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Supplemental Table 2: Telaprevir and Boceprevir Drug-Drug Interactions

for Health Care Providers

Supplemental Table 2: Telaprevir and Boceprevir Drug-Drug Interactions

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Contraindicated Drugs (those that strongly inhibit or induce CYP3A4)
The direction of the arrow (↑ = increase, ↓ = decrease, ↔ = no change) indicates the direction of the change.
Class/DrugDDI effect on the Class/Drug DDI effect on TelaprevirDDI effect on BoceprevirRecommendations/Comments
Alfuzosin↑ alfuzosin levels leading to
↑ potential for arrhythmias and hypotension
↔ telaprevir↔ boceprevirDo not co-administer with telaprevir or boceprevir.
Anticonvulsants
carbamazepine, phenytoin, phenobarbital
↔ phenytoin, carbamazepine, and phenobarbital levelsNot contraindicated with telaprevir. Refer to Established or Potentially Significant Drug-Drug Interactions↓ boceprevir levels potentially leading to a loss of virologic response to boceprevir

Do not co-administer with boceprevir.

For use with telaprevir: Refer to Established or Potentially Significant Drug-Drug Interactions. Caution is warranted with telaprevir co-administration; clinical and lab monitoring recommended.

Benzodiazepines
triazolam and oral midazolam
↑ BZD levels leading to
↑ potential for prolonged sedation or respiratory depression
↔ telaprevir↔ boceprevir

Do not co-administer with telaprevir or boceprevir.

Refer to Established and Potentially Significant Drug-Drug Interactions with other benzodiazepines.

Cisapride↑ cisapride levels leading to
↑ potential for arrhythmias
↔ telaprevir↔ boceprevir Do not co-administer with telaprevir or boceprevir.
Drosperinone↑ drosperinone levels leading to
↑ potential for hyperkalemia
Not contraindicated with telaprevir↔ boceprevirDo not co-administer with boceprevir.
Refer to Established or Potentially Significant Drug-Drug Interactions with oral contraceptives and boceprevir or telaprevir.
Ergot Derivatives
dihydroergotamine, ergonovine, ergotamine, methylergonovine
↑ levels of ergot derivatives potentially leading to ergot toxicity (characterized by peripheral vasospasm or ischemia)↔ telaprevir↔ boceprevirDo not co-administer with telaprevir or boceprevir.
HMG CoA Reductase Inhibitors
simvastatin, lovastatin, atorvastatin
↑ levels of HMG CoA Reductase Inhibitors potentially leading to myopathy, including rhabdomyolysis↔ telaprevir↔ boceprevirDo not co-administer with telaprevir.
For use with boceprevir: Do not co-administer simvastatin or lovastatin with boceprevir. Atorvastatin co-administration with boceprevir is not contraindicated. If atorvastatin is co-administered with boceprevir, titrate atorvastatin carefully and do not exceed 20 mg/day.
PDE-5 inhibitors for Pulmonary Hypertension*
sildenafil (Revatio),
tadalafil (Adcirca)
↑ levels of PDE-5 inhibitors potentially leading to visual abnormalities, hypotension, prolonged erection, and syncope.↔ telaprevir↔ boceprevirDo not co-administer with telaprevir or boceprevir.
*If PDE-5 Inhibitors are used for erectile dysfunction, refer to Established or Potentially Significant Drug-Drug Interactions for recommendations.
Pimozide↑ levels of pimozide potentially increasing the risk for arrhythmias↔ telaprevir↔ boceprevirDo not co-administer with telaprevir or boceprevir.
Rifampin↔ rifampin↓ telaprevir levels potentially leading to a loss of virologic response↓ boceprevir levels potentially leading to a loss of virologic responseDo not co-administer with telaprevir or boceprevir.
St. John's Wort↔ St. John's Wort↓ telaprevir levels potentially leading to a loss of virologic response↓ boceprevir levels potentially leading to a loss of virologic responseDo not co-administer with telaprevir or boceprevir.
Established (in trials) or Potentially Significant (predicted but not yet studied) Drug-Drug Interactions
Class/DrugDDI effect on the Class/Drug DDI effect on TelaprevirDDI effect on BoceprevirRecommendations/Comments
Antiarrhythmics
systemic lidocaine*, amiodarone, bepridil, flecainide, propafenone, quinidine
↑ antiarrhythmics
*Systemic lidocaine is not listed as DDI with boceprevir
↔ telaprevir
(Potentially Significant DDI)
↔ boceprevir
(Potentially Significant DDI except with systemic lidocaine)
For use with telaprevir or boceprevir: Caution warranted and clinical monitoring recommended if co-administered with antiarrhythmics.
*Systemic lidocaine is not listed as DDI with boceprevir.
Antibacterial agents
clarithromycin, erythromycin, telithromycin
↑ clarithromycin
↑ erythromycin (with telaprevir)
↑ telithromycin (with telaprevir)
↑ telaprevir
(Potentially Significant DDI)
↔ boceprevir
(Potentially Significant DDI)
For use with telaprevir: Caution warranted and clinical monitoring recommended when co-administered.
For use with boceprevir: Clarithromycin dose adjustment is not necessary with normal renal function.
Anticonvulsants
carbamazepine, phenobarbital, phenytoin
↑carbamazepine
↑ or ↓phenytoin
↑ or ↓phenobarbital
↓ telaprevir
(Potentially Significant DDI)
↓ boceprevir
(Contraindicated with boceprevir )
For use with telaprevir: Caution warranted and clinical monitoring recommended when co-administered with anticonvulsants.
For use with boceprevir: Refer to Contraindicated Drugs.
Antidepressants
desipramine, trazodone, escitalopram
↑ desipramine
↑ trazodone
↓ escitalopram
↔ telaprevir
(Established DDI with escitalopram; Potentially Significant DDI with desipramine, trazodone)
↔ boceprevir
(Potentially Significant DDI with desipramine and trazodone)
For use with telaprevir or boceprevir: Caution warranted when co-administered with antidepressants. Consider lowering dose of desipramine or trazodone. Escitalopram dose may need to be adjusted when co-administered with telaprevir.
Antifungals
ketoconazole, itraconazole, posaconazole, voriconazole
↑ ketoconazole
↑ itraconazole
↑ posaconazole
↑ voriconazole (with boceprevir) and
↑ or ↓ voriconazole (with telaprevir)
↑ telaprevir
(Established DDI with ketoconazole. Potentially Significant DDI with other listed antifungals)
↑ boceprevir
(Established DDI with ketoconazole. Potentially Significant DDI with other listed antifungals)
Caution and clinical monitoring warranted when co-administered with antifungals.
For use with telaprevir: Do not exceed 200 mg/day of ketoconazole or itraconazole. Avoid co-administration with voriconazole unless a benefit outweighs risk.
For use with boceprevir: Do not exceed 200 mg/day of ketoconazole or itraconazole.
Atorvastatin↑ atorvastatinContraindicated with telaprevir; refer to Contraindicated Drugs↔ boceprevir
(Potentially Significant DDI)
For use with telaprevir: Do not co-administer with HMG CoA Reductase Inhibitors: Refer to Contraindicated Drugs.
For use with boceprevir: Titrate atorvastatin carefully and do not exceed 20mg/day. Simvastatin and lovastatin coadministration are contraindicated; refer to Contraindicated Drugs.
Benzodiazepines
alprazolam, IV midazolam
↑ alprazolam
↑ IV midazolam
↔ telaprevir
(Established DDI)
↔ boceprevir
(Potentially Significant DDI)
Triazolam and oral midazolam are contraindicated with telaprevir or boceprevir; refer to Contraindicated Drugs.
For use with telaprevir:
Clinical monitoring warranted. Dose reduction of IV midazolam should be considered, especially if greater than a single dose is needed.
For use with boceprevir: Clinical monitoring warranted. Lower doses of midazolam IV or alprazolam should be considered.
Bosentan↑ bosentan↔ telaprevir
(Potentially Significant DDI)
↔ boceprevir
(Potentially Significant DDI)
For use with telaprevir or boceprevir: Caution warranted and clinical monitoring recommended if co-administered.
Calcium channel blockers
amlodipine, diltiazem, felodipine, nicardipine, nifedipine, and nisoldipine, verapamil
↑ calcium channel blocker levels↔ telaprevir
(Established DDI with amlodipine)
↔ boceprevir
(Established DDI with felodipine, nicardipine, nifedipine)
For use with telaprevir or boceprevir: Caution warranted if coadministered. Consider dose reduction and clinical monitoring recommended.
Colchicine↑ colchicine ↔ telaprevir
(Potentially Significant DDI)
↔ boceprevir
(Potentially Significant DDI)
For use with telaprevir and boceprevir: Avoid coadministration in renal or hepatic impairment (↑ risk of colchicine toxicity).
Colchicine dose reduction is necessary if co-administered with telaprevir or boceprevir in patients with normal renal and hepatic function:
Gout treatment: 0.6 mg for 1 dose, followed by 0.3 mg approx 1 hour later. Do not repeat dose before 3 days.
Gout prophylaxis: If original regimen was 0.6 mg twice a day, reduce dose to 0.3 mg daily. If original regimen was 0.6 mg daily, reduce dose to 0.3 mg every other day.
Treatment of familial Mediterranean fever (FMF): Maximum dose of 0.6 mg daily (or 0.3 mg twice a day).
Corticosteroids
systemic prednisone, systemic methylprednisolone, systemic dexamethasone, inhaled/nasal fluticasone and budesonide
↑ prednisone
↑ methylprednisolone
↑ fluticasone
↑budesonide
↔ dexamethasone
↓ telaprevir (with dexamethasone only)
(Established DDI)
↓boceprevir (with dexamethasone only)
(Established DDI listed for systemic dexamethasone, inhaled budesonide, and inhaled fluticasone).
For use with telaprevir: Avoid co-administration with systemic corticosteroids. Avoid co-administration with inhaled/nasal steroids unless benefits outweigh risks of systemic steroids.
For use with boceprevir: Avoid co-administration with systemic dexamethasone; use with caution if necessary. Avoid co-administration with inhaled steroids over an extended period of time (may decrease serum cortisol levels).
Digoxin↑ digoxin levels↔ telaprevir
(Established DDI)
↔ boceprevir
(Potentially Significant DDI)
For use with telaprevir: Start with lowest dose of digoxin and carefully titrate dose based on serum digoxin levels.
HIV meds
atazanavir/ritonavir, darunavir/ritonavir, fosamprenavir/ritonavir, lopinavir/ritonavir, efavirenz, tenofovir disoproxil fumarate

Telaprevir
↑ tenofovir
↑ atazanavir
↓ darunavir
↔ lopinavir
↓ fosamprenavir
↓ efavirenz

Boceprevir
↑ tenofovir
↓ atazanavir
↓ darunavir
↓ lopinavir

↓ telaprevir with listed HIV meds except tenofovir
↔ telaprevir with tenofovir
(Established DDI)
↓ boceprevir with listed HIV meds except atazanavir, tenofovir
↔ boceprevir with atazanavir, tenofovir
(Established DDI with HIV meds listed except fosamprenavir)
For use with telaprevir: If telaprevir is used in combination with efavirenz, higher telaprevir doses are needed. Avoid co-administration with ritonavir boosted with darunavir, fosamprenavir or lopinavir. Clinical and lab monitoring warranted with tenofovir co-administration; discontinue for tenofovir related toxicities.
For use with boceprevir: Avoid co-administration with efavirenz and ritonavir boosted with atazanavir, darunavir or lopinavir. DDI with fosamprenavir unknown. Clinical and lab monitoring warranted with tenofovir co-administration.
Immunosuppressants
cyclosporine, sirolimus tacrolimus
↑cyclosporine
↑ sirolimus
↑tacrolimus
↔ telaprevir
(Established DDI with cyclosporine and tacrolimus. Potentially Significant DDI with sirolimus)
↔ boceprevir
(Potentially Significant DDI)
For use with telaprevir: Significantly reduce dose and prolong dosing intervals of immunosuppressants; closely monitor blood levels and side effects.
Opioids
methadone, buprenorphine
↓ methadone with telaprevir
↑ or
↓ methadone with boceprevir
↑ or ↓ buprenorphine with boceprevir
↔ telaprevir
(Established DDI with methadone)
↔ boceprevir
(Potentially Significant DDI)
For use with telaprevir or boceprevir: Clinical monitoring is warranted.
Oral contraceptives
drospirenone, ethinyl estradiol
↓ethinyl estradiol
↑ drospirenone (only with boceprevir)
↔ telaprevir
(Established DDI only with ethinyl estradiol)
↔ boceprevir
(Drosperinone is contraindicated with boceprevir )
For use with telaprevir: Use two effective non-hormonal methods of contraception during treatment and up to two weeks after telaprevir treatment. After telaprevir has been discontinued for two weeks, oral contraceptives may be used as one of two forms of birth control during treatment and 6 months post-treatment.
For use with boceprevir: Use two effective non-hormonal methods of contraception during treatment and 6 months post-treatment.
PDE-5 Inhibitors for Erectile Dysfunction
sildenafil, tadalafil, vardenafil
↑ sildenafil
↑ vardenfail
↑ tadalafil
↔ telaprevir
(Potentially Significant DDI)
↔ boceprevir
(Potentially Significant DDI)
For use with telaprevir or boceprevir: Do NOT exceed sildenafil 25 mg in 48 hrs, vardenafil 2.5 mg in 72 hrs or tadalafil 10 mg in 72 hrs.
Co-administration is contraindicated if PDE-5 Inhibitors are used for pulmonary hypertension; refer to Contraindicated Drugs.
Rifabutin↑ rifabutin↔ telaprevir
(Potentially Significant DDI)
↓ boceprevir
(Potentially Significant DDI)
For use with telaprevir or boceprevir: Co-administration not recommended.
Salmeterol↑ salmeterol (potentially leading to increased risk of cardiovascular events)↔ telaprevir
(Potentially Significant DDI)
↔ boceprevir
(Potentially Significant DDI)
For use with telaprevir or boceprevir: Co-administration not recommended.
Warfarin↑ or ↓ warfarin↔ telaprevir
(Potentially Significant DDI)
↔ boceprevir
(Potentially Significant DDI)
For use with telaprevir or boceprevir: Monitor INR closely.
Zolpidem↓ zolpidem levels↔ telaprevir
(Established DDI)
Interaction not studied.For use with telaprevir: Clinical monitoring and dose titration as needed.