COMMENTARY

Domperidone for Gastroparesis: Beware of Drug Interactions

David A. Johnson, MD

Disclosures

September 11, 2017

Domperidone as an Alternative for Gastroparesis

Clinicians know well that the pharmacologic options for the treatment of gastroparesis are extremely limited, particularly in the United States. Currently, metoclopramide is the only prokinetic approved by the US Food and Drug Administration (FDA) for this indication. The potential for side effects with metoclopramide is well recognized and may occur in up to 40% of patients.[1]

The recent American College of Gastroenterology (ACG) guideline on gastroparesis[2] states: "For patients unable to use metoclopramide, domperidone can be prescribed with investigational new drug clearance from the Food and Drug Administration (FDA) and has been shown to be as effective as metoclopramide in reducing symptoms without the propensity for causing central nervous system side effects..."

Domperidone is a peripherally selective D2 dopamine receptor antagonist used as an antiemetic, gastroprokinetic agent, and galactagogue and is widely available in most countries in the world.[2,3,4] Domperidone has been extensively used over the past 30-plus years for gastroparesis, although there are only a few well-controlled, double-blind studies of patients with gastroparesis directly comparing the efficacy of domperidone with other prokinetic agents, such as metoclopramide and cisapride, which is no longer available.[2,3] In the United States, domperidone is not FDA-approved due to the concerns for public health risks. However, it may be available at select compounding pharmacies with a doctor's prescription using the Expanded Access to Investigational Drugs program.[5] Otherwise, most patients obtain it through foreign pharmacies, particularly Canadian pharmacies.

Serious risks associated with domperidone include cardiac arrhythmias, cardiac arrest, and sudden death. Domperidone may prolong the QT interval and cause life-threatening arrhythmias; torsades de pointes has been described with its use. These risks are related to the serum level of domperidone, and higher levels are associated with greater risks for these events.[4,5]The ACG guideline on gastroparesis[2] recommends that "Given the propensity of domperidone to prolong corrected QT interval on electrocardiogram and to rarely cause cardiac arrhythmias, a baseline electrocardiogram is recommended and treatment with this agent should be withheld if the corrected QT is > 470 ms in male and over 450 ms in female patients. Follow-up electrocardiogram on domperidone is also advised..."

Domperidone Drug Interactions Are Serious

It is extremely important that prescribers and patients using this drug are aware of the risk for drug interactions and pay particular attention to two types of drugs that may interact with domperidone[4]:

  • Those that inhibit cytochrome P450-3A4 (including some antiemetics and antidepressants frequently coadministered in patients with gastroparesis), thereby increasing serum levels of domperidone (and subsequent risk for QTc prolongation).

  • Those that prolong the QT interval (including some antimicrobials, antifungal agents, and ondansetron), thus enhancing overall risk for QT prolongation and the overall increase of the QT interval.

There is limited prescribing information emphasizing the possible interaction between domperidone and other QT-prolonging drugs.

More important, given that this is not an FDA-approved drug, it would not appear on the pharmacy listing nor on the electronic medical record (EMR) to enable a cross-check for potential drug-drug interactions. Accordingly, patients, prescribers, and pharmacists would probably not recognize the potential increased risk for cardiac arrhythmias and sudden death resulting from these interactions and inadequate cardiac monitoring.

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