25C.Is freely soluble in water and alcohol, sparingly soluble in isopropanol, and insoluble in hydrocarbon solvents.Aqueous solutions are made alkaline, the free base separates.Is designated chemically as 3-(5H-dibenzo cyclohepten-5-ylidene)-N, N-dimethyl-1-propanamine hydrochloride, and has the following structural formula: Cyclobenzaprine HCl is supplied as a 5 mg tablet for oral administration.Cyclobenzaprine HCl tablets, USP 5 mg contain the following inactive ingredients: carnauba wax powder, croscarmellose sodium, FD n=18); plasma clearance is 0. The plasma concentration of cyclobenzaprine is generally higher in the elderly and in patients with hepatic impairment.And ) ELDERLY In a pharmacokinetic study in elderly individuals (>65 yrs old), mean (n=10) steady-state cyclobenzaprine AUC values were approximately 1.(171.Range 96.Higher than those seen in a group of eighteen younger adults (101.Range 36.From another study.Subjects had the highest observed mean increase, approximately 2.(198.Range 155.Versus 83.Range 41.For younger males) while levels in elderly females were increased to a much lesser extent, approximately 1.(143.Range 96.Versus 115.Range 36.For younger females).In light of these findings, therapy with cyclobenzaprine HCl in the elderly should be initiated with a 5 mg dose and titrated slowly upward.HEPATIC IMPAIRMENT In a pharmacokinetic study of sixteen subjects with hepatic impairment (15 mild, 1 moderate per Child-Pugh score), both AUC and Cmax were approximately double the values seen in the healthy control group.On the findings, cyclobenzaprine HCl should be used with caution in subjects with mild hepatic impairment starting with the 5 mg dose and titrating slowly upward.To the lack of data in subjects with more severe hepatic insufficiency, the use of cyclobenzaprine HCl in subjects with moderate to severe impairment is not rmended.No significant effect on plasma levels or bioavailability of cyclobenzaprine HCl or aspirin was noted when single or multiple doses of the two drugs were administered coitantly.Of cyclobenzaprine HCl and naproxen or diflunisal was well tolerated with no reported unexpected adverse effects.Therapy of cyclobenzaprine HCl with naproxen was associated with more side effects than therapy with naproxen alone, primarily in the form of drowsiness.Well-controlled studies have been performed to indicate that cyclobenzaprine HCl enhances the clinical effect of aspirin or other analgesics, or whether analgesics enhance the clinical effect of cyclobenzaprine HCl in acute musculoskeletal conditions.CLINICAL STUDIES Eight double-blind controlled clinical studies were performed in 642 patientsparing cyclobenzaprine HCl tablets, USP 10 mg, diazepam, and placebo.Local pain and tenderness, limitation of motion, and restriction in activities of daily living were evaluated.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 wasparable.Although the frequency and severity of adverse reactions observed in patients treated with cyclobenzaprine HCl wereparable 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.Incidence of drowsiness, the most frequent adverse reaction, was similar with both drugs.The efficacy of cyclobenzaprine HCl tablets, USP 5 mg was demonstrated in two seven-day, double-blind, controlled clinical trials enrolling 1,405 patients.Studypared cyclobenzaprine HCl tablets, USP 5 mg and 10 mg t.To placebo; and a second studypared cyclobenzaprine HCl tablets, USP 5 mg and 2.T.To placebo.For both trials were determined by patient-generated data and included global impression of change, medication helpfulness, and relief from starting backache.Endpoint consisted of a score on a 5-point rating scale (from 0 or worst oue to 4 or best oue).Included a physician's evaluation of the presence and extent of palpable muscle spasm.Parison of cyclobenzaprine HCl tablets, USP 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 studyparing 5 and 10 mg, at day 3 or 4 as well.Similar effect was observed with cyclobenzaprine HCl tablets, USP 10 mg (all endpoints).Endpoints also showed that cyclobenzaprine HCl tablets, USP 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(R) (diazepam, Roche) SURVEILLANCE PROGRAM A post-marketing surveillance program was carried out in 7,607 patients with acute musculoskeletal disorders, and included 297 patients treated with cyclobenzaprine HCl tablets, USP 10 mg for 30 days or longer.Overall effectiveness of cyclobenzaprine HCl was similar to that observed in the double-blind controlled studies; the overall incidence of adverse effects was less (see ).AND USAGE Cyclobenzaprine HCl tablets, USP 5 mg 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.HCl tablets, USP 5 mg 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 5 mg has not been found effective in the treatment of spasticity associated with cerebral or spinal cord disease, or in children with cerebral palsy.Hypersensitivity to anyponent of this product.Use of monoamine oxidase (MAO) inhibitors or within 14 days after their discontinuation.Crisis seizures, and deaths have occurred in patients receiving cyclobenzaprine (or structurally similar tricyclic antidepressants) coitantly with MAO inhibitor drugs.Phase of myocardial infarction, and patients with arrhythmias, heart block or conduction disturbances, or congestive heart failure.WARNINGS Cyclobenzaprine is closely related to the tricyclic antidepressants, e.Amitriptyline and imipramine.Short term studies for indications other than muscle spasm associated with acute musculoskeletal conditions, and usually at doses somewhat greater than those rmended for skeletal muscle spasm, some of the more serious central nervous system reactions noted with the tricyclic antidepressants have occurred (see , below, and ).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 GENERAL Because of its atropine-like action, cyclobenzaprine HCl should be used with caution in patients with a history of urinary retention, angle-closure glaa, increased intraocular pressure, and in patients taking anticholinergic medication.IMPAIRED HEPATIC FUNCTION The plasma concentration of cyclobenzaprine is increased in patients with hepatic impairment (see , , ).These patients are generally more susceptible to drugs with potentially sedating effects, including cyclobenzaprine.Should be used with caution in subjects with mild hepatic impairment starting with a 5 mg dose and titrating slowly upward.To the lack of data in subjects with more severe hepatic insufficiency, the use of cyclobenzaprine HCl in subjects with moderate to severe impairment is not rmended.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.The elderly, the frequency and severity of adverse events associated with the use of cyclobenzaprine, with or without coitant medications, is increased.Elderly patients, cyclobenzaprine HCl should be initiated with a 5 mg dose and titrated slowly upward.INTERACTIONS Cyclobenzaprine HCl may have life-threatening interactions with MAO inhibitors..Cyclobenzaprine HCl may enhance the effects of alcohol, barbiturates, and other CNS depressants.Tricyclic antidepressants may block the antihypertensive action of guanethidine and similarly actingpounds.Tricyclic antidepressants may enhance the seizure risk in patients taking tramadol.ULTRAM(R) (tramadol HCl tablets, Ortho-McNeil Pharmaceutical) ULTRACET(R) (tramadol HCl and acetaminophen tablets, Ortho-McNeil Pharmaceutical) CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY In rats treated with cyclobenzaprine HCl for up to 67 weeks at doses of approximately 5 to 40 times the maximum rmended human dose, pale, sometimes enlarged, livers were noted and there was a dose-related hepatocyte vacuolation with lipidosis.The higher dose groups this microscopic change was seen after 26 weeks and even earlier in rats which died prior to 26 weeks; at lower doses, the change was not seen until after 26 weeks.Cyclobenzaprine did not affect the onset, incidence or distribution of neoplasia in an 81-week study in the mouse or in a 105-week study in the rat.At oral doses of up to 10 times the human dose, cyclobenzaprine did not adversely affect the reproductive performance or fertility of male or female rats.Did not demonstrate mutagenic activity in the male mouse at dose levels of up to 20 times the human dose.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.Are, however, no adequate and well-controlled studies in pregnant women.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.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.IN THE ELDERLY The plasma concentration of cyclobenzaprine is increased in the elderly (see , , ).Elderly may also be more at risk for CNS adverse events such as hallucinations and confusion, cardiac events resulting in falls or other sequelae, drug-drug and drug-disease interactions.These reasons, in the elderly, cyclobenzaprine should be used only if clearly needed.Such patients cyclobenzaprine HCl should be initiated with a 5 mg dose and titrated slowly upward.ADVERSE REACTIONS Incidence of mostmon adverse reactions in the 2 double-blind , placebo-controlled 5 mg studies (incidence of >3% on cyclobenzaprine HCl tablets, USP 5 mg): Cyclobenzaprine HCl Tablets, USP 5 mg N=464 Cyclobenzaprine HCl Tablets, USP 10 mg N=249 Placebo 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 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.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.Incidence of thesemon adverse reactions was lower in the surveillance program than in the controlled clinical studies: Clinical Studies With Cyclobenzaprine HCl Tablets, USP 10 mg Surveillance Program With Cyclobenzaprine HCl Tablets, USP 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.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.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.Urinary frequency and/or retention.Note: Cyclobenzaprine HCl tablets, USP 10 mg data are from one clinical trial.HCl tablets, USP 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.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.Dyspnea.Skin: Photosensitization; alopecia.Urogenital: Impaired urination; dilatation of urinary tract; impotence; testicular swelling; gynastia; breast enlargement; galactorrhea.DRUG ABUSE AND DEPENDENCE 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.Cessation of treatment after prolonged administration rarely may produce nausea, headache, and malaise.Are not indicative of addiction.Although rare, deaths may occur from overdosage with cyclobenzaprine HCl tablets.Drug ingestion (including alcohol) ismon in deliberate cyclobenzaprine overdose.Management of overdose isplex and changing, it is rmended that the physician contact a poison control center for current information on treatment.And symptoms of toxicity may develop rapidly after cyclobenzaprine overdose; therefore, hospital monitoring is required as soon as possible.Acute oral LD50 of cyclobenzaprine HCl is approximately 338 and 425 mg/kg in mice and rats, respectively.MANIFESTATIONS The mostmon effects associated with cyclobenzaprine overdose are drowsiness and tachycardia.Frequent manifestations include tremor, agitation,a, ataxia, hypertension, slurred speech, confusion, dizziness, nausea, vomiting, and hallucinations.But potentially critical manifestations of overdose are cardiac arrest, chest pain, cardiac dysrhythmias, severe hypotension, seizures, and neuroleptic malignant syndrome.In the electrocardiogram, particulary 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 isplex and changing, it is rmended 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.The patient's airway, establish an intravenous line and initiate gastric decontamination.With cardiac monitoring and observation for signs of CNS or respiratory depression, hypotension, cardiac dysrhythmias and/or conduction blocks, and seizures is necessary.Of toxicity occur at any time during this period, extended monitoring is required.Plasma drug levels should not guide management of the patient.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.Should include large volume gastric lavage followed by activated charcoal.Consciousness is impaired, the airway should be secured prior to lavage and emesis is contraindicated.CARDIOVASCULAR A maximal limb-lead QRS duration of >0.May be the best indication of the severity of the overdose.Alkalinization, to a pH of 7.7.Read more Alprazolam(alprazolam) tablet, extended release [teva pharmaceuticals usa]
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