displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3
Cyclobenzaprine hydrochloride, USP is a white, crystalline tricyclic amine salt with the chemical name C20H21N•HCl, and a molecular weight of 311.85. It has a melting point of 217°C, and a pKa 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 hydrochloride, USP is designated chemically as 3-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-N,N-dimethyl-1propanamine hydrochloride, and has the following structural formula:
C20H21N•HCl M.W. 311.9
Each tablet for oral administration contains 10 mg cyclobenzaprine hydrochloride, USP. In addition, each tablet contains the following inactive ingredients: anhydrous lactose, carnauba wax, corn starch, crospovidone, hypromellose, magnesium stearate, pregelatinized corn starch, polyethylene glycol, polysorbate 80, titanium dioxide, D&C Yellow #10 aluminum lake, FD&C Blue #2 aluminum lake, and FD&C Yellow #6 aluminum lake.
displayName: CLINICAL PHARMACOLOGY SECTION
FDA Article Code: 34090-1
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 (g) and alpha (a) 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.
INDICATIONS AND USAGE
displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9
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 have not been found effective in the treatment of spasticity associated with cerebral or spinal cord disease, or in children with cerebral palsy.
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3
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.
displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4
Incidence of most common adverse reactions in the 2 double-blind‡, placebo-controlled 5 mg studies (incidence of > 3% on cyclobenzaprine hydrochloride 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 cyclobenzaprine hydrochloride 10 mg in additional controlled clinical studies, 7607 patients in the post-marketing 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 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:
Cyclobenzaprine Hydrochloride 5 mg
N = 464
Cyclobenzaprine Hydrochloride 10 mg
N = 249
N = 469
Note: Cyclobenzaprine hydrochloride 10 mg data are from one clinical trial. Cyclobenzaprine hydrochloride 5 mg and placebo data are from two 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:
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.
Musculoskeletal: Local weakness.
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, serotonin syndrome.
Special Senses: Ageusia; tinnitus.
Urogenital: Urinary frequency and/or retention.
Clinical Studies With Cyclobenzaprine Hydrochloride 10 mg
Surveillance Program With Cyclobenzaprine Hydrochloride 10 mg
DRUG ABUSE AND DEPENDENCE
displayName: DRUG ABUSE AND DEPENDENCE SECTION
FDA Article Code: 42227-9
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.
displayName: OVERDOSAGE SECTION
FDA Article Code: 34088-5
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
displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7
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 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).
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5
Cyclobenzaprine Hydrochloride Tablets USP are available as:
Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].
Dispense in a tight, light-resistant container as defined in the USP, with a child resistant closure (as required).
KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.
All brand names listed are the registered trademarks of their respective owners and are not trademarks of Teva Pharmaceuticals USA.
Manufactured in Czech Republic By:
TEVA Czech Industries, s.r.o.
TEVA PHARMACEUTICALS USA
Sellersville, PA 18960
Rev. D 5/2013
Yellow, round, film-coated, unscored tablets debossed with 563 on one side and PLIVA on the other side. Available in bottles of 100, 500 and 1000.
PRINCIPAL DISPLAY PANEL
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4