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. COGENTIN* (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

Last updated on RxList: 6/20/2007

For use as an adjunct in the therapy of all forms of parkinsonism.

Useful also in the control of extrapyramidal disorders (except tardive dyskinesia — see PRECAUTIONS) due to neuroleptic drugs (e.g., phenothiazines).

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 nec-essary 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.

Postencephalitic and Idiopathic Parkinsonism —

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 ini-tiated 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 SINEMET* (Carbidopa-Levodopa), or with levodopa, in which case periodic dosage adjustment may be required in order to maintain optimum response.

Drug-Induced Extrapyramidal Disorders —

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.

Injection COGENTIN, 1 mg per mL, is a clear, colorless solution and is supplied in boxes of 5 x 2 mL ampuls.

NDC 67386-611-52

Manufactured by Merck & Co. Inc., Whitehouse Station, NJ 08889, U.S.A. for:OVATION Pharmaceuticals Deerfield, il 60015, u.s.a.
Revised SEPTEMBER 2005
* Registered trademark of Merck & Co., Inc., Whitehouse Station, NJ, U.S.A.
FDA rev date: 5/22/2001

Last updated on RxList: 6/20/2007

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

Cardiovascular

Tachycardia.

Digestive

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.

Nervous System

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

Special Senses

Blurred vision, dilated pupils.

Urogenital

Urinary retention, dysuria.

Metabolic/Immune or Skin

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

Other

Heat stroke, hyperthermia, fever.

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

Pediatric use

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

Last updated on RxList: 6/20/2007

Safe use in pregnancy has not been established.

COGENTIN may impair mental and/or physical abilities required for performance of hazardous tasks, such as operating machinery or driving a motor vehicle.

When COGENTIN is given concomitantly with phenothiazines, haloperidol, or other drugs with anticholinergic or antidopaminergic activity, patients should be advised to report gastrointestinal complaints, fever or heat intolerance promptly. Paralytic ileus, hyperthermia and heat stroke, all of which have sometimes been fatal, have occurred in patients taking anticholinergic-type antiparkinsonism drugs, including COGENTIN, in combination with phenothiazines and/or tricyclic antidepressants.

Since COGENTIN contains structural features of atropine, it may produce anhidrosis. For this reason, it should be administered with caution during hot weather, especially when given concomitantly with other atropine-like drugs to the chronically ill, the alcoholic, those who have central nervous system disease, and those who do manual labor in a hot environment. Anhidrosis may occur more readily when some disturbance of sweating already exists. If there is evidence of anhidro-sis, the possibility of hyperthermia should be considered. Dosage should be decreased at the discretion of the physician so that the ability to maintain body heat equilibrium by perspiration is not impaired. Severe anhidrosis and fatal hyperthermia have occurred.

General

Since COGENTIN has cumulative action, continued supervision is advisable. Patients with a tendency to tachycardia and patients with prostatic hypertrophy should be observed closely during treatment.

Dysuria may occur, but rarely becomes a problem. Urinary retention has been reported with COGENTIN.

The drug may cause complaints of weakness and inability to move particular muscle groups, especially in large doses. For example, if the neck has been rigid and suddenly relaxes, it may feel weak, causing some concern. In this event, dosage adjustment is required.

Mental confusion and excitement may occur with large doses, or in susceptible patients. Visual hallucinations have been reported occasionally. Furthermore, in the treatment of extrapyramidal disorders due to neuroleptic drugs (e.g., phenothiazines), in patients with mental disorders, occasionally there may be intensi-fication of mental symptoms. In such cases, antiparkinsonian drugs can precipitate a toxic psychosis. Patients with mental disorders should be kept under care-ful observation, especially at the beginning of treatment or if dosage is increased.

Tardive dyskinesia may appear in some patients on long-term therapy with phenothiazines and related agents, or may occur after therapy with these drugs has been discontinued. Antiparkinsonism agents do not alleviate the symptoms of tardive dyskinesia, and in some instances may aggravate them. COGENTIN is not recommended for use in patients with tardive dyskinesia.

The physician should be aware of the possible occurrence of glaucoma. Although the drug does not appear to have any adverse effect on simple glaucoma, it probably should not be used in angle-closure glaucoma.

Last updated on RxList: 6/20/2007

Manifestations —

May be any of those seen in atropine poisoning or antihistamine overdosage: CNS depression, preceded or followed by stimulation; confu-sion; nervousness; listlessness; 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; elevat-ed 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.

Treatment —

Physostigmine salicylate, 1 to 2 mg, SC or IV, reportedly will reverse symptoms of anticholinergic intoxication.** 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, convul-sive, or psychotic states). Maintain respiration. A short-acting barbiturate may be used for CNS excitement, 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.

Hypersensitivity to any component of COGENTIN injection.

Because of its atropine-like side effects, this drug is contraindicated in pediatric patients under three years of age, and should be used with caution in older pediatric patients.

** Duvoisin, R.C.; Katz, R.J.; Amer. Med. Ass. 206: 1963-1965, Nov. 25, 1968.

Last updated on RxList: 6/20/2007

Action

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.

Last updated on RxList: 6/20/2007

No information provided. Please refer to the WARNINGS and PRECAUTIONS sectrions.

Last updated on RxList: 6/20/2007

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

BENZTROPINE - ORAL

(benz-TROH-peen)

USES: Benztropine is used to treat symptoms of Parkinson's disease or involuntary movements due to the side effects of certain psychiatric drugs (antipsychotics such as chlorpromazine/haloperidol). Benztropine belongs to a class of medication called anticholinergics that work by blocking a certain natural substance (acetylcholine). This helps decrease muscle stiffness, sweating, and the production of saliva, and helps improve walking ability in people with Parkinson's disease.

Anticholinergics can stop severe muscle spasms of the back, neck, and eyes that are sometimes caused by psychiatric drugs. It can also decrease other side effects such as muscle stiffness/rigidity (extrapyramidal signs-EPS). It is not helpful in treating movement problems caused by tardive dyskinesia and may worsen them. Benztropine should not be used in children younger than 3 years.

HOW TO USE: Take this medication by mouth, usually 2 to 4 times a day with meals and at bedtime, or as a single dose at bedtime, or as directed by your doctor. Your doctor may start you at a low dose and increase your dose slowly to find the best dose for you. The dosage is based on your medical condition and response to therapy.

If you are using the oral solution, measure your dose with a special measuring spoon or device. Do not use a household spoon because it may not provide the correct dose.

Take this medication regularly in order to get the most benefit from it. To help you remember, take it at the same times each day.

Take this medication at least 1 hour before antacids containing magnesium, aluminum, or calcium. Allow at least 1-2 hours between doses of benztropine and certain drugs for diarrhea (adsorbent antidiarrheals such as kaolin, pectin, attapulgite). Take this medication at least 2 hours after ketoconazole. Antacids and some drugs for diarrhea may prevent the full absorption of benztropine, and this product may prevent the complete absorption of ketoconazole when these products are taken together.

If you are taking this medication for side effects from another medication, your doctor may instruct you to take it on a regular schedule or only as needed. If you are taking this medication for Parkinson's disease, your doctor may change the dose of your other medications (e.g., levodopa). Follow your doctor's instructions closely.

When used for an extended period, this medication may not work as well and may require different dosing. Talk with your doctor if this medication stops working well.

Rarely, abnormal drug-seeking behavior (addiction) is possible with this medication. Do not increase your dose, take it more frequently, or use it for a longer time than prescribed. Properly stop the medication when so directed. Some conditions may become worse when the drug is abruptly stopped. Your dose may need to be gradually decreased.

It may take 2-3 days before the benefit of this drug takes effect. Inform your doctor if your condition persists or worsens.

SIDE EFFECTS: Drowsiness, dizziness, constipation, flushing, nausea, nervousness, blurred vision, or dry mouth may occur. These effects usually lessen as your body gets used to the medicine. If any of these effects persist or worsen, contact your doctor or pharmacist promptly.

To relieve dry mouth, suck on (sugarless) hard candy or ice chips, chew (sugarless) gum, drink water, or use a saliva substitute.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: high fever, decreased sexual ability, severe stomach/abdominal pain, difficult/painful swallowing, difficulty urinating, vision changes, weakness.

Seek immediate medical attention if any of these very unlikely but very serious side effects occur: chest pain, severe dizziness/fainting, fast/irregular/slow heartbeat, mental/mood changes (e.g., confusion, hallucinations, memory problems).

A serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction include: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking benztropine, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: certain eye problem (narrow-angle glaucoma), blockage of the bladder/esophagus/stomach/intestines (e.g., bowel obstruction), severe ulcerative colitis.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: alcohol use, breathing problems (e.g., asthma, emphysema), diarrhea caused by an infection, certain eye problem (open-angle glaucoma), heart problems (e.g., angina, heart attack, heart failure, fast/irregular heartbeat), high/low blood pressure, intestinal problems (e.g., chronic constipation, ileus, ulcerative colitis), kidney disease, liver disease, mental/mood problems (e.g., anxiety, dementia, psychosis), certain muscle disease (myasthenia gravis), certain nerve disease (autonomic neuropathy), seizure, stomach problems (e.g., acid reflux, hiatal hernia, ulcer), stroke, overactive thyroid (hyperthyroidism), problems urinating (e.g., due to enlarged prostate, neurogenic bladder).

This drug may make you dizzy/drowsy or cause blurred vision; use caution while engaging in activities requiring alertness or clear vision such as driving or using machinery. Avoid alcohol beverages.

To minimize dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.

This medication decreases saliva production, an effect that can increase gum and tooth problems (e.g., cavities, gum disease). Take special care with your dental hygiene (e.g., brushing, flossing) and have regular dental check-ups.

This drug can cause decreased sweating, which could cause a severe rise in your body temperature (hyperthermia). The risk of this serious side effect is greater in hot weather, during vigorous exercise, and/or if you drink alcohol. Drink plenty of fluids and dress lightly while in hot weather and when exercising. If you experience signs of hyperthermia such as mental/mood changes, headache, or dizziness, promptly seek cool or air-conditioned shelter and/or stop exercising, and seek immediate medical attention. Consult your doctor for more details.

The elderly may be more sensitive to the effects of this drug, especially dizziness, heatstroke, memory problems, and constipation.

Children may be more sensitive to the effects of this drug, especially effects on heart rate.

This drug should be used only when clearly needed during pregnancy. Discuss the risks and benefits with your doctor.

It is not known if this drug passes into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your healthcare professionals (e.g., doctor or pharmacist) may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop or change the dosage of any medicine before checking with them first.

This drug should not be used with the following medication because very serious interactions may occur: pramlintide.

If you are currently using the medication listed above, tell your doctor or pharmacist before starting benztropine.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially: anticholinergics/antispasmodics (e.g., belladonna alkaloids, clidinium), amantadine, certain antiarrhythmics (e.g., disopyramide, procainamide, quinidine), cholinesterase inhibitors (e.g., donepezil, galantamine), corticosteroids (e.g., prednisone), monoamine oxidase inhibitors (e.g., furazolidone, isocarboxazid, linezolid, moclobemide, phenelzine, procarbazine, selegiline, tranylcypromine), motion sickness medication (e.g., meclizine, scopolamine), narcotic pain relievers (e.g., meperidine), potassium tablets/capsules, tricyclic antidepressants (e.g., amitriptyline, doxepin).

Tell your doctor or pharmacist if you also take drugs that cause drowsiness such as: certain antihistamines (e.g., diphenhydramine), anti-seizure drugs (e.g., carbamazepine), medicine for sleep or anxiety (e.g., alprazolam, diazepam, zolpidem), muscle relaxants, narcotic pain relievers (e.g., codeine), psychiatric medicines (e.g., risperidone, trazodone).

Check the labels on all your medicines (e.g., cough-and-cold products) because they may contain anticholinergics or drowsiness-causing ingredients. Ask your pharmacist about the safe use of those products.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly. Symptoms of overdose may include: unusually fast/slow heartbeat, slow/shallow breathing, unconsciousness, seizures, loss of coordination, fever, hot/dry/flushed skin, widened pupils, change in vision, change in the amount of urine, confusion, hallucinations.

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (e.g., eye exams) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store the United States product at room temperature below 86 degrees F (30 degrees C) away from light and moisture.

Store the Canadian product (solution and tablets) at room temperature between 59-86 degrees F (15-30 degrees C).

Do not store any form of this drug in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised August 2008 Copyright(c) 2008 First DataBank, Inc.