Drug Interactions between pralsetinib and Rythmol SR
This report displays the potential drug interactions for the following 2 drugs:
- pralsetinib
- Rythmol SR (propafenone)
Interactions between your drugs
propafenone pralsetinib
Applies to: Rythmol SR (propafenone) and pralsetinib
MONITOR: Pralsetinib can cause 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 clinical trials, QT prolongation occurred in 5.1% of 528 patients with non-small cell lung cancer (NSCLC) or other solid tumors. Two patients (0.4%) experienced grade 3 QT prolongation, which resolved in each case. There was no life-threatening or fatal QT prolongation. The QT interval prolongation potential of pralsetinib was assessed in 34 patients with rearranged during transfection (RET) altered solid tumors administered 400 mg once daily, and no mean increase in the corrected QT interval (QTc) greater than 20 ms was detected. 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: Some authorities recommend caution if pralsetinib is coadministered with other agents known to prolong the QT interval. 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
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- (2020) "Product Information. Gavreto (pralsetinib)." Blueprint Medicines Corporation
- (2023) "Product Information. Gavreto (pralsetinib)." Roche Products Pty Ltd, GAVRETO 20230406
Drug and food interactions
pralsetinib food
Applies to: pralsetinib
ADJUST DOSING INTERVAL: Food significantly increases the oral bioavailability of pralsetinib. According to the product labeling, administration of pralsetinib with a high-fat meal (approximately 800 to 1000 calories; 50% to 60% from fat) increased mean pralsetinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 104% and 122%, respectively. The median time to maximum concentration (Tmax) was delayed from 4 to 8.5 hours.
GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of pralsetinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. 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 exposure to pralsetinib may increase the risk of adverse effects such as musculoskeletal toxicity, fatigue, constipation, hypertension, and pneumonia.
MANAGEMENT: Pralsetinib should be administered on an empty stomach, at least 2 hours after or 1 hour before a meal. Patients should avoid consumption of grapefruit or grapefruit juice during treatment with pralsetinib.
References
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- (2020) "Product Information. Gavreto (pralsetinib)." Blueprint Medicines Corporation
- (2023) "Product Information. Gavreto (pralsetinib)." Roche Products Pty Ltd, GAVRETO 20230406
propafenone food
Applies to: Rythmol SR (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
- 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
- (2011) "Product Information. Rythmol SR (propafenone)." GlaxoSmithKline
- (2023) "Product Information. Apo-Propafenone (propafenone)." Apotex Incorporated
- (2022) "Product Information. Propafenone (propafenone)." Accord-UK Ltd
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
Drug Interaction Classification
| Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
| Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
| 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. | |
| No interaction information available. |
Further information
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