Xanomeline/trospium-induced polyuria: A patient case report

Xanomeline/trospium is a newly approved agent for the management of schizophrenia. Unlike traditional antipsychotics, which are D₂ receptor antagonists, xanomeline is an M₁/M₄ muscarinic acetylcholine receptor agonist coformulated with trospium, a peripheral muscarinic antagonist. The addition of the trospium constituent aims to reduce or prevent the peripheral effects of muscarinic acetylcholine receptor agonism by xanomeline, which would include classic cholinergic adverse effects such as increased salivation, defecation, and urination. The package insert reports that some of the most frequently observed adverse reactions (incidence ≥5%) throughout clinical trials were those congruent with the expected anticholinergic effects of trospium, such as urinary retention and constipation, as well as other reactions that likely coincide with xanomeline use, such as nausea, vomiting, and diarrhea.1 However, there is no documented incidence of polyuria secondary to xanomeline/trospium use in the current literature. We present a case of a 53-year-old White male who was treated with xanomeline/trospium for the management of schizophrenia who experienced polyuria after a dose titration to maximum dosing of xanomeline/trospium 125 mg/30 mg by mouth twice daily. Owing to the emergence of polyuria 3 days after the dose titration, the xanomeline/trospium was discontinued after discussion with the provider, and the polyuria resolved within 1 day.