Ketorolac

Evidence Level: L1

Predicted Indications: 3

Ketorolac

Pharmacist Assessment Report

Ketorolac: From Atopic, Papillary and Vernal Conjunctivitis to Headache Disorder

One-Sentence Summary

Ketorolac is a non-steroidal anti-inflammatory drug (NSAID) whose original indications in the knowledge base are atopic, papillary and vernal conjunctivitis. The TxGNN model predicts it may be effective for headache disorder (especially acute migraine and tension-type headache), with 17 clinical trials and 18 publications currently supporting this direction.

Quick Overview

Item	Content
Original Indication	Atopic conjunctivitis, papillary conjunctivitis, vernal conjunctivitis
Predicted New Indication	Headache disorder
TxGNN Prediction Score	0.9943
Evidence Level	L1
Canada Market Status	Marketed (marketed DINs: 11 of 14; dormant: 1; cancelled: 2)
Number of DINs	14 (marketed: 11)
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Detailed mechanism of action data is not available in the data compiled for this report. Based on established NSAID pharmacology, ketorolac is a non-selective COX-1/COX-2 inhibitor. By blocking prostaglandin synthesis, it reduces peripheral and central sensitization and neurogenic inflammation, which contribute to migraine and tension-type headache pain.

Its original indications are inflammatory eye conditions, where reducing prostaglandin-driven inflammation is the benefit. The same anti-inflammatory and analgesic action is plausible for headache pain. This link rests on general NSAID pharmacology, not on the supplied data, but it is consistent with the clinical evidence below. Parenteral ketorolac is already used in emergency departments for acute migraine.

Clinical Trial Evidence

The 17 registered trials include several direct tests of ketorolac. The table lists the 10 most relevant.

Trial Number	Phase	Status	Enrollment	Key Findings
NCT01807234	Phase 4	Completed	72	Ketorolac nasal spray vs sumatriptan nasal spray vs placebo for acute migraine
NCT01596166	Phase 4	Completed	56	IV ketorolac plus metoclopramide for pediatric migraine in the emergency department
NCT01011673	Phase 4	Completed	123	Metoclopramide/diphenhydramine vs ketorolac alone for tension-type headache (ketorolac as comparator)
NCT00483717	Phase 2	Completed	173	Double-blind, placebo-controlled study of intranasal ketorolac for acute migraine
NCT02358681	Phase 3	Completed	59	Intranasal vs IV ketorolac for pediatric migraine (non-inferiority)
NCT01267864	Phase 4	Completed	330	IV valproate vs IV metoclopramide vs IV ketorolac for acute migraine
NCT03221569	Phase 4	Unknown	60	Ketamine vs ketorolac for tension-type headache
NCT06083571	Phase 2	Terminated	41	Intranasal ketorolac cocktail vs IV ketorolac cocktail in pediatric migraine; ended early
NCT03066544	Phase 1/2	Unknown	50	Responders vs non-responders in status migrainosus; ketorolac role not isolated
NCT06729047	Phase 1/2	Not yet recruiting	330	Neostigmine plus atropine vs ketorolac for post-dural puncture headache prevention

Literature Evidence

PMID	Year	Type	Journal	Key Findings
35138658	2022	Meta-analysis	Acad Emerg Med	Efficacy of parenteral ketorolac in acute migraine attacks
23298250	2013	Systematic review	Headache	Effectiveness of parenteral ketorolac in acute migraine; evidence described as conflicting
37849443	2024	Systematic review / meta-analysis	Adv Clin Exp Med	IV ketorolac vs metoclopramide in adult migraine
41321235	2026	Guideline	Headache	American Headache Society 2025 update on parenteral therapies for acute migraine in the emergency department
24875925	2015	Systematic review / guideline	Cephalalgia	Canadian Headache Society recommendations on migraine pain treatment in emergency settings
25600718	2015	Guideline	Headache	American Headache Society evidence assessment of acute migraine pharmacotherapies
35670115	2022	RCT	Headache	Adding IV ketorolac to metoclopramide vs metoclopramide alone in children with migraine in the emergency department
24433525	2014	Systematic review	Headache	Parenteral treatment of episodic tension-type headache
26790849	2016	Systematic review	Headache	Acute treatments for pediatric migraine in the emergency department
1514724	1992	RCT	Ann Emerg Med	IM ketorolac vs meperidine plus hydroxyzine in acute migraine (double-blind)

Canada Market Information

Approved indication text and dosage form were not available in the compiled data.

DIN	Product Name	Dosage Form	Approved Indication
02369362	ACUVAIL	Not available	Not available
02245821	KETOROLAC	Not available	Not available
02162644	TORADOL IM	Not available	Not available
01968300	ACULAR	Not available	Not available
02390582	KETOROLAC TROMETHAMINE INJECTION USP	Not available	Not available

Safety Considerations

Contraindications (from knowledge-graph drug–disease edges, not label text): hypertension, gastric and peptic ulcer disease (including active), liver disease, gallbladder disease, rheumatoid arthritis, inflammatory bowel disease, asthma (intrinsic and allergic), diabetes mellitus and diabetic ketoacidosis, blood coagulation disorders and hemophilia, stroke and cerebrovascular disorders, cerebral infarction, myocardial infarction and coronary thrombosis, hemoglobinopathy and anemia, impaired renal function, cardiovascular and heart disease, and dry eye syndrome.
Safety signal in the literature: a case report describes renal papillary necrosis after emergency treatment of migraine with parenteral DHE, sumatriptan and ketorolac. Another case report describes lithium toxicity when ketorolac was co-administered.
Drug interactions: 100 interactions were identified; 20 are shown in the compiled data.
- Major: acetylsalicylic acid.
- Moderate: sulfonylureas (acetohexamide, chlorpropamide, glimepiride, glipizide, glyburide), corticosteroids (betamethasone, budesonide, dexamethasone, hydrocortisone), balsalazide, exenatide, fenfluramine, dexfenfluramine, kanamycin and levofloxacin.
- Minor: famotidine, ranitidine, cimetidine and linaclotide.
Package insert warnings were not available in the compiled data. Please refer to the Health Canada package insert for full safety information.

Other Predicted Indications (Lower Priority)

Predicted Indication	TxGNN Score	Evidence Level	Decision	Comment
Rosacea conjunctivitis	0.9940	L5	Hold	No trials or literature. Plausible because ketorolac is already used in related ocular inflammatory conditions, but this is a prediction only.
Trigeminal autonomic cephalalgia	0.9939	L4	Hold	The only trial was withdrawn with no enrolment. These headaches (e.g., cluster headache) generally respond poorly to NSAIDs.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: Several completed Phase 3/4 trials, meta-analyses and guidelines support parenteral ketorolac for acute migraine and tension-type headache, and the drug is already widely marketed in Canada. Known NSAID risks (renal toxicity, GI bleeding, cardiovascular events) and many interactions require explicit limits on dose and treatment duration.

To proceed, the following is needed:

Health Canada package insert warnings and contraindications (a blocking gap for safety screening)
Detailed mechanism of action data
Approved indication text and dosage forms for the Canadian licences, to confirm which formulations (e.g., injection vs ophthalmic) match headache use
A screening protocol for renal function, GI bleeding risk and cardiovascular history, and a check of concomitant medications (e.g., lithium, aspirin)
Route compatibility assessment for the intended headache formulations (IV, IM, intranasal)
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.