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Drug Interactions between panobinostat and sertraline

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

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Interactions between your drugs

Major

sertraline panobinostat

Applies to: sertraline and 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

Moderate

sertraline food

Applies to: sertraline

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of sertraline. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills. In addition, limited clinical data suggest that consumption of grapefruit juice during treatment with sertraline may result in increased plasma concentrations of sertraline. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism by certain compounds present in grapefruit. An in-vitro study demonstrated that grapefruit juice dose-dependently inhibits the conversion of sertraline to its metabolite, desmethylsertraline. In a study with eight Japanese subjects, mean plasma levels of sertraline increased by approximately 100% and maximum plasma concentrations increased by 66% after the ingestion of three 250 mL glasses of grapefruit juice per day for 5 days and administration of a single dose of sertraline 75 mg on the sixth day. In another small study with 5 patients, mean sertraline trough levels increased by 47% after taking sertraline for at least 6 weeks, then taking sertraline with 240 mL grapefruit juice daily for 1 week. The clinical significance is unknown; however, pharmacokinetic alterations associated with interactions involving grapefruit juice are often subject to a high degree of interpatient variability. The possibility of significant interaction in some patients should be considered.

MANAGEMENT: Patients receiving sertraline should be advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how sertraline affects them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities. Some authorities recommend that consumption of grapefruit juice should be avoided during sertraline therapy.

References

  1. (2001) "Product Information. Zoloft (sertraline)." Roerig Division
  2. Lee AJ, Chan WK, Harralson AF, Buffum J, Bui BCC (1999) "The effects of grapefruit juice on sertraline metabolism: An in vitro and in vivo study." Clin Ther, 21, p. 1890-9
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  4. Ueda N, Yoshimura R, Umene-Nakano W, et al. (2009) "Grapefruit juice alters plasma sertraline levels after single ingestion of sertraline in healthy volunteers." World J Biol Psychiatry, 10(4 Pt 3), p. 832-5
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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.

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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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