CYCLOBENZAPRINE HCl TABLETS USP

DESCRIPTION

DESCRIPTION SECTION

Cyclobenzaprine hydrochloride, USP is a white, crystalline tricyclic amine salt with the empirical 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 and alcohol, sparingly soluble in isopropanol, and insoluble in hydrocarbon solvents. If aqueous solutions are made alkaline, the free base separates. Cyclobenzaprine HCl, USP 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 HCl USP, 5 mg is supplied as a 5 mg tablet for oral administration. Cyclobenzaprine HCl USP, 10 mg is supplied as a 10 mg tablet for oral administration. Cyclobenzaprine HCl tablets USP, 5 mg contain the following inactive ingredients: lactose monohydrate, microcrystalline cellulose, pregelatinized starch, colloidal silicon dioxide, magnesium stearate and opadry beige (hypromellose 6cP, titanium dioxide, PEG 400, iron oxide yellow and iron oxide red). Cyclobenzaprine HCl tablets USP, 10 mg contain the following inactive ingredients: lactose monohydrate, microcrystalline cellulose, pregelatinized starch, colloidal silicon dioxide, magnesium stearate and opadry yellow (hypromellose 3cp, hypromellose 6cp, titanium dioxide, PEG 400, iron oxide yellow and polysorbate 80).

CLINICAL PHARMACOLOGY

CLINICAL PHARMACOLOGY SECTION

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.

INDICATIONS AND USAGE

INDICATIONS & USAGE SECTION

Cyclobenzaprine HCl 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 HCl 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 HCl has not been found effective in the treatment of spasticity associated with cerebral or spinal cord disease, or in children with cerebral palsy.

CONTRAINDICATIONS

CONTRAINDICATIONS SECTION

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.

WARNINGS

WARNINGS SECTION

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 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 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 HCl may enhance the effects of alcohol, barbiturates, and other CNS depressants.

PRECAUTIONS

PRECAUTIONS SECTION

ADVERSE REACTIONS

ADVERSE REACTIONS SECTION

Incidence of most common adverse reactions in the 2 double-blind ‡ , placebo-controlled 5 mg studies (incidence of > 3% on cyclobenzaprine HCl tablets, 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 HCl 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 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: ‡ Note: Cyclobenzaprine HCl tablets, 10 mg data are from one clinical trial. Cyclobenzaprine HCl tablets, 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. Skin: Sweating. Special Senses: Ageusia; tinnitus. Urogenital: Urinary frequency and/or retention. Causal Relationship Unknown Other reactions, reported rarely for cyclobenzaprine HCl 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: Paralytic ileus, 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. Musculoskeletal: Myalgia. 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. Respiratory: Dyspnea. Skin: Photosensitization; alopecia. Urogenital: Impaired urination; dilatation of urinary tract; impotence; testicular swelling; gynecomastia; breast enlargement; galactorrhea.

DRUG ABUSE AND DEPENDENCE

DRUG ABUSE AND DEPENDENCE SECTION

Pharmacologic similarities among the tricyclic drugs require that certain withdrawal symptoms be considered when 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.

OVERDOSAGE

OVERDOSAGE SECTION

DOSAGE AND ADMINISTRATION

DOSAGE & ADMINISTRATION SECTION

For most patients, the recommended dose of cyclobenzaprine HCl 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 HCl tablets USP 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 ).

HOW SUPPLIED

HOW SUPPLIED SECTION

Cyclobenzaprine hydrochloride tablets USP are available in 5 mg and 10 mg dosage strengths. The 5 mg tablets are beige colored, film coated, round, biconvex tablets debossed with 'IG' on one side and "282" on other. The 10 mg tablets are yellow colored, film coated, round, biconvex tablets debossed with 'IG' on one side and "283" on other. The two dosage strengths are supplied as follows: 5 mg – 90 count bottle NDC 68645-517-90 10 mg – 90 count bottle NDC 68645-518-90

STORAGE

STORAGE AND HANDLING SECTION

Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Rx Only Manufactured for: Cipla USA Inc., 9100 S. Dadeland Blvd., Suite 1500 Miami, FL 33156 Manufactured by: InvaGen Pharmaceuticals, Inc. (a subsidiary of Cipla Ltd.) Hauppauge, NY 11788 Revised: 07/2016 Distributed by: Wal-Mart Bentonville, AR 72716 Packaged by: Legacy Pharmaceutical Packaging LLC Earth City, MO 63045

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

NDC 68645-517-90 Rx Only Cyclobenzaprine Hydrochloride Tablets, USP 5 mg 90 Tablets NDC 68645-518-90 Rx Only Cyclobenzaprine Hydrochloride Tablets, USP 10 mg 90 Tablets