Incivek (telaprevir) - HCV Drug Information
Updated May 25, 2015.
Written or reviewed by a board-certified physician. See About.com's Medical Review Board.
Classification
Incivek (telaprevir) is protease inhibitor-class drug used in combination antiviral therapy for the treatment of hepatitis C (HCV) genotype 1 (HCV-1). Incivek works by binding to the active site of a nonstructural protein essential to HCV replication.
Incivek was approved in May 2011 by the U.S. Food and Drug Administration (FDA) for use in adults 18 years or over with compensated liver disease (i.e., where the liver is still functional).
Incivek is appropriate for use in previously untreated ("treatment-naïve") patients, as well as those who have had partial or no response to prior HCV therapy.
While the FDA has not formerly approved Incivek for use in HIV/HCV coinfection (citing that safety and efficacy has not yet been established), both the U.S. Department of Health and Human Services (DHHS) and the American Association for the Study of Liver Diseases (AASLD) recommend its use in HIV patients with HCV-1 infection.
Clinical research has indicated that the cure rate for treatment-naïve patients on a Incivek-based regimen is between 74% and 79%. The cure rate for patients with cirrhosis (scarring of the liver) is approximately 40%.
Incivek is marketed in Europe under the name Incivo.
Dosage
The Incivek dosage is two 375mg tablets taken three times daily with food (not low fat). Incivek tablets are film coated, oblong and light purple in color, with "375" embossed on one side.
Prescribing Information
Incivek is prescribed for use in combination therapy with pegylated interferon (peg-interferon) + ribavirin.
Incivek must never be used as monotherapy.
Upon initiation of therapy, Incivek + peg-interferon + ribavirin are prescribed for the first 12 weeks. Based on the patient's HCV viral load at weeks 4 and 12, therapy is continued for an additional 12 or 36 weeks with peg-interferon + ribavirin alone, as follows:
Duration of therapy for treatment-naïve patients or patients who have had HCV relapse:
- If an undetectable HCV viral load is achieved at weeks 4 and 12, continue with peg-interferon + ribavirin alone for an additional 12 weeks (24 weeks total).
- If the HCV viral load is detectable (1000 IU/mL or less) at week 4 and/or 12, continue with peg-interferon + ribavirin alone for an additional 36 weeks (48 weeks total).
Duration for treatment-naïve patients with cirrhosis:
- If a patient is able to achieve an undetectable viral load at weeks 4 and 12, there may be a benefit from continuing peg-interferon + ribavirin for an additional 36 weeks (48 weeks total.
Duration for patients who are partial responders (achieved at least a two-log drop in viral load on previous therapy) or null responders (achieve little or no decrease in viral load on previous therapy):
- Continue peg-interferon + ribavirin alone, irrespective of viral load, for an additional 36 weeks (48 weeks total).
Patients with inadequate viral response are unlikely to achieve a sustained virological response (or SVR, popularly defined as a "cure") and may quickly develop resistance to Incivek. To prevent treatment failure, the Incivek dosage should never be reduced or interrupted.
Studies have further concluded that a high proportion of previous null responders, particularly those with cirrhosis, do not achieve SVR and are resistance to Incivek at the start of therapy.
If the HCV viral load is above 1000 IU/mL at week 4 or 12, treatment futility is declared and discontinuation of therapy is recommended in all patients. Similarly, if the viral load is detectable at week 24, therapy should be stopped.
Common Drug Side Effects
Incivek-associated side effects can range from mild or moderate (Grades 1-2) to severe or potentially life-threatening (Grades 3-4). The most common side effects associated with the use of Victrelis + peg-inter+ ribavirin (i.e., occurring in 20% or less of patients) are:
- Fatigue
- Anemia
- Nausea
- Pruiritus (itchy sensation)
- Diarrhea
- Rash
In fact, 56% of patients on a Incivek-based regimen developed a rash while on therapy, according to clinical research. The FDA recommends that anyone who gets a serious skin reaction stop the drugs immediately and seek emergency medical care.
Other side effects can include chills; fever; lethargy; athralgia (joint pain or stiffness); unusual bleeding or bruising; and dark, tarry stools.
There is no underplaying the fact that the side effects associated with a Incivek-based therapy can sometimes be profound. According to pre-market research, 14% of patients abandoned therapy prematurely as a result of these intolerable side effects.
For patients with cirrhosis, the impact can even be greater. Based on data presented at the 2012 International Liver Conference, 46% of cirrhotic patients experienced serious drug side effects.The most frequently noted Grade 3-4 events were anemia (10%), thrombocytopenia (7%), and neutropenia (5%), while a large proportion experienced Grade 3-4 hepatic decomposition (the exacerbation or worsening of liver disease).
Understanding and anticipating potential side effects, as well as ensuring regular doctor visits, can help mitigate many of these events before they come serious, or at the very least lessen their severity.
Drug Contraindications
The following drugs should not be taken with Victrelis:
- Antiretroviral drugs: Viracept (nelvinavir), Norvir (ritonavir)
- Erectile dysfunction drugs: Viagra, Revatio, Cialis
- Ergot derivative medications: D.H.E. 45, Migranal, Methergine, ergonovine, ergotamine
- Rifampin-based anti-tuberculosis medications: Mycobutin, Rifater, Rifamate, Rimactane, Rifadin, Priftin
- Statin medications: Lipitor, Zocor, Mevacor
- Propulsid (cisapride) used to treat gastroesophageal reflux disease (GERD)
- Uroxatral (alfuzosin) used to treat enlarged prostate
- St. John's Wort
It's important to advise your treating doctor of any and all medications you may be taking to better prevent drug-drug interactions.
Additionally, for patients with HIV, it is suggested that the following antiretroviral drugs be substituted when using Incivek:
Pregnancy Warning
Victrelis is contraindicated for use during pregnancy (or in men whose partners are pregnant) as animal studies have suggested a potential risk for birth defects or fetal death.
It is recommended that all women of child-bearing age be monitored monthly for pregnancy during the course of therapy. It is also recommended that the patient and her male partner be provided at least two non-hormonal methods of contraception, and that they be used during the course of therapy and for six months after.
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Source:
U.S. Food and Drug Administration (FDA). "Approval of Incivek (telaprevir) a direct acting antiviral drug (DAA) to treat hepatitis C virus (HCV)." Silver Springs, Maryland; press release issued May 13.2012.
Jacobson, I.; Sanford, J.; et al. "A Special Meeting Review Edition: Advances in the Treatment of Hepatitis C Virus Infection From EASL 2013."Gastroenterololgy & Hepatology. 2013 June; 9(6 Suppl 3):1–18.
U.S. Department of Health and Human Services (DHHS). "Guidelines for the use of Antiretroviral Agents in HIV-1-infected Audlts and Adolescents." Washington, D.C.; accessed 8 January 2014.
Ghany, M.; Strader, D.; Thomas, D.; and Seeff, L. "AASLD Practice Guidelines: Diagnosis, Management, and Treatment of Hepatitis C: An Update." Hepatology. 2009; 49(4):1335-1374.
Hezode, C.; Dorival, C.; Zoulim, F.; et al. "Safety of telaprevir and boceprevir in combination with preginterferon alfa/ribavirin, in cirrhotic non responders." International Liver Congress 2012. Barcelona, Spain; April 18-22. (f
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