FDA Reinforces Domperidone Risks, Tightening Expanded Access IND Compliance Expectations

Compliance teams managing expanded access investigational new drug applications (INDs) face sharpened scrutiny following FDA's updated guidance on domperidone, an unapproved drug with a documented history of serious cardiac and neuropsychiatric adverse events. The agency's consolidated safety communication reinforces that facilities handling domperidone under any IND pathway must maintain rigorous adverse event monitoring and reporting infrastructure.

Domperidone holds no FDA approval for any human indication. While approved in certain countries for gastrointestinal disorders, it is unapproved globally for lactation stimulation. Despite this, FDA has documented off-label use in lactating individuals and has issued cardiac risk warnings in both 2004 and 2012, citing QT prolongation, torsade de pointes, cardiac arrest, and sudden death. Those warnings remain in force.

A 2023 FDA case review added a neuropsychiatric dimension to the risk profile. Across six identified cases involving sudden discontinuation or tapering of domperidone used for lactation, adverse events included agitation, anxiety, insomnia, intrusive thoughts, suicidal ideation, and homicidal ideation. Five of the six cases involved doses of at least 90 mg per day. FDA concluded the evidence is sufficient to suggest a potential drug-event association between withdrawal and neuropsychiatric harm, a finding with direct implications for CAPA documentation and pharmacovigilance protocols at any site managing domperidone under an IND.

For QA directors and regulatory affairs leads, the operational read is grounded in 21 CFR Part 312 obligations. Expanded access INDs for domperidone are available to patients 12 years and older with certain gastrointestinal conditions, including gastroparesis and gastroesophageal reflux disease with upper GI symptoms, who have failed standard therapies. Any facility sponsoring or participating in such an IND carries full adverse event reporting obligations, including expedited reporting for unexpected serious events, consistent with ICH E2A and FDA's IND safety reporting requirements.

The excretion of domperidone in breast milk introduces an additional layer of risk assessment for any site where lactating patients may be enrolled, requiring documented informed consent procedures and infant exposure monitoring considerations within the IND protocol.

Facilities with active domperidone INDs should audit current adverse event surveillance workflows against the neuropsychiatric signal identified in FDA's 2023 review, particularly around discontinuation management and dose-tapering documentation.

Source: U.S. Food and Drug Administration, Drugs RSS Feed, May 26, 2026.