Drug Interactions between Epitol and pralsetinib
This report displays the potential drug interactions for the following 2 drugs:
- Epitol (carbamazepine)
- pralsetinib
Interactions between your drugs
carBAMazepine pralsetinib
Applies to: Epitol (carbamazepine) and pralsetinib
GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A may significantly decrease the plasma concentrations of pralsetinib which is primarily metabolized by the isoenzyme. When a single 400 mg dose of pralsetinib was administered with rifampin (a potent CYP450 3A4 inducer), pralsetinib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 30% and 68%, respectively. Reduced therapeutic efficacy may occur.
MANAGEMENT: Concomitant use of pralsetinib with potent CYP450 3A inducers should generally be avoided. If coadministration with potent CYP450 3A inducers is necessary, the initial dose of pralsetinib should be doubled starting on Day 7 of coadministration with the strong CYP450 3A4 inducer. Once the potent CYP450 3A inducer has been discontinued for at least 14 days, the pralsetinib dose taken prior to initiating the potent CYP450 3A4 inducer may be resumed.
References
- (2020) "Product Information. Gavreto (pralsetinib)." Blueprint Medicines Corporation
Drug and food interactions
pralsetinib food
Applies to: pralsetinib
ADJUST DOSING INTERVAL: Food significantly increases the oral bioavailability of pralsetinib. According to the product labeling, administration of pralsetinib with a high-fat meal (approximately 800 to 1000 calories; 50% to 60% from fat) increased mean pralsetinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 104% and 122%, respectively. The median time to maximum concentration (Tmax) was delayed from 4 to 8.5 hours.
GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of pralsetinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Increased exposure to pralsetinib may increase the risk of adverse effects such as musculoskeletal toxicity, fatigue, constipation, hypertension, and pneumonia.
MANAGEMENT: Pralsetinib should be administered on an empty stomach, at least 2 hours after or 1 hour before a meal. Patients should avoid consumption of grapefruit or grapefruit juice during treatment with pralsetinib.
References
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- (2020) "Product Information. Gavreto (pralsetinib)." Blueprint Medicines Corporation
- (2023) "Product Information. Gavreto (pralsetinib)." Roche Products Pty Ltd, GAVRETO 20230406
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
- (2002) "Product Information. Tegretol (carbamazepine)." Novartis Pharmaceuticals
- 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
- 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
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
Drug Interaction Classification
Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
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. | |
No interaction information available. |
Further information
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.
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