indication

For use as an adjunct to rest and physical therapy for relief of muscle spasm associated with acute, painful musculoskeletal conditions.

pharmacology

Cyclobenzaprine, closely related to the antidepressant amitriptyline, is used as a skeletal muscle relaxant to reduce pain and tenderness and improve mobility. Unlike dantrolene, cyclobenzaprine cannot be used to treat muscle spasm secondary to cerebral or spinal cord disease.

mechanism of action

Like other tricyclic antidepressants, cyclobenzaprine exhibits anticholinergic activity, potentiation of norepinephrine, and antagonism of reserpine. Cyclobenzaprine does not directly act on the neuromuscular junction or the muscle but relieves muscle spasms through a central action, possibly at the brain stem level. Cyclobenzaprine binds to the serotonin receptor and is considered a 5-HT2 receptor antagonist that reduces muscle tone by decreasing the activity of descending serotonergic neurons.

toxicity

Oral mouse and rat LD₅₀ are 338 mg/kg and 425 mg/kg respectively. Signs of overdose include agitation, coma, confusion, congestive heart failure, convulsions, dilated pupils, disturbed concentration, drowsiness, hallucinations, high or low temperature, increased heartbeats, irregular heart rhythms, muscle stiffness, overactive reflexes, severe low blood pressure, stupor, and vomiting.

biotransformation

Extensively metabolized (gastrointestinal and hepatic).

absorption

Slowly but well absorbed after oral administration

half life

18 hours (range 8-37 hours)

route of elimination

Cyclobenzaprine is extensively metabolized, and is excreted primarily as glucuronides via the kidney.

drug interactions

Donepezil: Possible antagonism of action

Galantamine: Possible antagonism of action

Rasagiline: Increased risk of toxicity with this association

Rivastigmine: Possible antagonism of action

Tacrine: The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Cyclobenzaprine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.

Thiabendazole: The strong CYP1A2 inhibitor, Thiabendazole, may increase the effects and toxicity of Cyclobenzaprine by decreasing Cyclobenzaprine metabolism and clearance. Monitor for changes in the therapeutic and adverse effects of Cyclobenzaprine if Thiabendazole is initiated, discontinued or dose changed.

Tramadol: Increases risk of seizure.

Tranylcypromine: Increased risk of serotonin syndrome. Concomitant use should be avoided. These agents should not be administered within 14 days of each other.

Triprolidine: Triprolidine and Cyclobenzaprine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Additive CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.

Trospium: Trospium and Cyclobenzaprine, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.