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Drug Interactions between Epitol and telaprevir

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Major

carBAMazepine telaprevir

Applies to: Epitol (carbamazepine) and telaprevir

CONTRAINDICATED: Coadministration with certain anticonvulsants may significantly decrease the plasma concentrations of telaprevir. The mechanism involves induction of CYP450 3A4, the isoenzyme responsible for the metabolic clearance of telaprevir and other protease inhibitors. Anticonvulsants that are considered potent inducers of CYP450 3A4 include carbamazepine, phenobarbital, and phenytoin. In 11 study subjects, administration of telaprevir (750 mg every 8 hours for 10 days) with carbamazepine (200 mg every 12 hours for 17 days) decreased mean telaprevir peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) by 21%, 32% and 47%, respectively. When the same dosage regimen of telaprevir was coadministered with phenytoin (200 mg every 12 hours for 17 days) in 7 study subjects, mean telaprevir Cmax, AUC and Cmin reduced by 32%, 47% and 68%, respectively. In the presence of telaprevir, carbamazepine pharmacokinetics were not significantly altered, whereas phenytoin Cmax, AUC and Cmin increased by 27%, 31% and 36%, respectively. No data are available for phenobarbital.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic telaprevir levels, concomitant use with carbamazepine, phenobarbital, or phenytoin is considered contraindicated.

References

  1. (2011) "Product Information. Incivek (telaprevir)." Vertex Pharmaceuticals

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Drug and food interactions

Moderate

carBAMazepine food

Applies to: Epitol (carbamazepine)

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of carbamazepine. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

In a small, randomized, crossover study, the administration of carbamazepine with grapefruit juice (compared to water) increased plasma drug concentrations by approximately 40%. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

MANAGEMENT: Patients receiving carbamazepine should be advised to avoid or limit consumption of alcohol. Given the drug's narrow therapeutic index, patients receiving carbamazepine therapy should preferably avoid the regular consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels. Patients should be advised to report signs of carbamazepine toxicity (nausea, visual disturbances, dizziness, or ataxia) to their physicians.

References

  1. (2002) "Product Information. Tegretol (carbamazepine)." Novartis Pharmaceuticals
  2. Garg SK, Kumar N, Bhargava VK, Prabhakar SK (1998) "Effect of grapefruit juice on carbamazepine bioavailability in patients with epilepsy." Clin Pharmacol Ther, 64, p. 286-8
  3. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR (2000) "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther, 68, p. 468-77

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Moderate

telaprevir food

Applies to: telaprevir

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.

References

  1. (2011) "Product Information. Incivek (telaprevir)." Vertex Pharmaceuticals

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

See also

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

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