What precautions should pharmacists take when dispensing tirzepatide with over-the-counter medications?
Executive summary
Pharmacists must actively review all patient OTCs, supplements and herbal products before dispensing tirzepatide because the drug slows gastric emptying and can alter absorption of oral medicines (including OTC analgesics and hormonal contraceptives), and hundreds of medications have reported interactions with tirzepatide in interaction databases (424 listed on Drugs.com) [1] [2]. Professional references (Drugs.com, WebMD, Mayo Clinic, Cleveland Clinic) explicitly advise patients to tell pharmacists about every OTC, vitamin or herbal product because dose changes or monitoring may be needed [3] [4] [5] [6].
1. Know the mechanism that creates most OTC risks: slowed gastric emptying and pH changes
Tirzepatide is a dual GIP/GLP‑1 receptor agonist that slows gastric emptying and may reduce gastric acid secretion; those effects can lower systemic exposure of orally absorbed medicines that require timely intestinal absorption or an acidic environment (examples named in the literature include acetaminophen and pH‑dependent drugs such as rilpivirine) [1] [5]. This pharmacologic effect is the principal reason OTC drugs taken by mouth — analgesics, antacids, antacids’ altering agents, some supplements and hormonal contraceptives — deserve pharmacist scrutiny [1] [7].
2. Screen broadly — patients must disclose ALL OTCs, vitamins and herbal products
Clinical and patient resources uniformly instruct clinicians and pharmacists to obtain a complete list of prescription and nonprescription products because many interactions are possible and may require dose changes or monitoring [3] [4] [6]. Drugs.com’s interaction checker lists 424 medications reported to interact with tirzepatide, underscoring the breadth of potential issues that extend beyond classic prescription drugs [2].
3. Watch for hypoglycemia risks when OTCs affect glucose or are used with other glucose‑lowering agents
Although this is most relevant to prescription antidiabetics, pharmacists must be alert when patients use OTC products (including unregulated supplements) that could affect appetite, weight or glucose control; tirzepatide’s glucose‑lowering effects can be additive with insulin, sulfonylureas or meglitinides, increasing hypoglycemia risk and potentially demanding dose adjustments and patient counseling [3] [8].
4. Point out specific OTC categories that need counseling or monitoring
Available reporting highlights several OTC categories of concern: acetaminophen and other oral analgesics whose absorption may be delayed; antacids or proton‑pump inhibitors and other acid‑altering OTCs that can change pH‑dependent drug absorption; and hormonal contraceptives whose effectiveness might be altered by delayed gastric emptying — all require pharmacist assessment and possible reinforcement of alternate or backup strategies [1] [8].
5. Advise on contraception and infection drugs — raise red flags when appropriate
Academic reporting specifically flags oral rilpivirine (an antiretroviral) as vulnerable to reduced absorption due to pH or gastric emptying changes from tirzepatide; by analogy, pharmacists should counsel about any oral agents with narrow absorption windows or pH dependence, and ensure patients on important OTC or prescription hormonal regimens understand the potential for reduced effectiveness [1].
6. Document, communicate and recommend monitoring or alternatives
Given the thousands of real‑world reports and rising post‑marketing data collection, pharmacists should document disclosed OTCs, communicate concerns to prescribers, and recommend monitoring (blood glucose checks, therapeutic drug monitoring when applicable) or safer alternatives (non‑oral routes or different agents) when interactions are plausible [9] [2].
7. Beware of compounded and non‑standard tirzepatide preparations
Compounded tirzepatide was subject to FDA action and is no longer an approved route as of early 2025; pharmacists should confirm patients are using FDA‑approved products (Mounjaro or Zepbound) rather than compounded versions, and counsel that compounded products are not FDA‑reviewed and have been associated with adverse reports [10] [11] [12].
8. Limitations and gaps in available reporting
Available sources document mechanism‑based interactions and list hundreds of reported interactions, but they do not provide a complete, itemized, evidence‑grade list of every OTC product with quantified clinical risk in routine practice; they also emphasize that many potential interactions remain underreported and that guidance often rests on mechanistic and post‑marketing data rather than randomized trials [2] [9]. Where specific OTC‑by‑OTC guidance is needed, the literature recommends individualized assessment and consultation with prescribers [3] [4].
Actionable takeaway: before dispensing tirzepatide, pharmacists must perform a comprehensive OTC/supplement review, document findings, counsel on delayed absorption and contraceptive/hypoglycemia implications, coordinate with prescribers for monitoring or dose changes, and verify the product is an FDA‑approved formulation [3] [2] [10].