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Drug Interactions between avatrombopag and carbamazepine

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

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Interactions between your drugs

Major

carBAMazepine avatrombopag

Applies to: carbamazepine and avatrombopag

ADJUST DOSE: Concomitant use of avatrombopag with moderate to potent dual inducers of CYP450 2C9 and 3A4 may decrease the systemic exposure (AUC) of avatrombopag which may lead to reduced efficacy. An open-label study evaluated the pharmacokinetic and pharmacodynamic drug-drug interactions of avatrombopag in combination with dual or selective CYP450 2C9 and 3A4 interacting drugs. Administration of a single 20 mg dose of avatrombopag to healthy subjects (n=48) who had achieved steady-state concentrations of rifampin (a moderate CYP450 2C9 and potent CYP450 3A4 inducer) resulted in a 43% reduction in avatrombopag AUC, and a shortened terminal elimination phase half-life from 20.3 hours to 9.84 hours. However, no impact on the maximum platelet count was observed.

MANAGEMENT: For the treatment of patients with chronic immune thrombocytopenia, the manufacturer recommends an increased starting dose of avatrombopag 40 mg orally once daily when used concomitantly with a moderate to potent dual CYP450 2C9 and 3A4 inducer. In patients already receiving avatrombopag therapy and starting a moderate or strong dual CYP450 2C9 and 3A4 inducer, platelet counts should be monitored and avatrombopag dose adjusted according to the manufacturer's product labeling as necessary. Dose adjustments are not recommended when prescribed for the treatment of thrombocytopenia in adult patients with chronic liver disease undergoing a procedure.

References (4)
  1. Nomoto M, Zamora CA, Schuck E, et al. (2018) "Pharmacokinetic/pharmacodynamic drug-drug interactions of avatrombopag when coadministered with dual or selective CYP2C9 and CYP3A interacting drugs." Br J Clin Pharmacol, 84, p. 952-60
  2. (2023) "Product Information. Doptelet (avatrombopag)." Swedish Orphan Biovitrum Pty Ltd
  3. (2021) "Product Information. Doptelet (avatrombopag)." Swedish Orphan Biovitrum Ltd
  4. (2021) "Product Information. Doptelet (avatrombopag)." AkaRx, Inc.

Drug and food interactions

Moderate

carBAMazepine food

Applies to: 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 (3)
  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
Moderate

avatrombopag food

Applies to: avatrombopag

ADJUST DOSING INTERVAL: Food reduces the variability in oral absorption and bioavailability of avatrombopag. According to the product labeling, avatrombopag peak plasma concentration (Cmax) and systemic exposure (AUC) were not affected when administered with either a low-fat (500 calories; 3 g fat, 15 g proteins, 108 g carbohydrates) or high-fat (918 calories; 59 g fat, 39 g proteins, 59 g carbohydrates) meal. However, the variability of avatrombopag exposure was reduced by 40% to 60% with food, and the time to reach Cmax was delayed by 0 to 2 hours relative to the fasted state.

MANAGEMENT: To ensure consistent absorption and plasma drug levels, avatrombopag should be taken with food.

References (1)
  1. (2018) "Product Information. Doptelet (avatrombopag)." Dova Pharmaceuticals

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.

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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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