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  • CLASSES

    Anticholinergic Gastrointestinal Antispasmodics
    Respiratory Long-Acting Muscarinic Antagonists (LAMA)

    DEA CLASS

    Rx

    DESCRIPTION

    Parenteral, oral, and inhalational antimuscarinic anticholinergic; less CNS penetration than atropine or scopolamine
    Used parenterally to reduce GI secretions perioperatively; commonly used orally to reduce severe drooling in patients with certain neurologic conditions
    Long-acting muscarinic antagonist (LAMA) when used by inhalation and used in adults for the maintenance treatment of COPD

    COMMON BRAND NAMES

    Cuvposa, Dartisla, Glycate, GLYRX-PF, Lonhala Magnair, Robinul, Robinul Forte, Seebri Neohaler

    HOW SUPPLIED

    Cuvposa/Glycopyrrolate Oral Sol: 1mg, 5mL
    Dartisla Oral Tab Orally Dis: 1.7mg
    Glycate/Glycopyrrolate/Robinul/Robinul Forte Oral Tab: 1mg, 1.5mg, 2mg
    Glycopyrrolate/GLYRX-PF/Robinul Intramuscular Inj Sol: 0.2mg, 1mL
    Glycopyrrolate/GLYRX-PF/Robinul Intravenous Inj Sol: 0.2mg, 1mL
    Lonhala Magnair Respiratory (Inhalation) Sol: 1mL, 25mcg

    DOSAGE & INDICATIONS

    For use as a preoperative antimuscarinic to reduce salivary, tracheobronchial, and pharyngeal secretions; reduce gastric acid production and acidity (aspiration prophylaxis); and to block vagal inhibitory reflexes during intubation and induction of anesthesia.
    Intramuscular dosage
    Adults

    4 mcg/kg IM 30 to 60 minutes prior to induction or at the same time preanesthetic narcotics and/or sedation are given.

    Children and Adolescents 2 to 17 years

    4 mcg/kg IM 30 to 60 minutes prior to induction or at the same time preanesthetic narcotics and/or sedation are given.

    Infants and Children 1 month to 1 year

     4 to 9 mcg/kg IM 30 to 60 minutes prior to induction or at the same time preanesthetic narcotics and/or sedation are given.

    For the treatment of sialorrhea.
    For severe chronic sialorrhea (chronic drooling) associated with neurologic conditions such as cerebral palsy in pediatric patients.
    Oral dosage (oral solution)

    NOTE: Cuvposa has been designated an orphan drug by the FDA for this indication. 

    Children and Adolescents 3 to 16 years

    Initially, 0.02 mg/kg/dose PO 3 times daily; titrate in 0.02 mg/kg/dose increments every 5 to 7 days based on therapeutic response and adverse effects. Do not exceed 0.1 mg/kg/dose PO 3 times daily or the following maximum doses by weight: weight 13 to 17 kg: Max: 1.5 mg/dose; weight 18 to 22 kg: Max: 2 mg/dose; weight 23 to 27 kg: Max: 2.5 mg/dose; weight 28 kg or more: Max: 3 mg/dose.

    Oral dosage (oral tablet)†
    Children and Adolescents weighing 30 kg or more

    Glycopyrrolate has been used for the treatment of drooling in children and adolescents with neuropsychiatric disorders for many years. A variety of weight-based dose regimens have been employed. One double-blind, placebo-controlled, prospective trial of glycopyrrolate in children ages 4 to 19 years (n = 39) with neurodevelopmental conditions and severe sialorrhea used the following dose in children weighing 30 kg or more: initially, 1.2 mg/dose PO, and titrated weekly to 1.8 mg/dose, 2.4 mg/dose, and 3 mg/dose or the highest tolerated dose in this range. Doses were given 2 or 3 times per day. The mean highest tolerated dose was 0.11 mg/kg PO (range: 0.04 to 0.2 mg/kg PO). Caregivers scored drooling with a modified Teacher's Drooling Scale (mTDS) score of 1 (never drools) to 9 (clothing, hands, and objects frequently become wet). Titration could be halted for side effects; 27 children completed the study. Mean baseline drooling scores significantly improved with glycopyrrolate vs. placebo (p < 0.001). Twenty-five children improved their mean drooling score, defined as a reduction of 4 points or more. Adverse effects increased with dose, and 81% of children experienced side effects at highest titration. Adverse effects were seen more frequently in younger children than in older children (difference not statistically significant). Eight patients (21%) withdrew from the study due to side effects such as behavioral changes (irritability and hyperactivity), constipation, diarrhea, excessive oral dryness, thick secretions, urinary retention, dehydration, drowsiness, dizziness, dilated pupils, blurred vision, headache, nasal congestion, facial flushing, rash, urinary tract infection, and fever. Another study of pediatric patients with cerebral palsy and other developmental disabilities (n = 40) reported glycopyrrolate was effective in 90% of patients; the final effective dose range was 0.01 to 0.82 mg/kg/day PO. Side effects resulted in discontinuation of treatment in 28% of patients.

    Children weighing less than 30 kg

    Glycopyrrolate has been used for the treatment of drooling in children and adolescents with neuropsychiatric disorders for many years. A variety of weight-based dose regimens have been employed. One double-blind, placebo-controlled, prospective trial of glycopyrrolate in children ages 4 to 19 years (n = 39) with neurodevelopmental conditions and severe sialorrhea used the following dose in children weighing less than 30 kg: initially, 0.6 mg/dose PO, and titrated weekly to 1.2 mg/dose, 1.8 mg/dose, and 2.4 mg/dose or the highest tolerated dose in this range. Doses were given 2 or 3 times per day. The mean highest tolerated dose was 0.11 mg/kg PO (range: 0.04 to 0.2 mg/kg PO). Caregivers scored drooling with a modified Teacher's Drooling Scale (mTDS) score of 1 (never drools) to 9 (clothing, hands, and objects frequently become wet). Titration could be halted for side effects; 27 children completed the study. Mean baseline drooling scores significantly improved with glycopyrrolate vs. placebo (p < 0.001). Twenty-five children improved their mean drooling score, defined as a reduction of 4 points or more. Adverse effects increased with dose, and 81% of children experienced side effects at highest titration. Adverse effects were seen more frequently in younger children than in older children (difference not statistically significant). Eight patients (21%) withdrew from the study due to side effects such as behavioral changes (irritability and hyperactivity), constipation, diarrhea, excessive oral dryness, thick secretions, urinary retention, dehydration, drowsiness, dizziness, dilated pupils, blurred vision, headache, nasal congestion, facial flushing, rash, urinary tract infection, and fever. Another study of pediatric patients with cerebral palsy and other developmental disabilities (n = 40) reported glycopyrrolate was effective in 90% of patients; the final effective dose range was 0.01 to 0.82 mg/kg/day PO. Side effects resulted in discontinuation of treatment in 28% of patients.

    For clozapine-induced sialorrhea† in adults.
    Oral dosage
    Adults

    1 mg PO twice daily was found effective based on changes from baseline in the Drooling Rating Scale scores in 1 small, randomized, double-blind crossover trial. Glycopyrrolate was superior to biperiden, the comparator drug, in both efficacy and impact on cognition as assessed by changes in the Mini Mental State Examination (MMSE) scores. A dose of 1 mg PO twice daily was effective in improving the Drooling Severity Frequency Scale (DSFS) scores in 3 case reports. In a fourth case in the series, the dose was initiated at 1 mg PO twice daily and titrated up to 1 mg PO 4 times daily with minimal response; a final dose of 2 mg PO 3 times daily was prescribed.

    For the treatment of cardiac arrhythmias (e.g., bradycardia) that occur intraoperatively and are drug-induced or are associated with visceral traction stimulation of vagal reflexes.
    Intravenous dosage
    Adults

    100 mcg IV, repeated at 2 to 3 minute intervals as necessary.

    Infants, Children, and Adolescents 1 month and older

     4 mcg/kg IV (maximum single dose is 100 mcg), repeated at 2 to 3 minute intervals. If glycopyrrolate is given pre-operatively, intraoperative doses are rarely needed.

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

    200 mcg IV for every 1 mg of neostigmine or every 5 mg of pyridostigmine administered. Administer glycopyrrolate simultaneously with the cholinesterase inhibitor.

    Infants, Children, and Adolescents 1 month to 17 years

     200 mcg IV for every 1 mg of neostigmine or every 5 mg of pyridostigmine administered. Administer glycopyrrolate simultaneously with the cholinesterase inhibitor.

    For the reduction of symptoms of a peptic ulcer as an adjunct to treatment of gastric ulcer.
    Oral dosage (oral tablet)
    Adults

    1 to 2 mg PO 2 to 3 times per day. Use the lowest effective dose to attain clinical goals. LIMITATION OF USE: Glycopyrrolate is not indicated as monotherapy for treatment of peptic ulcer because effectiveness in peptic ulcer healing has not been established.

    Children and Adolescents 12 years and older

    1 to 2 mg PO 2 to 3 times per day. Use the lowest effective dose to attain clinical goals. LIMITATION OF USE: Glycopyrrolate is not indicated as monotherapy for treatment of peptic ulcer because effectiveness in peptic ulcer healing has not been established.

    Oral dosage (orally disintegrating tablet; i.e., Dartisla ODT)
    Adults

    1.7 mg PO 2 to 3 times daily. Max: 6.8 mg/day. Use the lowest effective dosage to control symptoms. The ODT is not recommended for patients who can take or are taking a lower dosage strength of glycopyrrolate (e.g., 1 mg tablet). Patients receiving a 2 mg oral tablet may be switched to the 1.7 mg glycopyrrolate ODT. LIMITATION OF USE: Glycopyrrolate ODT is not indicated as monotherapy for treatment of peptic ulcer because effectiveness in peptic ulcer healing has not been established.

    Intramuscular and Intravenous dosage
    Adults

    100 to 200 mcg IM or IV, may repeat at 4 hour intervals if needed. LIMITATION OF USE: Glycopyrrolate is not indicated as monotherapy for treatment of peptic ulcer because effectiveness in peptic ulcer healing has not been established.

    Adolescents 16 years and older

    100 to 200 mcg IM or IV, may repeat at 4 hour intervals if needed. LIMITATION OF USE: Glycopyrrolate is not indicated as monotherapy for treatment of peptic ulcer because effectiveness in peptic ulcer healing has not been established.

    For the maintenance treatment of chronic obstructive pulmonary disease (COPD) (e.g., chronic bronchitis or emphysema).
    Oral Inhalation dosage (inhalation powder; i.e., Seebri Neohaler)
    Adults

    Oral inhalation of the contents of 1 capsule (15.6 mcg glycopyrrolate) twice daily in the morning and the evening, at approximately the same times daily, is the recommended and max dosage. Not indicated for the relief of acute bronchospasm. Use an inhaled short-acting beta-2 agonist (SABA) for immediate relief of acute symptoms. Do not use other long-acting muscarinic antagonists (LAMAs) concurrently. According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, glycopyrrolate may be used as initial monotherapy in all groups of COPD patients; however, combination therapy with a long-acting beta-agonist (LABA) or inhaled corticosteroid (ICS) may be needed in patients in Group D or in those patients still experiencing dyspnea or exacerbations upon follow-up.

    Nebulizer Inhalation dosage (solution for nebulization; i.e., Lonhala Magnair)
    Adults

    25 mcg (1 vial) via nebulizer twice daily in the morning and the evening, at approximately the same times daily, is the recommended and max dosage. More frequent administration or a greater number of inhalations is not recommended. Not indicated for the relief of acute bronchospasm. Use an inhaled short-acting beta-2 agonist (SABA) for immediate relief of acute symptoms. Do not use other long-acting muscarinic antagonists (LAMAs) concurrently.[62673] According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, glycopyrrolate may be used as initial monotherapy in all groups of COPD patients; however, combination therapy with a long-acting beta-agonist (LABA) or inhaled corticosteroid (ICS) may be needed in patients in Group D or in those patients still experiencing dyspnea or exacerbations upon follow-up.[63765]

    For the treatment of irritable bowel syndrome† and/or diarrhea†.
    Oral dosage

    NOTE: Due to the potential for side effects, as well as the availability of more effective alternatives, glycopyrrolate is rarely used for this indication.

    Adults

    1—2 mg PO 2—3 times per day.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    0.004 mg/kg IM preanesthesia; 0.2 mg/dose IV; 6 mg/day PO for oral tablets and 6.8 mg/day PO for orally disintegrating tablets; 2 capsules/day (total of 31.2 mcg) via oral inhalation (Seebri Neohaler) or 2 vials/day (total of 50 mcg) via oral inhalation (Longhala Magnair).

    Geriatric

    0.004 mg/kg IM preanesthesia; 0.2 mg/dose IV; 6 mg/day PO for oral tablets and 6.8 mg/day PO for orally disintegrating tablets; 2 capsules/day (total of 31.2 mcg) via oral inhalation (Seebri Neohaler) or 2 vials/day (total of 50 mcg) via oral inhalation (Longhala Magnair).

    Adolescents

    17 years and older: Safety and efficacy of inhaled glycopyrrolate not established; maximum dosage is dependent on indication for parenteral therapy; 6 mg/day PO for oral tablets.
    16 years: Safety and efficacy of inhaled glycopyrrolate not established; maximum dosage is dependent on indication for parenteral therapy; 0.1 mg/kg/dose PO 3 times daily, not to exceed 1.5 to 3 mg/dose PO depending on weight for oral solution.
    13 to 15 years: Safety and efficacy of parenteral and inhaled glycopyrrolate have not been established; 0.1 mg/kg/dose PO 3 times daily, not to exceed 1.5 to 3 mg/dose PO depending on weight for oral solution.

    Children

    12 years: Safety and efficacy of parenteral and inhaled glycopyrrolate have not been established; 6 mg/day PO for oral tablets; 0.1 mg/kg/dose PO 3 times daily, not to exceed 1.5 to 3 mg/dose PO depending on weight for oral solution.
    3 to 11 years: Safety and efficacy of parenteral and inhaled glycopyrrolate have not been established; 0.1 mg/kg/dose PO 3 times daily, not to exceed 1.5 to 3 mg/dose PO depending on weight for oral solution.
    Less than 3 years: Safety and efficacy have not been established.

    Infants

    Safety and efficacy have not been established.

    Neonates

    Not indicated.

    DOSING CONSIDERATIONS

    Hepatic Impairment

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

    Renal Impairment

    Mild to moderate renal impairment (estimated GFR 30 mL/minute/1.73 m2 or more): No dosage adjustments are required.
    Severe renal impairment (estimated GFR less than 30 mL/minute/1.73 m2) or end stage renal disease (ESRD) requiring dialysis: Dose adjustments may be needed for systemic therapy; however, no specific recommendations are available. Use parenteral glycopyrrolate with caution. Use inhaled glycopyrrolate only if the expected benefits outweigh the potential risks; systemic exposure to glycopyrrolate may be increased in this population.

    ADMINISTRATION

    Oral Administration

    Oral Tablet
    Do not administer within 1 hour of antacids or antidiarrheal medications.

    Oral Solid Formulations

    Oral tablet
    Administer on an empty stomach, 1 hour before or 2 hours after meals to maximize absorption.
     
    Orally disintegrating tablet (e.g., Dartisla ODT)
    Administer at least 1 hour before or 2 hours after food.
    Use dry hands when opening the blister card and do not open the blister until ready to administer.
    Open the package and peel back the foil on the blister to expose the tablet and gently remove from the blister. Do not push the tablet through the foil.
    Do not break or cut the tablet.
    Immediately place the tablet on the tongue, allow it to disintegrate, and swallow without water.

    Oral Liquid Formulations

    Administer at least 1 hour before or 2 hours after meals to maximize absorption.
    Carefully measure the dose using a calibrated dosing cup or oral syringe. To facilitate administration, give each dose using an oral syringe.

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
    The closure system for some glycopyrrolate injectable products contains dry natural rubber that may cause hypersensitivity reactions when handled by or when the product is injected in persons with known or possible latex sensitivity.

    Intravenous Administration

    Direct IV injection:
    No dilution necessary.
    Inject via Y-site or through a 3-way stopcock at a rate of 0.2 mg over 1 to 2 minutes.
    Compatible with Dextrose 5% and 10% in Water injection or with Dextrose 5%/Sodium Chloride 0.9% injection, Dextrose 5%/Sodium Chloride 0.45% injection, Sodium Chloride 0.9% injection, and Ringer’s injection.
    NOT compatible with Lactated Ringer's injection.

    Intramuscular Administration

    No dilution necessary.
    Inject into a large muscle mass. Aspirate prior to injection to avoid injection into a blood vessel.

    Inhalation Administration
    Oral Inhalation Administration

    Dry powder inhalation (Seebri Neohaler)
    For oral inhalation only. Instruct patients NOT to swallow the capsules.
    Only use the supplied Neohaler device to administer Seebri capsules.
    Use dry hands to remove a capsule from the blister card. Tear along the perforation to separate one of the blisters from the blister card; do NOT push the capsule through the foil to remove it from the blister. Immediately place it into the inhaler's capsule chamber; do not place the capsule directly into the mouthpiece. Click the inhaler closed.
    Hold the inhaler upright with the mouthpiece pointing up and press both piercing buttons together firmly at the same time; a click will be heard. Do not press the piercing buttons more than 1 time.
    Have the patient breathe out fully away from the inhaler, then place the inhaler in the mouth with lips closed around the mouthpiece and the piercing buttons positioned to the left and right (not up and down).
    The patient should breathe deeply and steadily in through the inhaler. Do not press the piercing buttons during inhalation. There may be a sweet flavor during inhalation and a whirring sound should be heard; if no sound is heard, check the chamber as the capsule may be stuck. Gently tap the base of the device to loosen the capsule if necessary. Do not press the piercing buttons to loosen the capsule.
    After inhalation, the patient should hold their breath at least 5 to 10 seconds or as long as comfortable while removing the inhaler from their mouth.
    Open the inhaler to see if any powder is left in the capsule; repeat inhalation steps until no powder remains. Most patients can empty the capsule in 1 or 2 inhalations.
    Advise patients that coughing after administration is not problematic; as long as the capsule is empty the full dose has been administered.
    Occasionally, very small pieces of the capsule get past the screen and enter the mouth. Inhalation or ingestion of these pieces is harmless. Piercing the capsule more than once increases risk of shattering capsule.
    After administration of the entire dose, open the inhaler and discard the empty capsule by tipping it out.
    To avoid the spread of infection, do not share the inhaler device.
    Cleaning the inhaler is not necessary. If cleaning is desirable, wipe the mouthpiece inside and out with a clean, dry, lint-free cloth or clean, dry soft brush. Keep the inhaler dry and do not take it apart.
    Storage: Capsules should be stored in their blister card until use. Do not store capsules in the Neohaler device. Store all components of the pack in a dry place, away from light and moisture.
    Use a new inhaler with each new medication pack.
     
    Nebulizer inhalation solution (Lonhala Magnair)
    For oral inhalation via nebulizer only.
    Only use the supplied Magnair nebulization system. Before using glycopyrrolate inhalation solution for the first time, review the manufacturer’s instructions for use that come with the system to ensure the Magnair nebulizer system is working properly.
    Clean the handset according to the product instructions before initial use.
    Open the foil pouch enough to remove the 2 glycopyrrolate vials and separate them. Discard any vial if the solution is not colorless. Keep 1 vial out for the dose. Return 1 vial to the opened foil pouch and store in the carrying bag to be used at the next treatment.
    Insert 1 vial into the bottom of the medication cap until it clicks. Be sure not touch the part of the handset body that pierces the vial.
    Make sure the aerosol head is installed before attaching the medication cap because the medicine could leak and the patient will not get their full treatment. Place the medication cap with vial on the top of the handset body.
    To attach the medication cap to the handset body, turn the medication cap in a clockwise direction, until a click is heard. The notch in the medication cap (at the base of the opening) should line up with the blue line on the handset body.
    The patient should insert the mouthpiece into their mouth. Do not tilt the handset, loosen or remove the medication cap, or unclasp the handset body until the treatment is complete because the patient will not get their full treatment.
    Press the on/off button to turn on the controller.
    The patient should inhale and exhale normally through the mouthpiece for about 2 to 3 minutes until a beeping sound is heard indicating that the treatment is complete. The controller will automatically shut off.
    To avoid the spread of infection, do not share the inhaler device.
    Following treatment, check all parts of the nebulizer to ensure that they are clean and not damaged. See the manufacturer’s instructions for cleaning the system; make sure to clean the handset after every use.
    Storage: Vials should be stored in the protective foil pouch between 20 and 25 degrees C (68 and 77 degrees F) until use. Discard any unused vial in an open foil pouch if not used within 7 days. Store all components of the pack in a dry place, away from light and moisture.
    Throw away the old handset parts after using 60 vials of glycopyrrolate inhalation solution and use the replacement handset parts in the refill kit with the next 60 vials.

    STORAGE

    Cuvposa:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Dartisla:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Glycate:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    GLYRX-PF:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Lonhala Magnair:
    - After removing from pouch, protect from light and use product within one week
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Discard unused product 7 days after first opening the pouch
    - Store at controlled room temperature (between 68 and 77 degrees F)
    - Store in original unopened pouch
    Robinul:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Robinul Forte:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Seebri Neohaler:
    - Protect from moisture
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    - Store in a dry place

    CONTRAINDICATIONS / PRECAUTIONS

    Benzyl alcohol hypersensitivity, milk protein hypersensitivity

    The use of glycopyrrolate is contraindicated in any patient with a known or suspected hypersensitivity to glycopyrrolate or any of the inactive ingredients. Use inhaled glycopyrrolate (Seebri Neohaler) with caution in patients with a severe milk protein hypersensitivity, as the dry powder contains lactose. Discontinue the inhaler immediately and institute alternative therapy if reaction occurs. Immediate hypersensitivity reactions have been reported after administration of inhaled glycopyrrolate. If signs suggesting allergic reactions occur, particularly angioedema, urticaria, or skin rash, therapy should be discontinued immediately and alternative therapy instituted. Patients with benzyl alcohol hypersensitivity should avoid parenteral glycopyrrolate.

    Latex hypersensitivity

    The closure system of some glycopyrrolate injections contains dry natural rubber that may cause hypersensitivity reactions when handled by or when the product is injected in persons with known or possible latex hypersensitivity.

    Ambient temperature increase

    The anticholinergic effects of glycopyrrolate may be significant. Older adult patients may be more affected by anticholinergic effects such as decreased sweating. Heat prostration due to decreased sweating may occur. Patients receiving glycopyrrolate should be cautioned about exposure to hot or humid environments (ambient temperature increase), or heat prostration due to vigorous physical exercise because of the risk of heat stroke.

    Closed-angle glaucoma, ocular exposure

    Oral and parenteral glycopyrrolate is contraindicated in patients with closed-angle glaucoma due to its ability to cause mydriasis and possibly increase intraocular pressure. All anticholinergics may increase intraocular pressure and aqueous outflow resistance in patients with closed-angle glaucoma. Use inhaled glycopyrrolate with caution in patients with narrow-angle glaucoma and avoid inadvertent ocular exposure. Educate patients on the signs and symptoms of acute narrow-angle glaucoma (e.g., eye pain or discomfort, blurred vision, visual halos or colored images in association with red eyes from conjunctival congestion and corneal edema). Instruct patients to seek immediate medical attention if such symptoms occur.

    Prostatic hypertrophy, urinary retention, urinary tract obstruction

    Parenteral, oral, and inhaled glycopyrrolate can exacerbate urinary retention in patients with known urinary tract obstruction (e.g., bladder neck obstruction, such as might occur with hypertrophy of the prostate). Parenteral and oral glycopyrrolate products are contraindicated in these patients. Use inhaled, oral, or parenteral glycopyrrolate with caution in patients with predisposition for urinary retention, particularly those with prostatic hypertrophy since anticholinergic drugs may aggravate these conditions. Instruct patients to seek immediate medical attention if signs and symptoms of urinary retention (e.g., difficulty passing urine, painful urination) occur.

    Autonomic neuropathy, myasthenia gravis

    Although glycopyrrolate is considered an antimuscarinic anticholinergic, it also possesses significant action at nicotinic receptors. Glycopyrrolate is contraindicated in patients with myasthenia gravis, although glycopyrrolate's antagonism at the neuromuscular junction usually is seen only with toxic doses. Glycopyrrolate should be used cautiously in patients with autonomic neuropathy.

    Achalasia, biliary-GI fistula, constipation, diarrhea, esophagitis, gastroesophageal reflux disease (GERD), GI bleeding, GI obstruction, hemorrhagic shock, hiatal hernia, ileus, pyloric stenosis, toxic megacolon, ulcerative colitis

    Glycopyrrolate decreases GI motility and is contraindicated in GI obstruction (such as achalasia, biliary-GI fistula and pyloroduodenal or pyloric stenosis), toxic megacolon, severe ulcerative colitis, intestinal atony of the elderly or debilitated patient, unstable cardiovascular status in acute hemorrhagic shock, or GI bleeding, or paralytic ileus. Glycopyrrolate should be used cautiously in patients with gastroesophageal reflux disease (GERD) or hiatal hernia associated with reflux esophagitis. Antimuscarinics decrease gastric motility and relax the lower esophageal sphincter. These effects promote gastric retention and aggravate reflux in these patients. The use of anticholinergic drugs in the treatment of gastric ulcer may produce a delay in gastric emptying due to antral statis. Diarrhea may be an early symptom of incomplete intestinal obstruction, especially in patients with ileostomy or colostomy. In this instance treatment with glycopyrrolate injection would be inappropriate and possibly harmful. Constipation is a common dose-limiting adverse reaction that sometimes leads to discontinuation. Assess patients for constipation, particularly within 4 to 5 days of initial dosing or after a dose increase. Intestinal pseudo-obstruction has been reported and may present as abdominal distention, pain, nausea, or vomiting.

    Hepatic disease, renal failure, renal impairment

    Use with caution in patients with renal impairment since the renal elimination of systemic doses of glycopyrrolate may be severely impaired in patients with significant renal impairment or renal failure. Dosage adjustments for systemic therapy may be necessary. In one study glycopyrrolate was administered IV in uremic patients undergoing renal transplantation. The mean elimination half-life was significantly longer (46.8 minutes) than in healthy patients (18.6 minutes). The mean AUC, plasma clearance, and 3-hour urine excretion for glycopyrrolate were also significantly different than those of controls. These results suggest that the elimination of glycopyrrolate is severely impaired in patients with renal failure. Systemic forms of glycopyrrolate should also be used with caution in patients with hepatic disease, as a general precaution. No specific dose adjustments are needed for patients using inhaled glycopyrrolate, but caution is recommended in those with renal impairment.

    Cardiac arrhythmias, coronary artery disease, heart failure, hypertension, hyperthyroidism, tachycardia, ventricular tachycardia

    Glycopyrrolate can block the actions of acetylcholine on the heart, resulting in tachycardia. It should be used cautiously in patients with hyperthyroidism, coronary artery disease, congestive heart failure, hypertension, or cardiac arrhythmias (tachycardia, ventricular tachycardia) because the drug could worsen these conditions.

    Pregnancy

    There are no adequate and well-controlled studies in pregnant women; glycopyrrolate should only be used during pregnancy if the expected benefit to the patient outweighs the potential risk to the fetus. Animal studies have not shown evidence of teratogenic effects; however, use with caution in pregnancy since animal data are not always predictive of human response. Women should contact their physician if they become pregnant while taking glycopyrrolate. Concentrations of glycopyrrolate in umbilical venous and arterial blood and in the amniotic fluid are low after intramuscular administration to parturients. Therefore, glycopyrrolate does not appear to penetrate through the placental barrier in significant amounts. The effect of inhaled glycopyrrolate on labor and delivery is unknown. It should be used during labor and delivery only if the potential benefit to the patient justifies the potential risk to the fetus.

    Breast-feeding

    There are no data on the presence of glycopyrrolate or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. However, glycopyrrolate and its metabolites were detected in the milk of lactating rats. Drugs with anticholinergic properties, such as glycopyrrolate, may suppress lactation, particularly when lactation is starting to be established. However, single doses may be unlikely to cause concern; the quaternary ammonium structure of glycopyrrolate makes it unlikely that a single maternal dose (inhaled, oral, or injection) would result in oral intake by a nursing infant from breast milk that would result in significant concentrations. However, caution must be exercised in chronic administration of glycopyrrolate to a breast-feeding woman, since many drugs are excreted in human milk and there are no data regarding effect on the nursing infant. Inhaled glycopyrrolate (including its metabolites) have been detected in the milk of lactating rats and reached up to 10-fold higher concentrations in the milk than in the blood of the dam. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition.

    Children, Down's syndrome, infants, neonates

    Glycopyrrolate has been evaluated for chronic severe drooling in patients aged 3 to 16 years with neurologic conditions associated with problem drooling and has been used in the surgical setting; it has not been sytematically studied in infants or children less than 3 years of age. Safety and efficacy of glycopyrrolate inhalation products have not been established in pediatric patients under 18 years of age. Dysrhythmias associated with the use of glycopyrrolate intravenously as a premedicant or during anesthesia have been observed in pediatric patients. Infants, patients with Down's syndrome, and pediatric patients with spastic paralysis or brain damage may experience an increased response to anticholinergics, thus increasing the potential for side effects. A paradoxical reaction characterized by hyperexcitability may occur in pediatric patients taking large doses of any systemic anticholinergic. Infants and young children are especially susceptible to the toxic effects of anticholinergics. Benzyl alcohol, a component glycopyrrolate injection, has been associated with serious adverse events and death, particularly in neonates. The "gasping syndrome," (characterized by central nervous system depression, metabolic acidosis, gasping respirations, gradual neurologic deterioration, potential for seizures, and high levels of benzyl alcohol and its metabolites found in the blood and urine) has been associated with benzyl alcohol dosages above 99 mg/kg/day in neonates and low-birth-weight neonates.

    Driving or operating machinery

    Glycopyrrolate may cause blurred vision. Drowsiness may also occur, particularly if combined with other CNS depressants. If blurred vision or drowsiness occur, patients should be warned to avoid driving or operating machinery until the full effects of the medication have dissipated.

    Acute bronchospasm

    Inhaled glycopyrrolate is not indicated for the relief of acute bronchospasm. It is crucial to properly educate patients and prescribe an inhaled, short-acting beta agonist (SABA), such as albuterol, for symptomatic relief of acute respiratory symptoms. Inform patients that increasing SABA use is a signal of deteriorating pulmonary disease for which prompt medical attention is warranted. Do not initiate glycopyrrolate in patients with acutely deteriorating or potentially life-threatening episodes of chronic obstructive pulmonary disease (COPD). COPD may deteriorate acutely over a period of hours or chronically over several days or longer. If symptoms of bronchospasm worsen or if SABA use becomes less effective or more frequent, patients should be instructed to seek immediate medical attention so the COPD treatment regimen can be re-evaluated.

    Paradoxical bronchospasm

    Like other inhaled medications, glycopyrrolate can produce paradoxical bronchospasm, which may be life-threatening. If paradoxical bronchospasm occurs, treat immediately with an inhaled short-acting bronchodilator, discontinue glycopyrrolate immediately, and institute alternative therapy.

    Anticholinergic medications, dementia, geriatric

    Use glycopyrrolate with caution in geriatric patients. Geriatric patients should be monitored carefully due to an increased susceptibility to anticholinergic effects of the drug versus younger adults. The effects of other anticholinergic medications are additive to the effects of glycopyrrolate, and should be considered in prescribing for all patients, especially the older adult. According to the Beers Criteria, systemic anticholinergic medications should be avoided in geriatric patients with the following due to the potential for symptom exacerbation or 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).

    Infertility

    Whether glycopyrrolate can have an effect on male fertility is not known. In reproduction studies in rats, administration of glycopyrrolate resulted in diminished rates of conception (infertility) in a dose-related manner. Other studies in dogs suggest that this may be due to diminished seminal secretion which is evident at high doses of glycopyrrolate.

    ADVERSE REACTIONS

    Severe

    seizures / Delayed / 0-2.0
    atrial fibrillation / Early / 0-1.0
    bronchospasm / Rapid / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    angioedema / Rapid / Incidence not known
    GI obstruction / Delayed / Incidence not known
    arrhythmia exacerbation / Early / Incidence not known
    cardiac arrest / Early / Incidence not known
    ventricular tachycardia / Early / Incidence not known
    bradycardia / Rapid / Incidence not known
    ocular hypertension / Delayed / Incidence not known

    Moderate

    urinary retention / Early / 0-15.0
    dyspnea / Early / 2.0-4.9
    nystagmus / Delayed / 0-2.0
    wheezing / Rapid / 1.0-1.9
    peripheral edema / Delayed / 1.0-1.9
    dysuria / Early / 0-1.0
    hyperglycemia / Delayed / 0-1.0
    constipation / Delayed / 10.0
    hypertension / Early / 2.0
    edema / Delayed / 2.0
    anhidrosis / Delayed / Incidence not known
    confusion / Early / Incidence not known
    impotence (erectile dysfunction) / Delayed / Incidence not known
    lactation suppression / Early / Incidence not known
    chest pain (unspecified) / Early / Incidence not known
    hypotension / Rapid / Incidence not known
    QT prolongation / Rapid / Incidence not known
    palpitations / Early / Incidence not known
    sinus tachycardia / Rapid / Incidence not known
    blurred vision / Early / Incidence not known
    cycloplegia / Early / Incidence not known

    Mild

    nausea / Early / 1.0-10.0
    vomiting / Early / 1.0-10.0
    sinusitis / Delayed / 1.4-10.0
    infection / Delayed / 3.4-10.0
    pharyngitis / Delayed / 1.0-2.1
    xerosis / Delayed / 0-2.0
    pruritus / Rapid / 0-2.0
    rash / Early / 0-2.0
    insomnia / Early / 0-2.0
    restlessness / Early / 0-2.0
    emotional lability / Early / 0-2.0
    agitation / Early / 0-2.0
    abdominal pain / Early / 0-2.0
    flatulence / Early / 0-2.0
    dysgeusia / Early / 0-2.0
    pallor / Early / 0-2.0
    nasal congestion / Early / 0-2.0
    nasal dryness / Early / 0-2.0
    fatigue / Early / 1.0-1.9
    headache / Early / 10.0
    flushing / Rapid / 10.0
    xerostomia / Early / 10.0
    diarrhea / Early / 2.0
    cough / Delayed / 2.0
    back pain / Delayed / 2.0
    urticaria / Rapid / Incidence not known
    injection site reaction / Rapid / Incidence not known
    dizziness / Early / Incidence not known
    drowsiness / Early / Incidence not known
    weakness / Early / Incidence not known
    mydriasis / Early / Incidence not known

    DRUG INTERACTIONS

    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: (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: (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: (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: (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 : (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: (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; 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; 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; Pamabrom; Pyrilamine: (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; 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.
    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.
    Aclidinium; Formoterol: (Moderate) Although aclidinium is minimally absorbed into the systemic circulation after inhalation, there is the potential for aclidinium to have additive anticholinergic effects when administered with other anticholinergics or antimuscarinics.Per the manufaturer, avoid concomitant administration of aclidinium with other anticholinergic medications, when possible.
    Acrivastine; Pseudoephedrine: (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.
    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.
    Alogliptin; Metformin: (Moderate) Coadministration of glycopyrrolate with metformin my increase metformin plasma concentrations, which may lead to increased metformin effects and possible adverse events. If coadministration is necessary, monitor clinical response to metformin and adjust metformin dose accordingly.
    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) Additive anticholinergic effects may be seen when glycopyrrolate is used concomitantly with other drugs that possess antimuscarinic properties, such as amantadine.
    Ambenonium Chloride: (Minor) The muscarinic actions of ambenonium chloride can antagonize the antimuscarinic actions of glycopyrrolate.
    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; Caffeine; Orphenadrine: (Moderate) Additive anticholinergic effects may be seen when glycopyrrolate is used concomitantly with other drugs with moderate to significant anticholinergic effects including orphenadrine.
    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; Citric Acid; Sodium Bicarbonate: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    Aspirin, ASA; Oxycodone: (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.
    Atenolol: (Moderate) Atenolol bioavailability may increase with coadministration of glycopyrrolate. A reduction in the atenolol dose may be necessary.
    Atenolol; Chlorthalidone: (Moderate) Atenolol bioavailability may increase with coadministration of glycopyrrolate. A reduction in the atenolol dose may be necessary.
    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. The effects can be additive to antimuscarinic agents, such as glycopyrrolate. In some cases, constipation might occur, and effects on the CNS or bladder function may also be additive.
    Atropine; Edrophonium: (Minor) The muscarinic actions of edrophonium chloride can antagonize the antimuscarinic actions of glycopyrrolate.
    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: (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; Dextromethorphan; Phenylephrine: (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: (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; Phenylephrine: (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: (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; 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.
    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) Additive anticholinergic effects may be seen when glycopyrrolate is used concomitantly with bupropion. Additive drowsiness may occur. 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.
    Bupropion; Naltrexone: (Moderate) Additive anticholinergic effects may be seen when glycopyrrolate is used concomitantly with bupropion. Additive drowsiness may occur. 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.
    Butalbital; Acetaminophen; 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.
    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; Famotidine; Magnesium Hydroxide: (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 antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    Calcium Carbonate; Magnesium Hydroxide; 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.
    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.
    Calcium; Vitamin D: (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.
    Canagliflozin; Metformin: (Moderate) Coadministration of glycopyrrolate with metformin my increase metformin plasma concentrations, which may lead to increased metformin effects and possible adverse events. If coadministration is necessary, monitor clinical response to metformin and adjust metformin dose accordingly.
    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: (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: (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: (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: (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: (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: (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: (Moderate) Coadministration of glycopyrrolate with levodopa may decrease levodopa serum concentrations. If coadministration is necessary, monitor clinical response to levodopa and increase levodopa dose accordingly.
    Carbidopa; Levodopa; Entacapone: (Moderate) Coadministration of glycopyrrolate with levodopa may decrease levodopa serum concentrations. If coadministration is necessary, monitor clinical response to levodopa and increase levodopa dose accordingly.
    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: (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: (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: (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: (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: (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.
    Celecoxib; 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.
    Cetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with anticholinergics should generally be avoided. Coadministration may increase the risk of anticholinergic and CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive anticholinergic effects, sedation, and somnolence.
    Cetirizine; Pseudoephedrine: (Moderate) Concurrent use of cetirizine/levocetirizine with anticholinergics should generally be avoided. Coadministration may increase the risk of anticholinergic and CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive anticholinergic effects, sedation, and somnolence.
    Chlophedianol; Dexbrompheniramine: (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; Dexchlorpheniramine; Pseudoephedrine: (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.
    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: (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; Pseudoephedrine: (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: (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: (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: (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: (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: (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; Ibuprofen; Pseudoephedrine: (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: (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: (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) The use of drugs that decrease GI motility, such as glycopyrrolate, may pharmacodynamically oppose the effects of cisapride.
    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: (Major) Avoid co-prescribing clozapine with other anticholinergic medicines that can cause gastrointestinal hypomotility, due to a potential to increase serious constipation, ileus, and other potentially serious bowel conditions that may result in hospitalization. Clozapine exhibits potent anticholinergic effects. Additive anticholinergic effects may be seen when clozapine is used concomitantly with anticholinergic agents. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur, depending on the anticholinergic agent used.
    Codeine: (Moderate) Monitor 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; Guaifenesin; Pseudoephedrine: (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: (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.
    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. Monitor for effects such as constipation and urinary retention. 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.
    Dapagliflozin; Metformin: (Moderate) Coadministration of glycopyrrolate with metformin my increase metformin plasma concentrations, which may lead to increased metformin effects and possible adverse events. If coadministration is necessary, monitor clinical response to metformin and adjust metformin dose accordingly.
    Dasiglucagon: (Major) The concomitant use of intravenous glucagon and anticholinergics increases the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. Concomitant use is not recommended.
    Dexbrompheniramine: (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.
    Dexbrompheniramine; Pseudoephedrine: (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: (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: (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: (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; 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: (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: (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: (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.
    Diphenoxylate; Atropine: (Moderate) Diphenoxylate is a synthetic opiate derivative that appears to exert its effect locally and centrally on the smooth mucle cells of the GI tract to inhibit GI motility and slow excess GI propulsion. The effects can be additive to antimuscarinic agents, such as glycopyrrolate. In some cases, constipation might occur, and effects on the CNS or bladder function may also be additive.
    Disopyramide: (Moderate) In addition to its electrophysiologic effects, disopyramide exhibits clinically significant anticholinergic properties. These can be additive with other anticholinergics. Clinicians should be aware that urinary retention, particularly in males, and aggravation of glaucoma are realistic possibilities of using disopyramide with other anticholinergic agents.
    Donepezil: (Moderate) The therapeutic benefits of donepezil, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
    Donepezil; Memantine: (Moderate) The adverse effects of anticholinergics, such as dry mouth, urinary hesitancy or blurred vision may be enhanced with use of memantine; dosage adjustments of the anticholinergic drug may be required when memantine is coadministered. In addition, preliminary evidence indicates that chronic anticholinergic use in patients with Alzheimer's Disease may possibly have an adverse effect on cognitive function. Therefore, the effectiveness of drugs used in the treatment of Alzheimer's such as memantine, may be adversely affected by chronic antimuscarinic therapy. (Moderate) The therapeutic benefits of donepezil, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
    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: (Minor) The muscarinic actions of edrophonium chloride can antagonize the antimuscarinic actions of glycopyrrolate.
    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.
    Empagliflozin; Linagliptin; Metformin: (Moderate) Coadministration of glycopyrrolate with metformin my increase metformin plasma concentrations, which may lead to increased metformin effects and possible adverse events. If coadministration is necessary, monitor clinical response to metformin and adjust metformin dose accordingly.
    Empagliflozin; Metformin: (Moderate) Coadministration of glycopyrrolate with metformin my increase metformin plasma concentrations, which may lead to increased metformin effects and possible adverse events. If coadministration is necessary, monitor clinical response to metformin and adjust metformin dose accordingly.
    Ertugliflozin; Metformin: (Moderate) Coadministration of glycopyrrolate with metformin my increase metformin plasma concentrations, which may lead to increased metformin effects and possible adverse events. If coadministration is necessary, monitor clinical response to metformin and adjust metformin dose accordingly.
    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.
    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.
    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.
    Glipizide; Metformin: (Moderate) Coadministration of glycopyrrolate with metformin my increase metformin plasma concentrations, which may lead to increased metformin effects and possible adverse events. If coadministration is necessary, monitor clinical response to metformin and adjust metformin dose accordingly.
    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.
    Glyburide; Metformin: (Moderate) Coadministration of glycopyrrolate with metformin my increase metformin plasma concentrations, which may lead to increased metformin effects and possible adverse events. If coadministration is necessary, monitor clinical response to metformin and adjust metformin dose accordingly.
    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: (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.
    Haloperidol: (Moderate) Coadministration of glycopyrrolate with haloperidol may decrease haloperidol serum concentrations, which may lead to worsening of psychiatric symptoms and the development of tardive dyskinesia. If coadministration is necessary, closely monitor patient.
    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: (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: (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: (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.
    Ipratropium: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
    Ipratropium; Albuterol: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
    Itraconazole: (Moderate) Antimuscarinics can raise intragastric pH. This effect may decrease the oral bioavailability of itraconazole; antimuscarinics should be used cautiously in patients receiving itraconazole.
    Levocetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with anticholinergics should generally be avoided. Coadministration may increase the risk of anticholinergic and CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive anticholinergic effects, sedation, and somnolence.
    Levodopa: (Moderate) Coadministration of glycopyrrolate with levodopa may decrease levodopa serum concentrations. If coadministration is necessary, monitor clinical response to levodopa and increase levodopa dose accordingly.
    Levorphanol: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when levorphanol is used concomitantly with an anticholinergic drug. The concomitant use of levorphanol and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Linaclotide: (Moderate) Anticholinergics can promote constipation and pharmacodynamically oppose the action of drugs used for the treatment of constipation or constipation-associated irritable bowel syndrome, such as linaclotide.
    Linagliptin; Metformin: (Moderate) Coadministration of glycopyrrolate with metformin my increase metformin plasma concentrations, which may lead to increased metformin effects and possible adverse events. If coadministration is necessary, monitor clinical response to metformin and adjust metformin dose accordingly.
    Loperamide: (Moderate) Loperamide decreases GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. Other drugs that also decrease GI motility may produce additive effects with loperamide if used concomitantly. These include therapeutic doses of common systemic antimuscarinics (e.g., glycopyrrolate). Additive GI and CNS actions and may lead to undesirable side effects in some patients.
    Loperamide; Simethicone: (Moderate) Loperamide decreases GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. Other drugs that also decrease GI motility may produce additive effects with loperamide if used concomitantly. These include therapeutic doses of common systemic antimuscarinics (e.g., glycopyrrolate). Additive GI and CNS actions and may lead to undesirable side effects in some patients.
    Loxapine: (Moderate) Loxapine has anticholinergic activity. The concomitant use of loxapine and other anticholinergic drugs can increase the risk of anticholinergic adverse reactions including exacerbation of glaucoma, constipation, and urinary retention. Depending on the agent used, additive drowsiness/dizziness may also occur.
    Lubiprostone: (Moderate) Antimuscarinic drugs can promote constipation and pharmacodynamically oppose the action of drugs used for the treatment of constipation, such as lubiprostone. The clinical significance of these potential interactions is uncertain.
    Lurasidone: (Moderate) Antipsychotic agents may disrupt core temperature regulation; therefore, caution is recommended during concurrent use of lurasidone and medications with anticholinergic activity such as antimuscarinics. Concurrent use of lurasidone and medications with anticholinergic activity may contribute to heat-related disorders. Monitor patients for heat intolerance, decreased sweating, or increased body temperature if lurasidone is used with antimuscarinics.
    Macimorelin: (Major) Avoid use of macimorelin with drugs that may blunt the growth hormone response to macimorelin, such as antimuscarinic anticholinergic agents. Healthcare providers are advised to discontinue anticholinergics at least 1 week before administering macimorelin. Use of these medications together may impact the accuracy of the macimorelin growth hormone test.
    Magnesium Hydroxide: (Moderate) Antacids may inhibit the oral absorption of anticholinergics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    Maprotiline: (Moderate) Additive anticholinergic effects may be seen when glycopyrrolate is used concomitantly 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.
    Metformin: (Moderate) Coadministration of glycopyrrolate with metformin my increase metformin plasma concentrations, which may lead to increased metformin effects and possible adverse events. If coadministration is necessary, monitor clinical response to metformin and adjust metformin dose accordingly.
    Metformin; Repaglinide: (Moderate) Coadministration of glycopyrrolate with metformin my increase metformin plasma concentrations, which may lead to increased metformin effects and possible adverse events. If coadministration is necessary, monitor clinical response to metformin and adjust metformin dose accordingly.
    Metformin; Rosiglitazone: (Moderate) Coadministration of glycopyrrolate with metformin my increase metformin plasma concentrations, which may lead to increased metformin effects and possible adverse events. If coadministration is necessary, monitor clinical response to metformin and adjust metformin dose accordingly.
    Metformin; Saxagliptin: (Moderate) Coadministration of glycopyrrolate with metformin my increase metformin plasma concentrations, which may lead to increased metformin effects and possible adverse events. If coadministration is necessary, monitor clinical response to metformin and adjust metformin dose accordingly.
    Metformin; Sitagliptin: (Moderate) Coadministration of glycopyrrolate with metformin my increase metformin plasma concentrations, which may lead to increased metformin effects and possible adverse events. If coadministration is necessary, monitor clinical response to metformin and adjust metformin dose accordingly.
    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.
    Neostigmine: (Minor) The muscarinic actions of neostigmine can antagonize the antimuscarinic actions of glycopyrrolate.
    Nitrofurantoin: (Moderate) Antimuscarinics can delay gastric emptying, possibly increasing the bioavailability of nitrofurantoin.
    Olanzapine: (Moderate) Additive anticholinergic effects may be seen when olanzapine and anticholinergics are used concomitantly; use with caution. Use of olanzapine and other drugs with anticholinergic activity can increase the risk for severe gastrointestinal adverse reactions related to hypomotility. Olanzapine exhibits anticholinergic activity. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur, depending on the anticholinergic agent used.
    Olanzapine; Fluoxetine: (Moderate) Additive anticholinergic effects may be seen when olanzapine and anticholinergics are used concomitantly; use with caution. Use of olanzapine and other drugs with anticholinergic activity can increase the risk for severe gastrointestinal adverse reactions related to hypomotility. Olanzapine exhibits anticholinergic activity. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur, depending on the anticholinergic agent used.
    Olanzapine; Samidorphan: (Moderate) Additive anticholinergic effects may be seen when olanzapine and anticholinergics are used concomitantly; use with caution. Use of olanzapine and other drugs with anticholinergic activity can increase the risk for severe gastrointestinal adverse reactions related to hypomotility. Olanzapine exhibits anticholinergic activity. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur, depending on the anticholinergic agent used.
    Oliceridine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when oliceridine is used with glycopyrrolate. Use of anticholinergics may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
    Omeprazole; Sodium Bicarbonate: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    Orphenadrine: (Moderate) Additive anticholinergic effects may be seen when glycopyrrolate is used concomitantly with other drugs with moderate to significant anticholinergic effects including orphenadrine.
    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.
    Paroxetine: (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used concomitantly with anticholinergic agents. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur, depending on the specific anticholinergic used.
    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.
    Physostigmine: (Minor) The muscarinic actions of physostigmine can antagonize the antimuscarinic actions of glycopyrrolate.
    Pioglitazone; Metformin: (Moderate) Coadministration of glycopyrrolate with metformin my increase metformin plasma concentrations, which may lead to increased metformin effects and possible adverse events. If coadministration is necessary, monitor clinical response to metformin and adjust metformin dose accordingly.
    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.
    Promethazine; Dextromethorphan: (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.
    Promethazine; Phenylephrine: (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; 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.
    Pyridostigmine: (Minor) The muscarinic actions of pyridostigmine can antagonize the antimuscarinic actions of glycopyrrolate.
    Pyrilamine: (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.
    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.
    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.
    Tenapanor: (Moderate) Anticholinergics can promote constipation and pharmacodynamically oppose the action of drugs used for the treatment of constipation or constipation-associated irritable bowel syndrome, such as tenapanor.
    Thiazide diuretics: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
    Thioridazine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties like thioridazine are used concomitantly with anticholinergic agents. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur, depending on the interacting agent.
    Thiothixene: (Moderate) Anticholinergics may have additive effects with thiothixene, an antipsychotic with the potential for anticholinergic activity. Monitor for anticholinergic-related adverse effects such as xerostomia, blurred vision, constipation, and urinary retention during concurrent use.
    Tiotropium: (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.
    Tramadol; Acetaminophen: (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.
    Vibegron: (Moderate) Vibegron should be administered with caution in patients taking anticholinergics because of potential for an increased risk of urinary retention. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
    Zonisamide: (Moderate) Zonisamide use is associated with case reports of decreased sweating, hyperthermia, heat intolerance, or heat stroke and should be used with caution in combination with other drugs that may also predispose patients to heat-related disorders like anticholinergics.

    PREGNANCY AND LACTATION

    Pregnancy

    There are no adequate and well-controlled studies in pregnant women; glycopyrrolate should only be used during pregnancy if the expected benefit to the patient outweighs the potential risk to the fetus. Animal studies have not shown evidence of teratogenic effects; however, use with caution in pregnancy since animal data are not always predictive of human response. Women should contact their physician if they become pregnant while taking glycopyrrolate. Concentrations of glycopyrrolate in umbilical venous and arterial blood and in the amniotic fluid are low after intramuscular administration to parturients. Therefore, glycopyrrolate does not appear to penetrate through the placental barrier in significant amounts. The effect of inhaled glycopyrrolate on labor and delivery is unknown. It should be used during labor and delivery only if the potential benefit to the patient justifies the potential risk to the fetus.

    There are no data on the presence of glycopyrrolate or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. However, glycopyrrolate and its metabolites were detected in the milk of lactating rats. Drugs with anticholinergic properties, such as glycopyrrolate, may suppress lactation, particularly when lactation is starting to be established. However, single doses may be unlikely to cause concern; the quaternary ammonium structure of glycopyrrolate makes it unlikely that a single maternal dose (inhaled, oral, or injection) would result in oral intake by a nursing infant from breast milk that would result in significant concentrations. However, caution must be exercised in chronic administration of glycopyrrolate to a breast-feeding woman, since many drugs are excreted in human milk and there are no data regarding effect on the nursing infant. Inhaled glycopyrrolate (including its metabolites) have been detected in the milk of lactating rats and reached up to 10-fold higher concentrations in the milk than in the blood of the dam. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition.

    MECHANISM OF ACTION

    Antimuscarinic anticholinergic agents inhibit the action of acetylcholine at autonomic effectors innervated by postganglionic cholinergic nerves and on smooth muscles that respond to acetylcholine, but lack cholinergic innervation. The peripheral cholinergic receptors are present in the autonomic effector cells of smooth muscle, cardiac muscle, the sinoatrial node, the atrioventricular node, exocrine glands, and to a lesser degree, in the autonomic ganglia. Therefore, parenteral glycopyrrolate diminishes the volume and free acidity of gastric secretions and controls excessive pharyngeal, tracheal, and bronchial secretions.
     
    Clinically, parenteral glycopyrrolate is used mostly prior to general anesthesia to reduce GI and pulmonary secretions and lessen the chance of acid aspiration during surgery. Glycopyrrolate has similar affinity to the subtypes of muscarinic receptors M1 to M5. In the airway, inhalational glycopyrrolate exhibits pharmacological effects through inhibition of M3 receptor at the smooth muscle leading to bronchodilation. Oral glycopyrrolate inhibits the action of acetylcholine on salivary glands thereby reducing the extent of salivation.
     
    Glycopyrrolate has a polar quaternary ammonium group that reduces its ability to cross membranes such as the blood-brain barrier. This group differentiates the drug from other anticholinergic agents, such as scopolamine hydrobromide and atropine sulfate, which are nonpolar amines and readily cross the blood-brain barrier.

    PHARMACOKINETICS

    Glycopyrrolate is administered orally, via oral respiratory inhalation, or parenterally by intramuscular or intravenous routes. The drug distributes rapidly, but the exact metabolic fate of a dose is unknown. Mean volume of distribution is estimated to be 0.42 + 0.22 L/kg. Glycopyrrolate is primarily renally eliminated. In both urine and bile, greater than 80% of a radiolabeled dose corresponds to unchanged parent drug, suggesting that only a small proportion of the dose is excreted as 1 or more metabolites.
     
    Affected Cytochrome P450 (CYP450) isoenzymes and drug transporters: None

    Oral Route

    Glycopyrrolate is not well absorbed after oral administration.
    Oral tablet: In a study of pediatric patients (7 to 14 years) receiving either intravenous or the oral tablet formulation of glycopyrrolate, the mean absolute bioavailability of the tablet formulation was approximately 3% (range 1.3% to 13.3%); similar bioavailability is seen in adults.
    Orally disintegrating tablet (ODT): After administration of 1.7 mg ODT, the Cmax and AUC of glycopyrrolate were comparable to an oral 2 mg glycopyrrolate tablet. When the ODT was placed in the mouth and immediately swallowed with 240 mL water, the mean Cmax and AUC of glycopyrrolate decreased by 24% and 20%, respectively, compared to administration without water. In healthy adults, a high-fat, high-calorie meal (939 calories, 60% fat) significantly reduced the absorption of glycopyrrolate following administration of 1.7 mg ODT. The mean Cmax and AUC were approximately 83% and 77% lower, respectively, than those observed under fasted conditions.
    Oral solution: When compared to the oral tablet, the Cmax and AUC of glycopyrrolate oral solution in fasting patients is 23% and 28% (respectively) lower than the oral tablet. The mean time to maximum plasma concentration (mean Tmax) for the oral solution is 3.1 hours. The mean plasma half-life is 3 hours. Administering the oral solution with a high fat meal significantly lowers Cmax and AUC by 74% and 78% respectively, compared to administration while fasting.

    Intravenous Route

    The onset of action is within 1 minute following intravenous (IV) administration. Anticholinergic effects last up to 7 hours after parenteral administration, and vagal inhibition lasts 2 to 3 hours. The mean clearance and half-life values were reported to be 0.54 + 0.14 L/kg/hour and 0.83 + 0.13 hour, respectively post IV administration. After IV administration of a 0.2 mg radiolabeled glycopyrrolate, 85% of dose was recovered in urine 48 hours postdose and some of radioactivity was also recovered in bile.

    Intramuscular Route

    The onset of action is 15 to 30 minutes following intramuscular (IM) injection. Anticholinergic effects last up to 7 hours after parenteral administration, and vagal inhibition lasts 2 to 3 hours. After IM administration of glycopyrrolate to adults, the mean half-life value is reported to be 0.55 to 1.25 hours. Over 80% of IM dose administered was recovered in urine and the bile as unchanged drug and 50% of the IM dose is excreted within 3 hours.

    Inhalation Route

    Glycopyrrolate oral inhalation powder (i.e., Seebri Neohaler): Linear pharmacokinetics of glycopyrrolate were observed following inhalation of 31.2 mcg to 249.6 mcg per day via oral inhalation powder administration. Following oral inhalation, glycopyrrolate is rapidly absorbed and reaches peak plasma concentrations at 5 minutes post dose. The absolute bioavailability of inhaled glycopyrrolate is estimated to be about 40%; about 90% of systemic exposure is due to lung absorption and 10% is due to gastrointestinal absorption. Glycopyrrolate steady-state is reached within 1 week of treatment and there is no indication that the pharmacokinetics change over time. Glucuronide and/or sulfate conjugates of glycopyrrolate are found in urine of humans after repeated inhalation, accounting for about 3% of the dose. Following inhalation of single and repeated once-daily doses between 62.4 mcg and 249.6 mcg glycopyrrolate by healthy volunteers and patients with COPD, mean renal clearance of glycopyrrolate is in the range of 17.4 L/hour and 24.4 L/hour indicating active tubular secretion contributes to the renal elimination of glycopyrrolate. Glycopyrrolate plasma concentrations decline in a multi-phasic manner. The mean terminal elimination t1/2 is much longer after inhalation (33 to 53 hours) than after intravenous (6.2 hours) and oral (2.8 hours) administration.
    Glycopyrrolate oral inhalation solution (i.e., Lonhala Magnair): Following oral inhalation, glycopyrrolate was rapidly absorbed and reached peak plasma levels less than 20 minutes post dose. The steady-state plasma levels of glycopyrrolate were reached within 1 week of the start of treatment. A twice daily dose regimen leads to approximately 2 to 3 fold accumulation of systemic glycopyrrolate exposure at steady-state. The in vitro human plasma protein binding of glycopyrrolate was 38% to 41% at concentrations of 1 to 10 ng/mL. In vitro metabolism studies show glycopyrrolate hydroxylation resulting in a variety of mono- and bishydroxylated metabolites and direct hydrolysis resulting in the formation of a carboxylic acid derivative (M9). Further in vitro investigations showed that multiple CYP isoenzymes contribute to the oxidative biotransformation of glycopyrrolate and the hydrolysis to M9 is likely to be catalyzed by members from the cholinesterase family pre-systemically and/or via first pass metabolism from the swallowed dose fraction of orally inhaled glycopyrrolate.