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Drug Interactions between ceritinib and tolterodine

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

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Interactions between your drugs

Moderate

tolterodine ceritinib

Applies to: tolterodine and ceritinib

ADJUST DOSE: Coadministration with drugs that are inhibitors of CYP450 3A4 may increase the plasma concentrations of tolterodine, which is partially metabolized by the isoenzyme. The possibility of prolonged and/or increased pharmacologic effects of tolterodine should be considered. Although tolterodine is primarily metabolized by CYP450 2D6, there is some evidence that CYP450 3A4 may play a minor role, thus any alteration in its activity levels could conceivably affect the metabolism of tolterodine. The clinical significance of this interaction is yet unknown but may be greater in patients who are CYP450 2D6-deficient, or so-called poor metabolizers of CYP450 2D6 (approximately 7% of Caucasians and less than 2% of Asians and individuals of African descent).

MANAGEMENT: The manufacturer recommends a maximum tolterodine dosage of 1 mg twice daily in patients receiving concomitant CYP450 3A4 inhibitors. Close clinical and laboratory monitoring is advised whenever a CYP450 3A4 inhibitor is added to or withdrawn from therapy. Patients should be advised to notify their physician if they experience an irregular heartbeat, severe blurry vision, difficulty urinating, dry mouth, headache, drowsiness, dizziness, or GI upset.

References (2)
  1. (2001) "Product Information. Detrol (tolterodine)." Pharmacia and Upjohn
  2. Brynne N, Forslund C, Hallen B, Gustafsson LL, Bertilsson L (1999) "Ketoconazole inhibits the metabolism of tolterodine in subjects with deficient CYP2D6 activity." Br J Clin Pharmacol, 48, p. 564-72

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

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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