Meperidine
| Evidence Level: L3 | Predicted Indications: 10 |
Table of Contents
Meperidine: From Opioid Analgesia to Headache Disorder
One-Sentence Summary
Meperidine (pethidine) is a mu-opioid analgesic, and its Singapore registration is for an injectable solution; no approved indication text is recorded in the data compiled for this report. The TxGNN model predicts it may be effective for headache disorder (the highest-ranked prediction with real literature support; the top-ranked prediction overall is Tourette syndrome, which has no evidence). Currently there are 0 registered clinical trials and 18 publications for headache disorder, mostly historical emergency-department studies in which meperidine was often a comparator rather than a favoured treatment.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded (the Singapore licence has no approved indication text) |
| Predicted New Indication | Headache disorder (rank 3 of 10; see note below) |
| TxGNN Prediction Score | 98.69% |
| Evidence Level | L3 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 1 |
| Recommended Decision | Hold |
Note on selection: The top-ranked prediction, Tourette syndrome (99.46%), and the second-ranked, trichotillomania (99.39%), have no trials or literature (evidence level L5), so this report focuses on headache disorder, the best-supported candidate. Its evidence level is L3 because it rests on systematic reviews and meta-analysis rather than completed Phase 3 trials.
Why is This Prediction Reasonable?
Detailed mechanism-of-action data is not available in the data compiled for this report. Based on known information, meperidine is a mu-opioid agonist with analgesic effects (and weak serotonergic and anticholinergic activity). Its efficacy for pain has long been established, and mechanistically it may be applicable to severe headache pain.
Historically, meperidine has been given by injection for acute migraine in emergency departments, and North American emergency departments have used it widely. This is the main reason the prediction is plausible: the link is analgesic rather than disease-modifying.
However, the available comparative data do not show a clear advantage. Guideline-type reviews generally discourage opioids for migraine because of dependence, medication-overuse headache and rebound risk. Evidence is real but limited and mostly historical. Full texts and effect sizes were not available for review.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 18632186 | 2008 | Meta-analysis of RCTs | Ann Emerg Med | Compares the relative efficacy and adverse effects of meperidine versus non-opioid comparators in acute migraine; notes that guidelines advise against opioids as first-line treatment despite common ED use |
| 1514724 | 1992 | RCT | Ann Emerg Med | Randomized, double-blind comparison of IM ketorolac versus meperidine plus hydroxyzine in acute migraine |
| 2705667 | 1989 | RCT | Ann Emerg Med | IV chlorpromazine versus IV meperidine with dimenhydrinate in migraine refractory to oral medications |
| 25600718 | 2015 | Evidence assessment / guideline review | Headache | American Headache Society update of the evidence for acute migraine pharmacotherapies |
| 24875925 | 2015 | Systematic review | Cephalalgia | Canadian Headache Society recommendations for migraine pain treatment in emergency settings |
| 24433525 | 2014 | Systematic review | Headache | Parenteral treatments for episodic tension-type headache in acute care settings |
| 10986188 | 2000 | Review | West J Med | Reviews ED migraine therapies, including pethidine (meperidine) |
| 22404708 | 2012 | Review | Headache | Rescue therapy for acute migraine, part 3: opioids, NSAIDs, steroids |
| 34806767 | 2021 | Narrative review | Headache | Second-line injectable options for migraine in the ED after first-line failure |
| 7893296 | 1995 | Comparative study | Am J Emerg Med | IM ketorolac versus meperidine plus promethazine in 42 ED migraine patients |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN14662P | Pethidine-hameln Solution for Injection 50mg/ml | Injection, solution | Not recorded |
Safety Considerations
- Disease contraindications flagged by the knowledge graph (not package-insert text): liver failure and liver disease, epilepsy, chronic obstructive pulmonary disease, respiratory failure, sleep apnoea syndromes, hypothyroidism/myxedema, Addison disease, peptic ulcer disease, benign prostatic hyperplasia, hypotensive disorder, substance abuse/dependence, sickle cell anaemia, angle-closure glaucoma, hyperbilirubinaemia/Gilbert syndrome, gallbladder disease, thrombophlebitis, and several movement disorders (basal ganglia disease, focal hand dystonia, blepharospasm).
- Drug interactions: 100 interactions were identified; the main major ones are with alvimopan, bupropion, morphine, lorcaserin, dolasetron and palonosetron. Examples of moderate interactions include hyoscyamine, loperamide, atropine, glycopyrronium, cimetidine, naloxone, eluxadoline and dronabinol.
- Neuropsychiatric toxicity: The literature reports psychotic symptoms with meperidine intoxication, consistent with accumulation of the normeperidine metabolite.
Please also refer to the package insert for key warnings and contraindications, which were not available in the data compiled for this report.
Conclusion and Next Steps
Decision: Hold
Rationale: Evidence for headache disorder is limited to small, mostly historical emergency-department studies and reviews where meperidine is typically a comparator without a demonstrated advantage. Guidelines discourage opioids for migraine because of dependence, medication-overuse and rebound risk. The other nine predictions (including Tourette syndrome and trichotillomania) have no supporting evidence, and several have mechanistic directions that are questionable or point to harm.
To proceed, the following is needed:
- Package insert warnings and contraindications from the HSA (a blocking gap for safety screening)
- Mechanism-of-action data from DrugBank
- Full-text review of the key RCTs and the meta-analysis (PMID 18632186) to extract effect sizes versus non-opioid comparators
- Confirmation of the approved indication for the Singapore licence
- Assessment of whether any benefit outweighs dependence, medication-overuse headache and normeperidine neurotoxicity risks, compared with guideline-recommended first-line agents
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.