Extrapyramidal symptoms:
Note: Anticholinergic agents are not recommended for the treatment of akathisia or tardive dyskinesia (APA [Keepers 2020]; Kang 1986). Duration of therapy is based on the severity of extrapyramidal symptom reaction, pharmacologic profile of the causative agent (eg, half-life, adverse effects), and patient risk factors (Holloman 1997; Kreyenbuhl 2009). Some experts recommend attempting taper and discontinuation after several weeks to months (Desmarais 2012).
Oral: Initial: 2.5 mg 3 times daily after meals; increase in 2.5 mg daily increments until symptomatic relief; usual dose: 10 to 20 mg/day in divided doses.
Parkinsonism: Oral: Initial: 2.5 mg 3 times daily after meals; if tolerated, gradually increase to 5 mg 3 times daily after meals and 5 mg at bedtime as needed. Lower dosages may be effective in some patients; if bedtime dose is not tolerated, may omit and administer total daily dose in 3 equally divided daytime doses.
Conversion from alternative therapy: Gradually initiate procyclidine 2.5 mg 3 times daily (may be used to replace all or part of alternative therapy); titrate dosage up (procyclidine) and/or down (alternative therapy) until satisfactory effect is achieved with procyclidine monotherapy.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.
There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.
Avoid use (Beers Criteria [AGS 2023]).
The following adverse drug reactions are derived from product labeling unless otherwise specified.
Frequency not defined:
Cardiovascular: Tachycardia (Holloman 1997)
Gastrointestinal: Constipation (Holloman 1997), epigastric distress, nausea, vomiting, xerostomia (Holloman 1997)
Genitourinary: Urinary retention (Holloman 1997)
Hypersensitivity: Hypersensitivity reaction
Nervous system: Dizziness, memory impairment (Hollman 1997), myasthenia
Ophthalmic: Blurred vision (Holloman 1997), mydriasis
Angle-closure glaucoma
Concerns related to adverse effects:
• Anhidrosis/hyperthermia: Anticholinergic agents may cause anhidrosis and hyperthermia, which may be severe; use with caution in hot weather or during exercise. The risk is increased in hot environments, particularly in the elderly, patients with alcohol use disorder, patients with CNS disease, and those with prolonged outdoor exposure.
• CNS effects: May be associated with restlessness, confusion, hallucinations, or other CNS effects, particularly in the elderly and generally at higher dosages; intensification of symptoms or toxic psychosis may occur in patients with mental disorders. Dose reductions/discontinuation of therapy may be necessary. May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with tachycardia, cardiac arrhythmias, hypertension, or hypotension.
• GI obstruction: Use with caution in patients with obstructive disease of the GI.
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Prostatic hyperplasia/urinary stricture: Use with caution in patients with prostatic hyperplasia and/or urinary stricture or retention.
• Renal impairment: Use with caution in patients with renal impairment.
• Tardive dyskinesia: Not recommended for use in patients with tardive dyskinesia unless concomitant Parkinson disease or tardive dystonia exists (Kang 1986).
Special populations:
• Older adult: Frequently develop increased sensitivity and require strict dosage regulation - side effects may be more severe in older adult patients with atherosclerotic changes.
Not available in the US
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Elixir, Oral:
Generic: 2.5 mg/5 mL ([DSC])
Tablet, Oral:
Generic: 2.5 mg [DSC], 5 mg [DSC]
Oral: Administer after meals to minimize stomach upset and anticholinergic effects.
Note: Not available in the United States.
Extrapyramidal symptoms: Management of medication-induced extrapyramidal symptoms.
Parkinsonism: Treatment of parkinsonism, including postencephalitic, arteriosclerotic, and idiopathic types.
Beers Criteria: Avoid for the prevention or treatment of extrapyramidal symptoms caused by antipsychotics. In the treatment of Parkinson disease, more effective agents are available (Beers Criteria [AGS 2023]).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Risk C: Monitor therapy
Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Amantadine: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy
Anticholinergic Agents: May enhance the adverse/toxic effect of other Anticholinergic Agents. Risk C: Monitor therapy
Betel Nut: May diminish the therapeutic effect of Procyclidine. Risk C: Monitor therapy
Botulinum Toxin-Containing Products: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy
Cannabinoid-Containing Products: Anticholinergic Agents may enhance the tachycardic effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
Chloral Betaine: May enhance the adverse/toxic effect of Anticholinergic Agents. Risk C: Monitor therapy
Chlorprothixene: Anticholinergic Agents may enhance the anticholinergic effect of Chlorprothixene. Risk C: Monitor therapy
Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Risk X: Avoid combination
CloZAPine: Anticholinergic Agents may enhance the constipating effect of CloZAPine. Management: Consider alternatives to this combination whenever possible. If combined, monitor closely for signs and symptoms of gastrointestinal hypomotility and consider prophylactic laxative treatment. Risk D: Consider therapy modification
Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Risk X: Avoid combination
Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Risk C: Monitor therapy
Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Risk C: Monitor therapy
Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Risk X: Avoid combination
Glycopyrronium (Topical): May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Risk C: Monitor therapy
Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Risk X: Avoid combination
Lisuride: Procyclidine may enhance the adverse/toxic effect of Lisuride. Risk X: Avoid combination
Mianserin: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy
Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Risk C: Monitor therapy
Nitroglycerin: Anticholinergic Agents may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Risk C: Monitor therapy
Opioid Agonists: Anticholinergic Agents may enhance the adverse/toxic effect of Opioid Agonists. Specifically, the risk for constipation and urinary retention may be increased with this combination. Risk C: Monitor therapy
Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
PARoxetine: May increase the serum concentration of Procyclidine. Risk C: Monitor therapy
Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Risk X: Avoid combination
Potassium Citrate: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium citrate. Risk X: Avoid combination
Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Risk X: Avoid combination
Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Risk C: Monitor therapy
Revefenacin: Anticholinergic Agents may enhance the anticholinergic effect of Revefenacin. Risk X: Avoid combination
Rivastigmine: Anticholinergic Agents may diminish the therapeutic effect of Rivastigmine. Rivastigmine may diminish the therapeutic effect of Anticholinergic Agents. Management: Use of rivastigmine with an anticholinergic agent is not recommended unless clinically necessary. If the combination is necessary, monitor for reduced anticholinergic effects. Risk D: Consider therapy modification
Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. Risk D: Consider therapy modification
Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy
Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Risk X: Avoid combination
Topiramate: Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. Risk C: Monitor therapy
Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Safe use during pregnancy has not been established.
It is not known if procyclidine is present in breast milk.
Should be taken after meals to minimize stomach upset and anticholinergic effects.
Heart rate, anticholinergic effects (ie, CNS, bowel and bladder function).
Thought to act by blocking excess acetylcholine at cerebral synapses; many of its effects are due to its pharmacologic similarities with atropine; it exerts an antispasmodic effect on smooth muscle, is a potent mydriatic; inhibits salivation
Onset of action: 45 to 60 minutes (Whiteman 1985)
Duration: Significant autonomic effects have been observed up to 12 hours (Whiteman 1985)
Distribution: Vd: 1 L/kg (Whiteman 1985)
Metabolism: Hydroxylation of the alicyclic groups (Brocks 1999)
Bioavailability: ~75% (Whiteman 1985)
Half-life elimination: ~12.6 hours (Whiteman 1985)
Time to peak: ~1.1 hour (Whiteman 1985)
Excretion: Urine (predominantly as metabolites) (Whiteman 1985)
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