Pharmacological Class:
Hepatitis C virus NS3/4A protease inhibitor.

Active Ingredient(s):
Telaprevir 375mg; tablets.
Indication(s):
Chronic hepatitis C genotype 1 infection, in combination with peginterferon alfa and ribavirin in patients with compensated liver disease, including cirrhosis, who are treatment-naïve or who have previously been treated with interferon-based therapy, including prior null responders, and relapsers. Not for use as monotherapy.

Pharmacology:
Telaprevir works by inhibiting the HCV NS3/4A serine protease enzyme.

Clinical Trials:
A study was conducted in treatment-naïve patients to evaluate the safety and efficacy of telaprevir. Sustained virologic response (SVR) was defined as HCV-RNA <25 IU/mL at 24 weeks after the planned end of treatment. Telaprevir was given for the first 8 weeks (T8/PR) or the first 12 weeks of treatment (T12/PR) in combination with peginterferon alfa and ribavirin (peg-IFN-alfa-2a/RBV) for either 24 or 48 weeks. Subjects who had undetectable HCV-RNA at Weeks 4 and 12 received 24 weeks of peg-IFN-alfa-2a/RBV; those who did not have undetectable levels received 48 weeks of peg-IFN-alfa-2a/RBV. The control group received placebo for the first 12 weeks and peg-IFN-alfa-2a/RBV for 48 weeks. The overall SVR for the T12/PR group was 79% vs. 46% for placebo. In the T8/PR group, overall SVR was 72%.

In another study, prior relapsers and nonresponders were randomized to either of two telap­revir groups (with/without peg-IFN-alfa-2a/RBV lead-in) or control group. The SVRs for each of the study drug groups were significantly higher than the control groups (86% vs. 22%) for prior relapsers, 59% vs. 15% for prior partial responders, and 32% vs. 5% for prior null responders.
Legal Classification:
Rx

Adults:
Take with food (not low fat). 750mg three times daily. Treat for 12 weeks (with peginterferon + ribavirin), then continue peginterferon + ribavirin according to HCV-RNA response at Weeks 4 and 12. Do not reduce dose or interrupt therapy. Discontinue if futile (see literature).

Children:
≤18 years: not recommended.

Contraindication(s):
Concomitant strong CYP3A inducers (eg, rifampin, St. John’s wort), or narrow therapeutic index CYP3A substrates (eg, alfuzosin, ergots, atorvastatin, lovastatin, simvastatin, sildenafil/tadalafil for PAH, triazolam, oral midazolam). Pregnant women, or partners. Review peginterferon and ribavirin contraindications.
Warnings/Precautions:
Must have (–) pregnancy test before therapy, use effective contraception, and undergo monthly pregnancy test. Monitor for serious skin reactions (eg, DRESS, Stevens-Johnson syndrome). Moderate/severe hepatic impairment, decompensated liver disease: not recommended. Coinfection with HBV or HIV. Organ transplant recipients. Monitor hemoglobin, CBC with differential, HCV-RNA, and clinical chemistry. Pregnancy (Cat. B). Nursing mothers: not recommended.

Interaction(s):
Concomitant colchicine w/renal or hepatic impairment, voriconazole; lopinavir, fosamprenavir, darunavir (all w/ritonavir): not recommended. May be potentiated by macro­lides, azole antifungals. May be antagonized by anticonvulsants, rifabutin, dexamethasone, HIV pro­tease inhibitors, efavirenz. May potentiate anti­arrhythmics, digoxin, macrolides, carbamaz­e­pine, desipramine, trazodone, azole antifungals, colchicine, rifabutin, alprazolam, midazolam, calcium channel blockers, cortico­steroids, bosentan, atazanavir, tenofovir, immunosuppressants, salmet­erol, PDE5 inhibitors for ED (reduce dose). May antagonize escitalopram, zolpidem, efavirenz, ethinyl estradiol, methadone. Monitor warfarin.

Adverse Reaction(s):
Rash (if serious; discontinue therapy and treat, do not restart), pruritus, anemia, GI upset, anorectal effects, dysgeusia, fatigue, hyperbilirubinemia, hyperuricemia.
How Supplied:
Tabs (blister pack or bottle)—168
Last Updated:
7/14/2011