Current and Future Medications for Hepatitis C (cont.)
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Protease inhibitors include medications such as telaprevir (Incivek, which was voluntarily withdrawn from the market in August 2014) and boceprevir (Victrelis).
How do Protease Inhibitors work? Protease Inhibitors are termed direct-acting antiviral agents (DAA). They specifically work by inhibiting certain enzymes and proteins necessary for replication of the HCV virus.
Who should not use these medications? Because ribavirin may cause birth defects and fetal death, combinations of interferon, ribavirin, and protease inhibitors should not be used in pregnant women and in men whose female partners are pregnant. Women of childbearing potential and their male partners should not receive ribavirin unless they are using effective contraception (two reliable forms) during treatment with ribavirin and for 6 months after treatment.
Dosage and Administration: Telaprevir 750 mg is taken 3 times a day and boceprevir 800 mg is taken three times a day
Drug or Food Interactions: Many drugs are metabolized (eliminated) from the body by enzymes in the liver. Telaprevir and boceprevir block one of the more important of these enzymes in the liver (CYP3A). As a result, drugs that are normally eliminated by this enzyme are not eliminated, and the drugs' levels in the body increase and may lead to toxicity. The list of drugs that should not be used because of the seriousness of the toxicity or that must be used cautiously is large and includes many commonly-used drugs. Before treatment with telaprevir and boceprevir is begun, therefore, it is important to review all of the drugs that patients are taking to identify drugs that must be discontinued or given in reduced doses.
Although the protease inhibitors block CYP3A, they also are partially eliminated by the same enzyme. Some drugs increase the activity of CYP3A and result in reduced levels of the protease inhibitors and thereby reduce their effectiveness, for example, corticosteroids (for example, prednisone). Other drugs decrease the activity of CYP3A and result in elevated levels of the protease inhibitors and possibly can lead to toxicity, for example, some of the anti-fungal drugs (for example, etoconozole).
Side Effects: Telaprevir causes headache, dysgeusia (distortion of the sense of taste), fatigue, and nausea. Telaprevir also causes rash, itching (pruritus), anemia, vomiting, hemorrhoids, and anal itching. The addition of boceprevir to peginterferon alfa and ribavirin is associated with an additional decrease in red blood cells (anemia) and white blood cells (neutropenia) compared with peginterferon alfa and ribavirin alone.
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