2 mg/2 ml
For the use of a Registered Medical Practitioner or a Hospital or a Institution only.
BENCOGEN (Benztropine Mesylate) is a synthetic compound containing structural feature found in atropine and diphenhydramine. Chemically, Benztropine Mesylate is designated as 8-Azabicyclo[3.2.1]octane, 3-(diphenylmethoxy)-N -methyl-, endo -, methanesulfonate. Its molecular formula is C21H25NO·CH4O3S and its molecular weight is 403.53.
STRUCTURAL FORMULA :
Its structural formula is :
BENCOGEN is a clear colourless solution filled in 2 ml flint glass ampoule.
Each ml contains :
Benztropine Mesylate USP 1 mg
Sodium Chloride USP 9.0 mg
Water for Injection USP q.s.
Benztropine is a centrally acting anticholinergic agent with antihistaminic properties resulting from the combination of the tropine portion of the atropine molecule and the benzohydryl portion of diphenhydramine. Animal studies have indicated that anticholinergic activity of benztropine is approximately half that of atropine, while antihistaminic activity approaches that of pyrilamine. Its anticholinergic effects have been established as therapeutically significant in the management of parkinsonism. Benztropine antagonises the effect of acetylcholine, decreasing the imbalance between the neurotransmitters acetylcholine and dopamine, which may improve the symptoms of early parkinson’s disease.
The oral LD50 in the mouse is 94 mg/kg. The intravenous LD50 in the mouse is 24 mg/kg. In laboratory animals the antihistaminic activity and duration of action approach those of pyrilamine maleate. In the isolated guinea pig ileum, the anticholinergic activity of this agent is about equal to that of atropine; however, when administered orally to unanaesthetised cats, benztropine is only about half as active as atropine. In a clinical study measuring serum levels of neuroleptics and anticholinergics via radioreceptor assay, the correlation between total daily dose of benztropine and serum concentration was extremely poor (r=0.0281). Serum concentrations varied nearly 100-fold with given doses between 2 and 6 mg/day. A markedly non-linear relationship between daily dose and serum anticholinergic agent levels was observed with an increasing oral dosage of benztropine. In most cases, 2 mg increments in oral dose were associated with several fold increases in the serum level of anticholinergic activity. It has been reported that the duration of action for benztropine may persist for upto 24 to 48 hours following a single 2 mg I.M. injection. Benztropine binds extensively, approximately 95 %, with serum proteins. Benztropine crosses the blood-brain barrier.
BENCOGEN is recommended for all forms of parkinsonism including arteriosclerotic, postencephalitic, idiopathic, as well as medicine-induced extrapyramidal disorders (except tardive dyskinesia). It can be effective at any stage of the disease, even when a patient has become bedridden. BENCOGEN often is helpful in patients who have become unresponsive to other agents. BENCOGEN is a powerful anticholinergic agent which is mainly effective in relieving tremor and rigidity. Therapy is directed toward control of disturbing symptoms to permit the patient maximum integration of function with minimum discomfort. In non-medicine-induced parkinsonism, partial control of symptoms is usually achieved.
FOR INTRAVENOUS AND INTRAMUSCULAR USE.
INSTRUCTIONS FOR USE OF AMPOULE :
The ampoule used in this product is equipped with O.P.C (One Point Cut) opening system. No ampoule file is needed to open the ampoule. The neck of the ampoule is prescored at the point of constriction. A coloured dot on the ampoule head helps to orientate the ampoule. Take the ampoule and face the coloured dot. Let the solution at the head of the ampoule to flow down by shaking or a gentle stroke. The ampoule opens easily by placing the thumb on the coloured dot and gently pressing downwards as shown.
The injection is especially useful for psychotic patients with acute dystonic reactions or other reactions that make oral medication difficult or impossible. It is recommended also when a more rapid response is desired than can be obtained with the tablets. 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.
Postencephalitic and Idiopathic Parkinsonism :
The usual daily dose is 1 to 2 mg, with a range of 0.5 to 6 mg orally or 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 by taking the entire dose at bedtime; others react more favourably 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 BENCOGEN 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.BENCOGEN may be used concomitantly with Carbidopa-Levodopa Tablets, or with Levodopa tablets, 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 orally or 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. After that, the tablets, 1 to 2 mg twice a day, usually prevent recurrence. When extrapyramidal disorders develop soon after initiation of treatment with neuroleptic drug (e.g., phenothiazines), they are likely to be transient. 1 to 2 mg of Bencogen Tablets 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, BENCOGEN can be reinstituted. Certain drug - induced extrapyramidal disorders that develop slowly may not respond to BENCOGEN.
BENCOGEN is contraindicated in angleclosure glaucoma; myasthenia gravis; pyloric or duodenal obstruction; stenosing peptic ulcer; prostatic hypertrophy or bladder neck obstructions; megacolon; tardive dyskinesia; children less than 3 years old. BENCOGEN is contraindicated in patients who are hypersensitive to any component in this product.
When BENCOGEN 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 BENCOGEN, in combination with phenothiazines and/or tricyclic antidepressants. Since BENCOGEN (Benztropine Mesylate Injection) 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 labour in a hot environment. Anhidrosis may occur more readily when some disturbance of sweating already exists. If there is evidence of anhidrosis, 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 PRECAUTIONS :
Since BENCOGEN 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 BENCOGEN. 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 the 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 intensification of mental symptoms. In such cases, antiparkinsonian drugs can precipitate a toxic psychosis. Patients with mental disorders should be kept under careful 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 when these drugs has been discontinued. Antiparkinsonism agents do not alleviate the symptoms of tardive dyskinesia and in some instances may aggravate them. BENCOGEN 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. BENCOGEN should also be used with caution in patients with urinary retention, cardiovascular disease and hepatic or renal impairment.and fatal hyperthermia have occurred.
Pregnancy : Category C
It is not known whether BENCOGEN can cause foetal harm when administered to a pregnant woman or can affect reproductive capacity. BENCOGEN should be given to a pregnant woman only if clearly needed.
Nursing Mothers :
It is not known whether this medicine is excreted in human milk. Because many medicines are excreted in human milk, caution should be exercised when BENCOGEN is administered to a nursing mother.
Paediatric Use :
Because of the atropine-like side effects, BENCOGEN should be used with caution in paediatric patients over three years of age.
EFFECTS ON ABILITY TO DRIVE AND USE MACHINES :
BENCOGEN may impair mental and/or physical abilities required for performance of hazardous tasks, such as operating machinery or driving a motor vehicle.
Then BENCOGEN is given concomitantly with anticholinergics or those with antidopaminergic activity, such as phenothiazines, haloperidol or other such drugs, patients should be advised to report fever, heat intolerance and gastrointestinal complaints promptly. Paralytic ileus, sometimes fatal, has occurred in patients taking anticholinergic-type antiparkinsonism drugs, including BENCOGEN, in combination with phenothiazines and/or tricyclic antidepressants. Alcohol and other CNS depressants, such as anxiolytics, sedatives and hypnotics, can increase the sedative effects of benztropine. Drugs that exert anticholinergic properties may pharmacodynamically oppose the effects of prokinetic agents such as cisapride or metoclopramide. The doses of BENCOGEN and levodopa must be adjusted when the drugs are given simultaneously. Through its central anticholinergic actions BENCOGEN can potentate the dopaminergic effects of levodopa. While some patients may benefit from this interaction, clinicians should be ready to decrease doses of levodopa if benztropine is added. The anticholinergic properties of BENCOGEN, by slowing GI transit, may decrease levodopa bioavailability. However, this mechanism appears to be of modest clinical significance. Anticholinergics can raise intragastric pH. This effect may interfere with the oral bioavailability of metoconazole. BENCOGEN should be used cautiously in patients receiving ketoconazole.
Opiate agonists should be used cautiously with anticholinergics since additive depressive effects on GI motility or bladder function may be seen. The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonise the anticholinergic actions of benztropine. Benztropine might also antagonise some of the effects of the parasympathomimetics. Carbonic anhydrase inhibitors increase the alkalinity of the urine, thereby increasing the amount of nonionized drug available for renal tubular reabsorption. Use with caution if BENCOGEN is administered with carbonic anhydrase inhibitors, which can decrease excretion and enhance the effects of BENCOGEN. Monitor for excessive anticholinergic adverse effects.
SIDE EFFECTS :
Adverse effects, most of which are anticholinergic or antihistaminic in nature are listed below by body system in order of decreasing severity.
Cardiovascular : Tachycardia.
Digestive : Constipation, dry mouth, nausea, vomiting, paralyticileus. If dry mouth is so severe that there is difficulty in swallowing or speaking, or loss of appetite and weight occur, reduce dosage, or discontinue the medicine 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 and 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.
May be any of those seen in atropine poisoning or antihistamine overdosage : CNS depression, preceded or followed by stimulation; confusion; nervousness; listlessness; intensification of mental symptoms or toxic psychosis in patients with mental illness being treated with phenothiazine derivatives or reserpine; hallucinations (especially visual); dizziness; muscle weakness; ataxia; dry mouth; mydriasis; blurred vision; palpitations; tachycardia; 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.The intravenous LD50 in the mouse is 24 mg/kg.
TREATMENT OF OVERDOSAGE :
Physostigmine salicylate, 1 to 2 mg sc or iv, will reverse symptoms of anti-cholinergic 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, convulsive, 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.
PHARMACEUTICAL PRECAUTIONS :
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Store below 30°C (86°F), protected from light.
Do not refrigerate.
SHELF LIFE :
24 months from the date of manufacture.
BENCOGEN is supplied as 2 mg Benztropine Mesylate in 2 ml aqueous solution.
Such 5 ampoules of 2 ml are packed in a Box.
Disclaimer : For the use of a Registered Medical Practitioner or a Hospital or a Institution only. Also it is not intended to be used by healthcare professionals or patients for the purpose of prescribing or administering these products. Questions regarding the complete and current content of product labeling / specification / presentation should be directed to SGPharma.