Cyclobenzaprine
Cyclobenzaprine
Generic Name
Cyclobenzaprine
Mechanism
- Acts primarily in the central nervous system (CNS) rather than directly on skeletal muscle tissue.
- Inhibits excitatory neurotransmission by blocking the serotonergic 5‑HT₂ and adrenergic α₁ receptors in the brain stem, spinal cord, and reticular formation.
- Suppresses presynaptic acetylcholine release at motor neuron terminals, reducing spasmogenic drive.
- Reduces the frequency of alpha‑motor neuron firing, leading to decreased muscle tone.
- The exact site of action remains partially undefined, but the drug exerts its effects via CNS depression that diminishes reflex muscle contraction.
Pharmacokinetics
- Absorption: Rapid oral absorption; peak plasma concentration in ~3 h.
- Distribution: Highly lipophilic; extensive tissue binding (≈82%).
- Metabolism: Hepatic CYP2D6 → 1‑oxo‑cyclobenzaprine (active metabolite) and other sulfates.
- Elimination: Renal excretion (≈80 %) of unchanged drug and metabolites.
- Half‑life: 2–6 h (active metabolites extend clinical effect 8–10 h).
- Drug interactions:
- CYP2D6 inhibitors (e.g., fluoxetine) ↑ plasma levels.
- CNS depressants (benzodiazepines, opioids) → additive sedation.
- MAO‑I may increase neurotoxicity risk.
Indications
- Short‑term treatment (≤2 weeks) of:
- Acute musculoskeletal pain associated with muscle spasm.
- Back pain and neck pain that are aggravated by muscle spasms.
- Adjunct to physical therapy, rest, and NSAIDs.
Contraindications
| Category | Key Points |
| Contraindicated | Known hypersensitivity; narrow‑angle glaucoma; Pheochromocytoma (risk of hypertensive crisis). |
| Warnings | |
| • CNS depression | May enhance sedation when combined with alcohol, benzodiazepines, or opioids. |
| • Anticholinergic burden | Can precipitate dry mouth, constipation, urinary retention, and blurred vision. |
| • Seizure risk | Increased risk in patients with history of seizures. |
| • Pregnancy | Category C; potential teratogenic effects—use only if benefits outweigh risks. |
| • Pediatric use | Limited data; not routinely recommended. |
Dosing
| Formulation | Typical Dose | Duration |
| Oral tablets (5 mg) | 5 mg × 3 / day for 2–3 days; titrate to 2.5–10 mg × 3 / day up to 15 mg / day. | ≤ 2 weeks |
| Oral tablets (10 mg) | 10 mg × 3 / day for up to 3 days; may increase to 15 mg / day if needed. | ≤ 2 weeks |
• Take with food if GI upset occurs.
• Do not abruptly discontinue; taper if prolonged use.
Adverse Effects
- Common (≥ 10 %):
- Dry mouth, dizziness, fatigue, sedation.
- Constipation, blurred vision.
- Mild hypotension (postural drop).
- Serious (≤ 1 %):
- Severe CNS depression or loss of consciousness.
- Severe hypotension or bradycardia.
- Allergic reactions: rash, angioedema.
- Seizure exacerbation or onset.
- Drug‑induced psychosis/neurotoxicity (rare).
Monitoring
- Vitals: BP, pulse, orthostatic changes (especially when titrating).
- Neurological: Assess for sedation, ataxia, or seizures.
- Renal: Monitor serum creatinine if renal impairment exists (dose adjust if CrCl < 30 mL/min).
- Drug interactions: Review concurrent CNS depressants; adjust therapy accordingly.
- Therapeutic response: Efficacy at 48 h; discontinue if inadequate.
Clinical Pearls
- “Rule of 3”: Start low (5 mg) and go no higher than 15 mg / day; limit duration to 2 weeks to prevent tolerance and anticholinergic accumulation.
- Postural hypotension warning: In patients on antihypertensives, schedule doses in the early morning while upright and monitor systolic BP 15 min post‑dose.
- Combination therapy: Pair with non‑adrenergic muscle relaxants (e.g., baclofen) only after cyclobenzaprine trial; consider potential additive CNS depression.
- Withdrawal: Rare “cyclobenzaprine withdrawal syndrome” (headache, irritability) is reported after abrupt cessation—advise tapering when discontinuation is needed.
- Pediatric caution: Though data are scant, recent safety reviews recommend avoiding cyclobenzaprine in patients < 12 yrs.
- Pregnancy safety: Animal studies show low toxicity; human data are limited—use only if no safer alternatives.
- Drug–drug synergy: When combined with opioids, titrate opioid dose downward to offset increased sedation and respiratory depression risk.
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• *References*: UpToDate, 2024, “Cyclobenzaprine.” FDA prescribing information. DrugBank 2023.