Domperidone and the Risk of Serious Adverse Events

Prior treatment

• To ensure that patients are new domperidone users, the investigators will exclude those with any evidence of domperidone use in the 180 days before the index date.
• The investigators will exclude patients with a prescription for any other prokinetic drugs and non-oral study drugs in the previous 180 days (including index date) (Note: - Gastrointestinal drugs (Cisapride, Metoclopramide, Domperidone, Prucalopride, Linaclotide)).

Other illness

• Patients with a history of kidney failure (receipt of maintenance dialysis or a kidney transplant before cohort entry).

Lab values

• Patients with no serum creatinine measurement in the seven days prior to the year before the index date will be excluded. Patients with unstable baseline kidney function (i.e., if the most recent prior serum creatinine test was an inpatient test \[ER or hospitalization\] and if the corresponding eGFR differed from the most recent outpatient test by 10 mL/min/1.73 m2 or more). Previously been demonstrated that outpatient serum creatinine measurements in the province, conducted on a single occasion, indicate stable values.
• The investigators will exclude patients with eGFR ≥45 mL/min/1.73 m² - to restrict to patients with low kidney function only.

Age

• Data cleaning exclusions (e.g., missing or invalid age or sex, OHIP ineligible on index date, death on or before the index date, non-Ontario residents). The investigators anticipate that very few records will be excluded due to data cleaning.

Other

• The investigators will exclude patients with unusual daily doses of less than 10 mg/day or \>40 mg/day for domperidone. The recommended maximum daily dose for domperidone is 10 mg three times daily (30 mg/day). Some patients may require doses up to 4 times daily.
• Patients with more than one eligible domperidone prescription on the index date will be excluded, as this complicates the ability to ascertain the prescribed dose accurately.
• The investigators will exclude patients discharged from a hospital or emergency department within the two days preceding the index date. In Ontario, when patients initiate a domperidone prescription during a hospital admission, their outpatient prescription is typically dispensed on the day they are discharged or the following day.
• If more than one eligible prescription is available, restrict it to the first. The date of this prescription will be the index date.

• Older adults aged 66 years or older who filled a new oral prescription for domperidone at an outpatient pharmacy under the Ontario Drug Benefit (ODB) program from January 1, 2008, to September 30, 2024. The investigators will exclude individuals undergoing dialysis or those who have received a kidney transplant. The age criterion is set to guarantee that individuals in this population had at least one year of prior prescription drug coverage. The date when the prescription was filled will serve as the patient's entry or index date for the cohort, with each patient entering the cohort only once.