Cyclobenzaprine
| Evidence Level: L2 | Predicted Indications: 3 |
Table of Contents
- Cyclobenzaprine
- Pharmacist Assessment Report
- Cyclobenzaprine: From Muscle Spasm Treatment to Myofascial Pain Syndrome
- One-Sentence Summary
- Quick Overview
- Why is This Prediction Reasonable?
- Clinical Trial Evidence
- Literature Evidence
- India Market Information
- Safety Considerations
- Conclusion and Next Steps
- Disclaimer
Cyclobenzaprine: From Muscle Spasm Treatment to Myofascial Pain Syndrome
One-Sentence Summary
Cyclobenzaprine is a centrally acting skeletal muscle relaxant that is marketed in India in many oral formulations. The TxGNN model predicts it may be effective for myofascial pain syndrome, with 10 related clinical trials and 5 publications compiled for this report. Most of the trials are in fibromyalgia, not myofascial pain, so direct evidence is limited.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the India license records (the approved indication text is blank for all registrations) |
| Predicted New Indication | Myofascial pain syndrome |
| TxGNN Prediction Score | 0.9909 |
| Evidence Level | L2 |
| 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?
Cyclobenzaprine is structurally related to tricyclic antidepressants. It acts mainly in the brainstem, where it reduces tonic somatic motor activity. This effect is linked to 5-HT2 receptor antagonism, with additional antihistaminic and anticholinergic activity. Detailed mechanism of action data was not available in the drug record, so this description comes from the repurposing analysis.
Myofascial pain syndrome involves muscle spasm and painful trigger points. A drug that reduces muscle spasm is a direct pharmacological fit for this condition. The use of cyclobenzaprine in painful musculoskeletal conditions supports the prediction.
The other two predictions are much weaker. Neuralgia has only an indirect rationale through the tricyclic structure and no controlled evidence. Papillary conjunctivitis has no clear mechanistic link, and its score from the TxGNN model (deep learning) may reflect similarities the model learned between related diseases, not biological evidence. Both are rated Hold.
Clinical Trial Evidence
Only one registered trial is in a myofascial pain setting, and it tests a procedure rather than cyclobenzaprine. The other trials mostly test the sublingual cyclobenzaprine formulation TNX-102 SL in fibromyalgia, so they are adjacent evidence only.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT04704297 | Phase 4 | Recruiting | 180 | Trigger point injection for low back myofascial pain; the intervention is a procedure, not cyclobenzaprine |
| NCT01041495 | Phase 4 | Terminated | 37 | Cyclobenzaprine ER (Amrix) augmentation for fibromyalgia fatigue and muscle pain; small and stopped early |
| NCT01903265 | Phase 2/3 | Completed | 205 | TNX-102 SL 2.8 mg at bedtime in fibromyalgia; placebo-controlled dose-finding |
| NCT02436096 | Phase 3 | Completed | 519 | TNX-102 SL vs placebo in fibromyalgia over 12 weeks |
| NCT04172831 | Phase 3 | Completed | 503 | TNX-102 SL 5.6 mg vs placebo in fibromyalgia over 14 weeks |
| NCT04508621 | Phase 3 | Completed | 514 | TNX-102 SL 5.6 mg vs placebo in fibromyalgia over 14 weeks |
| NCT05273749 | Phase 3 | Completed | 457 | TNX-102 SL 5.6 mg vs placebo in fibromyalgia over 14 weeks |
| NCT02829814 | Phase 3 | Terminated | 51 | TNX-102 SL vs placebo in fibromyalgia; ended early with little information |
| NCT02015234 | Phase 3 | Completed | 158 | 12-month open-label safety extension of TNX-102 SL in fibromyalgia |
| NCT02589275 | Phase 3 | Completed | 375 | 3-month open-label extension of TNX-102 SL in fibromyalgia; safety and tolerability data |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 12764337 | 2003 | RCT | Annals of Emergency Medicine | Cyclobenzaprine plus ibuprofen vs ibuprofen alone in acute myofascial strain (double-blind) |
| 11889661 | 2002 | RCT | Journal of Orofacial Pain | Clonazepam or cyclobenzaprine vs placebo added to self-care for jaw pain on awakening |
| 24822235 | 2014 | RCT | Journal of Oral & Facial Pain and Headache | Cyclobenzaprine, tizanidine or placebo added to education and self-care in myofascial jaw pain |
| 20673246 | 2011 | RCT | Pain Practice | Acupuncture vs trigger point injection combined with cyclobenzaprine and dipyrone for myofascial trigger point pain |
| 3464212 | 1986 | Review | American Journal of Medicine | Clinical overview of fibrositis, a musculoskeletal pain disorder with tender points |
India Market Information
Twenty valid single-ingredient registrations are on file. The approved indication text is blank for all of them. Five are listed below.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 247698 | Zaprinmax 15mg Capsule ER | Extended-release capsule | Not stated |
| 28194 | Blobenz 5mg Tablet | Tablet | Not stated |
| 84163 | Flexabenz Tablet | Tablet | Not stated |
| 199658 | Skelebenz 15 Capsule ER | Extended-release capsule | Not stated |
| 139937 | Mobrine 5mg Tablet IR | Immediate-release tablet | Not stated |
All formulations are oral (immediate-release, extended-release and sustained-release tablets and capsules).
Safety Considerations
- Contraindications suggested by the knowledge graph (these are model-derived links, not label text): liver failure, open-angle glaucoma, glaucoma, sudden cardiac arrest, heart conduction disease, atrioventricular block, heart block, hyperthyroidism, Graves disease and thyrotoxicosis.
- Drug Interactions: 236 interactions were recorded. Major interactions include:
- Bupropion
- Morphine
- Potassium citrate
- Dexfenfluramine
- Fenfluramine
Moderate interactions are mostly with anticholinergic drugs (hyoscyamine, atropine, glycopyrronium, dicyclomine, clidinium, methscopolamine, mepenzolate), and also with loperamide, aprepitant, dronabinol and eluxadoline.
Please refer to the package insert for label warnings and contraindications, which were not available for this report.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: The muscle-relaxant mechanism fits myofascial pain well, and randomised trials in myofascial strain and myofascial jaw pain used cyclobenzaprine. However, the large Phase 3 programme is in fibromyalgia, and no completed trial tests cyclobenzaprine specifically in myofascial pain syndrome. The evidence is supportive but not definitive. The study listing also shows no completed Phase 3 RCTs in this indication, so the L2 level should be treated cautiously.
To proceed, the following is needed:
- Package insert warnings and contraindications for the Indian products, which are a blocking gap for safety screening
- The approved indication wording for the Indian registrations
- Detailed mechanism of action data from DrugBank
- A controlled trial of cyclobenzaprine in myofascial pain syndrome
- A safety plan for patients with glaucoma, cardiac conduction disease or hyperthyroidism, and for those taking serotonergic or anticholinergic drugs
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.