Source: Health Products and Food Branch (CA) Revision Year: 2020
Cyclobenzaprine is structurally related to the tricyclic antidepressants, e.g., amitriptyline and imipramine. Tricyclic antidepressants have been reported to produce arrhythmias, sinus tachycardia, prolongation of the conduction time leading to myocardial infarction and stroke (see CONTRAINDICATIONS). Some of the more serious central nervous system (CNS) reactions noted with the tricyclic antidepressants have occurred in short-term studies of cyclobenzaprine for indications other than muscle spasm associated with acute musculoskeletal conditions, and usually at doses somewhat greater than those recommended for skeletal muscle spasm. see also ADVERSE REACTIONS).
Because of its atropine-like action, cyclobenzaprine should be used with caution in patients with a history of urinary retention, angle-closure glaucoma, increased intraocular pressure, and in patients taking anticholinergic medication.
See TOXICOLOGY – Carcinogenicity.
The development of a potentially life-threatening serotonin syndrome has been reported with cyclobenzaprine when used in combination with other drugs, such as selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), tramadol, bupropion, meperidine, verapamil, or MAO inhibitors. Serotonin syndrome symptoms may include mental status changes (e.g., confusion, agitation, hallucinations), autonomic instability (e.g., diaphoresis, tachycardia, labile blood pressure, hyperthermia), neuromuscular abnormalities (e.g., tremor, ataxia, hyperreflexia, clonus, muscle rigidity), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).
Treatment with cyclobenzaprine and any concomitant serotonergic agents should be discontinued immediately if the above reactions occur and supportive symptomatic treatment should be initiated. If concomitant treatment with cyclobenzaprine and other serotonergic drugs is clinically warranted, careful observation is advised, particularly during treatment initiation or dosage increases. The concomitant use of cyclobenzaprine with MAO inhibitors is contraindicated (see CONTRAINDICATIONS).
Patients should be cautioned about the risk of serotonin syndrome with the concomitant use of cyclobenzaprine and other serotonergic drugs. Patients should be advised of the signs and symptoms of serotonin syndrome, and be instructed to seek medical care immediately if they experience these symptoms.
Due to their atropine-like action, tricyclic antidepressants and other antidepressants can cause mydriasis which may trigger an angle-closure attack in a patient with anatomically narrow ocular angles. Caution should be used when cyclobenzaprine is prescribed for patients with untreated narrow angles. Open-angle glaucoma is not a risk factor for angle-closure glaucoma. Patients should be advised to seek immediate medical assistance if they experience eye pain, changes in vision or swelling or redness in or around the eye.
Cyclobenzaprine may enhance the effects of alcohol, barbiturates, and other CNS depressants.
Cyclobenzaprine, especially when used with alcohol or other CNS depressants, may impair mental and/or physical abilities required for performance of hazardous tasks, such as operating machinery or driving a motor vehicle.
The safety of cyclobenzaprine administration in pregnant women has yet to be established. A clinical report showed that cyclobenzaprine use during late pregnancy should be considered a potential cause of early ductal closure. Cyclobenzaprine should not be used in women who are, or may become pregnant, unless the possible risk to the fetus is outweighed by the expected benefits for the mother.
Because it is likely that cyclobenzaprine is excreted in milk, cyclobenzaprine hydrochloride should not be given to nursing mothers.
The safety and effectiveness of cyclobenzaprine in children below 15 years of age have not been established.
The plasma concentration of cyclobenzaprine is increased in the elderly (see ACTION AND CLINICAL PHARMACOLOGY, Pharmacokinetics, Elderly). The elderly may also be more at risk for CNS adverse events such as hallucinations and confusion, cardiac events resulting in falls or other sequelae, drug-drug and drug-disease interactions. For these reasons, in the elderly, cyclobenzaprine should be used only if clearly needed. In such patients cyclobenzaprine should be initiated with a reduced dose (e.g. reduced dose frequency) and titrated slowly upward. (See DOSAGE AND ADMINISTRATION – Special Population, and ACTION AND CLINICAL PHARMACOLOGY – Pharmacokinetics, Elderly).
The plasma concentration of cyclobenzaprine is generally higher in patients with hepatic impairment (see ACTION AND CLINICAL PHARMACOLOGY, Pharmacokinetics). These patients are generally more susceptible to drugs with potentially sedating effects, including cyclobenzaprine. Cyclobenzaprine should be used with caution in patients with mild hepatic impairment and is not recommended in those with moderate to severe impairment (see DOSAGE AND ADMINISTRATION).
The following adverse reactions have been reported with cyclobenzaprine hydrochloride tablets:
Most frequent: Drowsiness (39%), dry mouth (27%), dizziness (11%).
Less frequent: Increased heart rate (and several cases or tachycardia), weakness, fatigue, dyspepsia, nausea, paresthesia, unpleasant taste, blurred vision, and insomnia, convulsions and abnormal liver function (hepatitis, jaundice and cholestasis).
Rare: Serotonin syndrome, sweating, myalgia, dyspnea, abdominal pain, constipation, coated tongue, tremors, dysarthria, euphoria, nervousness, disorientation, confusion, headache, urinary retention, decreased bladder tonus, ataxia, depressed mood, hallucinations, and allergic reaction including rash, urticaria, and edema of the face and tongue.
The listing which follows includes other adverse reactions which have been reported with tricyclic compounds, but not with cyclobenzaprine hydrochloride when used in short-term studies in muscle spasm of peripheral origin. Some of these reactions were noted, however, when cyclobenzaprine hydrochloride was studied for other indications, usually in higher dosage. Pharmacologic similarities among the tricyclic drugs require that each of the reactions be considered when cyclobenzaprine hydrochloride is administered.
Cardiovascular: Hypotension, hypertension, palpitation, myocardial infarction, arrhythmias, heart block, stroke.
CNS and Neuromuscular: Confusional states, disturbed concentration, delusions, excitement, anxiety, restlessness, nightmares, numbness and tingling of the extremities, peripheral neuropathy, incoordination, seizures, alteration in EEG patterns, extrapyramidal symptoms, tinnitus, syndrome of inappropriate ADH (antidiuretic hormone) secretion.
Anticholinergic: Disturbance of accommodation, paralytic ileus, dilatation of urinary tract.
Allergic: Skin rash, urticaria, photosensitization, edema of face and tongue.
Hematologic: Bone marrow depression including agranulocytosis, leukopenia, eosinophilia, purpura, thrombocytopenia.
Gastrointestinal: Epigastric distress, vomiting, anorexia, stomatitis, diarrhea, parotid swelling, black tongue. Rarely hepatitis (including altered liver function and jaundice).
Endocrine: Testicular swelling and gynecomastia in the male, breast enlargement and galactorrhea in the female. Increased or decreased libido, elevation and lowering of blood sugar levels.
Other: Weight gain or loss, urinary frequency, mydriasis, jaundice, alopecia.
Withdrawal symptoms: Abrupt cessation of treatment after prolonged administration may produce nausea, headache, and malaise. These are not indicative of addiction.
Serious Drug Interactions:
Postmarketing cases of serotonin syndrome have been reported during combined use of cyclobenzaprine and other drugs, such as SSRIs, SNRIs, TCAs, tramadol, bupropion, meperidine, verapamil, or MAO inhibitors. (See WARNINGS AND PRECAUTIONS)
Cyclobenzaprine should not be used concomitantly with MAO inhibitors or within 14 days after their discontinuation (see CONTRAINDICATIONS). Hyperpyretic crisis, severe seizures and deaths have occurred in patients receiving cyclobenzaprine (or structurally similar tricyclic antidepressants) concomitantly with MAO inhibitor drugs.
Based on its structural similarity to tricyclic antidepressants, cyclobenzaprine hydrochloride may enhance the effects of alcohol, barbiturates, and other CNS depressants, may enhance the seizure risk in patients taking tramadol, or may block the antihypertensive action of guanethidine and similarly acting compounds.
Cyclobenzaprine, especially when used with alcohol or other CNS depressants, may impair mental and/or physical abilities required for performance of hazardous tasks, such as operating machinery or driving a motor vehicle.
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