Cyclosed
(Tablets)
Cyclosed TabletsComposition:
Each film coated tablet contains:
Cyclobenzaprine HCL ………....... 10 mg
Inactive ingredients:
Lactose monohydrate, maize starch, magnesium stearate

Clinical pharmacology:
CYCLOSED is a centrally - acting muscle relaxant, pharmacologically related to tricyclic antidepressants.
CYCLOSED acts within CNS at brain stem (reduces tonic somatic motor activity influencing both gamma and alpha motor neurons.
CYCLOSED has shown a reduction of tonic somatic motor activity influencing systems.

Indications and usage:
CYCLOSED is indicated as an adjunct to rest and physical therapy for the relief of localized muscle spasms associated with local acute, painful musculoskeletal conditions without interfering with muscle function.
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.
CYCLOSED 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.
CYCLOSED has not been found effective in the treatment of spasticity associated with central nervous system (cerebral or spinal cord) diseases, or in children with cerebral palsy.
Pharmacokinetics:
CYCLOSED oral bioavailability range from 33% - 55%.
It is highly bound to plasma proteins, extensively metabolized in the liver, and is excreted primarily as glucuronides via the kidney with elimination half life of 18 hours and plasma clearance is 0.7 ml / min.

Contraindications:
Hypersensitivity to the active ingredient, or 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:
Cyclobenzaprine is closely related to the tricyclic antidepressants, e.g., amitriptyline and imipramine.
Tricyclic antidepressants have been reported to produce arrhythmias, sinus tachycardia, and prolongation of the conduction time leading to myocardial infarction and stroke.
CYCLOSED may enhance the CNS depressant effect of alcohol, barbiturates, and other CNS depressants.
Precautions:
General:
Because of its atropine-like action, CYCLOSED should be used with caution in patients with a history of urinary retention, angle-closure glaucoma, increased intraocular pressure, and in patients taking olinergic medication.

Impaired Hepatic Function:
The plasma concentration of cyclobenzaprine is increased in patients with hepatic impairment , these patients are generally more susceptible to drugs with potentially sedating effects, including cyclobenzaprine.
CYCLOSED should be used with caution in subjects with mild hepatic impairment starting with a 5 mg dose and titrating slowly upward.
Due to the lack of data in subjects with more severe hepatic insufficiency, the use of CYCLOSED in subjects with moderate to severe impairment is not recommended.

Driving vehicles or operating machines:
CYCLOSED may cause drowsiness, dizziness, or blurred vision, so consult doctor.

Adverse reactions:
The adverse reactions reported most frequently with CYCLOSED were related to:
CNS: drowsiness, dry mouth, dizziness.
Adverse reactions which were reported in 1% to 3% of the patients on CYCLOSED were: abdominal pain, acid regurgitation, constipation, diarrhea, nausea, irritability, mental acuity decreased, nervousness upper respiratory infection, and pharyngitis, fatigue / tiredness, asthenia, dyspepsia, unpleasant taste, blurred vision, headache, and confusion.
Adverse reactions, reported with an incidence of less than 1% of patients on CYCLOSED were: 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, exciterment, paresthesia, diplopia.
Skin; sweating. Special senses; ageusia, tinnitus.
Urogenital: urinary frequency and /or retention.

Drug interactions:
Avoid concomitant use of CYCLOSED with the following drugs:
MAO inhibitors or within 14 days after their discontinuation:
Hytperpyretic crisis seizures and deaths have occurred due to concomitant use with CNS depressants, e.g. Alcohol, barbiturates.
CYCLOSED may block the antihypertensive action of Guanithidine and similarly acting compounds CYCLOSED may enhance the seizure risk in patients taking tramadol.
Carcinogenesis, mutagenesis, impairment of fertility:
CYCLOSED did not demonstrate carcinogenic, mutagenic activities or affect the reproductive performance or fertility of male or female rats at doses higher than human dose.
Use during pregnancy and lactation:
CYCLOSED should only be used during pregnancy only if clearly needed due to lack of well-controlled studies in pregnant women. Caution should be exercised when CYCLOSED is administered to a nursing woman because it is not known whether this drug is excreted in human milk.
Pediatric use :
Safety and effectiveness of CYCLOSED in pediatric patients below 15 years of age have not been established.
Use in the elderly:
CYCLOSED should be used only if clearly needed. Dose should be initiated with a 5 mg dose and titrated slowly upward. CYCLOSED plasma concentration is increased in the elderly.
Elderly may also be more at risk for CNS adverse events such as hallucinations, confusion, cardiac events resulting in falls or other sequlae, drug-drug and drug-disease interactions.
Drug abuse and dependence:
Pharmacologic similarities among the tricyclic drugs require that certain withdrawal symptoms be considered when CYCLOSED 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.

Over dosage:
Although rare, deaths may occur from over dosage with CYCLOSED.
Multiple drug ingestion (including alcohol) is common in deliberate cyclobenzaprine overdose.
Signs and symptoms of toxicity may develop rapidly after cyclobenzaprine overdose; therefore hospital monitoring is required as soon as possible.

Manifestations:
The most common effects associated with CYCLOSED 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 dyshythmias, severe hypotension, seizures, and neuroleptic malignant syndrome.
Changes in the electrocardiogram, particularly in QRS axis or width, are clinically significant indicators of CYCLOSED toxicity.
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. Initiate cardiac monitoring, ECG, protect the patient's airway, establish an intravenous line and initiate gastric decontamination.
Monitoring of signs of toxicity: CNS or respiratory depression, hypotension, cardiac dysrhythmias and / or conduction blocks, and seizures are necessary.

N.B:
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:
Emesis is contra-indicated.
If consciousness is impaired, the airway should be secured prior to gastric
Patients should receive large volume gastric lavage followed by activated charcoal.
Cardiovascular :
A maximal limb-lead QRS duration of > 0.10 seconds may be the best indication of the severity of the overdose.
Patients with dysrhythmias and / or QRS widening:
Using intravenous sodium bicarbonate therapy (serum alkalinization to a pH of 7.45- 7.55). A pH > 7060 or a pCO2 < 20 mm Hg is undesirable. Patients with dysrhythmias unresponsive to sodium bicarbonate therapy / hyperventilation: - Lidocaine, phenytoin or bretylim should be used.
Type 1A and 1 C antiarrhythmics are generally contra-indicated, e.g quinidine, procainamide, disopyramide.
CNS Patients with CNS depression:
Early intubation is advised because of the potential for abrupt deterioration.
Seizures should be controlled with benzodiazepines or other anticonvulsants such as phenytoin or Phenobarbital.
Physostigmine is not recommended except to treat life-threatening symptoms that have been unresponsive to other therapies, and then close consultation with a poison control center.
Psychiatric follow - up:
Patients may attempt suicide by other means during the recovery phase.
Psychiatric referral may be appropriate.
Pediatric management:
It is strongly recommended that the physician contact the local poison control center.
Dosage and administration:
CYCLOSED is administered orally, preferably with food to minimize gastric upset.
For most patients, the recommended dose of CYCLOSED is 5 mg three times a day, based on individual patient response; the dose may be increased to 10 mg three times a day.
CYCLOSED 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.
less frequent dosing should be considered for hepatically impaired or elderly patients.
Storage:
store at temperature not exceeding 30°C in dry place .
keep out of reach of children.

Pack:
Carton box of 3 AL / PVC strips (each of 10 film-coated tablets) with leaflet.