Benztropine is an oral and parenteral synthetic muscarinic-receptor antagonist that is structurally similar to atropine and diphenhydramine. It is used adjunctively with other antiparkinsonian agents to treat all types of parkinsonian syndromes including antipsychotic-induced extrapyramidal symptoms. Although benztropine is a tertiary amine, and as such crosses into the CNS, it produces less CNS stimulation than does trihexyphenidyl. The drug may be helpful in geriatric patients who cannot tolerate cerebral-stimulating agents. Benztropine has cumulative effects, and therapeutic benefit can take up to 2-3 days. Benztropine has a longer duration of action and may require less frequent dosing than diphenhydramine. Benztropine was approved for use in 1954.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
NOTE: Doses may be divided or given as a single daily dose at bedtime.
Route-Specific Administration
Oral Administration
-May be administered without regard to meals.
Injectable Administration
-Administer intramuscularly or intravenously. There is no clinically important difference in onset of effects between IM or IV injection, therefore, the manufacturer states that IV administration is rarely necessary.
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
-There is no clinically important difference in onset of effects between IM or IV injection, therefore, the manufacturer states that IV administration is rarely necessary.
-The manufacturer has not conducted specific studies to determine the rate of administration or dilution requirements prior to IV administration.
Intramuscular Administration
-Inject into a large muscle mass.
Benztropine has both anticholinergic and antihistaminic activity. Anticholinergic effects are usually minor with the use of normal doses but can be serious in an acute overdose or in combination with other drugs that also possess anticholinergic effects. Centrally-mediated adverse reactions of benztropine or other atropine-like drugs include drowsiness, dizziness, confusion, disorientation, memory impairment, visual hallucinations, nervousness (anxiety), listlessness, depression, headache, and paresthesias. Symptoms of nervousness or anxiety may lead to insomnia. Confusion and excitement may occur with use of large doses or in patients with a susceptibility to these symptoms. In patients with psychiatric disorders, benztropine can precipitate toxic psychosis. Symptoms due to anticholinergic toxicity are primarily centrally-mediated and may include dysarthria, headache, hyperreflexia, hypertonia, restlessness, ataxia, disorientation, hallucinations, delirium, coma, insomnia, dizziness, drowsiness, weakness, paranoia, seizures, vertigo, excitement, agitation, and confusion. Patients should be informed that benztropine may impair mental or physical abilities required to perform hazardous tasks such as driving or operating heavy machinery. Use of anticholinergic agents, such as benztropine, may exacerbate cognitive impairment, dementia, or delirium, particularly in the elderly. Low initial doses and gradual titration are recommended in geriatric patients. In general, the elderly cannot tolerate large doses of benztropine.
Ophthalmic adverse reactions that have been reported during benztropine administration include blurred vision, mydriasis, and cycloplegia. A more serious effect is ocular hypertension with the exacerbation of narrow-angle glaucoma. These effects are due to the anticholinergic activity of benztropine.
Benztropine has both anticholinergic and antihistaminic activity. Anticholinergic effects are usually minor with the use of normal doses but can be serious in an acute overdose or in combination with other drugs that also possess anticholinergic effects. Gastrointestinal adverse reactions of benztropine include xerostomia, constipation, nausea/vomiting, and paralytic ileus. Some cases of paralytic ileus have been fatal in patients taking antiparkinson's medications, including benztropine, in combination with phenothiazines and/or tricyclic antidepressants. Isolated instances of suppurative parotitis secondary to excessive dryness of the mouth and dilatation of the colon (i.e., toxic megacolon) have been reported with other anticholinergic agents. If appropriate, patients may suck on hard candy, chew gum, or drink water to relieve dry mouth. If xerostomia or nausea is so severe that the patient has trouble swallowing, trouble speaking, appetite loss, or weight loss, reduce the benztropine dosage or temporarily discontinue the drug. Use of anticholinergic agents, such as benztropine, may exacerbate chronic constipation, particularly in the elderly. Low initial doses and gradual titration are recommended in geriatric patients. In general, the elderly cannot tolerate large doses of benztropine.
The anticholinergic effect of benztropine can result in a decrease in the amount of sweating (hypohidrosis) and heat release from the body; anhidrosis may also occur. Hyperthermia, fever, and heat stroke have also been reported. Therefore, benztropine should be administered cautiously to patients during hot weather and to patients who are chronically ill, drink alcohol, or have central nervous system disease. Also, cautious use of benztropine by manual laborers who work in a hot environment is recommended. Anhidrosis may occur more readily when some disturbance of sweating already exists. Cases of heat stroke and hyperthermia, sometimes fatal, have been reported in patients taking antiparkinson's medications, including benztropine, in combination with phenothiazines and/or tricyclic antidepressants. If there is evidence of anhidrosis such as heat intolerance, consider the possibility of hyperthermia. A decrease in the benztropine dose may restore the ability of the body to maintain body heat equilibrium by perspiration.
Occasionally, an allergic reaction such as a skin rash develops. Discontinue benztropine if the rash (unspecified) cannot be controlled by dosage reduction.
Genitourinary effects including urinary retention and dysuria have been reported during treatment with benztropine. Such side effects are the result of the anticholinergic action of the drug. Benztropine may exacerbate pre-existing symptoms of urinary retention or hesitancy, particularly in the elderly. Low initial doses and gradual titration are recommended in geriatric patients. In general, the elderly cannot tolerate large doses of benztropine. Caution is advisable when using benztropine in patients with conditions associated with urinary retention such as benign prostatic hypertrophy.
Benztropine can cause sinus tachycardia secondary to the anticholinergic actions of the drug. Caution is recommended when using benztropine in patients with a propensity for tachycardia or with conditions associated with arrhythmias.
Patients who receive benztropine may experience asthenia (weakness). Also, patients may feel unable to move certain muscle groups. Rigid muscles may suddenly relax; the patient may complain of muscle weakness (myasthenia). In such cases, the dose of benztropine should be reduced.
Benztropine is contraindicated in patients with known benztropine mesylate hypersensitivity.
Benztropine, like other anticholinergic medications, should be avoided in patients with closed-angle glaucoma because the drug can induce cycloplegia and mydriasis, resulting in increased intraocular pressure.
Benztropine exhibits anticholinergic effects and should be used cautiously in patients with benign prostatic hypertrophy or bladder obstruction because it can exacerbate urinary retention. Urinary retention has been reported. The anticholinergic effects of benztropine may be significant and are additive with other anticholinergic medications, especially in older adults.
As with other drugs with anticholinergic activity, use benztropine with caution in patients with cardiac disease and preexisting tachycardia because it causes tachycardia secondary to cholinergic antagonism at the sino-atrial node. Tachycardia has been reported with benztropine in clinical use.
Benztropine may impair mental and/or physical abilities and cause blurred vision due to the anticholinergic effects, thus impairing the performance of hazardous tasks, such as driving or operating machinery. 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 symptoms (EPS) due to neuroleptic drugs (e.g.,phenothiazines), in patients with psychiatric disease, occasionally there may be intensification of mental symptoms and behavioral changes. In such cases, antiparkinsonian drugs like benztropine 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. The anticholinergic effects of benztropine may exacerbate dementia symptoms and should be avoided in patients with dementia.
Tardive dyskinesia may appear in some patients on long-term therapy with phenothiazines and related agents, or may occur after therapy with these drugs has been discontinued. While useful also in the control of extrapyramidal disorders due to neuroleptic drugs (e.g., phenothiazines), it should be noted that benztropine is not useful in treating tardive dyskinesia. Antiparkinsonism agents do not alleviate the symptoms of tardive dyskinesia, and in some instances may aggravate them. Benztropine is not recommended for use in patients with tardive dyskinesia.
Benztropine should be generally avoided in patients with myasthenia gravis because the anticholinergic effects of the drug compete with acetylcholine and may exacerbate muscle weakness. Benztropine should be similarly used with extreme caution in patients with autonomic neuropathy. Benztropine may cause 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.Complaints of muscle weakness in a patient receiving benztropine may indicate that a dosage adjustment is required.
Clinical experience has not identified differences in efficacy or safety between geriatric and younger adults; however, older adults may be more sensitive to anticholinergic effects and the dose should be started at the low end of the dosage range and increased only as needed and with close monitoring for adverse events. According to the Beers Criteria, oral benztropine is considered a potentially inappropriate medication (PIM) in geriatric adults as a prophylactic agent for extrapyramidal symptoms (EPS) with antipsychotics due to the anticholinergic effects. In general, avoid in those with Parkinson's disease because more effective treatments are available. Also avoid drugs with strong anticholinergic properties in the following conditions due to the potential for symptom exacerbation or adverse effects: dementia/cognitive impairment (drug-induced CNS effects), delirium/high risk of delirium (possible new-onset or worsening delirium), or lower urinary tract symptoms/benign prostatic hyperplasia in men (urinary retention or hesitancy).
Since benztropine contains structural features of atropine, and thus significant anticholinergic effects, it may produce anhidrosis. For this reason, it should be administered with caution during hot weather (ambient temperature increase), especially when given concomitantly with other atropine-like drugs to the chronically ill, a person with alcoholism, those who have central nervous system disease, and those who do manual labor 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 and fatal hyperthermia have occurred. 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 benztropine, in combination with phenothiazines and/or tricyclic antidepressants (TCAs).
According to the manufacturer, the safe use of benztropine during pregnancy has not been established. There are no data in the published literature that affirm or contraindicate the use of benztropine in pregnancy for treating movement disorders, such as Parkinson's disease, or as a prophylactic for extrapyramidal effects in conjunction with antipsychotic use. Very few pregnancies are reported to have exposure to benztropine. Trihexyphenidyl, while also a drug with limited data, has been reported in use during pregnancy in a few cases. The effects of benztropine on labor and obstetric delivery are unknown.
It is unknown whether benztropine is excreted in human milk and there are no breast-feeding recommendations available from the manufacturer. Atropine, a structurally related anticholinergic agent, has previously considered to be compatible with breast-feeding due to the lack of reported effects on the nursing infant. However, antimuscarinic medications have been reported to inhibit lactation in animals and reduce serum prolactin in non-nursing women. Therefore, caution should be exercised when administering benztropine to a breast-feeding woman. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding baby experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.
Benztropine is contraindicated by the manufacturer for use in neonates, infants, and children under 3 years of age. Pediatric patients are typically more sensitive to the anticholinergic side effects of this drug. Caution is advisable during use of benztropine in adolescents and children 3 years of age and older.
The anticholinergic effects of benztropine may make the eyes dry. As with many anticholinergic drugs, use may cause discomfort or an increased lens awareness for wearers of contact lenses. The use of lubricating drops may be necessary, or in severe cases, discontinue the use of contact lenses while taking benztropine.
For the treatment of parkinsonism or Parkinson's disease as an adjunct:
-for the treatment of idiopathic parkinsonism or Parkinson's disease:
Oral dosage:
Adults: 0.5 to 1 mg PO once daily at bedtime, initially. May increase the dose by 0.5 mg/day every 5 to 6 days based on clinical response and tolerability. Usual dose: 1 to 2 mg/day. Max: 6 mg/day in 1 or more divided doses.
Intramuscular dosage:
Adults: 0.5 to 1 mg IM once daily, initially. May increase the dose by 0.5 mg/day every 5 to 6 days based on clinical response and tolerability. Usual dose: 1 to 2 mg/day. Max: 6 mg/day in 1 or more divided doses.
-for the treatment of postencephalitic Parkinsonism:
Oral dosage:
Adults: 2 mg/day PO in 1 or more divided doses, initially. Consider 0.5 mg PO once daily at bedtime, initially, for highly sensitive persons. May increase the dose by 0.5 mg/day every 5 to 6 days based on clinical response and tolerability. Usual dose: 1 to 2 mg/day. Max: 6 mg/day in 1 or more divided doses.
Intramuscular dosage:
Adults: 2 mg/day IM in 1 or more divided doses, initially. Consider 0.5 mg IM once daily at bedtime, initially, for highly sensitive persons. May increase the dose by 0.5 mg/day every 5 to 6 days based on clinical response and tolerability. Usual dose: 1 to 2 mg/day. Max: 6 mg/day in 1 or more divided doses.
For the treatment of drug-induced extrapyramidal symptoms:
Intravenous, Intramuscular, or Oral dosage:
Adults: The recommended dose is 1 to 4 mg IV, IM, or PO once or twice daily. Acute dystonic reactions generally respond to 1 or 2 mg IV or IM, followed by an oral dose to prevent recurrence. Reevaluate the need for benztropine after several days of treatment. Extrapyramidal symptoms that may develop after initiation of treatment with antipsychotics are often transient and usually respond to a dose of 1 or 2 mg PO twice daily or 3 times daily, within 1 or 2 days. In geriatric patients, initiate therapy at the low end of the dosing range and increase only as needed with monitoring for the emergence of adverse events. The manufacturer has not conducted specific studies to determine the rate of administration or dilution requirements prior to IV administration. According to the treatment guidelines of the American Academy of Neurology, there is insufficient evidence to determine the effectiveness of anticholinergic drugs in treating extrapyramidal symptoms such as tardive dyskinesia.
Adolescents: Specific dosing instructions for pediatric patients are not available from the manufacturer. A weight-based dose of 0.02 to 0.05 mg/kg/dose IV once or twice per day has been reported in children 3 to 12 years. The recommended adult dose range is 1 to 4 mg IV, IM, or PO once or twice daily. Acute dystonic reactions generally respond to 1 or 2 mg IV or IM, followed by an oral dose to prevent recurrence. Reevaluate the need for benztropine after several days of treatment. Extrapyramidal symptoms that may develop after initiation of treatment with antipsychotics are often transient and usually respond to a dose of 1 or 2 mg PO twice daily or 3 times daily, within 1 or 2 days. The manufacturer has not conducted specific studies to determine the rate of administration or dilution requirements prior to IV administration. According to the treatment guidelines of the American Academy of Neurology, there is insufficient evidence to determine the effectiveness of anticholinergic drugs in treating extrapyramidal symptoms such as tardive dyskinesia.
Children 3 years and older: Specific dosing instructions for pediatric patients are not available from the manufacturer. A weight-based dose of 0.02 to 0.05 mg/kg/dose IV once or twice per day has been reported in children 3 to 12 years; single doses rarely exceed 1 mg/dose. Reevaluate the need for benztropine after several days of treatment. The manufacturer has not conducted specific studies to determine the rate of administration or dilution requirements prior to IV administration. According to the treatment guidelines of the American Academy of Neurology, there is insufficient evidence to determine the effectiveness of anticholinergic drugs in treating extrapyramidal symptoms such as tardive dyskinesia.
For the treatment of chronic sialorrhea* (chronic drooling) in developmentally-disabled patients:
Oral dosage:
Adults: In a double-blind, placebo-controlled study of 20 developmentally-disabled patients, benztropine (mean dose 3.8 mg/day PO) was superior to placebo during 2 continuous weeks of administration. Minor side effects such as dry mouth were alleviated by minor dosage adjustments.
Maximum Dosage Limits:
-Adults
8 mg/day PO, IM, or IV.
-Geriatric
8 mg/day PO, IM, or IV.
-Adolescents
Weight-based doses up to 0.05 mg/kg/dose PO, IM or IV, not to exceed adult maximum of 8 mg/day PO, IM or IV, have been reported.
-Children
3 years and older: Weight-based doses up to 0.05 mg/kg/dose PO, IM or IV, generally not to exceed 1 mg/dose, have been reported.
Less than 3 years: Contraindicated.
-Infants
Contraindicated.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
AbobotulinumtoxinA: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when dihydrocodeine is used concomitantly with an anticholinergic drug. The concomitant use of dihydrocodeine and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Acetaminophen; Chlorpheniramine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Acetaminophen; Codeine: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant codeine and benztropine use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Acetaminophen; Diphenhydramine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Acetaminophen; Hydrocodone: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant hydrocodone and benztropine use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Acetaminophen; Oxycodone: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant oxycodone and benztropine use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Acetylcholine Chloride: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Aclidinium: (Moderate) Although aclidinium is minimally absorbed into the systemic circulation after inhalation, there is the potential for aclidinium to have additive anticholinergic effects when administered with other anticholinergics or antimuscarinics. Per the manufacturer, avoid concomitant administration of aclidinium with other anticholinergic medications, when possible.
Aclidinium; Formoterol: (Moderate) Although aclidinium is minimally absorbed into the systemic circulation after inhalation, there is the potential for aclidinium to have additive anticholinergic effects when administered with other anticholinergics or antimuscarinics. Per the manufacturer, avoid concomitant administration of aclidinium with other anticholinergic medications, when possible.
Acrivastine; Pseudoephedrine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Alfentanil: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when alfentanil is used concomitantly with an anticholinergic drug. The concomitant use of alfentanil and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Aliskiren; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Alosetron: (Major) Concomitant use of alosetron and anticholinergics, which can decrease GI motility, may seriously worsen constipation, leading to events such as GI obstuction, impaction, or paralytic ileus. Although specific recommendations are not available from the manufacturer, it would be prudent to avoid anticholinergics in patients taking alosetron.
Alprazolam: (Moderate) CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of benztropine.
Aluminum Hydroxide: (Moderate) Antacids may inhibit the oral absorption of anticholinergics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
Aluminum Hydroxide; Magnesium Carbonate: (Moderate) Antacids may inhibit the oral absorption of anticholinergics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
Aluminum Hydroxide; Magnesium Hydroxide: (Moderate) Antacids may inhibit the oral absorption of anticholinergics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Moderate) Antacids may inhibit the oral absorption of anticholinergics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
Aluminum Hydroxide; Magnesium Trisilicate: (Moderate) Antacids may inhibit the oral absorption of anticholinergics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
Amantadine: (Moderate) Additive anticholinergic effects may be seen when benztropine is used concomitantly with other drugs that possess anticholinergic properties, such as amantadine. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur.
Amiloride; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Amitriptyline: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant tricyclic antidepressant and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Amobarbital: (Moderate) CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of benztropine.
Amoxapine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when amoxapine is used concomitantly with other anticholinergic agents. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive CNS effects are also possible when these drugs are combined with amoxapine.
Antacids: (Moderate) Antacids may inhibit the oral absorption of anticholinergics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
Antidiarrheals: (Moderate) Both antidiarrheals and anticholinergics, such as benztropine, decrease GI motility. Use of these drugs together may produce additive effects on the GI track; thereby increasing the risk for toxic megacolon.
Anxiolytics; Sedatives; and Hypnotics: (Moderate) CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of benztropine.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of benztropine.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Additive anticholinergic effects may be seen when benztropine is used concomitantly with other drugs that possess anticholinergic properties, such as orphenadrine. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant codeine and benztropine use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Aspirin, ASA; Oxycodone: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant oxycodone and benztropine use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Atenolol; Chlorthalidone: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Azilsartan; Chlorthalidone: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Barbiturates: (Moderate) CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of benztropine.
Belladonna; Opium: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when opium is used concomitantly with an anticholinergic drug. The concomitant use of opium and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Benazepril; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Benzhydrocodone; Acetaminophen: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when benzhydrocodone is used concomitantly with an anticholinergic drug. The concomitant use of benzhydrocodone and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Benzodiazepines: (Moderate) CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of benztropine.
Bethanechol: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Bismuth Subsalicylate: (Moderate) Both antidiarrheals and anticholinergics, such as benztropine, decrease GI motility. Use of these drugs together may produce additive effects on the GI track; thereby increasing the risk for toxic megacolon.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Both antidiarrheals and anticholinergics, such as benztropine, decrease GI motility. Use of these drugs together may produce additive effects on the GI track; thereby increasing the risk for toxic megacolon.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Botulinum Toxins: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Brompheniramine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Brompheniramine; Phenylephrine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Brompheniramine; Pseudoephedrine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Buprenorphine: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant buprenorphine and benztropine use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Buprenorphine; Naloxone: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant buprenorphine and benztropine use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Bupropion: (Moderate) Additive anticholinergic effects may be seen when benztropine is used concomitantly with other drugs that possess anticholinergic properties, such as bupropion. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur.
Bupropion; Naltrexone: (Moderate) Additive anticholinergic effects may be seen when benztropine is used concomitantly with other drugs that possess anticholinergic properties, such as bupropion. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur.
Butalbital; Acetaminophen: (Moderate) CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of benztropine.
Butalbital; Acetaminophen; Caffeine: (Moderate) CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of benztropine.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of benztropine. (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant codeine and benztropine use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of benztropine. (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant codeine and benztropine use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Butorphanol: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when butorphanol is used concomitantly with an anticholinergic drug. The concomitant use of butorphanol and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Calcium Carbonate: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics.
Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics.
Calcium Carbonate; Magnesium Hydroxide: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics.
Calcium Carbonate; Magnesium Hydroxide; Simethicone: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics.
Calcium Carbonate; Simethicone: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics.
Calcium; Vitamin D: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics.
Candesartan; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Captopril; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Carbidopa; Levodopa: (Minor) Through its central antimuscarinic actions, antimuscarinics such as benztropine can potentiate 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.
Carbidopa; Levodopa; Entacapone: (Minor) Through its central antimuscarinic actions, antimuscarinics such as benztropine can potentiate 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.
Carbinoxamine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Celecoxib; Tramadol: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant tramadol and benztropine use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Cetirizine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant cetirizine and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Cetirizine; Pseudoephedrine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant cetirizine and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Cevimeline: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Chlophedianol; Dexbrompheniramine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Chlorcyclizine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Chlordiazepoxide: (Moderate) CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of benztropine.
Chlordiazepoxide; Amitriptyline: (Moderate) CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of benztropine. (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant tricyclic antidepressant and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Chlordiazepoxide; Clidinium: (Moderate) CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of benztropine.
Chlorothiazide: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Chlorpheniramine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Chlorpheniramine; Codeine: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant codeine and benztropine use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Chlorpheniramine; Dextromethorphan: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Chlorpheniramine; Hydrocodone: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant hydrocodone and benztropine use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Chlorpheniramine; Phenylephrine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Chlorpheniramine; Pseudoephedrine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Chlorpromazine: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including chlorpromazine. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other additive CNS effects may also occur.
Chlorthalidone: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Cholinergic agonists: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Cisapride: (Moderate) Benztropine is an antagonist at muscarinic cholinergic receptors (an anticholinergic drug), and thus, can antagonize the action of drugs that enhance gastrointestinal motility, such as cisapride. Avoid chronic administration of antimuscarinics along with prokinetic agents under most circumstances. The clinical significance of these potential interactions is uncertain.
Clemastine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Clomipramine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant tricyclic antidepressant and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Clonazepam: (Moderate) CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of benztropine.
Clorazepate: (Moderate) CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of benztropine.
Clozapine: (Major) Avoid co-prescribing clozapine with other anticholinergic medicines that can cause gastrointestinal hypomotility, due to a potential to increase serious constipation, ileus, and other potentially serious bowel conditions that may result in hospitalization. Clozapine exhibits potent anticholinergic effects. Additive anticholinergic effects may be seen when clozapine is used concomitantly with anticholinergic agents. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur, depending on the anticholinergic agent used.
Codeine: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant codeine and benztropine use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Codeine; Guaifenesin: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant codeine and benztropine use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant codeine and benztropine use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Codeine; Phenylephrine; Promethazine: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant codeine and benztropine use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant promethazine and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Codeine; Promethazine: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant codeine and benztropine use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant promethazine and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Crofelemer: (Moderate) Pharmacodynamic interactions between crofelemer and antimuscarinics are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as antimuscarinics, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Cyclobenzaprine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant cyclobenzaprine and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Cyproheptadine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Dasiglucagon: (Major) The concomitant use of intravenous glucagon and anticholinergics increases the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. Concomitant use is not recommended.
DaxibotulinumtoxinA: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Desipramine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant tricyclic antidepressant and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Dexbrompheniramine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Dexbrompheniramine; Pseudoephedrine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Dexchlorpheniramine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Dextromethorphan; Bupropion: (Moderate) Additive anticholinergic effects may be seen when benztropine is used concomitantly with other drugs that possess anticholinergic properties, such as bupropion. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Dextromethorphan; Quinidine: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
Diazepam: (Moderate) CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of benztropine.
Digoxin: (Moderate) Anticholinergics, because of their ability to cause tachycardia, can antagonize the beneficial actions of digoxin in atrial fibrillation/flutter. Routine therapeutic monitoring should be continued when an antimuscarinic agent is prescribed with digoxin until the effects of combined use are known.
Dimenhydrinate: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Diphenhydramine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Diphenhydramine; Ibuprofen: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Diphenhydramine; Naproxen: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Diphenhydramine; Phenylephrine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Disopyramide: (Moderate) In addition to its electrophysiologic effects, disopyramide exhibits clinically significant anticholinergic properties. These can be additive with other anticholinergics. Clinicians should be aware that urinary retention, particularly in males, and aggravation of glaucoma are realistic possibilities of using disopyramide with other anticholinergic agents.
Donepezil: (Moderate) The therapeutic benefits of donepezil, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
Donepezil; Memantine: (Moderate) The adverse effects of anticholinergics, such as dry mouth, urinary hesitancy or blurred vision may be enhanced with use of memantine; dosage adjustments of the anticholinergic drug may be required when memantine is coadministered. In addition, preliminary evidence indicates that chronic anticholinergic use in patients with Alzheimer's Disease may possibly have an adverse effect on cognitive function. Therefore, the effectiveness of drugs used in the treatment of Alzheimer's such as memantine, may be adversely affected by chronic antimuscarinic therapy. (Moderate) The therapeutic benefits of donepezil, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
Doxepin: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant tricyclic antidepressant and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Doxylamine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Doxylamine; Pyridoxine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Dronabinol: (Moderate) Use caution if coadministration of dronabinol with anticholinergics is necessary. Concurrent use of dronabinol, THC with anticholinergics may result in additive drowsiness, hypertension, tachycardia, and possibly cardiotoxicity.
Droperidol: (Moderate) CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of benztropine.
Eluxadoline: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as anticholinergics. Discontinue use of eluxadoline in patients who develop severe constipation lasting more than 4 days.
Enalapril; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Eprosartan; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Estazolam: (Moderate) CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of benztropine.
Eszopiclone: (Moderate) CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of benztropine.
Fentanyl: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant fentanyl and benztropine use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Fluphenazine: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including fluphenazine. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other additive CNS effects may also occur.
Flurazepam: (Moderate) CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of benztropine.
Fluticasone; Umeclidinium; Vilanterol: (Moderate) There is the potential for umeclidinium to have additive anticholinergic effects when administered with other anticholinergics or antimuscarinics. Per the manufaturer, avoid concomitant administration of umeclidinium with other anticholinergic medications when possible.
Fosinopril; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Galantamine: (Moderate) The therapeutic benefits of galantamine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
Glucagon: (Major) The concomitant use of intravenous glucagon and anticholinergics increases the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. Concomitant use is not recommended.
Glycopyrronium: (Moderate) Although glycopyrronium is minimally absorbed into the systemic circulation after topical application, there is the potential for glycopyrronium to have additive anticholinergic effects when administered with other antimuscarinics. Per the manufaturer, avoid concomitant administration of glycopyrronium with other anticholinergic medications.
Guanidine: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Haloperidol: (Moderate) Advise patients to promptly report gastrointestinal complaints, fever, or heat intolerance when benztropine is used with drugs with either anticholinergic activity or antidopaminergic activity (example is haloperidol). Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur.
Homatropine; Hydrocodone: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant hydrocodone and benztropine use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Hydrochlorothiazide, HCTZ; Moexipril: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Hydrocodone: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant hydrocodone and benztropine use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Hydrocodone; Ibuprofen: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant hydrocodone and benztropine use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Hydromorphone: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when hydromorphone is used concomitantly with an anticholinergic drug. The concomitant use of hydromorphone and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Hydroxyzine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Ibritumomab Tiuxetan: (Moderate) Use anticholinergics, such as benztropine, and concomitant solid oral dosage forms of potassium chloride with caution due to risk for gastrointestinal mucosal injury. Anticholinergics may decrease gastric motility and increase the transit time of solid oral dosage forms of potassium chloride leading to prolonged contact with the gastrointestinal mucosa.
Ibuprofen; Oxycodone: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant oxycodone and benztropine use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Imipramine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant tricyclic antidepressant and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
IncobotulinumtoxinA: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Ioflupane I 123: (Moderate) Benztropine binds to the dopamine transporter and may interfere with dopamine transporter (DAT) imaging that utilizes radiolabeled ioflupane.
Ipratropium: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
Ipratropium; Albuterol: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
Irbesartan; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Itraconazole: (Moderate) Antimuscarinics can raise intragastric pH. This effect may decrease the oral bioavailability of itraconazole; antimuscarinics should be used cautiously in patients receiving itraconazole.
Levocetirizine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant cetirizine and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Levodopa: (Minor) Through its central antimuscarinic actions, antimuscarinics such as benztropine can potentiate 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.
Levorphanol: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when levorphanol is used concomitantly with an anticholinergic drug. The concomitant use of levorphanol and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Linaclotide: (Moderate) Anticholinergics can promote constipation and pharmacodynamically oppose the action of drugs used for the treatment of constipation or constipation-associated irritable bowel syndrome, such as linaclotide.
Lisinopril; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Loperamide: (Moderate) Both antidiarrheals and anticholinergics, such as benztropine, decrease GI motility. Use of these drugs together may produce additive effects on the GI track; thereby increasing the risk for toxic megacolon.
Loperamide; Simethicone: (Moderate) Both antidiarrheals and anticholinergics, such as benztropine, decrease GI motility. Use of these drugs together may produce additive effects on the GI track; thereby increasing the risk for toxic megacolon.
Lorazepam: (Moderate) CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of benztropine.
Losartan; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Loxapine: (Moderate) Loxapine has anticholinergic activity. The concomitant use of loxapine and other anticholinergic drugs can increase the risk of anticholinergic adverse reactions including exacerbation of glaucoma, constipation, and urinary retention. Depending on the agent used, additive drowsiness/dizziness may also occur.
Lubiprostone: (Moderate) Antimuscarinic drugs can promote constipation and pharmacodynamically oppose the action of drugs used for the treatment of constipation, such as lubiprostone. The clinical significance of these potential interactions is uncertain.
Lurasidone: (Moderate) Antipsychotic agents may disrupt core temperature regulation; therefore, caution is recommended during concurrent use of lurasidone and medications with anticholinergic activity such as antimuscarinics. Concurrent use of lurasidone and medications with anticholinergic activity may contribute to heat-related disorders. Monitor patients for heat intolerance, decreased sweating, or increased body temperature if lurasidone is used with antimuscarinics.
Macimorelin: (Major) Avoid use of macimorelin with drugs that may blunt the growth hormone response to macimorelin, such as antimuscarinic anticholinergic agents. Healthcare providers are advised to discontinue anticholinergics at least 1 week before administering macimorelin. Use of these medications together may impact the accuracy of the macimorelin growth hormone test.
Magnesium Hydroxide: (Moderate) Antacids may inhibit the oral absorption of anticholinergics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
Magnesium Salts: (Moderate) Antacids may inhibit the oral absorption of anticholinergics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
Maprotiline: (Moderate) Additive anticholinergic effects may be seen when benztropine is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including maprotiline. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Meclizine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Memantine: (Moderate) The adverse effects of anticholinergics, such as dry mouth, urinary hesitancy or blurred vision may be enhanced with use of memantine; dosage adjustments of the anticholinergic drug may be required when memantine is coadministered. In addition, preliminary evidence indicates that chronic anticholinergic use in patients with Alzheimer's Disease may possibly have an adverse effect on cognitive function. Therefore, the effectiveness of drugs used in the treatment of Alzheimer's such as memantine, may be adversely affected by chronic antimuscarinic therapy.
Meperidine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when meperidine is used concomitantly with an anticholinergic drug. The concomitant use of meperidine and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Meprobamate: (Moderate) CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of benztropine.
Methadone: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when methadone is used concomitantly with an anticholinergic drug. The concomitant use of methadone and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Methohexital: (Moderate) CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of benztropine.
Metoclopramide: (Moderate) Drugs with significant antimuscarinic activity, such as anticholinergics and antimuscarinics, may slow GI motility and thus may reduce the prokinetic actions of metoclopramide. Monitor patients for an increase in gastrointestinal complaints, such as reflux or constipation. Additive drowsiness may occur as well. The clinical significance is uncertain.
Metolazone: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Metoprolol; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Midazolam: (Moderate) CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of benztropine.
Molindone: (Moderate) Antipsychotics are associated with anticholinergic effects; therefore, additive effects may be seen during concurrent use of molindone and other drugs having anticholinergic activity such as antimuscarinics. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other CNS effects may also occur.
Morphine: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant morphine and benztropine use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Morphine; Naltrexone: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant morphine and benztropine use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Nabilone: (Moderate) Concurrent use of nabilone with anticholinergics may result in pronounced tachycardia and drowsiness.
Nalbuphine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when nalbuphine is used concomitantly with an anticholinergic drug. The concomitant use of nalbuphine and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Neostigmine: (Major) The muscarinic actions of neostigmine can antagonize the antimuscarinic actions of benztropine. Benztropine might also antagonize some of the effects of neostigmine.
Neostigmine; Glycopyrrolate: (Major) The muscarinic actions of neostigmine can antagonize the antimuscarinic actions of benztropine. Benztropine might also antagonize some of the effects of neostigmine.
Nortriptyline: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant tricyclic antidepressant and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Olanzapine: (Moderate) Additive anticholinergic effects may be seen when olanzapine and anticholinergics are used concomitantly; use with caution. Use of olanzapine and other drugs with anticholinergic activity can increase the risk for severe gastrointestinal adverse reactions related to hypomotility. Olanzapine exhibits anticholinergic activity. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur, depending on the anticholinergic agent used.
Olanzapine; Fluoxetine: (Moderate) Additive anticholinergic effects may be seen when olanzapine and anticholinergics are used concomitantly; use with caution. Use of olanzapine and other drugs with anticholinergic activity can increase the risk for severe gastrointestinal adverse reactions related to hypomotility. Olanzapine exhibits anticholinergic activity. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur, depending on the anticholinergic agent used.
Olanzapine; Samidorphan: (Moderate) Additive anticholinergic effects may be seen when olanzapine and anticholinergics are used concomitantly; use with caution. Use of olanzapine and other drugs with anticholinergic activity can increase the risk for severe gastrointestinal adverse reactions related to hypomotility. Olanzapine exhibits anticholinergic activity. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur, depending on the anticholinergic agent used.
Oliceridine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when oliceridine is used with benztropine. Use of anticholinergics may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Olmesartan; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
OnabotulinumtoxinA: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Orphenadrine: (Moderate) Additive anticholinergic effects may be seen when benztropine is used concomitantly with other drugs that possess anticholinergic properties, such as orphenadrine. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur.
Oxazepam: (Moderate) CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of benztropine.
Oxycodone: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant oxycodone and benztropine use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Oxymorphone: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when oxymorphone is used concomitantly with an anticholinergic drug. The concomitant use of oxymorphone and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Paroxetine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant anticholinergic medication and paroxetine use. Concomitant use may result in additive anticholinergic adverse effects.
Pentazocine; Naloxone: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when pentazocine is used concomitantly with an anticholinergic drug. The concomitant use of pentazocine and anticholinergic medications may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Pentobarbital: (Moderate) CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of benztropine.
Perphenazine: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including perphenazine. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other additive CNS effects may also occur.
Perphenazine; Amitriptyline: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including perphenazine. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other additive CNS effects may also occur. (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant tricyclic antidepressant and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Phenobarbital: (Moderate) CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of benztropine.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of benztropine.
Phentermine; Topiramate: (Moderate) Monitor for decreased sweating and increased body temperature, especially in hot weather, during concomitant use of topiramate and other drugs that predispose persons to heat-related disorders, such as anticholinergic medications. Concomitant use increases the risk for oligohidrosis and hyperthermia.
Physostigmine: (Major) The muscarinic actions of physostigmine can antagonize the antimuscarinic actions of benztropine. Benztropine might also antagonize some of the effects of the parasympathomimetics.
Pilocarpine: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Potassium Bicarbonate: (Moderate) Use anticholinergics, such as benztropine, and concomitant solid oral dosage forms of potassium chloride with caution due to risk for gastrointestinal mucosal injury. Anticholinergics may decrease gastric motility and increase the transit time of solid oral dosage forms of potassium chloride leading to prolonged contact with the gastrointestinal mucosa.
Potassium Chloride: (Moderate) Use anticholinergics, such as benztropine, and concomitant solid oral dosage forms of potassium chloride with caution due to risk for gastrointestinal mucosal injury. Anticholinergics may decrease gastric motility and increase the transit time of solid oral dosage forms of potassium chloride leading to prolonged contact with the gastrointestinal mucosa.
Pralidoxime: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Pramlintide: (Major) Pramlintide therapy should not be considered in patients taking medications that alter gastric motility, such as anticholinergics. Pramlintide slows gastric emptying and the rate of nutrient delivery to the small intestine. Medications that have depressive effects on GI could potentiate the actions of pramlintide.
Primidone: (Moderate) CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of benztropine.
Procainamide: (Moderate) The anticholinergic effects of procainamide may be significant and may be enhanced when combined with anticholinergics. Anticholinergic agents administered concurrently with procainamide may produce additive antivagal effects on AV nodal conduction, although this is not as well documented for procainamide as for quinidine.
Prochlorperazine: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including prochlorperazine. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other additive CNS effects may also occur.
Promethazine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant promethazine and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Promethazine; Dextromethorphan: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant promethazine and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Promethazine; Phenylephrine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant promethazine and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Protriptyline: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant tricyclic antidepressant and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Pseudoephedrine; Triprolidine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Pyridostigmine: (Major) The muscarinic actions of pyridostigmine can antagonize the antimuscarinic actions of benztropine. Benztropine might also antagonize some of the effects of the parasympathomimetics.
Quazepam: (Moderate) CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of benztropine.
Quetiapine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant quetiapine and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Quinapril; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Quinidine: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
Rasagiline: (Moderate) MAOIs exhibit secondary anticholinergic actions. Additive anticholinergic effects may be seen when MAOIs are used concomitantly with antimuscarinics. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive CNS effects are also possible when many of these drugs are combined with MAOIs.
Remifentanil: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when remifentanil is used concomitantly with an anticholinergic drug. The concomitant use of remifentanil and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Remimazolam: (Moderate) CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of benztropine.
Revefenacin: (Moderate) Although revefenacin is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinics. Avoid concomitant administration with other anticholinergic and antimucarinic medications.
RimabotulinumtoxinB: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Rivastigmine: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
Secobarbital: (Moderate) CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of benztropine.
Secretin: (Major) Discontinue anticholinergic medications at least 5 half-lives before administering secretin. Patients who are receiving anticholinergics at the time of stimulation testing may be hyporesponsive to secretin stimulation and produce a false result. Consider additional testing and clinical assessments for aid in diagnosis.
Sedating H1-blockers: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Sincalide: (Moderate) Sincalide-induced gallbladder ejection fraction may be affected by anticholinergics. False study results are possible in patients with drug-induced hyper- or hypo-responsiveness; thorough patient history is important in the interpretation of procedure results.
Sodium Sulfate; Magnesium Sulfate; Potassium Chloride: (Moderate) Use anticholinergics, such as benztropine, and concomitant solid oral dosage forms of potassium chloride with caution due to risk for gastrointestinal mucosal injury. Anticholinergics may decrease gastric motility and increase the transit time of solid oral dosage forms of potassium chloride leading to prolonged contact with the gastrointestinal mucosa.
Solifenacin: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics. Blurred vision and dry mouth would be common effects. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Spironolactone; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Sufentanil: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when sufentanil is used concomitantly with an anticholinergic drug. The concomitant use of sufentanil and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Tapentadol: (Moderate) Tapentadol should be used cautiously with anticholinergic medications since additive depressive effects on GI motility or bladder function may occur. Monitor patients for signs of urinary retention or reduced gastric motility. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. Additive CNS effects like drowsiness or dizziness may also occur.
Tegaserod: (Major) Drugs that exert significant anticholinergic properties such as antimuscarinics may pharmacodynamically oppose the effects of prokinetic agents such as tegaserod. Avoid administering antimuscarinics along with tegaserod under most circumstances. Inhaled respiratory antimuscarinics, such as ipratropium, are unlikely to interact with tegaserod. Ophthalmic anticholinergics may interact if sufficient systemic absorption of the eye medication occurs.
Telmisartan; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Temazepam: (Moderate) CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of benztropine.
Tenapanor: (Moderate) Anticholinergics can promote constipation and pharmacodynamically oppose the action of drugs used for the treatment of constipation or constipation-associated irritable bowel syndrome, such as tenapanor.
Thiazide diuretics: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Thioridazine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties like thioridazine are used concomitantly with anticholinergic agents. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur, depending on the interacting agent.
Thiothixene: (Moderate) Anticholinergics may have additive effects with thiothixene, an antipsychotic with the potential for anticholinergic activity. Monitor for anticholinergic-related adverse effects such as xerostomia, blurred vision, constipation, and urinary retention during concurrent use.
Tiotropium: (Major) Avoid concomitant use of anticholinergic medications and tiotropium due to increased risk for anticholinergic adverse effects.
Tiotropium; Olodaterol: (Major) Avoid concomitant use of anticholinergic medications and tiotropium due to increased risk for anticholinergic adverse effects.
Tolterodine: (Moderate) Additive anticholinergic effects may be seen when tolterodine is used concomitantly with other antimuscarinics. When possible, avoid concurrent use, especially in the elderly, who are more susceptible to the anticholinergic effects. Consider alternatives to these other medications, if available. Clinicians should note that antimuscarinic effects might be seen not only on bladder smooth muscle, but also on GI function, the eye, and temperature regulation. Blurred vision, constipation, and dry mouth may be more prominent additive effects. With many of the listed agents, additive drowsiness may also occur when combined.
Topiramate: (Moderate) Monitor for decreased sweating and increased body temperature, especially in hot weather, during concomitant use of topiramate and other drugs that predispose persons to heat-related disorders, such as anticholinergic medications. Concomitant use increases the risk for oligohidrosis and hyperthermia.
Tramadol: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant tramadol and benztropine use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Tramadol; Acetaminophen: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant tramadol and benztropine use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Triamterene; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Triazolam: (Moderate) CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of benztropine.
Tricyclic antidepressants: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant tricyclic antidepressant and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Trifluoperazine: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including trifluoperazine. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other additive CNS effects may also occur.
Trimethobenzamide: (Moderate) Trimethobenzamide has CNS depressant effects and may cause drowsiness. The concurrent use of trimethobenzamide with other medications that cause CNS depression, like the anticholinergics, may potentiate the effects of either trimethobenzamide or the anticholinergic.
Trimipramine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant tricyclic antidepressant and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Triprolidine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Trospium: (Moderate) Additive anticholinergic effects may be seen when trospium is used concomitantly with other antimuscarinics. When possible, avoid concurrent use, especially in the elderly, who are more susceptible to the anticholinergic effects. Consider alternatives to these other medications, if available. Clinicians should note that antimuscarinic effects might be seen not only on bladder smooth muscle, but also on GI function, the eye, and temperature regulation. Blurred vision, constipation, and dry mouth may be more prominent additive effects. With many of the listed agents, additive drowsiness may also occur when combined with trospium.
Umeclidinium: (Moderate) There is the potential for umeclidinium to have additive anticholinergic effects when administered with other anticholinergics or antimuscarinics. Per the manufaturer, avoid concomitant administration of umeclidinium with other anticholinergic medications when possible.
Umeclidinium; Vilanterol: (Moderate) There is the potential for umeclidinium to have additive anticholinergic effects when administered with other anticholinergics or antimuscarinics. Per the manufaturer, avoid concomitant administration of umeclidinium with other anticholinergic medications when possible.
Valsartan; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Vibegron: (Moderate) Vibegron should be administered with caution in patients taking anticholinergics because of potential for an increased risk of urinary retention. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
Zaleplon: (Moderate) CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of benztropine.
Zolpidem: (Moderate) CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of benztropine.
Zonisamide: (Moderate) Zonisamide use is associated with case reports of decreased sweating, hyperthermia, heat intolerance, or heat stroke and should be used with caution in combination with other drugs that may also predispose patients to heat-related disorders like anticholinergics.
Benztropine has antimuscarinic, antihistaminic, and local anesthetic effects. Its antimuscarinic activity is about half that of atropine; its antihistaminic activity is roughly equivalent to that of pyrilamine. Benztropine competes with acetylcholine, and perhaps other cholinergic mediators, at muscarinic receptors in the CNS and, to a lesser extent, in smooth muscle. The muscarinic rather than the nicotinic properties of centrally active anticholinergics are thought to be responsible for the beneficial effects seen in parkinsonism. Benztropine and other synthetic, centrally active anticholinergics have a greater affinity for the low-affinity M1 site than for the high-affinity M2 site. By blocking muscarinic cholinergic receptors in the CNS, benztropine reduces the excessive cholinergic activity present in parkinsonism and related states. Also, benztropine can block dopamine reuptake and storage in CNS cells, thus prolonging dopamine's effects. In general, anticholinergic agents can help control tremor but are less effective for treating bradykinesia or rigidity.
Pharmacokinetics:
Benztropine is administered orally and parenterally. It crosses the blood-brain barrier, and may cross the placenta. Benztropine's metabolism is unknown, but most of the drug is excreted renally, both as parent drug and as metabolites; however, after oral administration, a small amount of drug is excreted unchanged in the feces.
-Route-Specific Pharmacokinetics
Oral Route
Benztropine is absorbed from the GI tract after oral administration; however, a small part of the dose may pass through the GI tract unchanged into the feces.
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