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Drug Interactions between Farydak and Hemangeol

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

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Interactions between your drugs

Moderate

propranolol panobinostat

Applies to: Hemangeol (propranolol) and Farydak (panobinostat)

GENERALLY AVOID: Coadministration with panobinostat may increase the plasma concentrations of drugs that are substrates of CYP450 2D6. The mechanism is decreased clearance due to inhibition of CYP450 2D6 activity by panobinostat. When a single 60 mg dose of dextromethorphan, a CYP450 2D6 probe substrate, was coadministered with panobinostat (20 mg once per day on days 3, 5, and 8) in 14 patients with advanced cancer, dextromethorphan peak plasma concentration (Cmax) increased by 20% to 200% (median 80%) and systemic exposure (AUC) increased by 20% to 130% (median 60%) compared to administration of dextromethorphan alone.

MANAGEMENT: Given the high interpatient variability with respect to magnitude of interaction, concomitant use of panobinostat with sensitive CYP450 2D6 substrates (e.g., atomoxetine, desipramine, dextromethorphan, metoprolol, nebivolol, perphenazine, tolterodine, venlafaxine) or CYP450 2D6 substrates that have a narrow therapeutic index (e.g., pimozide, thioridazine) should generally be avoided. Caution is advised when panobinostat is used with other drugs that are metabolized by CYP450 2D6.

References

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

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Drug and food interactions

Moderate

propranolol food

Applies to: Hemangeol (propranolol)

ADJUST DOSING INTERVAL: The bioavailability of propranolol may be enhanced by food.

MANAGEMENT: Patients may be instructed to take propranolol at the same time each day, preferably with or immediately following meals.

References

  1. Olanoff LS, Walle T, Cowart TD, et al. "Food effects on propranolol systemic and oral clearance: support for a blood flow hypothesis." Clin Pharmacol Ther 40 (1986): 408-14
  2. Byrne AJ, McNeil JJ, Harrison PM, Louis W, Tonkin AM, McLean AJ "Stable oral availability of sustained release propranolol when co-administered with hydralazine or food: evidence implicating substrate delivery rate as a determinant of presystemic drug interactions." Br J Clin Pharmacol 17 (1984): s45-50

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Moderate

panobinostat food

Applies to: Farydak (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." O 0
  2. Cerner Multum, Inc. "Australian Product Information." O 0
  3. "Product Information. Farydak (panobinostat)." Novartis Pharmaceuticals (2015):

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Moderate

propranolol food

Applies to: Hemangeol (propranolol)

ADJUST DOSING INTERVAL: Concurrent administration with calcium salts may decrease the oral bioavailability of atenolol and possibly other beta-blockers. The exact mechanism of interaction is unknown. In six healthy subjects, calcium 500 mg (as lactate, carbonate, and gluconate) reduced the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of atenolol (100 mg) by 51% and 32%, respectively. The elimination half-life increased by 44%. Twelve hours after the combination, beta-blocking activity (as indicated by inhibition of exercise tachycardia) was reduced compared to that with atenolol alone. However, during a 4-week treatment in six hypertensive patients, there was no difference in blood pressure values between treatments. The investigators suggest that prolongation of the elimination half-life induced by calcium coadministration may have led to atenolol cumulation during long-term dosing, which compensated for the reduced bioavailability.

MANAGEMENT: It may help to separate the administration times of beta-blockers and calcium products by at least 2 hours. Patients should be monitored for potentially diminished beta-blocking effects following the addition of calcium therapy.

References

  1. Kirch W, Schafer-Korting M, Axthelm T, Kohler H, Mutschler E "Interaction of atenolol with furosemide and calcium and aluminum salts." Clin Pharmacol Ther 30 (1981): 429-35

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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

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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