(tel A pre vir)
Chronic hepatitis C: Treatment of genotype 1 chronic hepatitis C (in combination with peginterferon alfa and ribavirin) in adult patients with compensated liver disease (including cirrhosis) who are treatment naive or who have received previous interferon-based treatment, including null or partial responders, and treatment relapsers.
Combination treatment with ribavirin: Pregnancy; male partners of pregnant women
Coadministration with alfuzosin, cisapride, ergot derivatives (eg, dihydroergotamine, ergonovine, ergotamine, methylergonovine), lovastatin, midazolam (oral), pimozide, sildenafil/tadalafil (when used for treatment of pulmonary arterial hypertension), simvastatin, triazolam, rifampin, St John 's wort, carbamazepine, phenobarbital, phenytoin
Canadian labeling: Additional contraindications (not in U.S. labeling): Hypersensitivity to telaprevir or any component of the formulation; coadministration with amiodarone, astemizole (not available in Canada), eletriptan, eplerenone, flecainide, propafenone, quinidine, terfenadine (not available in Canada), vardenafil
Also refer to Peginterferon Alfa and Ribavirin monographs for individual product contraindications.
Fatal and nonfatal serious skin reactions, including Stevens-Johnson syndrome, drug reaction with eosinophilia and systemic symptoms (DRESS), and toxic epidermal necrolysis (TEN), have been reported in patients treated with telaprevir combination treatment. Fatal cases have been reported in patients with progressive rash and systemic symptoms who continued to receive telaprevir combination treatment after a serious skin reaction was identified. For serious skin reactions, including rash with systemic symptoms or a progressive severe rash, telaprevir, peginterferon alfa, and ribavirin must be discontinued immediately. Discontinuing other medications known to be associated with serious skin reactions should be considered. Patients should be promptly referred for urgent medical care.
Note: Incivek has been discontinued in the US for more than 1 year.
Treatment of chronic hepatitis C (CHC): Oral: 1125 mg twice daily (in combination with peginterferon alfa and ribavirin).
Treatment-naive or prior relapse patients:Note: Relapse includes patients with an undetectable HCV-RNA upon completion of treatment (non-telaprevir based regimen) but with detectable HCV-RNA during the follow up period.
Weeks 1-12: Triple therapy: Telaprevir 1125 mg twice daily in combination with peginterferon alfa and ribavirin
Weeks 13-23 (based on HCV-RNA results at weeks 4 and 12):
HCV-RNA undetectable (level less than ~10-15 units/mL) at both weeks 4 and 12 (eRVR): Dual therapy: Peginterferon alfa with concomitant ribavirin only (through week 24)
HCV-RNA detectable (level greater than ~10-15 units/mL but ≤1000 units/mL) at week 4 and/or week 12: Dual therapy: Peginterferon alfa and ribavirin only (through week 48 discussed below)
HCV-RNA detectable (level >1000 units/mL) at week 4 or week 12 (treatment futility): Discontinue telaprevir, peginterferon alfa and ribavirin at week 12
Weeks ≥24 (based on HCV-RNA results at week 24):
HCV-RNA detectable (level greater than ~10-15 units/mL but ≤1000 units/mL) at week 4 and/or week 12: Peginterferon alfa with concomitant ribavirin only (through week 48)
HCV-RNA detectable (level greater than ~10-15 units/mL) at week 24 (treatment futility): Discontinue peginterferon alfa and concomitant ribavirin
Treatment-naive patients with cirrhosis, compensated:
Weeks 1-12: Triple therapy: Telaprevir 1125 mg twice daily in combination with peginterferon alfa and ribavirin
Weeks 13-24 (based on HCV-RNA results at weeks 4 and 12):
HCV-RNA undetectable at both weeks 4 and 12 (eRVR): Dual therapy: Peginterferon alfa and ribavirin only (through week 48 discussed below)
HCV-RNA detectable (level greater than ~10-15 units/mL but ≤1000 units/mL) at week 4 and/or week 12: Dual therapy: Peginterferon alfa and ribavirin only (through week 48 discussed below)
HCV-RNA detectable (level >1000 units/mL) at week 4 or week 12 (treatment futility): Discontinue telaprevir, peginterferon alfa and ribavirin at week 12
Weeks ≥24 (based on HCV-RNA results at week 24):
HCV-RNA undetectable at week 24: Peginterferon alfa with concomitant ribavirin only (through week 48)
HCV-RNA detectable (level greater than ~10-15 units/mL) at week 24 (treatment futility): Discontinue peginterferon alfa and ribavirin
Previously-treated patients (partial response or null responders):Note: Previously treated does not include prior treatment with telaprevir. Partial response includes patients with a >2-log10 HCV-RNA decrease by week 12 but a nonsustained virologic response thereafter. Null response includes patients with a <2-log10 HCV-RNA decrease at week 12.
Weeks 1-12: Triple therapy: Telaprevir 1125 mg twice daily with peginterferon alfa and ribavirin
Weeks 13-48 (based on HCV-RNA results at weeks 4 and 12):
HCV-RNA undetectable (level less than ~10-15 units/mL) or detectable (level ≤1000 units/mL) at both weeks 4 and 12: Dual therapy: Peginterferon alfa and ribavirin only (through week 48)
HCV-RNA detectable (level >1000 units/mL) at week 4 or week 12: Discontinue telaprevir, peginterferon alfa, and ribavirin at week 12
HCV-RNA detectable (level greater than ~10-15 units/mL) at week 24: Discontinue peginterferon alfa and concomitant ribavirin
Missed dose: If a dose is missed within 6 hours of the time it is usually taken, take as soon as possible. If more than 6 hours have passed since the dose is usually taken, do not take the missed dose and the patient should resume the usual schedule.
Refer to adult dosing.
Telaprevir: No dosage adjustment necessary. Not studied in patients with CrCl ≤50 mL/minute or in hemodialysis.
Peginterferon Alfa and Ribavirin: Refer to individual monographs.
Telaprevir:
Mild (Child-Pugh class A) impairment: No dosage adjustment necessary.
Moderate or severe impairment (Child-Pugh class B or C): Use is not recommended in patients with decompensated liver disease or with moderate or severe hepatic impairment (has not been studied).
Peginterferon Alfa and Ribavirin: Refer to individual monographs.
Administer with a meal (not low fat) within 30 minutes prior to each dose. Doses should be taken approximately every 10-14 hours. Administer concurrently with peginterferon alfa and ribavirin. Maintain adequate fluid intake/hydration. Swallow tablets whole; do not chew, crush, break, cut, or dissolve the tablets. If a dose is missed within 6 hours of the time it is usually taken, take as soon as possible. If more than 6 hours have passed since the dose is usually taken, the missed dose should not be taken and the patient should resume the usual schedule.
Take with a meal (not low fat).
Store at 25 ‚ °C (77 ‚ °F); excursions permitted to 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Tablet, Oral:
Incivek: 375 mg [DSC] [contains fd&c blue #2 (indigotine), fd&c red #40]
Ado-Trastuzumab Emtansine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Ado-Trastuzumab Emtansine. Specifically, strong CYP3A4 inhibitors may increase concentrations of the cytotoxic DM1 component. Avoid combination
Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: Per US labeling: reduce afatinib by 10mg if not tolerated. Per Canadian labeling: avoid combination if possible; if used, administer the P-gp inhibitor simultaneously with or after the dose of afatinib. Consider therapy modification
Alfuzosin: Telaprevir may increase the serum concentration of Alfuzosin. Avoid combination
Alitretinoin (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alitretinoin (Systemic). Management: Consider reducing the alitretinoin dose to 10 mg when used together with strong CYP3A4 inhibitors. Monitor for increased alitretinoin effects/toxicities if combined with a strong CYP3A4 inhibitor. Consider therapy modification
Almotriptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Almotriptan. Management: Limit initial almotriptan adult dose to 6.25 mg and maximum adult dose to 12.5 mg/24-hrs when used with a strong CYP3A4 inhibitor. Avoid concurrent use in patients with impaired hepatic or renal function. Consider therapy modification
Alosetron: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alosetron. Monitor therapy
ALPRAZolam: Telaprevir may increase the serum concentration of ALPRAZolam. Monitor therapy
Amiodarone: Telaprevir may enhance the adverse/toxic effect of Amiodarone. Telaprevir may increase the serum concentration of Amiodarone. Monitor therapy
Apixaban: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase the serum concentration of Apixaban. Management: US labeling recommends a 50% apixaban dose reduction in patients who would otherwise receive 5 or 10 mg twice daily, and avoiding in patients who would otherwise receive 2.5 mg twice daily. Canadian labeling lists any combined use as contraindicated. Consider therapy modification
Aprepitant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Aprepitant. Avoid combination
ARIPiprazole: CYP3A4 Inhibitors (Strong) may increase the serum concentration of ARIPiprazole. Management: See full interaction monograph for details. Consider therapy modification
ARIPiprazole Lauroxil: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of ARIPiprazole Lauroxil. Management: Please refer to the full interaction monograph for details concerning the recommended dose adjustments. Consider therapy modification
Astemizole: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Astemizole. Avoid combination
Asunaprevir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Asunaprevir. Avoid combination
Atazanavir: May decrease the serum concentration of Telaprevir. Telaprevir may increase the serum concentration of Atazanavir. Monitor therapy
AtorvaSTATin: Telaprevir may increase the serum concentration of AtorvaSTATin. Avoid combination
Avanafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Avanafil. Avoid combination
Axitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Axitinib. Management: Avoid concurrent use of axitinib with any strong CYP3A inhibitor whenever possible. If a strong CYP3A inhibitor must be used with axitinib, a 50% axitinib dose reduction is recommended. Avoid combination
Barnidipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Barnidipine. Avoid combination
Bedaquiline: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bedaquiline. Management: Limit the duration of concomitant administration of bedaquiline with CYP3A4 inhibitors to no more than 14 days, unless the benefit of continued administration is judged to outweigh the possible risks. Monitor for toxic effects of bedaquiline. Consider therapy modification
Bepridil: Telaprevir may enhance the adverse/toxic effect of Bepridil. Monitor therapy
Blonanserin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Blonanserin. Avoid combination
Bortezomib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bortezomib. Monitor therapy
Bosentan: May decrease the serum concentration of Telaprevir. Telaprevir may increase the serum concentration of Bosentan. Monitor therapy
Bosutinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bosutinib. Avoid combination
Bosutinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bosutinib. Avoid combination
Brentuximab Vedotin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Monitor therapy
Brentuximab Vedotin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Monitor therapy
Brexpiprazole: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brexpiprazole. Management: Reduce brexpiprazole dose to 50% of usual with a strong CYP3A4 inhibitor; reduce to 25% of usual if used with both a moderate CYP3A4 inhibitor and a CYP2D6 inhibitor, or if a strong CYP3A4 inhibitor is used in a CYP2D6 poor metabolizer. Consider therapy modification
Brinzolamide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brinzolamide. Monitor therapy
Bromocriptine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bromocriptine. Avoid combination
Budesonide (Nasal): Telaprevir may increase the serum concentration of Budesonide (Nasal). Management: Concurrent use of telaprevir with inhaled budesonide is not recommended, unless the risk for excessive systemic corticosteroid effects is outweighed by the potential benefits. Consider therapy modification
Budesonide (Oral Inhalation): Telaprevir may increase the serum concentration of Budesonide (Oral Inhalation). Management: Concomitant use of these agents is not recommended, unless the risk for excessive systemic corticosteroid effects is outweighed by the potential benefits. If combined, monitor patients closely for signs and symptoms of corticosteroid excess/toxicity. Consider therapy modification
Budesonide (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Systemic). Avoid combination
Budesonide (Topical): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Topical). Management: Per US prescribing information, avoid this combination. Canadian product labeling does not recommend strict avoidance. If combined, monitor for excessive glucocorticoid effects as budesonide exposure may be increased. Consider therapy modification
Buprenorphine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Buprenorphine. Monitor therapy
Cabazitaxel: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cabazitaxel. Management: Concurrent use of cabazitaxel with strong inhibitors of CYP3A4 should be avoided when possible. If such a combination must be used, consider a 25% reduction in the cabazitaxel dose. Consider therapy modification
Cabozantinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cabozantinib. Management: Avoid use of a strong CYP3A4 inhibitor with cabozantinib if possible. If combined, cabozantinib dose adjustments are recommended and vary based on the cabozantinib product used and the indication for use. See monograph for details. Consider therapy modification
Calcifediol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Calcifediol. Monitor therapy
Cannabis: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be increased. Monitor therapy
CarBAMazepine: Telaprevir may increase the serum concentration of CarBAMazepine. CarBAMazepine may decrease the serum concentration of Telaprevir. Avoid combination
Cariprazine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cariprazine. Management: Cariprazine dose reductions of 50% are required; specific recommended management varies slightly for those stable on cariprazine versus those just starting cariprazine. See prescribing information or full interaction monograph for details. Consider therapy modification
Ceritinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ceritinib. Management: If such combinations cannot be avoided, the ceritinib dose should be reduced by approximately one-third (to the nearest 150 mg). Resume the prior ceritinib dose after cessation of the strong CYP3A4 inhibitor. Avoid combination
Cilostazol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cilostazol. Management: Consider reducing the cilostazol dose to 50 mg twice daily in adult patients who are also receiving strong inhibitors of CYP3A4. Consider therapy modification
Cisapride: Telaprevir may increase the serum concentration of Cisapride. Avoid combination
Clarithromycin: May increase the serum concentration of Telaprevir. Telaprevir may increase the serum concentration of Clarithromycin. Monitor therapy
CloZAPine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of CloZAPine. Monitor therapy
Cobicistat: May increase the serum concentration of Telaprevir. Management: Avoid concomitant use of telaprevir with cobicistat. This warning does not apply to use of the combination product containing elvitegravir, cobicistat, emtricitabine, and tenofovir. Avoid combination
Cobimetinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cobimetinib. Avoid combination
Colchicine: Telaprevir may increase the serum concentration of Colchicine. Management: Colchicine should not be used with telaprevir in patients with impaired renal or hepatic function. In those with normal renal and hepatic function, reduced colchicine doses (as directed) are required if used with telaprevir. Consider therapy modification
Conivaptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Conivaptan. Avoid combination
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Contraceptives (Estrogens): Telaprevir may decrease the serum concentration of Contraceptives (Estrogens). Management: Two different nonhormonal forms of contraception are required for women of childbearing potential taking telaprevir. Hormonal contraceptives may be less effective during concurrent telaprevir and for up to 2 weeks after telaprevir discontinuation. Consider therapy modification
Contraceptives (Progestins): Telaprevir may decrease the serum concentration of Contraceptives (Progestins). Management: Two different nonhormonal forms of contraception are required for women of childbearing potential taking telaprevir. Hormonal contraceptives may be less effective during concurrent telaprevir and for up to 2 weeks after telaprevir discontinuation. Consider therapy modification
Corticosteroids (Orally Inhaled): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Corticosteroids (Orally Inhaled). Management: Orally inhaled fluticasone propionate with a strong CYP3A4 inhibitor is not recommended. Exceptions: Beclomethasone (Oral Inhalation); Triamcinolone (Systemic). Monitor therapy
Corticosteroids (Systemic): May decrease the serum concentration of Telaprevir. Telaprevir may increase the serum concentration of Corticosteroids (Systemic). Management: Concurrent use of telaprevir and systemic corticosteroids is not recommended. When possible, consider alternatives. If used together, employ extra caution and monitor closely for excessive corticosteroid effects and diminished telaprevir effects. Consider therapy modification
Crizotinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Crizotinib. Avoid combination
CycloSPORINE (Systemic): Telaprevir may increase the serum concentration of CycloSPORINE (Systemic). Management: Significant cyclosporine dose reductions are likely to be required if used with telaprevir. Concurrent use should be performed with great caution and close monitoring of both cyclosporine concentrations and clinical response. Consider therapy modification
CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Telaprevir. Avoid combination
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Consider therapy modification
CYP3A4 Substrates: CYP3A4 Inhibitors (Strong) may decrease the metabolism of CYP3A4 Substrates. Exceptions: Alitretinoin (Systemic); Buprenorphine; Gefitinib; HYDROcodone; Praziquantel; Telithromycin; Vinorelbine. Consider therapy modification
Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Management: Dabigatran dose reductions may be needed. Specific recommendations vary considerably according to US vs Canadian labeling, specific P-gp inhibitor, renal function, and indication for dabigatran treatment. Refer to full monograph or dabigatran labeling. Consider therapy modification
Dabrafenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dabrafenib. Avoid combination
Daclatasvir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Daclatasvir. Management: Decrease the daclatasvir dose to 30 mg once daily if combined with a strong CYP3A4 inhibitor. No dose adjustment is needed when daclatasvir is used with darunavir/cobicistat. Consider therapy modification
Dapoxetine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dapoxetine. Avoid combination
Darunavir: May decrease the serum concentration of Telaprevir. Telaprevir may decrease the serum concentration of Darunavir. Avoid combination
Dasatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dasatinib. Management: Use of this combination should be avoided; consider reducing dasatinib dose if a strong CYP3A4 inhibitor must be used. If using dasatinib 100 mg/day, consider reduction to 20 mg/day; if using dasatinib 140 mg/day, consider reduction to 40 mg/day. Consider therapy modification
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Digoxin: Telaprevir may increase the serum concentration of Digoxin. Management: Use the lowest possible digoxin dose when starting therapy in a patient who is being treated with telaprevir, and monitor clinical response and serum concentrations closely for further dosing adjustments. Consider therapy modification
Dihydroergotamine: Telaprevir may increase the serum concentration of Dihydroergotamine. Avoid combination
Dofetilide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dofetilide. Monitor therapy
Domperidone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Domperidone. Avoid combination
Doxercalciferol: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Doxercalciferol. Monitor therapy
DOXOrubicin (Conventional): CYP3A4 Inhibitors (Strong) may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to strong CYP3A4 inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification
DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to P-glycoprotein inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification
Dronabinol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dronabinol. Monitor therapy
Dronedarone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dronedarone. Avoid combination
Dutasteride: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dutasteride. Monitor therapy
Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Management: See full monograph for details. Reduced doses are recommended for patients receiving edoxaban for venous thromboembolism in combination with certain inhibitors. Similar dose adjustment is not recommended for edoxaban use in atrial fibrillation. Consider therapy modification
Efavirenz: May decrease the serum concentration of Telaprevir. Telaprevir may decrease the serum concentration of Efavirenz. Management: Initiate telaprevir at a dose of 1125 mg every 8 hours in patients receiving efavirenz (per adult/adolescent HIV guidelines). Consider therapy modification
Eletriptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eletriptan. Avoid combination
Eliglustat: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eliglustat. Management: Use should be avoided under some circumstances. See full drug interaction monograph for details. Consider therapy modification
Eplerenone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eplerenone. Avoid combination
Ergoloid Mesylates: Telaprevir may increase the serum concentration of Ergoloid Mesylates. Avoid combination
Ergonovine: Telaprevir may increase the serum concentration of Ergonovine. Avoid combination
Ergotamine: Telaprevir may increase the serum concentration of Ergotamine. Avoid combination
Erlotinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Erlotinib. Management: Avoid use of this combination when possible. When the combination must be used, monitor the patient closely for the development of severe adverse reactions, and if such severe reactions occur, reduce the erlotinib dose (in 50 mg decrements). Consider therapy modification
Erythromycin (Systemic): Telaprevir may increase the serum concentration of Erythromycin (Systemic). Erythromycin (Systemic) may increase the serum concentration of Telaprevir. Monitor therapy
Escitalopram: Telaprevir may decrease the serum concentration of Escitalopram. Monitor therapy
Estazolam: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Estazolam. Monitor therapy
Eszopiclone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eszopiclone. Management: Limit the eszopiclone dose to 2 mg daily when combined with strong CYP3A4 inhibitors and monitor for increased eszopiclone effects and toxicities (eg, somnolence, drowsiness, CNS depression). Consider therapy modification
Etizolam: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Etizolam. Management: Consider use of lower etizolam doses when using this combination; specific recommendations concerning dose adjustment are not available. Monitor clinical response to the combination closely. Consider therapy modification
Etravirine: May decrease the serum concentration of Telaprevir. Monitor therapy
Everolimus: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Everolimus. Avoid combination
FentaNYL: CYP3A4 Inhibitors (Strong) may increase the serum concentration of FentaNYL. Management: Monitor patients closely for several days following initiation of this combination, and adjust fentanyl dose as necessary. Consider therapy modification
Fesoterodine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Fesoterodine. Management: Avoid fesoterodine doses greater than 4 mg daily in adult patients who are also receiving strong CYP3A4 inhibitors. Consider therapy modification
Flecainide: Telaprevir may enhance the adverse/toxic effect of Flecainide. Monitor therapy
Flibanserin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Flibanserin. Avoid combination
Fluticasone (Nasal): Telaprevir may increase the serum concentration of Fluticasone (Nasal). Management: Concurrent use of telaprevir with inhaled fluticasone is not recommended, unless the risk for excessive systemic corticosteroid effects is outweighed by the potential benefits. Consider therapy modification
Fluticasone (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fluticasone (Oral Inhalation). Management: Use of orally inhaled fluticasone propionate with strong CYP3A4 inhibitors is not recommended. Use of orally inhaled fluticasone furoate with strong CYP3A4 inhibitors should be done with caution. Monitor patients using such a combination more closely. Consider therapy modification
Fluvastatin: Telaprevir may increase the serum concentration of Fluvastatin. Monitor therapy
Fosamprenavir: May decrease the serum concentration of Telaprevir. Telaprevir may decrease the serum concentration of Fosamprenavir. Avoid combination
Fosphenytoin: Telaprevir may increase the serum concentration of Fosphenytoin. Fosphenytoin may decrease the serum concentration of Telaprevir. Avoid combination
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Gefitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Gefitinib. Monitor therapy
GuanFACINE: CYP3A4 Inhibitors (Strong) may increase the serum concentration of GuanFACINE. Management: Reduce the guanfacine dose by 50% when initiating this combination. Consider therapy modification
Halofantrine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Halofantrine. Avoid combination
HYDROcodone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of HYDROcodone. Monitor therapy
Ibrutinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ibrutinib. Management: If a strong CYP3A inhibitor must be used short-term (e.g. antifungals and antibiotics for 7 days or less), consider stopping ibrutinib until the CYP3A inhibitor is no longer needed. Avoid combination
Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Ifosfamide: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Ifosfamide. Monitor therapy
Iloperidone: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolites P88 and P95 may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Iloperidone. Management: Reduce iloperidone dose by half when administered with a strong CYP3A4 inhibitor. Consider therapy modification
Imatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Imatinib. Monitor therapy
Imidafenacin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Imidafenacin. Monitor therapy
Irinotecan Products: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, serum concentrations of SN-38 may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Irinotecan Products. Avoid combination
Isavuconazonium Sulfate: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Isavuconazonium Sulfate. Specifically, CYP3A4 Inhibitors (Strong) may increase isavuconazole serum concentrations. Management: Combined use is considered contraindicated per US labeling. Lopinavir/ritonavir (and possibly other uses of ritonavir doses less than 400 mg every 12 hours) is treated as a possible exception to this contraindication despite strongly inhibiting CYP3A4. Avoid combination
Itraconazole: Telaprevir may increase the serum concentration of Itraconazole. Itraconazole may increase the serum concentration of Telaprevir. Management: Doses of itraconazole greater than 200 mg/day are not recommended in patients receiving telaprevir. Use extra caution when using these drugs in combination. Consider therapy modification
Ivabradine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ivabradine. Avoid combination
Ivacaftor: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ivacaftor. Management: Ivacaftor dose reductions are required; consult prescribing information for specific age- and weight-based recommendations. Consider therapy modification
Ixabepilone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ixabepilone. Consider therapy modification
Ketoconazole (Systemic): May increase the serum concentration of Telaprevir. Telaprevir may increase the serum concentration of Ketoconazole (Systemic). Management: Doses of ketoconazole greater than 200 mg/day are not recommended in patients receiving telaprevir. Use extra caution when using these drugs in combination. Consider therapy modification
Lacosamide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lacosamide. Monitor therapy
Lapatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lapatinib. Management: If an overlap in therapy cannot be avoided, consider reducing lapatinib adult dose to 500 mg/day during, and within 1 week of completing, treatment with the strong CYP3A4 inhibitor. Avoid combination
Lercanidipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lercanidipine. Avoid combination
Levobupivacaine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levobupivacaine. Monitor therapy
Levomilnacipran: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levomilnacipran. Management: Do not exceed a maximum adult levomilnacipran dose of 80 mg/day in patients also receiving strong CYP3A4 inhibitors. Consider therapy modification
Lidocaine (Systemic): Telaprevir may enhance the adverse/toxic effect of Lidocaine (Systemic). Telaprevir may increase the serum concentration of Lidocaine (Systemic). Monitor therapy
Lomitapide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lomitapide. Avoid combination
Lopinavir: May decrease the serum concentration of Telaprevir. Avoid combination
Lovastatin: Telaprevir may increase the serum concentration of Lovastatin. Avoid combination
Luliconazole: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Lumefantrine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lumefantrine. Monitor therapy
Lurasidone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lurasidone. Avoid combination
Macitentan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Macitentan. Avoid combination
Maraviroc: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Maraviroc. Management: Reduce the adult dose of maraviroc to 150 mg twice daily when used with a strong CYP3A4 inhibitor. Do not use maraviroc with strong CYP3A4 inhibitors in patients with Clcr less than 30 mL/min. Consider therapy modification
Methadone: Telaprevir may decrease the serum concentration of Methadone. Monitor therapy
Methylergonovine: Telaprevir may increase the serum concentration of Methylergonovine. Avoid combination
MethylPREDNISolone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of MethylPREDNISolone. Management: Consider methylprednisolone dose reduction in patients receiving strong CYP3A4 inhibitors and monitor for increased steroid related adverse effects. Consider therapy modification
Midazolam: Telaprevir may increase the serum concentration of Midazolam. Management: Use of oral midazolam with telaprevir is contraindicated. IV midazolam use may pose a lower risk, but dose reductions should be considered and patients should be monitored closely for signs/symptoms of toxicity. Avoid combination
MiFEPRIStone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of MiFEPRIStone. Management: Limit mifepristone adult dose, when used for treatment of hyperglycemia in Cushings syndrome, to a maximum of 300 mg/day when combined with a strong CYP3A4 inhibitor. Monitor for increased mifepristone toxicity regardless of dose or indication. Consider therapy modification
MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates. Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification
Mirodenafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mirodenafil. Management: Consider using a lower dose of mirodenafil when used with strong CYP3A4 inhibitors. Monitor for increased mirodenafil effects/toxicities with the use of this combination. Consider therapy modification
Naloxegol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Naloxegol. Avoid combination
Netupitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Nilotinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nilotinib. Avoid combination
NiMODipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of NiMODipine. Avoid combination
Nintedanib: Combined Inhibitors of CYP3A4 and P-glycoprotein may increase the serum concentration of Nintedanib. Monitor therapy
Nisoldipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nisoldipine. Avoid combination
Olaparib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Olaparib. Management: Avoid use of strong CYP3A4 inhibitors in patients being treated with olaparib. If such concurrent use cannot be avoided, the dose of olaparib should be reduced to 150 mg twice daily. Avoid combination
Osimertinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Osimertinib. Avoid combination
Ospemifene: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ospemifene. Monitor therapy
Oxybutynin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Oxybutynin. Monitor therapy
OxyCODONE: CYP3A4 Inhibitors (Strong) may enhance the adverse/toxic effect of OxyCODONE. CYP3A4 Inhibitors (Strong) may increase the serum concentration of OxyCODONE. Serum concentrations of the active metabolite oxymorphone may also be increased. Consider therapy modification
Palbociclib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Palbociclib. Avoid combination
Panobinostat: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Panobinostat. Management: Reduce the panobinostat dose to 10 mg when it must be used with a strong CYP3A4 inhibitor. Consider therapy modification
Parecoxib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Parecoxib. Monitor therapy
Paricalcitol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Paricalcitol. Monitor therapy
PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib. Avoid combination
P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy
P-glycoprotein/ABCB1 Substrates: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy
PHENobarbital: May decrease the serum concentration of Telaprevir. Avoid combination
Phenytoin: Telaprevir may increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Telaprevir. Avoid combination
Pimavanserin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pimavanserin. Consider therapy modification
Pimecrolimus: CYP3A4 Inhibitors (Strong) may decrease the metabolism of Pimecrolimus. Monitor therapy
Pimozide: Telaprevir may increase the serum concentration of Pimozide. Avoid combination
Pitavastatin: Telaprevir may increase the serum concentration of Pitavastatin. Monitor therapy
PONATinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of PONATinib. Management: Per ponatinib U.S. prescribing information, the adult starting dose of ponatinib should be reduced to 30 mg daily during treatment with any strong CYP3A4 inhibitor. Consider therapy modification
Posaconazole: Telaprevir may increase the serum concentration of Posaconazole. Posaconazole may increase the serum concentration of Telaprevir. Monitor therapy
Pranlukast: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pranlukast. Monitor therapy
Prasugrel: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Prasugrel. Monitor therapy
Pravastatin: Telaprevir may increase the serum concentration of Pravastatin. Monitor therapy
Praziquantel: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Praziquantel. Monitor therapy
Propafenone: Telaprevir may enhance the adverse/toxic effect of Propafenone. Monitor therapy
Prucalopride: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Prucalopride. Monitor therapy
QUEtiapine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of QUEtiapine. Management: In quetiapine treated patients, reduce the quetiapine dose to one sixth of the regular dose following strong CYP3A4 inhibitor initiation. In patients receiving strong CYP3A4 inhibitors, initiate quetiapine at the lowest dose and up-titrate as needed. Consider therapy modification
QuiNIDine: Telaprevir may enhance the adverse/toxic effect of QuiNIDine. Telaprevir may increase the serum concentration of QuiNIDine. Monitor therapy
Ramelteon: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ramelteon. Monitor therapy
Ranolazine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ranolazine. Avoid combination
Reboxetine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Reboxetine. Consider therapy modification
Red Yeast Rice: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Red Yeast Rice. Specifically, concentrations of lovastatin and related compounds found in Red Yeast Rice may be increased. Avoid combination
Regorafenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Regorafenib. Avoid combination
Repaglinide: Telaprevir may increase the serum concentration of Repaglinide. Monitor therapy
Retapamulin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Retapamulin. Management: Avoid this combination in patients less than 2 years old. No action is required in other populations. Monitor therapy
Rifabutin: May decrease the serum concentration of Telaprevir. Telaprevir may increase the serum concentration of Rifabutin. Avoid combination
RifAMPin: May decrease the serum concentration of Telaprevir. Avoid combination
RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Monitor therapy
Rilpivirine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Rilpivirine. Monitor therapy
Ritonavir: May decrease the serum concentration of Telaprevir. Ritonavir may increase the serum concentration of Telaprevir. Monitor therapy
Rivaroxaban: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase the serum concentration of Rivaroxaban. Avoid combination
RomiDEPsin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of RomiDEPsin. Monitor therapy
Rosuvastatin: Telaprevir may increase the serum concentration of Rosuvastatin. Monitor therapy
Ruxolitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ruxolitinib. Management: This combination should be avoided under some circumstances. See monograph for details. Consider therapy modification
Salmeterol: Telaprevir may increase the serum concentration of Salmeterol. Avoid combination
SAXagliptin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of SAXagliptin. Management: Saxagliptin U.S. product labeling recommends limiting saxagliptin adult dose to 2.5 mg/day when used with a strong CYP3A4 inhibitor. Monitor for increased saxagliptin levels/effects. A similar recommendation is not made in the Canadian product labeling. Consider therapy modification
Sildenafil: Telaprevir may increase the serum concentration of Sildenafil. Management: Concurrent use of sildenafil for treatment of pulmonary arterial hypertension is contraindicated with telaprevir. Sildenafil for erectile dysfunction should be limited to 25 mg per 48 hours, with close monitoring for sildenafil toxicity. Avoid combination
Silodosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Silodosin. Avoid combination
Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Avoid combination
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Simeprevir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Simeprevir. Avoid combination
Simvastatin: Telaprevir may increase the serum concentration of Simvastatin. Avoid combination
Sirolimus: Telaprevir may increase the serum concentration of Sirolimus. Management: Significant sirolimus dose reductions are likely to be required if used with telaprevir. Concurrent use should be performed with great caution and close monitoring of both sirolimus concentrations and clinical response. Consider therapy modification
Sonidegib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sonidegib. Avoid combination
SORAfenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of SORAfenib. Monitor therapy
St John's Wort: May decrease the serum concentration of Telaprevir. Avoid combination
Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification
Suvorexant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Suvorexant. Avoid combination
Tacrolimus (Systemic): Telaprevir may increase the serum concentration of Tacrolimus (Systemic). Management: Significant tacrolimus dose reductions are likely to be required if used with telaprevir. Concurrent use should be performed with great caution and close monitoring of both tacrolimus concentrations and clinical response. Consider therapy modification
Tadalafil: Telaprevir may increase the serum concentration of Tadalafil. Management: Concurrent use of tadalafil for treatment of pulmonary arterial hypertension is contraindicated with telaprevir. Tadalafil for erectile dysfunction should be limited to 10 mg per 72 hours, with close monitoring for tadalafil toxicity. Consider therapy modification
Tamsulosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tamsulosin. Avoid combination
Tasimelteon: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tasimelteon. Monitor therapy
Telithromycin: May increase the serum concentration of Telaprevir. Telaprevir may increase the serum concentration of Telithromycin. Monitor therapy
Tenofovir Disoproxil Fumarate: Telaprevir may increase the serum concentration of Tenofovir Disoproxil Fumarate. Monitor therapy
Terfenadine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Terfenadine. Avoid combination
Tetrahydrocannabinol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tetrahydrocannabinol. Monitor therapy
Ticagrelor: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ticagrelor. Avoid combination
Tipranavir: May decrease the serum concentration of Telaprevir. Avoid combination
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Tofacitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tofacitinib. Management: Reduce the adult dose of tofacitinib to 5 mg daily in patients receiving strong CYP3A4 inhibitors. Consider therapy modification
Tolterodine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tolterodine. Management: The maximum recommended adult dose of tolterodine is 2 mg/day when used together with a strong CYP3A4 inhibitor. Consider therapy modification
Tolvaptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tolvaptan. Avoid combination
Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Avoid combination
Toremifene: CYP3A4 Inhibitors (Strong) may enhance the adverse/toxic effect of Toremifene. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Toremifene. Avoid combination
Trabectedin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Trabectedin. Avoid combination
TraMADol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of TraMADol. Monitor therapy
TraZODone: Telaprevir may increase the serum concentration of TraZODone. Monitor therapy
Triazolam: Telaprevir may increase the serum concentration of Triazolam. Avoid combination
Udenafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Udenafil. Avoid combination
Ulipristal: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ulipristal. Management: This is specific for when ulipristal is being used for signs/symptoms of uterine fibroids (Canadian indication). When ulipristal is used as an emergency contraceptive, patients receiving this combo should be monitored for ulipristal toxicity. Avoid combination
Vardenafil: Telaprevir may increase the serum concentration of Vardenafil. Management: In patients receiving telaprevir, vardenafil dosing should be limited to 2.5 mg per 72-hour period with close monitoring for signs/symptoms of vardenafil toxicity (including hypotension, visual changes, syncope, and priapism). Consider therapy modification
Vemurafenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vemurafenib. Avoid combination
Venetoclax: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Venetoclax. Management: These combinations are contraindicated during venetoclax initiation and ramp-up. In patients receiving steady venetoclax doses after completing ramp-up, reduce the venetoclax by at least 75% if strong CYP3A4 inhibitor use cannot be avoided. Consider therapy modification
Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring these combinations. Consider therapy modification
Vilazodone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vilazodone. Management: Limit maximum adult vilazodone dose to 20 mg/day in patients receiving strong CYP3A4 inhibitors. The original vilazodone dose can be resumed following discontinuation of the strong CYP3A4 inhibitor. Consider therapy modification
VinCRIStine (Liposomal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of VinCRIStine (Liposomal). Avoid combination
VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). Avoid combination
Vindesine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vindesine. Monitor therapy
Vinflunine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vinflunine. Avoid combination
Vinorelbine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vinorelbine. Monitor therapy
Vorapaxar: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vorapaxar. Avoid combination
Voriconazole: May increase the serum concentration of Telaprevir. Telaprevir may decrease the serum concentration of Voriconazole. Telaprevir may increase the serum concentration of Voriconazole. Management: Concurrent use of telaprevir and voriconazole should be avoided due to the uncertain impact on drug concentrations and effects unless the benefit/risk ratio justifies its use. Consider therapy modification
Warfarin: Telaprevir may decrease the serum concentration of Warfarin. Telaprevir may increase the serum concentration of Warfarin. Monitor therapy
Zolpidem: Telaprevir may decrease the serum concentration of Zolpidem. Monitor therapy
Zopiclone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Zopiclone. Management: The initial starting adult dose of zopiclone should not exceed 3.75 mg if combined with a strong CYP3A4 inhibitor. Monitor patients for signs and symptoms of zopiclone toxicity if these agents are combined. Consider therapy modification
Zuclopenthixol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Zuclopenthixol. Management: Consider zuclopenthixol dosage reduction with concomitant use of a strong CYP3A4 inhibitor (eg, ketoconazole) in poor CYP2D6 metabolizers or with strong CYP2D6 inhibitors (eg, paroxetine). Monitor for increased zuclopenthixol levels/toxicity. Consider therapy modification
CBC with differential and platelet count, serum electrolytes, serum creatinine, TSH, bilirubin, liver enzymes, and uric acid at baseline and weeks 2, 4, 8 and 12, then periodically (and when clinically indicated)
Serum HCV-RNA at baseline, weeks 4, 8, 12 and 24, end of treatment, during treatment follow up, and when clinically indicated
Pretreatment and monthly pregnancy test up to 6 months following discontinuation of therapy for women of childbearing age
Hydration status, including fluid intake/output, urine output, signs/symptoms of dehydration
>10%:
Central nervous system: Fatigue (56%)
Dermatologic: Rash (56%), pruritus (47%)
Endocrine and Metabolic: Hyperuricemia (<12.1 mg/dL: 66%; ≥12.1 mg/dL: 7%)
Gastrointestinal: Nausea (39%), diarrhea (26%), vomiting (13%), hemorrhoids (12%), anorectal discomfort (11%)
Hematologic: Anemia (36%), lymphopenia (15%)
Hepatic: Hyperbilirubinemia (<2.6 x ULN: 37%; ≥2.6 x ULN: 4%)
1% to 10%:
Gastrointestinal: Abnormal taste (10%), anal pruritus (6%)
Hematologic: Thrombocytopenia (3%)
<1% (Limited to important or life-threatening): Drug reaction with eosinophilia and systemic symptoms (DRESS), erythema multiforme, prerenal azotemia (with or without acute renal failure/insufficiency), Stevens-Johnson syndrome, toxic epidermal necrolysis, uric acid nephropathy
Cmax and AUC increased 3% and 21%, respectively, in patients with severe renal impairment.
Steady-state exposure was reduced 15% and 46% in patients with mild and moderate hepatic impairment, respectively, compared with healthy subjects.
Concerns related to adverse effects:
- Anemia: Has been reported with peginterferon alfa and ribavirin; addition of telaprevir is associated with a further reduction in hemoglobin. Low hemoglobin levels were measured during the first 4 weeks of treatment, and the lowest at the end of telaprevir treatment (week 12). Dose modifications of ribavirin were needed more often in patients also taking telaprevir. Assess hematologic parameters (CBC with differential and platelet count) pretreatment, at weeks 2, 4, 8, and 12, and when clinically indicated. May require ribavirin dose reduction, interruption or discontinuation of treatment; if ribavirin dose reductions are inadequate, may consider discontinuing telaprevir. Do not reduce telaprevir dose. If ribavirin is discontinued, telaprevir must also be discontinued. Do not restart telaprevir if ribavirin therapy is reinitiated.
- Nephropathy: Prerenal azotemia (with or without acute renal failure) and uric acid nephropathy have been reported. Assess serum electrolytes, creatinine, and uric acid pretreatment, at weeks 2, 4, 8, and 12, and when clinically indicated. Maintain adequate hydration.
- Skin reactions: [U.S. Boxed Warning]: Serious skin reactions (some fatal) including Stevens-Johnson syndrome (SJS), drug reaction with eosinophilia and systemic symptoms (DRESS), and toxic epidermal necrolysis (TEN), have been reported with telaprevir combination therapy. Fatal cases have been reported in patients with progressive rash and systemic symptoms who received ongoing therapy after diagnoses of serious skin reactions. Discontinue telaprevir, peginterferon alfa, and ribavirin immediately for serious skin reactions (including rash with systemic symptoms or a progressive severe rash) and refer immediately for urgent medical care. Rash has been typically observed within first 4 weeks of therapy initiation but may occur at any time. Severe rashes (other than DRESS, SJS) are generalized, bullous, vesicular or ulcerative; may also have an eczematous appearance. Discontinue telaprevir (may continue peginterferon alfa and ribavirin) for severe rash or for mild-to-moderate rash that progresses; if no improvement in rash within 1 week of stopping telaprevir, interruption or discontinuation of peginterferon alfa and/or ribavirin should be considered (or sooner if clinically indicated). May use oral antihistamines/topical corticosteroids for rash treatment; do not use systemic corticosteroids. Do not restart telaprevir if discontinued due to any skin reaction.
Disease-related concerns:
- Hepatic impairment: Not recommended in moderate or severe hepatic impairment (Child-Pugh class B or C) or decompensated hepatic disease.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustments, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Special populations:
- Pregnancy and/or women of childbearing potential: Combination therapy with ribavirin may cause birth defects; avoid pregnancy in females and female partners of male patients. Combination therapy with ribavirin is contraindicated in pregnancy. Hormonal contraceptives may not be effective in patients taking telaprevir or for 2 weeks after discontinuing therapy. Use 2 effective nonhormonal forms of contraception during treatment and for 2 weeks after telaprevir completion.
Other warnings/precautions:
- Appropriate use: Should only be used in combination with peginterferon alfa and ribavirin (do not use as monotherapy). Safety and efficacy have not been established in patients who have received liver transplants, have decompensated cirrhosis, or who have failed to respond to other HCV NS3/4A inhibitors or on repeated courses of telaprevir.
- Limitations of therapy: Telaprevir-containing regimens are not recommended for treatment-naive patients or for prior relapse patients nonresponsive to peginterferon/ribavirin regimens with or without an HCV protease inhibitor (AASLD/IDSA, 2014).
B / X (in combination with ribavirin)
Adverse events were not observed in telaprevir animal developmental studies; however, telaprevir must not be used as monotherapy (must be used in combination with peginterferon alfa and ribavirin). Significant ribavirin teratogenic effects have been observed in all animal studies at ~0.01 times the maximum recommended daily human dose. Use of ribavirin is contraindicated in pregnancy. In addition, animal studies with interferons have demonstrated abortifacient effects. Negative pregnancy test is required before initiation and monthly thereafter. Hormonal contraceptive measures may not be effective in patients taking telaprevir or for 2 weeks after discontinuing therapy. Avoid pregnancy in female patients and female partners of male patients during therapy by using two effective nonhormonal forms of contraception; continue contraceptive measures for at least 6 months after completion of therapy. If patient or female partner becomes pregnant during treatment, she should be counseled about potential risks of exposure. If pregnancy occurs during use or within 6 months after treatment, report to the ribavirin pregnancy registry (800-593-2214).
Binds reversibly to nonstructural protein 3 (NS 3) serine protease and inhibits replication of the hepatitis C virus. Considered a direct-acting antiviral treatment for HCV, also called a specifically targeted antiviral therapy for HCV (STAT-C).
Food (not low fat) enhances absorption
Vd: ~252 L
Primarily hepatic to less active (30x) and inactive metabolites. Some oxidative CYP3A4 metabolism.
Feces (82%); urine (1%)
4-5 hours
Plasma: Adults: ~4-5 hours (single dose); steady state: ~9-11 hours
59% to 76%
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience fatigue, bad taste, itching, nausea, vomiting, diarrhea, or anal irritation. Have patient report immediately to prescriber signs of fluid and electrolyte problems (mood changes, confusion, muscle pain or weakness, abnormal heartbeat, very bad dizziness or passing out, fast heartbeat, more thirst, seizures, feeling very tired or weak, not hungry, unable to pass urine or change in the amount of urine produced, dry mouth, dry eyes, nausea, or vomiting), shortness of breath, loss of strength and energy, or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.