Drug Interactions between tirzepatide and Wegovy

ADJUST DOSING INTERVAL: Taking oral semaglutide with food, beverage, or other oral medications may alter semaglutide absorption and exposure. In a controlled study with healthy volunteers, limited or no measurable semaglutide exposure was observed in subjects that were fed 30 minutes prior to taking oral semaglutide, while all subjects that fasted overnight and 30 minutes after the oral semaglutide dose had measurable semaglutide exposure. Area under the curve (AUC) and semaglutide peak plasma concentration (Cmax) were approximately 40% greater in subjects that fasted compared to those who did not. AUC and Cmax were also increased with a post-dose fasting period greater than 30 minutes.

MANAGEMENT: It is recommended that oral semaglutide be taken 30 minutes before the first food, beverage, or other oral medications of the day with no more than 4 ounces of plain water to ensure its efficacy. Fasting longer than 30 minutes after the oral semaglutide dose may lead to increased gastrointestinal side effects including nausea, vomiting, or diarrhea.

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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.

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The recommended maximum number of medicines in the 'incretin-based therapies' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'incretin-based therapies' category:

• tirzepatide
• Wegovy (semaglutide)

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.