"Nov. 2, 2012 -- Safety steps taken in the wake of the fungal meningitis outbreak have worsened drug shortages, raising questions about whether the U.S. must choose between the safety and the availability of crucial medicines.
- Patient Information:
Details with Side Effects
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. The concomitant use of AMRIX with MAO inhibitors is contraindicated [see CONTRAINDICATIONS]. 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 AMRIX and any concomitant serotonergic agents should be discontinued immediately if the above reactions occur and symptomatic treatment should be initiated. If concomitant treatment with AMRIX and other serotonergic drugs is clinically warranted, careful observation is advised, particularly during treatment initiation or dose increases.
Tricyclic Antidepressant-like Effects
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]. AMRIX may enhance the effects of alcohol, barbiturates, and other CNS depressants.
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. If clinically significant CNS symptoms develop, consider discontinuation of AMRIX.
Use in the Elderly
As a result of a 40% increase in cyclobenzaprine plasma levels and a 56% increase in plasma half-life following administration of AMRIX in elderly subjects as compared to young adults, use of AMRIX is not recommended in the elderly. [See CLINICAL PHARMACOLOGY]
Use in Patients with Hepatic Impairment
As a result of two-fold higher cyclobenzaprine plasma levels in subjects with mild hepatic impairment, as compared to healthy subjects, following administration of immediate-release cyclobenzaprine and because there is limited dosing flexibility with AMRIX, use of AMRIX is not recommended in patients with mild, moderate or severe hepatic impairment. [See CLINICAL PHARMACOLOGY]
Because of its atropine-like action, AMRIX 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.
Patient Counseling Information
See FDA-approved patient labeling (PATIENT INFORMATION).
- Advise patients to stop taking AMRIX and to notify their physician right away if they experience symptoms of an allergic reaction, such as difficulty breathing, hives, swelling of face or tongue, or itching.
- Advise patients that AMRIX should not be taken with MAO inhibitors or within 14 days after their discontinuation.
- Caution patients about the risk of serotonin syndrome with concomitant use of AMRIX and other drugs, such as SSRIs, SNRIs, TCAs, tramadol, bupropion, meperidine, verapamil, or MAO inhibitors. Advise patients of the signs and symptoms of serotonin syndrome [see WARNINGS AND PRECAUTIONS] and instruct patients to seek medical care immediately if they experience these symptoms.
- Advise patients to stop taking AMRIX and to notify their physician right away if they experience arrhythmias or tachycardia.
- Advise patients that AMRIX may enhance the impairment effects of alcohol. These effects may also be seen if AMRIX is taken with other CNS depressants.
- Caution patients about operating an automobile or other hazardous machinery until it is reasonably certain that AMRIX therapy will not adversely affect their ability to engage in such activities.
- Advise patients to take AMRIX at approximately the same time each day.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term studies were conducted in CD-1 mice and Sprague-Dawley rats with cyclobenzaprine to evaluate its carcinogenic potential. In an 81-week carcinogenicity study, metastatic hemangiosarcoma was seen in 3 of 21 male mice at 10 mg/kg/day (2 times the MRHD on a mg/m² basis). In a 105-week carcinogenicity study, malignant astrocytoma was seen in 3 of 50 male rats at 10 mg/kg/day (3 times the MRHD on a mg/m² basis). There were no tumor findings in female mice or rats.
Cyclobenzaprine HCl was not mutagenic or clastogenic in the following assays: an in vitro Ames bacterial mutation assay, in vitro Chinese hamster ovary (CHO) cell chromosomal aberration test, and in vivo mouse bone marrow micronucleus assay.
Cyclobenzaprine HCl had no effects on fertility and reproductive performance in male or female rats at oral doses up to 20 mg/kg/day (6 times the MRHD on a mg/m² basis).
Use In Specific Populations
Pregnancy Category B
There are no adequate and well-controlled studies of AMRIX in pregnant women. Because animal reproduction studies are not always predictive of human response, AMRIX should be used during pregnancy only if clearly needed.
No treatment-related effects on embryofetal development were observed in mice and rabbits at approximately 3 and 15 times the maximum recommended human dose (MRHD), respectively (on a mg/m² basis at maternal doses of 20 mg/kg/day in both mice and rabbits).
Cyclobenzaprine has been shown to adversely affect pup postnatal development when dams were treated with the drug during pregnancy and lactation periods in rats. This study found that cyclobenzaprine decreased pup body weight and survival at approximately ≥ 3 times the MRHD (on a mg/m² basis at maternal doses of 10 and 20 mg/kg/day in rats).
It is not known whether this drug is excreted in human milk. Because cyclobenzaprine is closely related to the tricyclic antidepressants, some of which are known to be excreted in human milk, caution should be exercised when AMRIX is administered to a nursing woman.
Safety and effectiveness of AMRIX has not been studied in pediatric patients.
Clinical studies of AMRIX did not include sufficient numbers of patients aged 65 and over to determine the safety and efficacy of AMRIX in the elderly population. The plasma concentration and half-life of cyclobenzaprine are substantially increased in the elderly when compared to the general patient population. Accordingly, use of AMRIX is not recommended in the elderly. [See WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY]
The use of AMRIX is not recommended in patients with mild, moderate or severe hepatic impairment. [See WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY]
Last reviewed on RxList: 6/20/2013
This monograph has been modified to include the generic and brand name in many instances.
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