COGENTIN^®
(Benztropine Mesylate Injection)

Benztropine mesylate is a synthetic compound containing structural features found in atropine and diphenhydramine.
    It is designated chemically as 8-azabicyclo[3.2.1] octane, 3-(diphenylmethoxy)-, endo, methanesulfonate. Its empirical formula is C₂₁H₂₅NO•CH₄O₃S, and its structural formula is:

Benztropine mesylate is a crystalline white powder, very soluble in water, and has a molecular weight of 403.54.

COGENTINRegistered trademark of Merck &Co., Inc., Whitehouse Station, NJ, U.S.A. (Benztropine Mesylate) is supplied as a sterile injection for intravenous and intramuscular use.

Each milliliter of the injection contains:
Benztropine mesylate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1 mg
Sodium chloride . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9 mg
Water for injection q.s. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 mL

COGENTIN possesses both anticholinergic and antihistaminic effects, although only the former have been established as therapeutically significant in the management of parkinsonism.

In the isolated guinea pig ileum, the anticholinergic activity of this drug is about equal to that of atropine; however, when administered orally to unanesthetized cats, it is only about half as active as atropine.

In laboratory animals, its antihistaminic activity and duration of action approach those of pyrilamine maleate.

Antipsychotic drugs such as phenothiazines or haloperidol; tricyclic antidepressants (see WARNINGS).

Because of the atropine-like side effects, COGENTIN should be used with caution in pediatric patients over three years of age (see CONTRAINDICATIONS).

The adverse reactions below, most of which are anticholinergic in nature, have been reported and within each category are uled in order of decreasing severity.

Tachycardia.

Paralytic ileus, constipation, vomiting, nausea, dry mouth.

If dry mouth is so severe that there is difficulty in swallowing or speaking, or loss of appetite and weight, reduce dosage, or discontinue the drug temporarily.

Slight reduction in dosage may control nausea and still give sufficient relief of symptoms. Vomiting may be controlled by temporary discontinuation, followed by resumption at a lower dosage.

Toxic psychosis, including confusion, disorientation, memory impairment, visual hallucinations; exacerbation of pre-existing psychotic symptoms; nervousness; depression; ullessness; numbness of fingers.

Blurred vision, dilated pupils.

Urinary retention, dysuria.

Occasionally, an allergic reaction, e.g., skin rash, develops. If this cannot be controlled by dosage reduction, the medication should be discontinued.

Heat stroke, hyperthermia, fever.

Since there is no significant difference in onset of effect after intravenous or intramuscular injection, usually there is no need to use the intravenous route. The drug is quickly effective after either route, with improvement sometimes noticeable a few minutes after injection. In emergency situations, when the condition of the patient is alarming, 1 to 2 mL of the injection normally will provide quick relief. If the parkinsonian effect begins to return, the dose can be repeated.

Because of cumulative action, therapy should be initiated with a low dose which is increased gradually at five or six-day intervals to the smallest amount necessary for optimal relief. Increases should be made in increments of 0.5 mg, to a maximum of 6 mg, or until optimal results are obtained without excessive adverse reactions.

The usual daily dose is 1 to 2 mg, with a range of 0.5 to 6 mg parenterally.

As with any agent used in parkinsonism, dosage must be individualized according to age and weight, and the type of parkinsonism being treated. Generally, older patients, and thin patients cannot tolerate large doses. Most patients with postencephalitic parkinsonism need fairly large doses and tolerate them well. Patients with a poor mental outlook are usually poor candidates for therapy.

In idiopathic 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 a day may be required.

In postencephalitic parkinsonism, therapy may be initiated in most patients with 2 mg a day in one or more doses. In highly sensitive patients, therapy may be initiated with 0.5 mg at bedtime, and increased as necessary.

Some patients experience greatest relief when given the entire dose at bedtime; others react more favorably to divided doses, two to four times a day. Frequently, one dose a day is sufficient, and divided doses may be unnecessary or undesirable.

The long duration of action of this drug makes it particularly suitable for bedtime medication when its effects may last throughout the night, enabling patients to turn in bed during the night more easily, and to rise in the morning.

When COGENTIN is started, do not terminate therapy with other antiparkinsonian agents abruptly. If the other agents are to be reduced or discontinued, it must be done gradually. Many patients obtain greatest relief with combination therapy.

COGENTIN may be used concomitantly with SINEMETRegistered trademark of Merck &Co., Inc., Whitehouse Station, NJ, U.S.A. (Carbidopa-Levodopa), or with levodopa, in which case periodic dosage adjustment may be required in order to maintain optimum response.

In treating extrapyramidal disorders due to neuroleptic drugs (e.g., phenothiazines), the recommended dosage is 1 to 4 mg once or twice a day parenterally. Dosage must be individualized according to the need of the patient. Some patients require more than recommended; others do not need as much.

In acute dystonic reactions, 1 to 2 mL of the injection usually relieves the condition quickly.

When extrapyramidal disorders develop soon after initiation of treatment with neuroleptic drugs (e.g., phenothiazines), they are likely to be transient. One to 2 mg of COGENTIN two or three times a day usually provides relief within one or two days. After one or two weeks, the drug should be withdrawn to determine the continued need for it. If such disorders recur, COGENTIN can be reinstituted.

Certain drug-induced extrapyramidal disorders that develop slowly may not respond to COGENTIN.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.

May be any of those seen in atropine poisoning or antihistamine overdosage: CNS depression, preceded or followed by stimulation; confusion; nervousness; ullessness; intensification of mental symptoms or toxic psychosis in patients with mental illness being treated with neuroleptic drugs (e.g., phenothiazines); hallucinations (especially visual); dizziness; muscle weakness; ataxia; dry mouth; mydriasis; blurred vision; palpitations; tachycardia; elevated blood pressure; nausea; vomiting; dysuria; numbness of fingers; dysphagia; allergic reactions, e.g., skin rash; headache; hot, dry, flushed skin; delirium; coma; shock; convulsions; respiratory arrest; anhidrosis; hyperthermia; glaucoma; constipation.

Physostigmine salicylate, 1 to 2 mg, SC or IV, reportedly will reverse symptoms of anticholinergic intoxication.Duvoisin, R.C.; Katz, R.J.; Amer. Med. Ass. 206:1963-1965, Nov. 25, 1968. A second injection may be given after 2 hours if required. Otherwise treatment is symptomatic and supportive. Induce emesis or perform gastric lavage (contraindicated in precomatose, convulsive, or psychotic states). Maintain respiration. A short-acting barbiturate may be used for CNS exclient, but with caution to avoid subsequent depression; supportive care for depression (avoid convulsant stimulants such as picrotoxin, pentylenetetrazol, or bemegride); artificial respiration for severe respiratory depression; a local miotic for mydriasis and cycloplegia; ice bags or other cold applications and alcohol sponges for hyperpyrexia, a vasopressor and fluids for circulatory collapse. Darken room for photophobia.