Ketorolac

Evidence Level: L1

Predicted Indications: 3

Ketorolac

Pharmacist Assessment Report

Ketorolac: From Allergic Conjunctivitis (Atopic, Papillary, Vernal) to Headache Disorder

One-Sentence Summary

Ketorolac is a non-steroidal anti-inflammatory drug (NSAID). The original indications in the knowledge base are atopic, papillary and vernal conjunctivitis. The TxGNN model predicts it may be effective for headache disorder (mainly migraine and tension-type headache), with 17 clinical trials and 19 publications currently supporting this direction, including several systematic reviews and meta-analyses.

Quick Overview

Item	Content
Original Indication	Atopic conjunctivitis, papillary conjunctivitis, vernal conjunctivitis (from the knowledge base; no approved indication text is available in the India licence records)
Predicted New Indication	Headache disorder
TxGNN Prediction Score	0.9943
Evidence Level	L1
India Market Status	Listed in a compiled Indian medicine price dataset (at least 20) – CDSCO approval status is not included in this data
Number of Listed Products	at least 20
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Detailed mechanism-of-action data is not currently available in the data compiled for this report. Ketorolac is a non-selective COX-1/COX-2 inhibitor (an NSAID) that reduces prostaglandin synthesis. This is a well-established mechanism for the drug class.

Its original ocular indications are inflammatory conditions of the eye surface, where reducing prostaglandins eases inflammation and discomfort. Prostaglandins also contribute to peripheral and central sensitization and neurogenic inflammation in migraine and tension-type headache. COX inhibition therefore offers a plausible analgesic mechanism for headache, and the same anti-inflammatory action explains why the model links the two conditions.

Clinical practice already reflects this link: injectable ketorolac is widely used in emergency departments for acute migraine, and several trials have tested intravenous and intranasal formulations.

Clinical Trial Evidence

Of the 17 trials in the data, the 10 most relevant are listed below. Ketorolac is the direct intervention in some and an active comparator or background therapy in others.

Trial Number	Phase	Status	Enrollment	Key Findings
NCT01807234	Phase 4	Completed	72	Ketorolac nasal spray vs sumatriptan nasal spray vs placebo for acute migraine
NCT00483717	Phase 2	Completed	173	Double-blind, placebo-controlled study of intranasal ketorolac for acute migraine
NCT01596166	Phase 4	Completed	56	IV ketorolac plus metoclopramide for pediatric migraine in the emergency department
NCT02358681	Phase 3	Completed	59	Intranasal vs intravenous ketorolac for pediatric migraine (non-inferiority)
NCT01267864	Phase 4	Completed	330	IV valproate vs IV metoclopramide vs IV ketorolac for acute migraine
NCT01011673	Phase 4	Completed	123	Metoclopramide/diphenhydramine vs ketorolac alone for tension-type headache
NCT03221569	Phase 4	Unknown	60	Ketamine vs ketorolac for tension-type headache
NCT06083571	Phase 2	Terminated	41	Intranasal ketorolac combination vs IV ketorolac regimen in pediatric migraine
NCT03081416	Phase 3	Completed	80	Intranasal ketamine vs standard therapy for primary headache in the emergency department
NCT06729047	Phase 1/2	Not yet recruiting	330	Neostigmine plus atropine vs ketorolac for post-dural puncture headache

Several other trials, including withdrawn studies with no enrollment, provide no usable efficacy data and are omitted.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
35138658	2022	Systematic review / meta-analysis	Acad Emerg Med	Efficacy of parenteral ketorolac in acute migraine attacks
37849443	2024	Systematic review / meta-analysis	Adv Clin Exp Med	IV ketorolac vs metoclopramide in adult migraine
39674934	2025	Systematic review / network meta-analysis	Ann Emerg Med	Comparative effectiveness and safety of migraine therapies in the emergency department
41321235	2026	Guideline	Headache	American Headache Society update on parenteral drugs for acute migraine in the emergency department
23298250	2013	Systematic review	Headache	Effectiveness of parenteral ketorolac in acute migraine
35670115	2022	RCT	Headache	Adding IV ketorolac to metoclopramide in children with migraine in the emergency department
30783794	2019	RCT	Neurol Sci	IV dexamethasone, metoclopramide, ketorolac and chlorpromazine compared for migraine pain relief and recurrence
24875925	2015	Systematic review / recommendations	Cephalalgia	Canadian Headache Society recommendations for migraine in emergency settings
24433525	2014	Systematic review	Headache	Parenteral treatment of episodic tension-type headache
1514724	1992	RCT	Ann Emerg Med	IM ketorolac vs meperidine plus hydroxyzine for acute migraine

India Market Information

Twenty valid single-ingredient registrations are on record, covering oral tablets (mostly dispersible), injections and ophthalmic solutions. No approved indication text is available for any of them. The five main registrations are listed below.

Authorization Number	Product Name	Dosage Form	Approved Indication
117966	Ketoserve 30mg Injection	Vial of 1 injection	Not stated
118190	Ketam Injection	Vial of 1 ml injection	Not stated
137470	Mighty Mox-KT Eye Drop	Bottle of 5 ml ophthalmic solution	Not stated
164392	Olopine-KT Eye Drop	Bottle of 5 ml eye drop	Not stated
216327	Torodent-DT Tablet	Strip of 6 dispersible tablets	Not stated

Safety Considerations

Contraindications flagged in the knowledge graph (not taken from label text): hypertension, peptic ulcer disease (including active disease), liver disease, gallbladder disease, rheumatoid arthritis, inflammatory bowel disease, asthma, diabetes mellitus, diabetic ketoacidosis, blood coagulation disorders, haemophilia, stroke and cerebrovascular disorders, myocardial infarction, anaemia and haemoglobinopathy, impaired renal function, cardiovascular and heart disease, and dry eye syndrome.
Drug Interactions: 222 interactions are recorded. The major interaction listed is acetylsalicylic acid (aspirin). Moderate interactions include corticosteroids (betamethasone, budesonide, dexamethasone, hydrocortisone), sulfonylureas (glimepiride, glipizide, glyburide, chlorpropamide, acetohexamide), exenatide, levofloxacin, kanamycin, balsalazide and fenfluramine. Minor interactions include famotidine, ranitidine, cimetidine and linaclotide. A case report also describes lithium toxicity when ketorolac was co-administered.

Package insert warnings and contraindications were not available for this report, so please refer to the package insert for the official safety information.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: Multiple completed Phase 2 to 4 trials, together with systematic reviews, meta-analyses and an updated guideline, support ketorolac for acute migraine and tension-type headache, and the drug is already widely registered in India. However, the safety profile (gastrointestinal, renal, cardiovascular and bleeding risks) requires strict controls, and the package insert data was not available.

To proceed, the following is needed:

Package insert warnings and contraindications for the India products, since the missing safety data blocks formal safety screening
Detailed mechanism of action data from DrugBank
Confirmation of the approved indications and routes of the registered injectable and nasal/oral products for headache use
Guardrails: avoid in patients with GI bleeding risk, renal impairment, cardiovascular disease or pregnancy; limit treatment duration; check drug interactions (e.g. lithium); use careful dosing in children
Disclaimer

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