atropine

Browse PDR's full list of drug information

atropine

Classes

Anticholinergics for Cardiac conditions
Belladonna and Derivative Gastrointestinal Antispasmodics
Mydriatics and Cycloplegics

Administration
Oral Administration

Administer 30 minutes before meals.

Injectable Administration

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Intravenous Administration

IV Push
Administer undiluted or diluted in 10 mL of Sterile Water for Injection.
Inject via Y-site or through a 3-way stopcock at a rate of 0.6 mg over 1 minute. Doses less than 0.4 mg or IV administration over more than 1 minute may cause paradoxical slowing of the heart rate, which usually resolves within approximately 2 minutes.
During adult cardiopulmonary resuscitation (CPR): Resuscitation drugs may be administered intravenously by bolus injection into a peripheral vein, followed by an injection of 20 mL IV fluid.[32366] Elevate the extremity for 10 to 20 seconds to facilitate drug delivery to the central circulation. Although peak drug concentrations are lower when drugs are administered via peripheral vs. central sites, the establishment of peripheral access does not require interruption of CPR. Drugs generally reach the central circulation within 1 to 2 minutes when administered peripherally but require less time when given via central venous access.

Intramuscular Administration

Intramuscular (IM) Autoinjector
If possible, only persons with adequate training in the recognition and treatment of nerve agent or insecticide intoxication should administer the atropine autoinjector. If a trained provider is not available during an emergency, patient or caregiver administration is acceptable.
Remove the autoinjector from the plastic sleeve.
Firmly grasp the autoinjector with the green tip pointed downward. Pull off the yellow safety cap with the other hand.
Inject in the mid-lateral thigh area at a 90-degree angle. Inject through clothing if necessary, but make sure pockets at the injection site are empty. In smaller individuals, bunch up the thigh to provide a thicker area for injection.
Hold the autoinjector firmly in place for at least 10 seconds, then remove and massage the injection site in a circular motion for several seconds. If the needle is not visible after removing the autoinjector from the outer thigh, the injection is not complete. In this circumstance, check to make sure the yellow safety cap has been removed and repeat the steps for injection, pressing more firmly on the thigh. If the needle is still not visible, discard, and use a new autoinjector.
Each autoinjector has a single dose; if you need more than 1 injection, repeat the steps for injection using a new autoinjector.
After injection, bend the needle back against the autoinjector using a hard surface. Use the bent needle as a hook to pin the used autoinjector to the exposed person's clothing, or use an alternative method to notify medical professionals of the dose and number of autoinjectors given.
Move yourself and the victim away from the contaminated area immediately and locate additional medical care.
Closely observe treated patients for at least 48 to 72 hours.[30289]
 
Intramuscular (IM) Injection
Inject deeply into a large muscle mass (e.g., anterolateral thigh or deltoid [children and adolescents only]).[54416]

Subcutaneous Administration

Inject subcutaneously taking care not to inject intradermally.

Other Injectable Administration

Intraosseous (IO) Infusion
NOTE: Atropine is not approved by the FDA for IO administration.
During cardiopulmonary resuscitation, the same dosage may be given via the IO route when IV access is not available.

Ophthalmic Administration

For ophthalmic use only.
Instruct patient on proper instillation of eye ointment or solution.
Do not to touch the tip of the dropper or tube to the eye, fingertips, or other surface.

Other Administration Route(s)

Endotracheal (ET) Administration
NOTE: Atropine is not approved by the FDA for ET administration. According to ACLS and PALS guidelines, the parenteral atropine product may be administered via the ET route.
ET administration is associated with lower blood drug concentrations compared to IV administration and may be unreliable. Tracheal drug absorption may be unreliable; higher ET doses may be required.[32367] [32368] [43713] [45649] [60636]
ET administration should only be used if access to IV or intraosseous routes can not be achieved or is delayed.
The optimal dosage for ET administration has not been established.
Adults: Dilute each dose in 5 to 10 mL of sterile distilled water or 0.9% Sodium Chloride Injection. Administer via the ET tube. ET drug absorption may be improved by dilution with sterile distilled water instead of 0.9% Sodium Chloride Injection.[45649]
Children: After dose administration, flush the ET tube with a minimum of 5 mL 0.9% Sodium Chloride Injection and follow with 5 ventilations.[43713] [60636]

Adverse Reactions
Severe

laryngospasm / Rapid / Incidence not known
keratoconjunctivitis / Early / Incidence not known
visual impairment / Early / Incidence not known
ileus / Delayed / Incidence not known
asystole / Rapid / Incidence not known
bradycardia / Rapid / Incidence not known
myocardial infarction / Delayed / Incidence not known
ventricular tachycardia / Early / Incidence not known
atrial fibrillation / Early / Incidence not known
ventricular fibrillation / Early / Incidence not known
respiratory arrest / Rapid / Incidence not known
pulmonary edema / Early / Incidence not known
cyanosis / Early / Incidence not known
anaphylactic shock / Rapid / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
coma / Early / Incidence not known
seizures / Delayed / Incidence not known

Moderate

oral ulceration / Delayed / Incidence not known
photophobia / Early / Incidence not known
blurred vision / Early / Incidence not known
conjunctivitis / Delayed / Incidence not known
cycloplegia / Early / Incidence not known
blepharitis / Early / Incidence not known
dysphagia / Delayed / Incidence not known
constipation / Delayed / Incidence not known
QT prolongation / Rapid / Incidence not known
supraventricular tachycardia (SVT) / Early / Incidence not known
premature ventricular contractions (PVCs) / Early / Incidence not known
sinus tachycardia / Rapid / Incidence not known
hypertension / Early / Incidence not known
ST-T wave changes / Rapid / Incidence not known
palpitations / Early / Incidence not known
hypotension / Rapid / Incidence not known
tachypnea / Early / Incidence not known
respiratory depression / Rapid / Incidence not known
atopic dermatitis / Delayed / Incidence not known
urinary retention / Early / Incidence not known
urinary incontinence / Early / Incidence not known
hypokalemia / Delayed / Incidence not known
dehydration / Delayed / Incidence not known
anhidrosis / Delayed / Incidence not known
hypoglycemia / Early / Incidence not known
hyperglycemia / Delayed / Incidence not known
angina / Early / Incidence not known
hyponatremia / Delayed / Incidence not known
dysarthria / Delayed / Incidence not known
hypertonia / Delayed / Incidence not known
amnesia / Delayed / Incidence not known
mania / Early / Incidence not known
delirium / Early / Incidence not known
depression / Delayed / Incidence not known
EEG changes / Delayed / Incidence not known
confusion / Early / Incidence not known
hyperreflexia / Delayed / Incidence not known
ataxia / Delayed / Incidence not known
hallucinations / Early / Incidence not known
impotence (erectile dysfunction) / Delayed / Incidence not known

Mild

laryngitis / Delayed / Incidence not known
xerostomia / Early / Incidence not known
hypersalivation / Early / Incidence not known
nasal dryness / Early / Incidence not known
lacrimation / Early / Incidence not known
mydriasis / Early / Incidence not known
xerophthalmia / Early / Incidence not known
ocular irritation / Rapid / Incidence not known
abdominal pain / Early / Incidence not known
vomiting / Early / Incidence not known
nausea / Early / Incidence not known
petechiae / Delayed / Incidence not known
maculopapular rash / Early / Incidence not known
rash / Early / Incidence not known
urinary urgency / Early / Incidence not known
injection site reaction / Rapid / Incidence not known
flushing / Rapid / Incidence not known
syncope / Early / Incidence not known
fever / Early / Incidence not known
urticaria / Rapid / Incidence not known
leukocytosis / Delayed / Incidence not known
anxiety / Delayed / Incidence not known
hyporeflexia / Delayed / Incidence not known
paranoia / Early / Incidence not known
tremor / Early / Incidence not known
weakness / Early / Incidence not known
fatigue / Early / Incidence not known
drowsiness / Early / Incidence not known
lethargy / Early / Incidence not known
headache / Early / Incidence not known
agitation / Early / Incidence not known
dizziness / Early / Incidence not known
insomnia / Early / Incidence not known
vertigo / Early / Incidence not known
restlessness / Early / Incidence not known
libido decrease / Delayed / Incidence not known

Common Brand Names

Atropine Care, Atropisol, Isopto Atropine, Ocu-Tropine

Dea Class

Rx

Description

Natural tertiary amine extracted from belladonna alkaloid
Used for symptomatic bradycardia, secretion reduction prior to surgery, organophosphate toxicity, to produce mydriasis and cycloplegia, and treatment of amblyopia.
Consists of a racemic mixture of both d- and l-hyoscyamine

Dosage And Indications
For the treatment of bradyasystolic cardiac arrest. Intravenous or Intraosseous† Dosage Adults

1 mg IV every 3 to 5 minutes as needed up to a maximum total dose of 3 mg. Clinical practice guidelines do not include atropine due to unlikely therapeutic benefit in pulseless electrical activity (PEA) or asystole. Previously, atropine could be given via the intraosseous route when IV access was not available.

Infants, Children, and Adolescents

0.01 to 0.03 mg/kg/dose IV. Atropine is not included in the PALS algorithm for cardiac arrest and is no longer routinely recommended due to unlikely therapeutic benefit in PEA or asystole. The previous PALS dosage recommendation was 0.02 mg/kg/dose IV (minimum dose of 0.1 mg; Max: 0.5 mg) with a second dose administered if indicated. The same dosage may be given via the intraosseous route when IV access is not available. Do not interrupt CPR to administer drug therapy. Cardiac arrest in children is uncommon and usually results from progressive respiratory failure or shock (e.g., asphyxial arrest) rather than from cardiac etiology.

Neonates

0.01 to 0.03 mg/kg/dose IV. Atropine is not included in the PALS algorithm for cardiac arrest and is no longer routinely recommended due to unlikely therapeutic benefit in PEA or asystole. The previous PALS dosage recommendation was 0.02 mg/kg/dose IV with a second dose administered if indicated. When using atropine, PALS recommends a minimum single dose of 0.1 mg, however, some feel this dose may be excessive in very small neonates since the total dosage would be greater than 0.02 mg/kg. The same dosage may be given via the intraosseous route when IV access is not available. Do not interrupt CPR to administer drug therapy.

Endotracheal Dosage

NOTE: Endotracheal (ET) administration may be unreliable; use only if access to IV or intraosseous routes are not available.

Adults

1 to 2 mg ET (diluted in no more than 10 mL of 0.9% Sodium Chloride Injection or Sterile Water for Injection). Clinical practice guidelines do not include atropine due to unlikely therapeutic benefit in pulseless electrical activity (PEA) or asystole.

Infants, Children, and Adolescents

Atropine is not included in the PALS algorithm for cardiac arrest and is no longer routinely recommended due to unlikely therapeutic benefit in PEA or asystole. The previous PALS dosage recommendation was 0.04 to 0.06 mg/kg/dose for ET administration with a second dose administered if indicated. Flush the ET tube with 0.9% Sodium Chloride Injection (5 mL or more) and follow with 5 ventilations. Do not interrupt CPR to administer drug therapy.

Neonates

Atropine is not included in the PALS algorithm for cardiac arrest and is no longer routinely recommended due to unlikely therapeutic benefit in PEA or asystole.[43713] [60636] The previous PALS dosage recommendation was 0.04 to 0.06 mg/kg/dose for ET administration with a second dose administered if indicated.[43713] Flush the ET tube with 0.9% Sodium Chloride Injection (1 to 5 mL) and follow with 5 ventilations. Do not interrupt CPR to administer drug therapy.

For preoperative use to decrease secretions (i.e., aspiration prophylaxis), as well as block cardiovagal reflexes and/or succinylcholine-induced arrhythmias, during surgery. Oral Dosage Adults

2 mg PO 30 to 60 minutes prior to anesthesia.

Intravenous, Intramuscular, or Subcutaneous dosage Adults

0.2 to 1 mg (the usual dose is 0.4 mg) IV, IM, or subcutaneous 30 to 60 minutes prior to anesthesia.

Infants, Children, and Adolescents

0.01 to 0.02 mg/kg/dose IV or IM (minimum dose: 0.1 mg; Max: 1 mg) before administration of sedative/anesthetic and paralytic agents. According to the FDA-approved product labeling, dose may also be given subcutaneously 30 minutes before surgery. Various fixed dosing schedules are also available. The following is one example: 0.1 mg for patient weight 3.2 to 7 kg; 0.15 mg for weight 8 to 11 kg; 0.2 mg for weight 11 to 18 kg; 0.3 mg for weight 18 to 29 kg; and 0.4 mg for weight 30 to 41 kg.

Neonates

0.02 mg/kg/dose IV, IM, or subcutaneous before administration of sedative/anesthetic and paralytic agents. Use of 0.1 mg in neonates will result in dosages greater than 0.02 mg/kg; there is no documented minimum dosage in this age group.

For the treatment of cholinergic crisis (e.g., chemical nerve agent or carbamate or organophosphate insecticide toxicity).
NOTE: Give atropine as soon as symptoms of toxicity occur. In general, do not use atropine until cyanosis has been overcome; atropine may produce ventricular fibrillation and possible seizures in the presence of hypoxia.[64426]
Intravenous, Intramuscular, or Intraosseous† dosage (using parenteral solution; NOT autoinjector)

Adults

1 to 2 mg IV or IM initially; repeat every 20 to 30 minutes as needed until symptoms dissipate. IV route is preferred. In severe cases, the initial dose can be as large as 2 to 6 mg administered IV. Repeat doses of 2 to 6 mg can be administered IV or IM every 5 to 60 minutes. Up to 50 mg of atropine may be necessary in the first 24 hours. Therapy may be necessary for 48 hours or more, but lower doses administered orally may suffice after the acute phase has been stabilized.

Infants, Children, and Adolescents

0.05 to 0.1 mg/kg/dose IV, IM, or IO every 5 to 15 minutes as needed until symptoms dissipate. IV route is preferred. Repeat doses based on recurrence of symptoms for 2 to 12 hours or longer depending on severity of poisoning. When symptoms are stable for 6 hours or more, the dosing may be decreased. In severely poisoned patients, the dose may need to be more than 2 times suggested dose. The dosing interval may be decreased, or continuous IV infusion may be necessary with high atropine requirements. If continuous infusion is required to maintain atropinization, begin with 10% to 20% of the total loading dose administered hourly.[54402] [54403] [54548]

Neonates

0.05 to 0.1 mg/kg/dose IV, IM, or IO every 5 to 15 minutes as needed until symptoms dissipate. IV route is preferred. Repeat doses based on recurrence of symptoms for 2 to 12 hours or longer depending on severity of poisoning. When symptoms are stable for 6 hours or more, the dosing may be decreased. In severely poisoned patients, the dose may need to be more than 2 times suggested dose. The dosing interval may be decreased, or continuous IV infusion may be necessary with high atropine requirements. If continuous infusion is required to maintain atropinization, begin with 10% to 20% of the total loading dose administered hourly.[54402] [54403] [54548]

Intramuscular dosage (autoinjector only) Adults

2 mg/dose IM as soon as symptoms of poisoning appear (usually tearing, excess saliva, wheezing, drowsiness, muscle twitching). Give 1 dose for known or suspected poisoning with 2 or more mild symptoms (e.g., blurred vision, miosis, watery eyes, runny nose, increased salivation, chest tightness or difficulty breathing, tremors, muscle twitching, nausea or vomiting, unexplained wheezing or coughing, acute stomach cramping, tachycardia, or bradycardia). Give 2 additional doses in rapid succession 10 to 15 minutes after giving the first injection if any severe symptom appears (e.g., confusion, severe breathing difficulties, severe lung secretions, severe muscle twitching and general weakness, involuntary urination and defecation, seizures, unconsciousness). Give 3 doses in rapid succession to any victim found unconscious or presenting with severe symptoms. Anticonvulsants and pralidoxime may be administered concurrently.[30289] [64426]

Children and Adolescents weighing more than 41 kg

2 mg/dose IM as soon as symptoms of poisoning appear (usually tearing, excess saliva, wheezing, drowsiness, muscle twitching). Give 1 dose for known or suspected poisoning with 2 or more mild symptoms (e.g., blurred vision, miosis, watery eyes, runny nose, increased salivation, chest tightness or difficulty breathing, tremors, muscle twitching, nausea or vomiting, unexplained wheezing or coughing, acute stomach cramping, tachycardia, or bradycardia). Give 2 additional doses in rapid succession 10 to 15 minutes after giving the first injection if any severe symptom appears (e.g., confusion, severe breathing difficulties, severe lung secretions, severe muscle twitching and general weakness, involuntary urination and defecation, seizures, unconsciousness). Give 3 doses in rapid succession to any victim found unconscious or presenting with severe symptoms. Anticonvulsants and pralidoxime may be administered concurrently.[30289] [64426]

Children weighing 18 to 41 kg

1 mg/dose IM as soon as symptoms of poisoning appear (usually tearing, excess saliva, wheezing, drowsiness, muscle twitching). Give 1 dose for known or suspected poisoning with 2 or more mild symptoms (e.g., blurred vision, miosis, watery eyes, runny nose, increased salivation, chest tightness or difficulty breathing, tremors, muscle twitching, nausea or vomiting, unexplained wheezing or coughing, acute stomach cramping, tachycardia, or bradycardia). Give 2 additional doses in rapid succession 10 minutes after giving the first injection if any severe symptom appears (e.g., confusion, severe breathing difficulties, severe lung secretions, severe muscle twitching and general weakness, involuntary urination and defecation, seizures, unconsciousness). Give 3 doses in rapid succession to any victim found unconscious or presenting with severe symptoms. Anticonvulsants and pralidoxime may be administered concurrently.[30289]

Infants and Children weighing 7 to 18 kg

0.5 mg/dose IM as soon as symptoms of poisoning appear (usually tearing, excess saliva, wheezing, drowsiness, muscle floppiness). Give 1 dose for known or suspected poisoning with 2 or more mild symptoms (e.g., blurred vision, miosis, watery eyes, runny nose, increased salivation, chest tightness or difficulty breathing, tremors, muscle twitching, nausea or vomiting, unexplained wheezing or coughing, acute stomach cramping, tachycardia, or bradycardia). Give 2 additional doses in rapid succession 10 minutes after giving the first injection if any severe symptom appears (e.g., confusion, severe breathing difficulties, severe lung secretions, severe muscle twitching and general weakness, involuntary urination and defecation, seizures, unconsciousness). Give 3 doses in rapid succession to any victim found unconscious or presenting with severe symptoms. Anticonvulsants and pralidoxime may be administered concurrently.[30289]

Neonates and Infants weighing less than 7 kg

0.25 mg/dose IM as soon as symptoms of poisoning appear (usually tearing, excess saliva, wheezing, drowsiness, muscle floppiness). Give 1 dose for known or suspected poisoning with 2 or more mild symptoms (e.g., blurred vision, miosis, watery eyes, runny nose, increased salivation, chest tightness or difficulty breathing, tremors, muscle twitching, nausea or vomiting, unexplained wheezing or coughing, acute stomach cramping, tachycardia, or bradycardia). Give 2 additional doses in rapid succession 10 minutes after giving the first injection if any severe symptom appears (e.g., confusion, severe breathing difficulties, severe lung secretions, severe muscle twitching and general weakness, involuntary urination and defecation, seizures, unconsciousness). Give 3 doses in rapid succession to any victim found unconscious or presenting with severe symptoms. Anticonvulsants and pralidoxime may be administered concurrently.[30289]

For cholinesterase inhibitor-induced muscarinic effects prophylaxis when anticholinesterase agents (i.e., neostigmine, physostigmine, pyridostigmine) are used to reverse the neuromuscular blockade produced by curariform agents. Intravenous Dosage Adults

0.6 to 1.2 mg IV for each 0.5 to 2.5 mg of neostigmine or 10 to 20 mg of pyridostigmine; atropine is given a few minutes before (especially if bradycardia is present) or concurrently (in a separate syringe) with the cholinesterase inhibitor.

Children

0.05 mg/kg/dose IV (up to initial adult dose: 2 to 5 mg). Repeat/adjust dose every 10 to 20 minutes as needed; double the dose if inadequate response/atropinization to initial dose.

For adjunctive treatment of GI disorders caused by cholinergic stimulation, such as duodenal ulcer, irritable bowel syndrome, or GI hypermotility and diarrhea. Oral Dosage Adults

0.3 to 1.2 mg PO every 4 to 6 hours.

Children

0.01 mg/kg or 0.3 mg/m2, up to 0.4 mg, PO every 4 to 6 hours.

For mydriasis induction or cycloplegia induction. Ophthalmic Dosage (Ophthalmic solution only) Adults

1 drop of 1% solution topically to the cul-de-sac of the conjunctiva in 1 or both eyes as indicated, 40 minutes before the intended maximal dilation time. Dose may be repeated up to twice daily as needed.

Children and Adolescents 3 years and older

1 drop of 1% solution topically to the cul-de-sac of the conjunctiva in 1 or both eyes as indicated, 40 minutes before the intended maximal dilation time. Dose may be repeated up to twice daily as needed. In one study for cycloplegic refraction in strabismic children, 1 drop 3-times daily for 3 days administered prior to the procedure was compared to 2 drops given 5 minutes apart; children younger than 2.5 years received a 0.5% concentration and children 2.5 years or older received 1% concentration. The differences in cycloplegic refraction were not significant between the 2 groups.

Infants and Children 3 months up to 3 years

1 drop of 1% solution topically to the cul-de-sac of the conjunctiva in 1 or both eyes as indicated, 40 minutes before the intended maximal dilation time. In one study for cycloplegic refraction in strabismic children, 1 drop 3-times daily for 3 days administered prior to the procedure was compared to 2 drops given 5 minutes apart; children younger than 2.5 years received a 0.5% concentration and children 2.5 years or older received 1% concentration. The differences in cycloplegic refraction were not significant between the 2 groups.

Ophthalmic Dosage (Ophthalmic ointment only) Adults

Apply a small amount of the ointment in the conjunctival sac 1- to 2-times per day; take care to avoid overdosage.

Infants 3 months and older, Children, and Adolescents

Apply a small amount of the ointment in the conjunctival sac 1- to 2-times per day; take care to avoid overdosage.

For the treatment of iritis or uveitis. Ophthalmic Dosage (1% solution or ointment) Adults

1 to 2 drops to the affected eye(s) up to 4 times daily. For the ointment, apply a small amount in the conjunctival sac of the affected eye(s) 1 or 2 times daily.

Children and Adolescents

1 drop to the affected eye(s) 2 to 3 times daily; 1 to 2 drops once daily has also been used. For the ointment, apply a small amount in the conjunctival sac of the affected eye(s) 1 or 2 times daily.

For penalization of the healthy eye in the treatment of amblyopia. Ophthalmic Dosage Adults

1 drop of 1% solution topically to the cul-de-sac of the conjunctiva, 40 minutes before the intended maximal dilation time. Dose may be repeated up to twice daily as needed.

Children and Adolescents 3 years and older

1 drop of 1% solution topically to the cul-de-sac of the conjunctiva, 40 minutes before the intended maximal dilation time. Dose may be repeated up to twice daily as needed. 1 drop of 1% solution instilled in the unaffected eye once daily results comparable improvement in visual acuity to patching. In a clinical trial, 419 children ages 3 to 7 years with moderate amblyopia (i.e., visual acuity 20/40 to 20/100) were randomly assigned to receive patching for a minimum of 6 hours daily or 1 drop of atropine 1% ophthalmic solution in the unaffected eye every day. Although more rapid improvement was noted initially in the patching group, the difference was clinically insignificant after 6 months (about one-third of a line). After the initial 6 months of treatment, investigators were permitted to prescribe any type of amblyopia therapy. In 363 patients, visual acuity continued to be improved when evaluated 2 years after initial randomization; the authors concluded that use of atropine or patching for 6 months followed by regular care did not lend to differences in visual acuity 2 years later. Additionally, in a subgroup analysis of 176 children who were evaluated at age 10 years, improvement of amblyopia was maintained in both groups, although approximately half experienced mild residual amblyopia (i.e., visual acuity less than 20/25).

For the treatment of symptomatic bradycardia† (e.g., vasovagal response, AV block, or bradyarrhythmias). Intravenous or Intraosseus† dosage Adults

0.5 to 1 mg IV every 3 to 5 minutes as needed up to 3 mg.[45649] [60266] [63867] Doses less than 0.5 mg IV have been associated with paradoxical bradycardia. The same dosage may be given via the intraosseous route when IV access is not available.[45649] [60266]

Infants, Children, and Adolescents

0.02 mg/kg/dose IV (minimum dose: 0.1 mg IV) is recommended by PALS; the dose may be repeated 1 time. Max: 0.5 mg/dose IV. The same dosage may be given via the intraosseous route when IV access is not available.

Neonates

0.02 mg/kg/dose IV; may repeat dose 1 time. Per PALS, the minimum single dose is 0.1 mg, however, some argue that this may be an excessive dose in very small neonates since the total dosage would be greater than 0.02 mg/kg. The same dosage may be given via the intraosseous route when IV access is not available.

Endotracheal dosage

NOTE: Drug effects after endotracheal (ET) administration may not be uniform; use only if access to IV or IO routes is not available.

Adults

1 to 2 mg ET (diluted in no more than 10 mL of 0.9% Sodium Chloride Injection or Sterile Water for Injection) per product labeling for FDA-approved indications. Clinical practice guidelines do not include the endotracheal administration of atropine.

Infants, Children, and Adolescents

0.04 to 0.06 mg/kg/dose ET (minimum dose: 0.1 mg ET); may repeat dose 1 time. Max: 0.5 mg/dose ET. Flush the ET tube with a minimum of 5 mL 0.9% Sodium Chloride Injection and follow with 5 ventilations. The optimal dosage has not been established.

Neonates

0.01 to 0.03 mg/kg/dose ET; may repeat dose 1 time. Flush the ET tube with a minimum of 1 to 5 mL (dependent on body weight with smaller patients getting smaller volumes) 0.9% Sodium Chloride Injection and follow with 5 ventilations.

Intramuscular dosage Neonates, Infants, Children, and Adolescents

0.02 to 0.04 mg/kg/dose IM.

For management of early-onset irinotecan-induced diarrhea†. Intravenous Dosage Adults

Unless clinically contraindicated, a dose of 0.25 to 1 mg IV should be considered for patients experiencing early-onset (e.g., occurring within 24 hours following irinotecan administration) diarrhea, diaphoresis, or abdominal cramps.

For the prevention of bradycardia and reduction of oral secretions during rapid-sequence intubation†. Intravenous Dosage Infants, Children, and Adolescents

0.02 mg/kg/dose IV (with no minimum dose) given 1 to 2 minutes prior to intubation. Max: 0.5 mg/dose. Available evidence does not support routine use of atropine as a premedicant for emergency intubation in critically ill children; however, it may be considered when there is a high risk of bradycardia.

Neonates

0.02 mg/kg/dose IV.

For the treatment of symptomatic bradycardia associated with beta-blocker toxicity† or calcium-channel blocker toxicity†. Intravenous dosage Adults

0.5 to 1 mg IV every 3 to 5 minutes as needed up to 3 mg. Atropine is unlikely to have a significant or persisting effect on heart rate; anticipate quickly moving on to other resuscitation measures.

Infants, Children, and Adolescents

0.02 mg/kg/dose IV (minimum dose: 0.1 mg); may repeat once. Max: 0.5 mg/dose. Atropine is unlikely to have a significant or persisting effect on heart rate; anticipate quickly moving on to other resuscitation measures.

For use in coronary artery disease diagnosis† (i.e., stress echocardiography†). Intravenous dosage Adults

0.25 to 0.5 mg IV every 1 minute as needed. Use 0.25 mg dosage increments in patients with small physique and in those close to target heart rate. Max total dose: 2 mg; limit total dose to 1 mg in patients with prior neuropsychiatric symptoms or BMI less than 24 kg/m2. Add atropine when target heart rate cannot be achieved with dobutamine alone. The addition of atropine at 20 or 30 mcg/kg/minute of dobutamine (compared to 40 mcg/kg/minute) achieves target heart rate earlier with fewer adverse effects and shortens testing time. 

Geriatric

0.25 to 0.5 mg IV every 1 minute as needed. Use 0.25 mg dosage increments in patients with small physique and in those close to target heart rate. Max total dose: 1 mg. Add atropine when target heart rate cannot be achieved with dobutamine alone. The addition of atropine at 20 or 30 mcg/kg/minute of dobutamine (compared to 40 mcg/kg/minute) achieves target heart rate earlier with fewer adverse effects and shortened testing time.

†Indicates off-label use

Dosing Considerations
Hepatic Impairment

Specific guidelines for dosage adjustments in hepatic impairment are not available.

Renal Impairment

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

Drug Interactions

Abatacept: (Minor) Because abatacept has been shown to potentiate the onset of respiratory infections, concomitant use of drugs that decrease mucociliary clearance should be used cautiously. Anticholinergics, such as atropine, have been shown to be capable of depressing the mucociliary transport system.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when dihydrocodeine is used concomitantly with an anticholinergic drug. The concomitant use of dihydrocodeine and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect.
Acetaminophen; Codeine: (Major) Reserve concomitant use of codeine and atropine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Major) Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine.
Acetaminophen; Dextromethorphan; Phenylephrine: (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Major) Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine.
Acetaminophen; Guaifenesin; Phenylephrine: (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect.
Acetaminophen; Hydrocodone: (Major) Reserve concomitant use of hydrocodone and atropine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Acetaminophen; Oxycodone: (Major) Reserve concomitant use of oxycodone and atropine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Acetaminophen; Phenylephrine: (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect.
Acetaminophen; Pseudoephedrine: (Major) Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine.
Aclidinium: (Moderate) Although aclidinium is minimally absorbed into the systemic circulation after inhalation, there is the potential for aclidinium to have additive anticholinergic effects when administered with other anticholinergics or antimuscarinics. Per the manufacturer, avoid concomitant administration of aclidinium with other anticholinergic medications, when possible.
Aclidinium; Formoterol: (Moderate) Although aclidinium is minimally absorbed into the systemic circulation after inhalation, there is the potential for aclidinium to have additive anticholinergic effects when administered with other anticholinergics or antimuscarinics. Per the manufacturer, avoid concomitant administration of aclidinium with other anticholinergic medications, when possible.
Acrivastine; Pseudoephedrine: (Major) Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine.
Alfentanil: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when alfentanil is used concomitantly with an anticholinergic drug. The concomitant use of alfentanil and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Alosetron: (Major) Concomitant use of alosetron and anticholinergics, which can decrease GI motility, may seriously worsen constipation, leading to events such as GI obstuction, impaction, or paralytic ileus. Although specific recommendations are not available from the manufacturer, it would be prudent to avoid anticholinergics in patients taking alosetron.
Aluminum Hydroxide: (Moderate) Antacids may inhibit the oral absorption of anticholinergics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
Aluminum Hydroxide; Magnesium Carbonate: (Moderate) Antacids may inhibit the oral absorption of anticholinergics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
Aluminum Hydroxide; Magnesium Hydroxide: (Moderate) Antacids may inhibit the oral absorption of anticholinergics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Moderate) Antacids may inhibit the oral absorption of anticholinergics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
Aluminum Hydroxide; Magnesium Trisilicate: (Moderate) Antacids may inhibit the oral absorption of anticholinergics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
Amantadine: (Major) Amantadine may exhibit anticholinergic activity. Antimuscarinics, such as atropine, may potentiate the anticholinergic effects of amantadine, and may increase the risk of antimuscarinic-related side effects.
Amoxapine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when amoxapine is used concomitantly with other anticholinergic agents. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive CNS effects are also possible when these drugs are combined with amoxapine.
Antacids: (Moderate) Antacids may inhibit the oral absorption of anticholinergics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) The anticholinergic effects of atropine may be enhanced when combined with other commonly used drugs with moderate to significant anticholinergic effects including orphenadrine. Clinicians should note that anticholinergic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Aspirin, ASA; Carisoprodol; Codeine: (Major) Reserve concomitant use of codeine and atropine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) 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.
Aspirin, ASA; Oxycodone: (Major) Reserve concomitant use of oxycodone and atropine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Atomoxetine: (Major) Atropine and atomoxetine should be combined cautiously in patients with known cardiac disease. Atropine or scopolamine may alter the heart rate; the predominant clinical effect is sinus tachycardia. An additive effect on heart rate may occur as atomoxetine may elevate heart rate as well as blood pressure.
Atropine; Difenoxin: (Moderate) Diphenoxylate is a synthetic opiate derivative that appears to exert its effect locally and centrally on the smooth mucle cells of the GI tract to inhibit GI motility and slow excess GI propulsion. Atropine is commonly added in small amounts to these formulas for diarrhea as a deterrant to diphenoxylate abuse. However, therapeutic doses of systemic atropine may cause additive side effects. In some cases, constipation might occur, and effects on the CNS or bladder function may also be additive.
Belladonna; Opium: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when opium is used concomitantly with an anticholinergic drug. The concomitant use of opium and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Benzhydrocodone; Acetaminophen: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when benzhydrocodone is used concomitantly with an anticholinergic drug. The concomitant use of benzhydrocodone and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Botulinum Toxins: (Moderate) The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
Brompheniramine; Dextromethorphan; Phenylephrine: (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect.
Brompheniramine; Phenylephrine: (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect.
Brompheniramine; Pseudoephedrine: (Major) Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Major) Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine.
Buprenorphine: (Major) Reserve concomitant use of buprenorphine and atropine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Buprenorphine; Naloxone: (Major) Reserve concomitant use of buprenorphine and atropine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Bupropion: (Moderate) The anticholinergic effects of atropine may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including bupropion. 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 drowsiness may also occur.
Bupropion; Naltrexone: (Moderate) The anticholinergic effects of atropine may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including bupropion. 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 drowsiness may also occur.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Reserve concomitant use of codeine and atropine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Reserve concomitant use of codeine and atropine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Butorphanol: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when butorphanol is used concomitantly with an anticholinergic drug. The concomitant use of butorphanol and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Calcium Carbonate: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics.
Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics.
Calcium Carbonate; Magnesium Hydroxide: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics.
Calcium Carbonate; Magnesium Hydroxide; Simethicone: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics.
Calcium Carbonate; Simethicone: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics.
Calcium; Vitamin D: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics.
Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and atropine. CNS depressants can potentiate the effects of cannabidiol.
Carbidopa; Levodopa: (Minor) The doses of antimuscarinics and levodopa may need to be adjusted when the drugs are given simultaneously. Through central antimuscarinic actions, anticholinergics 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 an antimuscarinic is added.
Carbidopa; Levodopa; Entacapone: (Minor) The doses of antimuscarinics and levodopa may need to be adjusted when the drugs are given simultaneously. Through central antimuscarinic actions, anticholinergics 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 an antimuscarinic is added.
Celecoxib; Tramadol: (Major) Reserve concomitant use of tramadol and atropine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and atropine. Concurrent use may result in additive CNS depression.
Cetirizine: (Moderate) Monitor for unusual drowsiness or excess sedation and for signs or symptoms of anticholinergic toxicity during concomitant cetirizine and atropine use. Concomitant use may result in additive CNS depression or anticholinergic adverse effects.
Cetirizine; Pseudoephedrine: (Major) Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine. (Moderate) Monitor for unusual drowsiness or excess sedation and for signs or symptoms of anticholinergic toxicity during concomitant cetirizine and atropine use. Concomitant use may result in additive CNS depression or anticholinergic adverse effects.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Major) Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine.
Chlorpheniramine; Codeine: (Major) Reserve concomitant use of codeine and atropine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect. (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when dihydrocodeine is used concomitantly with an anticholinergic drug. The concomitant use of dihydrocodeine and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Chlorpheniramine; Hydrocodone: (Major) Reserve concomitant use of hydrocodone and atropine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine.
Chlorpheniramine; Phenylephrine: (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect.
Chlorpheniramine; Pseudoephedrine: (Major) Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine.
Chlorpromazine: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including chlorpromazine. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other additive CNS effects may also occur.
Cholinergic agonists: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Cisapride: (Moderate) Atropine is an anticholinergic drug and thus can antagonize the action of drugs that enhance gastrointestinal motility, such as cisapride. Use this combination with caution.
Clozapine: (Major) Avoid co-prescribing clozapine with other anticholinergic medicines that can cause gastrointestinal hypomotility, due to a potential to increase serious constipation, ileus, and other potentially serious bowel conditions that may result in hospitalization. Clozapine exhibits potent anticholinergic effects. Additive anticholinergic effects may be seen when clozapine is used concomitantly with anticholinergic agents. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur, depending on the anticholinergic agent used.
Codeine: (Major) Reserve concomitant use of codeine and atropine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Codeine; Guaifenesin: (Major) Reserve concomitant use of codeine and atropine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Codeine; Guaifenesin; Pseudoephedrine: (Major) Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine. (Major) Reserve concomitant use of codeine and atropine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Codeine; Phenylephrine; Promethazine: (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect. (Major) Reserve concomitant use of codeine and atropine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus. (Moderate) Monitor for unusual drowsiness or excess sedation and for signs or symptoms of anticholinergic toxicity during concomitant promethazine and atropine use. Concomitant use may result in additive CNS depression or anticholinergic adverse effects.
Codeine; Promethazine: (Major) Reserve concomitant use of codeine and atropine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus. (Moderate) Monitor for unusual drowsiness or excess sedation and for signs or symptoms of anticholinergic toxicity during concomitant promethazine and atropine use. Concomitant use may result in additive CNS depression or anticholinergic adverse effects.
Colesevelam: (Moderate) Colesevelam may decrease the absorption of atropine if coadministered. To minimize potential for interactions, consider administering atropine at least 1 hour before or at least 4 hours after colesevelam; monitor drug response and/or serum drug concentrations.
COMT inhibitors: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including systemic atropine, due to the possibility of additive sedation. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Crofelemer: (Moderate) Pharmacodynamic interactions between crofelemer and antimuscarinics are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as antimuscarinics, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Cyclobenzaprine: (Moderate) Monitor for unusual drowsiness or excess sedation and for signs or symptoms of anticholinergic toxicity during concomitant cyclobenzaprine and atropine use. Concomitant use may result in additive CNS depression or anticholinergic adverse effects.
Dasiglucagon: (Major) The concomitant use of intravenous glucagon and anticholinergics increases the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. Concomitant use is not recommended.
Desloratadine; Pseudoephedrine: (Major) Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine.
Dexbrompheniramine; Pseudoephedrine: (Major) Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine.
Dextromethorphan; Bupropion: (Moderate) The anticholinergic effects of atropine may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including bupropion. 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 drowsiness may also occur.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect.
Dextromethorphan; Guaifenesin; Phenylephrine: (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Major) Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine.
Dextromethorphan; Quinidine: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
Difelikefalin: (Moderate) Monitor for dizziness, somnolence, mental status changes, and gait disturbances if concomitant use of difelikefalin with CNS depressants is necessary. Concomitant use may increase the risk for these adverse reactions.
Digoxin: (Moderate) Anticholinergics, because of their ability to cause tachycardia, can antagonize the beneficial actions of digoxin in atrial fibrillation/flutter. Routine therapeutic monitoring should be continued when an antimuscarinic agent is prescribed with digoxin until the effects of combined use are known.
Diphenhydramine; Phenylephrine: (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect.
Diphenoxylate; Atropine: (Moderate) Diphenoxylate is a synthetic opiate derivative that appears to exert its effect locally and centrally on the smooth mucle cells of the GI tract to inhibit GI motility and slow excess GI propulsion. Atropine is commonly added in small amounts to these formulas for diarrhea as a deterrant to diphenoxylate abuse. However, therapeutic doses of systemic atropine may cause additive side effects. In some cases, constipation might occur, and effects on the CNS or bladder function may also be additive.
Disopyramide: (Moderate) In addition to its electrophysiologic effects, disopyramide exhibits clinically significant anticholinergic properties. These can be additive with other anticholinergics. Clinicians should be aware that urinary retention, particularly in males, and aggravation of glaucoma are realistic possibilities of using disopyramide with other anticholinergic agents.
Donepezil: (Moderate) The therapeutic benefits of donepezil, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
Donepezil; Memantine: (Moderate) The adverse effects of anticholinergics, such as dry mouth, urinary hesitancy or blurred vision may be enhanced with use of memantine; dosage adjustments of the anticholinergic drug may be required when memantine is coadministered. In addition, preliminary evidence indicates that chronic anticholinergic use in patients with Alzheimer's Disease may possibly have an adverse effect on cognitive function. Therefore, the effectiveness of drugs used in the treatment of Alzheimer's such as memantine, may be adversely affected by chronic antimuscarinic therapy. (Moderate) The therapeutic benefits of donepezil, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
Dronabinol: (Moderate) Use caution if coadministration of dronabinol with anticholinergics is necessary. Concurrent use of dronabinol, THC with anticholinergics may result in additive drowsiness, hypertension, tachycardia, and possibly cardiotoxicity.
Eluxadoline: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as anticholinergics. Discontinue use of eluxadoline in patients who develop severe constipation lasting more than 4 days.
Ephedrine: (Moderate) Carefully monitor blood pressure in patients who have received both ephedrine and atropine; atropine augments the pressor effect of ephedrine.
Ephedrine; Guaifenesin: (Moderate) Carefully monitor blood pressure in patients who have received both ephedrine and atropine; atropine augments the pressor effect of ephedrine.
Esketamine: (Moderate) Closely monitor patients receiving esketamine and atropine for sedation and other CNS depressant effects. Instruct patients who receive a dose of esketamine not to drive or engage in other activities requiring alertness until the next day after a restful sleep.
Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and atropine. Concurrent use may result in additive CNS depression.
Fentanyl: (Major) Reserve concomitant use of fentanyl and atropine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Fexofenadine; Pseudoephedrine: (Major) Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine.
Fluphenazine: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including fluphenazine. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other additive CNS effects may also occur.
Fluticasone; Umeclidinium; Vilanterol: (Moderate) There is the potential for umeclidinium to have additive anticholinergic effects when administered with other anticholinergics or antimuscarinics. Per the manufaturer, avoid concomitant administration of umeclidinium with other anticholinergic medications when possible.
Gabapentin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of atropine and gabapentin. Concurrent use may result in additive CNS depression.
Galantamine: (Moderate) The therapeutic benefits of galantamine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
Glucagon: (Major) The concomitant use of intravenous glucagon and anticholinergics increases the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. Concomitant use is not recommended.
Glycopyrronium: (Moderate) Although glycopyrronium is minimally absorbed into the systemic circulation after topical application, there is the potential for glycopyrronium to have additive anticholinergic effects when administered with other antimuscarinics. Per the manufaturer, avoid concomitant administration of glycopyrronium with other anticholinergic medications.
Guaifenesin; Hydrocodone: (Major) Reserve concomitant use of hydrocodone and atropine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Guaifenesin; Phenylephrine: (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect.
Guaifenesin; Pseudoephedrine: (Major) Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine.
Homatropine; Hydrocodone: (Major) Reserve concomitant use of hydrocodone and atropine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Hydrocodone: (Major) Reserve concomitant use of hydrocodone and atropine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Hydrocodone; Ibuprofen: (Major) Reserve concomitant use of hydrocodone and atropine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Hydrocodone; Pseudoephedrine: (Major) Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine. (Major) Reserve concomitant use of hydrocodone and atropine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Hydromorphone: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when hydromorphone is used concomitantly with an anticholinergic drug. The concomitant use of hydromorphone and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Ibritumomab Tiuxetan: (Moderate) Use anticholinergics, such as atropine, and concomitant solid oral dosage forms of potassium chloride with caution due to risk for gastrointestinal mucosal injury. Anticholinergics may decrease gastric motility and increase the transit time of solid oral dosage forms of potassium chloride leading to prolonged contact with the gastrointestinal mucosa.
Ibuprofen; Oxycodone: (Major) Reserve concomitant use of oxycodone and atropine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Ibuprofen; Pseudoephedrine: (Major) Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine.
Ipratropium: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
Ipratropium; Albuterol: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
Itraconazole: (Moderate) Antimuscarinics can raise intragastric pH. This effect may decrease the oral bioavailability of itraconazole; antimuscarinics should be used cautiously in patients receiving itraconazole.
Lasmiditan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and atropine. Concurrent use may result in additive CNS depression.
Lemborexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and atropine. Dosage adjustments of lemborexant and atropine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Levocetirizine: (Moderate) Monitor for unusual drowsiness or excess sedation and for signs or symptoms of anticholinergic toxicity during concomitant cetirizine and atropine use. Concomitant use may result in additive CNS depression or anticholinergic adverse effects.
Levodopa: (Minor) The doses of antimuscarinics and levodopa may need to be adjusted when the drugs are given simultaneously. Through central antimuscarinic actions, anticholinergics 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 an antimuscarinic is added.
Levorphanol: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when levorphanol is used concomitantly with an anticholinergic drug. The concomitant use of levorphanol and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Linaclotide: (Moderate) Anticholinergics can promote constipation and pharmacodynamically oppose the action of drugs used for the treatment of constipation or constipation-associated irritable bowel syndrome, such as linaclotide.
Lofexidine: (Moderate) Monitor for excessive hypotension and sedation during coadministration of lofexidine and atropine. Lofexidine can potentiate the effects of CNS depressants.
Loratadine; Pseudoephedrine: (Major) Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine.
Loxapine: (Moderate) Loxapine has anticholinergic activity. The concomitant use of loxapine and other anticholinergic drugs can increase the risk of anticholinergic adverse reactions including exacerbation of glaucoma, constipation, and urinary retention. Depending on the agent used, additive drowsiness/dizziness may also occur.
Lubiprostone: (Moderate) Antimuscarinic drugs can promote constipation and pharmacodynamically oppose the action of drugs used for the treatment of constipation, such as lubiprostone. The clinical significance of these potential interactions is uncertain.
Lumateperone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lumateperone and atropine. Concurrent use may result in additive CNS depression.
Lurasidone: (Moderate) Antipsychotic agents may disrupt core temperature regulation; therefore, caution is recommended during concurrent use of lurasidone and medications with anticholinergic activity such as antimuscarinics. Concurrent use of lurasidone and medications with anticholinergic activity may contribute to heat-related disorders. Monitor patients for heat intolerance, decreased sweating, or increased body temperature if lurasidone is used with antimuscarinics.
Macimorelin: (Major) Avoid use of macimorelin with drugs that may blunt the growth hormone response to macimorelin, such as antimuscarinic anticholinergic agents. Healthcare providers are advised to discontinue anticholinergics at least 1 week before administering macimorelin. Use of these medications together may impact the accuracy of the macimorelin growth hormone test.
Magnesium Hydroxide: (Moderate) Antacids may inhibit the oral absorption of anticholinergics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
Maprotiline: (Moderate) The anticholinergic effects of atropine may be enhanced when combined with other commonly used drugs with moderate to significant anticholinergic effects including maprotiline.
Memantine: (Moderate) The adverse effects of anticholinergics, such as dry mouth, urinary hesitancy or blurred vision may be enhanced with use of memantine; dosage adjustments of the anticholinergic drug may be required when memantine is coadministered. In addition, preliminary evidence indicates that chronic anticholinergic use in patients with Alzheimer's Disease may possibly have an adverse effect on cognitive function. Therefore, the effectiveness of drugs used in the treatment of Alzheimer's such as memantine, may be adversely affected by chronic antimuscarinic therapy.
Meperidine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when meperidine is used concomitantly with an anticholinergic drug. The concomitant use of meperidine and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Methadone: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when methadone is used concomitantly with an anticholinergic drug. The concomitant use of methadone and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Metoclopramide: (Moderate) Drugs with significant antimuscarinic activity, such as anticholinergics and antimuscarinics, may slow GI motility and thus may reduce the prokinetic actions of metoclopramide. Monitor patients for an increase in gastrointestinal complaints, such as reflux or constipation. Additive drowsiness may occur as well. The clinical significance is uncertain.
Mirtazapine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of mirtazapine and atropine due to the risk for additive CNS depression.
Molindone: (Moderate) Antipsychotics are associated with anticholinergic effects; therefore, additive effects may be seen during concurrent use of molindone and other drugs having anticholinergic activity such as antimuscarinics. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other CNS effects may also occur.
Morphine: (Major) Reserve concomitant use of morphine and atropine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Morphine; Naltrexone: (Major) Reserve concomitant use of morphine and atropine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Nabilone: (Moderate) Concurrent use of nabilone with anticholinergics may result in pronounced tachycardia and drowsiness.
Nalbuphine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when nalbuphine is used concomitantly with an anticholinergic drug. The concomitant use of nalbuphine and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Naproxen; Pseudoephedrine: (Major) Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine.
Neostigmine: (Major) Coadministration of atropine and neostigmine may produce a mutually antagonistic effect.
Neostigmine; Glycopyrrolate: (Major) Coadministration of atropine and neostigmine may produce a mutually antagonistic effect.
Norepinephrine: (Major) Pharmacologically, sufficient doses of atropine block various types of vagal reflex bradycardia. Because norepinephrine causes vagal reflex bradycardia, the concomitant use of atropine and norepinephrine may increase the pressor effect of norepinephrine.
Olanzapine: (Moderate) Additive anticholinergic effects may be seen when olanzapine and anticholinergics are used concomitantly; use with caution. Use of olanzapine and other drugs with anticholinergic activity can increase the risk for severe gastrointestinal adverse reactions related to hypomotility. Olanzapine exhibits anticholinergic activity. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur, depending on the anticholinergic agent used.
Olanzapine; Fluoxetine: (Moderate) Additive anticholinergic effects may be seen when olanzapine and anticholinergics are used concomitantly; use with caution. Use of olanzapine and other drugs with anticholinergic activity can increase the risk for severe gastrointestinal adverse reactions related to hypomotility. Olanzapine exhibits anticholinergic activity. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur, depending on the anticholinergic agent used.
Olanzapine; Samidorphan: (Moderate) Additive anticholinergic effects may be seen when olanzapine and anticholinergics are used concomitantly; use with caution. Use of olanzapine and other drugs with anticholinergic activity can increase the risk for severe gastrointestinal adverse reactions related to hypomotility. Olanzapine exhibits anticholinergic activity. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur, depending on the anticholinergic agent used.
Oliceridine: (Moderate) Concomitant use of oliceridine with atropine may cause excessive sedation and somnolence. Limit the use of oliceridine with atropine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Also monitor patients for signs of

urinary retention or reduced gastric motility when oliceridine is used concomitantly with atropine. The concomitant use of anticholinergic drugs may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Omeprazole; Sodium Bicarbonate: (Moderate) 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: (Moderate) The anticholinergic effects of atropine may be enhanced when combined with other commonly used drugs with moderate to significant anticholinergic effects including orphenadrine. Clinicians should note that anticholinergic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Oxycodone: (Major) Reserve concomitant use of oxycodone and atropine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Oxymorphone: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when oxymorphone is used concomitantly with an anticholinergic drug. The concomitant use of oxymorphone and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Paroxetine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant anticholinergic medication and paroxetine use. Concomitant use may result in additive anticholinergic adverse effects.
Pentazocine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when pentazocine is used concomitantly with an anticholinergic drug. The concomitant use of pentazocine and anticholinergic medications may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Pentazocine; Naloxone: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when pentazocine is used concomitantly with an anticholinergic drug. The concomitant use of pentazocine and anticholinergic medications may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Perphenazine: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including perphenazine. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other additive CNS effects may also occur.
Perphenazine; Amitriptyline: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including perphenazine. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other additive CNS effects may also occur.
Phentermine; Topiramate: (Moderate) Monitor for decreased sweating and increased body temperature, especially in hot weather, during concomitant use of topiramate and other drugs that predispose persons to heat-related disorders, such as anticholinergic medications. Concomitant use increases the risk for oligohidrosis and hyperthermia.
Phenylephrine: (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect.
Physostigmine: (Major) Coadministration of atropine and physostigmine may produce a mutually antagonistic effect.
Potassium Bicarbonate: (Moderate) Use anticholinergics, such as atropine, and concomitant solid oral dosage forms of potassium chloride with caution due to risk for gastrointestinal mucosal injury. Anticholinergics may decrease gastric motility and increase the transit time of solid oral dosage forms of potassium chloride leading to prolonged contact with the gastrointestinal mucosa.
Potassium Chloride: (Moderate) Use anticholinergics, such as atropine, and concomitant solid oral dosage forms of potassium chloride with caution due to risk for gastrointestinal mucosal injury. Anticholinergics may decrease gastric motility and increase the transit time of solid oral dosage forms of potassium chloride leading to prolonged contact with the gastrointestinal mucosa.
Pramlintide: (Major) Pramlintide therapy should not be considered in patients taking medications that alter gastric motility, such as anticholinergics. Pramlintide slows gastric emptying and the rate of nutrient delivery to the small intestine. Medications that have depressive effects on GI could potentiate the actions of pramlintide.
Pregabalin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of atropine and pregabalin. Concurrent use may result in additive CNS depression.
Procainamide: (Moderate) The anticholinergic effects of procainamide may be significant and may be enhanced when combined with anticholinergics. Anticholinergic agents administered concurrently with procainamide may produce additive antivagal effects on AV nodal conduction, although this is not as well documented for procainamide as for quinidine.
Prochlorperazine: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including prochlorperazine. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other additive CNS effects may also occur.
Promethazine: (Moderate) Monitor for unusual drowsiness or excess sedation and for signs or symptoms of anticholinergic toxicity during concomitant promethazine and atropine use. Concomitant use may result in additive CNS depression or anticholinergic adverse effects.
Promethazine; Dextromethorphan: (Moderate) Monitor for unusual drowsiness or excess sedation and for signs or symptoms of anticholinergic toxicity during concomitant promethazine and atropine use. Concomitant use may result in additive CNS depression or anticholinergic adverse effects.
Promethazine; Phenylephrine: (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect. (Moderate) Monitor for unusual drowsiness or excess sedation and for signs or symptoms of anticholinergic toxicity during concomitant promethazine and atropine use. Concomitant use may result in additive CNS depression or anticholinergic adverse effects.
Pseudoephedrine: (Major) Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine.
Pseudoephedrine; Triprolidine: (Major) Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine.
Pyridostigmine: (Major) Coadministration of atropine and pyridostigmine bromide may produce a mutually antagonistic effect.
Quetiapine: (Moderate) Monitor for unusual drowsiness or excess sedation and for signs or symptoms of anticholinergic toxicity during concomitant quetiapine and atropine use. Concomitant use may result in additive CNS depression or anticholinergic adverse effects.
Quinidine: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
Rasagiline: (Moderate) MAOIs exhibit secondary anticholinergic actions. Additive anticholinergic effects may be seen when MAOIs are used concomitantly with antimuscarinics. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive CNS effects are also possible when many of these drugs are combined with MAOIs.
Remifentanil: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when remifentanil is used concomitantly with an anticholinergic drug. The concomitant use of remifentanil and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Revefenacin: (Moderate) Although revefenacin is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinics. Avoid concomitant administration with other anticholinergic and antimucarinic medications.
Rivastigmine: (Moderate) The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
Secretin: (Major) Discontinue anticholinergic medications at least 5 half-lives before administering secretin. Patients who are receiving anticholinergics at the time of stimulation testing may be hyporesponsive to secretin stimulation and produce a false result. Consider additional testing and clinical assessments for aid in diagnosis.
Sedating H1-blockers: (Moderate) Monitor for unusual drowsiness or excess sedation and for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and atropine use. Concomitant use may result in additive CNS depression or anticholinergic adverse effects.
Sincalide: (Moderate) Sincalide-induced gallbladder ejection fraction may be affected by anticholinergics. False study results are possible in patients with drug-induced hyper- or hypo-responsiveness; thorough patient history is important in the interpretation of procedure results.
Sodium Bicarbonate: (Moderate) 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.
Sodium Sulfate; Magnesium Sulfate; Potassium Chloride: (Moderate) Use anticholinergics, such as atropine, and concomitant solid oral dosage forms of potassium chloride with caution due to risk for gastrointestinal mucosal injury. Anticholinergics may decrease gastric motility and increase the transit time of solid oral dosage forms of potassium chloride leading to prolonged contact with the gastrointestinal mucosa.
Solifenacin: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics. Blurred vision and dry mouth would be common effects. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Stiripentol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and atropine. CNS depressants can potentiate the effects of stiripentol.
Sufentanil: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when sufentanil is used concomitantly with an anticholinergic drug. The concomitant use of sufentanil and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Tapentadol: (Moderate) Tapentadol should be used cautiously with anticholinergic medications since additive depressive effects on GI motility or bladder function may occur. Monitor patients for signs of urinary retention or reduced gastric motility. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. Additive CNS effects like drowsiness or dizziness may also occur.
Tegaserod: (Major) Drugs that exert significant anticholinergic properties such as antimuscarinics may pharmacodynamically oppose the effects of prokinetic agents such as tegaserod. Avoid administering antimuscarinics along with tegaserod under most circumstances. Inhaled respiratory antimuscarinics, such as ipratropium, are unlikely to interact with tegaserod. Ophthalmic anticholinergics may interact if sufficient systemic absorption of the eye medication occurs.
Tenapanor: (Moderate) Anticholinergics can promote constipation and pharmacodynamically oppose the action of drugs used for the treatment of constipation or constipation-associated irritable bowel syndrome, such as tenapanor.
Thiazide diuretics: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Thioridazine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties like thioridazine are used concomitantly with anticholinergic agents. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur, depending on the interacting agent.
Thiothixene: (Moderate) Anticholinergics may have additive effects with thiothixene, an antipsychotic with the potential for anticholinergic activity. Monitor for anticholinergic-related adverse effects such as xerostomia, blurred vision, constipation, and urinary retention during concurrent use.
Tiotropium: (Major) Avoid concomitant use of anticholinergic medications and tiotropium due to increased risk for anticholinergic adverse effects.
Tiotropium; Olodaterol: (Major) Avoid concomitant use of anticholinergic medications and tiotropium due to increased risk for anticholinergic adverse effects.
Tolterodine: (Moderate) Additive anticholinergic effects may be seen when tolterodine is used concomitantly with other antimuscarinics. When possible, avoid concurrent use, especially in the elderly, who are more susceptible to the anticholinergic effects. Consider alternatives to these other medications, if available. Clinicians should note that antimuscarinic effects might be seen not only on bladder smooth muscle, but also on GI function, the eye, and temperature regulation. Blurred vision, constipation, and dry mouth may be more prominent additive effects. With many of the listed agents, additive drowsiness may also occur when combined.
Topiramate: (Moderate) Monitor for decreased sweating and increased body temperature, especially in hot weather, during concomitant use of topiramate and other drugs that predispose persons to heat-related disorders, such as anticholinergic medications. Concomitant use increases the risk for oligohidrosis and hyperthermia.
Tramadol: (Major) Reserve concomitant use of tramadol and atropine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Tramadol; Acetaminophen: (Major) Reserve concomitant use of tramadol and atropine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.
Tricyclic antidepressants: (Moderate) Monitor for unusual drowsiness or excess sedation and for signs or symptoms of anticholinergic toxicity during concomitant tricyclic antidepressant and atropine use. Concomitant use may result in additive CNS depression or anticholinergic adverse effects.
Trifluoperazine: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including trifluoperazine. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other additive CNS effects may also occur.
Trimethobenzamide: (Moderate) Trimethobenzamide has CNS depressant effects and may cause drowsiness. The concurrent use of trimethobenzamide with other medications that cause CNS depression, like the anticholinergics, may potentiate the effects of either trimethobenzamide or the anticholinergic.
Trospium: (Moderate) Additive anticholinergic effects may be seen when trospium is used concomitantly with other antimuscarinics. When possible, avoid concurrent use, especially in the elderly, who are more susceptible to the anticholinergic effects. Consider alternatives to these other medications, if available. Clinicians should note that antimuscarinic effects might be seen not only on bladder smooth muscle, but also on GI function, the eye, and temperature regulation. Blurred vision, constipation, and dry mouth may be more prominent additive effects. With many of the listed agents, additive drowsiness may also occur when combined with trospium.
Umeclidinium: (Moderate) There is the potential for umeclidinium to have additive anticholinergic effects when administered with other anticholinergics or antimuscarinics. Per the manufaturer, avoid concomitant administration of umeclidinium with other anticholinergic medications when possible.
Umeclidinium; Vilanterol: (Moderate) There is the potential for umeclidinium to have additive anticholinergic effects when administered with other anticholinergics or antimuscarinics. Per the manufaturer, avoid concomitant administration of umeclidinium with other anticholinergic medications when possible.
Vibegron: (Moderate) Vibegron should be administered with caution in patients taking anticholinergics because of potential for an increased risk of urinary retention. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
Zonisamide: (Moderate) Zonisamide use is associated with case reports of decreased sweating, hyperthermia, heat intolerance, or heat stroke and should be used with caution in combination with other drugs that may also predispose patients to heat-related disorders like anticholinergics.

How Supplied

Atropine/Atropine Care/Atropine Sulfate/Atropisol/Isopto Atropine Ophthalmic Sol: 1%
Atropine/Atropine Care/Atropine Sulfate/Ocu-Tropine Ophthalmic Ointment: 1%
Atropine/Atropine Sulfate Endotracheal Inj Sol: 0.4mg, 1mL
Atropine/Atropine Sulfate Intramuscular Inj Sol: 0.1mg, 0.4mg, 0.5mL, 1mL, 1mg
Atropine/Atropine Sulfate Intraosseal Inj Sol: 0.4mg, 1mL
Atropine/Atropine Sulfate Intravenous Inj Sol: 0.05mg, 0.1mg, 0.4mg, 0.5mg, 0.5mL, 1mL, 1mg, 5mL
Atropine/Atropine Sulfate Subcutaneous Inj Sol: 0.1mg, 0.4mg, 0.5mL, 1mL, 1mg

Maximum Dosage

The maximum dosage of atropine is variable depending on the indication for use, route of administration, and the individual patient response. In patients with known coronary artery disease, limit the total dose of parenteral atropine to 0.03 to 0.04 mg/kg.

Mechanism Of Action

Atropine is a competitive inhibitor at autonomic postganglionic cholinergic receptors. These include receptors found in GI and pulmonary smooth muscle, exocrine glands, the heart, and the eye. Atropine does not block the actions of acetylcholine at the neuromuscular junction. Activity is due primarily to l-hyoscyamine, which possesses all of the antimuscarinic activity, and not d-hyoscyamine, which essentially has no peripheral antimuscarinic activity. The degree of sensitivity of various muscarinic receptors to antimuscarinic agents is dose-dependent. The most sensitive receptors are those of the salivary, bronchial, and sweat glands. Next are the receptors in the eye and heart, followed by the receptors in the GI tract.
 
The principal clinical effects of atropine are a reduction in salivary, bronchial, and sweat gland secretions; mydriasis; cycloplegia; changes in heart rate; contraction of the bladder detrusor muscle and of the GI smooth muscle; decreased gastric secretion; and decreased GI motility. At lower doses, a paradoxical decrease in heart rate occurs, and at higher doses, effects are seen at nicotinic receptors in autonomic ganglia, causing restlessness, hallucinations, disorientation, and delirium. Unlike scopolamine, atropine does not produce CNS depression (drowsiness, euphoria, amnesia, fatigue, decreased REM sleep) at usual therapeutic doses. Also, atropine's antimuscarinic potency is greater in the heart, bronchial, and GI smooth muscle, and is lesser in the iris; ciliary body; and salivary, sweat, and bronchial glands.
 
When applied topically to the eye, atropine blocks muscarinic cholinoceptor activation of the pupillary constrictor muscle, resulting in unopposed sympathetic dilator activity and mydriasis. Atropine also weakens the contraction of the ciliary muscle, or cycloplegia. Cycloplegia causes a loss in the ability to accommodate, such that the eye cannot focus for near vision.
 
The respiratory effects of atropine include reducing the volume of secretions from the nose, mouth, pharynx, and bronchi and relaxing smooth muscles of the bronchi and bronchioles, which decrease airway resistance. Since atropine is a potent bronchodilator, it is especially effective in blocking the acetylcholine-induced stimulation of guanyl cyclase, which is responsible for producing cyclic guanosine monophosphate (cGMP), a mediator of bronchoconstriction released from mast cells. These actions of atropine are useful, but controversial, in the treatment of antigen-, methacholine-, and exercise-induced bronchospasm in asthmatic patients.

Pharmacokinetics

Atropine is administered via oral, parenteral, endotracheal, oral inhalation, or ophthalmic routes. After absorption, the drug is widely distributed throughout the body and crosses the blood-brain barrier and placenta. Protein binding is 14% to 22%. The primary route of metabolism is via enzymatic hydrolysis in the liver to metabolites, including tropic acid. The half-life of atropine is approximately 2 to 4 hours in adults. Atropine and metabolites are primarily excreted renally and, to a lesser extent, by the pulmonary and fecal routes. Approximately 13% to 57% of administered atropine is excreted unchanged in the urine.[30289] [44803] [54383] [54384] [54525] [54526]
 
Affected cytochrome P450 isoenzymes and drug transporters: none

Oral Route

Atropine is well absorbed after oral administration. Peak plasma concentrations are seen within 1 hour after oral administration in adult patients.[54525]

Intramuscular Route

Maximum concentrations (9.6 ng/mL) are attained in a mean of 3 minutes after administration of a 2 mg autoinjector in adult patients.[30289]

Inhalation Route

Atropine is well absorbed after oral inhalation. After oral inhalation, peak plasma concentrations are reached in about 0.5 to 1.5 hours.[22788] [54525] [54528]

Other Route(s)

Endotracheal Route
Atropine is well absorbed after endotracheal administration.[43713]

Pregnancy And Lactation
Pregnancy

Limited data with atropine injection use during pregnancy are insufficient to inform a drug associated risk of adverse developmental outcomes. Adequate animal development and reproduction studies have not been conducted with atropine. There are risks to the fetus and mother associated with untreated severe or life-threatening muscarinic effects; life-sustaining therapy for the pregnant woman should not be withheld due to potential concerns regarding the effects of atropine on the fetus. In a cohort study of 401 pregnancies in the first trimester and 797 pregnancies in the second or third trimester, atropine injection use was not associated with an increased risk of congenital malformation. In a surveillance study of 381 newborns exposed to atropine injection in the first trimester, 18 major birth defects were observed when 16 were expected. No specific pattern of major birth defects was identified. In another surveillance study of 50 pregnancies in the first trimester, atropine injection use was not associated with an increased risk of malformations. Atropine is systemically bioavailable after topical ocular administration. Use topical atropine ophthalmically during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Trace amounts of atropine have been reported in human breast milk after oral intake. There are no data on atropine concentrations in human milk after intravenous or ocular administration, the effects on the breast-fed infant, or the effects on milk production. The elimination half-life of atropine is more than doubled in children less than 2 years of age. To minimize potential infant exposure to atropine after injection, a breast-feeding woman may pump and discard her milk for 24 hours after use before resuming to breast-feed her infant. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for ocular atropine and any potential adverse effects on the breast-fed child from topical ophthalmic administration of atropine.