Telaprevir

Summary

Telaprevir (Incivek/Incivo) was a first-generation, direct-acting antiviral peptidomimetic approved for the treatment of chronic hepatitis C genotype 1 infection in combination with peginterferon alfa and ribavirin. It was withdrawn from markets in 2014–2016 due to the advent of more tolerable and effective all-oral DAA regimens.

Mechanism of Action

Covalently and reversibly inhibits the hepatitis C virus (HCV) NS3/4A serine protease, blocking viral polyprotein processing and thereby preventing viral replication.

Routes of Administration

Goals & Uses

• Sustained virologic response (SVR)Clinical EndpointHigh
• Chronic HCV genotype 1 treatmentAntiviral TherapyHigh
• Treatment-experienced HCV patientsAntiviral TherapyHigh

Contraindications

• PregnancyPopulationHighPotential fetal risk or insufficient safety data
• Concomitant use of strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, St. John's Wort)Drug InteractionHigh
• Hypersensitivity to telaprevir or excipientsAllergyHigh
• Concomitant use of drugs highly dependent on CYP3A4 with narrow therapeutic index (e.g., alfuzosin, ergot derivatives, cisapride, pimozide, simvastatin, lovastatin)Drug InteractionHigh

Adverse Effects

• HyperuricemiaMetabolicUncommon
• AnemiaHematologicCommonLow red blood cell count or hemoglobin
• Rash (including DRESS and Stevens-Johnson syndrome)DermatologicCommon
• NauseaGastrointestinalCommonFeeling of sickness or urge to vomit
• Anorectal discomfort/pruritus aniGastrointestinalCommon
• FatigueGeneralCommonLow energy or tiredness

Drug Interactions

• RifampinHigh
• Simvastatin / LovastatinHigh
• Tacrolimus / CyclosporineHigh
• Midazolam (oral)High
• Hormonal contraceptivesModerate
• Amiodarone / AntiarrhythmicsModerate

Population Constraints

• PregnancyReproductive SafetyAbsolute
• Pediatric patients (<18 years)AgeAbsolute
• Hepatic decompensation (Child-Pugh B/C)Hepatic ImpairmentAbsolute
• HIV/HCV co-infection with antiretroviralsDrug InteractionRelative
• HCV non-genotype 1 infectionIndicationAbsolute

Regulatory Status

• European UnionWithdrawnApproved: Chronic hepatitis C genotype 1 in adults in combination with peginterferon alfa and ribavirinEMA approval granted 2011; marketing authorization withdrawn at request of marketing authorisation holder in 2014.
• United StatesWithdrawnApproved: Chronic hepatitis C genotype 1 in adults in combination with peginterferon alfa and ribavirinFDA approved May 23, 2011; voluntarily withdrawn by Vertex Pharmaceuticals in October 2014 due to availability of superior therapies.
• United KingdomWithdrawnApproved: Chronic hepatitis C genotype 1 in adults in combination with peginterferon alfa and ribavirinFollowed EMA withdrawal; no longer available in the UK market.

FDA approved May 2011; withdrawn from US market October 2014. EMA approved 2011; withdrawn from EU market 2014. Manufacturer (Vertex Pharmaceuticals) voluntarily withdrew the product globally.

Evidence & Sources

No sources recorded yet.