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Drug Interactions between ceritinib and Scemblix

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

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Interactions between your drugs

Moderate

ceritinib asciminib

Applies to: ceritinib and Scemblix (asciminib)

MONITOR: Coadministration with potent inhibitors of CYP450 3A4 may increase the plasma concentrations of asciminib. According to the prescribing information, asciminib is metabolized by CYP450 3A4-mediated oxidation and uridine diphosphate glucuronosyl transferase (UGT) 2B7- and 2B17-mediated glucuronidation. When a single 40 mg dose of asciminib was coadministered with clarithromycin, a potent CYP450 3A4 inhibitor, asciminib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 19% and 36%, respectively. Coadministration of asciminib 200 mg twice daily and clarithromycin is predicted to increase asciminib Cmax and AUC by 49% and 77%, respectively, per physiologically-based pharmacokinetic (PBPK) models. However, no clinically significant differences in the pharmacokinetics of asciminib were observed when coadministered with itraconazole, another potent CYP450 3A4 inhibitor.

MANAGEMENT: Caution is advised when asciminib is prescribed with potent CYP450 3A4 inhibitors, particularly at higher dosages. The manufacturer recommends that patients treated with asciminib at 200 mg twice daily be monitored closely for adverse reactions, such as nausea, diarrhea, rash, myelosuppression, pancreatitis, hypertension, and cardiovascular toxicity including ischemic cardiac conditions, arterial thrombotic and embolic conditions, cardiac failure, QT prolongation, and arrhythmia.

References (1)
  1. (2021) "Product Information. Scemblix (asciminib)." Novartis Pharmaceuticals

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

asciminib food

Applies to: Scemblix (asciminib)

ADJUST DOSING INTERVAL: Food may reduce the oral bioavailability of asciminib. When a single 40 mg dose of asciminib was administered with a low-fat meal (400 calories; 25% fat) in healthy volunteers, asciminib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 35% and 30%, respectively, compared to asciminib administered in the fasted state. Administration with a high-fat meal (1000 calories; 50% fat) decreased the Cmax and AUC of asciminib by 68% and 62%, respectively.

MANAGEMENT: To ensure adequate asciminib exposures, food consumption should be avoided for at least 2 hours before and 1 hour after taking asciminib.

References (2)
  1. (2021) "Product Information. Scemblix (asciminib)." Novartis Pharmaceuticals
  2. (2022) "Product Information. Scemblix (asciminib)." Novartis Pharmaceuticals UK Ltd, Scemblix 20 mg film-

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

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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