Skip to main content

Drug Interactions between sonidegib and Tykerb

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

Edit list (add/remove drugs)

Interactions between your drugs

Moderate

lapatinib sonidegib

Applies to: Tykerb (lapatinib) and sonidegib

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of sonidegib, which is primarily metabolized by the isoenzyme. In 15 healthy volunteers, administration of a single 800 mg dose of sonidegib five days after starting treatment with the potent CYP450 3A4 inhibitor ketoconazole (200 mg orally twice daily for 14 days) increased mean sonidegib peak plasma concentration (Cmax) and systemic exposure (AUC) by 1.5- and 2.2-fold, respectively, compared to administration of sonidegib alone. Simulations using physiologically-based pharmacokinetic (PBPK) models suggest that sonidegib steady-state AUC would similarly increase in cancer patients taking sonidegib 200 mg once daily with a potent CYP450 3A4 inhibitor for 14 days. In addition, PBPK simulations predict that sonidegib steady-state AUC would increase approximately 1.8-fold when sonidegib 200 mg once daily is coadministered with the moderate CYP450 3A4 inhibitor erythromycin for 14 days, and 2.8-fold when coadministered with erythromycin for 4 months. No data are available for other, less potent CYP450 3A4 inhibitors.

MANAGEMENT: Caution is advised when sonidegib is prescribed with CYP450 3A4 inhibitors. Patients should be monitored for potentially increased adverse reactions, particularly musculoskeletal toxicity, and sonidegib treatment interrupted or discontinued accordingly.

References (1)
  1. (2015) "Product Information. Odomzo (sonidegib)." Novartis Pharmaceuticals

Drug and food interactions

Moderate

lapatinib food

Applies to: Tykerb (lapatinib)

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of lapatinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

ADJUST DOSING INTERVAL: Food can significantly increase the oral bioavailability of lapatinib. According to the manufacturer, lapatinib peak plasma concentration (Cmax) was approximately 2.5- and 3-fold higher and systemic exposure (AUC) 3- and 4-fold higher when administered with a low fat meal (5% fat; 500 calories) or with a high-fat meal (50% fat; 1000 calories), respectively, compared to fasting. Dividing the daily dose also resulted in an approximately 2-fold higher systemic exposure at steady state compared to the same total dose administered once daily.

MANAGEMENT: Patients treated with lapatinib should preferably avoid the consumption of grapefruit or grapefruit juice. The manufacturer recommends that lapatinib be administered at least one hour before or one hour after a meal. The lapatinib dose is administered once daily and should not be divided.

References (1)
  1. (2007) "Product Information. Tykerb (lapatinib)." Novartis Pharmaceuticals
Moderate

sonidegib food

Applies to: sonidegib

ADJUST DOSING INTERVAL: Food significantly increases the oral bioavailability of sonidegib. According to the product labeling, administration of sonidegib with a high-fat meal (approximately 1000 calories; 50% from fat) increased mean sonidegib peak plasma concentration (Cmax) and systemic exposure (AUC) by 7.4- to 7.8-fold.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of sonidegib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Increased exposure to sonidegib may increase the risk of adverse effects such as musculoskeletal toxicity, fatigue, nausea, vomiting, diarrhea, anorexia, weight loss, alopecia, pruritus, and dysgeusia.

MANAGEMENT: Sonidegib should be administered on an empty stomach, at least 1 hour before or 2 hours after a meal. Patients should avoid consumption of grapefruit or grapefruit juice during treatment with sonidegib.

References (1)
  1. (2015) "Product Information. Odomzo (sonidegib)." 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.

See also

Report options

Loading...
QR code containing a link to this page

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.

Medical Disclaimer