PROCYCLIDINE
DESCRIPTION:
KEMADRIN (procyclidine hydrochloride) is a synthetic antispasmodic compound of
relatively low toxicity. It has been shown to be useful for the symptomatic
treatment of parkinsonism (paralysis agitans) and extrapyramidal dysfunction
caused by tranquilizer therapy. Procyclidine hydrochloride was developed at The
Wellcome Research Laboratories as the most promising of a series of
antiparkinsonism compounds produced by chemical modification of antihistamines.
Procyclidine hydrochloride is a white crystalline substance which is soluble in
water and almost tasteless. It is known chemically as alpha-cyclohexyl-alpha-
phenyl- 1-pyrrolidinepropanol hydrochloride.
KEMADRIN is available in tablet form for oral administration. Each scored tablet
contains 5 mg procyclidine hydrochloride and the inactive ingredients corn and
potato starch, lactose, and magnesium stearate.
ACTIONS/CLINICAL PHARMACOLOGY:
Pharmacologic tests have shown that procyclidine hydrochloride has an atropine-
like action and exerts an antispasmodic effect on smooth muscle. It is a potent
mydriatic and inhibits salivation. It has no sympathetic ganglion-blocking
activity in doses as high as 4 mg/kg, as measured by the lack of inhibition of
the response of the nictitating membrane to preganglionic electrical
stimulation.
The intravenous LD50 in mice was about 60 mg/kg. Subcutaneously, doses of 300
mg/kg were not toxic. In dogs, the intraperitoneal administration of
procyclidine hydrochloride in doses of 5 mg/kg caused maximal dilation of the
pupil and inhibition of salivation, but had no toxic action. When the dose was
increased to 20 mg/kg the same symptoms occurred, and in addition there were
tremors and ataxia lasting 4 to 5 hours. In one animal, convulsions occurred
which were controlled by pentobarbital. In all animals behavior returned to
normal within 24 hours.
Chronic toxicity tests in rats showed that the compound caused only a very
slight retardation in growth, and no change in the erythrocyte count or the
histological appearance of the lungs, liver, spleen, and kidney when as much as
10 mg/kg body weight was given subcutaneously daily for 9 weeks.
INDICATIONS AND USAGE:
KEMADRIN (procyclidine hydrochloride) is indicated in the treatment of
parkinsonism including the postencephalitic, arteriosclerotic, and idiopathic
types. Partial control of the parkinsonism symptoms is the usual therapeutic
accomplishment. Procyclidine hydrochloride is usually more efficacious in the
relief of rigidity than tremor; but tremor, fatigue, weakness, and sluggishness
are frequently beneficially influenced. It can be substituted for all the
previous medications in mild and moderate cases. For the control of more severe
cases, other drugs may be added to procyclidine therapy as indications warrant.
Clinical reports indicate that procyclidine often successfully relieves the
symptoms of extrapyramidal dysfunction (dystonia, dyskinesia, akathisia, and
parkinsonism) which accompany the therapy of mental disorders with phenothiazine
and rauwolfia compounds. In addition to minimizing the symptoms induced by
tranquilizing drugs, the drug effectively controls sialorrhea resulting from
neuroleptic medication. At the same time, freedom from the side effects induced
by tranquilizer drugs, as provided by the administration of procyclidine,
permits a more sustained treatment of the patient's mental disorder.
Clinical results in the treatment of parkinsonism indicate that most patients
experience subjective improvement characterized by a feeling of well- being and
increased alertness, together with diminished salivation and a marked
improvement in muscular coordination as demonstrated by objective tests of
manual dexterity and by increased ability to carry out ordinary self-care
activities. While the drug exerts a mild atropine-like action and therefore
causes mydriasis, this may be kept minimal by careful adjustment of the daily
dosage.
CONTRAINDICATIONS:
Procyclidine hydrochloride should not be used in angle-closure glaucoma although
simple type glaucomas do not appear to be adversely affected.
WARNINGS:
USE IN CHILDREN: Safety and efficacy have not been established in the pediatric
age group; therefore, the use of procyclidine hydrochloride in this age group
requires that the potential benefits be weighed against the possible hazards to
the child.
PREGNANCY WARNING: The safe use of this drug in pregnancy has not been
established; therefore, the use of procyclidine hydrochloride in pregnancy,
lactation, or in women of childbearing age requires that the potential benefits
be weighed against the possible hazards to the mother and child.
PRECAUTIONS:
Conditions in which inhibition of the parasympathetic nervous system is
undesirable, such as tachycardia and urinary retention (such as may occur with
marked prostatic hypertrophy), require special care in the administration of the
drug. Hypotensive patients who receive the drug should be observed closely.
Occasionally, particularly in older patients, mental confusion and
disorientation may occur with the development of agitation, hallucinations, and
psychotic-like symptoms.
Patients with mental disorders occasionally experience a precipitation of a
psychotic episode when the dosage of antiparkinsonism drugs is increased to
treat the extrapyramidal side effects of phenothiazine and rauwolfia
derivatives.
ADVERSE REACTIONS:
Anticholinergic effects can be produced by therapeutic doses although these can
frequently be minimized or eliminated by careful dosage. They include: dryness
of the mouth, mydriasis, blurring of vision, giddiness, lightheadedness, and
gastrointestinal disturbances such as nausea, vomiting, epigastric distress, and
constipation. Occasionally an allergic reaction such as a skin rash may be
encountered. Feelings of muscular weakness may occur. Acute suppurative
parotitis as a complication of dry mouth has been reported.
DOSAGE AND ADMINISTRATION:
FOR PARKINSONISM: The dosage of the drug for the treatment of parkinsonism
depends upon the age of the patient, the etiology of the disease, and individual
responsiveness. Therefore, the dosage must remain flexible to permit adjustment
to the individual tolerance and requirements of each patient. In general,
younger and postencephalitic patients require and tolerate a somewhat higher
dosage than older patients and those with arteriosclerosis.
FOR PATIENTS WHO HAVE RECEIVED NO OTHER THERAPY: The usual dose of procyclidine
hydrochloride for initial treatment is 2.5 mg administered three times daily
after meals. If well tolerated, this dose may be gradually increased to 5 mg
three times a day and occasionally 5 mg given before retiring. In some cases
smaller doses may be employed with good therapeutic results.
Occasionally a patient is encountered who cannot tolerate a bedtime dose of the
drug. In such cases it may be desirable to adjust dosage so that the bedtime
dose is omitted and the total daily requirement is administered in three equal
daytime doses. It is best administered during or after meals to minimize the
development of side reactions.
TO TRANSFER PATIENTS TO KEMADRIN FROM OTHER THERAPY: Patients who have been
receiving other drugs may be transferred to procyclidine hydrochloride. This is
accomplished gradually by substituting 2.5 mg three times a day for all or part
of the original drug. The dose of procyclidine is then increased as required
while that of the other drug is correspondingly omitted or decreased until
complete replacement is achieved. The total daily dosage may then be adjusted to
the level which produces maximum benefit.
FOR DRUG-INDUCED EXTRAPYRAMIDAL SYMPTOMS: For treatment of symptoms of
extrapyramidal dysfunction induced by tranquilizer drugs during the therapy of
mental disorders, the dosage of procyclidine hydrochloride will depend on the
severity of side effects associated with tranquilizer administration. In
general, the larger the dosage of the tranquilizer, the more severe will be the
associated symptoms, including rigidity and tremors. Accordingly, the drug
dosage should be adjusted to suit the needs of the individual patient and to
provide maximum relief of the induced symptoms. A convenient method to establish
the daily dosage of procyclidine is to begin with the administration of 2.5 mg
three times daily. This may be increased by 2.5 mg daily increments until the
patient obtains relief of symptoms. In most cases excellent results will be
obtained with 10 to 20 mg daily.
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