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Drug Interactions between ivacaftor / lumacaftor and panobinostat

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

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Interactions between your drugs

Major

panobinostat lumacaftor

Applies to: panobinostat and ivacaftor / lumacaftor

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of panobinostat, which is partially metabolized by the isoenzyme. The interaction has not been evaluated clinically, but simulations using physiologically-based pharmacokinetic (PBPK) models suggest an approximately 70% decrease in panobinostat systemic exposure.

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

References

  1. (2015) "Product Information. Farydak (panobinostat)." Novartis Pharmaceuticals

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Moderate

ivacaftor panobinostat

Applies to: ivacaftor / lumacaftor and panobinostat

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of panobinostat, which is partially metabolized by the isoenzyme. In 14 patients with advanced or metastatic solid tumors, administration of a single 20 mg dose of panobinostat on day 4 of multiple once daily dosing of 400 mg ketoconazole, a potent CYP450 3A4 inhibitor, resulted in 1.6- and 1.8-fold increases in mean panobinostat peak plasma concentration (Cmax) and systemic exposure (AUC), respectively, compared to administration of panobinostat alone. Ketoconazole caused a greater than 2-fold increase in Cmax and AUC of panobinostat in a limited number of patients. QTc prolongation >30 ms over baseline occurred in 5 patients during concomitant administration, compared to 4 patients during panobinostat alone and 3 patients during ketoconazole alone. Other ECG abnormalities occurred in 6 patients during concomitant administration and 3 patients during either panobinostat or ketoconazole alone. No significant alteration in time to maximum concentration (Tmax) or half-life of panobinostat was observed. The interaction has not been studied with other, less potent inhibitors.

MANAGEMENT: Caution is advised when panobinostat is prescribed with CYP450 3A4 inhibitors. Patients should be monitored for adverse effects such as nausea, vomiting, diarrhea, anorexia, peripheral edema, cardiotoxicity, ECG abnormalities, electrolyte disturbances, bleeding complications, hepatotoxicity and myelosuppression, and the dosage of panobinostat adjusted as necessary in accordance with the product labeling.

References

  1. Hamberg P, Woo MM, Chen LC, et al. (2011) "Effect of ketoconazole-mediated CYP3A4 inhibition on clinical pharmacokinetics of panobinostat (LBH589), an orally active histone deacetylase inhibitor." Cancer Chemother Pharmacol, 68, p. 805-13
  2. (2015) "Product Information. Farydak (panobinostat)." Novartis Pharmaceuticals

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Drug and food interactions

Moderate

ivacaftor food

Applies to: 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

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Moderate

panobinostat food

Applies to: panobinostat

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of panobinostat. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Increased exposure to panobinostat may increase the risk of adverse effects such as nausea, vomiting, diarrhea, anorexia, peripheral edema, cardiotoxicity, ECG abnormalities, electrolyte disturbances, bleeding complications, hepatotoxicity, and myelosuppression.

Food may delay the rate of absorption of panobinostat, but does not significantly affect the overall extent of absorption. When a single oral dose of panobinostat was administered to 36 patients with advanced cancer 30 minutes after a high-fat meal, panobinostat peak plasma concentration (Cmax) and systemic exposure (AUC) were approximately 44% and 16% lower, respectively, compared to administration under fasting conditions. The median time to maximum concentration (Tmax) was prolonged by 2.5 hours.

MANAGEMENT: Patients should avoid consumption of grapefruit or grapefruit juice during treatment with panobinostat. The manufacturer also recommends avoiding star fruit, Seville oranges, pomegranate, and pomegranate juice. Panobinostat may be administered with or without food.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Cerner Multum, Inc. "Australian Product Information."
  3. (2015) "Product Information. Farydak (panobinostat)." 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.

See also

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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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