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Drug Interactions between Farydak and Sprycel

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

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Interactions between your drugs

Major

dasatinib panobinostat

Applies to: Sprycel (dasatinib) and Farydak (panobinostat)

GENERALLY AVOID: Panobinostat can cause dose-dependent prolongation of the QT interval. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. In a premarketing multiple myeloma trial, QTc prolongation with values between 451 to 480 msec and between 481 to 500 msec occurred in 10.8% and 1.3% of patients receiving panobinostat, respectively. A maximum QTcF increase from baseline of 31 to 60 msec and greater than 60 msec was observed in 14.5% and 0.8% of panobinostat-treated patients, respectively. No episodes of QTcF prolongation exceeding 500 msec were reported with panobinostat given at a dose of 20 mg in combination with bortezomib and dexamethasone in the multiple myeloma trial. Pooled clinical data from over 500 patients treated with panobinostat monotherapy at different dose levels for various indications have shown that the incidence of CTC Grade 3 QTc prolongation (i.e., QTcF >500 msec) was approximately 1% overall and 5% or more at a dose of 60 mg or higher. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypocalcemia). Moreover, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: Concomitant use of panobinostat with other drugs that can prolong the QT interval should generally be avoided. Anti-emetic drugs with known QT prolonging risk such as dolasetron, granisetron, ondansetron, palonosetron, and tropisetron may be used with frequent ECG monitoring. ECG and serum electrolytes, including potassium, magnesium and calcium, should be monitored before starting panobinostat therapy and periodically during treatment as clinically indicated. In the premarketing trial, ECGs were performed at baseline and prior to initiation of each cycle for the first 8 cycles. Panobinostat should not be started if baseline QTc is greater than 450 msec. Likewise, treatment should be interrupted in patients who develop QTc prolongation of 480 msec or greater until recovery to less than or equal to Grade 1, then resumed at a reduced dose. In case of recurrence, therapy should be withheld until recovery to less than or equal to Grade 1, then resumed at a further reduced dose if necessary. Permanently discontinue panobinostat therapy if Grade 3 or 4 QTc prolongation does not resolve. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

References

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

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Drug and food interactions

Major

dasatinib food

Applies to: Sprycel (dasatinib)

GENERALLY AVOID: Grapefruit and grapefruit juice may significantly increase the plasma concentrations of dasatinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruit. Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability). 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. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict. Because dasatinib prolongs the QT interval, high plasma levels of dasatinib may increase the risk of ventricular arrhythmias such as torsade de pointes and sudden death.

MANAGEMENT: Patients treated with dasatinib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Some authorities recommend close monitoring for toxicity (e.g., myelosuppression, bleeding complications, fluid retention, bradycardia or other conduction disturbances) and a reduction of dasatinib dosage to a range of 20 to 40 mg daily should be considered if there are no alternatives and concomitant use with a potent CYP450 3A4 inhibitor is necessary.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2006) "Product Information. Sprycel (dasatinib)." Bristol-Myers Squibb
  3. Cerner Multum, Inc. "Australian Product Information."

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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."
  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.


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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.