Incivek

Telaprevir is combined with ribavirin and peginterferon alfa which cause fetal harm and birth defects if used in pregnant mothers or in male partners of women who are pregnant. Female patients of childbearing potential and their male partners as well as male patients and their female partners must use two effective contraceptive methods during treatment and for 6 months after treatment. Female patients should have monthly pregnancy tests during treatment and for 6 months after stopping treatment.

It is not known whether telaprevir enters breast milk; therefore, it is best to be cautious before using it in nursing mothers. To avoid any potential risk to the newborn, a decision must be made to discontinue nursing or to discontinue the drug.

Incivek is part of the drug class:

• Protease inhibitors

Medicines can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Incivek there are no specific foods that you must exclude from your diet when receiving this medication.

Tell your healthcare provider if you are breastfeeding or plan to breastfeed. It is not known if Incivek passes into your breast milk. You and your healthcare provider should decide if you will take Incivek or breastfeed. You should not do both.

If you take too much Incivek or overdose, call your healthcare provider or local Poison Control Center, or go to the nearest hospital emergency room right away.

Chronic Hepatitis C Virus (HCV) Infection

Treatment of chronic HCV genotype 1 infection in adults with compensated liver disease (including cirrhosis) who are treatment naive (previously untreated) or were previously treated with interferon-based therapy (including those with prior null response, partial response, or relapse).1 2 3 17

Used in conjunction with peginterferon alfa (alfa-2a, alfa-2b) and ribavirin;1 do not use alone.1

Consider that a high proportion of prior null responders (particularly those with cirrhosis) failed to achieve sustained virologic response (SVR) and had treatment-emergent telaprevir resistance-associated mutations during treatment with telaprevir, peginterferon alfa, and ribavirin.1

Efficacy not established in patients who previously failed therapy with a regimen containing telaprevir or other HCV NS3/4A PI.1

Safety and efficacy not established in chronic HCV patients with HBV or HIV coinfection or in recipients of liver or other organ transplantations.1

Treatment of chronic HCV infection is complex and rapidly evolving; consult a specialist to obtain the most up-to-date information.119 Information from the American Association for the Study of Liver Diseases (AASLD), IDSA, and International Antiviral Society–USA (IAS–USA) regarding diagnosis and management of HCV infection, including current recommendations for initial treatment, is available at .119

• Direct-acting antiviral (DAA) agent active against HCV.1

• The α-ketoamide functional group of telaprevir reversibly binds the active serine site of HCV NS3 protease, thereby blocking proteolytic cleavage of NS4A, NS4B, NS5A, and NS5B from the HCV-encoded polyprotein and inhibiting HCV replication in host cells.1 6 11

• Causes biphasic viral decline; rapid first-phase occurs during first few days of treatment, followed by second phase of prolonged viral decline.10 12

• Has in vitro activity against HCV genotypes 1a, 1b, and 2, but is less active against genotypes 3a and 4a.1 5

• Certain amino acid substitutions (mutations) in the HCV NS3 protease domain (V36A/M, T54A/S, R155K/T, A156S/V/T, R155T with D168N, V36A with T54A, B36M/A with R155K/T, T54S/A with A156S/T) have been associated with reduced in vitro susceptibility to telaprevir.1 15

• Majority of HCV isolates from patients in phase 3 clinical studies who did not achieve sustained virologic response (SVR) had treatment-emergent resistance mutations.1 Clinical impact of prior exposure to HCV PIs (including telaprevir) is not known.1

• HCV isolates with treatment-emergent telaprevir resistance mutations with decreased in vitro susceptibility or cross-resistance to other HCV NS3/4A PIs (e.g., boceprevir) reported.1 15 Cross-resistance not expected between telaprevir and interferon, or ribavirin.1

Telaprevir is used in combination with injectable peginterferon alfa (Pegasys®, Pegintron®) and ribavirin (Copegus®, Rebetol®) to treat chronic hepatitis C infection. These medicines are used in patients with liver disease (including cirrhosis) who have not been treated before or who have received other medicines that did not work well. Telaprevir is an antiviral agent.

This medicine was available only with your doctor's prescription.

Telaprevir was withdrawn from the United States market on October 16, 2014.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of fluid and electrolyte problems like mood changes, confusion, muscle pain or weakness, a heartbeat that does not feel normal, 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, or very bad upset stomach or throwing up.
• Shortness of breath.
• Feeling very tired or weak.
• A very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause very bad health problems that may not go away, and sometimes death. Get medical help right away if you have signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.

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:

• Incivek must not be administered as monotherapy and must only be prescribed with both peginterferon alfa and ribavirin [see Warnings and Precautions (5.6)].
• 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)].
• 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)].

Mechanism of Action

Telaprevir is a direct-acting antiviral (DAA) agent against the hepatitis C virus [see Microbiology (12.4)].

Pharmacodynamics

ECG Evaluation

The effect of telaprevir 750 and 1875 mg on QTc interval was evaluated in a double-blind, double-dummy, randomized, placebo-, and active-controlled (moxifloxacin 400 mg) four period crossover thorough QT trial in 44 subjects. In the trial with demonstrated ability to detect small effects, the upper bound of the one-sided 95% confidence interval for the largest placebo adjusted, baseline-corrected QTc based on Fridericia correction method (QTcF) was below 10 ms, the threshold for regulatory concern. The dose of 1875 mg is adequate to represent the high exposure clinical scenario.

Pharmacokinetics

The pharmacokinetic properties of telaprevir have been evaluated in healthy adult subjects and in subjects with chronic hepatitis C. Following multiple doses of telaprevir (750 mg every 8 hours) in combination with peginterferon alfa and ribavirin in treatment-naïve subjects with genotype 1 chronic hepatitis C, mean (SD) Cmax was 3510 (1280) ng/mL, Cmin was 2030 (930) ng/mL, and AUC8h was 22,300 (8650) ng•hr/mL.

Telaprevir total exposure (AUC24h,ss) was similar regardless of whether the total daily dose of 2250 mg was administered as 750 mg every 8 hours or 1125 mg twice daily.

Absorption and Bioavailability

Telaprevir is orally available, most likely absorbed in the small intestine, with no evidence for absorption in the colon. Maximum plasma concentrations after a single dose of telaprevir are generally achieved after 4 to 5 hours. In vitro studies performed with human Caco-2 cells indicated that telaprevir is a substrate of P-glycoprotein (P-gp). Exposure to telaprevir is higher during co-administration of peginterferon alfa and ribavirin than after administration of telaprevir alone.

Effects of Food on Oral Absorption

The systemic exposure (AUC) to telaprevir was increased by 237% when telaprevir was administered with a standard fat meal (containing 533 kcal and 21 g fat) compared to when telaprevir was administered under fasting conditions. In addition, the type of meal significantly affects exposure to telaprevir. Relative to fasting, when telaprevir was administered with a low-fat meal (249 kcal, 3.6 g fat) and a high-fat meal (928 kcal, 56 g fat), the systemic exposure (AUC) to telaprevir was increased by approximately 117% and 330%, respectively. Doses of Incivek were administered within 30 minutes of completing a meal or snack containing approximately 20 grams of fat in the Phase 3 trials. Therefore, Incivek should always be taken with food (not low fat).

Distribution

In vitro, within a concentration range of 0.1 µM (68 ng per mL) to 20 µM (13600 ng per mL), telaprevir is approximately 59% to 76% bound to plasma proteins. Telaprevir binds primarily to alpha 1-acid glycoprotein and albumin and the binding is concentration dependent, decreasing with increasing concentrations of telaprevir. After oral administration, the typical apparent volume of distribution (Vd/F) was estimated to be 252 L, with an inter-individual variability of 72%.

Metabolism

Telaprevir is extensively metabolized in the liver, involving hydrolysis, oxidation, and reduction. Multiple metabolites were detected in feces, plasma, and urine. After repeated-oral administration, the R-diastereomer of telaprevir (30-fold less active), pyrazinoic acid, and a metabolite that underwent reduction at the α-ketoamide bond of telaprevir (not active) were found to be the predominant metabolites of telaprevir. In vitro studies using recombinant human cytochrome P450 (CYP) isoforms indicated that CYP3A4 was the major isoform responsible for CYP-mediated telaprevir metabolism. In vitro studies using recombinant aldo-ketoreductases indicated that these and potentially other reductases are also responsible for the reduction of telaprevir. Other proteolytic enzymes are also involved in the hydrolysis of telaprevir. These non-CYP mediated pathways of metabolism likely play a major role after multiple dosing of telaprevir.

Elimination

Following administration of a single oral dose of 750 mg 14C-telaprevir in healthy subjects, 90% of total radioactivity was recovered in feces, urine and expired air within 96 hours post-dose. The median recovery of the administered radioactive dose was approximately 82% in the feces, 9% in exhaled air and 1% in urine. The contribution of unchanged 14C-telaprevir and the R-diastereomer of telaprevir towards total radioactivity recovered in feces was 31.9% and 18.8%, respectively. After oral administration, the apparent total clearance (Cl/F) was estimated to be 32.4 L per hour with an inter-individual variability of 27.2%. The mean elimination half-life after single-dose oral administration of telaprevir 750 mg typically ranged from about 4.0 to 4.7 hours. At steady state, the effective half-life is about 9 to 11 hours.

Specific Populations

Hepatic Impairment

Steady-state exposure to telaprevir was reduced by 46% in HCV-negative subjects with moderate hepatic impairment (Child-Pugh Class B) compared to healthy subjects. The appropriate dose of Incivek in HCV-infected subjects with moderate or severe hepatic impairment has not been determined and therefore Incivek is not recommended in these populations.

Steady-state exposure to telaprevir was reduced by 15% in HCV-negative subjects with mild hepatic impairment (Child-Pugh Class A) compared to healthy subjects. Dose modification of Incivek is not required when administered to subjects with mild hepatic impairment. In previously treated subjects who had compensated liver disease and were treated with Incivek in combination with peginterferon alfa and ribavirin, subjects with cirrhosis had similar PK parameters compared to those without cirrhosis.

Renal Impairment

After administration of a single dose of 750 mg to HCV-negative subjects with severe renal impairment (CrCl less than 30 mL per min), the LS means of telaprevir Cmax and AUCinf were increased by 3% and 21%, respectively, compared to healthy subjects.

Gender

The effect of subject gender on telaprevir pharmacokinetics was evaluated using population pharmacokinetics of data from clinical trials of telaprevir. No dose adjustments are deemed necessary based on gender.

Race

Population pharmacokinetic analysis of telaprevir in HCV-infected subjects indicated that race had no apparent effect on the exposure to telaprevir.

Geriatric Use

Population pharmacokinetic analysis in HCV-infected subjects showed that within the age range (19-70 years) investigated (35 subjects 65 years of age and older), subject age did not have a clinically relevant effect on the exposure to telaprevir.

Pediatric Use

The pharmacokinetics of Incivek in pediatric patients have not been evaluated.

Drug Interactions

In vitro studies indicated that telaprevir is a substrate and a strong inhibitor of CYP3A and P-gp. In vitro studies indicated that telaprevir is also an inhibitor of OATP1B1 and OATP2B1. No inhibition by telaprevir of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP2E1 isozymes was observed in vitro. In vitro studies also suggest that telaprevir does not induce CYP1A, CYP3A, CYP2B6, or CYP2C. Furthermore, in vitro studies suggest that telaprevir is neither a substrate for BCRP, OATP1B1, OATP2B1, or MRP2, nor an inhibitor of BCRP, MRP2, OCT2, and OAT1 transporters. Clinical trials were conducted to evaluate the effect of drugs that can affect or be affected by telaprevir during co-administration (Tables 6 and 7).

Microbiology

Mechanism of Action

Telaprevir is an inhibitor of the HCV NS3/4A serine protease, necessary for the proteolytic cleavage of the HCV encoded polyprotein into mature forms of the NS4A, NS4B, NS5A and NS5B proteins and essential for viral replication. In a biochemical assay, telaprevir inhibited the proteolytic activity of the recombinant HCV NS3 protease domain with an IC50 value of 10 nM.

Antiviral Activity in Cell Culture

In an HCV subtype 1b replicon assay, the telaprevir EC50 value against wild-type HCV was 354 nM in a 2-day cell culture assay, and in a subtype 1a infectious virus assay, the EC50 value was 280 nM in a 5-day cell culture assay. In biochemical enzymatic assays, the median IC50 values of telaprevir against genotype 2, 3a, and 4a were 16 nM (range 6-32 nM; n=5), 40 nM (range 39-88 nM; n=5), and 130 nM (n=1), respectively, compared to a median IC50 value of 20 nM (range 16-23; n=2) for genotype 1a and 20 nM for genotype 1b (range 13-33; n=4). The presence of 40% human serum reduced the anti-HCV activity of telaprevir by approximately 10-fold. Evaluation of telaprevir in combination with interferon alfa or ribavirin showed no evidence of antagonism in reducing HCV RNA levels in HCV replicon cells.

Resistance

In Cell Culture

HCV genotype 1b replicons with reduced susceptibility to telaprevir have been selected in cell culture and characterized for telaprevir genotypic and phenotypic resistance. Additionally, resistance to telaprevir was evaluated in both biochemical and HCV genotype 1b replicon assays using site-directed mutants and recombinant NS3/4A from telaprevir Phase 2 clinical trials isolates. Variants V36A/M, T54A/S, R155K/T, A156S, R155T+D168N, and V36A+T54A conferred 3- to 25-fold reduced susceptibility to telaprevir; and A156V/T variants and the V36M/A+R155K/T and T54S/A+A156S/T double variants conferred greater than 62-fold reduced susceptibility to telaprevir. No amino acid substitutions were observed at the proteolytic cleavage sites.

In Clinical Trials

In a pooled analysis of subjects who did not achieve SVR (on-treatment virologic failure or relapse) from the controlled Phase 3 clinical trials, NS3 amino acid substitutions V36M/A/L, T54A/S, R155K/T, and A156S/T were determined to emerge frequently on Incivek treatment (Table 8). Nearly all of these substitutions have been shown to reduce telaprevir anti-HCV activity in cell culture or biochemical assays. No clear evidence of treatment-emergent substitutions in the NS3 helicase domain or NS4A coding regions of the HCV genome was observed among subjects treated with Incivek who did not achieve SVR.

Telaprevir treatment-emergent resistance substitutions emerged in the majority of isolates from subjects who did not achieve SVR (Table 8): in almost 100% of subjects who failed during 12 weeks of T/PR and in the majority of subjects who failed on PR after Week 12 or who relapsed.

HCV genotype 1 subtype-associated patterns of Incivek treatment-emergent amino acid substitutions were observed. Subjects with HCV genotype 1a predominately had V36M and R155K or the combination of these variants, while subjects with HCV genotype 1b predominately had V36A, T54A/S, and A156S/T variants (Table 8). Among subjects treated with telaprevir, on-treatment virologic failure was more frequent in subjects with genotype 1a than with genotype 1b and more frequent in prior null responders [see Clinical Studies (14)]. In the C211 Phase 3 clinical trial, there were no differences in the types of emerging variants between subjects receiving telaprevir 1125 mg twice daily and subjects receiving telaprevir 750 mg every 8 hours. Similar proportions of subjects in both treatment groups had telaprevir-resistant variants at the time of failure.

Persistence of Resistance-Associated Substitutions

Persistence of telaprevir-resistant NS3 amino acid substitutions has been observed following treatment failure. Of a combined 255 treatment-naïve and previously treated subjects from Trials 108, 111, and C216 in whom telaprevir-resistant variants had emerged during treatment, 103 (40%) had detectable resistant variants by population sequencing at end of trial (follow-up range 2-70 weeks, median 45 weeks) and results for loss of variants were similar across the 3 trials. In the combined trials, 46% of the telaprevir-resistant substitutions in subtype 1a and 16% of the substitutions in subtype 1b were still detected by the end of trial: 29% of V36, 16% of T54, 38% of R155, 14% of A156, and 44% of V36M+R155K variants were detected at the end of trial.

In a 3-year follow-up trial of 56 treatment-naïve and prior treatment-failure subjects who did not achieve SVR with a telaprevir regimen in a Phase 2 trial and had telaprevir-resistant variants after treatment failure, variants were detected by population sequencing in 11% (6/56) of subjects (median follow-up of 25 months). Telaprevir-resistant variants V36L/M, T54S, and R155K were detectable (present at greater than 25% of the viral population) in some subjects at 24 months. By 36 months, V36M, T54A/S, and A156N/S/T variants had fallen below the level of detection by population sequencing in all subjects. At 36 months, 3% of the subject isolates that had the R155K variant still had detectable R155K variants by population sequencing.

The lack of detection of a substitution based on a population-based assay does not necessarily indicate the substitution has declined to the pre-treatment level. The long-term clinical impact of the emergence or persistence of detectable Incivek resistance-associated substitutions is unknown. No data are available regarding Incivek efficacy among patients who were previously exposed to Incivek, or who previously failed treatment with a regimen containing Incivek.

Effect of Baseline HCV Substitutions/Polymorphisms on Treatment Response

A pooled analysis was conducted to explore the association between the detection (population-based assay) of baseline NS3/4A amino acid substitutions/polymorphisms and treatment outcome in Trials 108, 111, and C216. Baseline polymorphisms at NS3 position Q80 (Q80K, Q80L, Q80R), which are frequently observed in HCV genotype 1a-infected subjects and have been reported to reduce the activity of some HCV NS3/4A protease inhibitors, were not associated with reduced Incivek efficacy.

Telaprevir-associated resistance substitutions (substitutions at positions V36, T54, R155 or D168) were present at baseline in 5% (117/2217) of the available subject samples in the combined clinical trials. Given the small number of subjects with baseline telaprevir resistance substitutions, conclusions about their effect on response outcomes when these substitutions are present at baseline cannot be determined.

Cross-Resistance

Treatment-emergent NS3 amino acid substitutions detected in subjects treated with Incivek who did not achieve SVR in the clinical trials (substitutions at positions V36, T54, R155, A156 or D168) have been demonstrated to reduce the anti-HCV activity of boceprevir and other HCV NS3/4A protease inhibitors. The impact of prior Incivek exposure or treatment failure on the efficacy of boceprevir or other HCV NS3/4A protease inhibitors has not been studied. Incivek efficacy has not been established for patients with a history of exposure to NS3/4A protease inhibitors.

Cross-resistance is not expected between Incivek and interferons, or Incivek and ribavirin. HCV replicons expressing telaprevir-associated resistance substitutions remained fully sensitive to interferon-alfa and ribavirin, as well as other direct-acting antivirals with different mechanisms of action, such as NS5B polymerase inhibitors.

Pharmacogenomics

A genetic variant near the gene encoding interferon-lambda-3 (IL28B rs12979860, a C to T change) is a strong predictor of response to peginterferon alfa and ribavirin (PR). rs12979860 was genotyped in 454 of 1088 subjects in Trial 108 (treatment-naïve) and 527 of 662 subjects in Trial C216 (previously treated) [see Clinical Studies (14.2 and 14.3) for trial descriptions]. SVR rates tended to be lower in subjects with the CT and TT genotypes compared to those with the CC genotype, particularly among treatment-naïve subjects receiving PR48 (Table 9). Among both treatment-naïve and previous treatment failures, subjects of all IL28B genotypes appeared to have higher SVR rates with regimens containing Incivek. The results of this retrospective subgroup analysis should be viewed with caution because of the small sample size and potential differences in demographic or clinical characteristics of the subtrial population relative to the overall trial population. In Trial C211, all subjects were prospectively tested for IL28B variants; there were no clinically relevant differences in SVR12 responses between q8h and twice-daily dosing within the genetic subgroups.

You should not use Incivek if you are allergic to telaprevir.

Incivek be used in combination with peginterferon alfa and ribavirin. Read the medication guide or patient instructions provided with each medicine you take. In some cases, you may not be able to use this drug combination.

To make sure Incivek is safe for you, tell your doctor if you have:

• liver problems other than hepatitis C (including hepatitis B);

• kidney disease (or if you are on dialysis);

• anemia (lack of red blood cells);

• HIV or AIDS;

• a history of gout;

• if you have had an organ transplant; or

• if you have ever used medicine to treat hepatitis in the past and it did not work.

Some medicines can cause unwanted or dangerous effects when used with Incivek. Your doctor may need to change your treatment plan if you use any of the following drugs:

• alfuzosin;

• cisapride;

• pimozide;

• rifampin;

• St. John's wort;

• lovastatin, simvastatin;

• oral midazolam or triazolam;

• ergonovine, ergotamine, dihydroergotamine, methylergonovine;

• the seizure medications carbamazepine, phenobarbital, or phenytoin; or

• sildenafil (Revatio) or tadalafil (Adcirca) when used to treat pulmonary arterial hypertension.

FDA pregnancy category X. Incivek is given together with peginterferon alfa and ribavirin. Although Incivek is not expected to harm an unborn baby, ribavirin is known to cause birth defects or death in an unborn baby. Do not use this combination of drugs if you are pregnant, or if you are a man and your sexual partner is pregnant. If you are a woman, you may need to have a negative pregnancy test before using these medications and every month during your treatment.

• Use at least 2 non-hormonal forms of birth control while either sexual partner is using Incivek with peginterferon alfa and ribavirin. Keep using 2 forms of birth control for at least 6 months after treatment ends.

• If you are a woman, do not use Incivek with peginterferon alfa and ribavirin if you are pregnant.

• If you are a man, do not use Incivek with peginterferon alfa and ribavirin if your sexual partner is pregnant. An unborn baby could also be harmed if a man fathers the child while he is taking ribavirin.

• Hormonal contraception (such as birth control pills, injections, implants, skin patches, and vaginal rings) may not be effective enough to prevent pregnancy during your treatment. Ask your doctor about using a non-hormone method of birth control (such as a condom, intrauterine device (IUD), diaphragm with spermicide) to prevent pregnancy while taking Incivek.

• Tell your doctor right away if a pregnancy occurs while either the mother or the father is using Incivek with peginterferon alfa and ribavirin.

It is not known whether telaprevir passes into breast milk or if it could harm a nursing baby. Do not breast-feed a baby while taking this medicine.

Take the missed dose as soon as you remember. If you are more than 6 hours late, skip the missed dose. Do not take extra medicine to make up the missed dose.

Many drugs can interact with telaprevir. Not all possible interactions are listed here. Tell your doctor about all your medications and any you start or stop using during treatment with Incivek, especially:

• bosentan, colchicine, escitalopram, fentanyl, methadone, repaglinide, zolpidem (Ambien), warfarin (Coumadin);

• birth control pills or hormone replacement therapy;

• sildenafil (Viagra) and other erectile dysfunction medicines;

• an antibiotic or antifungal medicine--clarithromycin, erythromycin, itraconazole, ketoconazole, posaconazole, rifabutin, telithromycin, voriconazole; a sedative--alprazolam, trazodone; asthma or allergy medicine--budesonide, fluticasone, salmeterol (Advair, Serevent);

• cholesterol-lowering drugs--atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin; HIV or AIDS medicines--efavirenz, tenofovir, or ritonavir in combination with atazanavir, darunavir, fosamprenavir, or lopinavir;

• heart or blood pressure medicine--amlodipine, amiodarone, digoxin, diltiazem, felodipine, flecainide, nicardipine, nifedipine, nisoldipine, propafenone, quinidine, verapamil; or

• steroid medicine--dexamethasone, prednisone, methylprednisolone; medicine to prevent organ transplant rejection--cyclosporine, sirolimus, tacrolimus.

This list is not complete and many other drugs can interact with telaprevir. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Give a list of all your medicines to any healthcare provider who treats you.

Due to the potential for side effects in nursing infants, nursing should be discontinued before starting therapy. Excreted into human milk: Unknown Excreted into animal milk: Yes The effects in the nursing infant are unknown.