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Drug Interactions between Anoro Ellipta and ceritinib

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

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Interactions between your drugs

Moderate

vilanterol ceritinib

Applies to: Anoro Ellipta (umeclidinium / vilanterol) and ceritinib

MONITOR: Coadministration with potent inhibitors of CYP450 3A4 may increase the systemic exposure to vilanterol following oral inhalation, as it is primarily metabolized by the isoenzyme. The interaction has been studied with fluticasone-vilanterol and ketoconazole. When fluticasone-vilanterol (200 mcg-25 mcg once daily for 7 days) was coadministered with ketoconazole (400 once daily for 11 days) in healthy subjects, fluticasone and vilanterol systemic exposure (AUC) were 36% and 65% higher, respectively, compared to coadministration with placebo. The increase in fluticasone exposure was associated with a 27% reduction in 24-hour weighted mean serum cortisol, whereas the increase in vilanterol exposure was not associated with an increase in beta-2 adrenergic systemic effects on heart rate or blood potassium.

MANAGEMENT: Due to the risk of cardiovascular adverse effects such as increases in pulse rate and blood pressure and ECG changes such as flattening of the T wave, prolongation of the QTc interval, and ST segment depression, caution is recommended when medications containing vilanterol are coadministered with potent CYP450 3A4 inhibitors such as itraconazole, ketoconazole, posaconazole, voriconazole, conivaptan, nefazodone, cobicistat, delavirdine, protease inhibitors, and ketolide and certain macrolide antibiotics. An increased risk of systemic corticosteroid effects should also be considered when fluticasone-vilanterol is used.

References

  1. (2013) "Product Information. Breo Ellipta (fluticasone-vilanterol)." GlaxoSmithKline
  2. Kempsford R, Norris V, Siederer S (2013) "Vilanterol trifenatate, a novel inhaled long-acting beta2 adrenoceptor agonist, is well tolerated in healthy subjects and demonstrates prolonged bronchodilation in subjects with asthma and COPD." Pulm Pharmacol Ther, 26, p. 256-64
  3. (2022) "Product Information. Anoro Ellipta (umeclidinium-vilanterol)." GlaxoSmithKline

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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. (2014) "Product Information. Zykadia (ceritinib)." Novartis 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.

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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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