Cyclobenzaprine Hydrochloride Tablets USP, Revised: January 2009, Rx only

/Cyclobenzaprine Hydrochloride Tablets USP, Revised: January 2009, Rx only
Cyclobenzaprine Hydrochloride Tablets USP, Revised: January 2009, Rx only2018-09-06T09:12:40+00:00

Prescription Drug Name:

Cyclobenzaprine Hydrochloride Tablets USP, Revised: January 2009, Rx only

ID:

1313f0dc-5975-5ec7-e054-00144ff8d46c

Code:

34391-3

DESCRIPTION


id: 1312f227-e37b-34f5-e054-00144ff8d46c
displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3

Cyclobenzaprine hydrochloride is a white, crystalline tricyclic amine salt. 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 is designated chemically as 3-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-N,N-dimethyl-1-propanamine hydrochloride, and has the following structural formula:
C20H21N•HCl               M.W. 311.9 Cyclobenzaprine hydrochloride tablets, USP are available for oral administration as 5 mg, 7.5 mg and 10 mg tablets. Cyclobenzaprine hydrochloride 5 mg, 7.5 mg and 10 mg tablets contain the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, dibasic calcium phosphate, hydroxypropyl cellulose, hypromellose, polyethylene glycol, magnesium stearate, microcrystalline cellulose, and titanium dioxide.

CLINICAL PHARMACOLOGY


id: 1312f227-e37c-34f5-e054-00144ff8d46c
displayName: CLINICAL PHARMACOLOGY SECTION
FDA Article Code: 34090-1

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


id: 1312f227-e382-34f5-e054-00144ff8d46c
displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9

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. 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


id: 1312f227-e383-34f5-e054-00144ff8d46c
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. Hyperthyroidism.

WARNINGS


id: 1312f227-e384-34f5-e054-00144ff8d46c
displayName: WARNINGS SECTION
FDA Article Code: 34071-1

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.

ADVERSE REACTIONS


id: 1312f227-e38f-34f5-e054-00144ff8d46c
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 HCl 5 mg):

Cyclobenzaprine HCl Cyclobenzaprine HCl Placebo
5 mg 10 mg
N=464 N=249 N=469
Drowsiness 29% 38% 10%
Dry Mouth 21% 32% 7%
Fatigue 6% 6% 3%
Headache 5% 5% 8%
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 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:
Clinical Studies with Surveillance Program with
Cyclobenzaprine HCl Tablets 10 mg Cyclobenzaprine HCl Tablets 10 mg
Drowsiness 39% 16%
Dry mouth 27% 7%
Dizziness 11% 3%
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 postmarketing 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; pruritis; 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. Skin: Sweating. Special Senses: Ageusia; tinnitus. Urogenital: Urinary frequency and/or retention. ________________________________________________________________________ Note: Cyclobenzaprine HCl Tablets 10 mg data are from one clinical trial. Cyclobenzaprine HCl Tablets 5 mg and placebo data are from two studies.

________________________________________________________________________ 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


id: 1312f227-e390-34f5-e054-00144ff8d46c
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 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


id: 1312f227-e391-34f5-e054-00144ff8d46c
displayName: OVERDOSAGE SECTION
FDA Article Code: 34088-5

Although rare, deaths may occur from overdosage with cyclobenzaprine HCl. 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 HCl 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 HCl 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.

DOSAGE AND ADMINISTRATION


id: 1312f227-e392-34f5-e054-00144ff8d46c
displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7

For most patients, the recommended dose of cyclobenzaprine HCl is 5 mg three times a day. Based on individual patient response, the dose may be increased to either 7.5 mg or 10 mg three times a day. Use of cyclobenzaprine HCl 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


id: 1312f227-e393-34f5-e054-00144ff8d46c
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5

Cyclobenzaprine Hydrochloride Tablets USP, 10 mg are round, white, film-coated tablets imprinted
DAN and
5658 supplied in:

Bottles of 2 10544-072-02
Bottles of 9 10544-072-09
Bottles of 10 10544-072-10
Bottles of 14 10544-072-14
Bottles of 15 10544-072-15
Bottles of 20 10544-072-20
Bottles of 21 10544-072-21
Bottles of 30 10544-072-30
Bottles of 45 10544-072-45
Bottles of 60 10544-072-60
Bottles of 84 10544-072-84
Bottles of 90 10544-072-90
Dispense in a well-closed container with child-resistant closure.

Principal Display Panel – 10 mg 15s


id: 1312f227-e395-34f5-e054-00144ff8d46c
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4