ANTIARRHYTHMICS
|
lidocaine (systemic), amiodarone, bepridil, flecainide, propafenone, quinidine
|
↑ antiarrhythmics
|
Co-administration with telaprevir has the potential to produce serious and/or life-threatening adverse events and has not been studied. Caution is warranted and clinical monitoring is recommended when co-administered with telaprevir. |
digoxin
|
↑ digoxin
|
Concentrations of digoxin were increased when co-administered with telaprevir. The lowest dose of digoxin should be initially prescribed. The serum digoxin concentrations should be monitored and used for titration of digoxin dose to obtain the desired clinical effect. |
ANTIBACTERIALS
|
clarithromycin erythromycin telithromycin |
↑ telaprevir ↑ antibacterials |
Concentrations of both telaprevir and the antibacterial may be increased during co-administration. Caution is warranted and clinical monitoring is recommended when co-administered with telaprevir. QT interval prolongation and Torsade de Pointes have been reported with clarithromycin and erythromycin. QT interval prolongation has been reported with telithromycin. |
ANTICOAGULANT
|
warfarin |
↑ or warfarin |
Concentrations of warfarin may be altered when co-administered with telaprevir. The international normalized ratio (INR) should be monitored when warfarin is co-administered with telaprevir. |
ANTICONVULSANTS
|
carbamazepine phenobarbital phenytoin |
↓ telaprevir ↑ carbamazepine ↑ or phenytoin ↑ or phenobarbital
|
Concentrations of the anticonvulsant may be altered and concentrations of telaprevir may be decreased. Caution should be used when prescribing carbamazepine, phenobarbital, and phenytoin. Telaprevir may be less effective in patients taking these agents concomitantly. Clinical or laboratory monitoring of carbamazepine, phenobarbital, and phenytoin concentrations and dose titration are recommended to achieve the desired clinical response. |
ANTIDEPRESSANTS
|
escitalopram
|
↔ telaprevir ↓ escitalopram |
Concentrations of escitalopram were decreased when co-administered with telaprevir. Selective serotonin reuptake inhibitors such as escitalopram have a wide therapeutic index, but doses may need to be adjusted when combined with telaprevir. |
trazodone |
↑ trazodone |
Concomitant use of trazodone and telaprevir may increase plasma concentrations of trazodone which may lead to adverse events such as nausea, dizziness, hypotension and syncope. If trazodone is used with telaprevir, the combination should be used with caution and a lower dose of trazodone should be considered. |
ANTIFUNGALS
|
ketoconazole
itraconazole posaconazole voriconazole |
↑ ketoconazole ↑ telaprevir
↑ itraconazole ↑ posaconazole ↑ or voriconazole |
Ketoconazole increases the plasma concentrations of telaprevir. Concomitant systemic use of itraconazole or posaconazole with telaprevir may increase plasma concentration of telaprevir. Plasma concentrations of itraconazole, ketoconazole, or posaconazole may be increased in the presence of telaprevir. When co-administration is required, high doses of itraconazole or ketoconazole (greater than 200 mg/day) are not recommended.
Caution is warranted and clinical monitoring is recommended for itraconazole, posaconazole and voriconazole.
QT interval prolongation and Torsade de Pointes have been reported with voriconazole and posaconazole. QT interval prolongation has been reported with ketoconazole. Due to multiple enzymes involved with voriconazole metabolism, it is difficult to predict the interaction with telaprevir. Voriconazole should not be administered to patients receiving telaprevir unless an assessment of the benefit/risk ratio justifies its use. |
ANTI GOUT
|
colchicine |
↑ colchicine |
Patients with renal or hepatic impairment should not be given colchicine with telaprevir, due to the risk of colchicine toxicity. A reduction in colchicine dosage or an interruption of colchicine treatment is recommended in patients with normal renal or hepatic function.
Treatment of gout flares: co-administration of colchicine in patients on telaprevir:
0.6 mg (1 tablet) for 1 dose, followed by 0.3 mg (half tablet) 1 hour later. Not to be repeated before 3 days.
If used for prophylaxis of gout flares: co-administration of colchicine in patients on telaprevir:
If the original regimen was 0.6 mg twice a day, the regimen should be adjusted to 0.3 mg once a day. If the original regimen was 0.6 mg once a day, the regimen should be adjusted to 0.3 mg once every other day.
Treatment of familial Mediterranean fever (FMF): co-administration of colchicine in patients on telaprevir:
Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day). |
ANTIMYCOBACTERIAL
|
rifabutin |
↓ telaprevir ↑ rifabutin |
Concentrations of telaprevir may be decreased, while rifabutin concentrations may be increased during co-administration. Telaprevir may be less effective due to decreased concentrations. The concomitant use of rifabutin and telaprevir is not recommended. |
BENZODIAZEPINES
|
alprazolam
|
↑ alprazolam
|
Concomitant use of alprazolam and telaprevir increases exposure to alprazolam. Clinical monitoring is warranted. |
parenterally administered midazolam
|
↑ midazolam
|
Concomitant use of parenterally administered midazolam with telaprevir increased exposure to midazolam. Co-administration should be done in a setting which ensures clinical monitoring and appropriate medical management in case of respiratory depression and/or prolonged sedation. Dose reduction for midazolam should be considered, especially if more than a single dose of midazolam is administered.
Co-administration of oral midazolam with telaprevir is contraindicated. |
zolpidem (non-benzodiazepine sedative)
|
↓ zolpidem |
Exposure to zolpidem was decreased when co-administered with telaprevir. Clinical monitoring and dose titration of zolpidem is recommended to achieve the desired clinical response. |
CALCIUM CHANNEL BLOCKERS
|
amlodipine
|
↑amlodipine
|
Exposure to amlodipine was increased when co-administered with telaprevir. Caution should be used and dose reduction for amlodipine should be considered. Clinical monitoring is recommended. |
diltiazem felodipine nicardipine nifedipine nisoldipine verapamil |
↑calcium channel blockers |
Concentrations of other calcium channel blockers may be increased when telaprevir is co-administered. Caution is warranted and clinical monitoring of patients is recommended. |
CORTICOSTEROIDS
|
Systemic
prednisone methylprednisolone |
↑ prednisone ↑ methylprednisolone |
Systemic corticosteroids such as prednisone and methylprednisolone are CYP3A substrates. Since telaprevir is a potent CYP3A inhibitor, plasma concentrations of these corticosteroids can be increased significantly. Co-administration of systemic corticosteroids and telaprevir is not recommended [see
Warnings and Precautions
]. |
Systemic
dexamethasone |
↓ telaprevir
|
Systemic dexamethasone induces CYP3A and can thereby decrease telaprevir plasma concentrations. This may result in loss of therapeutic effect of telaprevir. Therefore this combination should be used with caution or alternatives should be considered. |
Inhaled/Nasal
fluticasone budesonide |
↑ fluticasone ↑ budesonide
|
Concomitant use of inhaled fluticasone or budesonide and telaprevir may increase plasma concentrations of fluticasone or budesonide resulting in significantly reduced serum cortisol concentrations. Co-administration of fluticasone or budesonide and telaprevir is not recommended unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side effects. |
ENDOTHELIN RECEPTOR ANTAGONIST
|
bosentan |
↑ bosentan |
Concentrations of bosentan may be increased when co-administered with telaprevir. Caution is warranted and clinical monitoring is recommended. |
HIV-ANTIVIRAL AGENTS: HIV-PROTEASE INHIBITORS (PIs)
|
atazanavir/ritonavir
|
↓ telaprevir ↑ atazanavir
|
Concomitant administration of telaprevir and atazanavir/ritonavir resulted in reduced steady-state telaprevir exposure, while steady-state atazanavir exposure was increased.
|
darunavir/ritonavir
|
↓ telaprevir ↓ darunavir
|
Concomitant administration of telaprevir and darunavir/ritonavir resulted in reduced steady-state exposures to telaprevir and darunavir. It is not recommended to co-administer darunavir/ritonavir and telaprevir. |
fosamprenavir/ritonavir
|
↓ telaprevir ↓ fosamprenavir
|
Concomitant administration of telaprevir and fosamprenavir/ritonavir resulted in reduced steady-state exposures to telaprevir and amprenavir. It is not recommended to co-administer fosamprenavir/ritonavir and telaprevir.
|
lopinavir/ritonavir
|
↓ telaprevir ↔ lopinavir
|
Concomitant administration of telaprevir and lopinavir/ritonavir resulted in reduced steady-state telaprevir exposure, while the steady-state exposure to lopinavir was not affected. It is not recommended to co-administer lopinavir/ritonavir and telaprevir.
|
HIV-ANTIVIRAL AGENTS: REVERSE TRANSCRIPTASE INHIBITORS
|
efavirenz
|
↓ telaprevir ↓ efavirenz |
Concomitant administration of telaprevir and efavirenz resulted in reduced steady-state exposures to telaprevir and efavirenz. |
tenofovir disoproxil fumarate
|
↔ telaprevir ↑ tenofovir
|
Concomitant administration of telaprevir and tenofovir disoproxil fumarate resulted in increased tenofovir exposure. Increased clinical and laboratory monitoring are warranted. Tenofovir disoproxil fumarate should be discontinued in patients who develop tenofovir-associated toxicities. |
HMG-CoA REDUCTASE INHIBITORS
|
atorvastatin
|
↑ atorvastatin |
Plasma concentrations of atorvastatin are markedly increased when co-administered with telaprevir. Avoid concomitant administration of telaprevir and atorvastatin. |
HORMONAL CONTRACEPTIVES/ESTROGEN
|
ethinyl estradiol
norethindrone |
↓ ethinyl estradiol ↔ norethindrone
|
Exposure to ethinyl estradiol was decreased when co-administered with telaprevir. Two effective non-hormonal methods of contraception should be used during treatment with telaprevir. Patients using estrogens as hormone replacement therapy should be clinically monitored for signs of estrogen deficiency. Refer also to
Contraindications (4)
,
Warnings and Precautions
,
Use in Specific Populations
, and
Patient Counseling Information
. |
IMMUNOSUPPRESSANTS
|
cyclosporine
sirolimus tacrolimus
|
↑ cyclosporine ↑ sirolimus ↑ tacrolimus
|
Plasma concentrations of cyclosporine and tacrolimus are markedly increased when co-administered with telaprevir. Plasma concentration of sirolimus may be increased when co-administered with telaprevir, though this has not been studied. Significant dose reductions and prolongation of the dosing interval of the immunosuppressant to achieve the desired blood levels should be anticipated. Close monitoring of the immunosuppressant blood levels, and frequent assessments of renal function and immunosuppressant-related side effects are recommended when co-administered with telaprevir. Tacrolimus may prolong the QT interval. The use of telaprevir in organ transplant patients has not been studied. |
INHALED BETA AGONIST
|
salmeterol |
↑ salmeterol |
Concentrations of salmeterol may be increased when co-administered with telaprevir. Concurrent administration of salmeterol and telaprevir is not recommended. The combination may result in increased risk of cardiovascular adverse events associated with salmeterol, including QT prolongation, palpitations and sinus tachycardia. |
NARCOTIC ANALGESIC
|
methadone
|
↓ R-methadone
|
Concentrations of methadone were reduced when co-administered with telaprevir. No adjustment of methadone dose is required when initiating co-administration of telaprevir. However, clinical monitoring is recommended as the dose of methadone during maintenance therapy may need to be adjusted in some patients. |
PDE5 INHIBITORS
|
sildenafil tadalafil vardenafil |
↑ PDE5 inhibitors |
Concentrations of PDE5 inhibitors may be increased when co-administered with telaprevir. For the treatment of erectile dysfunction, sildenafil at a single dose not exceeding 25 mg in 48 hours, vardenafil at a single dose not exceeding 2.5 mg dose in 72 hours, or tadalafil at a single dose not exceeding 10 mg dose in 72 hours can be used with increased monitoring for PDE5 inhibitor-associated adverse events. QT interval prolongation has been reported with vardenafil. Caution is warranted and clinical monitoring is recommended. Co-administration of sildenafil or tadalafil and telaprevir in the treatment of pulmonary arterial hypertension is contraindicated [see
Contraindications (4)
]. |