Ketorolac
| 證據等級: L5 | 預測適應症: 3 個 |
目錄
Ketorolac: From Original Indication (Data Not Available) to Headache Disorder
One-Sentence Summary
Ketorolac (DB00465) is a potent NSAID; its officially registered original indication could not be retrieved from current regulatory data. The TxGNN model predicts it may be effective for Headache Disorder, with 37 clinical trials and 19 publications currently supporting this direction — the strongest evidence base among the three candidate indications in this evaluation.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not available (no approved indication text on file) |
| Predicted New Indication | Headache Disorder |
| TxGNN Prediction Score | 99.43% |
| Evidence Level | L2 |
| Norway Market Status | Not marketed |
| Number of Authorizations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available for this record. Based on generally known pharmacology, ketorolac is a nonsteroidal anti-inflammatory drug (NSAID) of the pyrrolizine carboxylic acid class, widely used for short-term management of moderate-to-severe acute pain. Its analgesic and anti-inflammatory effects are exerted through inhibition of cyclooxygenase (COX)-mediated prostaglandin synthesis.
Prostaglandin-mediated neurogenic inflammation and vasodilation are well-established contributors to migraine and other headache pathophysiology. This provides a plausible mechanistic bridge between ketorolac's known analgesic/anti-inflammatory action and the predicted headache indication, independent of the TxGNN score alone.
Notably, this mechanistic plausibility is reinforced by substantial existing off-label clinical practice: injectable and intranasal ketorolac are already commonly used in emergency departments for acute migraine and tension-type headache, well ahead of any formal indication expansion. The volume of real-world trial and publication evidence (below) suggests the TxGNN prediction is capturing an already-active area of clinical practice rather than a purely novel hypothesis.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT02358681 | Phase 3 | Completed | 59 | Intranasal vs. IV ketorolac non-inferiority trial for pediatric migraine |
| NCT00483717 | Phase 2 | Completed | 173 | Safety, tolerability, and analgesic efficacy of intranasal ketorolac for acute migraine |
| NCT01807234 | Phase 4 | Completed | 72 | Ketorolac nasal spray vs. sumatriptan nasal spray vs. placebo for acute migraine |
| NCT01267864 | Phase 4 | Completed | 330 | IV valproate vs. metoclopramide vs. ketorolac for acute migraine |
| NCT01011673 | Phase 4 | Completed | 123 | Metoclopramide/diphenhydramine vs. ketorolac alone for tension-type headache |
| NCT01596166 | Phase 4 | Completed | 56 | IV ketorolac + metoclopramide combination for pediatric migraine in the ED |
| NCT03081416 | Phase 3 | Completed | 80 | Intranasal ketamine vs. standard therapy (incl. ketorolac) for primary headache in the ED |
| NCT01534806 | Phase 4 | Withdrawn | 0 | Prochlorperazine vs. prochlorperazine + ketorolac for pediatric migraine (not conducted) |
| NCT02664116 | Phase 4 | Unknown | 40 | IM ketorolac vs. oral diclofenac potassium for severe migraine |
| NCT03221569 | Phase 4 | Unknown | 60 | Sub-dissociative ketamine vs. ketorolac for tension-type headache |
27 additional trials are on file (mostly peri-operative pain, PDPH, or general ED headache management studies); available on request.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 9484382 | 1998 | RCT | Neurology | IM ketorolac vs. meperidine+promethazine vs. saline in tension-type headache; ketorolac showed significant effect |
| 35670115 | 2022 | RCT | Headache | IV ketorolac added to metoclopramide vs. metoclopramide alone for pediatric migraine in the ED |
| 30783794 | 2019 | RCT | Neurol Sci | Double-blind RCT comparing dexamethasone, metoclopramide, ketorolac, chlorpromazine for migraine pain relief and recurrence |
| 1514724 | 1992 | RCT | Ann Emerg Med | IM ketorolac vs. meperidine+hydroxyzine for acute migraine |
| 28286809 | 2017 | RCT | Emergency (Tehran) | Ketorolac vs. magnesium sulfate for migraine pain management |
| 35138658 | 2022 | Meta-analysis | Acad Emerg Med | Systematic review/meta-analysis confirming efficacy of parenteral ketorolac for acute migraine |
| 37849443 | 2024 | Meta-analysis | Adv Clin Exp Med | Updated systematic review comparing IV ketorolac vs. metoclopramide for migraine |
| 39674934 | 2025 | Meta-analysis | Ann Emerg Med | Bayesian network meta-analysis ranking pharmacologic therapies (incl. ketorolac) for ED migraine |
| 41321235 | 2026 | Guideline | Headache | 2025 American Headache Society update on parenteral pharmacotherapy for acute migraine in the ED |
| 24875925 | 2015 | Guideline/Review | Cephalalgia | Canadian Headache Society systematic review and recommendations on migraine treatment in emergency settings |
Norway Market Information
No marketing authorizations are currently on file for ketorolac in this dataset (total_licenses = 0). The drug's market status is recorded as not marketed.
Safety Considerations
Please refer to the package insert for safety information. No key warnings, contraindications, or drug interaction records are currently available in this evidence pack. Note: retrieval of the official product label (TFDA/equivalent) is flagged as a blocking data gap (DG001) — this must be resolved before any formal safety evaluation (S1 stage) can proceed.
Conclusion and Next Steps
Decision: Hold
Rationale: Efficacy evidence for ketorolac in headache disorder is unusually strong for a TxGNN-derived candidate — multiple completed RCTs, several meta-analyses, and an active AHS/Canadian Headache Society guideline literature base already support this use in clinical practice. However, two blocking data gaps prevent progression: (1) the official product label/warnings (DG001) are unavailable, precluding any safety assessment, and (2) the drug currently has zero marketing authorizations and is not marketed locally, so no regulatory pathway exists yet for indication expansion.
To proceed, the following is needed:
- Official TFDA (or equivalent) product label with warnings and contraindications (resolves DG001)
- Confirmed mechanism of action from DrugBank (resolves DG002)
- Drug-drug interaction data (current query returned no results)
- Clarification of local marketing/registration status and route-of-administration availability (IV/IM/intranasal), since headache-disorder evidence is concentrated in parenteral and intranasal formulations
- Formal relevance grading of the 37 clinical trials and 19 publications currently marked "pending"
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.