Drug Interaction Report

MONITOR: Coadministration with fostamatinib may increase the plasma concentrations of drugs that are substrates of the CYP450 3A4 isoenzyme and/or P-glycoprotein (P-gp) transporter. The proposed mechanism is decreased clearance in the intestine and/or liver due to inhibition of CYP450 3A4-mediated metabolism and P-gp-mediated efflux by fostamatinib. According to the product labeling, administration of a single 40 mg dose of the CYP450 3A4 substrate simvastatin with fostamatinib 100 mg twice daily increased simvastatin peak plasma concentration (Cmax) and systemic exposure (AUC) by 113% and 64%, respectively. In addition, simvastatin acid Cmax increased by 83% and AUC increased by 64%. When the P-gp substrate digoxin (0.25 mg once daily) was administered with fostamatinib (100 mg twice daily), digoxin Cmax and AUC increased by 70% and 37%, respectively.

MANAGEMENT: Caution is advised when fostamatinib is used concurrently with drugs that are known substrates of CYP450 3A4 and/or P-gp, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever fostamatinib is added to or withdrawn from therapy.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of zopiclone and eszopiclone. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

ADJUST DOSING INTERVAL: Administration of eszopiclone (the S-enantiomer of zopiclone) with or immediately after a high-fat/heavy meal may delay the onset of hypnotic effects. In healthy adults, administration of a 3 mg dose of eszopiclone after a high-fat meal decreased the mean peak plasma drug concentration (Cmax) by 21% and delayed the time to reach peak plasma drug concentration (Tmax) by approximately 1 hour. Theoretically, this interaction should also affect racemic zopiclone.

MANAGEMENT: Patients receiving zopiclone or eszopiclone should be advised to avoid consumption of alcohol. For faster sleep onset, it may be advisable to not administer eszopiclone and zopiclone with or immediately after a high-fat/heavy meal.