Telaprevir Dosage

Usual Adult Dose for Chronic Hepatitis C

750 mg orally 3 times a day (7 to 9 hours apart) with food (not low fat)

Duration: 12 weeks in combination with peginterferon alfa and ribavirin; HCV-RNA levels should be monitored at weeks 4 and 12 to determine combination therapy duration and assess for treatment futility

Renal Dose Adjustments

Mild, moderate, or severe renal impairment: No adjustment recommended.
End-stage renal disease: Data not available

Liver Dose Adjustments

Mild hepatic impairment (Child-Pugh A, score 5 to 6): No adjustment recommended.
Moderate or severe hepatic impairment (Child-Pugh B or C, score 7 or greater) or decompensated liver disease: Not recommended.

Dose Adjustments

To prevent treatment failure, telaprevir dosage must not be reduced or interrupted. The prescribing information for peginterferon alfa and/or ribavirin should be consulted for appropriate dose adjustments. If peginterferon alfa or ribavirin is stopped for any reason, telaprevir must also be discontinued.

Recommended therapy duration in therapy-naive and prior relapse patients:
HCV-RNA undetectable at weeks 4 and 12:
Triple therapy (telaprevir, peginterferon alfa, and ribavirin): First 12 weeks
Dual therapy (peginterferon alfa and ribavirin): Additional 12 weeks
Total therapy duration: 24 weeks

HCV-RNA detectable (1000 international units/mL or less) at weeks 4 and/or 12:
Triple therapy: First 12 weeks
Dual therapy: Additional 36 weeks
Total therapy duration: 48 weeks

Recommended therapy duration in prior partial and null responder patients:
Triple therapy: First 12 weeks
Dual therapy: Additional 36 weeks
Total therapy duration: 48 weeks

Therapy discontinuation is recommended in all patients if HCV-RNA levels are 1000 international units/mL or greater at 4 or 12 weeks of therapy (telaprevir therapy complete at 12 weeks), or if HCV-RNA levels remain detectable at 24 weeks of therapy.

Precautions

Telaprevir must be used in combination with peginterferon alfa and ribavirin; therefore, any contraindication and warning associated with peginterferon alfa and/or ribavirin also apply to telaprevir combination therapy.

Telaprevir combination therapy is contraindicated in women who are or may become pregnant and men whose female partners are pregnant. During therapy and for 6 months after discontinuation, extreme care must be taken to avoid pregnancy in female patients and female partners of male patients, including the use of at least 2 reliable forms of effective birth control. Hormonal contraceptives may not be reliable during and for up to 2 weeks after telaprevir use; therefore, during this time, female patients of childbearing potential should use 2 effective nonhormonal methods of contraception. A negative pregnancy test should be obtained immediately before initiation of therapy, monthly during therapy, and for 6 months after discontinuation.

Coadministration of telaprevir is contraindicated with drugs highly dependent on CYP450 3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events. Coadministration of telaprevir is contraindicated with potent CYP450 3A inducers where lower exposure may lead to loss of efficacy of telaprevir. Contraindicated drugs include alfuzosin, rifampin, dihydroergotamine, ergonovine, ergotamine, methylergonovine, cisapride, St. John's wort, pimozide, oral midazolam, triazolam, lovastatin, simvastatin, and sildenafil or tadalafil for treatment of pulmonary arterial hypertension.

Serious skin reactions (including drug rash with eosinophilia and systemic symptoms and Stevens-Johnson syndrome) have been associated with telaprevir. Telaprevir combination therapy (all components) must be stopped at once and appropriate medical care instituted if a serious skin reaction develops.

Patients with mild to moderate rashes should be monitored for worsening of rash or development of systemic symptoms. If rash becomes severe or if systemic symptoms develop, telaprevir should be discontinued; however, peginterferon alfa and ribavirin may be continued. Sequential or simultaneous interruption or discontinuation of ribavirin and/or peginterferon alfa should be considered if improvement is not seen within 7 days (or earlier if medically indicated) of telaprevir discontinuation. Patients should be monitored until rash has resolved. If telaprevir discontinuation is due to rash, it must not be reduced or restarted. Systemic corticosteroids are not recommended for treatment of rash.

Anemia has been reported with peginterferon alfa and ribavirin, and an additional hemoglobin level reduction has been observed with the addition of telaprevir. Hemoglobin should be monitored prior to and at least every 4 weeks during telaprevir combination therapy. Dose reduction guidelines for ribavirin should be followed to manage anemia. If such reductions are inadequate, telaprevir discontinuation should be considered. If ribavirin is permanently discontinued due to anemia, telaprevir must also be permanently discontinued. The telaprevir dose must not be reduced and telaprevir must not be restarted if discontinued.

Hematology evaluations (including white cell differential count) and chemistry evaluations (electrolytes, serum creatinine, uric acid, hepatic enzymes, bilirubin, and TSH) are recommended at weeks 2, 4, 8, and 12, or as clinically appropriate thereafter. Additional testing is recommended as clinically indicated.

HCV-RNA levels should be monitored at weeks 4 and 12 and as clinically indicated. A sensitive real-time RT-PCR assay should be used for monitoring such levels during therapy. The lower limit of HCV-RNA quantification should be 25 international units/mL or less and the limit of HCV-RNA detection should be about 10 to 15 international units/mL. To assess response-guided therapy eligibility, an "undetectable" HCV-RNA result is required; a confirmed "detectable but below limit of quantification" HCV-RNA result does not equal an "undetectable" HCV-RNA result.

Efficacy of telaprevir has not been established in patients who previously failed therapy with a regimen that included telaprevir or other HCV NS3/4A protease inhibitors. Safety and efficacy have not been established in solid organ transplant patients or in patients coinfected with hepatitis B or HIV.

Safety and efficacy have not been established in pediatric patients (less than 18 years of age).

Dialysis

Data not available

Other Comments

Telaprevir must be administered in combination with peginterferon alfa and ribavirin. The prescribing information for peginterferon alfa and ribavirin should be consulted for additional information.

See also...