Drug Interactions between aspirin / butalbital and Qulipta

GENERALLY AVOID: Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.

MANAGEMENT: The combination of ethanol and barbiturates should be avoided.

MONITOR: Coadministration with grapefruit products or green tea, inhibitors of CYP450 3A4, may increase the plasma concentrations of atogepant, which is primarily metabolized by the isoenzyme. When atogepant was administered with the potent CYP450 3A4 inhibitor itraconazole in healthy study subjects, atogepant peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 2.2- and 5.5-fold, respectively. However, moderate and weak inhibitors may interact to a much lesser extent. Population pharmacokinetic modeling has suggested that moderate (e.g., cyclosporine, ciprofloxacin, fluconazole, fluvoxamine, grapefruit juice) or weak (e.g., cimetidine, esomeprazole) CYP450 3A4 inhibitors may increase atogepant AUC by 1.7- and 1.1-fold, respectively. The changes in atogepant exposure when coadministered with moderate or weak CYP450 3A4 inhibitors are not expected to be clinically significant.

MANAGEMENT: Caution is advised for patients taking atogepant and consuming grapefruit products, large amounts of green tea beverages or green tea extract. Patients should be monitored for nausea, constipation, and fatigue.

GENERALLY AVOID: The concurrent use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol may lead to gastrointestinal (GI) blood loss. The mechanism may be due to a combined local effect as well as inhibition of prostaglandins leading to decreased integrity of the GI lining.

MANAGEMENT: Patients should be counseled on this potential interaction and advised to refrain from alcohol consumption while taking aspirin or NSAIDs.

One study has reported that coadministration of caffeine and aspirin lead to a 25% increase in the rate of appearance and 17% increase in maximum concentration of salicylate in the plasma. A significantly higher area under the plasma concentration time curve of salicylate was also reported when both drugs were administered together. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that coadministration of aspirin and caffeine may lead to higher salicylate levels faster.