Drug Interactions between mavorixafor and MS Contin

GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics including morphine and diamorphine. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.

GENERALLY AVOID: Consumption of alcohol while taking some sustained-release formulations of morphine may cause rapid release of the drug, resulting in high systemic levels of morphine that may be potentially lethal. Alcohol apparently can disrupt the release mechanism of some sustained-release formulations. The interaction was observed in in vitro studies using a 24-hour morphine formulation (Avinza 30 mg capsule, available in the U.S. from Ligand Pharmaceuticals). When the capsule was mixed with 900 mL of buffer solutions containing ethanol 20% and 40%, the dose of morphine that was released was alcohol concentration-dependent, leading to a more rapid release of morphine. Although the clinical relevance of this finding is unknown, 'dose-dumping' into the bloodstream is conceivable.

MANAGEMENT: Until more information is available, patients taking sustained-release formulations of morphine should not consume alcohol or use medications that contain alcohol. In general, potent narcotics such as morphine or diamorphine should not be combined with alcohol.

GENERALLY AVOID: Grapefruit products may significantly increase the plasma concentrations and effects of mavorixafor, which is primarily metabolized by the isoenzyme CYP450 3A4. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. A study examining mavorixafor in combination with the strong CYP450 3A4 and P-glycoprotein inhibitor, itraconazole, suggests an increase in mavorixafor's systemic exposure (AUC) of approximately 2-fold. Clinical data with grapefruit products are not available. Pharmacokinetic interactions involving grapefruit are subject to a high degree of interpatient variability and can also be affected by the product and amount consumed; therefore, the extent to which a given patient may be affected is difficult to predict. Additionally, since mavorixafor is associated with concentration-dependent prolongation of the QT interval, increased levels may potentiate the risk of ventricular arrhythmias such as torsade de pointes and sudden death.

ADJUST DOSING INTERVAL: Food may significantly reduce the peak plasma concentration (Cmax) and systemic exposure (AUC) of mavorixafor. When a single-dose of mavorixafor (400 mg) was administered with a high-fat meal (1000 calories, 50% fat) to healthy subjects, the Cmax and AUC decreased by 66% and 55%, respectively. Similarly, when the same dose was given with a low-fat meal (500 calories, 25% fat) to healthy subjects, mavorixafor's Cmax and AUC decreased by 55% and 51%, respectively. Additionally, a single dose of mavorixafor (400 mg) administered with a low-fat meal to healthy subjects following an overnight fast resulted in a 14% higher Cmax and an 18% lower AUC than those obtained from subjects who fasted for an additional 4 hours after the dose.

MANAGEMENT: Mavorixafor should be taken on an empty stomach after an overnight fast, 30 minutes before food. Patients should be advised to avoid eating or drinking products containing grapefruit, as this could increase the risk of experiencing adverse effects from mavorixafor such as QT prolongation.