Drug Interactions between lacosamide and lorlatinib
This report displays the potential drug interactions for the following 2 drugs:
- lacosamide
- lorlatinib
Interactions between your drugs
lacosamide lorlatinib
Applies to: lacosamide and lorlatinib
MONITOR: Lacosamide has been shown to prolong the PR interval of the electrocardiogram in some patients. Theoretically, coadministration with other agents that prolong the PR interval (e.g., beta blockers, calcium channel blockers, digoxin, atazanavir, mefloquine) may result in elevated risk of conduction disturbances and atrioventricular block. Dose-dependent prolongations in PR interval have been observed in clinical studies of lacosamide in both patients and healthy volunteers. In clinical trials of patients with partial-onset epilepsy, asymptomatic first-degree atrioventricular (AV) block was observed as an adverse reaction in 0.4% (4/944) of patients randomized to receive lacosamide and 0% (0/364) of patients randomized to receive placebo. In clinical trials of patients with diabetic neuropathy, asymptomatic first-degree AV block was observed as an adverse reaction in 0.5% (5/1023) of patients receiving lacosamide and 0% (0/291) of patients receiving placebo.
MANAGEMENT: Caution is advised if lacosamide is used concomitantly with other agents that prolong the PR interval, especially in the elderly and patients with known conduction problems (e.g., marked first-degree AV block, second-degree or higher AV block and sick sinus syndrome without pacemaker) or severe cardiac disease such as myocardial ischemia or heart failure. An ECG should be obtained in these patients before initiating lacosamide and after titration to steady-state. Patients should be advised to notify their physician if they experience dizziness, lightheadedness, fainting, or irregular heartbeat.
References
- (2008) "Product Information. Vimpat (lacosamide)." UCB Pharma Inc
Drug and food interactions
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
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.
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