Drug Interactions between Nuedexta and tirzepatide

GENERALLY AVOID: In a small, randomized, crossover study, the administration of quinidine with grapefruit juice (compared to water) to healthy volunteers significantly prolonged the time to reach peak plasma quinidine concentrations and decreased the plasma concentrations of its major metabolite, 3-hydroxyquinidine. These changes were associated pharmacodynamically with both a delay and a reduction in the maximal effect on QTc interval. The proposed mechanism is delay of gastric emptying as well as inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits.

MANAGEMENT: Given the drug's narrow therapeutic index, patients receiving quinidine therapy should avoid the consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels.

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

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

MONITOR: Glucagon-like peptide-1 (GLP-1) receptor agonists and dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists can delay gastric emptying, which may impact the absorption of concomitantly administered oral medications. Mild to moderate decreases in plasma concentrations of coadministered drugs have been demonstrated in pharmacokinetic studies for some GLP-1 receptor agonists (e.g., exenatide, lixisenatide), but not others. According to the prescribing information, liraglutide did not affect the absorption of several orally administered drugs to any clinically significant extent, including acetaminophen, atorvastatin, digoxin, griseofulvin, lisinopril, and an oral contraceptive containing ethinyl estradiol-levonorgestrel. Likewise, no clinically relevant effect on absorption was observed for concomitantly administered oral drugs studied with albiglutide (digoxin, ethinyl estradiol-norethindrone, simvastatin, warfarin), dulaglutide (acetaminophen, atorvastatin, digoxin, ethinyl estradiol-norelgestromin, lisinopril, metformin, metoprolol, sitagliptin, warfarin), or semaglutide (atorvastatin, digoxin, ethinyl estradiol-levonorgestrel, metformin, warfarin). The impact of dual GLP-1 and GIP receptor agonist tirzepatide on gastric emptying was reported to be dose- and time-dependent, with the greatest effect observed after a single 5 mg dose but diminished after subsequent doses. When acetaminophen was administered following a single 5 mg dose of tirzepatide, acetaminophen peak plasma concentration (Cmax) was decreased by 50% and its median time to peak plasma concentration (Tmax) delayed by 1 hour. However, no significant impact on acetaminophen Cmax and Tmax was observed after 4 consecutive weekly doses of tirzepatide (5 mg/5 mg/8 mg/10 mg), and the overall exposure (AUC) of acetaminophen was unaffected. Tirzepatide at lower doses of 0.5 mg and 1.5 mg also had minimal effects on acetaminophen exposure.

MANAGEMENT: Although no specific dosage adjustment of concomitant medications is generally recommended based on available data, potential clinical impact on some oral medications cannot be ruled out, particularly those with a narrow therapeutic index or low bioavailability, those that depend on threshold concentrations for efficacy (e.g., antibiotics), and those that require rapid gastrointestinal absorption (e.g., hypnotics, analgesics). Pharmacologic response to concomitantly administered oral medications should be monitored more closely following initiation, dose adjustment, or discontinuation of a GLP-1 receptor agonist or a dual GLP-1 and GIP receptor agonist.