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  • atropine sulfate - Drug Summary

  • CLASSES

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

    DEA CLASS

    Rx

    DESCRIPTION

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

    COMMON BRAND NAMES

    Atropine Care, Atropisol, Isopto Atropine, Ocu-Tropine

    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: 0.05mg, 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, 0.5mL, 1mL, 1mg
    Atropine/Atropine Sulfate Subcutaneous Inj Sol: 0.05mg, 0.1mg, 0.4mg, 0.5mL, 1mL, 1mg

    DOSAGE & 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.[60267] 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.

    Neonates, 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 (1 to 5 mL for neonates and 5 mL or more for infants, children, and adolescents) and follow with 5 ventilations. Do not interrupt CPR to administer drug therapy.

    For pre-operative 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 organophosphate insecticide toxicity).
    NOTE: Start atropine as soon as symptoms of toxicity occur. A survey of accidental auto-injections of atropine in children found that even relatively large doses (up to 0.175 mg/kg) were not associated with mortality or life-threatening complications (i.e., seizures, arrhythmias). In 48% of children (116/240), systemic atropine effects were noted, with 8% experiencing severe atropinization. Severity of atropinization was dose-related in a non-linear fashion.
    Intravenous, Intramuscular, or Intraosseous† dosage (using parenteral solution; NOT autoinjector)

    Adults

    Administer 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.

    Neonates, 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.

    Intramuscular dosage (AtroPen auto-injector only)
    Adults, Adolescents, Children, Infants, and Neonates

    Dosage is based on weight and symptoms: weight less than 7 kg, give 0.25 mg/dose IM; weight 7 to 18 kg, give 0.5 mg/dose IM; weight 18.1 to 41 kg, give 1 mg/dose IM; weight greater than 41 kg, give 2 mg/dose IM. Give 1 dose if poisoning is suspected and 2 or more mild symptoms appear (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 more doses in rapid succession 10 minutes after the first if any severe symptoms appear (confusion, severe breathing difficulties, severe lung secretions, severe muscle twitching and general weakness, involuntary urination and defecation, seizures, unconsciousness). Also give 3 doses in rapid succession to a patient found unconscious and suspected of being exposed to the poison. Administer as soon as symptoms of poisoning occur (usually tearing, excess saliva, wheezing, twitching). Anticonvulsants and pralidoxime may also need to be administered concurrently.

    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
    Adults

    1 drop of 1% solution instilled in eye 1 hour prior to procedure or 0.3 to 0.5 cm of 1% ointment placed in conjunctival sac up to 3 times daily.

    Infants 3 months and older, Children, and Adolescents

    Give 1 drop topically in the eye(s) as required or apply a small amount of the ointment in the conjunctival sac 1 to 2 times/day; take care to avoid overdosage. Typical dosage is 1 eye drop instilled 3 times/day for 3 days before the procedure in pediatric patients. In one study for cycloplegic refraction in strabismic children, 1 drop 3 times daily for 3 days prior 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.

    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 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 the treatment of moderate amblyopia†.
    Ophthalmic Dosage
    Children

    1 drop of 1% solution instilled in the unaffected eye once daily results in 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 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.

    †Indicates off-label use

    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.

    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.

    ADMINISTRATION

    Oral Administration

    Administer 30 minutes before meals.

    Injectable Administration

    Administer intramuscularly, intravenously, subcutaneously, or intraosseously. The auto-injector Atropen, for use only in nerve agent and insecticide poisoning, is exclusively for intramuscular (IM) use.
    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Direct intravenous (IV) injection:
    May be given 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. 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

    Atropen intramuscular (IM) auto-injection:
    Only to be administered by persons with adequate training in the recognition and treatment of nerve agent or insecticide intoxication.
    Snap the grooved end of the plastic sleeve down and over the yellow safety cap. Remove the Atropen from the plastic sleeve.
    Firmly grasp the Atropen with the green tip pointed downward. Pull off the yellow safety cap with the other hand.
    The auto-injector should be injected at rotating sites around the mid-lateral thigh.
    Aim and firmly jab the green tip straight down (90 degree angle) against the outer thigh. The device will activate and deliver the atropine. Bunch up and hold the thigh to provide a thicker injection area in children or very thin adults. Hold the auto-injector in place for 10 seconds before removing from thigh. Once the auto-injection has been removed from the thigh, massage the injection site for several seconds. The auto-injector may be injected through clothing, but be sure any pockets at the injection site are empty. After injection the needle should be visible; if not, be sure the yellow cap is removed and repeat the steps for injection, but press harder against the thigh.
    After use, using a hard surface, bend the needle back against the Atropen. Either pin the used Atropen to the victim's clothing, or show the used Atropen to the first medical personnel that is encountered. This will allow other medical personnel to see the number and dose of Atropen auto-injectors administered. Move the victim away from the contaminated area immediately. Try to locate additional medical help at this point.
    Intense flushing of the face and trunk may occur 15 to 20 minutes following IM injection. This is called the 'atropine flush' and is not harmful when it occurs.
    Intramuscular (IM) injection:
    Inject into a large muscle mass. Aspirate prior to injection to avoid injection into a blood vessel. Intense flushing of the face and trunk may occur 15 to 20 minutes following IM injection. This is called the 'atropine flush' and is not harmful when it occurs.

    Subcutaneous Administration

    Inject subcutaneously taking care not to inject intradermally.

    Other Injectable Administration

    Intraosseous infusion:
    NOTE: Atropine is not approved by the FDA for intraosseous administration.
    During cardiopulmonary resuscitation, the same dosage may be given via the intraosseous 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 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.
    Endotracheal (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.
    Endotracheal (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.
    Children: After dose administration, flush the ET tube with a minimum of 5 mL 0.9% Sodium Chloride injection and follow with 5 ventilations.

    STORAGE

    Generic:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused product within 24 hours of opening bottle
    - Store between 68 to 77 degrees F
    Atreza:
    - Store at room temperature (between 59 to 86 degrees F)
    Atropine Care :
    - Store between 36 to 77 degrees F
    Atropisol :
    - Store between 36 to 77 degrees F
    Isopto Atropine:
    - Store between 36 to 77 degrees F
    Ocu-Tropine:
    - Store at room temperature (between 59 to 86 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Atropine should not be used in patients with known atropine or other belladonna alkaloids hypersensitivity because they may develop an allergic or other adverse reaction, including anaphylaxis. NOTE: Intense flushing of the face (blush area) and trunk may occur following parenteral injection of atropine. This is called the 'atropine flush' and is not harmful when it occurs.
     
    Parenteral atropine products may contain sodium metabisulfite. These formulations should be used with caution in patients with known sulfite hypersensitivity in which sulfites may precipitate an allergic reaction.
     
    The primary protection against exposure to chemical nerve agents and insecticide poisoning is a protective garment including a mask designed for this use. Do not rely solely on the availability of antidotes such as atropine (i.e., AtroPen) and pralidoxime to provide complete protection from chemical nerve agent and insecticide poisoning. Immediate evacuation from the contaminated site is essential. Medical help should be sought. Decontamination of the poisoned individual should occur as quickly as possible. Clothing should be removed and the hair and skin washed thoroughly with sodium bicarbonate or alcohol. Provide symptomatic support as needed (i.e., respiration, bronchial secretion suction).

    Driving or operating machinery

    Because of the potential for toxicity, systemic atropine should not be taken in amounts above prescription limits. Because atropine may cause blurred vision, drowsiness, or dizziness, patients should use caution when driving or operating machinery until they are aware of the effects of the drug.

    Acute myocardial infarction, angina, bleeding, cardiac arrhythmias, cardiac disease, coronary artery disease, heart failure, hypertension, hyperthyroidism, mitral stenosis, myocardial infarction, tachycardia, thyrotoxicosis

    Use atropine with caution in patients with known cardiac disease or a recent myocardial infarction. Atropine may alter the heart rate; the predominant clinical effect is tachycardia. The increase in heart rate caused by atropine increases the oxygen demand on the heart and can exacerbate myocardial ischemia. Use atropine with caution in patients with cardiac arrhythmias, congestive heart failure, coronary artery disease, angina, or other cardiac instability where an increase in heart rate could be detrimental. Increased heart rate is undesirable in patients with hyperthyroidism (thyrotoxicosis) or cardiovascular instability in acute hemorrhage (bleeding). To minimize tachycardia, restrict the total dose of atropine to 2 to 3 mg (maximum 0.03 to 0.04 mg/kg). Use atropine with caution during acute myocardial infarction because the drug can potentiate arrhythmias. Use antimuscarinics with caution in patients with mitral stenosis since tachycardia could exacerbate the clinical symptoms of this condition and in patients with hypertension since they have some actions on the heart that can exacerbate this condition.

    Heart transplant

    Do not use atropine to treat sinus bradycardia in patients who have undergone heart transplant without evidence for autonomic reinnervation. Atropine is ineffective for treatment of post heart transplant sinus node dysfunction because of denervation.[45649] [63867] A small uncontrolled study documented paradoxical slowing of the heart rate and high-degree AV block when atropine was administered after cardiac transplantation.[45649]

    Asthma, chronic lung disease (CLD), chronic obstructive pulmonary disease (COPD), respiratory infection

    Atropine should be used cautiously in patients with chronic lung disease (CLD). The use of atropine can dry and thicken bronchial secretions in the respiratory tract, thereby aggravating respiratory infection, or asthma or chronic obstructive pulmonary disease (COPD) in some patients. However, depending on the dosage and route of administration, antimuscarinics may have beneficial effect in some patients with pulmonary disease. Atropine is considered a potent bronchodilator.

    Hepatic disease

    Atropine is extensively metabolized in the liver. Those with hepatic disease may be at increased risk for developing increased drug concentrations, with resultant side effects. Use systemic formulations with caution.

    Bladder obstruction, prostatic hypertrophy, renal failure, renal impairment, urinary retention, urinary tract obstruction

    Antimuscarinics, including atropine, should be used with caution in patients with renal impairment or renal failure. Metabolites and unchanged drug are excreted in the kidneys. Additionally, the antimuscarinic actions of atropine may cause urinary retention and should be avoided in patients with prostatic hypertrophy, bladder obstruction, or urinary tract obstruction.

    Autonomic neuropathy, myasthenia gravis

    Atropine should be avoided in patients with myasthenia gravis, because the anticholinergic competes with the small amount of acetylcholine that has potential to act in the bodies of these patients. However, atropine may be administered if it is used to reduce the adverse muscarinic effects of a cholinesterase inhibitor. Atropine should similarly be used with extreme caution in patients with autonomic neuropathy.

    Achalasia, colostomy, diarrhea, esophagitis, gastroesophageal reflux disease (GERD), GI disease, GI obstruction, hiatal hernia, ileostomy, ileus, peptic ulcer disease, pseudomembranous colitis, pyloric stenosis, toxic megacolon, ulcerative colitis

    Atropine should be administered with caution to patients with GI disease, including those with partial organic pyloric stenosis or GI obstruction (e.g., achalasia, etc.) as the drugs antimuscarinic effects may further decrease GI motility and cause paralytic ileus. Likewise, antimuscarinic use should be avoided in patients with ulcerative colitis, ileus, and intestinal atony because they decrease GI motility and can exacerbate these conditions. Toxic megacolon may also be precipitated or aggravated. Use extreme caution in persons with suspected or known GI infection such as infectious diarrhea (e.g., pseudomembranous colitis) because atropine can decrease GI motility and may decrease elimination of the bacteria or toxin from the body and thus prolong the infection. Also, atropine should be used with caution in patients with diarrhea that may be an early sign of incomplete GI obstruction, especially in patients with ileostomy or colostomy. This drug should be used cautiously in patients with gastroesophageal reflux disease (GERD) or hiatal hernia associated with reflux esophagitis. Atropine may decrease gastric motility and relax the lower esophageal sphincter, promoting gastric retention and reflux. Although antimuscarinics have been used as adjunct treatment of peptic ulcer disease, there are no conclusive data that the drug aids in healing, decreases rate of recurrence, or prevents the complications of peptic ulcer. In patients with gastric ulcer, antimuscarinics may delay gastric emptying and promote antral stasis.

    Closed-angle glaucoma, contact lenses, glaucoma, increased intraocular pressure, synechia

    Avoid use of atropine in patients with closed-angle glaucoma as the drug, administered either systemically or ophthalmically, can increase intraocular pressure by inducing cycloplegia and mydriasis. Atropine should be avoided in patients with synechia (iris adhesion to the cornea or the capsule of the crystalline lens) or increased intraocular pressure. The anticholinergic effect of atropine may also make the eyes dry; this can cause an increased lens awareness, or blurred vision for wearers of contact lenses. The use of lubricating drops may be necessary, or in severe cases discontinued use of contact lenses while taking this drug.

    Ambient temperature increase, dehydration, fever, strenuous exercise

    Atropine can suppress sweat gland activity causing increases in body temperature. Antimuscarinics should be prescribed cautiously for patients who experience conditions that would elevate core body temperature (e.g., strenuous exercise, ambient temperature increase, fever, or dehydration). It is recommended that patients avoid excessive exposure to heat.

    Children, infants, neonates

    Special care and close monitoring may be necessary when administering atropine and related antimuscarinic drugs to children and adolescents. Neonates, infants, and young children are especially sensitive to the anticholinergic effects. Intoxication has been observed even upon conjunctival instillation in some circumstances. The AtroPen auto-injector for use in the treatment of nerve agent or organophosphate insecticide toxicity is approved for use in children weighing >= 6.8 kg (dose is weight-specific). In children < 6.8 kg, a dose is not available with the auto-injector; individualize atropine doses at 0.05 mg/kg IM or IV. In a survey of children accidentally exposed to higher doses of atropine (up to 0.175 mg/kg), it was reported that serious adverse events were few, primarily consisting of tachycardia.

    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.

    Breast-feeding

    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.

    Dental disease

    Atropine may aggravate dental disease with chronic use because the anticholinergic effects may decrease salivary flow.

    Anticholinergic medications, geriatric

    Systemic forms of atropine should be used with caution in geriatric patients. The elderly are more likely to have medical conditions aggravated by the use of this drug, or to experience paradoxical CNS stimulation or anticholinergic effects from antimuscarinics. The anticholinergic effects of atropine may be significant and are additive with other anticholinergic medications. According to the Beers Criteria, anti-spasmodics such as oral or parenteral atropine are considered potentially inappropriate medications (PIMs) in geriatric patients and should be avoided due to high anticholinergic activity and uncertain effectiveness. The Beers expert panel also recommends avoiding drugs with strong anticholinergic properties, including oral or parenteral atropine, in geriatric patients with the following disease states or symptoms due to the potential for exacerbation of the condition or increased risk of adverse effects: dementia/cognitive impairment (adverse CNS effects), delirium/high risk of delirium (possible new-onset or worsening delirium), or lower urinary tract symptoms/benign prostatic hyperplasia in men (possible urinary retention or hesitancy). The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). According to the OBRA guidelines, medications with anticholinergic properties, such as atropine, may cause mental status changes, constipation, drowsiness, dizziness, dryness of mucus membranes, blurred vision, urinary retention, or other adverse effects that are common and problematic, especially in older individuals. The use of multiple medications with anticholinergic properties may be particularly problematic because of cumulative effects.

    ADVERSE REACTIONS

    Severe

    laryngospasm / Rapid / Incidence not known
    ileus / Delayed / Incidence not known
    asystole / Rapid / Incidence not known
    bradycardia / Rapid / 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
    anaphylactic shock / Rapid / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    seizures / Delayed / Incidence not known
    coma / Early / Incidence not known

    Moderate

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

    Mild

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

    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; Butalbital; Caffeine; Codeine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when codeine is used concomitantly with an anticholinergic drug. The concomitant use of codeine and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when dihydrocodeine is used concomitantly with an anticholinergic drug. The concomitant use of dihydrocodeine and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect. (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (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) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect. (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Acetaminophen; Codeine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when codeine is used concomitantly with an anticholinergic drug. The concomitant use of codeine 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; Dextromethorphan; Doxylamine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect.
    Acetaminophen; Dextromethorphan; Phenylephrine: (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect. (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Acetaminophen; 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; Diphenhydramine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Acetaminophen; Guaifenesin; Phenylephrine: (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect.
    Acetaminophen; Hydrocodone: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when hydrocodone is used concomitantly with an anticholinergic drug. The concomitant use of hydrocodone 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; Oxycodone: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when oxycodone is used concomitantly with an anticholinergic drug. The concomitant use of oxycodone 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; 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 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; 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; Tramadol: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when tramadol is used concomitantly with an anticholinergic drug. The concomitant use of tramadol 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.
    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 manufaturer, 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. (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Albuterol; Ipratropium: (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.
    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.
    Ambenonium Chloride: (Severe) Routine administration of atropine with ambenonium chloride is contraindicated. Belladonna derivatives, such as atropine, may suppress the parasympathomimetic symptoms of excessive gastrointestinal stimulation. This leaves only the more serious symptoms (fasciculation and paralysis of voluntary muscles) as signs of overdosage.
    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; Butalbital; Caffeine; Codeine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when codeine is used concomitantly with an anticholinergic drug. The concomitant use of codeine 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.
    Aspirin, ASA; 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.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when codeine is used concomitantly with an anticholinergic drug. The concomitant use of codeine 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.
    Aspirin, ASA; Oxycodone: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when oxycodone is used concomitantly with an anticholinergic drug. The concomitant use of oxycodone 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.
    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.
    Atropine; Diphenoxylate: (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.
    Atropine; Edrophonium: (Major) Coadministration of Atropine and Edrophonium Chloride can produce mutually antagonistic effects.
    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: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Brompheniramine; Carbetapentane; Phenylephrine: (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect. (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including anticholinergics. (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Brompheniramine; Dextromethorphan; Guaifenesin: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Brompheniramine; Guaifenesin; Hydrocodone: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when hydrocodone is used concomitantly with an anticholinergic drug. The concomitant use of hydrocodone 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. (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (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 patients for signs of urinary retention or reduced gastric motility when hydrocodone is used concomitantly with an anticholinergic drug. The concomitant use of hydrocodone 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. (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Brompheniramine; Pseudoephedrine: (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) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Buprenorphine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when buprenorphine is used concomitantly with an anticholinergic drug. The concomitant use of buprenorphine 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.
    Buprenorphine; Naloxone: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when buprenorphine is used concomitantly with an anticholinergic drug. The concomitant use of buprenorphine 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.
    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.
    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: (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.
    Calcium Carbonate; 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. (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.
    Calcium Carbonate; Risedronate: (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.
    Calcium Carbonate; Simethicone: (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.
    Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and atropine. CNS depressants can potentiate the effects of cannabidiol.
    Carbetapentane; Chlorpheniramine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including anticholinergics. (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Carbetapentane; Chlorpheniramine; Phenylephrine: (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect. (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including anticholinergics. (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect. (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including anticholinergics. (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Carbetapentane; Guaifenesin: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including anticholinergics.
    Carbetapentane; Guaifenesin; Phenylephrine: (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect. (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including anticholinergics.
    Carbetapentane; Phenylephrine: (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect. (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including anticholinergics.
    Carbetapentane; Phenylephrine; Pyrilamine: (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect. (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including anticholinergics. (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Carbetapentane; Pseudoephedrine: (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) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including anticholinergics.
    Carbetapentane; Pyrilamine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including anticholinergics. (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Carbidopa; Levodopa: (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.
    Carbinoxamine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (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) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Carbinoxamine; Hydrocodone; Phenylephrine: (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 hydrocodone is used concomitantly with an anticholinergic drug. The concomitant use of hydrocodone 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. (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (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 patients for signs of urinary retention or reduced gastric motility when hydrocodone is used concomitantly with an anticholinergic drug. The concomitant use of hydrocodone 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. (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Carbinoxamine; Phenylephrine: (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect. (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Carbinoxamine; Pseudoephedrine: (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) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Cetirizine: (Moderate) Dry mouth and drowsiness were more common in patients receiving cetirizine/levocetirizine vs. placebo, and caution may be necessary during concomitant use of cetirizine/levocetirizine with the antimuscarinics.
    Cetirizine; Pseudoephedrine: (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) Dry mouth and drowsiness were more common in patients receiving cetirizine/levocetirizine vs. placebo, and caution may be necessary during concomitant use of cetirizine/levocetirizine with the antimuscarinics.
    Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (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) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Chlophedianol; Guaifenesin; Phenylephrine: (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect.
    Chlorcyclizine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Chlorpheniramine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Chlorpheniramine; Codeine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when codeine is used concomitantly with an anticholinergic drug. The concomitant use of codeine 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. (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Chlorpheniramine; Dextromethorphan: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect. (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (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. (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (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 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. (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (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 patients for signs of urinary retention or reduced gastric motility when hydrocodone is used concomitantly with an anticholinergic drug. The concomitant use of hydrocodone 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. (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Chlorpheniramine; Hydrocodone: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when hydrocodone is used concomitantly with an anticholinergic drug. The concomitant use of hydrocodone 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. (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (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 hydrocodone is used concomitantly with an anticholinergic drug. The concomitant use of hydrocodone 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. (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (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 patients for signs of urinary retention or reduced gastric motility when hydrocodone is used concomitantly with an anticholinergic drug. The concomitant use of hydrocodone 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. (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Chlorpheniramine; Phenylephrine: (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect. (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Chlorpheniramine; Pseudoephedrine: (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) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Chlorpromazine: (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.
    Clemastine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Clozapine: (Moderate) The anticholinergic effects of atropine may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including clozapine.
    Codeine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when codeine is used concomitantly with an anticholinergic drug. The concomitant use of codeine 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.
    Codeine; Guaifenesin: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when codeine is used concomitantly with an anticholinergic drug. The concomitant use of codeine 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.
    Codeine; Phenylephrine; Promethazine: (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect. (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including promethazine. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other additive CNS effects may also occur. (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when codeine is used concomitantly with an anticholinergic drug. The concomitant use of codeine 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.
    Codeine; Promethazine: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including promethazine. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other additive CNS effects may also occur. (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when codeine is used concomitantly with an anticholinergic drug. The concomitant use of codeine 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.
    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.
    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.
    Cyclizine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Cyclobenzaprine: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like cyclobenzaprine are used concomitantly with other anticholinergics. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur, depending on the interacting agent.
    Cyproheptadine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    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.
    Dexchlorpheniramine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (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) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect. (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Dextromethorphan; 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; Promethazine: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including promethazine. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other additive CNS effects may also occur.
    Dextromethorphan; Quinidine: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
    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.
    Dihydrocodeine; 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. (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.
    Dimenhydrinate: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Diphenhydramine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Diphenhydramine; Hydrocodone; Phenylephrine: (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 hydrocodone is used concomitantly with an anticholinergic drug. The concomitant use of hydrocodone 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. (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Diphenhydramine; Ibuprofen: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Diphenhydramine; Naproxen: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Diphenhydramine; Phenylephrine: (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect. (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Disopyramide: (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.
    Doxylamine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Doxylamine; Pyridoxine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Dronabinol: (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.
    Edrophonium: (Major) Coadministration of Atropine and Edrophonium Chloride can produce mutually antagonistic effects.
    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: (Major) Atropine can potentiate the pressor effects of ephedra alkaloids. Atropine is thought to block the compensatory reflex sinus bradycardia normally seen after the administration of ephedrine, the primary alkaloid found in ephedra, ma huang and consequently can increase pressor response.
    Erythromycin: (Moderate) Anticholinergics can antagonize the stimulatory effects of erythromycin on the GI tract (when erythromycin is used therapeutically for improving GI motility). Avoid chronic administration of antimuscarinics along with prokinetic agents under most circumstances. In addition, erythromycin is a CYP3A4 inhibitor and can reduce the metabolism of drugs metabolized by CYP3A4, including some anticholinergics.
    Erythromycin; Sulfisoxazole: (Moderate) Anticholinergics can antagonize the stimulatory effects of erythromycin on the GI tract (when erythromycin is used therapeutically for improving GI motility). Avoid chronic administration of antimuscarinics along with prokinetic agents under most circumstances. In addition, erythromycin is a CYP3A4 inhibitor and can reduce the metabolism of drugs metabolized by CYP3A4, including some anticholinergics.
    Ezogabine: (Moderate) Caution is advisable during concurrent use of ezogabine and medications that may affect voiding such as anticholinergic agents. Ezogabine has caused urinary retention requiring catheterization in some cases. The anticholinergic effects of antimuscariinic and anticholinergic medications on the urinary tract may be additive. Additive sedation or other CNS effects may also occur.
    Fentanyl: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when fentanyl is used concomitantly with an anticholinergic drug. The concomitant use of fentanyl 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.
    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.
    Fluoxetine; Olanzapine: (Moderate) The anticholinergic effects of atropine may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including olanzapine. 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.
    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.
    Food: (Major) Avoid administering marijuana and atropine together as concurrent use may result in adverse cardiovascular effects, such as tachycardia and cardiac arrhythmias. Marijuana is known to produce significant increases in heart rate and cardiac output lasting for 2-3 hours. Further, rare case reports of myocardial infarction and cardiac arrhythmias have been associated with marijuana use. Atropine has also been reported to produce a wide range of cardiovascular effects including asystole, atrial fibrillation, premature ventricular contractions (PVCs), ventricular fibrillation, palpitations, and sinus tachycardia. Coadministration of marijuana with atropine may result in significant cardiovascular adverse events and thus, should be avoided.
    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: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when hydrocodone is used concomitantly with an anticholinergic drug. The concomitant use of hydrocodone 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.
    Guaifenesin; 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. (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when hydrocodone is used concomitantly with an anticholinergic drug. The concomitant use of hydrocodone 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.
    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: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when hydrocodone is used concomitantly with an anticholinergic drug. The concomitant use of hydrocodone 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.
    Hydrocodone: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when hydrocodone is used concomitantly with an anticholinergic drug. The concomitant use of hydrocodone 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.
    Hydrocodone; Ibuprofen: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when hydrocodone is used concomitantly with an anticholinergic drug. The concomitant use of hydrocodone 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.
    Hydrocodone; 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 hydrocodone is used concomitantly with an anticholinergic drug. The concomitant use of hydrocodone 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.
    Hydrocodone; Potassium Guaiacolsulfonate: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when hydrocodone is used concomitantly with an anticholinergic drug. The concomitant use of hydrocodone 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.
    Hydrocodone; Potassium Guaiacolsulfonate; 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 patients for signs of urinary retention or reduced gastric motility when hydrocodone is used concomitantly with an anticholinergic drug. The concomitant use of hydrocodone 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.
    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. (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when hydrocodone is used concomitantly with an anticholinergic drug. The concomitant use of hydrocodone 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.
    Hydromorphone: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when hydromorphone is used concomitantly with an anticholinergic drug. The concomitant use of hydromorphone and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Hydroxyzine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Ibuprofen; Oxycodone: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when oxycodone is used concomitantly with an anticholinergic drug. The concomitant use of oxycodone 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.
    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.
    Itraconazole: (Moderate) Antimuscarinics can raise intragastric pH. This effect may decrease the oral bioavailability of itraconazole; antimuscarinics should be used cautiously in patients receiving itraconazole.
    Levocetirizine: (Moderate) Dry mouth and drowsiness were more common in patients receiving cetirizine/levocetirizine vs. placebo, and caution may be necessary during concomitant use of cetirizine/levocetirizine with the antimuscarinics.
    Levodopa: (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, such as linaclotide. The clinical significance of these potential interactions is uncertain.
    Lofexidine: (Moderate) Monitor for excessive hypotension and sedation during coadministration of lofexidine and atropine. Lofexidine can potentiate the effects of CNS depressants.
    Loperamide: (Moderate) Loperamide decreases GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. Systemic atropine, an anticholinergic, may produce additive GI and CNS effects with loperamide if used concomitantly. Atropine is commonly added in small amounts to atropine; diphenoxylate 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.
    Loperamide; Simethicone: (Moderate) Loperamide decreases GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. Systemic atropine, an anticholinergic, may produce additive GI and CNS effects with loperamide if used concomitantly. Atropine is commonly added in small amounts to atropine; diphenoxylate 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.
    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.
    Lubiprostone: (Moderate) Antimuscarinic drugs can promote constipation and pharmacodynamically oppose the action of drugs used for the treatment of constipation, such as lubiprostone. The clinical significance of these potential interactions is uncertain.
    Lurasidone: (Moderate) Antipsychotic agents may disrupt core temperature regulation; therefore, caution is recommended during concurrent use of lurasidone and medications with anticholinergic activity such as antimuscarinics. Concurrent use of lurasidone and medications with anticholinergic activity may contribute to heat-related disorders. Monitor patients for heat intolerance, decreased sweating, or increased body temperature if lurasidone is used with antimuscarinics.
    Macimorelin: (Major) Avoid use of macimorelin with drugs that may blunt the growth hormone response to macimorelin, such as antimuscarinic anticholinergic agents. Healthcare providers are advised to discontinue anticholinergics at least 1 week before administering macimorelin. Use of these medications together may impact the accuracy of the macimorelin growth hormone test.
    Magnesium Hydroxide: (Moderate) Antacids may inhibit the oral absorption of anticholinergics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    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.
    Meclizine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Memantine: (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.
    Meperidine; Promethazine: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including promethazine. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other additive CNS effects may also occur. (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) Mirtazapine exhibits weak anticholinergic activity that is not expected to be clinically significant. However, the anticholinergic effects may be additive to the antimuscarinics. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation.
    Molindone: (Moderate) Antipsychotics are associated with anticholinergic effects; therefore, additive effects may be seen during concurrent use of molindone and other drugs having anticholinergic activity such as antimuscarinics. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other CNS effects may also occur.
    Morphine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when morphine is used concomitantly with an anticholinergic drug. The concomitant use of morphine 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.
    Morphine; Naltrexone: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when morphine is used concomitantly with an anticholinergic drug. The concomitant use of morphine 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.
    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.
    Nitrofurantoin: (Moderate) Antimuscarinics can delay gastric emptying, possibly increasing the bioavailability of nitrofurantoin.
    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) The anticholinergic effects of atropine may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including olanzapine. 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.
    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: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when oxycodone is used concomitantly with an anticholinergic drug. The concomitant use of oxycodone 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.
    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.
    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 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.
    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 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.
    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) Use caution if carbonic anhydrase inhibitors are administered with anticholinergics and monitor for excessive anticholinergic adverse effects. The use of topiramate with agents that may increase the risk for heat-related disorders, such as anticholinergics, may lead to oligohidrosis, hyperthermia and/or heat stroke.
    Phenylephrine: (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect.
    Phenylephrine; Promethazine: (Major) Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect. (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including promethazine. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other additive CNS effects may also occur.
    Physostigmine: (Major) Coadministration of atropine and physostigmine may produce a mutually antagonistic effect.
    Potassium: (Major) Drugs that decrease GI motility may increase the risk of GI irritation from sustained-release solid oral dosage forms of potassium salts. The use of solid oral dosage forms of potassium chloride is contraindicated in patients taking glycopyrrolate oral solution. In one study, healthy subjects were examined for GI irritation following the administration of oral potassium for at least 7 days. Glycopyrrolate was coadministered to some subjects in order to study the additional effects of delayed gastric emptying. Results indicated that subjects administered wax-matrix tablets had the highest incidence of erosions (43%) and ulcers (11%). Evidence of GI irritation was less frequent among subjects receiving liquid (0%) and microencapsulated (10.5% erosions, 1.2% ulcers) formulations. Therefore, if oral potassium supplementation is necessary in a patient taking antimuscarinics, a liquid formulation should be considered. If a solid formulation is being prescribed, the patient should be counseled on strategies that can be used to avoid GI irritation such as taking potassium products only while seated or standing, remaining upright for 10 minutes after each dose, and ingesting each dose with plenty of fluids.
    Pramlintide: (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.
    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) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including promethazine. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other additive CNS effects may also occur.
    Proton pump inhibitors: (Moderate) The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.
    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.
    Pyridostigmine: (Major) Coadministration of atropine and pyridostigmine bromide may produce a mutually antagonistic effect.
    Quetiapine: (Moderate) When administering systemic anticholinergics and quetiapine together, monitor for additive anticholinergic effects such as constipation, blurred vision, urinary retention, xerostomia, and tachycardia. Constipation is a commonly reported adverse effect of quetiapine and anticholinergic agents. Constipation in some cases may lead to ileus. Intestinal obstruction has been reported with quetiapine, including fatal cases in patients who were receiving multiple concomitant medications that decrease intestinal motility. Anticholinergic effects observed during therapeutic use of quetiapine are thought to be associated with norquetiapine, the active metabolite of quetiapine which has demonstrated a moderate to strong in vitro affinity for several muscarinic receptor subtypes.
    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.
    Ritodrine: (Moderate) Ritodrine induced systemic hypertension may be exagerrated in the presence of parasympatholytic agents like atropine.
    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) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Sincalide: (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.
    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.
    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.
    Tacrine: (Moderate) The therapeutic benefits of tacrine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
    Tapentadol: (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.
    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.
    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: (Moderate) Although tiotropium is minimally absorbed into the systemic circulation after inhalation, tiotropium may have additive anticholinergic effects when administered with other antimuscarinics. Per the manufacturer, avoid concomitant administration of tiotropium with other anticholinergic medications when possible.
    Tiotropium; Olodaterol: (Moderate) Although tiotropium is minimally absorbed into the systemic circulation after inhalation, tiotropium may have additive anticholinergic effects when administered with other antimuscarinics. Per the manufacturer, avoid concomitant administration of tiotropium with other anticholinergic medications when possible.
    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) Use caution if carbonic anhydrase inhibitors are administered with anticholinergics and monitor for excessive anticholinergic adverse effects. The use of topiramate with agents that may increase the risk for heat-related disorders, such as anticholinergics, may lead to oligohidrosis, hyperthermia and/or heat stroke.
    Tramadol: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when tramadol is used concomitantly with an anticholinergic drug. The concomitant use of tramadol 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.
    Tricyclic antidepressants: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when tricyclic antidepressants (TCAs) are used concomitantly with other anticholinergics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive CNS effects are also possible when many of these drugs are combined with tricyclic antidepressants.
    Trifluoperazine: (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.
    Triprolidine: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Trospium: (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.
    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.

    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.

    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/or 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.
     
    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 the placenta. It is metabolized in the liver to several metabolites including tropic acid. The initial half-life of atropine is about 2 to 3 hours, and the terminal half-life is about 12.5 hours. Atropine and metabolites are primarily excreted renally and, to a lesser extent, by the pulmonary and fecal routes.

    Oral Route

    Atropine is well absorbed after oral administration. Peak plasma concentrations are seen within 1 hour after oral administration.

    Intramuscular Route

    Atropine is well absorbed after intramuscular administration. Peak plasma concentrations are seen within 30 minutes following IM administration.

    Inhalation Route

    Atropine is well absorbed after oral inhalation. Following oral inhalation, peak plasma concentrations are reached in 1.5 to 4 hours.

    Other Route(s)

    Atropine is well absorbed after endotracheal administration.