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  • CLASSES

    Anti-Parkinson drugs, Anticholinergic

    DEA CLASS

    Rx

    DESCRIPTION

    Synthetic muscarinic-receptor antagonist; structurally similar to atropine and diphenhydramine; has a longer duration of action and may require less frequent dosing than diphenhydramine; produces less CNS stimulation than does trihexyphenidyl and, thus, may be useful in geriatric patients.

    COMMON BRAND NAMES

    Cogentin

    HOW SUPPLIED

    Benztropine/Benztropine Mesylate/Cogentin Intramuscular Inj Sol: 1mg, 1mL
    Benztropine/Benztropine Mesylate/Cogentin Intravenous Inj Sol: 1mg, 1mL
    Benztropine/Benztropine Mesylate/Cogentin Oral Tab: 0.5mg, 1mg, 2mg

    DOSAGE & INDICATIONS

    For the treatment of Parkinsonism or Parkinson's disease.
    For idiopathic parkinsonism or Parkinson's disease.
    Oral or Intramuscular dosage
    Adults

    The recommended initial dose is 0.5—1 mg PO or IM at bedtime. Increase in 0.5 mg increments at 5—6 day intervals if necessary. The dosage range is 0.5—6 mg and must be individualized according to age and weight. 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.

    For the treatment of tremor in patients with Parkinson's disease:.
    Oral dosage
    Adults

    In a study of 19 patients with Parkinson's disease, benztropine was compared to clozapine for the management of tremor. Three subjects dropped out of the study. Both drugs improved tremor to approximately the same degree. At the end of the study, 5 subjects chose to continue benztropine and 4 chose clozapine. In this one study, benztropine was started at 0.75 mg PO once daily initially and was increased by 0.75/week to a maximum of 4.5 mg/day (administered in 2 divided doses).

    For the treatment of postencephalitic Parkinsonism.
    Oral or Intramuscular dosage
    Adults

    The recommended initial dose is 2 mg PO or IM. Some patients may respond to 0.5 mg PO or IM at bedtime. Range is 0.5—6 mg/day. 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.

    For the treatment of drug-induced extrapyramidal symptoms (except tardive dyskinesia).
    NOTE: The manufacturer has not conducted specific studies to determine the rate of administration or dilution requirements prior to IV administration.
    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 neuroleptic drugs, (e.g., phenothiazines), 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.

    Children > 3 years

    The recommended dose is 0.02 to 0.05 mg/kg/dose PO, IM, or IV once or twice per day.

    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.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    8 mg/day PO, IM, or IV.

    Geriatric

    8 mg/day PO, IM, or IV.

    Adolescents

    Maximum dosage information is not available.

    Children

    >= 3 years: Maximum dosage information is not available.
    < 3 years: Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

    ADMINISTRATION

     
    NOTE: Doses may be divided or given as a single daily dose at bedtime.

    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. Aspirate prior to injection to avoid injection into a blood vessel.

    STORAGE

    Generic:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Cogentin:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Benztropine is contraindicated in patients with known benztropine mesylate hypersensitivity.

    Closed-angle glaucoma

    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.

    Bladder obstruction, prostatic hypertrophy, urinary retention

    Benztropine exhibits anticholinergic effects and should be used cautiously in patients with benign prostatic hypertrophy or bladder obstruction because it can exacerbate urinary retention. Dysuria may occur, but rarely becomes a problem. Urinary retention has been reported.

    Cardiac disease, tachycardia

    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.

    Behavioral changes, dementia, driving or operating machinery, psychosis

    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

    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.

    Autonomic neuropathy, myasthenia gravis

    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.

    Anticholinergic medications, geriatric

    The anticholinergic effects of benztropine may be significant and are additive with other anticholinergic medications, especially in the geriatric patient. Clinical experience has not identified differences in efficacy or safety relevant to younger adults; however, because geriatric patients may be more sensitive to anticholinergic effects, 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) for use in geriatric patients and benztropine use should be avoided in this population as a prophylactic for extrapyramidal symptoms (EPS) with antipsychotics due to the anticholinergic effects of the drug. In addition, avoidance is recommended in those with Parkinson's disease because more effective treatments are available. The Beers expert panel also recommends avoiding drugs with strong anticholinergic properties, such as benztropine, in geriatric patients with the following disease states or symptoms due to the potential for exacerbation of the condition or increased risk of 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 (possible urinary retention or hesitancy).

    Alcoholism, ambient temperature increase, hyperthermia

    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).

    Pregnancy

    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.

    Breast-feeding

    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.

    Children, infants, neonates

    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.

    Contact lenses

    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.

    ADVERSE REACTIONS

    Severe

    ocular hypertension / Delayed / Incidence not known
    toxic megacolon / Delayed / Incidence not known
    ileus / Delayed / Incidence not known

    Moderate

    constipation / Delayed / 10.0
    confusion / Early / Incidence not known
    hallucinations / Early / Incidence not known
    delirium / Early / Incidence not known
    psychosis / Early / Incidence not known
    depression / Delayed / Incidence not known
    memory impairment / Delayed / Incidence not known
    cycloplegia / Early / Incidence not known
    blurred vision / Early / Incidence not known
    parotitis / Delayed / Incidence not known
    hyperthermia / Delayed / Incidence not known
    heat intolerance / Early / Incidence not known
    anhidrosis / Delayed / Incidence not known
    urinary retention / Early / Incidence not known
    dysuria / Early / Incidence not known
    sinus tachycardia / Rapid / Incidence not known
    myasthenia / Delayed / Incidence not known

    Mild

    xerostomia / Early / 10.0
    nausea / Early / 10.0
    drowsiness / Early / Incidence not known
    headache / Early / Incidence not known
    anxiety / Delayed / Incidence not known
    dizziness / Early / Incidence not known
    insomnia / Early / Incidence not known
    paresthesias / Delayed / Incidence not known
    mydriasis / Early / Incidence not known
    vomiting / Early / Incidence not known
    fever / Early / Incidence not known
    rash (unspecified) / Early / Incidence not known
    weakness / Early / Incidence not known
    asthenia / Delayed / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Butalbital; Caffeine; Codeine: Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids 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. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Acetaminophen; Codeine: Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids 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. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Acetaminophen; Dextromethorphan; Doxylamine: The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Acetaminophen; Diphenhydramine: The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Acetaminophen; Hydrocodone: Concurrent use of antidiarrheals and hydrocodone can lead to severe constipation and possibly additive CNS depression. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use.
    Acetaminophen; Oxycodone: Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids 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. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Acetaminophen; Pentazocine: Use pentazocine with caution in any patient receiving anticholinergic agents. Coadministration of pentazocine with antimuscarinics may result in additive anticholinergic effects, such as urinary retention and constipation.
    Aclidinium: 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 manufaturer, avoid concomitant administration of aclidinium with other anticholinergic medications, when possible.
    Acrivastine; Pseudoephedrine: The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Albuterol; Ipratropium: Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for tiotropium to have additive anticholinergic effects when administered with other antimuscarinics. Per the manufaturer, avoid concomitant administration of ipratropium with other anticholinergic medications, such as antimucarinics.
    Alfentanil: Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids 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. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Alosetron: Alosetron, if combined with antimuscarinics, may seriously worsen constipation, leading to events such as GI obstruction, impaction or paralytic ileus. Although specific recommendations are not available from the manufacturer, it would be prudent to avoid antimuscarinics in patients taking alosetron.
    Aluminum Hydroxide: 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: 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: 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: 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: 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: 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.
    Ambenonium Chloride: The muscarinic actions of ambenonium chloride, can antagonize the antimuscarinic actions of benztropine. Benztropine might also antagonize some of the effects of ambenonium chloride.
    Amoxapine: 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: 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: 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: CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of benztropine.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids 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. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Aspirin, ASA; Carisoprodol; Codeine: Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids 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. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Aspirin, ASA; Oxycodone: Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids 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. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Atropine; Edrophonium: The muscarinic actions of edrophonium chloride can antagonize the antimuscarinic actions of benztropine. Benztropine might also antagonize some of the effects of edrophonium.
    Barbiturates: CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of benztropine.
    Benzodiazepines: CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of benztropine.
    Bismuth Subsalicylate: 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: 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.
    Botulinum Toxins: 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: The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Brompheniramine; Carbetapentane; Phenylephrine: Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including anticholinergics. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Brompheniramine; Dextromethorphan; Guaifenesin: The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Brompheniramine; Guaifenesin; Hydrocodone: Concurrent use of antidiarrheals and hydrocodone can lead to severe constipation and possibly additive CNS depression. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Brompheniramine; Hydrocodone; Pseudoephedrine: Concurrent use of antidiarrheals and hydrocodone can lead to severe constipation and possibly additive CNS depression. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Brompheniramine; Pseudoephedrine: The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Buprenorphine: Buprenorphine is an opioid analgesic. Opioids 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. In addition, concurrent use may also lead to additive CNS depression.
    Buprenorphine; Naloxone: Buprenorphine is an opioid analgesic. Opioids 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. In addition, concurrent use may also lead to additive CNS depression.
    Bupropion: 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: 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.
    Calcium Carbonate: Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    Calcium Carbonate; Magnesium Hydroxide: 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. Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    Calcium Carbonate; Risedronate: Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    Calcium; Vitamin D: Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    Carbetapentane; Chlorpheniramine: Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including anticholinergics. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Carbetapentane; Chlorpheniramine; Phenylephrine: Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including anticholinergics. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Carbetapentane; Diphenhydramine; Phenylephrine: Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including anticholinergics. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Carbetapentane; Guaifenesin: Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including anticholinergics.
    Carbetapentane; Guaifenesin; Phenylephrine: Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including anticholinergics.
    Carbetapentane; Phenylephrine: Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including anticholinergics.
    Carbetapentane; Phenylephrine; Pyrilamine: Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including anticholinergics. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Carbetapentane; Pseudoephedrine: Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including anticholinergics.
    Carbetapentane; Pyrilamine: Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including anticholinergics. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Carbidopa; Levodopa: 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: 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: The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Carbinoxamine; Hydrocodone; Phenylephrine: Concurrent use of antidiarrheals and hydrocodone can lead to severe constipation and possibly additive CNS depression. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: Concurrent use of antidiarrheals and hydrocodone can lead to severe constipation and possibly additive CNS depression. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Carbinoxamine; Phenylephrine: The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Carbinoxamine; Pseudoephedrine: The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Cetirizine: Dry mouth and drowsiness were more common in patients receiving cetirizine/levocetirizine vs. placebo, and caution may be necessary during concomitant use of cetirizine/levocetirizine with the antimuscarinics.
    Cetirizine; Pseudoephedrine: Dry mouth and drowsiness were more common in patients receiving cetirizine/levocetirizine vs. placebo, and caution may be necessary during concomitant use of cetirizine/levocetirizine with the antimuscarinics.
    Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Chlorcyclizine: The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Chlorpheniramine: The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Chlorpheniramine; Codeine: Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids 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. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Chlorpheniramine; Dextromethorphan: The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: Concurrent use of antidiarrheals and hydrocodone can lead to severe constipation and possibly additive CNS depression. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Chlorpheniramine; Hydrocodone: Concurrent use of antidiarrheals and hydrocodone can lead to severe constipation and possibly additive CNS depression. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Chlorpheniramine; Hydrocodone; Phenylephrine: Concurrent use of antidiarrheals and hydrocodone can lead to severe constipation and possibly additive CNS depression. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: Concurrent use of antidiarrheals and hydrocodone can lead to severe constipation and possibly additive CNS depression. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Chlorpheniramine; Phenylephrine: The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Chlorpheniramine; Pseudoephedrine: The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Chlorpromazine: 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.
    Cholinergic agonists: 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: 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: The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Clozapine: Additive anticholinergic effects may be seen when benztropine is used concomitantly with other drugs that possess anticholinergic properties, such as clozapine. 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.
    Codeine: Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids 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. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Codeine; Guaifenesin: Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids 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. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Codeine; Phenylephrine; Promethazine: Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including promethazine. 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. Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids 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. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Codeine; Promethazine: Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including promethazine. 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. Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids 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. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Crofelemer: 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.
    Cyclizine: The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Cyclobenzaprine: Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like cyclobenzaprine are used concomitantly with other anticholinergics. 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, depending on the interacting agent.
    Cyproheptadine: The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Dexchlorpheniramine: The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Dextromethorphan; Diphenhydramine; Phenylephrine: The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Dextromethorphan; Promethazine: Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including promethazine. 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.
    Dextromethorphan; Quinidine: The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
    Digoxin: 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: The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Diphenhydramine: The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Diphenhydramine; Hydrocodone; Phenylephrine: Concurrent use of antidiarrheals and hydrocodone can lead to severe constipation and possibly additive CNS depression. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Diphenhydramine; Ibuprofen: The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Diphenhydramine; Phenylephrine: The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Disopyramide: 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: 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: 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. 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.
    Doxylamine: The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Doxylamine; Pyridoxine: The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Dronabinol, THC: 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: CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of benztropine.
    Edrophonium: The muscarinic actions of edrophonium chloride can antagonize the antimuscarinic actions of benztropine. Benztropine might also antagonize some of the effects of edrophonium.
    Eluxadoline: 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.
    Erythromycin: Anticholinergics can antagonize the stimulatory effects of erythromycin on the GI tract (when erythromycin is used therapeutically for improving GI motility). Avoid chronic administration of antimuscarinics along with prokinetic agents under most circumstances. In addition, erythromycin is a CYP3A4 inhibitor and can reduce the metabolism of drugs metabolized by CYP3A4, including some anticholinergics.
    Erythromycin; Sulfisoxazole: Anticholinergics can antagonize the stimulatory effects of erythromycin on the GI tract (when erythromycin is used therapeutically for improving GI motility). Avoid chronic administration of antimuscarinics along with prokinetic agents under most circumstances. In addition, erythromycin is a CYP3A4 inhibitor and can reduce the metabolism of drugs metabolized by CYP3A4, including some anticholinergics.
    Ethanol: Ethanol and other CNS depressants can increase the sedative effects of benztropine.
    Ezogabine: Caution is advisable during concurrent use of ezogabine and medications that may affect voiding such as anticholinergic agents. Ezogabine has caused urinary retention requiring catheterization in some cases. The anticholinergic effects of antimuscariinic and anticholinergic medications on the urinary tract may be additive. Additive sedation or other CNS effects may also occur.
    Fentanyl: Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids 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. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Fluoxetine; Olanzapine: Additive anticholinergic effects may be seen when benztropine is used concomitantly with other drugs that possess anticholinergic properties, such as olanzapine. 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.
    Fluphenazine: 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.
    Galantamine: 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: 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.
    Guaifenesin; Hydrocodone: Concurrent use of antidiarrheals and hydrocodone can lead to severe constipation and possibly additive CNS depression. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use.
    Guaifenesin; Hydrocodone; Pseudoephedrine: Concurrent use of antidiarrheals and hydrocodone can lead to severe constipation and possibly additive CNS depression. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use.
    Haloperidol: 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: Concurrent use of antidiarrheals and hydrocodone can lead to severe constipation and possibly additive CNS depression. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use.
    Hydrocodone: Concurrent use of antidiarrheals and hydrocodone can lead to severe constipation and possibly additive CNS depression. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use.
    Hydrocodone; Ibuprofen: Concurrent use of antidiarrheals and hydrocodone can lead to severe constipation and possibly additive CNS depression. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use.
    Hydrocodone; Phenylephrine: Concurrent use of antidiarrheals and hydrocodone can lead to severe constipation and possibly additive CNS depression. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use.
    Hydrocodone; Potassium Guaiacolsulfonate: Concurrent use of antidiarrheals and hydrocodone can lead to severe constipation and possibly additive CNS depression. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: Concurrent use of antidiarrheals and hydrocodone can lead to severe constipation and possibly additive CNS depression. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use.
    Hydrocodone; Pseudoephedrine: Concurrent use of antidiarrheals and hydrocodone can lead to severe constipation and possibly additive CNS depression. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use.
    Hydromorphone: Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids 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. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Hydroxyzine: The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Ibuprofen; Oxycodone: Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids 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. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Ipratropium: Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for tiotropium to have additive anticholinergic effects when administered with other antimuscarinics. Per the manufaturer, avoid concomitant administration of ipratropium with other anticholinergic medications, such as antimucarinics.
    Itraconazole: Antimuscarinics can raise intragastric pH. This effect may decrease the oral bioavailability of itraconazole; antimuscarinics should be used cautiously in patients receiving itraconazole.
    Lanthanum Carbonate: Oral compounds known to interact with antacids, like anticholinergics, should not be taken within 2 hours of dosing with lanthanum carbonate. If these agents are used concomitantly, space the dosing intervals appropriately. Monitor serum concentrations and clinical condition.
    Levocetirizine: Dry mouth and drowsiness were more common in patients receiving cetirizine/levocetirizine vs. placebo, and caution may be necessary during concomitant use of cetirizine/levocetirizine with the antimuscarinics.
    Levodopa: 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.
    Linaclotide: Several agents (e.g., antimuscarinics) have an antagonistic effect at muscarinic cholinergic receptors (an anticholinergic effect). Thus antimuscarinic drugs can promote constipation and pharmacodynamically oppose the action of drugs used for the treatment of constipation, such as linaclotide. The clinical significance of these potential interactions is uncertain.
    Loperamide: 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: 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.
    Loxapine: The anticholinergic effects of benztropine will be increased if used concomitantly with loxapine, which exhibits anticholinergic activity. Such drug combinations can cause severe constipation, increased intraocular pressure, or paralytic ileus. Patients should be asked about any GI problems or changes in vision.
    Lubiprostone: 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: 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.
    Magnesium Hydroxide: 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: 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: The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Memantine: 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: Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids 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. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Meperidine; Promethazine: Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including promethazine. 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. Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids 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. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Methadone: Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids 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. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Metoclopramide: 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.
    Mirtazapine: Mirtazapine exhibits weak anticholinergic activity that is not expected to be clinically significant. However, the anticholinergic effects may be additive to the antimuscarinics. 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.
    Molindone: 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: Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids 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. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Morphine; Naltrexone: Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids 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. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Nabilone: Concurrent use of nabilone with anticholinergics may result in pronounced tachycardia and drowsiness.
    Neostigmine: The muscarinic actions of neostigmine can antagonize the antimuscarinic actions of benztropine. Benztropine might also antagonize some of the effects of neostigmine
    Nitrofurantoin: Antimuscarinics can delay gastric emptying, possibly increasing the bioavailability of nitrofurantoin.
    Olanzapine: Additive anticholinergic effects may be seen when benztropine is used concomitantly with other drugs that possess anticholinergic properties, such as olanzapine. 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.
    Omeprazole; Sodium Bicarbonate: Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    Orphenadrine: 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.
    Oxycodone: Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids 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. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Oxymorphone: Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids 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. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Pentazocine: Use pentazocine with caution in any patient receiving anticholinergic agents. Coadministration of pentazocine with antimuscarinics may result in additive anticholinergic effects, such as urinary retention and constipation.
    Pentazocine; Naloxone: Use pentazocine with caution in any patient receiving anticholinergic agents. Coadministration of pentazocine with antimuscarinics may result in additive anticholinergic effects, such as urinary retention and constipation.
    Perphenazine: 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: 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.
    Phentermine; Topiramate: Use caution if carbonic anhydrase inhibitors are administered with anticholinergics and monitor for excessive anticholinergic adverse effects. The use of topiramate with agents that may increase the risk for heat-related disorders, such as anticholinergics, may lead to oligohidrosis, hyperthermia and/or heat stroke.
    Phenylephrine; Promethazine: Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including promethazine. 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.
    Physostigmine: The muscarinic actions of physostigmine can antagonize the antimuscarinic actions of benztropine. Benztropine might also antagonize some of the effects of the parasympathomimetics.
    Potassium: Drugs that decrease GI motility may increase the risk of GI irritation from sustained-release solid oral dosage forms of potassium salts. The use of solid oral dosage forms of potassium chloride is contraindicated in patients taking glycopyrrolate oral solution. In one study, healthy subjects were examined for GI irritation following the administration of oral potassium for at least 7 days. Glycopyrrolate was coadministered to some subjects in order to study the additional effects of delayed gastric emptying. Results indicated that subjects administered wax-matrix tablets had the highest incidence of erosions (43%) and ulcers (11%). Evidence of GI irritation was less frequent among subjects receiving liquid (0%) and microencapsulated (10.5% erosions, 1.2% ulcers) formulations. Therefore, if oral potassium supplementation is necessary in a patient taking antimuscarinics, a liquid formulation should be considered. If a solid formulation is being prescribed, the patient should be counseled on strategies that can be used to avoid GI irritation such as taking potassium products only while seated or standing, remaining upright for 10 minutes after each dose, and ingesting each dose with plenty of fluids.
    Pramlintide: 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.
    Procainamide: 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: 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: Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including promethazine. 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.
    Proton pump inhibitors: The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.
    Pyridostigmine: The muscarinic actions of pyridostigmine can antagonize the antimuscarinic actions of benztropine. Benztropine might also antagonize some of the effects of the parasympathomimetics.
    Quinidine: The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
    Rasagiline: 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: Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids 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. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Rivastigmine: 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.
    Secretin: 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: The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Sincalide: 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 Bicarbonate: Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    Solifenacin: 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.
    Sufentanil: Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids 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. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Tacrine: The therapeutic benefits of tacrine, 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.
    Tapentadol: Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids 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. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Tegaserod: 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.
    Thiazide diuretics: 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.
    Thiothixene: Depending on the specific agent, additive anticholinergic effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity.
    Tiotropium: Although tiotropium is minimally absorbed into the systemic circulation after inhalation, tiotropium may have additive anticholinergic effects when administered with other antimuscarinics. Per the manufaturer, avoid concomitant administration of tiotropium with other anticholinergic medications when possible.
    Tiotropium; Olodaterol: Although tiotropium is minimally absorbed into the systemic circulation after inhalation, tiotropium may have additive anticholinergic effects when administered with other antimuscarinics. Per the manufaturer, avoid concomitant administration of tiotropium with other anticholinergic medications when possible.
    Tolterodine: 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: Use caution if carbonic anhydrase inhibitors are administered with anticholinergics and monitor for excessive anticholinergic adverse effects. The use of topiramate with agents that may increase the risk for heat-related disorders, such as anticholinergics, may lead to oligohidrosis, hyperthermia and/or heat stroke.
    Tricyclic antidepressants: Depending on the specific agent, additive anticholinergic effects may be seen when tricyclic antidepressants (TCAs) are used concomitantly with other anticholinergics. 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 many of these drugs are combined with tricyclic antidepressants.
    Trifluoperazine: 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: 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.
    Triprolidine: The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. 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 when antimuscarinics are combined with sedating antihistamines.
    Trospium: 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: 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: 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.
    Zonisamide: 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.

    PREGNANCY AND LACTATION

    Pregnancy

    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.

    MECHANISM OF ACTION

    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.

    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.