Drug-induced extrapyramidal symptoms (eg, dystonia, parkinsonism):
Note: Anticholinergic agents may be ineffective for akathisia or worsen tardive dyskinesia (Ref).
Acute treatment:
Note: Parenteral administration is preferred for initial treatment of severe acute symptoms. Once severe symptoms have resolved, transition to oral treatment. Duration of therapy and prophylactic use should be based on severity of extrapyramidal symptoms (EPS), pharmacologic profile of the causative agent (eg, half-life, receptor-binding affinities), and patient risk factors (Ref). The manufacturer recommends withdrawing benztropine after 1 to 2 weeks, while some experts recommend attempting taper and discontinuation after several weeks to months (Ref).
General dosing recommendations: Initial: IM, IV, Oral: 1 to 2 mg/day given in divided doses (Ref) or may administer up to 1 to 2 mg 2 or 3 times daily; adjust total daily dose based on response and tolerability in 0.5 mg increments at intervals ≥3 days up to 6 mg/day; some patients may require up to 8 mg/day (Ref).
Dystonic reactions:
Initial dose: IM, IV, Oral: 1 to 2 mg once (Ref).
Subsequent doses: Oral: 1 to 2 mg once or twice daily (Ref).
Prevention, dystonic reactions (off-label use):
Note: Prophylactic use is generally not recommended when administering medications with increased risk of causing such reactions (eg, haloperidol, metoclopramide) since these reactions are uncommon and adding this agent may increase the risk of adverse events (Ref). May consider short-term use in patients at high risk for reactions (eg, high dose of high potency first generation antipsychotic, prior reaction) (Ref).
IM, IV, Oral: 1 to 2 mg once prior to administration of a high-risk medication (eg, if high-risk medication is to be administered IM, administer benztropine IM as well) (Ref).
Parkinson disease:
Note: For management of Parkinson disease–associated tremor. Due to adverse effects, avoid use in older patients and patients with cognitive impairment (Ref).
IM, IV, Oral: Initial: 1 mg/day in 2 to 4 divided doses. May titrate in increments of 0.5 mg/day at intervals of ≥5 days based on response and tolerability to 4 mg/day. Maximum: 6 mg/day (Ref).
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.
There are no dosage adjustments provided in the manufacturer's labeling.
Avoid use (Ref).
(For additional information see "Benztropine (benzatropine): Pediatric drug information")
Drug-induced extrapyramidal symptoms (EPS): Limited data available: Note: Prophylactic use is generally not recommended to prevent antipsychotic-associated EPS, especially for second-generation antipsychotics; consider individual preferences, history of EPS, and baseline risk factors for EPS, including antipsychotic receptor binding and adverse effect profile (Ref).
Children >3 years and Adolescents: Oral, IM, IV: 0.02 to 0.05 mg/kg/dose 1 to 2 times daily has been used for treatment of EPS; usual adult dose range: 1 to 4 mg/dose (Ref). The IV route should be reserved for situations when oral or IM are not appropriate. In clinical trials of pediatric patients ≥8 years with early-onset schizophrenia spectrum disorders (EOSS), benztropine 0.5 mg orally twice daily has been used to reduce the risk of development of anti-psychotic drug-induced EPS due to first-generation antipsychotics (ie, molindone) (Ref). Prophylactic benztropine is not recommended in patients treated with second-generation antipsychotics (Ref).
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.
There are no dosage adjustments provided in the manufacturer's labeling.
Benztropine may cause anticholinergic effects, such as blurred vision, constipation, mydriasis, paralytic ileus, tachycardia, urinary retention, and xerostomia. Anticholinergic effects may require dose reduction or treatment discontinuation. (Ref)
Mechanism: Dose-related; related to the pharmacologic action. Directly related to antagonism of muscarinic receptors (Ref).
Risk factors:
• Higher doses (Ref)
• Older age (Ref)
• Concomitant use with medications with anticholinergic properties (Ref)
Benztropine can cause anhidrosis, which may result in life-threatening hyperthermia or heatstroke (Ref).
Mechanism: Dose-related; related to the pharmacologic action. Antagonism of central and peripheral muscarinic receptors results in increased heat production due to increased muscle activity and impaired sweat gland function (Ref).
Risk factors:
• Environmental heat exposure (Ref)
• Concomitant use with other anticholinergic medications (Ref)
• Existing sweating disorder
Benztropine may cause psychiatric effects, including confusion, depression, delirium, psychotic symptoms, memory impairment, and nervousness. Psychiatric effects are reversible with discontinuation (Ref)
Mechanism: Dose-related; related to pharmacologic action. Related to antagonism of muscarinic receptors (Ref). Dopaminergic and noradrenergic activity may also contribute to effects of CNS activation (Ref).
Onset: Varied; hallucinations and psychosis have been reported as early as 45 minutes and up to several months following treatment initiation (Ref). Effects on memory and cognition have been reported within 4 days of treatment initiation (Ref).
Risk factors
• Higher doses (Ref)
• Older patients (>60 years) (Ref)
• Pediatric patients (Ref)
The following adverse drug reactions are derived from product labeling unless otherwise specified.
Postmarketing:
Cardiovascular: Tachycardia
Endocrine & metabolic: Heatstroke (Stadnyk 1983)
Gastrointestinal: Constipation, nausea, paralytic ileus (Kwiatkowski 2011), vomiting, xerostomia
Genitourinary: Dysuria, urinary retention
Hypersensitivity: Hypersensitivity reaction
Nervous system: Depression, hyperthermia (Manivannan 2021), lethargy, nervousness, numbness of fingers, psychotic symptoms, toxic psychosis (including confusion, disorientation, memory impairment, visual hallucination) (Grace 1997)
Ophthalmic: Blurred vision, mydriasis
Miscellaneous: Fever, hyperpyrexia (Green 2001)
Hypersensitivity to benztropine mesylate or any component of the formulation.
Children <3 years of age (due to atropine-like adverse effects including severe anhidrosis and fatal hyperthermia) and should be used cautiously in older children.
Concerns related to adverse effects:
• Muscle weakness: When given in large doses or to susceptible patients, may cause weakness and inability to move particular muscle groups.
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with tachycardia.
• GI obstruction: Use with caution in patients with obstructive disease of the GI tract (eg, pyloric or duodenal obstruction).
• Glaucoma: Use with caution in patients with glaucoma; avoid use in angle-closure glaucoma.
• Prostatic hyperplasia/urinary stricture: Use with caution in patients with prostatic hyperplasia and/or urinary stricture or retention.
Special populations:
• Pediatric: Use with caution in children >3 years of age due to its anticholinergic effects; dose has not been established. Use is contraindicated in children <3 years of age.
Other warnings/precautions:
• Tardive dyskinesia: Not recommended for use in patients with tardive dyskinesia; benztropine does not relieve symptoms of tardive dyskinesia and may potentially exacerbate symptoms.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Injection, as mesylate:
Cogentin: 1 mg/mL (2 mL [DSC])
Generic: 1 mg/mL (2 mL)
Solution, Injection, as mesylate [preservative free]:
Generic: 1 mg/mL (2 mL)
Tablet, Oral, as mesylate:
Generic: 0.5 mg, 1 mg, 2 mg
Yes
Solution (Benztropine Mesylate Injection)
1 mg/mL (per mL): $27.00 - $37.50
Tablets (Benztropine Mesylate Oral)
0.5 mg (per each): $0.17 - $0.53
1 mg (per each): $0.19 - $0.57
2 mg (per each): $0.25 - $0.68
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Injection, as mesylate:
Generic: 1 mg/mL (2 mL)
Tablet, Oral, as mesylate:
Generic: 1 mg
Oral: Administer with or without food.
Injectable: Administer IM or IV if oral route is unacceptable. Manufacturer’s labeling states there is no difference in onset of effect after IV or IM injection and therefore there is usually no need to use the IV route. No specific instructions on administering benztropine IV are provided in the labeling. The IV route has been reported in the literature (slow IV push when reported), although specific instructions are lacking (Ref).
Oral: May be given with or without food; administration with food may decrease GI upset.
Parenteral: IV route should be reserved for situations when oral or IM are not appropriate. Manufacturer's labeling states there is no difference in onset of effect after IV or IM injection and therefore there is usually no need to use the IV route. No specific instructions on administering benztropine IV are provided in the labeling. The IV route has been reported in the literature in adults (slow IV push when reported), although specific instructions are lacking (Ref).
Drug-induced extrapyramidal symptoms, acute treatment: Acute treatment of drug-induced extrapyramidal symptoms (excluding tardive dyskinesia).
Parkinsonism: Adjunctive therapy of all forms of parkinsonism.
Drug-induced extrapyramidal symptoms, prevention, acute dystonic reactions
Benztropine may be confused with bromocriptine
Beers Criteria: Benztropine (oral) is identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients 65 years and older due to its highly anticholinergic properties. It is not recommended for the prevention or treatment of extrapyramidal symptoms with antipsychotics. In the treatment of Parkinson disease, more effective agents are available (Beers Criteria [AGS 2023]).
Substrate of CYP2D6 (Minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
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 drug interactions program by clicking on the “Launch drug interactions program” link above.
Acetylcholinesterase Inhibitors: May decrease therapeutic effects of Agents with Clinically Relevant Anticholinergic Effects. Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Acetylcholinesterase Inhibitors. Risk C: Monitor
Aclidinium: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid
Acrivastine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Agents with Clinically Relevant Anticholinergic Effects: May increase anticholinergic effects of Benztropine. Risk C: Monitor
Amantadine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Benperidol: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Benperidol. Risk C: Monitor
Biperiden: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Biperiden. Risk C: Monitor
Bornaprine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Bornaprine. Risk C: Monitor
Botulinum Toxin-Containing Products: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Bromperidol: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Bromperidol. Risk C: Monitor
Buclizine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Buclizine. Risk C: Monitor
Cannabinoid-Containing Products: Agents with Clinically Relevant Anticholinergic Effects may increase tachycardic effects of Cannabinoid-Containing Products. Risk C: Monitor
Chlorprothixene: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Chlorprothixene. Risk C: Monitor
Cimetropium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Cimetropium. Risk X: Avoid
CloZAPine: Agents with Clinically Relevant Anticholinergic Effects may increase constipating effects 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
Cyclizine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Darifenacin: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Darifenacin. Risk C: Monitor
Dicyclomine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Dicyclomine. Risk C: Monitor
Dimethindene (Systemic): Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Dimethindene (Systemic). Risk C: Monitor
DroNABinol: Agents with Clinically Relevant Anticholinergic Effects may increase tachycardic effects of DroNABinol. Risk X: Avoid
Eluxadoline: Agents with Clinically Relevant Anticholinergic Effects may increase constipating effects of Eluxadoline. Risk X: Avoid
Fesoterodine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Fesoterodine. Risk C: Monitor
FluPHENAZine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Gastrointestinal Agents (Prokinetic): Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Gastrointestinal Agents (Prokinetic). Risk C: Monitor
Gepotidacin: May decrease anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Glucagon: Agents with Clinically Relevant Anticholinergic Effects may increase adverse/toxic effects of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Risk C: Monitor
Glycopyrrolate (Oral Inhalation): Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Glycopyrrolate (Oral Inhalation). Risk X: Avoid
Glycopyrrolate (Systemic): Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Glycopyrrolate (Systemic). Risk C: Monitor
Glycopyrronium (Topical): May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid
Ioflupane I 123: Coadministration of Benztropine and Ioflupane I 123 may alter diagnostic results. Risk C: Monitor
Ipratropium (Nasal): May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Ipratropium (Oral Inhalation): May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid
Itopride: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Itopride. Risk C: Monitor
Levosulpiride: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Levosulpiride. Risk X: Avoid
Lisuride: Benztropine may increase adverse/toxic effects of Lisuride. Risk X: Avoid
Maprotiline: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Maprotiline. Risk C: Monitor
Melperone: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Metergoline: May increase adverse/toxic effects of Anticholinergic Anti-Parkinsonian Agents. Risk C: Monitor
Methotrimeprazine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Methotrimeprazine. Risk C: Monitor
Methscopolamine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Methscopolamine. Risk C: Monitor
Mirabegron: Agents with Clinically Relevant Anticholinergic Effects may increase adverse/toxic effects of Mirabegron. Risk C: Monitor
Nitroglycerin: Agents with Clinically Relevant Anticholinergic Effects may decrease absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Risk C: Monitor
OLANZapine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of OLANZapine. Risk C: Monitor
Opioid Agonists: Agents with Clinically Relevant Anticholinergic Effects may increase adverse/toxic effects of Opioid Agonists. Specifically, the risk for constipation and urinary retention may be increased with this combination. Risk C: Monitor
Opipramol: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Oxatomide: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid
OxyBUTYnin: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of OxyBUTYnin. Risk C: Monitor
Perazine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Perphenazine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Perphenazine. Risk C: Monitor
Potassium Chloride: Agents with Clinically Relevant Anticholinergic Effects may increase ulcerogenic effects 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
Potassium Citrate: Agents with Clinically Relevant Anticholinergic Effects may increase ulcerogenic effects 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
Pramlintide: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. These effects are specific to the GI tract. Risk X: Avoid
Promethazine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Promethazine. Risk C: Monitor
Propantheline: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Propantheline. Risk C: Monitor
Propiverine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
QuiNIDine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Ramosetron: Agents with Clinically Relevant Anticholinergic Effects may increase constipating effects of Ramosetron. Risk C: Monitor
Revefenacin: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Revefenacin. Risk X: Avoid
Rivastigmine: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Rivastigmine. Rivastigmine may decrease therapeutic effects of Agents with Clinically Relevant Anticholinergic Effects. 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
Scopolamine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Scopolamine. Risk C: Monitor
Secretin: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects 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
Sofpironium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Sofpironium. Risk X: Avoid
Thiazide and Thiazide-Like Diuretics: Agents with Clinically Relevant Anticholinergic Effects may increase serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor
Thiothixene: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Thiothixene. Risk C: Monitor
Tiapride: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Tiapride. Risk C: Monitor
Tiotropium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Tiotropium. Risk X: Avoid
Tolterodine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Tolterodine. Risk C: Monitor
Topiramate: Agents with Clinically Relevant Anticholinergic Effects may increase adverse/toxic effects of Topiramate. Risk C: Monitor
Trimethobenzamide: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Trimethobenzamide. Risk C: Monitor
Trospium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Trospium. Risk C: Monitor
Umeclidinium: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid
Zuclopenthixol: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Zuclopenthixol. Risk C: Monitor
Paralytic ileus (which resolved rapidly) was reported in two newborns exposed to a combination of benztropine and chlorpromazine during the second and third trimesters and the last 6 weeks of pregnancy, respectively (Falterman 1980).
It is not known if benztropine is excreted in breast milk. Anticholinergic agents may suppress lactation.
Pulse, anticholinergic effects (baseline; as clinically indicated), mental alertness.
Possesses both anticholinergic and antihistaminic effects. In vitro anticholinergic activity approximates that of atropine; in vivo it is only about half as active as atropine. Animal data suggest its antihistaminic activity and duration of action approach that of pyrilamine maleate.
Onset of action:
IM, IV: Within a few minutes; there is no significant difference between onset of effect after intravenous or intramuscular injection
Oral: Within 1 hour
Metabolism: Hepatic (N-oxidation, N-dealkylation, and ring hydroxylation) (from animal studies only) (Brocks 1999)
Time to peak, plasma: Oral: 7 hours (Brocks 1999)