Cyclobenzaprine hydrochloride tablet
Cyclobenzaprine hydrochloride 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 () and alpha () 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.
Estimates of mean oral bioavailability of cyclobenzaprine range from 33% to 55%. Cyclobenzaprine exhibits linear pharmacokinetics over the dose range 2.5 mg to 10 mg, and is subject to enterohepatic circulation. It is highly bound to plasma proteins. Drug accumulates when dosed three times a day, reaching steady-state within 3-4 days at plasma concentrations about four-fold higher than after a single dose. At steady state in healthy subjects receiving 10 mg t.i.d. (n=18), peak plasma concentration was 25.9 ng/mL (range, 12.8-46.1 ng/mL), and area under the concentration-time (AUC) curve over an 8-hour dosing interval was 177 ng.hr/mL (range, 80-319 ng.hr/mL).
Cyclobenzaprine is extensively metabolized, and is excreted primarily as glucuronides via the kidney. Cytochromes P-450 3A4, 1A2, and, to a lesser extent, 2D6, mediate N-demethylation, one of the oxidative pathways for cyclobenzaprine. Cyclobenzaprine is eliminated quite slowly, with an effective half-life of 18 hours (range 8-37 hours; n=18); plasma clearance is 0.7 L/min.
The plasma concentration of cyclobenzaprine is generally higher in the elderly and in patients with hepatic impairment. (See PRECAUTIONS, Use in the Elderly and PRECAUTIONS, Impaired Hepatic Function .)
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 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 has not been found effective in the treatment of spasticity associated with cerebral or spinal cord disease, or in children with cerebral palsy.
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.
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 WARNINGS, 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.
Because of its atropine-like action, cyclobenzaprine hydrochloride 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.
Information for patients
Cyclobenzaprine hydrochloride, 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. In the elderly, the frequency and severity of adverse events associated with the use of cyclobenzaprine, with or without concomitant medications, is increased. In elderly patients, cyclobenzaprine hydrochloride should be initiated with a 5 mg dose and titrated slowly upward.
Cyclobenzaprine hydrochloride may have life-threatening interactions with MAO inhibitors. (See CONTRAINDICATIONS.)
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 hydrochloride tablets, Ortho-McNeil Pharmaceutical)
ULTRACET® (tramadol hydrochloride and acetaminophen tablets, Ortho-McNeil Pharmaceutical)
Carcinogenesis, mutagenesis, impairment of fertility
In rats treated with cyclobenzaprine hydrochloride 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.
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.
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 is administered to a nursing woman.
Safety and effectiveness of cyclobenzaprine hydrochloride in pediatric patients below 15 years of age have not been established.
Incidence of most common adverse reactions in the 2 double-blind, placebo-controlled 5 mg studies (incidence of > 3% on cyclobenzaprine hydrochloride tablets, 5 mg):
Tablets, 5 mg
Tablets, 10 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 cyclobenzaprine hydrochloride tablets, 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 cyclobenzaprine hydrochloride 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:
Note: Cyclobenzaprine Hydrochloride tablets, 10 mg data are from one clinical trial. Cyclobenzaprine Hydrochloride tablets, 5 mg and placebo data are from two studies.
Clinical Studies With
Tablets, 10 mg
With Cyclobenzaprine HCl
Tablets, 10 mg
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:
Body as a Whole:Syncope; malaise.
Cardiovascular:Tachycardia; arrhythmia; vasodilatation; palpitation; hypotension.
Digestive:Vomiting; anorexia; diarrhea; gastrointestinal pain; gastritis; thirst; flatulence; edema of the tongue; abnormal liver function and rare reports of hepatitis, jaundice and cholestasis.
Hypersensitivity:Anaphylaxis; angioedema; pruritus; facial edema; urticaria; rash.
Nervous System and Psychiatric:Seizures, ataxia; vertigo; dysarthria; tremors; hypertonia; convulsions; muscle twitching; disorientation; insomnia; depressed mood; abnormal sensations; anxiety; agitation; psychosis, abnormal thinking and dreaming; hallucinations; excitement; paresthesia; diplopia.
Special Senses:Ageusia; tinnitus.
Urogenital:Urinary frequency and/or retention.
Causal Relationship Unknown
Other reactions, reported rarely for cyclobenzaprine hydrochloride under circumstances where a causal relationship could not be established or reported for other tricyclic drugs, are listed to serve as alerting information to physicians:
Body as a whole:Chest pain; edema.
Cardiovascular:Hypertension; myocardial infarction; heart block; stroke.
Digestive:Paralyticileus, tongue discoloration; stomatitis; parotid swelling.
Endocrine:Inappropriate ADH syndrome.
Hematic and Lymphatic:Purpura; bone marrow depression; leukopenia; eosinophilia; thrombocytopenia.
Metabolic, Nutritional and Immune:Elevation and lowering of blood sugar levels; weight gain or loss.
Nervous System and Psychiatric:Decreased or increased libido; abnormal gait; delusions; aggressive behavior; paranoia; peripheral neuropathy; Bell's palsy; alteration in EEG patterns; extrapyramidal symptoms.
Urogenital:Impaired urination; dilatation of urinary tract; impotence; testicular swelling; gynecomastia; breast enlargement; galactorrhea.
Drug abuse and dependence
Pharmacologic similarities among the tricyclic drugs require that certain withdrawal symptoms be considered when cyclobenzaprine hydrochloride 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.
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 LD50 of cyclobenzaprine hydrochloride is approximately 338 and 425 mg/kg in mice and rats, respectively.
Dosage and administration
For most patients, the recommended dose of cyclobenzaprine hydrochloride tablets USP 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 cyclobenzaprine hydrochloride tablets USP for periods longer than two or three weeks is not recommended. (see INDICATIONS AND USAGE).
Ingredients and appearance - Product information
Cyclobenzaprine hydrochloride tablet- Cyclobenzaprine hydrochloride
|Product Type||HUMAN PRESCRIPTION DRUG LABEL||Item Code (Source)||NDC: 45865-433|
|Route of Administration||Oral|
|Cyclobenzaprine hydrochloride ( UNII: 0VE05JYS2P)( Cyclobenzaprine - UNII: 69O5WQQ5TI )||10 mgin 1|
|Lactose monohydrate||( UNII: EWQ57Q8I5X)|
|Cellulose, microcrystalline||( UNII: OP1R32D61U)|
|Starch, corn||( UNII: O8232NY3SJ)|
|Silicon dioxide||( UNII: ETJ7Z6XBU4)|
|Magnesium stearate||( UNII: 70097M6I30)|
|Hypromelloses||( UNII: 3NXW29V3WO)|
|Titanium dioxide||( UNII: 15FIX9V2JP)|
|Polyethylene glycol 400||( UNII: B697894SGQ)|
|Ferric oxide yellow||( UNII: EX438O2MRT)|
|Polysorbate 80||( UNII: 6OZP39ZG8H)|
|Marketing Category||Application Number or Monograph Citation||Territorial Authority||Marketing Start Date|
Labeler - Medsource Pharmaceuticals( 833685915)
|Medsource Pharmaceuticals||833685915||repack( 45865-433)|