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Drug Interactions between Alecensa and Rythmol

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

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Interactions between your drugs

Moderate

propafenone alectinib

Applies to: Rythmol (propafenone) and Alecensa (alectinib)

MONITOR: Coadministration of alectinib with other agents that can slow the heart rate may increase the risk of bradycardia. In clinical trials, 7.5% of patients developed bradycardia during treatment with alectinib. Twenty percent of 221 patients for whom serial electrocardiograms were available had heart rates of less than 50 beats per minute (bpm).

MANAGEMENT: Caution is advised when alectinib is prescribed with other drugs that can cause bradycardia (e.g., beta-blockers; calcium channel blockers; digitalis; dolasetron; flecainide; ivabradine; lacosamide; mefloquine; moricizine; propafenone; quinine; succinylcholine; sunitinib; thalidomide; anticholinesterase or cholinergic agents; protease inhibitors such as atazanavir, lopinavir/ritonavir, and saquinavir/ritonavir). Heart rate and blood pressure should be monitored regularly, and patients should be counseled to seek medical attention if they experience dizziness, lightheadedness, fainting, or irregular heartbeat. Dosage modification of alectinib is not required in cases of asymptomatic bradycardia. However, if symptomatic bradycardia occurs, the manufacturer recommends withholding alectinib until recovery to asymptomatic bradycardia or to a heart rate of >=60 bpm. Evaluate concomitant medications known to cause bradycardia and all antihypertensive medications, then consider dosage adjustments or discontinuation of concomitant medication(s) or alectinib in accordance with the product labeling.

References

  1. (2015) "Product Information. Alecensa (alectinib)." Genentech

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Drug and food interactions

Moderate

propafenone food

Applies to: Rythmol (propafenone)

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of propafenone. The proposed mechanism 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. In over 90% of patients, propafenone is rapidly and extensively converted to 2 active metabolites: 5-hydroxypropafenone via CYP450 2D6 and N-depropylpropafenone (norpropafenone) via CYP450 3A4 and 1A2. In less than 10% of patients (approximately 6% of Caucasians in the U.S. population), however, metabolism of propafenone is slower because the 5-hydroxy metabolite is not formed, or minimally formed, due to a genetic deficiency in CYP450 2D6. In these poor metabolizers of CYP450 2D6, clearance of propafenone via the CYP450 3A4 and 1A2 metabolic pathways becomes more important, and inhibition of these pathways may substantially increase systemic exposure to propafenone. Likewise, patients taking concomitant inhibitors of CYP450 2D6 and 3A4 may experience similar pharmacokinetic effects. 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. Increased systemic exposure to propafenone may result in proarrhythmic events and exaggerated beta-adrenergic blocking activity.

MANAGEMENT: It may be advisable for patients to avoid the consumption of grapefruit, grapefruit juice, or supplements that contain grapefruit during treatment with propafenone.

References

  1. Botsch S, Gautier JC, Beaune P, Eichelbaum M, Kroemer HK (1993) "Identification and characterization of the cytochrome P450 enzymes involved in N-dealkylation of propafenone: molecular base for interaction potential and variable disposition of active metabolites." Mol Pharmacol, 43, p. 120-6
  2. (2011) "Product Information. Rythmol SR (propafenone)." GlaxoSmithKline
  3. (2023) "Product Information. Apo-Propafenone (propafenone)." Apotex Incorporated
  4. (2022) "Product Information. Propafenone (propafenone)." Accord-UK Ltd
View all 4 references

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Moderate

alectinib food

Applies to: Alecensa (alectinib)

ADJUST DOSING INTERVAL: Food significantly enhances the oral bioavailability of alectinib and its major active metabolite, M4. According to the manufacturer, a high-fat, high-calorie meal increased the combined systemic exposure (AUC) of alectinib and M4 by 3.1-fold following oral administration of a single 600 mg dose of alectinib.

MANAGEMENT: To ensure maximal oral absorption, alectinib should be administered with food.

References

  1. (2015) "Product Information. Alecensa (alectinib)." Genentech

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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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