Benclopro Capsule

BENCLOPRO is indicated as an adjunct to rest and physiotherapy for relief of muscle spasm associated with acute, painful musculoskeletal conditions. BENCLOPRO 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. BENCLOPRO has been found to be not effective in the treatment of spasticity associated with cerebral or spinal cord disease or in children with cerebral palsy.

Doses must be taken at approximately the same time each day. Use of BENCLOPRO for periods longer than two or three weeks is not recommended (see INDICATIONS). The recommended adult dose is one (1) BENCLOPRO 15 capsule taken once daily. Some patients may require up to 30 mg/day, given as one (1) BENCLOPRO 30 capsule taken once daily or as two (2) BENCLOPRO 15 capsules taken once daily.

• Hypersensitivity to cyclobenzaprine or to any of the list of excipients of BENCLOPRO (see COMPOSITION).
• Patients with dysrhythmias, heart block conduction disturbances, or congestive heart failure. During the acute recovery phase of myocardial infarction.
• Hyperthyroidism.
• Concomitant use of monoamine oxidase (MAO) inhibitors or within 14 days after their discontinuation (see INTERACTIONS).
• Use of BENCLOPRO is not recommended in patients with mild, moderate or severe hepatic impairment. This is as a result of a two-fold higher cyclobenzaprine plasma level in subjects with mild hepatic impairment, as compared to healthy subjects, following administration of immediate release cyclobenzaprine and because there is limited dosing flexibility with BENCLOPRO.
• Use of BENCLOPRO is not recommended in the elderly. This is due to a 40 % increase in cyclobenzaprine plasma levels and a 56 % increase in plasma half-life following administration of BENCLOPRO in elderly subjects as compared to young adults.

Cyclobenzaprine is structurally related to the tricyclic antidepressants, e.g., amitriptyline and imipramine. As a result, some of the more serious central nervous system reactions noted with the tricyclic antidepressants have occurred. The cardiotoxic potential of tricyclic antidepressants is widely acknowledged. They have been reported to produce dysrhythmias, sinus tachycardia, prolongation of the conduction time leading to myocardial infarction and stroke. BENCLOPRO may enhance the effects of alcohol, barbiturates and other CNS depressants. Hyperpyretic crisis seizures and deaths have occurred in patients receiving BENCLOPRO concomitantly with MAO inhibitor medicines (see CONTRAINDICATIONS and INTERACTIONS).

Paediatric use: Safety and effectiveness of BENCLOPRO has not been established in paediatric patients.

Use in the elderly: The plasma concentration and half-life of cyclobenzaprine are substantially increased in the elderly (see Pharmacokinetic properties, Elderly and CONTRAINDICATIONS). Accordingly, BENCLOPRO should not be used in the elderly.

General: The antimuscarinic-like effects of BENCLOPRO (cyclobenzaprine hydrochloride extended release capsules) warrant care in patients with a history of urinary retention, angle-closure glaucoma, increased intraocular pressure and in patients taking anticholinergic medication. The epileptogenic potential requires care in patients with a history of epilepsy.

MAOI: BENCLOPRO is contraindicated in patients receiving mono-amine oxidase inhibitors, and for at least 14 days after discontinuation of the MAOIu2019s. Life-threatening interactions may occur (see CONTRAINDICATIONS).

Alcohol, barbiturates, CNS depressants: BENCLOPRO may enhance the effects of alcohol, barbiturates, and other CNS depressants.

Guanethidine: BENCLOPRO may block the antihypertensive action of guanethidine and similarly acting compounds.

Tramadol: BENCLOPRO may enhance the risk of seizures in patients taking tramadol.

The safe use of BENCLOPRO has not been established in pregnancy or lactation.

As BENCLOPRO frequently causes drowsiness, patients using BENCLOPRO should not drive or operate machinery.

The following side effects may occur: Table 1: Incidence of the most common adverse reactions occurring in u2265 3 % of subjects in any treatment group in the two phase 3, double-blind BENCLOPRO trials.
BENCLOPRO 15 N=127 BENCLOPRO 30 N=126 Placebo N=128

• Dry mouth 6 % 14 % 2 %
• Dizziness 3 % 6 % 2 %
• Fatigue 3 % 3 % 2 %
• Constipation 1 % 3 % 0 %
• Somnolence 1 % 2 % 0 %
• Nausea 3 % 3 % 1 %
• Dyspepsia 0 % 4 % 1 %

• Somnolence 100 %
• Dry mouth 58 %
• Headache NOS 17 %
• Dizziness 19 %
• Vision blurred 3 %
• Nausea 8 %
• Dysgeusia 6 %
• Palpitations 6 %
• Tremor 6 %
• Dry throat 8 %
• Acne NOS 6 %
• Disturbance in attention 6 %
• Insomnia 0 %

Post marketing surveillance: In a post marketing surveillance program (7 607 patients treated with cyclobenzaprine 10 mg TID), the adverse reactions reported most frequently were drowsiness, dry mouth and dizziness. 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.

Symptoms: The most common effects associated with cyclobenzaprine overdose are drowsiness and tachycardia. Less frequent symptoms include tremor, agitation, coma, ataxia, hypertension, slurred speech, confusion, dizziness, nausea, vomiting and hallucinations. Rare but potentially critical symptoms 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 u201cSIDE EFFECTSu201d.

Treatment: Treatment is symptomatic and supportive. Medical professionals to consult the nearest poison control centre. 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 is approximately 338 and 425 mg/kg in mice and rats, respectively.

General: Obtain an ECG and immediately initiate cardiac monitoring. Protect the patient's airway, establish an intravenous line, and initiate gastric lavage. 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 medicine levels should not guide management of the patient. Dialysis is probably of no value because of low plasma concentrations of the medicine.

Gastric lavage: 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 alkalinisation, 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 antidysrhythmics 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 centre.

Psychiatric follow-up: Since overdosage is often deliberate, patients may attempt suicide by other means during the recovery phase. Psychiatric referral may be appropriate.

Paediatric management: The principles of management of child and adult overdosage are similar. It is strongly recommended that the medical practitioner contact the local poison control center for specific paediatric treatment.