Cyclobenzaprine
| Evidence Level: L3 | Predicted Indications: 3 |
Table of Contents
- Cyclobenzaprine
- Pharmacist Assessment Report
- Cyclobenzaprine: From Muscle Spasm (Musculoskeletal Conditions) to Myofascial Pain Syndrome
- One-Sentence Summary
- Quick Overview
- Why is This Prediction Reasonable?
- Clinical Trial Evidence
- Literature Evidence
- Canada Market Information
- Safety Considerations
- Conclusion and Next Steps
- Disclaimer
Cyclobenzaprine: From Muscle Spasm (Musculoskeletal Conditions) to Myofascial Pain Syndrome
One-Sentence Summary
Cyclobenzaprine is a centrally acting skeletal muscle relaxant. It is marketed in Canada under 10 licences, and the data compiled for this report do not include approved indication text. The TxGNN model predicts it may be effective for myofascial pain syndrome, with 10 clinical trials and 5 publications listed for this direction. Most of the trials, however, test a sublingual formulation in fibromyalgia, so direct evidence for myofascial pain is limited to a few small or older randomized studies.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not available in the data compiled for this report (the Canadian licence records contain no indication text). Cyclobenzaprine is generally known as a muscle relaxant for muscle spasm associated with acute, painful musculoskeletal conditions. |
| Predicted New Indication | Myofascial pain syndrome |
| TxGNN Prediction Score | 0.9909 |
| Evidence Level | L3 |
| Canada Market Status | Marketed (marketed DINs: 10 of 10) |
| Number of DINs | 10 (marketed: 10) |
| Recommended Decision | Hold (treat as a research question) |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on general pharmacology, cyclobenzaprine is a centrally acting muscle relaxant structurally related to tricyclic antidepressants. It is thought to act mainly in the brainstem to reduce tonic somatic motor activity. It also has 5-HT2 antagonist, antihistaminic and anticholinergic effects.
Myofascial pain syndrome involves painful muscle trigger points and muscle tension. A drug that reduces muscle hypertonicity and spasm is therefore biologically plausible for this condition. The high TxGNN score (0.9909) is consistent with this link, but it comes from the TxGNN model (deep learning) and may reflect similarities the model learned between related diseases, not biological evidence. It is not clinical validation.
Important caveat: most of the Phase 3 trials listed are for TNX-102 SL, a low-dose sublingual cyclobenzaprine, and they appear to be in fibromyalgia, a related but different chronic pain condition. They support the drug’s analgesic activity in a related setting, but they do not directly show benefit in myofascial pain.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT04704297 | Phase 4 | Recruiting | 180 | Trigger point injection for low back myofascial pain; the disease matches, but the intervention appears to be a procedure rather than cyclobenzaprine |
| NCT04508621 | Phase 3 | Completed | 514 | 14-week placebo-controlled study of TNX-102 SL 5.6 mg at bedtime in fibromyalgia |
| NCT04172831 | Phase 3 | Completed | 503 | 14-week placebo-controlled study of TNX-102 SL 5.6 mg at bedtime in fibromyalgia |
| NCT02436096 | Phase 3 | Completed | 519 | 12-week placebo-controlled study of TNX-102 SL 2.8 mg at bedtime in fibromyalgia |
| NCT05273749 | Phase 3 | Completed | 457 | 14-week placebo-controlled study of TNX-102 SL 5.6 mg at bedtime in fibromyalgia |
| NCT02589275 | Phase 3 | Completed | 375 | 3-month open-label extension of TNX-102 SL in fibromyalgia (safety and tolerability) |
| NCT01903265 | Phase 2/3 | Completed | 205 | Phase 2b placebo-controlled study of TNX-102 SL 2.8 mg in fibromyalgia |
| NCT02015234 | Phase 3 | Completed | 158 | 12-month open-label extension of TNX-102 SL in fibromyalgia (long-term safety) |
| NCT02829814 | Phase 3 | Terminated | 51 | Placebo-controlled study of TNX-102 SL in fibromyalgia, terminated early |
| NCT01041495 | Phase 4 | Terminated | 37 | Cyclobenzaprine ER (Amrix) augmentation for fibromyalgia fatigue and muscle pain, terminated early |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 12764337 | 2003 | RCT | Annals of Emergency Medicine | Cyclobenzaprine added to ibuprofen versus ibuprofen alone in acute myofascial strain (analgesic and side effects evaluated in emergency department patients) |
| 11889661 | 2002 | RCT | Journal of Orofacial Pain | Clonazepam or cyclobenzaprine added to patient education and self-care for jaw pain upon awakening, compared with placebo |
| 24822235 | 2014 | RCT | Journal of Oral & Facial Pain and Headache | Cyclobenzaprine, tizanidine or placebo added to education and self-care in myofascial pain with jaw pain upon awakening |
| 20673246 | 2011 | RCT | Pain Practice | Acupuncture versus trigger point injection combined with cyclobenzaprine and dipyrone for myofascial trigger point pain |
| 3464212 | 1986 | Review | American Journal of Medicine | Clinical overview of fibrositis (musculoskeletal pain with tender points) |
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02212048 | PMS-CYCLOBENZAPRINE - TAB 10MG | Not listed | Not listed |
| 02357127 | JAMP-CYCLOBENZAPRINE | Not listed | Not listed |
| 02424584 | CYCLOBENZAPRINE | Not listed | Not listed |
| 02348853 | AURO-CYCLOBENZAPRINE | Not listed | Not listed |
| 02080052 | TEVA-CYCLOBENZAPRINE | Not listed | Not listed |
Ten valid single-ingredient licences are held in total; the five above are shown.
Safety Considerations
- Contraindications suggested by the knowledge graph (not label text): liver failure, glaucoma (including open-angle glaucoma), sudden cardiac arrest, heart conduction disease, atrioventricular block and heart block, hyperthyroidism (including Graves disease and thyrotoxicosis). These should be confirmed against the Canadian product monograph.
- Drug interactions (100 recorded; examples):
- Major: bupropion, morphine, potassium citrate, fenfluramine, dexfenfluramine.
- Moderate: anticholinergic agents such as atropine, hyoscyamine, glycopyrronium, dicyclomine and clidinium, plus loperamide, aprepitant, dronabinol and eluxadoline.
- Additive anticholinergic and central nervous system effects are the main concern.
For label warnings and contraindications, please refer to the package insert.
Conclusion and Next Steps
Decision: Hold (treat as a research question)
Rationale:
- The mechanism is plausible, and a few small randomized studies (an acute myofascial strain trial and jaw myofascial pain trials) point in the right direction. However, the large Phase 3 programme is for a different formulation in fibromyalgia, and none of the evidence is decisive for myofascial pain syndrome. The evidence therefore falls short of L1 or L2.
- Label safety data are missing, so safety screening cannot yet be completed.
To proceed, the following is needed:
- Canadian product monograph warnings and contraindications.
- Detailed mechanism of action data.
- Verification of the intervention and population in the trigger point injection trial (NCT04704297).
- A controlled trial of cyclobenzaprine specifically in myofascial pain syndrome, with attention to anticholinergic effects and interactions.
Note on other predictions: neuralgia (score 0.9908) has no registered trials and only indirect literature (evidence level L4), and papillary conjunctivitis (score 0.9908) has no trials or literature (evidence level L5). Both are on Hold.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.