Cyclobenzaprine

Cyclobenzaprine is Skeletal muscle relaxants belonging to Central Alpha2 agonist

Cyclobenzaprine is used in the treatment of Muscle spasm. It is also used to treat Fibromyalgia; Temporomandibular disorder.

Centrally-acting skeletal muscle relaxant pharmacologically related to tricyclic antidepressants; reduces tonic somatic motor activity influencing both alpha and gamma motor neurons.

Cyclobenzaprine is available in the form of Tablets and Capsules.

Cyclobenzaprine is used in the treatment of Muscle spam. It is also used to treat Fibromyalgia; Temporomandibular disorder.

Cyclobenzaprine is a centrally-acting synthetic analgesic which inhibits ascending pain pathways by binding to μ-opiate receptor in the CNS and inhibiting norepinephrine reuptake, thus altering pain perception and response.

Cyclobenzaprine is approved for use in the following clinical indications

Muscle spasm: As an adjunct to rest and physical therapy for short-term (2 to 3 weeks) relief of muscle spasm associated with acute, painful musculoskeletal conditions.

• Although not approved there have been certain off labelled uses documented for cyclobenzaprine which includes:

Fibromyalgia; Temporomandibular disorder, acute

Fibromyalgia (alternative agent) (off-label use):

Note: For mild to moderate symptoms, particularly with sleep disturbance.

Oral: Immediate release: Initial: 5 to 10 mg once daily before bedtime; may gradually titrate as needed and tolerated up to 10 to 40 mg daily in 1 to 3 divided doses. If excessive sedation occurs, may divide dose so larger portion is taken at bedtime (eg, 5 mg in morning and 10 or 15 mg at bedtime).

Muscle spasm and/or musculoskeletal pain (adjunctive therapy):

Note: For skeletal muscle spasm and/or pain (eg, low back pain, neck pain) with muscle spasm, usually in combination with a nonsteroidal anti-inflammatory drug (NSAID) and/or acetaminophen. In general, muscle relaxants should be used temporarily (eg, for a few days or intermittently for a few days when needed).

Oral: Immediate release: Initial: 5 mg 3 times daily scheduled or as needed with one of the doses administered at bedtime. May increase dose based on response and tolerability up to 10 mg 3 times daily as needed. Once-daily use at bedtime (with daytime NSAID and/or acetaminophen) may be better tolerated .

Oral: Extended release: Usual: 15 mg once daily; some patients may require up to 30 mg once daily.

Temporomandibular disorder, acute (adjunctive therapy) (off-label use):

Note: Adjunct to an NSAID in select patients with pain on palpation of the lower jaw muscle .

Oral: Immediate release: Usual: 5 to 10 mg once daily at bedtime for 10 to 14 days; some patients with persistent muscular pain may require an additional 7 days of therapy.

Cyclobenzaprine is available in the dosage strength of 5 mg, 7.5 mg, 10 mg, 15 mg, 30 mg.

Cyclobenzaprine is available in the form of Tablets and Capsules.

Cyclobenzaprine is contraindicated in patients with:

Hypersensitivity to cyclobenzaprine or any component of the formulation; during or within 14 days of MAO inhibitors; hyperthyroidism; heart failure; arrhythmias; heart block or conduction disturbances; acute recovery phase of MI.

Concerns related to adverse effects:

• Toxicity: Cyclobenzaprine shares the toxic potentials of the tricyclic antidepressants, including prolongation of conduction time, arrhythmias, and tachycardia; the usual precautions of tricyclic antidepressant therapy should be observed.

Disease-related concerns:

• Hepatic impairment: Use with caution in patients with mild hepatic impairment; plasma concentrations increased twofold in presence of mild impairment. Not recommended in moderate to severe hepatic impairment. ER capsules not recommended in patients with hepatic impairment of any severity (mild, moderate, or severe).

• Ophthalmic conditions: Use with caution in patients with certain ophthalmic conditions (eg, increased intraocular pressure, angle-closure glaucoma) as anticholinergic effects may exacerbate underlying condition.

• Urinary frequency/hesitancy: Use with caution in patients with urinary frequency/hesitancy as anticholinergic effects may exacerbate underlying condition.

Ethanol: Concomitant use with alcohol can increase the bioavailability of extended release Tablets and Capsules. Management: Avoid use of alcohol during therapy.

Cyclobenzaprine is present in breast milk.

The relative infant dose (RID) of cyclobenzaprine is 1.4% when calculated using the highest breast milk concentration located, compared to a weight-adjusted maternal dose of 10 mg twice daily.

In general, breastfeeding is considered acceptable when the RID of a medication is <10%.

The RID of cyclobenzaprine was calculated using a milk concentration of 24.5 ng/mL, providing an estimated daily infant dose via breast milk of 0.004 mg/kg/day. This milk concentration was obtained following maternal administration of cyclobenzaprine 10 mg twice daily for 3 years following delivery. This same study also sampled breast milk of a mother taking cyclobenzaprine 5 mg once daily for 3 months following delivery. Authors of the study calculated the RID of cyclobenzaprine in both cases to be 0.5% using average breast milk concentrations and actual maternal weight. Adverse events were not observed in the breastfed infants. Until additional information is available, assessment of the infant for adverse events is recommended.

Food: When administered after a high fat/calorie meal, the AUC and C_max increased by 25% and 16%, respectively. Management: May administer without regard to meals.

• Common Adverse effects:

Antimuscarinic effects, neurological adverse effects, GI disorders, orthostatic hypotension,

• Less Common Adverse effects:

Tachycardia, hypersensitivity reactions. Rarely, cholestatic jaundice and blood disorders.

• Rare Adverse effects

Endocrine effects, sexual dysfunction, changes in blood sugar. Increased appetite with wt gain, sweating.

Plasma concentration may be increased with the use of cimetidine, diltiazem, disulfiram, methylphenidate, ritonavir, and verapamil. Side-effects are increased by adrenaline, amiodarone, general anesthetics, SSRIs, antihistamines, antimuscarinics, antipsychotics, anxiolytics and hypnotics, clozapine, disopyramide, diuretics, flecainide, MAOIs, moclobemide, moxifloxacin, nefopam, nicorandil, noradrenaline, phenothiazine, pimozide, procainamide, propafenone, quinidine, selegiline, sibutramine, sotalol, terfenadine, thioridazine, and tramadol. Effects of adrenergic neurone blockers, clonidine, barbiturates, nitrates, and primidone are reduced while effects of baclofen, opioid analgesics, and thyroid hormones are enhanced with concomitant use of cyclobenzaprine. Carbamazepine and rifampicin may increase metabolism of cyclobenzaprine. Effects may be antagonized by oestrogens. Avoid use with brimonidine, entacapone, artemether with lumefantrine, or sibutramine. CNS effects may be enhanced by other CNS depressants.

The common side effects of Cyclobenzaprine include the following :

Antimuscarinic effects, neurological adverse effects, GI disorders, orthostatic hypotension.

Drowsiness, tachycardia, tremor, agitation, coma, ataxia, hypertension, slurred speech, confusion, dizziness, nausea, vomiting, and hallucinations, cardiac arrest, chest pain, cardiac dysrhythmias, changes in the electrocardiogram, particularly in QRS axis or width, severe hypotension, seizures, and neuroleptic malignant syndrome. Emesis or gastric lavage followed by activated charcoal. Treatment is symptomatic and supportive with monitoring of ECG and observing for signs of CNS or respiratory depression, hypotension, cardiac dysrhythmias and/or conduction blocks and seizures. For patients with with dysrhythmias and/or QRS widening, use IV sodium bicarbonate and hyperventilationv to correct pH to 7.45 to 7.55. Dysrhythmias unresponsive to sodium bicarbonate therapy/hyperventilation may respond to lidocaine, bretylium or phenytoin but type 1A and 1C antiarrhythmics are generally contraindicated. Seizures may be controlled with benzodiazepines or, if ineffective, other anticonvulsants (e.g. phenobarbital, phenytoin) may be used. Monitoring of plasma drug levels should not guide management of the patient and dialysis is probably of no value because of low plasma concentrations of the drug. Consult local poison centre for latest treatment infomation.

• Pharmacodynamics

Cyclobenzaprine is a skeletal muscle relaxant that works on areas of the brainstem to reduce skeletal muscle spasm, though its exact pharmacodynamic behaviour is currently unclear. Despite its long half-life, it is relatively short-acting with a typical duration of action of 4-6 hours. Cyclobenzaprine has been reported to contribute to the development of serotonin syndrome when used in combination with other serotonergic medications. Symptoms of serotonin syndrome may include autonomic instability, changes to mental status, neuromuscular abnormalities, or gastrointestinal symptoms - treatment with cyclobenzaprine should be discontinued immediately if any of these reactions occur during therapy.

• Pharmacokinetics

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1364710/
2. https://reference.medscape.com/drug/colestid-Cyclobenzaprine -342452
3. https://go.drugbank.com/drugs/DB00375
4. https://www.sciencedirect.com/topics/medicine-and-dentistry/Cyclobenzaprine
5. https://europepmc.org/article/med/6988203