Cyclotens starter pak kit

Description

Cyclobenzaprine hydrochloride, USP is a white, crystalline tricyclic amine salt with the empirical formula C 20H 21NHCl and a molecular weight of 311.9. It has a melting point of 217C, and a pK aof 8.47 at 25C. 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-( 5Hdibenzo[ a, d]cyclohepten-5-ylidene)- N, N-dimethyl-1-propanamine hydrochloride, and has the following structural formula:

Cyclotens starter pak

Cyclobenzaprine HCl USP, 10 mg is supplied as a 10 mg tablet for oral administration.

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

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 () 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.

Pharmacokinetics

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 Elderlyand PRECAUTIONS, Impaired Hepatic Function.)

Clinical studies

Eight double-blind controlled clinical studies were performed in 642 patients comparing cyclobenzaprine HCl 10 mg, diazepam **, and placebo. Muscle spasm, local pain and tenderness, limitation of motion, and restriction in activities of daily living were evaluated. In three of these studies there was a significantly greater improvement with cyclobenzaprine HCl than with diazepam, while in the other studies the improvement following both treatments was comparable.

Although the frequency and severity of adverse reactions observed in patients treated with cyclobenzaprine HCl were comparable to those observed in patients treated with diazepam, dry mouth was observed more frequently in patients treated with cyclobenzaprine HCl and dizziness more frequently in those treated with diazepam. The incidence of drowsiness, the most frequent adverse reaction, was similar with both drugs.

The efficacy of cyclobenzaprine HCl tablets, 5 mg was demonstrated in two seven-day, double-blind, controlled clinical trials enrolling 1405 patients. One study compared cyclobenzaprine HCl tablets, 5 mg and 10 mg t.i.d. to placebo; and a second study compared cyclobenzaprine HCl tablets, 5 mg and 2.5 mg t.i.d. to placebo. Primary endpoints for both trials were determined by patient-generated data and included global impression of change, medication helpfulness, and relief from starting backache. Each endpoint consisted of a score on a 5-point rating scale (from 0 or worst outcome to 4 or best outcome). Secondary endpoints included a physician's evaluation of the presence and extent of palpable muscle spasm.

Comparisons of cyclobenzaprine HCl tablets, 5 mg and placebo groups in both trials established the statistically significant superiority of the 5 mg dose for all three primary endpoints at day 8 and, in the study comparing 5 and 10 mg, at day 3 or 4 as well. A similar effect was observed with cyclobenzaprine HCl tablets, 10 mg (all endpoints). Physician-assessed secondary endpoints also showed that cyclobenzaprine HCl tablets, 5 mg was associated with a greater reduction in palpable muscle spasm than placebo.

Analysis of the data from controlled studies shows that cyclobenzaprine HCl produces clinical improvement whether or not sedation occurs.

**VALIUM ®(diazepam, Roche)

Indications and usage

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

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

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

Information for patients

Cyclobenzaprine HCl, 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 HCl should be initiated with a 5 mg dose and titrated slowly upward.

Patients should be cautioned about the risk of serotonin syndrome with the concomitant use of

Cyclobenzaprine Hydrochloride and other drugs, such as selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), tramadol, bupropion, meperidine, verapamil, or MAO inhibitors. Patients should be advised of the signs and symptoms of serotonin syndrome, and be instructed to seek medical care immediately if they experience these symptoms (see WARNINGS, and see PRECAUTIONS, Drug Interactions)

Drug interactions

Cyclobenzaprine HCl may have life-threatening interactions with MAO inhibitors. (See CONTRAINDICATIONS.) Postmarketing cases of serotonin syndrome have been reported during combined use of Cyclobenzaprine Hydrochloride and other drugs, such as SSRIs, SNRIs, TCAs, tramadol, bupropion, meperidine, verapamil, or MAO inhibitors. 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 WARNINGS).

Cyclobenzaprine HCl 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)

Pregnancy

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 HCl. 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.

Nursing mothers

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 HCl is administered to a nursing woman.

Pediatric use

Safety and effectiveness of cyclobenzaprine HCl in pediatric patients below 15 years of age have not been established.

Adverse reactions

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):

Cyclotens starter pak

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 .

Cyclotens starter pak

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

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

Spl unclassified section

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 LD50 of cyclobenzaprine HCl is approximately 338 and 425 mg/kg in mice and rats, respectively.

Dosage and administration

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

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:

10 mg 30 count bottle NDC70914-011-30

Storage

Store at 20 to 25C (68 to 77F) [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

Distributed by:
Hudson Scientific LLC
103 W. Main ST
Hudson, MI 49247


Revised: January 2017

Ingredients and appearance - Product information

Cyclotens starter pak kit- Cyclobenzaprine

Product information

Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC: 70914-012
Route of Administration Oral

Product Characteristics

Color YELLOW Shape ROUND
Size 7 mm Score 1
Imprint Code IG;283

Marketing Information

Marketing Category Application Number or Monograph Citation Territorial Authority Marketing Start Date
ANDA ANDA090478 USA 2017/01/23

Labeler - Hudson Scientific LLC( 080339637)

Establishment

Name ID/FEI Business Operations
Hudson Scientific LLC 080339637 analysis( 70914-011), manufacture( 70914-011)

Package label.principal display panel

NDC 70914-012-00 CycloTENS Starter Pak

TENS Unit

TENS Replacement Pads
NDC 70914-011-30
Cyclobenzaprine Hydrochloride

RX Only

Tablets, USP

10 mg

30 Tablets