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Drug Interactions between papaverine and taletrectinib

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

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Interactions between your drugs

Major

papaverine taletrectinib

Applies to: papaverine and taletrectinib

Consumer information for this interaction is not currently available.

MONITOR CLOSELY: Intracoronary administration of papaverine has been associated with QT interval prolongation and torsade de pointes (TdP) arrhythmia. The risk may theoretically increase in patients receiving concomitant medications that can also prolong the QT interval or cause bradycardia. QT interval prolongation has not been reported following systemic or intracavernosal administration of papaverine. The precise mechanism of papaverine-induced ventricular tachyarrhythmias has not been delineated, but may involve inhibition of potassium currents and prolongation of the action potential duration. In a study involving 182 consecutive patients undergoing fractional flow reserve measurements, premature ventricular beats occurred in 15.9% of patients following administration of intracoronary papaverine. TdP occurred in 2.8% of patients, and of those, 1.7% developed ventricular fibrillation. The incidence of intracoronary papaverine-induced ventricular tachyarrhythmias has not been determined, but has ranged between <0.67% and 8.8% following intracoronary administration of 6 mg to 20 mg. Based on numerous reports, female gender, hypokalemia, alkalosis, bradycardia, administration of papaverine into the left coronary artery, and a prior history of drug-induced QT prolongation may be risk factors for papaverine-induced fatal ventricular tachyarrhythmias. Apart from isolated case reports, there are no published data regarding the potential interaction between intracoronary papaverine and its use with other QT-prolonging drugs. 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). In addition, the extent of drug-induced QT prolongation is dependent on the particular drugs involved and dosages of the drugs.

MANAGEMENT: Caution and close monitoring are advised during intracoronary administration of papaverine, particularly in patients receiving concomitant drugs that can prolong the QT interval or cause bradycardia and in patients with other risk factors described above. Some QT prolonging medications have specific monitoring, dosing, and/or other recommendations present in their labeling to help mitigate or monitor this side effect; therefore, it may be advisable to consult the package labeling of the concomitant medication if coadministration with intracoronary papaverine is being considered or deemed necessary.

Drug and food/lifestyle interactions

Major

taletrectinib food/lifestyle

Applies to: taletrectinib

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Coadministration with grapefruit juice may increase the plasma concentrations of taletrectinib. The proposed mechanism for the interaction is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice but has been reported for other CYP450 3A4 inhibitors. In a clinical study, taletrectinib peak plasma concentration (Cmax) increased by 1.8-fold and systemic exposure (AUC) increased by 3.3-fold following concomitant administration of itraconazole, a potent CYP450 3A inhibitor. According to the product labeling, administration of taletrectinib with a moderate CYP450 3A inhibitor is predicted to increase taletrectinib Cmax and AUC by up to 1.5- and 2.6-fold, respectively. Increased exposure to taletrectinib may increase the risk and/or severity of adverse effects such as hepatotoxicity with liver enzyme elevations, lung toxicities, QT prolongation, hyperuricemia, myalgia with creatine phosphokinase elevation, and skeletal fractures.

ADJUST DOSING INTERVAL: Coadministration with high-fat food (1000 calories, 50% fat) increased taletrectinib Cmax and AUC by 1.5-fold, and the predicted increase in the QTc interval is 20.5 msec.

MANAGEMENT: The manufacturer recommends avoiding food or drink containing grapefruit during treatment with taletrectinib. In addition, taletrectinib should be administered on an empty stomach at about the same time each day, at least 2 hours before or 2 hours after food intake.

Moderate

papaverine food/lifestyle

Applies to: papaverine

Papaverine and ethanol (alcohol) may have additive effects in lowering your blood pressure. You may experience headache, dizziness, lightheadedness, fainting, and/or changes in pulse or heart rate. These side effects are most likely to be seen at the beginning of treatment, following a dose increase, or when treatment is restarted after an interruption. Let your doctor know if you develop these symptoms and they do not go away after a few days or they become troublesome. Avoid driving or operating hazardous machinery until you know how the medications affect you, and use caution when getting up from a sitting or lying position. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

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.