Kemadrin

Administration

Administer orally, preferably after meals.a b

Dosage

Available as procyclidine hydrochloride; dosage expressed in terms of the salt.a

Adjust dosage carefully according to individual requirements and response.a b

Adults

Younger and postencephalitic patients require and tolerate a higher dosage than geriatric patients or those with arteriosclerosis.a b

Initially, 2.5 mg 3 times daily after meals.a As tolerated, gradually increase to 5 mg 3 times daily or the minimum dosage needed to control symptoms.a If needed, administer an additional 5-mg dose at bedtime.a b

If bedtime dosage is not tolerated, total daily dosage may be administered in 3 divided doses.b

Gradually substitute 2.5 mg 3 times daily for all or part of original drug.a Increase procyclidine dose as needed while decreasing other drug until complete replacement achieved. a

Initially, 2.5 mg 3 times daily; increase by 2.5-mg increments until symptoms controlled.a b

Usual dosage: 10–20 mg daily.a a

Special Populations

No special population dosage recommendations at this time.a

• Exhibits atropine-like action and exerts antispasmodic effects on parasympathetic-innervated peripheral structures including smooth muscle.a b

• Competitively inhibits acetylcholine or other cholinergic stimuli at autonomic effectors innervated by postganglionic nerves.c

• Antagonizes certain muscarinic effects; may produce mydriasis and reduction in salivation.a

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

5 mg Scored Tablets

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 asα-cyclohexyl-α-phenyl-1-pyrrolidinepropanol hydrochloride and has the following structural formula:

Kemadrin is available in tablet form for oral administration. Each scored tablet contains5 mg procyclidine hydrochloride and the inactive ingredients corn and potato starch, lactose, and magnesium stearate.

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.

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.

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.