, or immediately after meal).

Pregnancy

Boceprevir is a pregnancy risk category B drug if administered alone and a pregnancy risk category X drug when administered in combination with peginterferon alfa and ribavirin. There are no well controlled studies evaluating the use of boceprevir in pregnant women; however since boceprevir must be administered in combination with peginterferon alfa and ribavirin, use of boceprevir is contraindicated in pregnant women and in the male partners of women who are pregnant. Use of ribavirin may cause birth defects and/or death of the exposed fetus. Ribavirin therapy also may cause male-mediated teratogenicity and is contraindicated for use during pregnancy (FDA pregnancy risk category X), in females who may become pregnant, or in men whose female partners are pregnant. Studies of ribavirin indicate teratogenic (e.g., malformations of skull, palate, eye, jaw, limbs, skeleton, and GI tract) or embryocidal properties in most of the animal species tested. Use of peginterferon alfa has produced abortifacient effects in animals and, thus, the potential for abortifacient effects in humans must be considered. Patients and their partners are required use 2 forms of effective contraception during treatment and for 6 months post-therapy. One of these forms may be a combined oral contraceptive product containing at least 1 mg of norethindrone; those with lower norethindrone doses or other forms of hormonal contraception have not been studied or are contraindicated. Health care providers must consider the potential for decreased efficacy of systemic hormonal contraception as interferon therapy may decrease serum estradiol and progesterone concentrations and boceprevir may decrease the serum concentrations of ethinyl estradiol. Patients who are not willing to practice strict contraception should not receive treatment with boceprevir, peginterferon alfa, and ribavirin. Females must also undergo a pregnancy test prior to initiation of therapy, monthly during therapy, and for 6 months post-therapy. To monitor maternal-fetal outcomes of pregnancies in female patients and female partners of male patients exposed to boceprevir, peginterferon alfa, and ribavirin during treatment and for six months following cessation of treatment, health care providers are encouraged to report any cases of prenatal ribavirin exposure to the Ribavirin Pregnancy registry; telephone (800) 593-2214.