Benztropine Mesylate

BENZTROPINE MESYLATE

Antiparkinsonian Agent

Pharmacology: Benztropine is a synthetic tertiary amine with structural similarities to atropine and diphenhydramine. Benztropine exhibits anticholinergic, antihistaminic and local anesthetic properties. Its mechanism of action as an antiparkinsonian agent is not clearly known. The pharmacologic effects of the drug may not be apparent until 2 to 3 days after initiation of therapy and may persist for up to 24 hours after discontinuation of the drug.

Pharmacokinetics: When given orally, benztropine has an onset of action of between 1 and 2 hours. When given by i.m. or i.v. injection, the onset of action is within minutes.

Indications: The symptomatic treatment of all etiologic groups of parkinsonism and drug-induced extrapyramidal reactions.

Contraindications: Benztropine is contraindicated in patients with a known hypersensitivity to benztropine or to any of its excipients, in patients with angle-closure glaucoma, or in patients with tardive dyskinesia because it has been of little benefit and may actually aggravate this condition. Because of its adverse anticholinergic effects, this drug is contraindicated in children under 3 years of age and should be used with caution in older children.

Precautions: Since benztropine has cumulative action, continued supervision is advisable.

Patients with tachycardia and patients with prostatic hypertrophy should be closely observed during treatment.

The occurrence of glaucoma is possible. Although the drug does not appear to have any adverse effect on simple glaucoma, it should not be used in narrow angle glaucoma (see Contraindications).

Tardive dyskinesia may appear in some patients on long-term therapy with neuroleptics and related agents, or may occur after these drugs have been discontinued. Antiparkinsonian agents usually do not alleviate the symptoms of tardive dyskinesia and in some instances may aggravate or unmask such symptoms. Benztropine is not recommended in tardive dyskinesia (see Contraindications).

When benztropine is used to treat extrapyramidal symptoms caused by neuroleptic therapy in patients with a psychiatric illness, there may be an intensification of psychiatric illness. Although benztropine need not be discontinued when this occurs, the psychogenic potential of antiparkinsonian drugs should be considered when planning the management of patients with psychiatric illnesses. When using benztropine in these patients, they should be kept under careful observation, especially at the beginning of treatment or if dosage is increased.

Benztropine may produce anhidrosis. It should be given with caution during hot weather, especially to the elderly, chronically ill, alcoholics, those with CNS disease and those who do manual labor in a hot environment. Anhidrosis may be anticipated to occur more readily when some disturbance of sweating already exists. If there is evidence of anhidrosis, dosage should be decreased so that the ability to maintain body heat equilibrium by perspiration is not impaired. Severe anhidrosis and fatal hyperthermia have occurred.

Drug Interactions : Anticholinergics: Additive anticholinergic effects may occur when benztropine is used concurrently with drugs such as amantadine, atropine, MAO inhibitors, tricyclic antidepressants and phenothiazines. Paralytic ileus (sometimes fatal), hyperthermia and heat stroke may occur. Patients should be advised to report gastrointestinal problems, fever or heat intolerance promptly.

CNS depressants: Benztropine may enhance the CNS depressant effects of drugs including alcohol, anticonvulsants, barbiturates, MAO inhibitors, opioid analgesics, phenothiazines and tricyclic antidepressants.

Occupational Hazards: Benztropine may impair mental and/or physical abilities required for performance of hazardous tasks such as operating machinery or driving a motor vehicle.

Pregnancy: The safe use of this drug in pregnancy has not been established.

Lactation: It is not known if benztropine is excreted into breast milk.

Children: Benztropine is not recommended in children under 3 years of age (see Contraindications).

Adverse Effects: The adverse effects of benztropine are usually an extension of its pharmacologic action. They are usually dose related and may be reduced by lowering the dose.

CNS: nervousness, impaired memory, numbness of fingers, listlessness, depression. Mental confusion, excitement and visual hallucinations with high doses.

Gastrointestinal: dry mouth, constipation, nausea, vomiting, rarely paralytic ileus.

Ophthalmic: blurred vision, mydriasis.

Endocrine: hyperthermia, anhidrosis, heat stroke.

Genitourinary: urinary retention and/or dysuria.

Skeletomuscular: weakness and inability to move particular muscle groups.

Hypersensitivity: skin rash may occur occasionally.

Cardiovascular: tachycardia, arrhythmias.

Symptoms: Symptoms of benztropine overdosage are related to an extension of its pharmacologic action. Severe anticholinergic side effects may include: clumsiness; unsteadiness, severe dryness of the mouth, nose or throat; tachycardia; shortness of breath; warmth, dryness and flushing of the skin. CNS depression or severe drowsiness may be preceded or followed by CNS stimulation including hallucinations, seizures and confusion. Toxic psychosis may occur in patients with psychiatric illness being treated with neuroleptic drugs. Other symptoms may include: nausea, vomiting, blurred vision, mydriasis, seizures, respiratory and circulatory failure.

Treatment: For oral overdoses, perform gastric lavage followed by administration of activated charcoal and a cathartic. Cathartics should not be administered to patients with an ileus or impaired renal function. Treatment is symptomatic and supportive. Monitor the patient for development of seizures, hypertension and arrhythmias. Maintain respiration, fluid and electrolyte balance. A local miotic for mydriasis and cycloplegia may be used and ice bags or sponging with tepid water for hyperpyrexia. Physostigmine is not routinely recommended for the treatment of anticholinergic toxicity because of its potential for adverse effects. Peritoneal dialysis and hemodialysis are of no value in the management of benztropine overdose.

Dosage: Benztropine should be used orally in all cases when patients are able to take oral medication. In other cases, where more rapid response is desired, benztropine mesylate may be administered i.v. or i.m.

Since there is no significant difference in onset of effect after i.v. and i.m. injection, usually there is no need to give benztropine i.v. It is quickly effective after either route, with improvement sometimes noticeable a few minutes after injection.

Because benztropine has cumulative action, therapy should be initiated with a low dose, which is increased gradually by 0.5 mg increments at 5- or 6-day intervals, to the smallest amount necessary for optimal relief without excessive adverse effects. The maximum adult dose is 6 mg. Generally, older patients, thin patients and those with arteriosclerotic parkinsonism cannot tolerate large doses. Most patients with postencephalitic parkinsonism need fairly large doses and tolerate them well. Patients with dementia or mental confusion are usually poor candidates for therapy.

In arteriosclerotic, idiopathic, and post encephalitic parkinsonism, therapy may be initiated with a single daily dose of 0.5 to 1 mg at bedtime. In some patients, this will be adequate; in others 4 to 6 mg daily may be required.

Some patients experience optimal relief by taking the entire daily dose at bedtime; others respond more favorably to divided doses 2 to 4 times daily.

Therapy with other agents should not be terminated abruptly when therapy with benztropine is initiated, but may be reduced or discontinued gradually. Benztropine may be administered concomitantly with levodopa or a levodopa/carbidopa combination, in which case the dose of each may need adjustment.

Drug-induced Extrapyramidal Symptoms: In treating extrapyramidal disorders caused by neuroleptics, the recommended dosage is 1 to 4 mg once or twice daily, orally or parenterally. Dosage must be individualized according to the needs of the patient.

In acute dystonic reactions, 2 mg of benztropine given i.m./i.v. quickly relieves the condition. After that, 1 to 2 mg given orally twice daily for 2 to 3 days usually prevents recurrence.

When extrapyramidal disorders develop soon after initiation of treatment with neuroleptics, they are likely to be transient. One to 2 mg given orally 2 or 3 times daily usually provides relief within 1 or 2 days. After 1 or 2 weeks, the need for continued therapy with benztropine should be re-evaluated.

Benztropine mesylate should not be used beyond the period necessary to counteract the extrapyramidal manifestations. In the majority of patients, the use of anticholinergic agents is not required after 3 months of neuroleptic therapy. Although therapy with the drug causing parkinsonism can frequently be continued without change of dosage when adjunctive therapy with benztropine is used, a reduction in dosage of the psychotropic drug might be indicated.

Patients must be closely observed for severe reactions and benztropine discontinued temporarily if they appear (see Precautions and Adverse Effects).

BENZTROPINE MESYLATE Antiparkinsonian Agent

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