Cyclobenzaprine (Flexeril®)
Cyclobenzaprine
Flexeril®
Classification:
Musculoskeletal Agents
- Skeletal Muscle Relaxants
Description: Cyclobenzaprine is a skeletal muscle relaxant approved for the relief of muscle spasm associated with acute, painful musculoskeletal conditions. Cyclobenzaprine is not effective for the treatment of muscle spasm due to central nervous system disease (e.g., cerebral palsy, spinal cord disease). Cyclobenzaprine is very closely related to the antidepressant amitriptyline. Although it is not used clinically as an antidepressant, cyclobenzaprine does possess some pharmacologic effects similar to tricyclic antidepressants. Flexeril® (cyclobenzaprine 10 mg) was approved by the FDA in 1977. Flexeril® came off patent in 1993. In February 2003, the manufacturer made available cyclobenzaprine 5 mg tablets, and reduced the dosage recommendations for cyclobenzaprine based on efficacy and safety data. In early 2006, a 7.5 mg oral dosage strength of cyclobenzaprine became available from various manufacturers.
Mechanism of Action: Since cyclobenzaprine is so closely similar to amitriptyline in chemical structure, some of its effects are similar to the tricyclic antidepressants, including anticholinergic activity, potentiation of norepinephrine, and antagonism of reserpine. Cyclobenzaprine relieves muscle spasms through a central action, possibly at the brain stem level, with no direct action on the neuromuscular junction or the muscle involved. It is not a peripheral neuromuscular blocker. Treatment with the drug reduces pain and tenderness, and improves mobility. Unlike dantrolene, cyclobenzaprine is not effective for muscle spasm secondary to cerebral or spinal cord disease.
Pharmacokinetics: Cyclobenzaprine is well aborbed from the GI tract following oral administration, is extensively metabolized, and it undergoes enterohepatic recirculation. Estimates of mean oral biovailability range from 33 - 55%. Cyclobenzaprine exhibits linear pharmacokinetics at recommended doses, and reaches steady-state within 3 - 4 days. The onset of skeletal muscle relaxant action occurs in about 1 hour, and duration of action ranges from 12 - 24 hours. Spasmolytic effects may take 1 - 2 days to be fully manifest. Cyclobenzaprine is 93% protein-bound, and no evidence is available as to whether it crosses the placenta or is distributed into breast milk. Cyclobenzaprine undergoes extensive metabolism in the liver and is excreted mainly as conjugated inactive metabolites in the urine, and as unchanged drug via the bile in the feces. Hepatic cytochrome P-450 isoenzymes (CYP3A4, CYP1A2, and to a lesser extent CYP2D6) are primarily responsible for the N-demethylation pathway of cyclobenzaprine metabolism (one of the oxidative pathways). Cyclobenzaprine half-life ranges from 8 to 37 hours (mean 18 hours).
Cyclobenzaprine Tablets(Tab 10 mg ) 
Special Populations: The plasma concentrations of cyclobenzaprine are elevated in elderly patients, and patients with hepatic impairment; cautious dosage titration is warranted (see Dosage). Steady-state plasma concentrations of cyclobenzaprine are 1.7 higher in elderly compared to younger adults. Peak plasma concentrations and AUC of cyclobenzaprine are nearly doubled in patients with hepatic impairment (15 of 16 patients studied had mild hepatic impairment). Cyclobenzaprine has not been sufficiently studied in patients with moderate to severe hepatic impairment.
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[ Revised 4/13/2006 5:05:00 PM ]
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