Drug Interactions between eluxadoline and nifedipine

CONTRAINDICATED: Consumption of more than 3 alcoholic beverages per day may increase the risk of acute pancreatitis during treatment with eluxadoline. Pancreatitis has been reported rarely during clinical trials of eluxadoline, and may or may not be related to sphincter of Oddi spasm.

ADJUST DOSING INTERVAL: High-fat meals may reduce the oral bioavailability of eluxadoline. In 28 healthy volunteers, administration of a single 100 mg dose of eluxadoline with a high-fat meal (approximately 800 to 1000 total calories, 50% from fat) decreased eluxadoline peak plasma concentration (Cmax) and systemic exposure (AUC) by 50% and 60%, respectively, compared to administration in the fasted state. There was no significant effect on the time to peak concentration (Tmax). The clinical relevance of this interaction is unknown. It should be noted that phase 3 clinical trials were conducted under fed conditions.

MANAGEMENT: Chronic or acute excessive use of alcohol should be avoided during treatment with eluxadoline. Alcoholism, alcohol abuse, alcohol addiction, and consumption of more than 3 alcoholic beverages per day are considered contraindications to the use of eluxadoline. The product labeling recommends taking eluxadoline with food. Patients should be advised to stop taking eluxadoline and seek medical attention if they experience potential symptoms of pancreatitis such as persistent nausea, vomiting, abdominal tenderness, and upper abdominal pain, especially that which is made worse after eating or radiates to the back or shoulders.

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GENERALLY AVOID: The consumption of grapefruit juice may be associated with significantly increased plasma concentrations of some calcium channel blockers (CCBs) when they are administered orally. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. The interaction has been reported with the dihydropyridine CCBs (in roughly decreasing order of magnitude) felodipine, nisoldipine, nifedipine, and nimodipine, often with a high degree of interindividual variability. Grapefruit juice caused more than twofold increases in felodipine, nifedipine, and nisoldipine AUCs.

MANAGEMENT: The manufacturers of nifedipine and nisoldipine recommend avoiding grapefruit juice. Patients treated orally with other calcium channel blockers should be advised to avoid consumption of large amounts of grapefruits and grapefruit juice to prevent any undue fluctuations in serum drug levels. Increased effects on blood pressure may persist for up to 4 days after the consumption of grapefruit juice. Monitoring for calcium channel blocker adverse effects (e.g., headache, hypotension, syncope, tachycardia, edema) is recommended.

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MONITOR: Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation. Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

MANAGEMENT: Caution and close monitoring for development of hypotension is advised during coadministration of these agents. Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

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MONITOR: Calcium-containing products may decrease the effectiveness of calcium channel blockers by saturating calcium channels with calcium. Calcium chloride has been used to manage acute severe verapamil toxicity.

MANAGEMENT: Management consists of monitoring the effectiveness of calcium channel blocker therapy during coadministration with calcium products.

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