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Telaprevir

Pronunciation

(tel A pre vir)

Index Terms

  • LY570310
  • MP - 424
  • MP424
  • VRT111950
  • VX - 950
  • VX950

Dosage Forms

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]

Brand Names: U.S.

  • Incivek [DSC]

Pharmacologic Category

  • Antihepaciviral, Protease Inhibitor (Anti-HCV)
  • NS3/4A Inhibitor

Pharmacology

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).

Absorption

Food (not low fat) enhances absorption

Distribution

Vd: ~252 L

Metabolism

Primarily hepatic to less active (30x) and inactive metabolites. Some oxidative CYP3A4 metabolism.

Excretion

Feces (82%); urine (1%)

Time to Peak

4-5 hours

Half-Life Elimination

Plasma: Adults: ~4-5 hours (single dose); steady state: ~9-11 hours

Protein Binding

59% to 76%

Special Populations: Renal Function Impairment

Cmax and AUC increased 3% and 21%, respectively, in patients with severe renal impairment.

Special Populations: Hepatic Function Impairment

Steady-state exposure was reduced 15% and 46% in patients with mild and moderate hepatic impairment, respectively, compared with healthy subjects.

Use: Labeled Indications

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.

Contraindications

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.

Dosing: Adult

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.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment

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.

Dosing: Hepatic Impairment

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.

Administration

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.

Dietary Considerations

Take with a meal (not low fat).

Storage

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

Drug Interactions

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

AmLODIPine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of AmLODIPine. 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); AmLODIPine; 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 Cushing's 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

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

Adverse Reactions

>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

ALERT: U.S. Boxed Warning

Serious skin rections:

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.

Warnings/Precautions

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).

Monitoring Parameters

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

Pregnancy Risk Factor

B / X (in combination with ribavirin)

Pregnancy Considerations

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).

Patient Education

• 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.

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