Cyclobenzaprine HCl Tablets, USP 5 mg and 10 mg

DESCRIPTION

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displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3

Cyclobenzaprine hydrochloride is a white, crystalline tricyclic amine salt with the empirical formula C₂₀H₂₁N•HCl and a molecular weight of 311.9. 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 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:
Cyclobenzaprine HCl is supplied as 5 and 10 mg tablets for oral administration. Cyclobenzaprine HCl tablets, USP 5 mg contain the following inactive ingredients: carnauba wax powder, croscarmellose sodium, FD&C Yellow #6 Aluminum Lake, iron oxide yellow, lactose monohydrate, lecithin, macrogol, magnesium stearate, microcrystalline cellulose, polyvinyl alcohol, silicon dioxide, talc, titanium dioxide.Cyclobenzaprine HCl tablets, USP 10 mg contain the following inactive ingredients: carnauba wax powder, croscarmellose sodium, D&C Yellow #10 Aluminum Lake, FD&C Yellow #6 Aluminum Lake, hypromellose, iron oxide yellow, lactose monohydrate, macrogol, magnesium stearate, methylparaben, microcrystalline cellulose, polysorbate, potassium sorbate, propylparaben, propylene glycol, silicon dioxide, sodium citrate, titanium dioxide, xanthan gum.

CLINICAL PHARMACOLOGY

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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

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displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9

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

CONTRAINDICATIONS

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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

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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

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displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4

Incidence of most common adverse reactions in the 2 double-blindNote: Cyclobenzaprine HCl tablets, USP 10 mg data are from one clinical trial. Cyclobenzaprine HCl tablets, USP 5 mg and placebo data are from two studies. , placebo-controlled 5 mg studies (incidence of >3% on cyclobenzaprine HCl tablets, USP 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, USP 10 mg in additional controlled clinical studies, 7,607 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 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: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.

DRUG ABUSE AND DEPENDENCE

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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 tablets are 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

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displayName: OVERDOSAGE SECTION
FDA Article Code: 34088-5

Although rare, deaths may occur from overdosage with cyclobenzaprine HCl tablets. 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 HCl is approximately 338 and 425 mg/kg in mice and rats, respectively.

MANAGEMENT

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displayName: SPL UNCLASSIFIED SECTION
FDA Article Code: 42229-5

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 tablets 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 pCO₂ < 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

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displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7

For most patients, the recommended dose of cyclobenzaprine HCl tablet 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 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

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displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5

Cyclobenzaprine HCl tablets, USP 5 mg are orange-colored, film- coated, round biconvex tablets, debossed “148 O” on one side. Available in bottles of 100’s (NDC 69584-148-10) and 1000’s (NDC 69584-148-90). Cyclobenzaprine HCl tablets, USP 10 mg are yellow-colored, film- coated, round biconvex tablets, debossed “149 O” on one side. Available in bottles of 100’s (NDC 69584-149-10) and 1000’s (NDC 69584-149-90). Store at controlled room temperature, 20° to 25°C (68° to 77°F) excursions permitted between 15° to 30°C (59° to 86°F). [See USP Controlled Room Temperature]. Rx Only For more information call 844‑508‑1455, 8:00 am – 6:00 pm CT, Monday – Friday MANUFACTURED BY: Oxford Pharmaceuticals LLC
301 Leaf lake Parkway
Birmingham, AL 35211

8200003
Rev. 0118-00

PACKAGE LABEL

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displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4

NDC 69584-148-10

Cyclobenzaprine
TABLETS, USP

5 mg

Rx only

100 Tablets

OXFORD PHARMACEUTICALS, LLC

EACH TABLET CONTAINS:

Cyclobenzaprine hydrochloride, USP…5mg

USUAL DOSAGE: See package insert for full prescribing information.

DISPENSE in a tight, light-resistant container as defined in the USP, using a child-resistant closure.

STORE at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].

Keep container tightly closed.

KEEP THIS AND ALL MEDICATIONS OUT OF REACH OF CHILDREN.

Manufactured by:
OXFORD PHARMACEUTICALS, LLC
BIRMINGHAM, AL 35211

8000015
Rev: 0118-00

NDC 69584-149-10

Cyclobenzaprine
TABLETS, USP

10 mg

Rx only

100 Tablets

OXFORD PHARMACEUTICALS, LLC

EACH TABLET CONTAINS:

Cyclobenzaprine hydrochloride, USP…10mg

USUAL DOSAGE: See package insert for full prescriing information.

DISPENSE in a tight, light-resistant container as defined in the USP, using a child-resistant closure.

STORE at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].

Keep container tightly closed.

KEEP THIS AND ALL MEDICATIONS OUT OF REACH OF CHILDREN.

Manufactured by:
OXFORD PHARMACEUTICALS, LLC
BIRMINGHAM, AL 35211

8000013
Rev: 0118-00