Flexeril Information
Flexeril (Cyclobenzaprine hcl) Description
Cyclobenzaprine hydrochloride is a white, crystalline tricyclic amine salt with the empirical formula CHN•HCl and a molecular weight of 311.9. It has a melting point of 217°C, and a pK of 8.47 at 25°C. It is freely soluble in water and alcohol, sparingly soluble in isopropanol, and insoluble in hydrocarbon solvents. If aqueous solutions are made alkaline, the free base separates. Cyclobenzaprine HCl is designated chemically as 3-( -dibenzo[,] cyclohepten-5-ylidene)-, -dimethyl-1-propanamine hydrochloride, and has the following structural formula:
Flexeril (Cyclobenzaprine hcl) 5 mg (Cyclobenzaprine HCl) is supplied as a 5 mg tablet for oral administration. Flexeril (Cyclobenzaprine hcl) 10 mg (Cyclobenzaprine HCl) is supplied as a 10 mg tablet for oral administration.
Flexeril (Cyclobenzaprine hcl) 5 mg (Cyclobenzaprine HCl) tablets contain the following inactive ingredients: lactose hydrous, pre-gelatinized starch, corn starch, magnesium stearate, hydroxypropyl cellulose, hypromellose, titanium dioxide, Yellow D&C #10 Aluminum Lake HT, Yellow FD&C #6 Aluminum Lake, and carnauba wax.
Flexeril (Cyclobenzaprine hcl) 10 mg (Cyclobenzaprine HCl) tablets contain the following inactive ingredients: lactose hydrous, pre-gelatinized starch, corn starch, magnesium stearate, hydroxypropyl cellulose, hypromellose, titanium dioxide, yellow iron oxide, and carnauba wax.
Flexeril (Cyclobenzaprine hcl) Clinical Pharmacology
Cyclobenzaprine HCl relieves skeletal muscle spasm of local origin without interfering with muscle function. It is ineffective in muscle spasm due to central nervous system disease.
Cyclobenzaprine reduced or abolished skeletal muscle hyperactivity in several animal models. Animal studies indicate that cyclobenzaprine does not act at the neuromuscular junction or directly on skeletal muscle. Such studies show that cyclobenzaprine acts primarily within the central nervous system at brain stem as opposed to spinal cord levels, although its action on the latter may contribute to its overall skeletal muscle relaxant activity. Evidence suggests that the net effect of cyclobenzaprine is a reduction of tonic somatic motor activity, influencing both gamma (γ) and alpha (α) motor systems.
Pharmacological studies in animals showed a similarity between the effects of cyclobenzaprine and the structurally related tricyclic antidepressants, including reserpine antagonism, norepinephrine potentiation, potent peripheral and central anticholinergic effects, and sedation. Cyclobenzaprine caused slight to moderate increase in heart rate in animals.
Flexeril (Cyclobenzaprine hcl) Indications And Usage
Flexeril (Cyclobenzaprine hcl) is 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.
Flexeril (Cyclobenzaprine hcl) has not been found effective in the treatment of spasticity associated with cerebral or spinal cord disease, or in children with cerebral palsy.
Flexeril (Cyclobenzaprine hcl) Contraindications
Hypersensitivity to any component of this product.
Concomitant use of monoamine oxidase (MAO) inhibitors or within 14 days after their discontinuation. Hyperpyretic crisis seizures, and deaths have occurred in patients receiving cyclobenzaprine (or structurally similar tricyclic antidepressants) concomitantly with MAO inhibitor drugs.
Acute recovery phase of myocardial infarction, and patients with arrhythmias, heart block or conduction disturbances, or congestive heart failure.
Hyperthyroidism.
Flexeril (Cyclobenzaprine hcl) Warnings
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 ).
Tricyclic antidepressants have been reported to produce arrhythmias, sinus tachycardia, prolongation of the conduction time leading to myocardial infarction and stroke.
Flexeril (Cyclobenzaprine hcl) may enhance the effects of alcohol, barbiturates, and other CNS depressants.
Flexeril (Cyclobenzaprine hcl) Precautions
Flexeril (Cyclobenzaprine hcl) may have life-threatening interactions with MAO inhibitors. (See .)
Flexeril (Cyclobenzaprine hcl) 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.
In rats treated with Flexeril (Cyclobenzaprine hcl) for up to 67 weeks at doses of approximately 5 to 40 times the maximum recommended human dose, pale, sometimes enlarged, livers were noted and there was a dose-related hepatocyte vacuolation with lipidosis. In the higher dose groups this microscopic change was seen after 26 weeks and even earlier in rats which died prior to 26 weeks; at lower doses, the change was not seen until after 26 weeks.
Cyclobenzaprine did not affect the onset, incidence or distribution of neoplasia in an 81-week study in the mouse or in a 105-week study in the rat.
At oral doses of up to 10 times the human dose, cyclobenzaprine did not adversely affect the reproductive performance or fertility of male or female rats. Cyclobenzaprine did not demonstrate mutagenic activity in the male mouse at dose levels of up to 20 times the human dose.
P11413352
Pregnancy Category B:
Flexeril (Cyclobenzaprine hcl) Adverse Reactions
Incidence of most common adverse reactions in the 2 double-blind, placebo-controlled 5 mg studies (incidence of > 3% on Flexeril (Cyclobenzaprine hcl) 5 mg):
Adverse reactions which were reported in 1% to 3% of the patients were: abdominal pain, acid regurgitation, constipation, diarrhea, dizziness, nausea, irritability, mental acuity decreased, nervousness, upper respiratory infection, and pharyngitis.
The following list of adverse reactions is based on the experience in 473 patients treated with Flexeril (Cyclobenzaprine hcl) 10 mg in additional controlled clinical studies, 7607 patients in the postmarketing surveillance program, and reports received since the drug was marketed. The overall incidence of adverse reactions among patients in the surveillance program was less than the incidence in the controlled clinical studies.
The adverse reactions reported most frequently with Flexeril (Cyclobenzaprine hcl) were drowsiness, dry mouth and dizziness. The incidence of these common adverse reactions was lower in the surveillance program than in the controlled clinical studies:
Among the less frequent adverse reactions, there was no appreciable difference in incidence in controlled clinical studies or in the surveillance program. Adverse reactions which were reported in 1% to 3% of the patients were: fatigue/tiredness, asthenia, nausea, constipation, dyspepsia, unpleasant taste, blurred vision, headache, nervousness, and confusion.
The following adverse reactions have been reported in post-marketing experience or with an incidence of less than 1% of patients in clinical trials with the 10 mg tablet:
Flexeril (Cyclobenzaprine hcl) Drug Abuse And Dependence
Pharmacologic similarities among the tricyclic drugs require that certain withdrawal symptoms be considered when Flexeril (Cyclobenzaprine hcl) is administered, even though they have not been reported to occur with this drug. Abrupt cessation of treatment after prolonged administration rarely may produce nausea, headache, and malaise. These are not indicative of addiction.
Flexeril (Cyclobenzaprine hcl) Overdosage
Although rare, deaths may occur from overdosage with Flexeril (Cyclobenzaprine hcl) . Multiple drug ingestion (including alcohol) is common in deliberate cyclobenzaprine overdose. Signs and symptoms of toxicity may develop rapidly after cyclobenzaprine overdose; therefore, hospital monitoring is required as soon as possible. The acute oral LD of Flexeril (Cyclobenzaprine hcl) is approximately 338 and 425 mg/kg in mice and rats, respectively.
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 .
Flexeril (Cyclobenzaprine hcl) Dosage And Administration
For most patients, the recommended dose of Flexeril (Cyclobenzaprine hcl) is 5 mg three times a day. Based on individual patient response, the dose may be increased to 10 mg three times a day. Use of Flexeril (Cyclobenzaprine hcl) for periods longer than two or three weeks is not recommended. (see ).
Less frequent dosing should be considered for hepatically impaired or elderly patients (see , and ).
Flexeril (Cyclobenzaprine hcl) How Supplied
Flexeril (Cyclobenzaprine hcl) tablets are available in 5 mg and 10 mg dosage strengths. The 5 mg tablets are yellow-orange, 5-sided, film coated tablets, coded FLEX over 5 on one side and without coding on the other. The 10 mg tablets are butterscotch yellow, 5-sided D-shaped, bi-convex, film coated tablets, coded Flexeril (Cyclobenzaprine hcl) on one side and without coding on the other. The two dosage strengths are supplied as follows:
Flexeril (Cyclobenzaprine hcl) Storage
Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F). [see USP Controlled Room Temperature].
Rx Only
For more information call 1-888-440-7903 or visit www.Flexeril (Cyclobenzaprine hcl) .info
Manufactured by:McNeil Consumer HealthcareDivision of McNeil-PPC, Inc.Fort Washington, PA 19034
Manufactured for:McNeil PediatricsDivision of Ortho-McNeil-Janssen Pharmaceuticals, Inc.Titusville, NJ 08560
Edition: January 2010Update Component Code
Flexeril (Cyclobenzaprine hcl) Flexeril Mg Tablet
USUAL ADULT DOSAGE: See accompanying product information.
