Telaprevir
Telaprevir Uses, Dosage, Side Effects, Food Interaction and all others data.
Telaprevir is a direct acting antiviral medication used as part of combination therapy to treat chronic Hepatitis C, an infectious liver disease caused by infection with Hepatitis C Virus (HCV). HCV is a single-stranded RNA virus that is categorized into nine distinct genotypes, with genotype 1 being the most common in the United States, and affecting 72% of all chronic HCV patients . Treatment options for chronic Hepatitis C have advanced significantly since 2011, with the development of Direct Acting Antivirals (DAAs) such as Telaprevir. Telaprevir is an inhibitor of NS3/4A, a serine protease enzyme, encoded by HCV genotype 1 . These enzymes are essential for viral replication and serve to cleave the virally encoded polyprotein into mature proteins like NS4A, NS4B, NS5A and NS5B. The barrier for develoment of resistance to NS3/4A inhibitors is lower than that of NS5B inhibitors, another class of DAAs . Subtitutions at amino acid positions 155, 156, or 168 are known to confer resistance. The substitutions of the enzyme's catalytic triad consisting of H58, D82, and S139 are also likely to alter the affinity of the drug for NS3/4A or the activity of the enzyme itself. Despite this disadvantage Telaprevir is still effective against HCV when paired with Ribavirin, Peginterferon alfa-2a, and Peginterferon alfa-2b.
Telaprevir, Ribavirin, Peginterferon alfa-2a, and Peginterferon alfa-2b were used with the intent to cure, or achieve a sustained virologic response (SVR), after 12 weeks of daily administration of the combination therapy followed by 12 or 36 weeks of therapy with Ribavirin, Peginterferon alfa-2a, and Peginterferon alfa-2b. SVR and eradication of HCV infection is associated with significant long-term health benefits including reduced liver-related damage, improved quality of life, reduced incidence of Hepatocellular Carcinoma, and reduced all-cause mortality .
Telaprevir was available as a fixed dose product (tradename Incivek) used for the treatment of chronic Hepatitis C. Approved in May 2011 by the FDA, Incivek was indicated for the treatment of HCV genotype 1 in combination with Ribavirin, Peginterferon alfa-2a, and Peginterferon alfa-2b . Incivek has since been withdrawn from the market.
| Trade Name | Telaprevir |
| Availability | Discontinued |
| Generic | Telaprevir |
| Telaprevir Other Names | Telaprevir |
| Related Drugs | Epclusa, Mavyret, ribavirin, Harvoni, Sovaldi, Vosevi |
| Type | Oral |
| Formula | C36H53N7O6 |
| Weight | Average: 679.8493 Monoisotopic: 679.405732463 |
| Protein binding | Telapravir is 59-76% bound to human plasma proteins following a single dose . It binds to both human serum albumin and α1-acid glycoprotein. |
| Groups | Approved, Withdrawn |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Telaprevir is an NS3/4A viral protease inhibitor used in combination with other antivirals for the curative treatment of chronic Hepatitis C Virus infections.
Telaprevir, when used in combination with Ribavirin, Peginterferon alfa-2a, and Peginterferon alfa-2b is indicated for use in the treatment of chronic HCV genotype 1 infection in adults .
Telaprevir is also used to associated treatment for these conditions: Chronic Hepatitis C Genotype 1
How Telaprevir works
Telaprevir is a NS3/4a protease inhibitor used to inhibit viral HCV replication . NS3/4a protease is an integral part of viral replication and mediates the cleavage the virally encoded polyprotein to mature proteins (NS4A, NS4B, NS5A and NS5B) . Telaprevir inhibits NS3/4A with an IC50 of 10nM.
Toxicity
Serious skin reactions, including Stevens Johnson Syndrome, Drug Reaction with Eosinophilia and Systemic Symptoms, and Toxic Epidermal Necrolysis, have been reported in patients treated with telaprevir combination treatment. Use of Ribavirin, Peginterferon alfa-2a, Peginterferon alfa-2b and Telaprevir is associated with a further increase in anemia frequency than in Ribavirin, Peginterferon alfa-2a, and Peginterferon alfa-2b without telaprevir.
Food Interaction
- Avoid St. John's Wort. St. John's Wort will decrease levels of this medication.
[Moderate] ADJUST DOSING INTERVAL: Food significantly enhances the oral bioavailability of telaprevir.
When given with a meal containing 533 kcal and 21 g fat, telaprevir systemic exposure (AUC) increased by 237% compared to administration under fasting conditions.
The type of meal also affects the exposure to telaprevir.
Relative to fasting, telaprevir AUC increased by approximately 117% with a low-fat meal (249 kcal; 3.6 g fat) and 330% with a high-fat meal (928 kcal; 56 g fat).
In Phase 3 clinical trials, telaprevir doses were administered within 30 minutes of completing a meal or snack containing approximately 20 grams of fat.
MANAGEMENT: Telaprevir should be administered with food containing approximately 20 grams of fat.
Patients should be advised that the fat content of the meal or snack is critical to the absorption of telaprevir.
Food taken with telaprevir should be ingested within 30 minutes prior to each dose.
Examples of some foods that could be taken with telaprevir include: bagel with cream cheese; half cup of nuts; 3 tablespoons of peanut butter; 1 cup of ice cream; 2 ounces of American or cheddar cheese; 2 ounces of potato chips; or half cup of trail mix.
Telaprevir Drug Interaction
Major: colchicineModerate: etravirine, saxagliptin, darunavir, emtricitabine / tenofovirUnknown: amoxicillin / clavulanate, mycophenolate mofetil, glucose, interferon alfa-2b, sitagliptin, acetaminophen, peginterferon alfa-2a, peginterferon alfa-2b, omeprazole, sulfamethoxazole / trimethoprim, tiotropium
Volume of Distribution
The estimated apparent volume of distribution for Telapravir is 252 litres with an inter-individual variability of 72% .
Elimination Route
Telaprevir reaches peak plasma concentration 4-5hours after administration . Absolute bioavailability has not been determined. When taken with a normal fat meal (21g of fat), exposure increases by 235% compared to fasting conditions. With low (3.6g of fat) and high fat (56g of fat) meals, exposure increased 117% and 330% respectively.
Half Life
Telaprevir has a half-life of elimination of 4.0-4.7 hours after a single dose and an effective half life of 9-11 hours at steady state .
Clearance
Telaprevir has an estimated aparent total body clearance of 32.4 liters per hour with an interindividual variability of 27.2% .
Elimination Route
Telaprevir is mainly eliminated in the feces (82%) with a smaller amount eliminated via expiration (9%) and very little in the urine (1%) . 31.9% and 18.8% of drug in the feces was present as the parent compound and R-diastereomer of the parent compound respectively.
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