Drug Interactions between lorlatinib and Ranexa
This report displays the potential drug interactions for the following 2 drugs:
- lorlatinib
- Ranexa (ranolazine)
Interactions between your drugs
ranolazine lorlatinib
Applies to: Ranexa (ranolazine) and lorlatinib
CONTRAINDICATED: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of ranolazine, which is primarily metabolized by the isoenzyme. In pharmacokinetic studies, the potent inducer rifampin (600 mg once a day) has been shown to reduce the plasma concentrations of ranolazine (1000 mg twice a day) by approximately 95%. No data are available for other CYP450 3A4 inducers.
MANAGEMENT: The manufacturer considers the use of ranolazine to be contraindicated in patients taking potent CYP450 3A4 inducers such as carbamazepine, enzalutamide, lumacaftor, mitotane, phenobarbital, phenytoin, primidone (partially metabolized to phenobarbital), rifamycins, and St. John's wort. The extent to which other, less potent CYP450 3A4 inducers may interact with ranolazine is unknown. Caution is advised if they are used with ranolazine.
References
- (2006) "Product Information. Ranexa (ranolazine)." Calmoseptine Inc
Drug and food interactions
ranolazine food
Applies to: Ranexa (ranolazine)
GENERALLY AVOID: Grapefruit and grapefruit juice may significantly increase the plasma concentrations of orally administered ranolazine. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Because ranolazine prolongs QT interval in a dose-dependent manner, high plasma levels of ranolazine may increase the risk of ventricular arrhythmias such as ventricular tachycardia, ventricular fibrillation, and torsade de pointes.
MANAGEMENT: Patients treated with ranolazine should avoid consumption of grapefruit juice and other grapefruit products if possible. Otherwise, the dosage of ranolazine should be limited to 500 mg twice a day.
References
- (2006) "Product Information. Ranexa (ranolazine)." Calmoseptine Inc
lorlatinib food
Applies to: lorlatinib
GENERALLY AVOID: Grapefruit and grapefruit juice may significantly increase the plasma concentrations of lorlatinib. 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.
MANAGEMENT: Patients treated with lorlatinib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. If coadministration is unavoidable, some authorities recommend reducing the initial dosage of lorlatinib from 100 mg orally once daily to 75 mg orally once daily. In patients who have had a dosage reduction to 75 mg orally once daily due to adverse reactions, the lorlatinib dosage should be further reduced to 50 mg orally once daily upon initiation of a potent CYP450 3A4 inhibitor. After 3 plasma half-lives following discontinuation of the potent CYP450 3A4 inhibitor, the lorlatinib dosage may be increased to that used prior to initiation of the inhibitor.
References
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- (2018) "Product Information. Lorbrena (lorlatinib)." Pfizer U.S. Pharmaceuticals Group
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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