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Drug Interactions between ceritinib and Doptelet

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

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Interactions between your drugs

Major

ceritinib avatrombopag

Applies to: ceritinib and Doptelet (avatrombopag)

ADJUST DOSE: Concomitant use of avatrombopag with moderate to potent dual inhibitors of CYP450 2C9 and 3A4 may increase the systemic exposure (AUC) to avatrombopag. This may lead to an increased risk of avatrombopag toxicities including thromboembolic events such as portal vein thrombosis and septic thrombophlebitis. Metabolic clearance via CYP450 2C9 appears be more significant than CYP450 3A4. 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 fluconazole (a moderate dual CYP450 3A4 and 2C9 inhibitor) led to a 2.16-fold increase in avatrombopag AUC, an increase in the terminal elimination phase half-life from 19.7 hours to 39.9 hours, and a clinically significant 1.66-fold increase in the maximum platelet count. In addition, pooled pharmacogenomic analysis of avatrombopag studies suggests that CYP450 2C9 polymorphisms may also impact the clearance of avatrombopag. Compared to normal metabolizers, intermediate and poor metabolizers for CYP450 2C9 showed a 1.4- and 2-fold increase in avatrombopag exposure, respectively .

MANAGEMENT: For the treatment of patients with chronic immune thrombocytopenia, the manufacturer recommends a reduced starting dose of avatrombopag 20 mg orally three times a week when used concomitantly with a moderate to potent dual inhibitor of CYP450 2C9 and 3A4. In patients already receiving avatrombopag therapy, monitoring of platelet counts is recommended when a moderate to potent dual CYP450 2C9 and 3A4 inhibitor is added, and the avatrombopag dose adjusted according to the manufacturer's product labeling as necessary. Dosage adjustments are not available for poor metabolizers of CYP450 2C9. 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

Major

ceritinib food

Applies to: ceritinib

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of ceritinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Because ceritinib is associated with concentration-dependent prolongation of the QT interval, increased levels may potentiate the risk of ventricular arrhythmias such as torsade de pointes and sudden death. Other, more common side effects such as diarrhea, nausea, vomiting, abdominal pain, hyperglycemia, and bradycardia may also increase.

ADJUST DOSING INTERVAL: Food increases the oral bioavailability of ceritinib. The mechanism of interaction is unknown. Compared to the fast state, administration of a single 500 mg dose of ceritinib with a high-fat meal (approximately 1000 calories; 58 grams of fat) increased ceritinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 41% and 73%, respectively, and administration with a low-fat meal (approximately 330 calories; 9 grams of fat) increased ceritinib Cmax and AUC by 43% and 58%, respectively. A dose of 600 mg or higher taken with a meal is expected to produce systemic exposure exceeding that from a 750 mg dose taken in the fasted state, which may lead to increased adverse effects.

MANAGEMENT: Patients treated with ceritinib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Ceritinib should be administered on an empty stomach (i.e., avoid administration within 2 hours of a meal).

References (1)
  1. (2014) "Product Information. Zykadia (ceritinib)." Novartis Pharmaceuticals
Moderate

avatrombopag food

Applies to: Doptelet (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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