Skip to main content

Drug Interactions between Odomzo and Orkambi

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

Edit list (add/remove drugs)

Interactions between your drugs

Major

lumacaftor sonidegib

Applies to: Orkambi (ivacaftor / lumacaftor) and Odomzo (sonidegib)

GENERALLY AVOID: Coadministration with potent and moderate inducers of CYP450 3A4 may significantly decrease the plasma concentrations of sonidegib, which is primarily metabolized by the isoenzyme. In 16 healthy volunteers, administration of a single 800 mg dose of sonidegib five days after starting treatment with the potent CYP450 3A4 inducer rifampin (600 mg daily for 14 days) decreased mean sonidegib peak plasma concentration (Cmax) and systemic exposure (AUC) by 54% and 72%, respectively, compared to administration of sonidegib alone. Simulations using physiologically-based pharmacokinetic (PBPK) models suggest that sonidegib steady-state AUC would decrease 56% in cancer patients taking sonidegib 200 mg once daily with the moderate CYP450 3A4 inducer efavirenz for 14 days, and 69% when coadministered with efavirenz for 4 months.

MANAGEMENT: Concomitant use of sonidegib with potent and moderate CYP450 3A4 inducers should generally be avoided.

References

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

Switch to consumer interaction data

Moderate

ivacaftor sonidegib

Applies to: Orkambi (ivacaftor / lumacaftor) and Odomzo (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. (2015) "Product Information. Odomzo (sonidegib)." Novartis Pharmaceuticals

Switch to consumer interaction data

Drug and food interactions

Moderate

ivacaftor food

Applies to: Orkambi (ivacaftor / lumacaftor)

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of ivacaftor. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Elexacaftor and tezacaftor are also CYP450 3A4 substrates in vitro and may interact similarly with grapefruit juice, whereas lumacaftor is not expected to interact.

ADJUST DOSING INTERVAL: According to prescribing information, systemic exposure to ivacaftor increased approximately 2.5- to 4-fold, systemic exposure to elexacaftor increased approximately 1.9- to 2.5-fold, and systemic exposure to lumacaftor increased approximately 2-fold following administration with fat-containing foods relative to administration in a fasting state. Tezacaftor exposure is not significantly affected by administration of fat-containing foods.

MANAGEMENT: Patients treated with ivacaftor-containing medications should avoid consumption of grapefruit juice and any food that contains grapefruit or Seville oranges. All ivacaftor-containing medications should be administered with fat-containing foods such as eggs, avocados, nuts, meat, butter, peanut butter, cheese pizza, and whole-milk dairy products. A typical cystic fibrosis diet will satisfy this requirement.

References

  1. (2012) "Product Information. Kalydeco (ivacaftor)." Vertex Pharmaceuticals
  2. (2015) "Product Information. Orkambi (ivacaftor-lumacaftor)." Vertex Pharmaceuticals
  3. (2022) "Product Information. Symdeko (ivacaftor-tezacaftor)." Vertex Pharmaceuticals
  4. (2019) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
View all 4 references

Switch to consumer interaction data

Moderate

sonidegib food

Applies to: Odomzo (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. (2015) "Product Information. Odomzo (sonidegib)." Novartis Pharmaceuticals

Switch to consumer interaction data

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