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HIGHLIGHTS OF PRESCRIBING INFORMATION |
These highlights do not include all the information needed to use INCIVEK safely and effectively. See full prescribing information for INCIVEK.
INCIVEK™ (telaprevir) Film Coated Tablets Initial U.S. Approval: 2011
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INDICATIONS AND USAGE
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INCIVEK is a hepatitis C virus (HCV) NS3/4A protease inhibitor indicated, in combination with peginterferon alfa and ribavirin, for the treatment of genotype 1 chronic hepatitis C (CHC) in adult patients with compensated liver disease, including cirrhosis, who are treatment-naïve or who have been previously treated with interferon-based treatment, including prior null responders, partial responders, and relapsers. (1)
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INCIVEK must not be used as monotherapy and must only be used in combination with peginterferon alfa and ribavirin. (5.7)
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A high proportion of previous null responders (particularly those with cirrhosis) did not achieve Sustained Virologic Response (SVR) and had telaprevir resistance-associated substitutions emerge on treatment with INCIVEK. (12.4, 14.3)
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INCIVEK efficacy has not been established for patients who have previously failed therapy with a treatment regimen that includes INCIVEK or other HCV NS3/4A protease inhibitors. (12.4)
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DOSAGE AND ADMINISTRATION
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750 mg taken 3 times a day (7-9 hours apart) with food (not low fat). (2, 12.3, 17.4)
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INCIVEK must be administered with both peginterferon alfa and ribavirin for all patients for 12 weeks, followed by a response-guided regimen of either 12 or 36 additional weeks of peginterferon alfa and ribavirin depending on viral response and prior response status. (2)
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For specific dosage instructions for peginterferon alfa and ribavirin, refer to their respective prescribing information. (2)
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DOSAGE FORMS AND STRENGTHS
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CONTRAINDICATIONS
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All contraindications to peginterferon alfa and ribavirin also apply since INCIVEK must be administered with peginterferon alfa and ribavirin. (4)
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Pregnant women and men whose female partners are pregnant: Because ribavirin may cause birth defects and fetal death, telaprevir in combination with peginterferon alfa and ribavirin is contraindicated in pregnant women and in men whose female partners are pregnant. (4, 5.1, 8.1, 17.1)
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Co-administration with drugs that:
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are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events. (4)
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strongly induce CYP3A which may lead to lower exposure and loss of efficacy of INCIVEK. (4)
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WARNINGS AND PRECAUTIONS
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Pregnancy: Use with Ribavirin and Peginterferon alfa: Ribavirin may cause birth defects and fetal death; avoid pregnancy in female patients and female partners of male patients. Patients must have a negative pregnancy test prior to initiating therapy, use at least 2 effective methods of contraception, and undergo monthly pregnancy tests. (5.1, 8.1)
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Serious Skin Reactions: Serious skin reactions including Drug Rash with Eosinophilia and Systemic Symptoms and Stevens-Johnson Syndrome have been reported. For serious skin reactions, all components of INCIVEK combination treatment should be discontinued immediately. (5.2)
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Rash: Patients with mild to moderate rash should be monitored for progression. If rash progresses and becomes severe, INCIVEK should be discontinued. (5.3)
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Anemia: Monitor hemoglobin prior to and at regular intervals during INCIVEK combination treatment. Follow dose modifications for ribavirin; discontinue INCIVEK if required. (5.4)
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ADVERSE REACTIONS
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The most common adverse drug reactions to INCIVEK (incidence at least 5% higher with INCIVEK than in controls) were rash, pruritus, anemia, nausea, hemorrhoids, diarrhea, anorectal discomfort, dysgeusia, fatigue, vomiting, and anal pruritus. (6)
To report SUSPECTED ADVERSE REACTIONS, contact Vertex Pharmaceuticals Incorporated at 877-824-4281 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
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DRUG INTERACTIONS
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Co-administration of INCIVEK combination treatment with other drugs can alter the concentration of other drugs and other drugs may alter the concentrations of telaprevir. Consult the full prescribing information prior to and during treatment for potential drug-drug interactions. (4, 7, 12.3)
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USE IN SPECIFIC POPULATIONS
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Hepatic Impairment: Safety and efficacy have not been established in patients with Child-Pugh score greater than or equal to 7 (class B and C). (5.8, 8.6)
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Co-infection: Safety and efficacy have not been established in HCV/HIV and HCV/HBV co-infected patients. (8.8)
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Pediatrics: Safety and efficacy have not been established in pediatric patients. (8.4)
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Solid Organ Transplant: Safety and efficacy have not been established in patients undergoing solid organ transplants. (8.9)
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Ribavirin Pregnancy Registry available (8.1)
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See 17 for PATIENT COUNSELING INFORMATION and Medication Guide |
Revised: 05/2011 |
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FULL PRESCRIBING INFORMATION: CONTENTS* |
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*
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FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
1.1 Chronic Hepatitis C
INCIVEK™ (telaprevir), in combination with peginterferon alfa and ribavirin, is indicated for the treatment of genotype 1 chronic hepatitis C in adult patients with compensated liver disease, including cirrhosis, who are treatment-naïve or who have previously been treated with interferon-based treatment, including prior null responders, partial responders, and relapsers [see Clinical Studies (14.2 and 14.3), including definitions of these terms].
The following points should be considered when initiating treatment with INCIVEK:
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INCIVEK must not be administered as monotherapy and must only be prescribed with both peginterferon alfa and ribavirin [see Warnings and Precautions (5.7)].
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A high proportion of previous null responders (particularly those with cirrhosis) did not achieve a Sustained Virologic Response (SVR) and had telaprevir resistance-associated substitutions emerge on treatment with INCIVEK combination treatment [see Microbiology (12.4) and Clinical Studies (14.3)].
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INCIVEK efficacy has not been established for patients who have previously failed therapy with a treatment regimen that includes INCIVEK or other HCV NS3/4A protease inhibitors [see Microbiology (12.4)].
2 DOSAGE AND ADMINISTRATION
2.1 INCIVEK/Peginterferon Alfa/Ribavirin Combination Treatment
The recommended dose of INCIVEK tablets is 750 mg (two 375-mg tablets) taken orally 3 times a day (7-9 hours apart) with food (not low fat) [see Clinical Pharmacology (12.3) and Patient Counseling Information (17.4)].
For specific dosage instructions for peginterferon alfa and ribavirin, refer to their respective prescribing information.
Duration of Treatment
The recommended duration of treatment with INCIVEK is 12 weeks in combination with peginterferon alfa and ribavirin. HCV-RNA levels should be monitored at weeks 4 and 12 to determine combination treatment duration and assess for treatment futility (Tables 1 and 2).
Table 1: Recommended Treatment Duration (See also Table 2 for Treatment Futility Rules)
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Treatment-Naïve and Prior Relapse Patients |
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HCV-RNA* |
Triple Therapy
INCIVEK,
peginterferon alfa and ribavirin |
Dual Therapy
peginterferon alfa and ribavirin |
Total Treatment Duration |
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Undetectable at Weeks 4 and 12 |
First 12 weeks |
Additional 12 weeks |
24 weeks |
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Detectable (1000 IU/mL or less) at Weeks 4 and/or 12 |
First 12 weeks |
Additional 36 weeks |
48 weeks |
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Prior Partial and Null Responder Patients |
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Triple Therapy
INCIVEK,
peginterferon alfa and ribavirin |
Dual Therapy
peginterferon alfa and ribavirin |
Total Treatment Duration |
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All Patients |
First 12 weeks |
Additional 36 weeks |
48 weeks |
For the purpose of assessing response-guided therapy eligibility at weeks 4 and 12 (see Table 1), an "undetectable" HCV-RNA result is required; a confirmed "detectable but below limit of quantification" HCV-RNA result should not be considered equivalent to an "undetectable" HCV-RNA result [see Laboratory Tests (5.6)].
Treatment-naïve patients with cirrhosis who have undetectable HCV-RNA at weeks 4 and 12 of INCIVEK combination treatment may benefit from an additional 36 weeks of peginterferon alfa and ribavirin (48 weeks total) [see Clinical Studies (14.2)].
2.2 Dose Reduction
To prevent treatment failure, the dose of INCIVEK must not be reduced or interrupted. Refer to the respective prescribing information for dose modification of peginterferon alfa and ribavirin [see Warnings and Precautions (5.7)].
2.3 Discontinuation of Dosing
Patients with inadequate viral response are unlikely to achieve SVR, and may develop treatment-emergent resistance substitutions [see Microbiology (12.4)]. Discontinuation of therapy is recommended in all patients with (1) HCV-RNA levels of greater than or equal to 1000 IU/mL at Treatment Week 4 or 12; or (2) confirmed detectable HCV-RNA levels at Treatment Week 24 (see Table 2).
Table 2: Treatment Futility Rules: All Patients
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HCV-RNA |
Action |
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Week 4 or Week 12: Greater than 1000 IU/mL |
Discontinue INCIVEK and peginterferon alfa and ribavirin (INCIVEK treatment complete at 12 weeks) |
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Week 24: Detectable |
Discontinue peginterferon alfa and ribavirin |
If peginterferon alfa or ribavirin is discontinued for any reason, INCIVEK must also be discontinued.
3 DOSAGE FORMS AND STRENGTHS
Each tablet contains 375 mg of telaprevir. Tablets are available as purple, film-coated, capsule-shaped tablets debossed with the characters "V 375" on one side.
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