Domperidone
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Domperidone: From Upper Gastrointestinal Symptoms to Headache Disorder
One-Sentence Summary
Domperidone is a peripheral dopamine D2/D3 receptor antagonist, used as an antiemetic and prokinetic agent for dyspepsia, nausea and vomiting. The TxGNN model's top-ranked prediction is nephrogenic syndrome of inappropriate antidiuresis, but it has no supporting evidence. The best-supported prediction is headache disorder (mainly migraine), with 0 clinical trials and 20 publications, most of them reviews supporting adjunctive use for migraine-associated nausea.
Note: Only 10 of the 20 publications for headache disorder were available in the data compiled for this report. The assessment below is based on those 10.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the Singapore licence records. Pharmacology data describe use for dyspepsia, heartburn, epigastric pain, nausea and vomiting |
| Predicted New Indication | Headache disorder (rank 4 of the top 10; the rank 1 prediction, nephrogenic syndrome of inappropriate antidiuresis, has no supporting evidence) |
| TxGNN Prediction Score | 96.72% (headache disorder); rank 1 prediction: 99.08% |
| Evidence Level | L4 (headache disorder); L5 for rank 1 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 9 |
| Recommended Decision | Hold (overall); headache disorder is a research question |
Why is This Prediction Reasonable?
Detailed mechanism of action data are not available in the compiled data. From the pharmacology information, domperidone blocks dopamine D2 and D3 receptors. It does not readily cross the blood-brain barrier, so its effects are mainly peripheral. It is used as an antiemetic and an upper gastrointestinal prokinetic.
The rank 1 prediction (nephrogenic syndrome of inappropriate antidiuresis) is caused by a gain-of-function change in the vasopressin V2 receptor. No plausible link to dopamine antagonism can be established from the available data. The same applies to most other top-10 predictions (Plasmodium falciparum malaria, collagenopathy, RAAS-blocker-induced angioedema, lymphocytic hypereosinophilic syndrome, hypertrichosis). These remain computational predictions only.
Headache disorder is the one prediction with a plausible rationale. Migraine attacks are often accompanied by nausea, vomiting and delayed gastric emptying (gastric stasis). The literature describes domperidone, like metoclopramide, as an adjunct that relieves nausea and may improve the absorption of oral analgesics and triptans. The evidence supports symptomatic or adjunctive use rather than a direct effect on the headache itself.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
Selected from the 10 publications available for headache disorder, with priority given to the more directly relevant ones (the remaining studies were not individually classified):
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 11191009 | 2000 | Randomised primary care study | Curr Med Res Opin | Fixed combination of domperidone and paracetamol compared with sumatriptan 50 mg in 120 patients with moderate to severe migraine |
| 27837002 | 2016 | Cohort/Retrospective safety study | Neurology | Safety of domperidone for nausea associated with dihydroergotamine infusion and headache |
| 23968886 | 2013 | Guideline | Can J Neurol Sci | Canadian Headache Society guideline on acute drug therapy for migraine |
| 25877672 | 2015 | Review | Headache | Review of office-based acute migraine therapy in adults |
| 12463273 | 2001 | Review | Curr Med Res Opin | Metoclopramide and domperidone have an added prokinetic effect that may help overcome gastric stasis and improve oral drug absorption in migraine |
| 17924297 | 2007 | Review | Dtsch Med Wochenschr | Combining prokinetic/antiemetic drugs such as domperidone with NSAIDs for mild to moderate migraine attacks |
| 10494007 | 1999 | Review | Can J Clin Pharmacol | Prokinetic antiemetics may improve gastrointestinal absorption of analgesics and triptans |
| 8749241 | 1995 | Review | Cephalalgia | Domperidone 20 mg orally commonly used as an antiemetic alongside analgesics or ergot preparations |
| 9876882 | 1998 | Review | Cephalalgia | Role of antiemetics and prokinetic agents in migraine treatment strategies |
| 38822165 | 2024 | Review | CNS Drugs | Pharmacotherapy options in the premonitory phase of migraine |
For the other predictions, the only literature was for common cold (one case report of anaphylaxis to levodropropizine, which does not concern domperidone and is likely an artifact of co-mentioned terms) and allergic urticaria (a pregnancy medication appropriateness study and a Kounis syndrome case report with prolonged QT, neither showing benefit). Other predictions have no literature.
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN02500P | MOTILIUM TABLET 10 mg | Tablet, film coated | Not recorded |
| SIN02891P | MOTILIUM SUSPENSION 1 mg/ml | Suspension | Not recorded |
| SIN10187P | DOMPEL TABLET 10 mg | Tablet | Not recorded |
| SIN10198P | GASTRIUM TABLET 10 mg | Tablet | Not recorded |
| SIN09583P | DOMPER SUPPOSITORY 10 mg | Suppository | Not recorded |
There are 9 valid single-ingredient registrations in total. Available forms include oral tablets, suspension and suppository.
Safety Considerations
- Contraindications suggested by the knowledge graph (derived from drug-disease relationships, not from label text): long QT syndrome, familial long QT syndrome, torsades de pointes, liver disease, gallbladder disease.
- QT prolongation is a key concern. It would need particular attention for co-use with other QT-prolonging drugs (for example, some antimalarials), and the case report in the allergic urticaria literature also flags a QT signal.
- Drug interactions: The interaction data contain only pharmacological targets (dopamine D2 and D3 receptors), not specific interacting drugs.
Please refer to the package insert for further safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: Nine of the ten top predictions, including the top-ranked one, have no clinical or literature support and no plausible mechanism, so they remain computational predictions at L5. Headache disorder (migraine) is the only one with a plausible role and is best treated as a research question at L4. The evidence supports adjunctive relief of nausea and possible absorption benefits, not direct headache treatment, and no registered trials exist. QT-related safety must also be weighed.
To proceed, the following is needed:
- Singapore package insert warnings and contraindications (a blocking gap for safety screening)
- Mechanism of action data from DrugBank
- Approved indication text for the Singapore licences
- Controlled trial evidence for domperidone in migraine, with a cardiac safety (QT) assessment
- Review of the full set of 20 headache publications, since only 10 were available
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.