Cyclobenzaprine hydrochloride 7.5 MG Oral Tablet
WARNINGS
Serotonin Syndrome The development of a potentially life-threatening serotonin syndrome has been reported with cyclobenzaprine hydrochloride 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 monoamine oxidase (MAO) inhibitors.
The concomitant use of cyclobenzaprine hydrochloride 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 cyclobenzaprine hydrochloride 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 hydrochloride and other serotonergic drugs is clinically warranted, careful observation is advised, particularly during treatment initiation or dose increases (see PRECAUTIONS, Drug Interactions ).
Cyclobenzaprine is closely related to the tricyclic antidepressants, e.g., amitriptyline and imipramine.
In short term studies for indications other than muscle spasm associated with acute musculoskeletal conditions, and usually at doses somewhat greater than those recommended for skeletal muscle spasm, some of the more serious central nervous system reactions noted with the tricyclic antidepressants have occurred (see , below, and ADVERSE REACTIONS ).
Tricyclic antidepressants have been reported to produce arrhythmias, sinus tachycardia, prolongation of the conduction time leading to myocardial infarction and stroke.
Cyclobenzaprine hydrochloride may enhance the effects of alcohol, barbiturates, and other CNS depressants.
DRUG INTERACTIONS
Drug Interactions Cyclobenzaprine may have life-threatening interactions with MAO inhibitors (see CONTRAINDICATIONS ).
Postmarketing cases of serotonin syndrome have been reported during combined use of cyclobenzaprine hydrochloride and other drugs, such as selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), tramadol, bupropion, meperidine, verapamil, or monoamine oxidase (MAO) inhibitors.
If concomitant treatment with cyclobenzaprine hydrochloride and other serotonergic drugs is clinically warranted, careful observation is advised, particularly during treatment initiation or dose increases (see WARNINGS ).
Cyclobenzaprine hydrochloride may enhance the effects of alcohol, barbiturates, and other CNS depressants.
Tricyclic antidepressants may block the antihypertensive action of guanethidine and similarly acting compounds.
Tricyclic antidepressants may enhance the seizure risk in patients taking tramadol.
† † ULTRAM ® (tramadol HCl tablets, Ortho-McNeil Pharmaceutical) ULTRACET ® (tramadol HCl and acetaminophen tablets, Ortho-McNeil Pharmaceutical)
OVERDOSAGE
Although rare, deaths may occur from overdosage with cyclobenzaprine hydrochloride.
Multiple drug ingestion (including alcohol) is common in deliberate cyclobenzaprine overdose.
As management of overdose is complex and changing, it is recommended that the physician contact a poison control center for current information on treatment .
Signs and symptoms of toxicity may develop rapidly after cyclobenzaprine overdose; therefore, hospital monitoring is required as soon as possible.
The acute oral LD 50 of cyclobenzaprine hydrochloride is approximately 338 and 425 mg/kg in mice and rats, respectively.
MANIFESTATIONS The most common effects associated with cyclobenzaprine overdose are drowsiness and tachycardia.
Less frequent manifestations include tremor, agitation, coma, ataxia, hypertension, slurred speech, confusion, dizziness, nausea, vomiting, and hallucinations.
Rare but potentially critical manifestations of overdose are cardiac arrest, chest pain, cardiac dysrhythmias, severe hypotension, seizures, and neuroleptic malignant syndrome.
Changes in the electrocardiogram, particularly in QRS axis or width, are clinically significant indicators of cyclobenzaprine toxicity.
Other potential effects of overdosage include any of the symptoms listed under ADVERSE REACTIONS.
MANAGEMENT General As management of overdose is complex and changing, it is recommended that the physician contact a poison control center for current information on treatment.
In order to protect against the rare but potentially critical manifestations described above, obtain an ECG and immediately initiate cardiac monitoring.
Protect the patient’s airway, establish an intravenous line and initiate gastric decontamination.
Observation with cardiac monitoring and observation for signs of CNS or respiratory depression, hypotension, cardiac dysrhythmias and/or conduction blocks, and seizures is necessary.
If signs of toxicity occur at any time during this period, extended monitoring is required.
Monitoring of plasma drug levels should not guide management of the patient.
Dialysis is probably of no value because of low plasma concentrations of the drug.
Gastrointestinal Decontamination All patients suspected of an overdose with cyclobenzaprine hydrochloride should receive gastrointestinal decontamination.
This should include large volume gastric lavage followed by activated charcoal.
If consciousness is impaired, the airway should be secured prior to lavage and emesis is contraindicated.
Cardiovascular A maximal limb-lead QRS duration of ≥ 0.10 seconds may be the best indication of the severity of the overdose.
Serum alkalinization, to a pH of 7.45 to 7.55, using intravenous sodium bicarbonate and hyperventilation (as needed), should be instituted for patients with dysrhythmias and/or QRS widening.
A pH > 7.60 or a pCO 2 < 20 mmHg is undesirable.
Dysrhythmias unresponsive to sodium bicarbonate therapy/hyperventilation may respond to lidocaine, bretylium or phenytoin.
Type 1A and 1C antiarrhythmics are generally contraindicated (e.g., quinidine, disopyramide, and procainamide).
CNS In patients with CNS depression, early intubation is advised because of the potential for abrupt deterioration.
Seizures should be controlled with benzodiazepines or, if these are ineffective, other anticonvulsants (e.g.
phenobarbital, phenytoin).
Physostigmine is not recommended except to treat life-threatening symptoms that have been unresponsive to other therapies, and then only in close consultation with a poison control center.
PSYCHIATRIC FOLLOW-UP Since overdosage is often deliberate, patients may attempt suicide by other means during the recovery phase.
Psychiatric referral may be appropriate.
PEDIATRIC MANAGEMENT The principles of management of child and adult overdosages are similar.
It is strongly recommended that the physician contact the local poison control center for specific pediatric treatment.
DESCRIPTION
Cyclobenzaprine hydrochloride, USP is a white to off-white crystalline powder with the molecular formula C 20 H 21 N•HCl and a molecular weight of 311.9.
It has a melting point of 217° C, and a pK a of 8.47 at 25° C.
It is freely soluble in water, in alcohol and in methanol, sparingly soluble in isopropanol, slightly soluble in chloroform and in methylene chloride and insoluble in hydrocarbons.
If aqueous solutions are made alkaline, the free base separates.
Cyclobenzaprine HCl is designated chemically as 3-( 5H -dibenzo[ a,d ] cyclohepten-5-ylidene)- N, N -dimethyl-1-propanamine hydrochloride, and has the following structural formula: Cyclobenzaprine hydrochloride is supplied as a 5 mg, 7.5 mg and 10 mg tablets for oral administration.
Cyclobenzaprine hydrochloride 7.5 mg tablets contain the following inactive ingredients: corn starch, hydroxypropyl cellulose, hypromellose, lactose monohydrate, magnesium stearate, polyethylene glycol, pregelatinized starch, talc and titanium dioxide.
structure
HOW SUPPLIED
Cyclobenzaprine hydrochloride tablets, USP are available in 7.5 mg dosage strength.
The three dosage strength is supplied as follows: The 7.5 mg tablets are white, round shaped, biconvex, film coated tablets debossed with ‘ RE ’ on one side and ‘ 33 ’ on other side.
NDC 76218-1219-7 Bottles of 1000 Store between 20 – 25° C (68 – 77° F).
(See USP Controlled Room Temperature).
To report SUSPECTED ADVERSE REACTIONS, contact the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Distributed by: KLE 2, Inc.
8654 Ellis Ave.
Los Angeles, CA 90034 August 2014 FDA-04
INDICATIONS AND USAGE
Cyclobenzaprine hydrochloride tablets, USP are indicated as an adjunct to rest and physical therapy for relief of muscle spasm associated with acute, painful musculoskeletal conditions.
Improvement is manifested by relief of muscle spasm and its associated signs and symptoms, namely, pain, tenderness, limitation of motion, and restriction in activities of daily living.
Cyclobenzaprine hydrochloride tablets, USP should be used only for short periods (up to two or three weeks) because adequate evidence of effectiveness for more prolonged use is not available and because muscle spasm associated with acute, painful musculoskeletal conditions is generally of short duration and specific therapy for longer periods is seldom warranted.
Cyclobenzaprine hydrochloride tablets, USP has not been found effective in the treatment of spasticity associated with cerebral or spinal cord disease, or in children with cerebral palsy.
PEDIATRIC USE
Pediatric Use Safety and effectiveness of cyclobenzaprine hydrochloride tablets in pediatric patients below 15 years of age have not been established.
PREGNANCY
Pregnancy Pregnancy Category B : Reproduction studies have been performed in rats, mice and rabbits at doses up to 20 times the human dose, and have revealed no evidence of impaired fertility or harm to the fetus due to cyclobenzaprine hydrochloride.
There are, however, no adequate and well-controlled studies in pregnant women.
Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
NUSRING MOTHERS
Nursing Mothers 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 cyclobenzaprine hydrochloride tablets are administered to a nursing woman.
DOSAGE AND ADMINISTRATION
For most patients, the recommended dose of cyclobenzaprine hydrochloride tablets is 5 mg three times a day.
Based on individual patient response, the dose may be increased to either 7.5 or 10 mg three times a day.
Use of cyclobenzaprine hydrochloride tablets for periods longer than two or three weeks is not recommended.
(see INDICATIONS AND USAGE ).
Less frequent dosing should be considered for hepatically impaired or elderly patients (see PRECAUTIONS, Impaired Hepatic Function , and Use in the Elderly ).