INCIVEK

Protease Inhibitors for Hepatitis

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

Oral Administration

Administer with food (not low fat).

Severe

rash (unspecified) / Early / 4.0-4.0
bullous rash / Early / 4.0-4.0
vesicular rash / Delayed / 4.0-4.0
Stevens-Johnson syndrome / Delayed / 0-1.0
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / 0-1.0
toxic epidermal necrolysis / Delayed / Incidence not known
erythema multiforme / Delayed / Incidence not known
renal failure (unspecified) / Delayed / Incidence not known
azotemia / Delayed / Incidence not known

Moderate

anemia / Delayed / 36.0-36.0
lymphopenia / Delayed / 15.0-15.0
neutropenia / Delayed / 12.0-12.0
hemorrhoids / Delayed / 12.0-12.0
leukopenia / Delayed / 8.0-8.0
hyperuricemia / Delayed / 7.0-7.0
hyperbilirubinemia / Delayed / 4.0-4.0
thrombocytopenia / Delayed / 3.0-3.0
eosinophilia / Delayed / 0-1.0
skin erosion / Delayed / 0-1.0
gout / Delayed / 0-1.0

Mild

fatigue / Early / 56.0-56.0
pruritus / Rapid / 47.0-47.0
nausea / Early / 39.0-39.0
diarrhea / Early / 26.0-26.0
vomiting / Early / 13.0-13.0
dysgeusia / Early / 10.0-10.0
pruritus ani / Early / 6.0-6.0
fever / Early / 0-1.0

Serious rash

Fatal and non-fatal skin reactions, including drug rash with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and erythema multiforme (EM), have been reported in patients receiving the three-drug regimen of telaprevir, peginterferon alfa, and ribavirin. Fatal cases occurred in patients with progressive rash and systemic symptoms who continued combination therapy after a serious rash was identified. Health care providers are advised to monitor for signs indicating the development of DRESS (including rash, fever, facial edema, hepatitis, nephritis, with or without eosinophilia) and/or SJS (including fever, target lesions, mucosal erosions, ulcerations). If a serious rash occurs, immediately discontinue all components of the three-drug regimen and refer the patient for urgent medical care. In addition, discontinuation of other mediations known to be associated with serious rash should be considered. For patients who develop a mild to moderate rash, close monitoring for rash progression and development of systemic symptoms is recommended. If progression occurs, discontinue telaprevir; peginterferon alfa and ribavirin may be continued in these patients. Monitor patients until the rash has resolved and do not restart telaprevir. If improvement does not occur within 7 days of stopping telaprevir, interruption/discontinuation of peginterferon alfa and/or ribavirin should be considered. Treatment of rash with systemic corticosteroids is not recommended; use of topical corticosteroids and/or oral antihistamines may provide symptomatic relief.

INCIVEK

Rx

Hepatitis C virus NS3/4A protease inhibitor
For the treatment of chronic hepatitis C in adults with compensated liver disease
Must be used with peginterferon alfa and ribavirin; avoid monotherapy

For the treatment of chronic hepatitis C infection (HCV, genotype 1) in adults with compensated liver disease.
NOTE: MUST be administered in combination with peginterferon alfa and ribavirin; never administer as monotherapy. If peginterferon alfa or ribavirin are discontinued for any reason, then telaprevir must also be discontinued.
Oral dosage Adults

NOTE: This drug is discontinued in the US. 1125 mg PO twice daily, administered 10—14 hours apart, in combination with peginterferon alfa and ribavirin for an initial 12 weeks of treatment. Monitor hepatitis C virus (HCV) RNA using a real-time RT-PCR assay at treatment weeks 4 and 12 to determine combination treatment duration as listed below. AASLD guidelines recommend against the use of telaprevir due to inferiority compared to other regimens; however, the WHO suggests it may be an appropriate option.
   - Treatment-naive and prior relapse patients with undetectable HCV RNA at weeks 4 and 12: After the initial three-drug regimen, give an additional 12 weeks of only peginterferon alfa and ribavirin (24 weeks for total course).
   - Treatment-naive and prior relapse patients with HCV RNA that is detectable but <= 1000 international units/ml at weeks 4 and/or 12: After the initial three-drug regimen, give an additional 36 weeks of only peginterferon alfa and ribavirin (48 weeks for total course).
   - Patients without cirrhosis who are previously partial or null responders to interferon and ribavirin therapy: After the initial three-drug regimen, give an additional 36 weeks (48 weeks for total course) of only peginterferon alfa and ribavirin.
   - Patients with cirrhosis: After the initial three drug regimen, give an additional 36 weeks (48 weeks for total course) of only peginterferon alfa and ribavirin. According to the manufacturer, all patients with cirrhosis, including those who are treatment naive and have undetectable HCV RNA concentrations at weeks 4 and 12, may benefit from the 48 week treatment regimen.
  - Patients with HCV RNA concentrations > 1000 international units/ml at treatment weeks 4 or 12 or a confirmed detectable HCV RNA concentration at treatment week 24: Discontinue therapy.
  - Patients with HIV coinfection: Guidelines state that concurrent treatment is feasible, but may be complicated due to high pill burden, drug interactions, and overlapping toxicities and that some clinicians may choose to defer HCV therapy in patients with little or no liver fibrosis.

Hepatic Impairment

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed for mild hepatic impairment (Child-Pugh A). Telaprevir is not recommended for patients with moderate to severe hepatic impairment (Child-Pugh B or C) or in patients with decompensated liver disease.

Renal Impairment

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
 
Other Dosage Adjustments
-Dosage adjustments based on adverse reactions: NOTE: Telaprevir dosage modifications are not recommended. NOTE: For dosage adjustment of peginterferon or ribavirin based on adverse reactions and hematologic parameters, see Peginterferon or Ribavirin Dosage/Therapeutic Drug Monitoring.

Acetaminophen: Close clinical monitoring is advised when administering acetaminophen with telaprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen 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 acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations.
Acetaminophen; Aspirin, ASA; Caffeine: Close clinical monitoring is advised when administering acetaminophen with telaprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen 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 acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations.
Acetaminophen; Butalbital: Close clinical monitoring is advised when administering acetaminophen with telaprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen 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 acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations.
Acetaminophen; Butalbital; Caffeine: Close clinical monitoring is advised when administering acetaminophen with telaprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen 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 acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations.
Acetaminophen; Butalbital; Caffeine; Codeine: Close clinical monitoring is advised when administering acetaminophen with telaprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen 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 acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations.
Acetaminophen; Caffeine; Dihydrocodeine: Close clinical monitoring is advised when administering acetaminophen with telaprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen 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 acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations.
Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: Close clinical monitoring is advised when administering acetaminophen with telaprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen 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 acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations.
Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: Close clinical monitoring is advised when administering acetaminophen with telaprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen 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 acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: Close clinical monitoring is advised when administering acetaminophen with telaprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen 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 acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations. Close clinical monitoring is advised when administering dextromethorphan with telaprevir due to an increased potential for dextromethorphan-related adverse events. If dextromethorphan 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 dextromethorphan. Dextromethorphan is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated dextromethorphan plasma concentrations.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: Close clinical monitoring is advised when administering acetaminophen with telaprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen 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 acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations. Close clinical monitoring is advised when administering dextromethorphan with telaprevir due to an increased potential for dextromethorphan-related adverse events. If dextromethorphan 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 dextromethorphan. Dextromethorphan is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated dextromethorphan plasma concentrations.
Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: Close clinical monitoring is advised when administering acetaminophen with telaprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen 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 acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations.
Acetaminophen; Codeine: Close clinical monitoring is advised when administering acetaminophen with telaprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen 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 acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations.
Acetaminophen; Dextromethorphan: Close clinical monitoring is advised when administering acetaminophen with telaprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen 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 acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations. Close clinical monitoring is advised when administering dextromethorphan with telaprevir due to an increased potential for dextromethorphan-related adverse events. If dextromethorphan 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 dextromethorphan. Dextromethorphan is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated dextromethorphan plasma concentrations.
Acetaminophen; Dextromethorphan; Doxylamine: Close clinical monitoring is advised when administering acetaminophen with telaprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen 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 acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations. Close clinical monitoring is advised when administering dextromethorphan with telaprevir due to an increased potential for dextromethorphan-related adverse events. If dextromethorphan 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 dextromethorphan. Dextromethorphan is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated dextromethorphan plasma concentrations.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: Close clinical monitoring is advised when administering acetaminophen with telaprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen 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 acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations. Close clinical monitoring is advised when administering dextromethorphan with telaprevir due to an increased potential for dextromethorphan-related adverse events. If dextromethorphan 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 dextromethorphan. Dextromethorphan is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated dextromethorphan plasma concentrations.
Acetaminophen; Dextromethorphan; Phenylephrine: Close clinical monitoring is advised when administering acetaminophen with telaprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen 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 acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations. Close clinical monitoring is advised when administering dextromethorphan with telaprevir due to an increased potential for dextromethorphan-related adverse events. If dextromethorphan 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 dextromethorphan. Dextromethorphan is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated dextromethorphan plasma concentrations.
Acetaminophen; Dextromethorphan; Pseudoephedrine: Close clinical monitoring is advised when administering acetaminophen with telaprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen 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 acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations. Close clinical monitoring is advised when administering dextromethorphan with telaprevir due to an increased potential for dextromethorphan-related adverse events. If dextromethorphan 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 dextromethorphan. Dextromethorphan is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated dextromethorphan plasma concentrations.
Acetaminophen; Dichloralphenazone; Isometheptene: Close clinical monitoring is advised when administering acetaminophen with telaprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen 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 acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations.
Acetaminophen; Diphenhydramine: Close clinical monitoring is advised when administering acetaminophen with telaprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen 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 acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations.
Acetaminophen; Guaifenesin; Phenylephrine: Close clinical monitoring is advised when administering acetaminophen with telaprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen 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 acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations.
Acetaminophen; Hydrocodone: Monitor for respiratory depression and sedation if hydrocodone and telaprevir are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as telaprevir, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects. Close clinical monitoring is advised when administering acetaminophen with telaprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen 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 acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations.
Acetaminophen; Oxycodone: Close clinical monitoring is advised when administering acetaminophen with telaprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen 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 acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations. Close clinical monitoring is advised when administering oxycodone with telaprevir due to an increased potential for oxycodone-related adverse events. If oxycodone 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 oxycodone. Oxycodone is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated oxycodone plasma concentrations.
Acetaminophen; Pentazocine: Close clinical monitoring is advised when administering acetaminophen with telaprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen 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 acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations.
Acetaminophen; Propoxyphene: Close clinical monitoring is advised when administering acetaminophen with telaprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen 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 acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations.
Acetaminophen; Pseudoephedrine: Close clinical monitoring is advised when administering acetaminophen with telaprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen 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 acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations.
Acetaminophen; Tramadol: Close clinical monitoring is advised when administering acetaminophen with telaprevir due to an increased potential for acetaminophen-related adverse events. If acetaminophen 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 acetaminophen. Acetaminophen is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated acetaminophen plasma concentrations. Close clinical monitoring is advised when administering tramadol with telaprevir due to an increased potential for tramadol-related adverse events. If tramadol 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 tramadol. Tramadol is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated tramadol plasma concentrations.
Ado-Trastuzumab emtansine: Avoid concomitant use of ado-trastuzumab emtansine, a CYP3A4 substrate, and telaprevir, a strong CYP3A4 inhibitor, as ado-trastuzumab emtansine plasma exposure may be increased.
Afatinib: Concomitant use of afatinib, a P-glycoprotein (P-gp) substrate, and telaprevir, a P-gp inhibitor, may increase the exposure of afatinib. If the use of both agents is necessary, consider reducing the starting afatinib dose to 30 mg/day if the original dose is not tolerated. Resume the previous dose if telaprevir is discontinued.
Aldesleukin, IL-2: Close clinical monitoring is advised when administering aldesleukin, IL-2 with telaprevir due to an increased potential for aldesleukin-related adverse events. If aldesleukin 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 pathways of aldesleukin and telaprevir. Both aldesleukin and telaprevir are inhibitors of the hepatic isoenzyme CYP3A4. When used in combination, the plasma concentrations of both medications may be elevated.
Alfentanil: Close clinical monitoring is advised when administering alfentanil with telaprevir due to an increased potential for alfentanil-related adverse events. If alfentanil 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 alfentanil. Alfentanil is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated alfentanil plasma concentrations.
Alfuzosin: The concurrent use of alfuzosin and telaprevir is contraindicated due to the potential for serious/life-threatening reactions. Telaprevir is an 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 and cardiac arrhythmias.
Aliskiren: Close clinical monitoring is advised when administering aliskiren with telaprevir due to an increased potential for aliskiren-related adverse events. If aliskiren 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 aliskiren. Aliskiren is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated aliskiren plasma concentrations.
Aliskiren; Amlodipine: Close clinical monitoring is advised when administering aliskiren with telaprevir due to an increased potential for aliskiren-related adverse events. If aliskiren 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 aliskiren. Aliskiren is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated aliskiren plasma concentrations. Close clinical monitoring is advised when administering amlodipine with telaprevir due to an increased potential for amlodipine-related adverse events. A reduction in the dose of amlodipine should be considered. If amlodipine dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Predictions about the interaction can be made based on the metabolic pathway of amlodipine. Amlodipine is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated amlodipine plasma concentrations.
Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: Close clinical monitoring is advised when administering aliskiren with telaprevir due to an increased potential for aliskiren-related adverse events. If aliskiren 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 aliskiren. Aliskiren is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated aliskiren plasma concentrations. Close clinical monitoring is advised when administering amlodipine with telaprevir due to an increased potential for amlodipine-related adverse events. A reduction in the dose of amlodipine should be considered. If amlodipine dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Predictions about the interaction can be made based on the metabolic pathway of amlodipine. Amlodipine is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated amlodipine plasma concentrations.
Aliskiren; Hydrochlorothiazide, HCTZ: Close clinical monitoring is advised when administering aliskiren with telaprevir due to an increased potential for aliskiren-related adverse events. If aliskiren 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 aliskiren. Aliskiren is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated aliskiren plasma concentrations.
Aliskiren; Valsartan: Close clinical monitoring is advised when administering aliskiren with telaprevir due to an increased potential for aliskiren-related adverse events. If aliskiren 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 aliskiren. Aliskiren is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated aliskiren plasma concentrations.
Almotriptan: Close clinical monitoring is advised when administering almotriptan with telaprevir due to an increased potential for almotriptan-related adverse events. If almotriptan 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 almotriptan. Almotriptan is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated almotriptan plasma concentrations.
Alogliptin; Pioglitazone: Close clinical monitoring is advised when administering pioglitazone with telaprevir due to an increased potential for pioglitazone-related adverse events and the potential for telaprevir treatment failure. If pioglitazone 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 pathways of pioglitazone and telaprevir. Pioglitazone is a substrate and inducer of the hepatic isoenzyme CYP3A4; telaprevir is a substrate and an inhibitor of this isoenzyme. When used in combination, the plasma concentrations of pioglitazone may increase and the plasma concentrations of telaprevir may decrease.
Alosetron: Close clinical monitoring is advised when administering alosetron with telaprevir due to an increased potential for alosetron-related adverse events. If alosetron 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 alosetron. Alosetron is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated alosetron plasma concentrations.
Alprazolam: Close clinical monitoring is advised when administering alprazolam with telaprevir due to an increased potential for serious alprazolam-related adverse events. If alprazolam dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Predictions about the interaction can be made based on the metabolic pathway of alprazolam. Alprazolam is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated alprazolam plasma concentrations.
Amiodarone: Close clinical monitoring is advised when administering amiodarone with telaprevir 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 telaprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of amiodarone and telaprevir. Both amiodarone and telaprevir 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 telaprevir. When used in combination, the plasma concentrations of both medications may be elevated.
Amitriptyline: Close clinical monitoring is advised when administering amitriptyline with telaprevir due to an increased potential for amitriptyline-related adverse events. If amitriptyline 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 amitriptyline. Amitriptyline is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; telaprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated amitriptyline plasma concentrations.
Amitriptyline; Chlordiazepoxide: Close clinical monitoring is advised when administering amitriptyline with telaprevir due to an increased potential for amitriptyline-related adverse events. If amitriptyline 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 amitriptyline. Amitriptyline is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; telaprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated amitriptyline plasma concentrations.
Amlodipine: Close clinical monitoring is advised when administering amlodipine with telaprevir due to an increased potential for amlodipine-related adverse events. A reduction in the dose of amlodipine should be considered. If amlodipine dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Predictions about the interaction can be made based on the metabolic pathway of amlodipine. Amlodipine is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated amlodipine plasma concentrations.
Amlodipine; Atorvastatin: The concurrent use of atorvastatin and telaprevir should be avoided because of the potential for serious adverse reactions, including myopathy and rhabdomyolysis. Telaprevir is an inhibitor of CYP3A4, which is responsible for atorvastatin metabolism; coadministration results in significant increases in the pharmacokineitic parameters (AUC and Cmax) of atorvastatin. Close clinical monitoring is advised when administering amlodipine with telaprevir due to an increased potential for amlodipine-related adverse events. A reduction in the dose of amlodipine should be considered. If amlodipine dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Predictions about the interaction can be made based on the metabolic pathway of amlodipine. Amlodipine is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated amlodipine plasma concentrations.
Amlodipine; Benazepril: Close clinical monitoring is advised when administering amlodipine with telaprevir due to an increased potential for amlodipine-related adverse events. A reduction in the dose of amlodipine should be considered. If amlodipine dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Predictions about the interaction can be made based on the metabolic pathway of amlodipine. Amlodipine is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated amlodipine plasma concentrations.
Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: Close clinical monitoring is advised when administering amlodipine with telaprevir due to an increased potential for amlodipine-related adverse events. A reduction in the dose of amlodipine should be considered. If amlodipine dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Predictions about the interaction can be made based on the metabolic pathway of amlodipine. Amlodipine is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated amlodipine plasma concentrations.
Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: Close clinical monitoring is advised when administering amlodipine with telaprevir due to an increased potential for amlodipine-related adverse events. A reduction in the dose of amlodipine should be considered. If amlodipine dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Predictions about the interaction can be made based on the metabolic pathway of amlodipine. Amlodipine is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated amlodipine plasma concentrations.
Amlodipine; Olmesartan: Close clinical monitoring is advised when administering amlodipine with telaprevir due to an increased potential for amlodipine-related adverse events. A reduction in the dose of amlodipine should be considered. If amlodipine dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Predictions about the interaction can be made based on the metabolic pathway of amlodipine. Amlodipine is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated amlodipine plasma concentrations.
Amlodipine; Telmisartan: Close clinical monitoring is advised when administering amlodipine with telaprevir due to an increased potential for amlodipine-related adverse events. A reduction in the dose of amlodipine should be considered. If amlodipine dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Predictions about the interaction can be made based on the metabolic pathway of amlodipine. Amlodipine is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated amlodipine plasma concentrations.
Amlodipine; Valsartan: Close clinical monitoring is advised when administering amlodipine with telaprevir due to an increased potential for amlodipine-related adverse events. A reduction in the dose of amlodipine should be considered. If amlodipine dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Predictions about the interaction can be made based on the metabolic pathway of amlodipine. Amlodipine is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated amlodipine plasma concentrations.
Amoxicillin; Clarithromycin; Lansoprazole: Close clinical monitoring is advised when administering clarithromycin with telaprevir due to an increased potential for serious clarithromycin-related adverse events, such as QT prolongation and torsade de pointes (TdP). Predictions about the interaction can be made based on the metabolic pathways of clarithromycin and telaprevir. Both clarithromycin and telaprevir are substrates and inhibitors of the hepatic isoenzyme CYP3A4. Additionally, clarithromycin is an inhibitor of P-glycoprotein (P-gp), an efflux transporter partially responsible for the metabolism of telaprevir. When used in combination, the plasma concentrations of both medications may be elevated. Monitor for evidence of interactions. If clarithromycin dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Close clinical monitoring is advised when administering lansoprazole with telaprevir due to an increased potential for lansoprazole-related adverse events. If lansoprazole 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 lansoprazole. Lansoprazole is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; telaprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated lansoprazole plasma concentrations.
Amoxicillin; Clarithromycin; Omeprazole: Close clinical monitoring is advised when administering clarithromycin with telaprevir due to an increased potential for serious clarithromycin-related adverse events, such as QT prolongation and torsade de pointes (TdP). Predictions about the interaction can be made based on the metabolic pathways of clarithromycin and telaprevir. Both clarithromycin and telaprevir are substrates and inhibitors of the hepatic isoenzyme CYP3A4. Additionally, clarithromycin is an inhibitor of P-glycoprotein (P-gp), an efflux transporter partially responsible for the metabolism of telaprevir. When used in combination, the plasma concentrations of both medications may be elevated. Monitor for evidence of interactions. If clarithromycin dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Close clinical monitoring is advised when administering omeprazole with telaprevir due to an increased potential for omeprazole-related adverse events. If omeprazole 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 omeprazole. Omeprazole is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; telaprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated omeprazole plasma concentrations.
Aprepitant, Fosaprepitant: Close clinical monitoring is advised when administering aprepitant, fosaprepitant with telaprevir due to an increased potential for aprepitant, fosaprepitant-related adverse events. If aprepitant, fosaprepitant 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 pathways of aprepitant, fosaprepitant and telaprevir. Aprepitant, fosaprepitant is a substrate, inducer, and inhibitor of the hepatic isoenzyme CYP3A4; telaprevir is a substrate and an inhibitor of this isoenzyme. When used in combination, the plasma concentrations of both medications may be altered.
Aripiprazole: Because aripiprazole is 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 telaprevir. In adults receiving 300 mg or 400 mg of the extended-release aripiprazole injection, dose reductions to 200 mg or 300 mg, respectively, are recommended if the CYP3A4 inhibitor is used for more than 14 days. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. 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 of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving the extended-release aripiprazole injection who are PMs 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 extended-release aripiprazole intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
Artemether; Lumefantrine: Close clinical monitoring is advised when administering artemether with telaprevir due to an increased potential for artemether-related adverse events. If artemether 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. Artemether is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated artemether plasma concentrations.
Aspirin, ASA; Omeprazole: Close clinical monitoring is advised when administering omeprazole with telaprevir due to an increased potential for omeprazole-related adverse events. If omeprazole 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 omeprazole. Omeprazole is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; telaprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated omeprazole plasma concentrations.
Aspirin, ASA; Oxycodone: Close clinical monitoring is advised when administering oxycodone with telaprevir due to an increased potential for oxycodone-related adverse events. If oxycodone 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 oxycodone. Oxycodone is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated oxycodone plasma concentrations.
Atazanavir; Cobicistat: Avoid concurrent use of cobicistat with telaprevir, as drug interaction data are not available. Clinically significant drug interactions may occur during coadministration.
Atorvastatin: The concurrent use of atorvastatin and telaprevir should be avoided because of the potential for serious adverse reactions, including myopathy and rhabdomyolysis. Telaprevir is an inhibitor of CYP3A4, which is responsible for atorvastatin metabolism; coadministration results in significant increases in the pharmacokineitic parameters (AUC and Cmax) of atorvastatin.
Atorvastatin; Ezetimibe: The concurrent use of atorvastatin and telaprevir should be avoided because of the potential for serious adverse reactions, including myopathy and rhabdomyolysis. Telaprevir is an inhibitor of CYP3A4, which is responsible for atorvastatin metabolism; coadministration results in significant increases in the pharmacokineitic parameters (AUC and Cmax) of atorvastatin.
Atropine; Hyoscyamine; Phenobarbital; Scopolamine: The concomitant use of telaprevir and phenobarbital is contraindicated due to the potential loss of efficacy of telaprevir. Predictions about the interaction can be made based on the metabolic pathways of phenobarbital and telaprevir. Phenobarbital is an inducer of the hepatic isoenzyme CYP3A4; an isoenzyme partially responsible for the metabolism of telaprevir. When used in combination, the plasma concentrations of telaprevir may be deceased and phenobarbital plasma concentration may be altered, resulting in an increased potential for telaprevir treatment failure and phenobarbital-related adverse events.
Avanafil: 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 telaprevir, should not take avanafil.
Azelastine; Fluticasone: Concurrent administration of fluticasone and telaprevir is not recommended unless the benefits outweigh the risks. If they are coadministered, close monitoring for corticosteroid-related adverse events is advised. If fluticasone dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment.
Azithromycin: Close clinical monitoring is advised when administering azithromycin with telaprevir due to an increased potential for azithromycin-related adverse events. If azithromycin 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 pathways of azithromycin and telaprevir. Both azithromycin and telaprevir are substrates and inhibitors of drug efflux transporter, P-glycoprotein (PGP). When used in combination, the plasma concentrations of both medications may be elevated.
Basiliximab: Close clinical monitoring is advised when administering basiliximab with telaprevir due to an increased potential for telaprevir-related adverse events. If basiliximab 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 pathways of basiliximab and telaprevir. Basiliximab is an inhibitor of the hepatic isoenzyme CYP3A4; telaprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of telaprevir may be elevated.
Bedaquiline: Concurrent use of bedaquiline and a strong CYP3A4 inhibitor, such as telaprevir, for more than 14 days should be avoided unless the benefits justify the risks. When administered together, telaprevir 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: Concurrent use of ergot alkaloids and telaprevir is contraindicated due to the potential for serious/life-threatening ergot toxicities, such as peripheral vasospasm and ischemia of the extremities and other tissues. Telaprevir is an 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. The concomitant use of telaprevir and phenobarbital is contraindicated due to the potential loss of efficacy of telaprevir. Predictions about the interaction can be made based on the metabolic pathways of phenobarbital and telaprevir. Phenobarbital is an inducer of the hepatic isoenzyme CYP3A4; an isoenzyme partially responsible for the metabolism of telaprevir. When used in combination, the plasma concentrations of telaprevir may be deceased and phenobarbital plasma concentration may be altered, resulting in an increased potential for telaprevir treatment failure and phenobarbital-related adverse events.
Bepridil: Close clinical monitoring is advised when administering bepridil with telaprevir 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 telaprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of bepredil. Bepridil is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Additionally, bepridil is an inhibitor of P-glycoprotein (PGP), an efflux transporter partially responsible for the metabolism of telaprevir. When used in combination, the plasma concentrations of both medications may be elevated.
Bexarotene: Close clinical monitoring is advised when administering bexarotene with telaprevir due to an increased potential for bexarotene-related adverse events and for the potential for telaprevir treatment failure. If bexarotene 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 pathways of bexarotene and telaprevir. Bexarotene is a substrate and inducer of the hepatic isoenzyme CYP3A4; telaprevir is a substrate and an inhibitor of this isoenzyme. When used in combination, the plasma concentrations of bexarotene may increase and the plasma concentration of telaprevir may decrease.
Bortezomib: Close clinical monitoring is advised when administering bortezomib with telaprevir due to an increased potential for bortezomib-related adverse events. If bortezomib 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 bortezomib. Bortezomib is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated bortezomib plasma concentrations.
Bosentan: Close clinical monitoring is advised when administering bosentan with telaprevir due to an increased potential for bosentan-related adverse events and the potential for decreased telaprevir efficacy. If bosentan dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Predictions about the interaction can be made based on the metabolic pathways of bosentan and telaprevir. Bosentan is an inducer and substrate of the hepatic isoenzyme CYP3A4; telaprevir is an inhibitor and substrate of this isoenzyme. When used in combination, bosentan plasma concentrations may be elevated and telaprevir plasma concentrations may be deceased, resulting in an increased potential for bosentan-related adverse events and telaprevir treatment failure.
Bosutinib: Avoid concomitant use of bosutinib and telaprevir; 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 telaprevir 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.
Brexpiprazole: 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 telaprevir. 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 and moderate to strong CYP2D6 inhibitor should have their brexpiprazole dose reduced to one-quarter (25%) of the usual dose.
Bromocriptine: Close clinical monitoring is advised when administering bromocriptine with telaprevir due to an increased potential for telaprevir-related adverse events. If bromocriptine 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 pathways of bromocriptine and telaprevir. Bromocriptine is an inhibitor of the hepatic isoenzyme CYP3A4; telaprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of telaprevir may be elevated.
Brompheniramine; Dextromethorphan; Guaifenesin: Close clinical monitoring is advised when administering dextromethorphan with telaprevir due to an increased potential for dextromethorphan-related adverse events. If dextromethorphan 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 dextromethorphan. Dextromethorphan is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated dextromethorphan plasma concentrations.
Brompheniramine; Guaifenesin; Hydrocodone: Monitor for respiratory depression and sedation if hydrocodone and telaprevir are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as telaprevir, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects.
Brompheniramine; Hydrocodone; Pseudoephedrine: Monitor for respiratory depression and sedation if hydrocodone and telaprevir are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as telaprevir, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects.
Budesonide: Concurrent administration of budesonide and telaprevir 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, re-adjust the dose upon completion of telaprevir 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); telaprevir inhibits both the isoenzyme and the drug efflux pump. Coadministration may result in elevated budesonide plasma concentrations.
Budesonide; Formoterol: Concurrent administration of budesonide and telaprevir 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, re-adjust the dose upon completion of telaprevir 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); telaprevir inhibits both the isoenzyme and the drug efflux pump. Coadministration may result in elevated budesonide plasma concentrations.
Bupivacaine Liposomal: Close clinical monitoring is advised when administering bupivacaine with telaprevir due to an increased potential for bupivacaine-related adverse events. If bupivacaine 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 bupivacaine. Bupivacaine is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated bupivacaine plasma concentrations.
Bupivacaine: Close clinical monitoring is advised when administering bupivacaine with telaprevir due to an increased potential for bupivacaine-related adverse events. If bupivacaine 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 bupivacaine. Bupivacaine is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated bupivacaine plasma concentrations.
Bupivacaine; Lidocaine: Close clinical monitoring is advised when administering systemic lidocaine with telaprevir 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 telaprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on metabolic pathways. Lidocaine is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated lidocaine plasma concentrations. Close clinical monitoring is advised when administering bupivacaine with telaprevir due to an increased potential for bupivacaine-related adverse events. If bupivacaine 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 bupivacaine. Bupivacaine is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated bupivacaine plasma concentrations.
Buprenorphine: Close clinical monitoring is advised when administering buprenorphine with telaprevir due to an increased potential for buprenorphine-related adverse events. If buprenorphine 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 buprenorphine. buprenorphine is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated buprenorphine plasma concentrations.
Buprenorphine; Naloxone: Close clinical monitoring is advised when administering buprenorphine with telaprevir due to an increased potential for buprenorphine-related adverse events. If buprenorphine 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 buprenorphine. buprenorphine is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated buprenorphine plasma concentrations.
Buspirone: Close clinical monitoring is advised when administering buspirone with telaprevir due to an increased potential for buspirone-related adverse events. If buspirone 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 buspirone. Buspirone is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated buspirone plasma concentrations.
Cabazitaxel: Cabazitaxel is a CYP3A4 substrate, and telaprevir is a strong CYP3A4 inhibitor. Repeated administration of another strong CYP3A4 inhibitor, ketoconazole, increased the exposure of cabazitaxel (5 mg/m2) by 25% in a drug interaction study of patients with advanced cancers (n = 23). Concomitant administration of cabazitaxel and strong CYP3A4 inhibitors should be avoided; if co-administration is necessary, consider reducing the cabazitaxel dose by 25%.
Caffeine; Ergotamine: Concurrent use of ergot alkaloids and telaprevir is contraindicated due to the potential for serious/life-threatening ergot toxicities, such as peripheral vasospasm and ischemia of the extremities and other tissues. Telaprevir is an 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.
Canagliflozin: Canagliflozin is a substrate/weak inhibit

or of drug transporter P glycoprotein (P-gp). Telaprevir is a mild PGP inhibitor and PGP substrate. Theoretically, concentrations of either drug may be increased. Patients should be monitored for changes in glycemic control and possible adverse reactions.
Canagliflozin; Metformin: Canagliflozin is a substrate/weak inhibitor of drug transporter P glycoprotein (P-gp). Telaprevir is a mild PGP inhibitor and PGP substrate. Theoretically, concentrations of either drug may be increased. Patients should be monitored for changes in glycemic control and possible adverse reactions.
Carbamazepine: The concomitant use of telaprevir and carbamazepine is contraindicated due to the potential loss of efficacy of telaprevir. Telapravir exposure (AUC) decreases to 68% of normal and the Cmax decreases to 79% of normal with concomitant carbamazepine use. The change in carbamazepine concentrations is minimal. Carbamazepine is an inducer and substrate of the hepatic isoenzyme CYP3A4; telaprevir is an inhibitor and substrate of this isoenzyme. Additionally, carbamazepine induces P-glycoprotein (PGP), a drug efflux transporter partially responsible for the metabolism of telaprevir.
Carbinoxamine; Dextromethorphan; Pseudoephedrine: Close clinical monitoring is advised when administering dextromethorphan with telaprevir due to an increased potential for dextromethorphan-related adverse events. If dextromethorphan 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 dextromethorphan. Dextromethorphan is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated dextromethorphan plasma concentrations.
Carbinoxamine; Hydrocodone; Phenylephrine: Monitor for respiratory depression and sedation if hydrocodone and telaprevir are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as telaprevir, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects.
Carbinoxamine; Hydrocodone; Pseudoephedrine: Monitor for respiratory depression and sedation if hydrocodone and telaprevir are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as telaprevir, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects.
Cariprazine: Cariprazine and its active metabolites are extensively metabolized by CYP3A4. When a strong CYP3A4 inhibitor, such as telaprevir, 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: Altered concentrations of telaprevir and/or carvedilol may occur during coadministration. Carvedilol and telaprevir are both substrates and inhibitors of P-glycoprotein (P-gp). Use caution if concomitant use is necessary and monitor for increased side effects.
Ceritinib: Telaprevir is a strong inhibitor of CYP3A4 and is a substrate of P-glycoprotein (P-gp). Ceritinib is a substrate of CYP3A4 and P-gp, and is associated with QT prolongation. Ceritinib should not be given with a strong CYP3A4 inhibitor. If co-administration is necessary, decrease the ceritinib dose by approximately one-third, rounded to the nearest 150 mg, and monitor the patient for QT interval prolongation and other ceritinib toxicities. If telaprevir is discontinued, resume the recommended ceritinib dose after a washout period based on the half-life of telaprevir.
Cevimeline: Close clinical monitoring is advised when administering cevimeline with telaprevir due to an increased potential for cevimeline-related adverse events. If cevimeline 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 cevimeline. Cevimeline is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated cevimeline plasma concentrations.
Chloramphenicol: Close clinical monitoring is advised when administering chloramphenicol with telaprevir due to an increased potential for telaprevir-related adverse events. If chloramphenicol 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 pathways of chloramphenicol and telaprevir. Chloramphenicol is an inhibitor of the hepatic isoenzyme CYP3A4; telaprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of telaprevir may be elevated.
Chloroquine: Close clinical monitoring is advised when administering chloroquine with telaprevir due to an increased potential for chloroquine-related adverse events. If chloroquine 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 chloroquine. Chloroquine is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated chloroquine plasma concentrations.
Chlorpheniramine; Dextromethorphan: Close clinical monitoring is advised when administering dextromethorphan with telaprevir due to an increased potential for dextromethorphan-related adverse events. If dextromethorphan 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 dextromethorphan. Dextromethorphan is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated dextromethorphan plasma concentrations.
Chlorpheniramine; Dextromethorphan; Phenylephrine: Close clinical monitoring is advised when administering dextromethorphan with telaprevir due to an increased potential for dextromethorphan-related adverse events. If dextromethorphan 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 dextromethorphan. Dextromethorphan is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated dextromethorphan plasma concentrations.
Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: Monitor for respiratory depression and sedation if hydrocodone and telaprevir are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as telaprevir, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects.
Chlorpheniramine; Hydrocodone: Monitor for respiratory depression and sedation if hydrocodone and telaprevir are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as telaprevir, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects.
Chlorpheniramine; Hydrocodone; Phenylephrine: Monitor for respiratory depression and sedation if hydrocodone and telaprevir are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as telaprevir, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects.
Chlorpheniramine; Hydrocodone; Pseudoephedrine: Monitor for respiratory depression and sedation if hydrocodone and telaprevir are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as telaprevir, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects.
Cilostazol: Close clinical monitoring is advised when administering cilostazol with telaprevir due to an increased potential for cilostazol-related adverse events. If cilostazol 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 cilostazol. Cilostazol is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated cilostazol plasma concentrations.
Cimetidine: Close clinical monitoring is advised when administering cimetidine with telaprevir due to an increased potential for telaprevir-related adverse events. If cimetidine 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 pathways of cimetidine and telaprevir. Cimetidine is an inhibitor of the hepatic isoenzyme CYP3A4; telaprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of telaprevir may be elevated.
Cinacalcet: Close clinical monitoring is advised when administering cinacalcet with telaprevir due to an increased potential for cinacalcet-related adverse events. If cinacalcet 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 cinacalcet. Cinacalcet is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated cinacalcet plasma concentrations.
Cisapride: The concurrent use of cisapride and telaprevir is contraindicated due to the potential for serious/life-threatening reactions. Telaprevir is an 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 serious cardiac arrhythmias, including QT prolongation.
Citalopram: Close clinical monitoring is advised when administering citalopram with telaprevir due to an increased potential for citalopram-related adverse events. If citalopram 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 citalopram. Citalopram is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated citalopram plasma concentrations.
Clarithromycin: Close clinical monitoring is advised when administering clarithromycin with telaprevir due to an increased potential for serious clarithromycin-related adverse events, such as QT prolongation and torsade de pointes (TdP). Predictions about the interaction can be made based on the metabolic pathways of clarithromycin and telaprevir. Both clarithromycin and telaprevir are substrates and inhibitors of the hepatic isoenzyme CYP3A4. Additionally, clarithromycin is an inhibitor of P-glycoprotein (P-gp), an efflux transporter partially responsible for the metabolism of telaprevir. When used in combination, the plasma concentrations of both medications may be elevated. Monitor for evidence of interactions. If clarithromycin dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment.
Clofarabine: Concomitant use of clofarabine, a substrate of OAT1 and OAT3, and telaprevir, an inhibitor of OAT protein (OATP), may result in increased clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OATP inhibitors.
Clomipramine: Close clinical monitoring is advised when administering clomipramine with telaprevir due to an increased potential for clomipramine-related adverse events. If clomipramine 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 clomipramine. Clomipramine is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated clomipramine plasma concentrations.
Clonazepam: Close clinical monitoring is advised when administering clonazepam with telaprevir due to an increased potential for clonazepam-related adverse events. If clonazepam 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 clonazepam. Clonazepam is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated clonazepam plasma concentrations.
Clopidogrel: Close clinical monitoring is advised when administering clopidogrel with telaprevir due to an increased potential for clopidogrel-related adverse events. If clopidogrel 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 clopidogrel. Clopidogrel is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated clopidogrel plasma concentrations.
Clozapine: Caution is advisable during concurrent use of telaprevir and clozapine. Telaprevir 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 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.
Cobicistat: Avoid concurrent use of cobicistat with telaprevir, as drug interaction data are not available. Clinically significant drug interactions may occur during coadministration.
Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide: Avoid concurrent use of cobicistat with telaprevir, as drug interaction data are not available. Clinically significant drug interactions may occur during coadministration. Avoid concurrent use of elvitegravir containing antiretroviral regimens with telaprevir. If these drugs are used together, there is a potential for reduced telaprevir 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.
Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate: Avoid concurrent use of cobicistat with telaprevir, as drug interaction data are not available. Clinically significant drug interactions may occur during coadministration. Avoid concurrent use of elvitegravir containing antiretroviral regimens with telaprevir. If these drugs are used together, there is a potential for reduced telaprevir 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. Close clinical monitoring is advised when coadministering tenofovir, PMPA with telaprevir due to an increased potential for tenofovir-related adverse events. When used in combination, the plasma concentrations of tenofovir were increased, resulting in an increased potential for tenofovir-associated adverse reactions. If tenofovir dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment.
Colchicine: Coadministration of colchicine and telaprevir should be avoided due to the potential for serious and life-threatening toxicity. Colchicine is a P-glycoprotein (P-gp) and CYP3A4 substrate and telaprevir is a mild P-gp inhibitor and strong CYP3A4 inhibitor; increased concentrations of colchicine are expected with concurrent use. Colchicine accumulation may be greater in patients with renal or hepatic impairment; therefore, the coadministration of colchicine and combined P-gp/CYP3A4 inhibitors is contraindicated in this population. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine either by reducing the daily dose or reducing the dose frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations for patients who have received a strong CYP3A4 inhibitor within the prior 14 days are provided by the manufacturer of Colcrys.
Conivaptan: Close clinical monitoring is advised when administering conivaptan with telaprevir due to an increased potential for conivaptan-related adverse events. If conivaptan 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 pathways of conivaptan and telaprevir. Both conivaptan and telaprevir are substrates and inhibitors of the hepatic isoenzyme CYP3A4. When used in combination, the plasma concentrations of both medications may be elevated.
Conjugated Estrogens; Medroxyprogesterone: Coadministration of medroxyprogesterone, a CYP3A substrate with telaprevir, a strong CYP3A inhibitor should be avoided since it is expected to increase concentrations of medroxyprogesterone acetate. Formal drug interaction studies have not been conducted; however, medroxyprogesterone is metabolized primarily by hydroxylation via the CYP3A4 in vitro.
Cyclobenzaprine: Close clinical monitoring is advised when administering cyclobenzaprine with telaprevir due to an increased potential for cyclobenzaprine-related adverse events. If cyclobenzaprine 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 cyclobenzaprine. Cyclobenzaprine is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated cyclobenzaprine plasma concentrations.
Cyclosporine: Close monitoring of cyclosporine serum concentrations and frequent assessments of renal function are advised when coadministering cyclosporine with telaprevir. Cyclosporine is a substrate of the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Additionally, both cyclosporine and telaprevir 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 4.5-fold and 1.3-fold, respectively, when administered in combination with telaprevir; 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 telaprevir treatment.
Dabigatran: Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with telaprevir, 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 telaprevir 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 telaprevir, 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.
Dalfopristin; Quinupristin: Close clinical monitoring is advised when administering dalfopristin; quinupristin with telaprevir due to an increased potential for telaprevir-related adverse events. If dalfopristin; quinupristin 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 pathways of dalfopristin; quinupristin and telaprevir. Dalfopristin; quinupristin is an inhibitor of the hepatic isoenzyme CYP3A4; telaprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of telaprevir may be elevated.
Danazol: Close clinical monitoring is advised when administering danazol with telaprevir due to an increased potential for telaprevir-related adverse events. If danazol 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 pathways of danazol and telaprevir. Danazol is an inhibitor of the hepatic isoenzyme CYP3A4; telaprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of telaprevir may be elevated.
Dapsone: Close clinical monitoring is advised when administering dapsone with telaprevir due to an increased potential for dapsone-related adverse events. If dapsone 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 dapsone. Dapsone is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated dapsone plasma concentrations.
Darifenacin: Close clinical monitoring is advised when administering darifenacin with telaprevir due to an increased potential for darifenacin-related adverse events. If darifenacin 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 darifenacin. Darifenacin is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated darifenacin plasma concentrations.
Darunavir: Concurrent administration of darunavir and ritonavir with telaprevir is not recommended due to the potential for HIV and hepatitis C treatment failures. When administered in combination, the steady-state exposures of both darunavir and telaprevir were reduced. If darunavir/ritonavir and telaprevir are coadministered, monitor the patient closely for decreased treatment response and virologic rebound.
Darunavir; Cobicistat: Avoid concurrent use of cobicistat with telaprevir, as drug interaction data are not available. Clinically significant drug interactions may occur during coadministration. Concurrent administration of darunavir and ritonavir with telaprevir is not recommended due to the potential for HIV and hepatitis C treatment failures. When administered in combination, the steady-state exposures of both darunavir and telaprevir were reduced. If darunavir/ritonavir and telaprevir are coadministered, monitor the patient closely for decreased treatment response and virologic rebound.
Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: Concurrent administration of telaprevir with dasabuvir; ombitasvir; paritaprevir; ritonavir or ombitasvir; paritaprevir; ritonavir may result in elevated plasma concentrations of both drugs. Both ritonavir and telaprevir are substrates and inhibitors of the hepatic isoenzyme CYP3A4 and the drug transporter P-glycoprotein (P-gp). Paritaprevir and dasabuvir (minor) are CYP3A4 substrates. In addition, dasabuvir, ombitasvir, and paritaprevir are all substrates of P-gp. Telaprevir also inhibits the organic anion transporting polypeptides (OATP) 1B1. Paritaprevir is a substrate of OATP1B1. Caution and close monitoring is advised if these drugs are administered together.
Dasatinib: Close clinical monitoring is advised when administering dasatinib with telaprevir due to an increased potential for dasatinib-related adverse events. If dasatinib 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 pathways of dasatinib and telaprevir. Both dasatinib and telaprevir are substrates and inhibitors of the hepatic isoenzyme CYP3A4. When used in combination, the plasma concentrations of both medications may be elevated.
Daunorubicin: Close clinical monitoring is advised when administering daunorubicin with telaprevir due to an increased potential for daunorubicin-related adverse events. If daunorubicin 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 daunorubicin. Daunorubicin is a substrate of the drug efflux transporter P-glycoprotein (PGP); telaprevir is an inhibitor of this efflux protein. Coadministration may result in elevated daunorubicin plasma concentrations.
Delavirdine: Close clinical monitoring is advised when administering delavirdine with telaprevir due to an increased potential for delavirdine-related adverse events. If delavirdine 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 pathways of delavirdine and telaprevir. Both delavirdine and telaprevir are substrates and inhibitors of the hepatic isoenzyme CYP3A4. When used in combination, the plasma concentrations of both medications may be elevated.
Desloratadine: Close clinical monitoring is advised when administering desloratadine with telaprevir due to an increased potential for desloratadine-related adverse events. If desloratadine 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 desloratadine. Desloratadine is a substrate of the drug efflux transporter P-glycoprotein (PGP); telaprevir is an inhibitor of this efflux protein. Coadministration may result in elevated desloratadine plasma concentrations.
Desloratadine; Pseudoephedrine: Close clinical monitoring is advised when administering desloratadine with telaprevir due to an increased potential for desloratadine-related adverse events. If desloratadine 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 desloratadine. Desloratadine is a substrate of the drug efflux transporter P-glycoprotein (PGP); telaprevir is an inhibitor of this efflux protein. Coadministration may result in elevated desloratadine plasma concentrations.
Dexamethasone: Coadministration of dexamethasone and telaprevir is not recommended. If coadministered, close clinical monitoring for increased dexamethasone-related adverse events and for decreased telaprevir efficacy is advised. If dexamethasone dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Predictions about the interaction can be made based on the metabolic pathways of dexamethasone and telaprevir. Dexamethasone is an inducer and substrate of the hepatic isoenzyme CYP3A4; telaprevir is an inhibitor and substrate of this isoenzyme. Additionally, both dexamethasone and telaprevir 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 telaprevir may be deceased, resulting in an increased potential for dexamethasone-related adverse events and telaprevir treatment failure.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: Close clinical monitoring is advised when administering dextromethorphan with telaprevir due to an increased potential for dextromethorphan-related adverse events. If dextromethorphan 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 dextromethorphan. Dextromethorphan is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated dextromethorphan plasma concentrations.
Dexlansoprazole: Close clinical monitoring is advised when administering dexlansoprazole with telaprevir due to an increased potential for dexlansoprazole-related adverse events. If dexlansoprazole 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 dexlansoprazole. Dexlansoprazole is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated dexlansoprazole plasma concentrations.
Dextromethorphan: Close clinical monitoring is advised when administering dextromethorphan with telaprevir due to an increased potential for dextromethorphan-related adverse events. If dextromethorphan 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 dextromethorphan. Dextromethorphan is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated dextromethorphan plasma concentrations.
Dextromethorphan; Diphenhydramine; Phenylephrine: Close clinical monitoring is advised when administering dextromethorphan with telaprevir due to an increased potential for dextromethorphan-related adverse events. If dextromethorphan 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 dextromethorphan. Dextromethorphan is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated dextromethorphan plasma concentrations.
Dextromethorphan; Guaifenesin: Close clinical monitoring is advised when administering dextromethorphan with telaprevir due to an increased potential for dextromethorphan-related adverse events. If dextromethorphan 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 dextromethorphan. Dextromethorphan is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated dextromethorphan plasma concentrations.
Dextromethorphan; Guaifenesin; Phenylephrine: Close clinical monitoring is advised when administering dextromethorphan with telaprevir due to an increased potential for dextromethorphan-related adverse events. If dextromethorphan 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 dextromethorphan. Dextromethorphan is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated dextromethorphan plasma concentrations.
Dextromethorphan; Guaifenesin; Potassium Guaiacolsulfonate: Close clinical monitoring is advised when administering dextromethorphan with telaprevir due to an increased potential for dextromethorphan-related adverse events. If dextromethorphan 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 dextromethorphan. Dextromethorphan is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated dextromethorphan plasma concentrations.
Dextromethorphan; Guaifenesin; Pseudoephedrine: Close clinical monitoring is advised when administering dextromethorphan with telaprevir due to an increased potential for dextromethorphan-related adverse events. If dextromethorphan 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 dextromethorphan. Dextromethorphan is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated dextromethorphan plasma concentrations.
Dextromethorphan; Promethazine: Close clinical monitoring is advised when administering dextromethorphan with telaprevir due to an increased potential for dextromethorphan-related adverse events. If dextromethorphan 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 dextromethorphan. Dextromethorphan is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated dextromethorphan plasma concentrations.
Dextromethorphan; Quinidine: Close clinical monitoring is advised when administering quinidine with telaprevir 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 telaprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of quinidine and telaprevir. Quinidine is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Additionally, both quinidine and telaprevir are substrates and inhibitors of P-glycoprotein (P-gp) drug efflux transporter. When used in combination, the plasma concentrations of both medications may be elevated. Close clinical monitoring is advised when administering dextromethorphan with telaprevir due to an increased potential for dextromethorphan-related adverse events. If dextromethorphan 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 dextromethorphan. Dextromethorphan is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated dextromethorphan plasma concentrations.
Diazepam: Close clinical monitoring is advised when administering diazepam with telaprevir due to an increased potential for diazepam-related adverse events. If diazepam 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 diazepam. Diazepam is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated diazepam plasma concentrations.
Diclofenac: Close clinical monitoring is advised when administering diclofenac with telaprevir due to an increased potential for diclofenac-related adverse events. If diclofenac 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 diclofenac. Diclofenac is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated diclofenac plasma concentrations.
Diclofenac; Misoprostol: Close clinical monitoring is advised when administering diclofenac with telaprevir due to an increased potential for diclofenac-related adverse events. If diclofenac 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 diclofenac. Diclofenac is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated diclofenac plasma concentrations.
Dienogest; Estradiol valerate: Close clinical monitoring for signs of estrogen deficiency is advised when administering ethinyl estradiol in combination with telaprevir. When used concurrently, ethinyl estradiol plasma concentrations may be decreased, potentially resulting in impaired efficacy. If ethinyl estradiol dose adjustments are made during combination therapy, re-adjust the dose upon completion of telaprevir treatment. Telaprevir will also likely reduce estrogen levels when administered as mestranol, which is further metabolized to EE. Close clinical monitoring for contraception failure is advised when coadministering combined hormonal oral contraceptives or ethinyl estradiol; etonogestrel contraceptive vaginal ring with telaprevir. Two effective non-hormonal methods of contraception should be used during treatment with telaprevir.
Digoxin: Monitoring of digoxin serum concentrations is advised when administering digoxin with telaprevir due to an increased potential for digoxin-related adverse events. 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 telaprevir treatment.
Dihydroergotamine: Concurrent use of ergot alkaloids and telaprevir is contraindicated due to the potential for serious/life-threatening ergot toxicities, such as peripheral vasospasm and ischemia of the extremities and other tissues. Telaprevir is an 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.
Diltiazem: Close clinical monitoring is advised when administering diltiazem with telaprevir due to an increased potential for diltiazem-related adverse events. If diltiazem dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Predictions about the interaction can be made based on the metabolic pathways of diltiazem and telaprevir. Both diltiazem and telaprevir 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.
Diphenhydramine; Hydrocodone; Phenylephrine: Monitor for respiratory depression and sedation if hydrocodone and telaprevir are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as telaprevir, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects.
Disopyramide: Close clinical monitoring is advised when administering disopyramide with telaprevir due to an increased potential for disopyramide-related adverse events. If disopyramide 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 disopyramide. Disopyramide is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated disopyramide plasma concentrations.
Disulfiram: Close clinical monitoring is advised when administering disulfiram with telaprevir due to an increased potential for disulfiram-related adverse events. If disulfiram 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 disulfiram. disulfiram is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated disulfiram plasma concentrations.
Docetaxel: Close clinical monitoring is advised when administering docetaxel with telaprevir due to an increased potential for docetaxel-related adverse events. If docetaxel 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 docetaxel. Docetaxel is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; telaprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated docetaxel plasma concentrations.
Dolasetron: Close clinical monitoring is advised when administering dolasetron with telaprevir due to an increased potential for dolasetron-related adverse events. If dolasetron 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 dolasetron. Dolasetron is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated dolasetron plasma concentrations.
Donepezil: Close clinical monitoring is advised when administering donepezil with telaprevir due to an increased potential for donepezil-related adverse events. If donepezil 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 donepezil. Donepezil is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated donepezil plasma concentrations.
Donepezil; Memantine: Close clinical monitoring is advised when administering donepezil with telaprevir due to an increased potential for donepezil-related adverse events. If donepezil 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 donepezil. Donepezil is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated donepezil plasma concentrations.
Doxorubicin: Avoid coadministration of telaprevir and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity. Telaprevir is a potent CYP3A4 inhibitor and a mild inhibitor of P-glycoprotein; 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.
Dronedarone: Close clinical monitoring is advised when administering dronedarone with telaprevir due to an increased potential for dronedarone-related adverse events. If dronedarone 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 pathways of dronedarone and telaprevir. Both dronedarone and telaprevir are substrates and inhibitors of the hepatic isoenzyme CYP3A4. Additionally, dronedarone is an inhibitor of the drug efflux transporter P-glycoprotein (PGP); telaprevir is partially metabolized by this efflux protein. When used in combination, the plasma concentrations of both medications may be elevated.
Droperidol: Close clinical monitoring is advised when administering droperidol with telaprevir due to an increased potential for droperidol-related adverse events. If droperidol 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 droperidol. Droperidol is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; telaprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated droperidol plasma concentrations.
Drospirenone; Ethinyl Estradiol: Close clinical monitoring for signs of estrogen deficiency is advised when administering ethinyl estradiol in combination with telaprevir. When used concurrently, ethinyl estradiol plasma concentrations may be decreased, potentially resulting in impaired efficacy. If ethinyl estradiol dose adjustments are made during combination therapy, re-adjust the dose upon completion of telaprevir treatment. Telaprevir will also likely reduce estrogen levels when administered as mestranol, which is further metabolized to EE. Close clinical monitoring for contraception failure is advised when coadministering combined hormonal oral contraceptives or ethinyl estradiol; etonogestrel contraceptive vaginal ring with telaprevir. Two effective non-hormonal methods of contraception should be used during treatment with telaprevir.
Drospirenone; Ethinyl Estradiol; Levomefolate: Close clinical monitoring for signs of estrogen deficiency is advised when administering ethinyl estradiol in combination with telaprevir. When used concurrently, ethinyl estradiol plasma concentrations may be decreased, potentially resulting in impaired efficacy. If ethinyl estradiol dose adjustments are made during combination therapy, re-adjust the dose upon completion of telaprevir treatment. Telaprevir will also likely reduce estrogen levels when administered as mestranol, which is further metabolized to EE. Close clinical monitoring for contraception failure is advised when coadministering combined hormonal oral contraceptives or ethinyl estradiol; etonogestrel contraceptive vaginal ring with telaprevir. Two effective non-hormonal methods of contraception should be used during treatment with telaprevir.
Dutasteride; Tamsulosin: Plasma concentrations of tamsulosin may be increased with concomitant use of telaprevir. Tamsulosin is extensively metabolized by CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Such increases in tamsulosin concentrations may be expected to produce clinically significant and potentially serious side effects, such as hypotension. Therefore, concomitant use with a strong CYP3A4 inhibitor, such as telaprevir, should be avoided.
Edoxaban: Coadministration of edoxaban and telaprevir may result in increased concentrations of edoxaban. Edoxaban is a P-glycoprotein (P-gp) substrate and telaprevir is a mild P-gp inhibitor. Increased concentrations of edoxaban may occur during concomitant use of telaprevir; monitor for increased adverse effects of edoxaban. Dosage reduction may be considered for patients being treated for deep venous thrombosis (DVT) or pulmonary embolism.
Efavirenz: The HIV guidelines recommend increasing the telaprevir dose to 1125 mg every 8 hours when coadministered with efavirenz. Close clinical monitoring is advised during coadministration due to the potential for HIV and hepatitis C treatment failures. If dose adjustments are made, re-adjust the dose upon completion of concurrent treatment. Predictions about the interaction can be made based on each drugs metabolic pathways. Efavirenz is an inducer and substrate of the hepatic isoenzyme CYP3A4; telaprevir is an inhibitor and substrate of this isoenzyme. When used in combination, the mean plasma concentrations (AUC) of telaprevir and efavirenz were deceased by 26% and 7%, respectively.
Efavirenz; Emtricitabine; Tenofovir: Close clinical monitoring is advised when coadministering tenofovir, PMPA with telaprevir due to an increased potential for tenofovir-related adverse events. When used in combination, the plasma concentrations of tenofovir were increased, resulting in an increased potential for tenofovir-associated adverse reactions. If tenofovir dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. The HIV guidelines recommend increasing the telaprevir dose to 1125 mg every 8 hours when coadministered with efavirenz. Close clinical monitoring is advised during coadministration due to the potential for HIV and hepatitis C treatment failures. If dose adjustments are made, re-adjust the dose upon completion of concurrent treatment. Predictions about the interaction can be made based on each drugs metabolic pathways. Efavirenz is an inducer and substrate of the hepatic isoenzyme CYP3A4; telaprevir is an inhibitor and substrate of this isoenzyme. When used in combination, the mean plasma concentrations (AUC) of telaprevir and efavirenz were deceased by 26% and 7%, respectively.
Eletriptan: Close clinical monitoring is advised when administering eletriptan with telaprevir due to an increased potential for eletriptan-related adverse events. If eletriptan 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 eletriptan. Eletriptan is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; telaprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated eletriptan plasma concentrations.
Eliglustat: In intermediate or poor CYP2D6 metabolizers (IMs or PMs), coadministration of telaprevir 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 telaprevir and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Telaprevir 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 telaprevir, 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 telaprevir'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., telaprevir) may result in increased concentrations of the concomitant drug; monitor patients closely for adverse events including nausea, headache, diarrhea, dysgeusia, and vomiting.
Elvitegravir: Avoid concurrent use of elvitegravir containing antiretroviral regimens with telaprevir. If these drugs are used together, there is a potential for reduced telaprevir 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.
Empagliflozin; Linagliptin: 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 disoproxil fumarate: Close clinical monitoring is advised when coadministering tenofovir, PMPA with telaprevir due to an increased potential for tenofovir-related adverse events. When used in combination, the plasma concentrations of tenofovir were increased, resulting in an increased potential for tenofovir-associated adverse reactions. If tenofovir dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment.
Emtricitabine; Tenofovir disoproxil fumarate: Close clinical monitoring is advised when coadministering tenofovir, PMPA with telaprevir due to an increased potential for tenofovir-related adverse events. When used in combination, the plasma concentrations of tenofovir were increased, resulting in an increased potential for tenofovir-associated adverse reactions. If tenofovir dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment.
Enalapril; Felodipine: Close clinical monitoring is advised when administering felodipine with telaprevir due to an increased potential for felodipine-related adverse events. If felodipine dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Predictions about the interaction can be made based on the metabolic pathway of felodipine. Felodipine is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated felodipine plasma concentrations.
Eplerenone: Close clinical monitoring is advised when administering eplerenone with telaprevir due to an increased potential for eplerenone-related adverse events. If eplerenone 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 eplerenone. Eplerenone is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated eplerenone plasma concentrations.
Ergoloid Mesylates: Concurrent use of ergot alkaloids and telaprevir is contraindicated due to the potential for serious/life-threatening ergot toxicities, such as peripheral vasospasm and ischemia of the extremities and other tissues. Telaprevir is an 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: Concurrent use of ergot alkaloids and telaprevir is contraindicated due to the potential for serious/life-threatening ergot toxicities, such as peripheral vasospasm and ischemia of the extremities and other tissues. Telaprevir is an 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: Concurrent use of ergot alkaloids and telaprevir is contraindicated due to the potential for serious/life-threatening ergot toxicities, such as peripheral vasospasm and ischemia of the extremities and other tissues. Telaprevir is an 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: Concurrent use of ergot alkaloids and telaprevir is contraindicated due to the potential for serious/life-threatening ergot toxicities, such as peripheral vasospasm and ischemia of the extremities and other tissues. Telaprevir is an 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.
Erythromycin: Close clinical monitoring is advised when administering clarithromycin with telaprevir due to an increased potential for serious erythromycin-related adverse events, such as QT prolongation and torsade de pointes (TdP). Predictions about the interaction can be made based on the metabolic pathways of erythromycin and telaprevir. Both erythromycin and telaprevir are substrates and inhibitors of the hepatic isoenzyme CYP3A4 and the drug efflux transporter, P-glycoprotein (P-gp). When used in combination, the plasma concentrations of both medications may be elevated. Monitor for evidence of interactions. If erythromycin dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment.
Erythromycin; Sulfisoxazole: Close clinical monitoring is advised when administering clarithromycin with telaprevir due to an increased potential for serious erythromycin-related adverse events, such as QT prolongation and torsade de pointes (TdP). Predictions about the interaction can be made based on the metabolic pathways of erythromycin and telaprevir. Both erythromycin and telaprevir are substrates and inhibitors of the hepatic isoenzyme CYP3A4 and the drug efflux transporter, P-glycoprotein (P-gp). When used in combination, the plasma concentrations of both medications may be elevated. Monitor for evidence of interactions. If erythromycin dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment.
Escitalopram: Close clinical monitoring is advised when administering escitalopram with telaprevir due to a potential decreased escitalopram efficacy. When used in combination, the plasma concentrations of escitalopram were decreased, resulting in an increased potential for mood alterations. If escitalopram dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment.
Eslicarbazepine: In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Telaprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of telaprevir may decrease, resulting in decreased telaprevir efficacy. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of eslicarbazpine and telaprevir. Close clinical monitoring is advised when administering eslicarbazpine with telaprevir due to the potential for telaprevir treatment failure.
Esomeprazole: Although clinical trials found no doses adjustments are needed for either medications, close monitoring is advised when administering esomeprazole with telaprevir due to the potential for esomeprazole-related adverse events. Esomeprazole is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated esomeprazole plasma concentrations.
Esomeprazole; Naproxen: Although clinical trials found no doses adjustments are needed for either medications, close monitoring is advised when administering esomeprazole with telaprevir due to the potential for esomeprazole-related adverse events. Esomeprazole is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated esomeprazole plasma concentrations.
Estazolam: Close clinical monitoring is advised when administering estazolam with telaprevir due to an increa sed potential for estazolam-related adverse events. If estazolam 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 estazolam. Estazolam is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated estazolam plasma concentrations.
Estradiol Cypionate; Medroxyprogesterone: Coadministration of medroxyprogesterone, a CYP3A substrate with telaprevir, a strong CYP3A inhibitor should be avoided since it is expected to increase concentrations of medroxyprogesterone acetate. Formal drug interaction studies have not been conducted; however, medroxyprogesterone is metabolized primarily by hydroxylation via the CYP3A4 in vitro.
Estradiol: Close clinical monitoring for signs of estrogen deficiency is advised when administering ethinyl estradiol in combination with telaprevir. When used concurrently, ethinyl estradiol plasma concentrations may be decreased, potentially resulting in impaired efficacy. If ethinyl estradiol dose adjustments are made during combination therapy, re-adjust the dose upon completion of telaprevir treatment. Telaprevir will also likely reduce estrogen levels when administered as mestranol, which is further metabolized to EE. Close clinical monitoring for contraception failure is advised when coadministering combined hormonal oral contraceptives or ethinyl estradiol; etonogestrel contraceptive vaginal ring with telaprevir. Two effective non-hormonal methods of contraception should be used during treatment with telaprevir.
Estradiol; Norethindrone: Close clinical monitoring for contraception failure is advised when coadministering norethindrone with telaprevir. It is not known if telaprevir reduces the efffectiveness of progestin-only contraception.Two effective non-hormonal methods of contraception should be used during treatment with telaprevir.
Eszopiclone: Close clinical monitoring is advised when administering eszopiclone with telaprevir due to an increased potential for eszopiclone-related adverse events. If eszopiclone 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 eszopiclone. Eszopiclone is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated eszopiclone plasma concentrations.
Ethinyl Estradiol: Close clinical monitoring for signs of estrogen deficiency is advised when administering ethinyl estradiol in combination with telaprevir. When used concurrently, ethinyl estradiol plasma concentrations may be decreased, potentially resulting in impaired efficacy. If ethinyl estradiol dose adjustments are made during combination therapy, re-adjust the dose upon completion of telaprevir treatment. Telaprevir will also likely reduce estrogen levels when administered as mestranol, which is further metabolized to EE. Close clinical monitoring for contraception failure is advised when coadministering combined hormonal oral contraceptives or ethinyl estradiol; etonogestrel contraceptive vaginal ring with telaprevir. Two effective non-hormonal methods of contraception should be used during treatment with telaprevir.
Ethinyl Estradiol; Desogestrel: Close clinical monitoring for signs of estrogen deficiency is advised when administering ethinyl estradiol in combination with telaprevir. When used concurrently, ethinyl estradiol plasma concentrations may be decreased, potentially resulting in impaired efficacy. If ethinyl estradiol dose adjustments are made during combination therapy, re-adjust the dose upon completion of telaprevir treatment. Telaprevir will also likely reduce estrogen levels when administered as mestranol, which is further metabolized to EE. Close clinical monitoring for contraception failure is advised when coadministering combined hormonal oral contraceptives or ethinyl estradiol; etonogestrel contraceptive vaginal ring with telaprevir. Two effective non-hormonal methods of contraception should be used during treatment with telaprevir.
Ethinyl Estradiol; Ethynodiol Diacetate: Close clinical monitoring for signs of estrogen deficiency is advised when administering ethinyl estradiol in combination with telaprevir. When used concurrently, ethinyl estradiol plasma concentrations may be decreased, potentially resulting in impaired efficacy. If ethinyl estradiol dose adjustments are made during combination therapy, re-adjust the dose upon completion of telaprevir treatment. Telaprevir will also likely reduce estrogen levels when administered as mestranol, which is further metabolized to EE. Close clinical monitoring for contraception failure is advised when coadministering combined hormonal oral contraceptives or ethinyl estradiol; etonogestrel contraceptive vaginal ring with telaprevir. Two effective non-hormonal methods of contraception should be used during treatment with telaprevir.
Ethinyl Estradiol; Etonogestrel: Close clinical monitoring for signs of estrogen deficiency is advised when administering ethinyl estradiol in combination with telaprevir. When used concurrently, ethinyl estradiol plasma concentrations may be decreased, potentially resulting in impaired efficacy. If ethinyl estradiol dose adjustments are made during combination therapy, re-adjust the dose upon completion of telaprevir treatment. Telaprevir will also likely reduce estrogen levels when administered as mestranol, which is further metabolized to EE. Close clinical monitoring for contraception failure is advised when coadministering combined hormonal oral contraceptives or ethinyl estradiol; etonogestrel contraceptive vaginal ring with telaprevir. Two effective non-hormonal methods of contraception should be used during treatment with telaprevir.
Ethinyl Estradiol; Levonorgestrel: Close clinical monitoring for signs of estrogen deficiency is advised when administering ethinyl estradiol in combination with telaprevir. When used concurrently, ethinyl estradiol plasma concentrations may be decreased, potentially resulting in impaired efficacy. If ethinyl estradiol dose adjustments are made during combination therapy, re-adjust the dose upon completion of telaprevir treatment. Telaprevir will also likely reduce estrogen levels when administered as mestranol, which is further metabolized to EE. Close clinical monitoring for contraception failure is advised when coadministering combined hormonal oral contraceptives or ethinyl estradiol; etonogestrel contraceptive vaginal ring with telaprevir. Two effective non-hormonal methods of contraception should be used during treatment with telaprevir.
Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: Close clinical monitoring for signs of estrogen deficiency is advised when administering ethinyl estradiol in combination with telaprevir. When used concurrently, ethinyl estradiol plasma concentrations may be decreased, potentially resulting in impaired efficacy. If ethinyl estradiol dose adjustments are made during combination therapy, re-adjust the dose upon completion of telaprevir treatment. Telaprevir will also likely reduce estrogen levels when administered as mestranol, which is further metabolized to EE. Close clinical monitoring for contraception failure is advised when coadministering combined hormonal oral contraceptives or ethinyl estradiol; etonogestrel contraceptive vaginal ring with telaprevir. Two effective non-hormonal methods of contraception should be used during treatment with telaprevir.
Ethinyl Estradiol; Norelgestromin: Close clinical monitoring for signs of estrogen deficiency is advised when administering ethinyl estradiol in combination with telaprevir. When used concurrently, ethinyl estradiol plasma concentrations may be decreased, potentially resulting in impaired efficacy. If ethinyl estradiol dose adjustments are made during combination therapy, re-adjust the dose upon completion of telaprevir treatment. Telaprevir will also likely reduce estrogen levels when administered as mestranol, which is further metabolized to EE. Close clinical monitoring for contraception failure is advised when coadministering combined hormonal oral contraceptives or ethinyl estradiol; etonogestrel contraceptive vaginal ring with telaprevir. Two effective non-hormonal methods of contraception should be used during treatment with telaprevir.
Ethinyl Estradiol; Norethindrone Acetate: Close clinical monitoring for contraception failure is advised when coadministering norethindrone with telaprevir. It is not known if telaprevir reduces the efffectiveness of progestin-only contraception.Two effective non-hormonal methods of contraception should be used during treatment with telaprevir. Close clinical monitoring for signs of estrogen deficiency is advised when administering ethinyl estradiol in combination with telaprevir. When used concurrently, ethinyl estradiol plasma concentrations may be decreased, potentially resulting in impaired efficacy. If ethinyl estradiol dose adjustments are made during combination therapy, re-adjust the dose upon completion of telaprevir treatment. Telaprevir will also likely reduce estrogen levels when administered as mestranol, which is further metabolized to EE. Close clinical monitoring for contraception failure is advised when coadministering combined hormonal oral contraceptives or ethinyl estradiol; etonogestrel contraceptive vaginal ring with telaprevir. Two effective non-hormonal methods of contraception should be used during treatment with telaprevir.
Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate: Close clinical monitoring for contraception failure is advised when coadministering norethindrone with telaprevir. It is not known if telaprevir reduces the efffectiveness of progestin-only contraception.Two effective non-hormonal methods of contraception should be used during treatment with telaprevir. Close clinical monitoring for signs of estrogen deficiency is advised when administering ethinyl estradiol in combination with telaprevir. When used concurrently, ethinyl estradiol plasma concentrations may be decreased, potentially resulting in impaired efficacy. If ethinyl estradiol dose adjustments are made during combination therapy, re-adjust the dose upon completion of telaprevir treatment. Telaprevir will also likely reduce estrogen levels when administered as mestranol, which is further metabolized to EE. Close clinical monitoring for contraception failure is advised when coadministering combined hormonal oral contraceptives or ethinyl estradiol; etonogestrel contraceptive vaginal ring with telaprevir. Two effective non-hormonal methods of contraception should be used during treatment with telaprevir.
Ethinyl Estradiol; Norethindrone: Close clinical monitoring for contraception failure is advised when coadministering norethindrone with telaprevir. It is not known if telaprevir reduces the efffectiveness of progestin-only contraception.Two effective non-hormonal methods of contraception should be used during treatment with telaprevir. Close clinical monitoring for signs of estrogen deficiency is advised when administering ethinyl estradiol in combination with telaprevir. When used concurrently, ethinyl estradiol plasma concentrations may be decreased, potentially resulting in impaired efficacy. If ethinyl estradiol dose adjustments are made during combination therapy, re-adjust the dose upon completion of telaprevir treatment. Telaprevir will also likely reduce estrogen levels when administered as mestranol, which is further metabolized to EE. Close clinical monitoring for contraception failure is advised when coadministering combined hormonal oral contraceptives or ethinyl estradiol; etonogestrel contraceptive vaginal ring with telaprevir. Two effective non-hormonal methods of contraception should be used during treatment with telaprevir.
Ethinyl Estradiol; Norethindrone; Ferrous fumarate: Close clinical monitoring for contraception failure is advised when coadministering norethindrone with telaprevir. It is not known if telaprevir reduces the efffectiveness of progestin-only contraception.Two effective non-hormonal methods of contraception should be used during treatment with telaprevir. Close clinical monitoring for signs of estrogen deficiency is advised when administering ethinyl estradiol in combination with telaprevir. When used concurrently, ethinyl estradiol plasma concentrations may be decreased, potentially resulting in impaired efficacy. If ethinyl estradiol dose adjustments are made during combination therapy, re-adjust the dose upon completion of telaprevir treatment. Telaprevir will also likely reduce estrogen levels when administered as mestranol, which is further metabolized to EE. Close clinical monitoring for contraception failure is advised when coadministering combined hormonal oral contraceptives or ethinyl estradiol; etonogestrel contraceptive vaginal ring with telaprevir. Two effective non-hormonal methods of contraception should be used during treatment with telaprevir.
Ethinyl Estradiol; Norgestimate: Close clinical monitoring for signs of estrogen deficiency is advised when administering ethinyl estradiol in combination with telaprevir. When used concurrently, ethinyl estradiol plasma concentrations may be decreased, potentially resulting in impaired efficacy. If ethinyl estradiol dose adjustments are made during combination therapy, re-adjust the dose upon completion of telaprevir treatment. Telaprevir will also likely reduce estrogen levels when administered as mestranol, which is further metabolized to EE. Close clinical monitoring for contraception failure is advised when coadministering combined hormonal oral contraceptives or ethinyl estradiol; etonogestrel contraceptive vaginal ring with telaprevir. Two effective non-hormonal methods of contraception should be used during treatment with telaprevir.
Ethinyl Estradiol; Norgestrel: Close clinical monitoring for signs of estrogen deficiency is advised when administering ethinyl estradiol in combination with telaprevir. When used concurrently, ethinyl estradiol plasma concentrations may be decreased, potentially resulting in impaired efficacy. If ethinyl estradiol dose adjustments are made during combination therapy, re-adjust the dose upon completion of telaprevir treatment. Telaprevir will also likely reduce estrogen levels when administered as mestranol, which is further metabolized to EE. Close clinical monitoring for contraception failure is advised when coadministering combined hormonal oral contraceptives or ethinyl estradiol; etonogestrel contraceptive vaginal ring with telaprevir. Two effective non-hormonal methods of contraception should be used during treatment with telaprevir.
Ethosuximide: Close clinical monitoring is advised when administering ethosuximide with telaprevir due to an increased potential for ethosuximide-related adverse events. If ethosuximide 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 ethosuximide. Ethosuximide is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated ethosuximide plasma concentrations.
Etoposide, VP-16: Close clinical monitoring is advised when administering etoposide, VP-16 with telaprevir due to an increased potential for etoposide-related adverse events. If etoposide 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 etoposide. Etoposide is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; telaprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated etoposide plasma concentrations.
Etravirine: Close clinical monitoring is advised when administering etravirine with telaprevir due to an increased potential for etravirine-related adverse events and the potential for telaprevir treatment failure. Predictions about the interaction can be made based on the metabolic pathways of etravirine and telaprevir. Etravirine is a substrate and inducer of the hepatic isoenzyme CYP3A4; telaprevir is a substrate and an inhibitor of this isoenzyme. Additionally, etravirine is an inhibitor of the drug efflux transporter P-glycoprotein (P-gp); telaprevir is partially metabolized by this efflux protein. When used in combination, the plasma concentrations of etravirine may increase and the plasma concentration of telaprevir may decrease.
Everolimus: Avoid concurrent use of Afinitor (CYP3A4 substrate) and strong CYP3A4 inhibitors such as telaprevir. For Zortress, coadministration with strong inhibitors of CYP3A4 is not recommended, as patients may experience an increase in systemic exposure to everolimus if these drugs are coadministered. If Zortress and telaprevir are coadministered, close monitoring of everolimus whole blood trough concentrations and consideration of Zortress dose adjustment are recommended.
Exemestane: Close clinical monitoring is advised when administering exemestane with telaprevir due to an increased potential for exemestane-related adverse events. If exemestane 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 exemestane. Exemestane is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated exemestane plasma concentrations.
Ezetimibe; Simvastatin: The concurrent use of simvastatin and telaprevir is contraindicated due to the potential for serious/life-threatening reactions. Telaprevir is an 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: Close clinical monitoring is advised when administering felodipine with telaprevir due to an increased potential for felodipine-related adverse events. If felodipine dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Predictions about the interaction can be made based on the metabolic pathway of felodipine. Felodipine is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated felodipine plasma concentrations.
Fentanyl: Close clinical monitoring is advised when administering fentanyl with telaprevir due to an increased potential for fentanyl-related adverse events. If fentanyl 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 fentanyl. Fentanyl is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; telaprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated fentanyl plasma concentrations.
Fesoterodine: Fesoterodine is rapidly hydrolyzed to its active metabolite, 5-hydroxymethyltolterodine, which is metabolized via hepatic CYP3A4. Although not studied, the weak CYP3A4 inhibitory effects of telaprevir, in theory, may result in an increase in plasma concentrations of 5-hydroxymethyltolterodine. Of note, the manufacturer does not recommend dosage adjustments of fesoterodine during concurrent use of moderate CYP3A4 inhibitors.
Fexofenadine: Close clinical monitoring is advised when administering fexofenadine with telaprevir due to an increased potential for fexofenadine-related adverse events. If fexofenadine 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 fexofenadine. Fexofenadine is a substrate of the drug efflux transporter P-glycoprotein (P-gp); telaprevir is an inhibitor of this efflux protein. Coadministration may result in elevated fexofenadine plasma concentrations.
Fexofenadine; Pseudoephedrine: Close clinical monitoring is advised when administering fexofenadine with telaprevir due to an increased potential for fexofenadine-related adverse events. If fexofenadine 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 fexofenadine. Fexofenadine is a substrate of the drug efflux transporter P-glycoprotein (P-gp); telaprevir is an inhibitor of this efflux protein. Coadministration may result in elevated fexofenadine plasma concentrations.
Flecainide: Close clinical monitoring is advised when administering flecainide with telaprevir due to an increased potential for serious and/or life-threatening flecainide-related adverse events, such as QT prolongation and torsade de pointe (TdP). If flecainide dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment.
Flibanserin: The concomitant use of flibanserin and strong CYP3A4 inhibitors, such as telaprevir, 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: Close clinical monitoring is advised when administering fluconazole with telaprevir due to an increased potential for telaprevir-related adverse events. If fluconazole 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 pathways of fluconazole and telaprevir. Fluconazole is an inhibitor of the hepatic isoenzyme CYP3A4; telaprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of telaprevir may be elevated.
Fluoxetine: Close clinical monitoring is advised when administering fluoxetine with telaprevir due to an increased potential for telaprevir-related adverse events. If fluoxetine 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 pathways of fluoxetine and telaprevir. Fluoxetine is an inhibitor of the hepatic isoenzyme CYP3A4; telaprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of telaprevir may be elevated.
Fluoxetine; Olanzapine: Close clinical monitoring is advised when administering fluoxetine with telaprevir due to an increased potential for telaprevir-related adverse events. If fluoxetine 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 pathways of fluoxetine and telaprevir. Fluoxetine is an inhibitor of the hepatic isoenzyme CYP3A4; telaprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of telaprevir may be elevated.
Flurazepam: Close clinical monitoring is advised when administering flurazepam with telaprevir due to an increased potential for flurazepam-related adverse events. If flurazepam 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 flurazepam. Flurazepam is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated flurazepam plasma concentrations.
Flutamide: Close clinical monitoring is advised when administering flutamide with telaprevir due to an increased potential for flutamide-related adverse events and the potential for telaprevir treatment failure. If flutamide 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 pathways of flutamide and telaprevir. Flutamide is a substrate and inducer of the hepatic isoenzyme CYP3A4; telaprevir 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 telaprevir may decrease, resulting in an increased risk for flutamide-related adverse events and decreased telaprevir efficacy.
Fluticasone: Concurrent administration of fluticasone and telaprevir is not recommended unless the benefits outweigh the risks. If they are coadministered, close monitoring for corticosteroid-related adverse events is advised. If fluticasone dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment.
Fluticasone; Salmeterol: Concurrent administration of fluticasone and telaprevir is not recommended unless the benefits outweigh the risks. If they are coadministered, close monitoring for corticosteroid-related adverse events is advised. If fluticasone dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Concurrent administration of salmeterol with telaprevir is not recommended. If salmeterol and telaprevir are coadministered, monitor the patient closely for salmeterol-related cardiovascular adverse events, such as QT interval prolongation, palpitations, and sinus tachycardia.
Fluticasone; Vilanterol: Concurrent administration of fluticasone and telaprevir is not recommended unless the benefits outweigh the risks. If they are coadministered, close monitoring for corticosteroid-related adverse events is advised. If fluticasone dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment.
Fluvastatin: Close clinical monitoring is advised when administering fluvastatin with telaprevir due to the potential for fluvastatin-related adverse events. When used in combination, the plasma concentrations of fluvastatin may be elevated.
Fluvoxamine: Close clinical monitoring is advised when administering fluvoxamine with telaprevir due to an increased potential for telaprevir-related adverse events. If fluvoxamine 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 pathways of fluvoxamine and telaprevir. Fluvoxamine is an inhibitor of the hepatic isoenzyme CYP3A4; telaprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of telaprevir may be elevated.
Formoterol; Mometasone: Concomitant administration of telaprevir and mometasone may increase systemic exposure to mometasone, increasing the risk of corticosteroid-related adverse events. Exercise caution when administering mometasone with telaprevir long-term and monitor closely for hypercorticism and adrenal suppression. Mometasone is a CYP3A4 substrate and telaprevir is a strong CYP3A4 inhibitor.
Fosamprenavir: Due to the potential for HIV and hepatitis C treatment failures, concurrent administration of fosamprenavir boosted with ritonavir and telaprevir is not recommended. When given concurrently, the Cmax, AUC, and Cmin of telaprevir is reduced by 33%, 32%, and 30%, respectively. The pharmacokinetic parameters of fosamprenavir, even in the precence of ritonavir, are also decreased during coadministration. Studies have shown coadministration of these drugs results in reduced fosamprenavir Cmax (35% to 40%), AUC (47% to 49%), and Cmin (56% to 58%). If fosamprenavir/ritonavir and telaprevir are coadministered, monitor the patient closely for HIV and hepatitis C treatment failures.
Galantamine: Close clinical monitoring is advised when administering galantamine with telaprevir due to an increased potential for galantamine-related adverse events. If galantamine 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 galantamine. Galantamine is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated galantamine plasma concentrations.
Gefitinib: Close clinical monitoring is advised when administering gefitinib with telaprevir due to an increased potential for gefitinib-related adverse events. If gefitinib 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 gefitinib. Gefitinib is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated gefitinib plasma concentrations.
Glimepiride; Pioglitazone: Close clinical monitoring is advised when administering pioglitazone with telaprevir due to an increased potential for pioglitazone-related adverse events and the potential for telaprevir treatment failure. If pioglitazone 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 pathways of pioglitazone and telaprevir. Pioglitazone is a substrate and inducer of the hepatic isoenzyme CYP3A4; telaprevir is a substrate and an inhibitor of this isoenzyme. When used in combination, the plasma concentrations of pioglitazone may increase and the plasma concentrations of telaprevir may decrease.
Glyburide: Close clinical monitoring is advised when administering glyburide with telaprevir due to an increased potential for glyburide-related adverse events. If glyburide 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 glyburide. Glyburide is a substrate of the drug efflux transporter P-glycoprotein (PGP); telaprevir is an inhibitor of this efflux protein. Coadministration may result in elevated glyburide plasma concentrations.
Glyburide; Metformin: Close clinical monitoring is advised when administering glyburide with telaprevir due to an increased potential for glyburide-related adverse events. If glyburide 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 glyburide. Glyburide is a substrate of the drug efflux transporter P-glycoprotein (PGP); telaprevir is an inhibitor of this efflux protein. Coadministration may result in elevated glyburide plasma concentrations.
Granisetron: Close clinical monitoring is advised when administering granisetron with telaprevir due to an increased potential for granisetron-related adverse events. If granisetron 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 granisetron. Granisetron is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated granisetron plasma concentrations.
Grapefruit juice: Close clinical monitoring is advised when administering grapefruit juice with telaprevir due to an increased potential for telaprevir-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 telaprevir. Grapefruit juice is an inhibitor of the hepatic isoenzyme CYP3A4; telaprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of telaprevir may be elevated.
Griseofulvin: Close clinical monitoring is advised when administering griseofulvin with telaprevir due to the potential for telaprevir treatment failure. If griseofulvin 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 pathways of griseofulvin and telaprevir. Griseofulvin is an inducer of the hepatic isoenzyme CYP3A4; telaprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of telaprevir may decrease, resulting in decreased telaprevir efficacy.
Guaifenesin; Hydrocodone: Monitor for respiratory depression and sedation if hydrocodone and telaprevir are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as telaprevir, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects.
Guaifenesin; Hydrocodone; Pseudoephedrine: Monitor for respiratory depression and sedation if hydrocodone and telaprevir are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as telaprevir, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects.
Guanfacine: Telaprevir 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 telaprevir is discontinued, the guanfacine ER dosage should be increased back to the recommended dose. Guanfacine is primarily metabolized by CYP3A4, and telaprevir is a strong CYP3A4 inhibitor.
Haloperidol: Close clinical monitoring is advised when administering haloperidol with telaprevir due to an increased potential for haloperidol-related adverse events. If haloperidol 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 haloperidol. Haloperidol is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated haloperidol plasma concentrations.
Homatropine; Hydrocodone: Monitor for respiratory depression and sedation if hydrocodone and telaprevir are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as telaprevir, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects.
Hydrochlorothiazide, HCTZ; Losartan: Close clinical monitoring is advised when administering losartan with telaprevir due to an increased potential for losartan-related adverse events. If losartan 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 losartan. Losartan is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated losartan plasma concentrations.
Hydrocodone: Monitor for respiratory depression and sedation if hydrocodone and telaprevir are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as telaprevir, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects.
Hydrocodone; Ibuprofen: Monitor for respiratory depression and sedation if hydrocodone and telaprevir are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as telaprevir, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects.
Hydrocodone; Phenylephrine: Monitor for respiratory depression and sedation if hydrocodone and telaprevir are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as telaprevir, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects.
Hydrocodone; Potassium Guaiacolsulfonate: Monitor for respiratory depression and sedation if hydrocodone and telaprevir are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as telaprevir, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects.
Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: Monitor for respiratory depression and sedation if hydrocodone and telaprevir are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as telaprevir, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects.
Hydrocodone; Pseudoephedrine: Monitor for respiratory depression and sedation if hydrocodone and telaprevir are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as telaprevir, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects.
Ibrutinib: Avoid concomitant use of telaprevir, a strong CYP3A4 inhibitor, with ibrutinib, a CYP3A4 substrate. For short-term (<= 7 days) of telaprevir, consider interrupting ibrutinib therapy until telaprevir is no longer needed. Monitor patients for signs of increased ibrutinib toxicity.
Ibuprofen; Oxycodone: Close clinical monitoring is advised when administering oxycodone with telaprevir due to an increased potential for oxycodone-related adverse events. If oxycodone 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 oxycodone. Oxycodone is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated oxycodone plasma concentrations.
Idelalisib: Concomitant use of idelalisib, a CYP3A4 substrate, and telaprevir, a strong CYP3A4 inhibitor, may increase the exposure of idelalisib. Additionally, idelalisib is a strong CYP3A inhibitor while telaprevir 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 telaprevir.
Ifosfamide: The concomitant use of ifosfamide, a CYP3A4 substrate, and telaprevir, a strong CYP3A4 inhibitor and substrate, may decrease the metabolism of ifosfamide to its active metabolite, 4-hydroxy-ifosfamide. As a result of this interaction, ifosfamide treatment effectiveness may be reduced.
Iloperidone: In vitro studies indicate that CYP3A4 is involved in the metabolism of iloperidone. In theory, potent inhibitors of CYP3A4 such as telaprevir may decrease the elimination of iloperidone. The manufacturer recommends a reduction in the iloperidone dose by one-half during co-administration with strong inhibitors of CYP3A4.
Imatinib, STI-571: Close clinical monitoring is advised when administering imatinib, STI-571 with telaprevir due to an increased potential for imatinib-related adverse events. If imatinib 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 pathways of imatinib and telaprevir. Both imatinib and telaprevir are substrates and inhibitors of the hepatic isoenzyme CYP3A4. When used in combination, the plasma concentrations of both medications may be elevated.
Imipramine: Close clinical monitoring is advised when administering imipramine with telaprevir due to an increased potential for imipramine-related adverse events. If imipramine 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 imipramine. Imipramine is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated imipramine plasma concentrations.
Indinavir: Close clinical monitoring is advised when administering indinavir with telaprevir due to an increased potential for indinavir-related adverse events. If indinavir 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 pathways of indinavir and telaprevir. Both indinavir and telaprevir are substrates and inhibitors of the hepatic isoenzyme CYP3A4. When used in combination, the plasma concentrations of both medications may be elevated.
Irinotecan Liposomal: If possible, avoid concomitant use of irinotecan liposomal with telaprevir, a strong CYP3A4 inhibitor, due to increased risk of irinotecan-related toxicity. Discontinue telaprevir at least 1 week prior to initiation of liposomal irinotecan therapy. The metabolism of liposomal irinotecan has not been evaluated; however, coadministration of ketoconazole, a strong CYP3A4 and UGT1A1 inhibitor, with non-liposomal irinotecan HCl resulted in increased exposure to both irinotecan and its active metabolite, SN-38.
Irinotecan: Telaprevir is a strong CYP3A4 and mild P-glycoprotein (P-gp) inhibitor; irinotecan is a CYP3A4 and P-gp substrate. Exposure to irinotecan and to the active metabolite, SN-38, will increase when the drugs are used together. Do not administer telaprevir concurrently with irinotecan unless there are no therapeutic alternatives; discontinue telaprevir at least 1 week before starting irinotecan. If concomitant use is necessary, monitor for increased irinotecan side effects, including diarrhea, nausea, vomiting, and myelosuppression.
Isoniazid, INH: Close clinical monitoring is advised when administering isoniazid, INH with telaprevir due to an increased potential for telaprevir-related adverse events. If isoniazid 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 pathways of isoniazid and telaprevir. Isoniazid is an inhibitor of the hepatic isoenzyme CYP3A4; telaprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of telaprevir may be elevated.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: There is a potential for telaprevir treatment failure when telaprevir is administered with rifampin; concurrent use is contraindicated. Rifampin is a potent inducer of CYP3A4, which is responsible for telaprevir metabolism. Coadministration may result in decreased telaprevir serum concentrations and impaired virologic response. Close clinical monitoring is advised when administering isoniazid, INH with telaprevir due to an increased potential for telaprevir-related adverse events. If isoniazid 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 pathways of isoniazid and telaprevir. Isoniazid is an inhibitor of the hepatic isoenzyme CYP3A4; telaprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of telaprevir may be elevated.
Isoniazid, INH; Rifampin: There is a potential for telaprevir treatment failure when telaprevir is administered with rifampin; concurrent use is contraindicated. Rifampin is a potent inducer of CYP3A4, which is responsible for telaprevir metabolism. Coadministration may result in decreased telaprevir serum concentrations and impaired virologic response. Close clinical monitoring is advised when administering isoniazid, INH with telaprevir due to an increased potential for telaprevir-related adverse events. If isoniazid 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 pathways of isoniazid and telaprevir. Isoniazid is an inhibitor of the hepatic isoenzyme CYP3A4; telaprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of telaprevir may be elevated.
Isradipine: Close clinical monitoring is advised when administering isradipine with telaprevir due to an increased potential for isradipine-related adverse events. If isradipine 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 isradipine. Isradipine is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated isradipine plasma concentrations.
Itraconazole: Close clinical monitoring is advised when administering itraconazole with telaprevir due to an increased potential for itraconazole and telaprevir-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 telaprevir treatment. Predictions about the interaction can be made based on the metabolic pathways of itraconazole and telaprevir. Both itraconazole and telaprevir 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.
Ivacaftor: If telaprevir 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 telaprevir is a strong CYP3A inhibitor. Ivacaftor is also an inhibitor of CYP3A and P-glycoprotein (P-gp); telaprevir is partially metabolized by CYP3A and is a substrate of P-gp. Coadministration may increase telaprevir exposure leading to increased or prolonged therapeutic effects and adverse events.
Ivermectin: Close clinical monitoring is advised when administering ivermectin with telaprevir due to an increased potential for ivermectin-related adverse events. If ivermectin 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 ivermectin. Ivermectin is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated ivermectin plasma concentrations.
Ixabepilone: Close clinical monitoring is advised when administering ixabepilone with telaprevir due to an increased potential for ixabepilone-related adverse events. If ixabepilone 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 ixabepilone. Ixabepilone is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated ixabepilone plasma concentrations.
Ketoconazole: Close clinical monitoring is advised when administering ketoconazole with telaprevir due to an increased potential for serious ketoconazole and telaprevir-related adverse events. 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 telaprevir treatment. Predictions about the interaction can be made based on the metabolic pathways of ketaconazole and telaprevir. Both ketoconazole and telaprevir 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 telaprevir. When used in combination, the plasma concentrations of both medications may be elevated.
Lacosamide: Use caution during concurrent use of lacosamide and telaprevir, particularly in patients with renal or hepatic impairment. Lacosamide is a CYP3A4 substrate; telaprevir 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.
Lanreotide: Close clinical monitoring is advised when administering lanreotide with telaprevir due to an increased potential for telaprevir-related adverse events. If lanreotide 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 pathways of lanreotide and telaprevir. Lanreotide is an inhibitor of the hepatic isoenzyme CYP3A4; telaprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of telaprevir may be elevated.
Lansoprazole: Close clinical monitoring is advised when administering lansoprazole with telaprevir due to an increased potential for lansoprazole-related adverse events. If lansoprazole 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 lansoprazole. Lansoprazole is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; telaprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated lansoprazole plasma concentrations.
Lansoprazole; Naproxen: Close clinical monitoring is advised when administering lansoprazole with telaprevir due to an increased potential for lansoprazole-related adverse events. If lansoprazole 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 lansoprazole. Lansoprazole is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; telaprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated lansoprazole plasma concentrations.
Lapatinib: Close clinical monitoring is advised when administering lapatinib with telaprevir due to an increased potential for lapatinib-related adverse events. If lapatinib 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 pathways of lapatinib and telaprevir. Both lapatinib and telaprevir are substrates and inhibitors of the hepatic isoenzyme CYP3A4. Additionally, lapatinib is an inhibitor of the drug efflux transporter P-glycoprotein (PGP); telaprevir is partially metabolized by this efflux protein. When used in combination, the plasma concentrations of both medications may be elevated.
Leuprolide; Norethindrone: Close clinical monitoring for contraception failure is advised when coadministering norethindrone with telaprevir. It is not known if telaprevir reduces the efffectiveness of progestin-only contraception.Two effective non-hormonal methods of contraception should be used during treatment with telaprevir.
Levomilnacipran: The adult dose of levomilnacipran should not exceed 80 mg/day during concurrent use of strong CYP3A4 inhibitors. Telaprevir 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.
Lidocaine: Close clinical monitoring is advised when administering systemic lidocaine with telaprevir 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 telaprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on metabolic pathways. Lidocaine is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated lidocaine plasma concentrations.
Linagliptin: 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: 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: Concomitant use of telaprevir and lomitapide is contraindicated. If treatment with telaprevir is unavoidable, lomitapide should be stopped during the course of treatment. Telaprevir is a strong CYP3A4 inhibitor. The exposure to lomitapide was increased 27-fold in the presence of ketoconazole, a strong CYP3A4 inhibitor.
Loperamide: Close clinical monitoring is advised when administering loperamide with telaprevir due to an increased potential for loperamide-related adverse events. If loperamide 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 loperamide. Loperamide is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; telaprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated loperamide plasma concentrations.
Loperamide; Simethicone: Close clinical monitoring is advised when administering loperamide with telaprevir due to an increased potential for loperamide-related adverse events. If loperamide 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 loperamide. Loperamide is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; telaprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated loperamide plasma concentrations.
Lopinavir; Ritonavir: Concurrent administration of lopinavir; ritonavir with telaprevir is not recommended. If lopinavir; ritonavir and telaprevir are coadministered, monitor the patient closely for HIV and hepatitis C treatment failures.
Loratadine: Close clinical monitoring is advised when administering loratadine with telaprevir due to an increased potential for loratadine-related adverse events. If loratadine 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 loratadine. Loratadine is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; telaprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated loratadine plasma concentrations.
Loratadine; Pseudoephedrine: Close clinical monitoring is advised when administering loratadine with telaprevir due to an increased potential for loratadine-related adverse events. If loratadine 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 loratadine. Loratadine is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; telaprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated loratadine plasma concentrations.
Losartan: Close clinical monitoring is advised when administering losartan with telaprevir due to an increased potential for losartan-related adverse events. If losartan 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 losartan. Losartan is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated losartan plasma concentrations.
Lovastatin: The concurrent use of lovastatin and telaprevir is contraindicated due to the potential for serious/life-threatening reactions. Telaprevir is an inhibitor of CYP3A4, which is responsible lovastatin metabolism. Coadministration may result in large increases in lovastatin serum concentrations, which could cause adverse events such as myopathy and rhabdomyolysis.
Lovastatin; Niacin: The concurrent use of lovastatin and telaprevir is contraindicated due to the potential for serious/life-threatening reactions. Telaprevir is an inhibitor of CYP3A4, which is responsible lovastatin metabolism. Coadministration may result in large increases in lovastatin serum concentrations, which could cause adverse events such as myopathy and rhabdomyolysis.
Lumacaftor; Ivacaftor: If telaprevir 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 telaprevir is a strong CYP3A inhibitor. Ivacaftor is also an inhibitor of CYP3A and P-glycoprotein (P-gp); telaprevir is partially metabolized by CYP3A and is a substrate of P-gp. Coadministration may increase telaprevir exposure leading to increased or prolonged therapeutic effects and adverse events.
Macitentan: Avoid concurrent use of macitentan and telaprevir. Telaprevir 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 telaprevir is necessary.
Maraviroc: Coadministration of maraviroc, a CYP3A substrate, with telaprevir, a strong CYP3A4 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 telaprevir (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.
Medroxyprogesterone: Coadministration of medroxyprogesterone, a CYP3A substrate with telaprevir, a strong CYP3A inhibitor should be avoided since it is expected to increase concentrations of medroxyprogesterone acetate. Formal drug interaction studies have not been conducted; however, medroxyprogesterone is metabolized primarily by hydroxylation via the CYP3A4 in vitro.
Mefloquine: Close clinical monitoring is advised when administering mefloquine with telaprevir due to an increased potential for mefloquine-related adverse events. If mefloquine 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 mefloquine. Mefloquine is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; telaprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated mefloquine plasma concentrations.
Meloxicam: Close clinical monitoring is advised when administering meloxicam with telaprevir due to an increased potential for meloxicam-related adverse events. If meloxicam 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 meloxicam. Meloxicam is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated meloxicam plasma concentrations.
Mestranol; Norethindrone: Close clinical monitoring for contraception failure is advised when coadministering norethindrone with telaprevir. It is not known if telaprevir reduces the efffectiveness of progestin-only contraception.Two effective non-hormonal methods of contraception should be used during treatment with telaprevir.
Metformin; Pioglitazone: Close clinical monitoring is advised when administering pioglitazone with telaprevir due to an increased potential for pioglitazone-related adverse events and the potential for telaprevir treatment failure. If pioglitazone 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 pathways of pioglitazone and telaprevir. Pioglitazone is a substrate and inducer of the hepatic isoenzyme CYP3A4; telaprevir is a substrate and an inhibitor of this isoenzyme. When used in combination, the plasma concentrations of pioglitazone may increase and the plasma concentrations of telaprevir may decrease.
Metformin; Repaglinide: Close clinical monitoring is advised when administering repaglinide with telaprevir due to an increased potential for repaglinide-related adverse events. If repaglinide 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 repaglinide. Repaglinide is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated repaglinide plasma concentrations.
Methadone: Close clinical monitoring is advised when administering methadone with telaprevir due to the potential for decreased methadone efficacy. When initiating concurrent treatment with methadone and telaprevir, no dose adjustments are required; however, the dose of methadone may need to be adjusted during maintenance therapy. If methadone dose adjustments are made, they should be re-adjusted upon completion of telaprevir treatment.
Methylergonovine: Concurrent use of ergot alkaloids and telaprevir is contraindicated due to the potential for serious/life-threatening ergot toxicities, such as peripheral vasospasm and ischemia of the extremities and other tissues. Telaprevir is an 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: Concurrent administration of systemic corticosteroids, such as methylprednisolone, and telaprevir is not recommended. If methylprednisolone and telaprevir are coadministered, close monitoring for corticosteroid-related adverse events is advised. If methylprednisolone dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Predictions about the interaction can be made based on the metabolic pathway of methylprednisolone. Methylprednisolone is metabolized by the hepatic isoenzyme CYP3A4 and the drug efflux transporter P-glycoprotein (P-gp); telaprevir inhibits both the isoenzyme and the drug efflux pump. Coadministration may result in elevated methylprednisolone plasma concentrations.
Methysergide: Concurrent use of ergot alkaloids and telaprevir is contraindicated due to the potential for serious/life-threatening ergot toxicities, such as peripheral vasospasm and ischemia of the extremities and other tissues. Telaprevir is an 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.
Metyrapone: Close clinical monitoring is advised when administering metyrapone with telaprevir due to the potential for telaprevir treatment failure. If metyrapone 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 pathways of metyrapone and telaprevir. Metyrapone is an inducer of the hepatic isoenzyme CYP3A4; telaprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of telaprevir may decrease.
Midazolam: Concurrent use of oral midazolam and telaprevir is contraindicated due to the risk of life threatening reactions, such as prolonged or increased sedation or respiratory depression. Telaprevir is an inhibitor of CYP3A4, which is responsible for the metabolism of orally administered midazolam. Coadministration may result in large increases in midazolam serum concentrations, which could cause fatal toxicities. Increased midazolam serum concentrations resulting from telaprevir CYP3A4 inhibition are higher for oral midazolam than for the intravenous formulation; use of intravenous midazolam is not contraindicated with telaprevir, 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 telaprevir, as they are not oxidatively metabolized.
Mifepristone, RU-486: Close clinical monitoring is advised when administering mifepristone, RU-486 with telaprevir due to an increased potential for mifepristone-related adverse events. If mifepristone 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 pathways of mifepristone and telaprevir. Both mifepristone and telaprevir are substrates and inhibitors of the hepatic isoenzyme CYP3A4. Additionally, mifepristone is an inhibitor of the drug efflux transporter P-glycoprotein (PGP); telaprevir is partially metabolized by this efflux protein. When used in combination, the plasma concentrations of both medications may be elevated. In general, caution is warranted when mifepristone is used in the treatment of Cushing's syndrome and coadministered with drugs that inhibit CYP3A4; limit the dose of mifepristone to 300 mg/day PO during times of coadministration.
Mirtazapine: Close clinical monitoring is advised when administering mirtazapine with telaprevir due to an increased potential for mirtazapine-related adverse events. If mirtazapine 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 mirtazapine. Mirtazapine is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated mirtazapine plasma concentrations.
Mitomycin: Close clinical monitoring is advised when administering mitomycin with telaprevir due to an increased potential for mitomycin-related adverse events. If mitomycin 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 mitomycin. Mitomycin is a substrate of the drug efflux transporter P-glycoprotein (PGP); telaprevir is an inhibitor of this efflux protein. Coadministration may result in elevated mitomycin plasma concentrations.
Modafinil: Close clinical monitoring is advised when administering modafinil with telaprevir due to an increased potential for modafinil-related adverse events and the potential for telaprevir treatment failure. If modafinil 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 pathways of modafinil and telaprevir. Modafinil is a substrate and inducer of the hepatic isoenzyme CYP3A4; telaprevir 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 telaprevir may decrease.
Mometasone: Concomitant administration of telaprevir and mometasone may increase systemic exposure to mometasone, increasing the risk of corticosteroid-related adverse events. Exercise caution when administering mometasone with telaprevir long-term and monitor closely for hypercorticism and adrenal suppression. Mometasone is a CYP3A4 substrate and telaprevir is a strong CYP3A4 inhibitor.
Montelukast: Close clinical monitoring is advised when administering montelukast with telaprevir due to an increased potential for montelukast-related adverse events. If montelukast 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 montelukast. Montelukast is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated montelukast plasma concentrations.
Morphine: Close clinical monitoring is advised when administering morphine with telaprevir due to an increased potential for morphine-related adverse events. If morphine 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 morphine. Morphine is a substrate of the drug efflux transporter P-glycoprotein (PGP); telaprevir is an inhibitor of this efflux protein. Coadministration may result in elevated morphine plasma concentrations.
Morphine; Naltrexone: Close clinical monitoring is advised when administering morphine with telaprevir due to an increased potential for morphine-related adverse events. If morphine 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 morphine. Morphine is a substrate of the drug efflux transporter P-glycoprotein (PGP); telaprevir is an inhibitor of this efflux protein. Coadministration may result in elevated morphine plasma concentrations.
Nafcillin: Close clinical monitoring is advised when administering nafcillin with telaprevir due to the potential for telaprevir treatment failure. If nafcillin 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 pathways of nafcillin and telaprevir. Nafcillin is an inducer of the hepatic isoenzyme CYP3A4; telaprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of telaprevir may decrease, resulting in decreased telaprevir efficacy.
Nanoparticle Albumin-Bound Paclitaxel: Close clinical monitoring is advised when administering paclitaxel with telaprevir due to an increased potential for paclitaxel-related adverse events. If paclitaxel 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 paclitaxel. Paclitaxel is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; telaprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated paclitaxel plasma concentrations.
Nateglinide: Close clinical monitoring is advised when administering nateglinide with telaprevir due to an increased potential for nateglinide-related adverse events. If nateglinide 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 nateglinide. Nateglinide is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated nateglinide plasma concentrations.
Nefazodone: Close clinical monitoring is advised when administering nefazodone with telaprevir due to an increased potential for nefazodone-related adverse events. If nefazodone 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 pathways of nefazodone and telaprevir. Both nefazodone and telaprevir are substrates and inhibitors of the hepatic isoenzyme CYP3A4. When used in combination, the plasma concentrations of both medications may be elevated.
Nelfinavir: Close clinical monitoring is advised when administering nelfinavir with telaprevir due to an increased potential for nelfinavir-related adverse events. If nelfinavir 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 pathways of nelfinavir and telaprevir. Both nelfinavir and telaprevir 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.
Netupitant; Palonosetron: 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. Telaprevir is partially metabolized by CYP3A4. In addition, netupitant is mainly metabolized by CYP3A4. Coadministration of netupitant; palonosetron with a strong CYP3A4 inhibitor such as telaprevir can significantly increase the systemic exposure to netupitant. No dosage adjustment is necessary for single dose administration of netupitant; palonosetron.
Nevirapine: Nevirapine and telaprevir should not be coadministered due to an increased potential for nevirapine-related adverse events and the potential for telaprevir treatment failure. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of nevirapine and telaprevir. Nevirapine is a substrate and inducer of the hepatic isoenzyme CYP3A4; telaprevir is a substrate and an inhibitor of this isoenzyme. When used in combination, the plasma concentrations of nevirapine may increase and the plasma concentrations of telaprevir may decrease.
Niacin; Simvastatin: The concurrent use of simvastatin and telaprevir is contraindicated due to the potential for serious/life-threatening reactions. Telaprevir is an 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: Close clinical monitoring is advised when administering nicardipine with telaprevir 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 telaprevir treatment.
Nifedipine: Close clinical monitoring is advised when administering nifedipine with telaprevir due to an increased potential for nifedipine-related adverse events. If nifedipine dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Predictions about the interaction can be made based on the metabolic pathways of nifedipine and telaprevir. Nifedipine is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Additionally, nifedipine inhibits P-glycoprotein (PGP), a drug efflux transporter partially responsible for the metabolism of telaprevir. Coadministration may result in elevated nifedipine plasma concentrations.
Nintedanib: Telaprevir is a potent CYP3A4 inhibitor and a mild inhibitor of P-glycoprotein (P-gp); nintedanib is a P-gp substrate as well as a minor substrate of CYP3A4. Coadministration may increase the concentration and clinical effect of nintedanib. If concomitant use of telaprevir and nintedanib is necessary, closely monitor for increased nintedanib side effects including gastrointestinal toxicity, elevated liver enzymes, and hypertension. A dose reduction, interruption of therapy, or discontinuation of therapy may be necessary.
Nisoldipine: Close clinical monitoring is advised when administering nisoldipine with telaprevir due to an increased potential for nisoldipine-related adverse events. If nisoldipine dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Predictions about the interaction can be made based on the metabolic pathway of nisoldipine. Nisoldipine is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated nisoldipine plasma concentrations.
Norethindrone: Close clinical monitoring for contraception failure is advised when coadministering norethindrone with telaprevir. It is not known if telaprevir reduces the efffectiveness of progestin-only contraception.Two effective non-hormonal methods of contraception should be used during treatment with telaprevir.
Nortriptyline: Close clinical monitoring is advised when administering nortriptyline with telaprevir due to an increased potential for nortriptyline-related adverse events. If nortriptyline 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 nortriptyline. Nortriptyline is a substrate of the drug efflux transporter P-glycoprotein (PGP); telaprevir is an inhibitor of this efflux protein. Coadministration may result in elevated nortriptyline plasma concentrations.
Octreotide: Close clinical monitoring is advised when administering octreotide with telaprevir due to an increased potential for telaprevir-related adverse events. If octreotide 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 pathways of octreotide and telaprevir. Octreotide is an inhibitor of the hepatic isoenzyme CYP3A4; telaprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of telaprevir may be elevated.
Olaparib: Avoid the coadministration of olaparib with telaprevir due to the risk of increased olaparib-related adverse reactions; if concomitant use is necessary, decrease the dose of olaparib to 150 mg by mouth twice daily. Telapravir is no longer manufactured in the United States. Olaparib is a CYP3A4 substrate and telaprevir is a strong CYP3A4 inhibitor. Coadministration with itraconazole, another strong CYP3A4 inhibitor, increased the AUC and Cmax of olaparib by 2.7- and 1.4-fold, respectively; telaprevir may also increase olaparib exposure.
Ombitasvir; Paritaprevir; Ritonavir: Concurrent administration of telaprevir with dasabuvir; ombitasvir; paritaprevir; ritonavir or ombitasvir; paritaprevir; ritonavir may result in elevated plasma concentrations of both drugs. Both ritonavir and telaprevir are substrates and inhibitors of the hepatic isoenzyme CYP3A4 and the drug transporter P-glycoprotein (P-gp). Paritaprevir and dasabuvir (minor) are CYP3A4 substrates. In addition, dasabuvir, ombitasvir, and paritaprevir are all substrates of P-gp. Telaprevir also inhibits the organic anion transporting polypeptides (OATP) 1B1. Paritaprevir is a substrate of OATP1B1. Caution and close monitoring is advised if these drugs are administered together.
Omeprazole: Close clinical monitoring is advised when administering omeprazole with telaprevir due to an increased potential for omeprazole-related adverse events. If omeprazole 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 omeprazole. Omeprazole is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; telaprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated omeprazole plasma concentrations.
Omeprazole; Sodium Bicarbonate: Close clinical monitoring is advised when administering omeprazole with telaprevir due to an increased potential for omeprazole-related adverse events. If omeprazole 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 omeprazole. Omeprazole is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; telaprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated omeprazole plasma concentrations.
Ondansetron: Close clinical monitoring is advised when administering ondansetron with telaprevir due to an increased potential for ondansetron-related adverse events. If ondansetron 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 ondansetron. Ondansetron is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; telaprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated ondansetron plasma concentrations.
Oritavancin: Telaprevir is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of telaprevir may be reduced if these drugs are administered concurrently. Caution is warranted with the use of oritavancin and telaprevir. The concomitant use of telaprevir and strong CYP3A4 inducers is contraindicated due to the potential loss of efficacy and treatment failure of telaprevir; however, oritavancin is a weak inducer.
Ospemifene: Coadministration of telaprevir and ospemifene may increase ospemifene systemic concentrations and, thus, increase the risk of ospemifene-related adverse reactions. Telaprevir is a strong CYP3A4 inhibitor, and ospemifene is a CYP3A4 substrate. Ketoconazole, a strong CYP3A4 inhibitor increases the systemic exposure of ospemifene by 1.4-fold.
Oxcarbazepine: Close clinical monitoring is advised when administering oxcarbazepine with telaprevir due to the potential for telaprevir treatment failure. If oxcarbazepine 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 pathways of oxcarbazepine and telaprevir. Oxcarbazepine is an inducer of the hepatic isoenzyme CYP3A4; telaprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of telaprevir may decrease, resulting in decreased telaprevir efficacy.
Oxybutynin: Close clinical monitoring is advised when administering oxybutynin with telaprevir due to an increased potential for oxybutynin-related adverse events. If oxybutynin 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 oxybutynin. Oxybutynin is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated oxybutynin plasma concentrations.
Oxycodone: Close clinical monitoring is advised when administering oxycodone with telaprevir due to an increased potential for oxycodone-related adverse events. If oxycodone 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 oxycodone. Oxycodone is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated oxycodone plasma concentrations.
Paclitaxel: Close clinical monitoring is advised when administering paclitaxel with telaprevir due to an increased potential for paclitaxel-related adverse events. If paclitaxel 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 paclitaxel. Paclitaxel is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; telaprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated paclitaxel plasma concentrations.
Palbociclib: Avoid concomitant use of telaprevir with palbociclib. If coadministration cannot be avoided, reduce the dose of palbociclib to 75 mg by mouth once daily and monitor for increased adverse reactions including myelosuppression, diarrhea, asthenia, and fatigue. If telaprevir is discontinued, increase the palbociclib dosage upward to the recommended dose after a washout period of 3 to 5 half-lives of telaprevir. Palbociclib is a primary substrate of CYP3A and telaprevir is a strong CYP3A inhibitor. Coadministration of multiple daily doses of another strong CYP3A inhibitor, itraconazole, increased the plasma exposure and Cmax after a single dose of palbociclib in healthy patients by 87% and 34%, respectively (n = 12).
Paliperidone: Close clinical monitoring is advised when administering paliperidone with telaprevir due to an increased potential for telaprevir-related adverse events. If paliperidone 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 pathways of paliperidone and telaprevir. Paliperidone is an inhibitor of the drug efflux transporter P-glycoprotein (PGP); telaprevir is partially metabolized by this efflux protein. When used in combination, the plasma concentrations of telaprevir may be elevated.
Panobinostat: Use caution when administering panobinostat and telaprevir together; reduce the initial panobinostat dose from 20 mg PO to 10 mg PO. Telaprevir 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.
Pantoprazole: Close clinical monitoring is advised when administering pantoprazole with telaprevir due to an increased potential for pantoprazole-related adverse events. If pantoprazole 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 pathways of pantoprazole and telaprevir. Both pantoprazole and telaprevir 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.
Paricalcitol: Close clinical monitoring is advised when administering paricalcitol with telaprevir due to an increased potential for paricalcitol-related adverse events. If paricalcitol 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 paricalcitol. Paricalcitol is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated paricalcitol plasma concentrations.
Pazopanib: Avoid administering pazopanib with strong CYP3A4 inhibitors, such as telaprevir. 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 telaprevir, a CYP3A4 and P-gp inhibitor and a CYP3A4 and P-gp substrate, may result in altered pazopanib and/or telaprevir concentrations.
Perampanel: Concurrent use of perampanel with telaprevir, may increase exposure to perampanel and lead to elevated plasma concentrations. Telaprevir 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: Concurrent use of ergot alkaloids and telaprevir is contraindicated due to the potential for serious/life-threatening ergot toxicities, such as peripheral vasospasm and ischemia of the extremities and other tissues. Telaprevir is an 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: Close clinical monitoring is advised when administering amlodipine with telaprevir due to an increased potential for amlodipine-related adverse events. A reduction in the dose of amlodipine should be considered. If amlodipine dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Predictions about the interaction can be made based on the metabolic pathway of amlodipine. Amlodipine is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated amlodipine plasma concentrations.
Perphenazine; Amitriptyline: Close clinical monitoring is advised when administering amitriptyline with telaprevir due to an increased potential for amitriptyline-related adverse events. If amitriptyline 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 amitriptyline. Amitriptyline is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; telaprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated amitriptyline plasma concentrations.
Phenobarbital: The concomitant use of telaprevir and phenobarbital is contraindicated due to the potential loss of efficacy of telaprevir. Predictions about the interaction can be made based on the metabolic pathways of phenobarbital and telaprevir. Phenobarbital is an inducer of the hepatic isoenzyme CYP3A4; an isoenzyme partially responsible for the metabolism of telaprevir. When used in combination, the plasma concentrations of telaprevir may be deceased and phenobarbital plasma concentration may be altered, resulting in an increased potential for telaprevir treatment failure and phenobarbital-related adverse events.
Phenytoin: The concomitant use of telaprevir and phenytoin is contraindicated due to the potential loss of efficacy of telaprevir. Telapravir exposure (AUC) decreases to 53% of normal and the Cmax decreases to 68% of normal with concomitant carbamazepine use. The phenytoin AUC increases to 131% of normal and the Cmax increases to 127% of normal with concomitant use. Phenytoin is an inducer of the hepatic isoenzyme CYP3A4; an isoenzyme partially responsible for the metabolism of telaprevir. When used in combination, the plasma concentrations of telaprevir may be deceased and phenytoin plasma concentration may be altered, resulting in an increased potential for telaprevir treatment failure and phenytoin-related adverse events.
Pimavanserin: Because pimavanserin is primarily metabolized by CYP3A4 and CYP3A5, the manufacturer recommends that the pimavanserin dose be reduced to 17 mg/day PO in patients receiving strong inhibitors of CYP3A4 such as telaprevir. If these agents are used in combination, the patient should be carefully monitored for pimavanserin-related adverse reactions.
Pimozide: The concurrent use of pimozide and telaprevir is contraindicated due to the risk of life threatening arrhythmias such as torsades de pointes (TdP). Telaprevir is an 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.
Pioglitazone: Close clinical monitoring is advised when administering pioglitazone with telaprevir due to an increased potential for pioglitazone-related adverse events and the potential for telaprevir treatment failure. If pioglitazone 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 pathways of pioglitazone and telaprevir. Pioglitazone is a substrate and inducer of the hepatic isoenzyme CYP3A4; telaprevir is a substrate and an inhibitor of this isoenzyme. When used in combination, the plasma concentrations of pioglitazone may increase and the plasma concentrations of telaprevir may decrease.
Pitavastatin: Close clinical monitoring is advised when administering pitavastatin with telaprevir due to the potential for pitavastatin-related adverse events. When used in combination, the plasma concentrations of pitavastatin may be elevated.
Ponatinib: Concomitant use of ponatinib, a CYP3A4 substrate, and telaprevir, 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.
Posaconazole: Close clinical monitoring is advised when administering posaconazole with telaprevir due to an increased potential for posaconazole and telaprevir-related adverse events, such as QT prolongation and torsade de pointes (TdP). If posaconazole dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Predictions about the interaction can be made based on the metabolic pathways of posaconazole and telaprevir. Both posaconazole and telaprevir are substrates and inhibitors of the drug efflux transporter P-glycoprotein (P-gp). Additionally, posaconazole is an inhibitor of the hepatic isoenzyme CYP3A4, an isoenzyme partially responsible for the metabolism of telaprevir. When used in combination, the plasma concentrations of both medications may be elevated.
Prasugrel: Close clinical monitoring is advised when administering prasugrel with telaprevir due to an increased potential for prasugrel-related adverse events. If prasugrel 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 prasugrel. Prasugrel is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated prasugrel plasma concentrations.
Prednisolone: Close clinical monitoring is advised when administering prednisolone with telaprevir due to an increased potential for corticosteroid-related adverse events. If prednisolone 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 prednisolone. Prednisolone is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated prednisolone plasma concentrations.
Prednisone: Concurrent administration of systemic corticosteroids, such as prednisone, and telaprevir is not recommended. If prednisone and telaprevir are coadministered, close monitoring for corticosteroid-related adverse events is advised. If prednisone dose adjustments are made, re-adjust the dose upon completion of telaprevir 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-pg); telaprevir inhibits both the isoenzyme and the drug efflux pump. Coadministration may result in elevated prednisone plasma concentrations.
Primidone: Close clinical monitoring is advised when administering primidone with telaprevir due to the potential for telaprevir treatment failure. If primidone 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 pathways of primidone and telaprevir. Primidone is an inducer of the hepatic isoenzyme CYP3A4; telaprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of telaprevir may decrease.
Propafenone: Close clinical monitoring is advised when administering propafenone with telaprevir 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 telaprevir 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; telaprevir inhibits this isoenzyme. Additionally, propafenone is an inhibitor of P-glycoprotein (P-gp), an efflux transporter partially responsible for the metabolism of telaprevir. When used in combination, the plasma concentrations of both medications may be elevated.
Quetiapine: Close clinical monitoring is advised when administering quetiapine with telaprevir due to an increased potential for quetiapine-related adverse events. If quetiapine 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 quetiapine. Quetiapine is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated quetiapine plasma concentrations.
Quinidine: Close clinical monitoring is advised when administering quinidine with telaprevir 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 telaprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of quinidine and telaprevir. Quinidine is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Additionally, both quinidine and telaprevir are substrates and inhibitors of P-glycoprotein (P-gp) drug efflux transporter. When used in combination, the plasma concentrations of both medications may be elevated.
Quinine: Close clinical monitoring is advised when administering quinine with telaprevir due to an increased potential for quinine-related adverse events. If quinine 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 pathways of quinine and telaprevir. Quinine is a substrate, inducer, and inhibitor of the hepatic isoenzyme CYP3A4; telaprevir is a substrate and an inhibitor of this isoenzyme. When used in combination, the plasma concentrations of both medications may be altered.
Rabeprazole: Close clinical monitoring is advised when administering rabeprazole with telaprevir due to an increased potential for rabeprazole-related adverse events. If rabeprazole 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 rabeprazole. Rabeprazole is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated rabeprazole plasma concentrations.
Raltegravir: Although clinical trials found no dose adjustments are needed for either medication, close monitoring is advised when administering raltegravir with telaprevir due to the potential for raltegravir-related adverse events. In one study, coadministration resulted in increases in the mean AUC and mean Cmin of raltegravir.
Ramelteon: Close clinical monitoring is advised when administering ramelteon with telaprevir due to an increased potential for ramelteon-related adverse events. If ramelteon 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 ramelteon. Ramelteon is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated ramelteon plasma concentrations.
Ranolazine: Close clinical monitoring is advised when administering ranolazine with telaprevir due to an increased potential for ranolazine-related adverse events. If ranolazine 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 pathways of ranolazine and telaprevir. Both ranolazine and telaprevir 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.
Regorafenib: Avoid concomitant use of regorafenib, a CYP3A4 substrate, and telaprevir, a strong CYP3A4 inhibitor, as the exposure of regorafenib may increase and the exposure of the active metabolites, M-2 and M-5, may decrease.
Repaglinide: Close clinical monitoring is advised when administering repaglinide with telaprevir due to an increased potential for repaglinide-related adverse events. If repaglinide 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 repaglinide. Repaglinide is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated repaglinide plasma concentrations.
Rifabutin: Coadministration of rifabutin and telaprevir is not recommended. If rifabutin and telaprevir are coadministered, close clinical monitoring is advised due to the increased potential for rifabutin-related adverse events and for the potential of decreased telaprevir efficacy. If rifabutin dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Predictions about the interaction can be made based on the metabolic pathways of rifabutin and telaprevir. Rifabutin is an inducer and substrate of the hepatic isoenzyme CYP3A4; telaprevir is an inhibitor and substrate of this isoenzyme. When used in combination, rifabutin plasma concentrations may be elevated and the plasma concentration of telaprevir may be deceased, resulting in an increased potential for rifabutin-related adverse events and telaprevir treatment failure.
Rifampin: There is a potential for telaprevir treatment failure when telaprevir is administered with rifampin; concurrent use is contraindicated. Rifampin is a potent inducer of CYP3A4, which is responsible for telaprevir metabolism. Coadministration may result in decreased telaprevir serum concentrations and impaired virologic response.
Rifaximin: Close clinical monitoring is advised when administering rifaximin with telaprevir due to potential alterations in the plasma concentration of both drugs. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of rifaximin and telaprevir. Since rifaximin and telaprevir are substrates and inhibitors of the drug efflux transporter P-glycoprotein (P-gp), coadministation may result in increased plasma concentrations of both drugs. However, because rifaximin is also a mild inducer of CYP3A4, and telaprevir is metabolized by this enzyme, concurrent use may also result in reduced telaprevir exposure. In patients with hepatic impairment, reduced drug metabolism may increase the effects of P-gp inhibition/CYP induction, thereby resulting in further alterations in drug exposure. If these drugs are used in combination, monitor patients closely for adverse events and potential telaprevir treatment failure.
Riociguat: Concomitant use of riociguat with strong cytochrome CYP3A inhibitors may result in hypotension. Telaprevir 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: Close clinical monitoring is advised when administering risperidone with telaprevir due to an increased potential for risperidone-related adverse events. If risperidone 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 risperidone. Risperidone is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; telaprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated risperidone plasma concentrations.
Rivaroxaban: Avoid concomitant administration of rivaroxaban and telaprevir; significant increases in rivaroxaban exposure may increase bleeding risk. Rivaroxaban is a substrate of CYP3A4/5 and the P-glycoprotein (P-gp) transporter. Telaprevir is a combined P-gp inhibitor and strong CYP3A4 inhibitor. Concurrent use of a single dose of rivaroxaban and ritonavir, a combined P-gp and strong CYP3A4 inhibitor, led to an increase in the steady-state rivaroxaban AUC by 150% and to an increase in Cmax by 60%. Similar increases in pharmacodynamic effects such as factor Xa inhibition and PT prolongation were also observed.
Romidepsin: The concomitant use of romidepsin, a CYP3A4 substrate and a P-glycoprotein (P-gp) substrate, and telaprevir, 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: Close clinical monitoring is advised when administering ropivacaine with telaprevir due to an increased potential for ropivacaine-related adverse events. If ropivacaine 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 ropivacaine. Ropivacaine is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated ropivacaine plasma concentrations.
Rosuvastatin: Close clinical monitoring is advised when administering rosuvastatin with telaprevir due to the potential for rosuvastatin-related adverse events. When used in combination, the plasma concentrations of rosuvastatin may be elevated.
Ruxolitinib: Avoid coadministration of ruxolitinib and telaprevir in patients with platelet counts < 100 x 10^9/L. In patients with platelet counts >= 100 x 10^9/L, ruxolitinib may be administered concurrently with telaprevir if the initial ruxolitinib dose is reduced to 10 mg PO twice daily. Additional dose modification should be made only after close monitoring of ruxolitinib's safety and efficacy. Predictions about the interaction can be made based on the metabolic pathway of ruxolitinib. Ruxolitinib is primarily metabolized by CYP3A4; telaprevir is a potent inhibitor of this isoenzyme. Coadministration may result in a large increase in ruxolitinib serum concentrations, which could cause adverse events such as thrombocytopenia, anemia, neutropenia, or infection.
Salmeterol: Concurrent administration of salmeterol with telaprevir is not recommended. If salmeterol and telaprevir are coadministered, monitor the patient closely for salmeterol-related cardiovascular adverse events, such as QT interval prolongation, palpitations, and sinus tachycardia.
Saquinavir: Close clinical monitoring is advised when administering saquinavir with telaprevir due to an increased potential for saquinavir-related adverse events. If saquinavir 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 pathways of saquinavir and telaprevir. Both saquinavir and telaprevir are substrates and inhibitors of the hepatic isoenzyme CYP3A4 and the drug efflux transporter, P-glycoprotein (P-gp). When used in combination, the plasma concentrations of both medications may be elevated.
Selegiline, Transdermal: Close clinical monitoring is advised when administering selegiline with telaprevir due to an increased potential for selegiline-related adverse events. If selegiline 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 selegiline. Selegiline is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated selegiline plasma concentrations.
Selegiline: Close clinical monitoring is advised when administering selegiline with telaprevir due to an increased potential for selegiline-related adverse events. If selegiline 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 selegiline. Selegiline is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated selegiline plasma concentrations.
Sertraline: Close clinical monitoring is advised when administering sertraline with telaprevir due to an increased potential for sertraline-related adverse events. If sertraline 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 sertraline. Sertraline is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; telaprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated sertraline plasma concentrations.
Sibutramine: Close clinical monitoring is advised when administering sibutramine with telaprevir due to an increased potential for sibutramine-related adverse events. If sibutramine 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 sibutramine. Sibutramine is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated sibutramine plasma concentrations.
Sildenafil: Sildenafil, when used for pulmonary arterial hypertension (PAH), is contraindicated with telaprevir. Coadministration of telaprevir 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. Telaprevir can be used cautiously with sildenafil for erectile dysfunction; use sildenafil at a reduced dose of 25 mg no more frequently than every 48 hours with increased monitoring for adverse reactions.
Silodosin: Close clinical monitoring is advised when administering silodosin with telaprevir due to an increased potential for silodosin-related adverse events. If silodosin 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 silodosin. Silodosin is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; telaprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated silodosin plasma concentrations.
Simvastatin: The concurrent use of simvastatin and telaprevir is contraindicated due to the potential for serious/life-threatening reactions. Telaprevir is an 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: The concurrent use of simvastatin and telaprevir is contraindicated due to the potential for serious/life-threatening reactions. Telaprevir is an 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: Close monitoring of sirolimus serum concentrations and frequent assessments of renal function are advised when coadministering sirolimus with telaprevir. Plasma concentrations of sirolimus may be increased if administered in combination with telaprevir; thus, sirolimus dose reductions and prolongation of the dosing interval are recommended to achieve desired sirolimus concentrations. If sirolimus dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. 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); telaprevir inhibits both the isoenzyme and the drug efflux protein. When used in combination, the plasma concentrations of sirolimus may be increased.
Solifenacin: Close clinical monitoring is advised when administering solifenacin with telaprevir due to an increased potential for solifenacin-related adverse events. If solifenacin 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 solifenacin. Solifenacin is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated solifenacin plasma concentrations.
Sonidegib: Avoid the concomitant use of sonidegib and telaprevir; sonidegib levels may be significantly increased resulting in an increased risk of adverse events, particularly musculoskeletal toxicity. Sonidegib is a CYP3A4 substrate and telaprevir is a strong CYP3A4 inhibitor. The sonidegib geometric mean Cmax and AUC (0-10 days) values were increased 2.2-fold and 1.5-fold, respectively, in healthy subjects who received a single 800-mg dose of sonidegib after taking 14 days of a strong CYP3A4 inhibitor. Physiologic-based pharmacokinetics simulations indicate that the sonidegib geometric mean steady-state AUC (0-24 hours) would be increased to a similar extent in cancer patients who received 14 days of sonidegib 200 mg/day with a strong CYP3A inhibitor.
St. John's Wort, Hypericum perforatum: There is a potential for telaprevir treatment failure when telaprevir 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 responsible telaprevir metabolism. Coadministration may result in decreased telaprevir serum concentrations and impaired virologic response.
Streptogramins: Close clinical monitoring is advised when administering dalfopristin; quinupristin with telaprevir due to an increased potential for telaprevir-related adverse events. If dalfopristin; quinupristin 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 pathways of dalfopristin; quinupristin and telaprevir. Dalfopristin; quinupristin is an inhibitor of the hepatic isoenzyme CYP3A4; telaprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of telaprevir may be elevated.
Sufentanil: Close clinical monitoring is advised when administering sufentanil with telaprevir due to an increased potential for sufentanil-related adverse events. If sufentanil 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 sufentanil. Sufentanil is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated sufentanil plasma concentrations.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: Close clinical monitoring is advised when administering sulfamethoxazole with telaprevir due to an increased potential for sulfamethoxazole-related adverse events. If sulfamethoxazole 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 sulfamethoxazole. Sulfamethoxazole is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated sulfamethoxazole plasma concentrations.
Sunitinib: Close clinical monitoring is advised when administering sunitinib with telaprevir due to an increased potential for sunitinib-related adverse events. If sunitinib 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 sunitinib. Sunitinib is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated sunitinib plasma concentrations.
Suvorexant: Suvorexant is primarily metabolized by CYP3A, and the manufacturer recommends against concurrent use of suvorexant with strong CYP3A inhibitors such as telaprevir and boceprevir. Strong inhibitors of CYP3A significantly increase suvorexant exposure (AUC).
Tacrolimus: Coadministration with strong CYP3A4-inhibitors such as telaprevir 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. Tacrolimus is a substrate of the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Increased tacrolimus concentrations could potentially result in adverse events such as QT interval prolongatio n.
Tadalafil: Tadalafil, when used for pulmonary arterial hypertension (PAH), is contraindicated with telaprevir. Coadministration of telaprevir 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. Telaprevir can be used cautiously with tadalafil for erectile dysfunction; use tadalafil at a reduced dose of 10 mg no more frequently than every 72 hours with increased monitoring for adverse reactions.
Tamoxifen: Telaprevir is a strong CYP3A4 inhibitor. Tamoxifen is metabolized by CYP3A4, CYP2D6, and to a lesser extent by both CYP2C9 and CYP2C19, to other potent, active metabolites including endoxifen, which have up to 33 times more affinity for the estrogen receptor than tamoxifen. These metabolites are then inactivated by sulfotransferase 1A1 (SULT1A1). Telaprevir may inhibit the CYP3A4 metabolism of tamoxifen to these metabolites. Additionally, telaprevir is a substrate of CYP3A4 and P-glycoprotein (P-gp); tamoxifen inhibits both CYP3A4 and P-gp. Concomitant use of telaprevir and tamoxifen may result in increased telaprevir exposure and decreased concentrations of the active metabolites of tamoxifen, which can compromise efficacy. If it is not possible to avoid concomitant use, monitor patients for increased side effects of telaprevir and changes in the therapeutic efficacy of tamoxifen. If tamoxifen dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment.
Tamsulosin: Plasma concentrations of tamsulosin may be increased with concomitant use of telaprevir. Tamsulosin is extensively metabolized by CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Such increases in tamsulosin concentrations may be expected to produce clinically significant and potentially serious side effects, such as hypotension. Therefore, concomitant use with a strong CYP3A4 inhibitor, such as telaprevir, should be avoided.
Tasimelteon: Concurrent use of tasimelteon and strong inhibitors of CYP3A4, such as telaprevir, 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: Close clinical monitoring is advised when administering telithromycin with telaprevir due to an increased potential for serious adverse events, such as QT prolongation. If telithromycin dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Predictions about the interaction can be made based on the metabolic pathways of telithromycin and telaprevir. Telithromycin is an inhibitor of the hepatic isoenzyme CYP3A4 and the drug efflux transporter P-glycoprotein (P-gp); telaprevir is metabolized by CYP3A4 and P-gp. When used in combination, the plasma concentrations of both medications may be elevated.
Teniposide: Close clinical monitoring is advised when administering teniposide with telaprevir due to an increased potential for teniposide-related adverse events. If teniposide 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 teniposide. Teniposide is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; telaprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated teniposide plasma concentrations.
Tenofovir, PMPA: Close clinical monitoring is advised when coadministering tenofovir, PMPA with telaprevir due to an increased potential for tenofovir-related adverse events. When used in combination, the plasma concentrations of tenofovir were increased, resulting in an increased potential for tenofovir-associated adverse reactions. If tenofovir dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment.
Terbinafine: Due to the risk for terbinafine related adverse effects, caution is advised when coadministering telaprevir. 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; telaprevir is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
Terfenadine: Close clinical monitoring is advised when administering terfenadine with telaprevir due to an increased potential for terfenadine-related adverse events. If terfenadine 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 terfenadine. Terfenadine is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; telaprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated terfenadine plasma concentrations.
Testosterone: Close clinical monitoring is advised when administering testosterone with telaprevir due to an increased potential for testosterone-related adverse events. If testosterone 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 testosterone. Testosterone is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; telaprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated testosterone plasma concentrations.
Theophylline, Aminophylline: Close clinical monitoring is advised when administering theophylline, aminophylline with telaprevir due to an increased potential for theophylline-related adverse events. If theophylline 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 theophylline. Theophylline is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated theophylline plasma concentrations.
Tiagabine: Close clinical monitoring is advised when administering tiagabine with telaprevir due to an increased potential for tiagabine-related adverse events. If tiagabine 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 tiagabine. Tiagabine is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated tiagabine plasma concentrations.
Ticagrelor: Coadministration of ticagrelor and telaprevir may result in increased exposure to ticagrelor which may increase the bleeding risk. Ticagrelor is a P-glycoprotein (P-gp) substrate and telaprevir is a P-gp inhibitor (potency unknown). 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: Close clinical monitoring is advised when administering tinidazole with telaprevir due to an increased potential for tinidazole-related adverse events. If tinidazole 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 tinidazole. Tinidazole is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated tinidazole plasma concentrations.
Tipranavir: Close clinical monitoring is advised when administering tipranavir with telaprevir due to an increased potential for adverse events. If tipranavir 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 pathways of tipranavir and telaprevir. Both tipranavir and telaprevir are substrates and inhibitors of the hepatic isoenzyme CYP3A4. When used in combination, the plasma concentrations of both medications may be elevated.
Tolterodine: Close clinical monitoring is advised when administering tolterodine with telaprevir due to an increased potential for tolterodine-related adverse events. If tolterodine 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 tolterodine. Tolterodine is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated tolterodine plasma concentrations.
Tolvaptan: Close clinical monitoring is advised when administering tolvaptan with telaprevir due to an increased potential for tolvaptan-related adverse events. If tolvaptan 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 tolvaptan. Tolvaptan is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; telaprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated tolvaptan plasma concentrations.
Toremifene: Metabolism of toremifene may be inhibited by drugs known to inhibit CYP3A4 hepatic enzymes. Examples of CYP3A4 inhibitors include anti-retroviral protease inhibitors. Formal interaction studies with toremifene have not been performed, and the clinical relevance of potential interactions is uncertain.
Trabectedin: Avoid the concomitant use of trabectedin with telaprevir due to significantly increased trabectedin exposure. If short-term telaprevir (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 telaprevir 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: Close clinical monitoring is advised when administering tramadol with telaprevir due to an increased potential for tramadol-related adverse events. If tramadol 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 tramadol. Tramadol is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated tramadol plasma concentrations.
Trandolapril; Verapamil: Close clinical monitoring is advised when administering verapamil with telaprevir due to an increased potential for verapamil-related adverse events. If verapamil dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Predictions about the interaction can be made based on the metabolic pathways of verapamil and telaprevir. Both verapamil and telaprevir 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: Close clinical monitoring is advised when administering trazodone with telaprevir due to an increased potential for trazodone-related adverse event, such as nausea, 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 telaprevir treatment.
Triazolam: Concurrent use of triazolam and telaprevir is contraindicated due to the risk of life threatening reactions, such as prolonged or increased sedation or respiratory depression. Telaprevir is an 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 telaprevir, as they are not oxidatively metabolized.
Ulipristal: 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 telaprevir may telaprevir 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.
Vardenafil: Close clinical monitoring is advised when administering vardenafil with telaprevir due to an increased potential for vardenafil-related adverse events, such as QT interval prolongation. During coadministration, do not exceed a maximum vardenafil dosage of 2.5 mg in 72 hours. If vardenafil dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Predictions about the interaction can be made based on the metabolic pathways of vardenafil. Vardenafil is a substrate of the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. When used in combination, the plasma concentrations of vardenafil may be elevated.
Vemurafenib: Concomitant use of vemurafenib and telaprevir may result in altered concentrations of telaprevir and increased concentrations of vemurafenib. Vemurafenib is a substrate/inducer of CYP3A4 and a substrate/inhibitor of P-glycoprotein (P-gp). Telaprevir is a substrate/inhibitor of CYP3A4 and P-gp. Avoid using these agents together if possible.
Venetoclax: Avoid the concomitant use of venetoclax and telaprevir; venetoclax is a substrate of CYP3A4 and P-glycoprotein (P-gp) and telaprevir is a strong CYP3A4 and P-gp inhibitor. The concomitant use of these agents together is contraindicated during the initial and dose titration phase of venetoclax. If concomitant use of these drugs is required when the patient is on a steady venetoclax dose (after the titration phase), reduce the venetoclax dosage by at least 75% (maximum dose of 100 mg/day). If telaprevir is discontinued, wait 2 to 3 days and then resume the recommended venetoclax dosage (or prior dosage if less). Monitor patients for signs and symptoms of venetoclax toxicity such as hematologic toxicity, GI toxicity, and tumor lysis syndrome. In a drug interaction study, the venetoclax Cmax and AUC values were increased by 2.3-fold and 6.4-fold, respectively, when a strong CYP3A4 inhibitor was co-administered in NHL patients.
Venlafaxine: Close clinical monitoring is advised when administering venlafaxine with telaprevir due to an increased potential for venlafaxine-related adverse events. If venlafaxine 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 venlafaxine. Venlafaxine is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated venlafaxine plasma concentrations.
Verapamil: Close clinical monitoring is advised when administering verapamil with telaprevir due to an increased potential for verapamil-related adverse events. If verapamil dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Predictions about the interaction can be made based on the metabolic pathways of verapamil and telaprevir. Both verapamil and telaprevir 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: Because CYP3A4 is the primary isoenzyme involved in the metabolism of vilazodone, the manufacturer recommends that the daily vilazodone dose be reduced to 20 mg in adult patients receiving strong inhibitors of CYP3A4 such as telaprevir. Plasma concentrations of vilazodone can increase by 50% during concurrent use of strong CYP3A4 inhibitors.
Vinblastine: Close clinical monitoring is advised when administering vinblastine with telaprevir due to an increased potential for vinblastine-related adverse events. If vinblastine 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 vinblastine. Vinblastine is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; telaprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated vinblastine plasma concentrations.
Vincristine Liposomal: Close clinical monitoring is advised when administering vincristine with telaprevir due to an increased potential for vincristine-related adverse events. If vincristine 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 vincristine. Vincristine is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; telaprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated vincristine plasma concentrations.
Vincristine: Close clinical monitoring is advised when administering vincristine with telaprevir due to an increased potential for vincristine-related adverse events. If vincristine 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 vincristine. Vincristine is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; telaprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated vincristine plasma concentrations.
Vinorelbine: Use caution with concurrent use of telaprevir, a CYP3A4 inhibitor, and vinorelbine, a CYP3A4 substrate, as the metabolism of vinorelbine may be decreased. Monitor patients for an earlier onset and/or an increased severity of adverse effects including neurotoxicity and myelosuppression.
Vorapaxar: Avoid coadministration of vorapaxar and telaprevir. Increased serum concentrations of vorapaxar are possible when vorapaxar, a CYP3A4 substrate, is coadministered with telaprevir, a strong CYP3A inhibitor. Increased exposure to vorapaxar may increase the risk of bleeding complications.
Voriconazole: Close clinical monitoring is advised when administering voriconazole with telaprevir due to an increased potential for voriconazole and telaprevir-related adverse events, such as QT prolongation and torsade de pointes (TdP). Voriconazole should not be administered to patients receiving telaprevir unless the potential risk is justified by the potential benefit. If voriconazole dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Predictions about the interaction can be made based on the metabolic pathways of voriconazole and telaprevir. Both voriconazole and telaprevir are substrates and inhibitors of the hepatic isoenzyme CYP3A4. When used in combination, the plasma concentration of telaprevir may be elevated. Alterations in voriconazole plasma concentrations, however, are more difficult to predict because multiple enzymes are involved with voriconazole metabolism.
Warfarin: Monitoring of the international normalized ratio (INR) is advised when administering warfarin with telaprevir 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 telaprevir treatment. Predictions about the interaction can be made based on the metabolic pathway of warfarin. Warfarin is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in altered warfarin plasma concentrations.
Yohimbine: Close clinical monitoring is advised when administering yohimbine with telaprevir due to an increased potential for yohimbine-related adverse events. If yohimbine 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 yohimbine. Yohimbine is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated yohimbine plasma concentrations.
Zafirlukast: Close clinical monitoring is advised when administering zafirlukast with telaprevir due to an increased potential for telaprevir-related adverse events. If zafirlukast 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 pathways of zafirlukast and telaprevir. Zafirlukast is an inhibitor of the hepatic isoenzyme CYP3A4; telaprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of telaprevir may be elevated.
Zileuton: Close clinical monitoring is advised when administering zileuton with telaprevir due to an increased potential for zileuton-related adverse events. If zileuton 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 zileuton. Zileuton is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated zileuton plasma concentrations.
Ziprasidone: Close clinical monitoring is advised when administering ziprasidone with telaprevir due to an increased potential for ziprasidone-related adverse events. If ziprasidone 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 ziprasidone. Ziprasidone is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated ziprasidone plasma concentrations.
Zolpidem: Clinical monitoring is advised when administering zolpidem with telaprevir due to the potential for decreased zolpidem efficacy. The dose of zolpidem should be titrated to achieve desired clinical response. If zolpidem dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment.
Zonisamide: Close clinical monitoring is advised when administering zonisamide with telaprevir due to an increased potential for zonisamide-related adverse events. If zonisamide 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 zonisamide. Zonisamide is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated zonisamide plasma concentrations.

INCIVEK Oral Tab: 375mg

Adults

2250 mg/day PO.

Geriatric

2250 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.

Telaprevir 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 mature/functioning viral proteins. These mature proteins, NS4A, NS4B, NS5A, and NS5B, are essential for viral replication.
 
Hepatitis C viral resistance to telaprevir has been demonstrated in both cell cultures and during clinical studies. Biochemical analysis of cell cultures found NS3 amino acid substitutions frequently developing in patients receiving treatment with telaprevir. In nearly all cases, these substitutions resulted in reduced telaprevir antiviral activity. During clinical studies, these treatment emergent amino acid substitutions were isolated in almost 100% of patients who failed to achieve a sustained viral response.

Telaprevir is administered orally. Following administration, approximately 59—76% of systemically absorbed drug is bound to plasma protein, primarily to alpha 1-acid glycoprotein and albumin. Protein binding is concentration dependent with the percentage decreasing as telaprevir serum concentrations increase. Metabolism, via hydrolysis, oxidation, and reduction, occurs extensively in the liver. The primary hepatic isoenzyme involved metabolism is CYP3A4; non-CYP mediated metabolism may also occur following multiple doses. Telaprevir is primarily excreted through the feces (82%). Other routes of elimination include exhaled air (9%) and through the urine (1%). The mean elimination half life following administration of a single 750 mg dose ranges from 4—4.7 hours; however at steady state, the half life increases to approximately 9—11 hours.
 
Affected cytochrome P450 isoenzymes and drug transporters:  CYP3A4, p-glycoprotein (P-gp), OATP
Telaprevir is a strong inhibitor of the hepatic isoenzymes CYP3A4. In vitro studies suggest it does not induce CYP2B6, CYP2C, CYP3A, or CYP1A. It is also an inhibitor and substrate of the efflux transporter p-glycoprotein (P-gp), and an inhibitor of OATP1B1 and OATP2B1.

Oral Route

Following oral administration of a single dose, maximum telaprevir plasma concentrations (Cmax) are obtained in approximately 4—5 hours. Total exposure is similar regardless of whether the total daily dose of 2240 mg was administered as 750 mg PO every 8 hours or as 1125 mg PO twice daily. The presence of food significantly affects systemic exposure (AUC). Relative to the fasting state, administration with a low-fat meal (249 kcal, 3.6 gm fat), standard high-fat meal (533 kcal, 21 gm fat), or high-fat meal (928 kcal, 56 gm fat) increases AUC by 117%, 237%, and 330%, respectively. During clinical trials, patients received telaprevir within 30 minutes of eating a meal or snack containing 20 gm of fat; thus, telaprevir should always be taken with non-low fat food.

Pregnancy

Telaprevir 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 telaprevir in pregnant women; however, because telaprevir must be administered in combination with peginterferon alfa and ribavirin, use of telaprevir 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. Health care providers must also consider the potential for decreased efficacy of systemic hormonal contraception as interferon therapy may decreased serum estradiol and progesterone concentrations and telaprevir may decrease the serum concentrations of ethinyl estradiol. Patients and their partners are required use 2 forms of effective contraception (e.g., intrauterine devices and barrier methods) during treatment and for 6 months post-therapy. Patients who are not willing to practice strict contraception should not receive treatment with telaprevir, 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 telaprevir, 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.