Utibron Neohaler

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Utibron Neohaler

Classes

Respiratory Long-Acting Beta-2 Agonists in Combination with Respiratory Long-Acting Muscarinic Antagonists

Administration
Inhalation Administration Oral Inhalation Administration

Dry powder inhalation (Utibron Neohaler)
For oral inhalation only. Instruct patients NOT to swallow the capsules.
Only use the supplied Neohaler device to administer Utibron capsules; a new device should be utilized with each new medication pack.
Immediately prior to administration, use dry hands to remove a capsule from the blister card and 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 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).
Then, 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.

Adverse Reactions
Severe

atrial fibrillation / Early / 0-1.0
bronchospasm / Rapid / Incidence not known
asthma-related death / Delayed / Incidence not known
ocular hypertension / Delayed / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
angioedema / Rapid / Incidence not known

Moderate

hypertension / Early / 2.0-2.0
chest pain (unspecified) / Early / 0-1.0
sinus tachycardia / Rapid / 0-1.0
palpitations / Early / 0-1.0
edema / Delayed / 0-1.0
hyperglycemia / Delayed / 2.0
ST-T wave changes / Rapid / Incidence not known
QT prolongation / Rapid / Incidence not known
hypokalemia / Delayed / Incidence not known
constipation / Delayed / Incidence not known
blurred vision / Early / Incidence not known
urinary retention / Early / Incidence not known

Mild

pharyngitis / Delayed / 4.1-4.1
back pain / Delayed / 1.8-1.8
dizziness / Early / 0-1.0
fatigue / Early / 0-1.0
insomnia / Early / 0-1.0
dyspepsia / Early / 0-1.0
pruritus / Rapid / 0-1.0
rash / Early / 0-1.0
infection / Delayed / 2.0
rhinitis / Early / 2.0
headache / Early / 2.0
gastroesophageal reflux / Delayed / 2.0
diarrhea / Early / 2.0
cough / Delayed / Incidence not known
ocular pain / Early / Incidence not known

Common Brand Names

Utibron Neohaler

Dea Class

Rx

Description

Inhaled combination of a long-acting beta-2 adrenergic agonist (LABA), (indacaterol) and a long-acting muscarinic antagonist (LAMA), (glycopyrrolate)
Used in adults for the treatment of chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema
Not indicated for the treatment of acute bronchospasm and is not to be used for the treatment of asthma

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

The contents of 1 capsule (27.5 mcg indacaterol with 15.6 mcg glycopyrrolate) via oral inhalation twice daily (morning and evening), at the same times each day, is the recommended and max dose. 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 beta-agonists (LABAs) or long-acting muscarinic antagonists (LAMAs) concurrently.[60263] According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, indacaterol; glycopyrrolate may be used as initial therapy for patients in group D (those with a high risk of exacerbation). At follow-up, if the patient is still experiencing dyspnea, consider switching inhaler device and investigate for other causes of dyspnea. If the patient has exacerbations, consider triple therapy with a LAMA, a LABA, and an inhaled corticosteroid (ICS).[63765] Both LAMAs and LABAs reduce the risk of COPD exacerbations. Combination therapy is associated with greater improvements in lung function compared to monotherapy. However, more data are needed to confirm an increased effect on exacerbation rates compared to either component alone.[60288] [60933] [63765]

Dosing Considerations
Hepatic Impairment

No dosage adjustments are required for patients with mild to moderate hepatic impairment; studies in subjects with severe hepatic impairment have not been performed.

Renal Impairment

Mild to moderate renal impairment (estimated GFR >= 30 mL/min/1.73 m2): No dosage adjustments are required.
Severe renal impairment (estimated GFR < 30 mL/min/1.73 m2) or end stage renal disease (ESRD) requiring dialysis: Use only if the expected benefits outweigh the potential risks; systemic exposure to glycopyrrolate may be increased in this population.

Drug Interactions

Abarelix: (Major) Since abarelix can cause QT prolongation, abarelix should be used cautiously, if at all, with other drugs that are associated with QT prolongation. Prescribers need to weigh the potential benefits and risks of abarelix use in patients with prolonged QT syndrome or in patients taking other drugs that may prolong the QT interval. Agents associated with a lower, but possible risk for QT prolongation and torsade de pointes (TdP) based on varying levels of documentation include the beta-agonists. Beta-agonists may cause cardiovascular effects, particularly when used in high doses and/or when associated with hypokalemia.
Acebutolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Acetaminophen; Caffeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists. (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when dihydrocodeine is used concomitantly with an anticholinergic drug. The concomitant use of dihydrocodeine and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Acetaminophen; Codeine: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant codeine and glycopyrrolate use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Acetaminophen; Hydrocodone: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant hydrocodone and glycopyrrolate use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Acetaminophen; Oxycodone: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant oxycodone and glycopyrrolate use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
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 medications may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Acetaminophen; Pseudoephedrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Aclidinium: (Moderate) Although aclidinium is minimally absorbed into the systemic circulation after inhalation, there is the potential for aclidinium to have additive anticholinergic effects when administered with other anticholinergics or antimuscarinics. Per the manufacturer, avoid concomitant administration of aclidinium with other anticholinergic medications, when possible.
Aclidinium; Formoterol: (Major) Formoterol should not be used in conjunction with other medications containing a long-acting beta-2 agonist for any reason, as overdose may result. Coadministration can result in overdosage. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Acute symptoms should be treated with inhaled short-acting beta-2 agonists (SABA) such as albuterol. SABAs should not be used on a regular basis (e.g., 4 times a day) while taking formoterol. Increasing SABA use is a sign of deteriorating disease for which prompt medical attention is required. Prompt re-evaluation of the patient and their COPD treatment regimen should occur if formoterol no longer controls symptoms of bronchoconstriction, the patient's SABA rescue becomes less effective, or the patient requires more SABA rescue doses than usual. Use formoterol and drugs known to prolong the QTc interval together with extreme caution; this combination may increase the risk of cardiovascular effects and ventricular arrhythmias; this includes combination with other beta-agonists. (Moderate) Although aclidinium is minimally absorbed into the systemic circulation after inhalation, there is the potential for aclidinium to have additive anticholinergic effects when administered with other anticholinergics or antimuscarinics. Per the manufacturer, avoid concomitant administration of aclidinium with other anticholinergic medications, when possible.
Acrivastine; Pseudoephedrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Alfentanil: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when alfentanil is used concomitantly with an anticholinergic drug. The concomitant use of alfentanil and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
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.
Amphetamine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Amphetamine; Dextroamphetamine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
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.
Apalutamide: (Moderate) Monitor for decreased efficacy of indacaterol if coadministration with apalutamide is necessary. Indacaterol is a substrate of CYP3A4, UGT, and P-glycoprotein (P-gp). Apalutamide is a strong CYP3A4 inducer, as well as an inducer of UGT and a weak P-gp inducer.
Arformoterol: (Major) Indacaterol; glycopyrrolate should not be used in conjunction with other medications containing a long-acting beta-2 agonist, such as arformoterol, for any reason, as overdose may result. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Acute symptoms should be treated with an inhaled short-acting beta-2 agonist (SABA) such as albuterol. SABAs should not be used on a regular basis (e.g., 4 times a day) while taking indacaterol; glycopyrrolate. Increasing SABA use is a sign of deteriorating disease for which prompt medical attention is required. Prompt re-evaluation of the patient and their COPD treatment regimen should occur if indacaterol; glycopyrrolate no longer controls symptoms of bronchoconstriction, the patient's SABA rescue becomes less effective, or the patient requires more SABA rescue doses than usual.
Articaine; Epinephrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists. (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant codeine and glycopyrrolate use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Aspirin, ASA; Caffeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
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. (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant codeine and glycopyrrolate use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
Aspirin, ASA; Oxycodone: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant oxycodone and glycopyrrolate use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Atazanavir; Cobicistat: (Moderate) Clinical monitoring for adverse effects, such as headache, nervousness, tremor, or cardiovascular effects, is recommended during coadministration. Plasma concentrations of indacaterol may be elevated when administered concurrently with cobicistat. Cobicistat is a CYP3A4, CYP2D6, and P-glycoprotein (P-gp) inhibitor, while indacaterol is a CYP3A4, CYP2D6, and P-gp substrate. Coadministration with other dual inhibitors of CYP3A4 and P-gp has increased exposure of indacaterol from 1.4- to 1.9- fold.
Atenolol: (Moderate) Atenolol bioavailability may increase with coadministration of glycopyrrolate. A reduction in the atenolol dose may be necessary. (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
Atenolol; Chlorthalidone: (Moderate) Atenolol bioavailability may increase with coadministration of glycopyrrolate. A reduction in the atenolol dose may be necessary. (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
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.
Bendroflumethiazide; Nadolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
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.
Benzphetamine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Beta-adrenergic blockers: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
Betaxolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
Bisoprolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
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).
Brimonidine; Timolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Brompheniramine; Phenylephrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Brompheniramine; Pseudoephedrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Budesonide; Formoterol: (Major) Formoterol should not be used in conjunction with other medications containing a long-acting beta-2 agonist for any reason, as overdose may result. Coadministration can result in overdosage. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Acute symptoms should be treated with inhaled short-acting beta-2 agonists (SABA) such as albuterol. SABAs should not be used on a regular basis (e.g., 4 times a day) while taking formoterol. Increasing SABA use is a sign of deteriorating disease for which prompt medical attention is required. Prompt re-evaluation of the patient and their COPD treatment regimen should occur if formoterol no longer controls symptoms of bronchoconstriction, the patient's SABA rescue becomes less effective, or the patient requires more SABA rescue doses than usual. Use formoterol and drugs known to prolong the QTc interval together with extreme caution; this combination may increase the risk of cardiovascular effects and ventricular arrhythmias; this includes combination with other beta-agonists.
Budesonide; Glycopyrrolate; Formoterol: (Major) Formoterol should not be used in conjunction with other medications containing a long-acting beta-2 agonist for any reason, as overdose may result. Coadministration can result in overdosage. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Acute symptoms should be treated with inhaled short-acting beta-2 agonists (SABA) such as albuterol. SABAs should not be used on a regular basis (e.g., 4 times a day) while taking formoterol. Increasing SABA use is a sign of deteriorating disease for which prompt medical attention is required. Prompt re-evaluation of the patient and their COPD treatment regimen should occur if formoterol no longer controls symptoms of bronchoconstriction, the patient's SABA rescue becomes less effective, or the patient requires more SABA rescue doses than usual. Use formoterol and drugs known to prolong the QTc interval together with extreme caution; this combination may increase the risk of cardiovascular effects and ventricular arrhythmias; this includes combination with other beta-agonists.
Bumetanide: (Moderate) Use beta-agonists and loop diuretics with caution due to risk for ECG changes and/or hypokalemia. The ECG changes and/or hypokalemia that may result from administration of loop diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded.
Bupivacaine; Epinephrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Buprenorphine: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant buprenorphine and glycopyrrolate use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Buprenorphine; Naloxone: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant buprenorphine and glycopyrrolate use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Bupropion: (Moderate) Additive anticholinergic effects may be seen when 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: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists. (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant codeine and glycopyrrolate use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Butorphanol: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when butorphanol is used concomitantly with an anticholinergic drug. The concomitant use of butorphanol and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Caffeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Caffeine; Sodium Benzoate: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
Calcium Carbonate: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics.
Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics.
Calcium Carbonate; Magnesium Hydroxide: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics.
Calcium Carbonate; Magnesium Hydroxide; Simethicone: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics.
Calcium Carbonate; Risedronate: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics.
Calcium Carbonate; Simethicone: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics.
Calcium; Vitamin D: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics.
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.
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; Dextromethorphan; Pseudoephedrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Carbinoxamine; Phenylephrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Carbinoxamine; Pseudoephedrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Carteolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
Carvedilol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
Celecoxib; Tramadol: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant tramadol and glycopyrrolate use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Cetirizine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant cetirizine and glycopyrrolate use. Concomitant use may result in additive anticholinergic adverse effects.
Cetirizine; Pseudoephedrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects. (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant cetirizine and glycopyrrolate use. Concomitant use may result in additive anticholinergic adverse effects.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Chlorpheniramine; Codeine: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant codeine and glycopyrrolate use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects. (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when dihydrocodeine is used concomitantly with an anticholinergic drug. The concomitant use of dihydrocodeine and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Chlorpheniramine; Hydrocodone: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant hydrocodone and glycopyrrolate use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Chlorpheniramine; Phenylephrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Chlorpheniramine; Pseudoephedrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Chlorpromazine: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including chlorpromazine. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other additive CNS effects may also occur.
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: (Contraindicated) QT prolongation and ventricular arrhythmias, including torsade de pointes (TdP) and death, have been reported with cisapride. Because of the potential for TdP, use of other drugs that might increase the QT interval is contraindicated with cisapride. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. (Moderate) The use of drugs that decrease GI motility, such as glycopyrrolate, may pharmacodynamically oppose the effects of cisapride.
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.
Cobicistat: (Moderate) Clinical monitoring for adverse effects, such as headache, nervousness, tremor, or cardiovascular effects, is recommended during coadministration. Plasma concentrations of indacaterol may be elevated when administered concurrently with cobicistat. Cobicistat is a CYP3A4, CYP2D6, and P-glycoprotein (P-gp) inhibitor, while indacaterol is a CYP3A4, CYP2D6, and P-gp substrate. Coadministration with other dual inhibitors of CYP3A4 and P-gp has increased exposure of indacaterol from 1.4- to 1.9- fold.
Cocaine: (Moderate) Additive effects and increased toxicity might be observed when using cocaine with beta-agonists, which are sympathomimetic agents. The combined use of these agents may have the potential for additive adrenergic stimulation and side effects, such as nervousness, insomnia, palpitations, or adverse cardiovascular effects.
Codeine: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant codeine and glycopyrrolate use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Codeine; Guaifenesin: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant codeine and glycopyrrolate use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects. (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant codeine and glycopyrrolate use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Codeine; Phenylephrine; Promethazine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects. (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant codeine and glycopyrrolate use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant promethazine and glycopyrrolate use. Concomitant use may result in additive anticholinergic adverse effects.
Codeine; Promethazine: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant codeine and glycopyrrolate use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant promethazine and glycopyrrolate use. Concomitant use may result in additive anticholinergic adverse effects.
Crofelemer: (Moderate) Pharmacodynamic interactions between crofelemer and antimuscarinics are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as antimuscarinics, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Cyclobenzaprine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant cyclobenzaprine and glycopyrrolate use. Concomitant use may result in additive anticholinergic adverse effects.
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.
Darunavir; Cobicistat: (Moderate) Clinical monitoring for adverse effects, such as headache, nervousness, tremor, or cardiovascular effects, is recommended during coadministration. Plasma concentrations of indacaterol may be elevated when administered concurrently with cobicistat. Cobicistat is a CYP3A4, CYP2D6, and P-glycoprotein (P-gp) inhibitor, while indacaterol is a CYP3A4, CYP2D6, and P-gp substrate. Coadministration with other dual inhibitors of CYP3A4 and P-gp has increased exposure of indacaterol from 1.4- to 1.9- fold.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Clinical monitoring for adverse effects, such as headache, nervousness, tremor, or cardiovascular effects, is recommended during coadministration. Plasma concentrations of indacaterol may be elevated when administered concurrently with cobicistat. Cobicistat is a CYP3A4, CYP2D6, and P-glycoprotein (P-gp) inhibitor, while indacaterol is a CYP3A4, CYP2D6, and P-gp substrate. Coadministration with other dual inhibitors of CYP3A4 and P-gp has increased exposure of indacaterol from 1.4- to 1.9- fold.
Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Although no dosage adjustment of the 75 mcg indacaterol daily dose is needed, use caution if coadministered with dasabuvir; ombitasvir; paritaprevir; ritonavir. By inhibiting CYP3A4 and CYP2D6, ritonavir alters indacaterol metabolism. In drug interaction studies, coadministration of indacaterol 300 mcg (single dose) with ritonavir (300 mg bid for 7.5 days) resulted in a 1.7-fold increase in indacaterol AUC(0 to 24) whereas indacaterol Cmax was unaffected. In addition, indaceterol is a substrate for uridine glucuronyltransferase (UGT) 1A1 and P-glycoprotein (P-gp). Ombitasvir, dasabuvir, and paritaprevir are UGT1A1 inhibitors, while ritonavir and paritaprevir are P-gp inhibitors. Monitor the patient clinically for tremor, palpitations, or increased heart rate. (Moderate) Although no dosage adjustment of the 75 mcg indacaterol daily dose is needed, use caution if indacaterol and ritonavir are used concurrently. Monitor the patient clinically for beta-agonist side effects like tremor, nervousness, or fast, irregular heart rate. In addition, both ritonavir and long-acting beta agonists (LABAs) are associated with QT prolongation; concomitant use may increase the risk of QT prolongation. By inhibiting CYP3A4, CYP2D6, and P-glycoprotein, ritonavir reduces indacaterol metabolism. In drug interaction studies, coadministration of indacaterol 300 mcg (single dose) with ritonavir (300 mg twice daily for 7.5 days) resulted in a 1.7-fold increase in indacaterol exposure (AUC) whereas indacaterol maximal concentration (Cmax) was unaffected.
Dasiglucagon: (Major) The concomitant use of intravenous glucagon and anticholinergics increases the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. Concomitant use is not recommended.
Desloratadine; Pseudoephedrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Dexbrompheniramine; Pseudoephedrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Dexmethylphenidate: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Dextroamphetamine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Dextromethorphan; 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.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Dextromethorphan; Quinidine: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
Diethylpropion: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Digoxin: (Moderate) Anticholinergics, because of their ability to cause tachycardia, can antagonize the beneficial actions of digoxin in atrial fibrillation/flutter. Routine therapeutic monitoring should be continued when an antimuscarinic agent is prescribed with digoxin until the effects of combined use are known.
Diphenhydramine; Phenylephrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
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.
Dobutamine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
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.
Dopamine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Dorzolamide; Timolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
Doxapram: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Dronabinol: (Moderate) Use caution if coadministration of dronabinol with anticholinergics is necessary. Concurrent use of dronabinol, THC with anticholinergics may result in additive drowsiness, hypertension, tachycardia, and possibly cardiotoxicity.
Dyphylline: (Moderate) Concomitant use of indacaterol and dyphylline may potentiate the hypokalemic effect of indacaterol. Monitor the patient appropriately and consider checking serum potassium concentrations if clinically indicated.
Dyphylline; Guaifenesin: (Moderate) Concomitant use of indacaterol and dyphylline may potentiate the hypokalemic effect of indacaterol. Monitor the patient appropriately and consider checking serum potassium concentrations if clinically indicated.
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.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Clinical monitoring for adverse effects, such as headache, nervousness, tremor, or cardiovascular effects, is recommended during coadministration. Plasma concentrations of indacaterol may be elevated when administered concurrently with cobicistat. Cobicistat is a CYP3A4, CYP2D6, and P-glycoprotein (P-gp) inhibitor, while indacaterol is a CYP3A4, CYP2D6, and P-gp substrate. Coadministration with other dual inhibitors of CYP3A4 and P-gp has increased exposure of indacaterol from 1.4- to 1.9- fold.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Clinical monitoring for adverse effects, such as headache, nervousness, tremor, or cardiovascular effects, is recommended during coadministration. Plasma concentrations of indacaterol may be elevated when administered concurrently with cobicistat. Cobicistat is a CYP3A4, CYP2D6, and P-glycoprotein (P-gp) inhibitor, while indacaterol is a CYP3A4, CYP2D6, and P-gp substrate. Coadministration with other dual inhibitors of CYP3A4 and P-gp has increased exposure of indacaterol from 1.4- to 1.9- fold.
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 increa

sed metformin effects and possible adverse events. If coadministration is necessary, monitor clinical response to metformin and adjust metformin dose accordingly.
Ephedrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Ephedrine; Guaifenesin: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Epinephrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Ergotamine; Caffeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
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.
Esmolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
Ethacrynic Acid: (Moderate) Use beta-agonists and loop diuretics with caution due to risk for ECG changes and/or hypokalemia. The ECG changes and/or hypokalemia that may result from administration of loop diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded.
Fentanyl: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant fentanyl and glycopyrrolate use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Fexofenadine; Pseudoephedrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
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; Salmeterol: (Major) Indacaterol should not be used in conjunction with other medications containing a long-acting beta-2 agonist, such as salmeterol for any reason, as overdose may result. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Acute symptoms should be treated with an inhaled short-acting beta-2 agonist (SABA) such as albuterol. SABAs should not be used on a regular basis (e.g., 4 times a day) while taking indacaterol. Increasing SABA use is a sign of deteriorating disease for which prompt medical attention is required. Prompt re-evaluation of the patient and their COPD treatment regimen should occur if indacaterol no longer controls symptoms of bronchoconstriction, the patient's SABA rescue becomes less effective, or the patient requires more SABA rescue doses than usual.
Fluticasone; Umeclidinium; Vilanterol: (Major) Indacaterol should not be used with vilanterol for any reason, as sympathomimetic overdose and additive anticholinergic effects may result. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Acute symptoms should be treated with an inhaled short-acting beta-2 agonist (SABA) such as albuterol. SABAs should not be used on a regular basis (e.g., 4 times a day) while taking indacaterol. Increasing SABA use is a sign of deteriorating disease for which prompt medical attention is required. Prompt re-evaluation of the patient and their COPD treatment regimen should occur if indacaterol no longer controls symptoms of bronchoconstriction, the patient's SABA rescue becomes less effective, or the patient requires more SABA rescue doses than usual. (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.
Fluticasone; Vilanterol: (Major) Indacaterol should not be used with vilanterol for any reason, as sympathomimetic overdose and additive anticholinergic effects may result. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Acute symptoms should be treated with an inhaled short-acting beta-2 agonist (SABA) such as albuterol. SABAs should not be used on a regular basis (e.g., 4 times a day) while taking indacaterol. Increasing SABA use is a sign of deteriorating disease for which prompt medical attention is required. Prompt re-evaluation of the patient and their COPD treatment regimen should occur if indacaterol no longer controls symptoms of bronchoconstriction, the patient's SABA rescue becomes less effective, or the patient requires more SABA rescue doses than usual.
Formoterol: (Major) Formoterol should not be used in conjunction with other medications containing a long-acting beta-2 agonist for any reason, as overdose may result. Coadministration can result in overdosage. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Acute symptoms should be treated with inhaled short-acting beta-2 agonists (SABA) such as albuterol. SABAs should not be used on a regular basis (e.g., 4 times a day) while taking formoterol. Increasing SABA use is a sign of deteriorating disease for which prompt medical attention is required. Prompt re-evaluation of the patient and their COPD treatment regimen should occur if formoterol no longer controls symptoms of bronchoconstriction, the patient's SABA rescue becomes less effective, or the patient requires more SABA rescue doses than usual. Use formoterol and drugs known to prolong the QTc interval together with extreme caution; this combination may increase the risk of cardiovascular effects and ventricular arrhythmias; this includes combination with other beta-agonists.
Formoterol; Mometasone: (Major) Formoterol should not be used in conjunction with other medications containing a long-acting beta-2 agonist for any reason, as overdose may result. Coadministration can result in overdosage. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Acute symptoms should be treated with inhaled short-acting beta-2 agonists (SABA) such as albuterol. SABAs should not be used on a regular basis (e.g., 4 times a day) while taking formoterol. Increasing SABA use is a sign of deteriorating disease for which prompt medical attention is required. Prompt re-evaluation of the patient and their COPD treatment regimen should occur if formoterol no longer controls symptoms of bronchoconstriction, the patient's SABA rescue becomes less effective, or the patient requires more SABA rescue doses than usual. Use formoterol and drugs known to prolong the QTc interval together with extreme caution; this combination may increase the risk of cardiovascular effects and ventricular arrhythmias; this includes combination with other beta-agonists.
Fostamatinib: (Moderate) Clinical monitoring for adverse effects, such as headache, nervousness, tremor, or cardiovascular effects, is recommended during coadministration. Plasma concentrations of indacaterol may be elevated when administered concurrently with fostamatinib. Fostamatinib is a CYP3A4 and P-gp inhibitor, while indacaterol is a CYP3A4 and P-gp substrate. Coadministration with other dual inhibitors of CYP3A4 and P-gp has increased exposure of indacaterol from 1.4- to 1.9- fold.
Furosemide: (Moderate) Use beta-agonists and loop diuretics with caution due to risk for ECG changes and/or hypokalemia. The ECG changes and/or hypokalemia that may result from administration of loop diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded.
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.
Glycopyrrolate; Formoterol: (Major) Formoterol should not be used in conjunction with other medications containing a long-acting beta-2 agonist for any reason, as overdose may result. Coadministration can result in overdosage. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Acute symptoms should be treated with inhaled short-acting beta-2 agonists (SABA) such as albuterol. SABAs should not be used on a regular basis (e.g., 4 times a day) while taking formoterol. Increasing SABA use is a sign of deteriorating disease for which prompt medical attention is required. Prompt re-evaluation of the patient and their COPD treatment regimen should occur if formoterol no longer controls symptoms of bronchoconstriction, the patient's SABA rescue becomes less effective, or the patient requires more SABA rescue doses than usual. Use formoterol and drugs known to prolong the QTc interval together with extreme caution; this combination may increase the risk of cardiovascular effects and ventricular arrhythmias; this includes combination with other beta-agonists.
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 for signs of urinary retention or reduced gastric motility during concomitant hydrocodone and glycopyrrolate use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects. (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant hydrocodone and glycopyrrolate use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Guaifenesin; Phenylephrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Guaifenesin; Pseudoephedrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
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 for signs of urinary retention or reduced gastric motility during concomitant hydrocodone and glycopyrrolate use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Hydrocodone: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant hydrocodone and glycopyrrolate use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Hydrocodone; Ibuprofen: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant hydrocodone and glycopyrrolate use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Hydrocodone; Pseudoephedrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects. (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant hydrocodone and glycopyrrolate use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Hydromorphone: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when hydromorphone is used concomitantly with an anticholinergic drug. The concomitant use of hydromorphone and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Ibritumomab Tiuxetan: (Major) Glycopyrrolate oral solution is contraindicated with concomitant solid oral dosage forms of potassium chloride due to risk for gastrointestinal mucosal injury. Glycopyrrolate orally disintegrating tablets are not recommended for use with solid oral dosage forms of potassium chloride. Use other glycopyrrolate dosage forms with solid oral dosage forms of potassium chloride with caution. Anticholinergics may decrease gastric motility and increase the transit time of solid oral dosage forms of potassium chloride leading to prolonged contact with the gastrointestinal mucosa.
Ibuprofen; Oxycodone: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant oxycodone and glycopyrrolate use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Ibuprofen; Pseudoephedrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
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.
Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with indacaterol may result in increased serum concentrations of indacaterol. Indacaterol is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Caution and close monitoring are advised if these drugs are used together.
Isocarboxazid: (Moderate) Use beta-agonists with caution in patients receiving concomitant monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping treatment with MAOIs because the action of beta-agonists on the cardiovascular system may be potentiated.
Isoproterenol: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Itraconazole: (Major) Although no dosage adjustment of the 75 mcg/day indacaterol dose is needed, avoid use if possible. Consider alternatives. By inhibiting CYP3A4 and P-gp, itraconazole inhibits indacaterol metabolism. In drug interaction studies, coadministration of indacaterol inhalation powder 300 mcg (single dose) with another systemic azole antifungal with similar CYP3A4/P-gp activity caused a 1.9-fold increase in indacaterol exposure (AUC), and a 1.3-fold increase in indacaterol maximal concentration (Cmax). This may result in indacaterol side effects like tremor, nervousness, or a fast, irregular heart rate. Itraconazole has been associated with prolongation of the QT interval. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously and with close monitoring with itraconazole include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. (Moderate) Antimuscarinics can raise intragastric pH. This effect may decrease the oral bioavailability of itraconazole; antimuscarinics should be used cautiously in patients receiving itraconazole.
Ketoconazole: (Moderate) Monitor for beta-agonist side effects like tremor, nervousness, or fast, irregular heart rate, if indacaterol is coadministered with ketoconazole. Concurrent use may increase indacaterol exposure, although such increases in indacaterol exposure are unlikely to require any dose adjustment. Indacaterol is a CYP3A4 and P-gp substrate; ketoconazole is a strong CYP3A4 and P-gp inhibitor. In drug interaction studies, coadministration with ketoconazole caused an approximately 2-fold increase in indacaterol exposure.
Labetalol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
Levobetaxolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
Levobunolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
Levocetirizine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant cetirizine and glycopyrrolate use. Concomitant use may result in additive anticholinergic adverse effects.
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.
Levoketoconazole: (Moderate) Monitor for beta-agonist side effects like tremor, nervousness, or fast, irregular heart rate, if indacaterol is coadministered with ketoconazole. Concurrent use may increase indacaterol exposure, although such increases in indacaterol exposure are unlikely to require any dose adjustment. Indacaterol is a CYP3A4 and P-gp substrate; ketoconazole is a strong CYP3A4 and P-gp inhibitor. In drug interaction studies, coadministration with ketoconazole caused an approximately 2-fold increase in indacaterol exposure.
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.
Levothyroxine: (Moderate) Monitor blood pressure and heart rate during concomitant beta-agonist and thyroid hormone use. Concurrent use may increase the effects of sympathomimetics or thyroid hormone. Thyroid hormones may increase the risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease.
Levothyroxine; Liothyronine (Porcine): (Moderate) Monitor blood pressure and heart rate during concomitant beta-agonist and thyroid hormone use. Concurrent use may increase the effects of sympathomimetics or thyroid hormone. Thyroid hormones may increase the risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease.
Levothyroxine; Liothyronine (Synthetic): (Moderate) Monitor blood pressure and heart rate during concomitant beta-agonist and thyroid hormone use. Concurrent use may increase the effects of sympathomimetics or thyroid hormone. Thyroid hormones may increase the risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease.
Lidocaine; Epinephrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
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.
Linezolid: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
Liothyronine: (Moderate) Monitor blood pressure and heart rate during concomitant beta-agonist and thyroid hormone use. Concurrent use may increase the effects of sympathomimetics or thyroid hormone. Thyroid hormones may increase the risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease.
Lisdexamfetamine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Lonafarnib: (Moderate) Monitor for beta-agonist side effects like tremor, nervousness, or fast, irregular heart rate, if indacaterol is coadministered with lonafarnib. Concurrent use may increase indacaterol exposure, although such increases in indacaterol exposure are unlikely to require any dose adjustment. Indacaterol is a CYP3A4 and P-gp substrate; lonafarnib is a P-gp and strong CYP3A4 inhibitor. In drug interaction studies, coadministration of indacaterol inhalation powder 300 mcg (single dose) with another dual strong CYP3A4 and P-gp inhibitor caused an approximately 2-fold increase in indacaterol exposure.
Loop diuretics: (Moderate) Use beta-agonists and loop diuretics with caution due to risk for ECG changes and/or hypokalemia. The ECG changes and/or hypokalemia that may result from administration of loop diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded.
Lopinavir; Ritonavir: (Moderate) Although no dosage adjustment of the 75 mcg indacaterol daily dose is needed, use caution if indacaterol and ritonavir are used concurrently. Monitor the patient clinically for beta-agonist side effects like tremor, nervousness, or fast, irregular heart rate. In addition, both ritonavir and long-acting beta agonists (LABAs) are associated with QT prolongation; concomitant use may increase the risk of QT prolongation. By inhibiting CYP3A4, CYP2D6, and P-glycoprotein, ritonavir reduces indacaterol metabolism. In drug interaction studies, coadministration of indacaterol 300 mcg (single dose) with ritonavir (300 mg twice daily for 7.5 days) resulted in a 1.7-fold increase in indacaterol exposure (AUC) whereas indacaterol maximal concentration (Cmax) was unaffected.
Loratadine; Pseudoephedrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
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.
Lumacaftor; Ivacaftor: (Moderate) Lumacaftor; ivacaftor may alter the systemic exposure of indacaterol; use together with caution. Indacaterol is a substrate of CYP3A4 and the P-glycoprotein (P-gp) drug transporter. Lumacaftor is a strong CYP3A inducer; in vitro data suggests lumacaftor; ivacaftor may also induce and/or inhibit P-gp. While the induction of indacaterol through the CYP3A pathway may lead to decreased plasma concentrations of indacaterol, the net effect of lumacaftor; ivacaftor on P-gp transport is not clear.
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.
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) Monitor for signs or symptoms of anticholinergic toxicity during concomitant promethazine and glycopyrrolate use. Concomitant use may result in additive anticholinergic adverse effects. (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.
Methacholine: (Major) Discontinue use of indacaterol 48 hours before a methacholine challenge test. Beta-agonists inhibit the airway response to methacholine.
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.
Methamphetamine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Methylphenidate: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
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.
Metoprolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
Midodrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Mirabegron: (Minor) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as indacaterol may be increased when administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Mitotane: (Major) Use caution if mitotane and indacaterol are used concomitantly, and monitor for decreased efficacy of indacaterol and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and indacaterol is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of indacaterol.
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.
Monoamine oxidase inhibitors: (Moderate) Use beta-agonists with caution in patients receiving concomitant monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping treatment with MAOIs because the action of beta-agonists on the cardiovascular system may be potentiated.
Morphine: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant morphine and glycopyrrolate use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Morphine; Naltrexone: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant morphine and glycopyrrolate use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Nabilone: (Moderate) Concurrent use of nabilone with anticholinergics may result in pronounced tachycardia and drowsiness.
Nadolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
Nalbuphine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when nalbuphine is used concomitantly with an anticholinergic drug. The concomitant use of nalbuphine and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Naproxen; Pseudoephedrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Nebivolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
Nebivolol; Valsartan: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
Neostigmine: (Minor) The muscarinic actions of neostigmine can antagonize the antimuscarinic actions of glycopyrrolate.
Nirmatrelvir; Ritonavir: (Moderate) Although no dosage adjustment of the 75 mcg indacaterol daily dose is needed, use caution if indacaterol and ritonavir are used concurrently. Monitor the patient clinically for beta-agonist side effects like tremor, nervousness, or fast, irregular heart rate. In addition, both ritonavir and long-acting beta agonists (LABAs) are associated with QT prolongation; concomitant use may increase the risk of QT prolongation. By inhibiting CYP3A4, CYP2D6, and P-glycoprotein, ritonavir reduces indacaterol metabolism. In drug interaction studies, coadministration of indacaterol 300 mcg (single dose) with ritonavir (300 mg twice daily for 7.5 days) resulted in a 1.7-fold increase in indacaterol exposure (AUC) whereas indacaterol maximal concentration (Cmax) was unaffected.
Norepinephrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Olanzapine: (Moderate) Additive anticholinergic effects may be seen when olanzapine and anticholinergics are used concomitantly; use with caution. Use of olanzapine and other drugs with anticholinergic activity can increase the risk for severe gastrointestinal adverse reactions related to hypomotility. Olanzapine exhibits anticholinergic activity. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur, depending on the anticholinergic agent used.
Olanzapine; Fluoxetine: (Moderate) Additive anticholinergic effects may be seen when olanzapine and anticholinergics are used concomitantly; use with caution. Use of olanzapine and other drugs with anticholinergic activity can increase the risk for severe gastrointestinal adverse reactions related to hypomotility. Olanzapine exhibits anticholinergic activity. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur, depending on the anticholinergic agent used.
Olanzapine; Samidorphan: (Moderate) Additive anticholinergic effects may be seen when olanzapine and anticholinergics are used concomitantly; use with caution. Use of olanzapine and other drugs with anticholinergic activity can increase the risk for severe gastrointestinal adverse reactions related to hypomotility. Olanzapine exhibits anticholinergic activity. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur, depending on the anticholinergic agent used.
Oliceridine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when oliceridine is used with glycopyrrolate. Use of anticholinergics may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Olodaterol: (Major) Indacaterol should not be used in conjunction with other medications containing a long-acting beta-2 agonist, such as olodaterol, for any reason, as overdose may result. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Acute symptoms should be treated with an inhaled short-acting beta-2 agonist (SABA) such as albuterol. SABAs should not be used on a regular basis (e.g., 4 times a day) while taking indacaterol. Increasing SABA use is a sign of deteriorating disease for which prompt medical attention is required. Prompt re-evaluation of the patient and their COPD treatment regimen should occur if indacaterol no longer controls symptoms of bronchoconstriction, the patient's SABA rescue becomes less effective, or the patient requires more SABA rescue doses than usual.
Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Although no dosage adjustment of the 75 mcg indacaterol daily dose is needed, use caution if indacaterol and ritonavir are used concurrently. Monitor the patient clinically for beta-agonist side effects like tremor, nervousness, or fast, irregular heart rate. In addition, both ritonavir and long-acting beta agonists (LABAs) are associated with QT prolongation; concomitant use may increase the risk of QT prolongation. By inhibiting CYP3A4, CYP2D6, and P-glycoprotein, ritonavir reduces indacaterol metabolism. In drug interaction studies, coadministration of indacaterol 300 mcg (single dose) with ritonavir (300 mg twice daily for 7.5 days) resulted in a 1.7-fold increase in indacaterol exposure (AUC) whereas indacaterol maximal concentration (Cmax) was unaffected.
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 for signs of urinary retention or reduced gastric motility during concomitant oxycodone and glycopyrrolate use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Oxymorphone: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when oxymorphone is used concomitantly with an anticholinergic drug. The concomitant use of oxymorphone and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Paroxetine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant anticholinergic medication and paroxetine use. Concomitant use may result in additive anticholinergic adverse effects.
Penbutolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are 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 medications may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Pentazocine; Naloxone: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when pentazocine is used concomitantly with an anticholinergic drug. The concomitant use of pentazocine and anticholinergic medications may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Perphenazine: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including perphenazine. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other additive CNS effects may also occur.
Perphenazine; Amitriptyline: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including perphenazine. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other additive CNS effects may also occur.
Phendimetrazine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Phenelzine: (Moderate) Use beta-agonists with caution in patients receiving concomitant monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping treatment with MAOIs because the action of beta-agonists on the cardiovascular system may be potentiated.
Phentermine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Phentermine; Topiramate: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects. (Moderate) Monitor for decreased sweating and increased body temperature, especially in hot weather, during concomitant use of topiramate and other drugs that predispose persons to heat-related disorders, such as anticholinergic medications. Concomitant use increases the risk for oligohidrosis and hyperthermia.
Phenylephrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Physostigmine: (Minor) The muscarinic actions of physostigmine can antagonize the antimuscarinic actions of glycopyrrolate.
Pindolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
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 Bicarbonate: (Major) Glycopyrrolate oral solution is contraindicated with concomitant solid oral dosage forms of potassium chloride due to risk for gastrointestinal mucosal injury. Glycopyrrolate orally disintegrating tablets are not recommended for use with solid oral dosage forms of potassium chloride. Use other glycopyrrolate dosage forms with solid oral dosage forms of potassium chloride with caution. Anticholinergics may decrease gastric motility and increase the transit time of solid oral dosage forms of potassium chloride leading to prolonged contact with the gastrointestinal mucosa.
Potassium Chloride: (Major) Glycopyrrolate oral solution is contraindicated with concomitant solid oral dosage forms of potassium chloride due to risk for gastrointestinal mucosal injury. Glycopyrrolate orally disintegrating tablets are not recommended for use with solid oral dosage forms of potassium chloride. Use other glycopyrrolate dosage forms with solid oral dosage forms of potassium chloride with caution. Anticholinergics may decrease gastric motility and increase the transit time of solid oral dosage forms of potassium chloride leading to prolonged contact with the gastrointestinal mucosa.
Pramlintide: (Major) Pramlintide therapy should not be considered in patients taking medications that alter gastric motility, such as anticholinergics. Pramlintide slows gastric emptying and the rate of nutrient delivery to the small intestine. Medications that have depressive effects on GI could potentiate the actions of pramlintide.
Prilocaine; Epinephrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
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.
Procarbazine: (Major) Procarbazine has MAOI activity and the cardiovascular effects of beta-2 agonists may be potentiated by concomitant use of MAOIs. Although no data are available, procarbazine may interact similarly. Close observation for such effects is prudent, particularly if beta-agonists are administered within two weeks of stopping the MAOI.
Prochlorperazine: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including prochlorperazine. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other additive CNS effects may also occur.
Promethazine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant promethazine and glycopyrrolate use. Concomitant use may result in additive anticholinergic adverse effects.
Promethazine; Dextromethorphan: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant promethazine and glycopyrrolate use. Concomitant use may result in additive anticholinergic adverse effects.
Promethazine; Phenylephrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects. (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant promethazine and glycopyrrolate use. Concomitant use may result in additive anticholinergic adverse effects.
Propranolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
Pseudoephedrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by c oncomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Pseudoephedrine; Triprolidine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Pyridostigmine: (Minor) The muscarinic actions of pyridostigmine can antagonize the antimuscarinic actions of glycopyrrolate.
Quetiapine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant quetiapine and glycopyrrolate use. Concomitant use may result in additive anticholinergic adverse effects.
Quinidine: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
Racepinephrine: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
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. (Moderate) The concomitant use of rasagiline and sympathomimetic agents was not allowed in clinical studies; therefore, caution is advised during concurrent use of rasagiline and respiratory adrenergic agents (e.g., the beta-agonists). Although sympathomimetic agents are contraindicated for use with traditional non-selective monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with rasagiline because of the selective monoamine oxidase-B (MAO-B) inhibition of rasagiline at manufacturer recommended doses. However, the cardiovascular effects of beta-2 agonists may be potentiated by concomitant use of MAOIs. At least one case of hypertension occurred in a patient with previous episodes of high blood pressure who was receiving albuterol and selegiline, a selective MAOI related to rasagiline, concurrently. Close observation for such effects is prudent, particularly if beta-2 agonists are administered during or within 2 weeks of use of an MAOI.
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.
Ribociclib: (Moderate) Due to a possible risk for QT prolongation, ribociclib and long-acting beta-agonists should be used together cautiously. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval like ribociclib. This risk may be more clinically significant with long-acting beta-agonists such as indacaterol as compared to short-acting beta-agonists.
Ribociclib; Letrozole: (Moderate) Due to a possible risk for QT prolongation, ribociclib and long-acting beta-agonists should be used together cautiously. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval like ribociclib. This risk may be more clinically significant with long-acting beta-agonists such as indacaterol as compared to short-acting beta-agonists.
Ritonavir: (Moderate) Although no dosage adjustment of the 75 mcg indacaterol daily dose is needed, use caution if indacaterol and ritonavir are used concurrently. Monitor the patient clinically for beta-agonist side effects like tremor, nervousness, or fast, irregular heart rate. In addition, both ritonavir and long-acting beta agonists (LABAs) are associated with QT prolongation; concomitant use may increase the risk of QT prolongation. By inhibiting CYP3A4, CYP2D6, and P-glycoprotein, ritonavir reduces indacaterol metabolism. In drug interaction studies, coadministration of indacaterol 300 mcg (single dose) with ritonavir (300 mg twice daily for 7.5 days) resulted in a 1.7-fold increase in indacaterol exposure (AUC) whereas indacaterol maximal concentration (Cmax) was unaffected.
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.
Salmeterol: (Major) Indacaterol should not be used in conjunction with other medications containing a long-acting beta-2 agonist, such as salmeterol for any reason, as overdose may result. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Acute symptoms should be treated with an inhaled short-acting beta-2 agonist (SABA) such as albuterol. SABAs should not be used on a regular basis (e.g., 4 times a day) while taking indacaterol. Increasing SABA use is a sign of deteriorating disease for which prompt medical attention is required. Prompt re-evaluation of the patient and their COPD treatment regimen should occur if indacaterol no longer controls symptoms of bronchoconstriction, the patient's SABA rescue becomes less effective, or the patient requires more SABA rescue doses than usual.
Secretin: (Major) Discontinue anticholinergic medications at least 5 half-lives before administering secretin. Patients who are receiving anticholinergics at the time of stimulation testing may be hyporesponsive to secretin stimulation and produce a false result. Consider additional testing and clinical assessments for aid in diagnosis.
Sedating H1-blockers: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and glycopyrrolate use. Concomitant use may result in additive anticholinergic adverse effects.
Serdexmethylphenidate; Dexmethylphenidate: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
Simeprevir: (Moderate) Simeprevir is a P-glycoprotein (P-gp) inhibitor and a CYP3A4 inhibitor, and might increase the concentrations and AUC of indacaterol, which is a P-gp and CYP3A4 substrate. When indacaterol has been administered with dual CYP3A4/P-gp inhibitors, the AUC has increased by 1.4- to 1.9-fold, depending on the agent used. An increase in maximal concentrations may also occur. Monitor patients for adverse effects of indacaterol, such as nervousness, tremor, and increased heart rate.
Sincalide: (Moderate) Sincalide-induced gallbladder ejection fraction may be affected by anticholinergics. False study results are possible in patients with drug-induced hyper- or hypo-responsiveness; thorough patient history is important in the interpretation of procedure results.
Sodium Bicarbonate: (Moderate) Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
Sodium Sulfate; Magnesium Sulfate; Potassium Chloride: (Major) Glycopyrrolate oral solution is contraindicated with concomitant solid oral dosage forms of potassium chloride due to risk for gastrointestinal mucosal injury. Glycopyrrolate orally disintegrating tablets are not recommended for use with solid oral dosage forms of potassium chloride. Use other glycopyrrolate dosage forms with solid oral dosage forms of potassium chloride with caution. Anticholinergics may decrease gastric motility and increase the transit time of solid oral dosage forms of potassium chloride leading to prolonged contact with the gastrointestinal mucosa.
Solifenacin: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics. Blurred vision and dry mouth would be common effects. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
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.
Sympathomimetics: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects.
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.
Theophylline, Aminophylline: (Moderate) Beta-agonists are commonly used in conjunction with aminophylline or theophylline therapy. Concomitant use can cause additive CNS stimulation; some patients may experience tremor or nervousness with combined use. More serious effects are rare, but may result in additive cardiovascular effects such as increased blood pressure and heart rate. Methylxanthine derivatives, ((e.g., theophylline and aminophylline) may rarely aggravate the hypokalemic effect seen with beta-agonists. Consider checking potassium levels if clinically indicated. (Moderate) Beta-agonists are commonly used in conjunction with aminophylline or theophylline therapy. Concomitant use can cause additive CNS stimulation; some patients may experience tremor or nervousness with combined use. More serious effects are rare, but may result in additive cardiovascular effects such as increased blood pressure and heart rate. Methylxanthine derivatives, (e.g., theophylline, aminophylline) may rarely aggravate the hypokalemic effect seen with beta-agonists. Consider checking potassium levels if clinically indicated.
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. (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
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.
Thyroid hormones: (Moderate) Monitor blood pressure and heart rate during concomitant beta-agonist and thyroid hormone use. Concurrent use may increase the effects of sympathomimetics or thyroid hormone. Thyroid hormones may increase the risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease.
Timolol: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
Tiotropium: (Major) Avoid concomitant use of anticholinergic medications and tiotropium due to increased risk for anticholinergic adverse effects.
Tiotropium; Olodaterol: (Major) Avoid concomitant use of anticholinergic medications and tiotropium due to increased risk for anticholinergic adverse effects. (Major) Indacaterol should not be used in conjunction with other medications containing a long-acting beta-2 agonist, such as olodaterol, for any reason, as overdose may result. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Acute symptoms should be treated with an inhaled short-acting beta-2 agonist (SABA) such as albuterol. SABAs should not be used on a regular basis (e.g., 4 times a day) while taking indacaterol. Increasing SABA use is a sign of deteriorating disease for which prompt medical attention is required. Prompt re-evaluation of the patient and their COPD treatment regimen should occur if indacaterol no longer controls symptoms of bronchoconstriction, the patient's SABA rescue becomes less effective, or the patient requires more SABA rescue doses than usual.
Tolterodine: (Moderate) Additive anticholinergic effects may be seen when tolterodine is used concomitantly with other antimuscarinics. When possible, avoid concurrent use, especially in the elderly, who are more susceptible to the anticholinergic effects. Consider alternatives to these other medications, if available. Clinicians should note that antimuscarinic effects might be seen not only on bladder smooth muscle, but also on GI function, the eye, and temperature regulation. Blurred vision, constipation, and dry mouth may be more prominent additive effects. With many of the listed agents, additive drowsiness may also occur when combined.
Topiramate: (Moderate) Monitor for decreased sweating and increased body temperature, especially in hot weather, during concomitant use of topiramate and other drugs that predispose persons to heat-related disorders, such as anticholinergic medications. Concomitant use increases the risk for oligohidrosis and hyperthermia.
Torsemide: (Moderate) Use beta-agonists and loop diuretics with caution due to risk for ECG changes and/or hypokalemia. The ECG changes and/or hypokalemia that may result from administration of loop diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded.
Tramadol: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant tramadol and glycopyrrolate use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Tramadol; Acetaminophen: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant tramadol and glycopyrrolate use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Trandolapril; Verapamil: (Minor) Although no dosage adjustment of the 75 mcg indacaterol daily dose is needed, use caution if indacaterol and verapamil are used concurrently. By inhibiting CYP3A4 and P-gp, verapamil alters indacaterol metabolism. In drug interaction studies, coadministration of indacaterol 300 mcg (single dose) with verapamil (80 mcg 3 times daily for 4 days) resulted in a 2-fold increase in indacaterol AUC (0-24), and 1.5-fold increase in indacaterol Cmax.
Tranylcypromine: (Moderate) Use beta-agonists with caution in patients receiving concomitant monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping treatment with MAOIs because the action of beta-agonists on the cardiovascular system may be potentiated.
Tricyclic antidepressants: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant tricyclic antidepressant and glycopyrrolate use. Concomitant use may result in additive anticholinergic adverse effects.
Trifluoperazine: (Moderate) Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including trifluoperazine. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other additive CNS effects may also occur.
Trimethobenzamide: (Moderate) Trimethobenzamide has CNS depressant effects and may cause drowsiness. The concurrent use of trimethobenzamide with other medications that cause CNS depression, like the anticholinergics, may potentiate the effects of either trimethobenzamide or the anticholinergic.
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.
Tucatinib: (Moderate) Monitor for indacaterol-related adverse effects, such as headache, nervousness, tremor, or cardiovascular effects, during coadministration with tucatinib. Concurrent use may increase plasma concentrations of indacaterol. Indacaterol is a CYP3A4 and P-glycoprotein (P-gp) substrate; tucatinib is a strong CYP3A4 inhibitor and P-gp inhibitor. Coadministration with other dual inhibitors of CYP3A4 and P-gp has increased exposure of indacaterol from 1.4- to 1.9- fold.
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: (Major) Indacaterol should not be used with vilanterol for any reason, as sympathomimetic overdose and additive anticholinergic effects may result. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Acute symptoms should be treated with an inhaled short-acting beta-2 agonist (SABA) such as albuterol. SABAs should not be used on a regular basis (e.g., 4 times a day) while taking indacaterol. Increasing SABA use is a sign of deteriorating disease for which prompt medical attention is required. Prompt re-evaluation of the patient and their COPD treatment regimen should occur if indacaterol no longer controls symptoms of bronchoconstriction, the patient's SABA rescue becomes less effective, or the patient requires more SABA rescue doses than usual. (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.
Verapamil: (Minor) Although no dosage adjustment of the 75 mcg indacaterol daily dose is needed, use caution if indacaterol and verapamil are used concurrently. By inhibiting CYP3A4 and P-gp, verapamil alters indacaterol metabolism. In drug interaction studies, coadministration of indacaterol 300 mcg (single dose) with verapamil (80 mcg 3 times daily for 4 days) resulted in a 2-fold increase in indacaterol AUC (0-24), and 1.5-fold increase in indacaterol Cmax.
Vibegron: (Moderate) Vibegron should be administered with caution in patients taking anticholinergics because of potential for an increased risk of urinary retention. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
Zonisamide: (Moderate) Zonisamide use is associated with case reports of decreased sweating, hyperthermia, heat intolerance, or heat stroke and should be used with caution in combination with other drugs that may also predispose patients to heat-related disorders like anticholinergics.

How Supplied

Indacaterol, Glycopyrrolate/Utibron Neohaler Respiratory (Inhalation) Pwd: 27.5-15.6mcg

Maximum Dosage
Adults

Contents of 2 capsules/day (total of 55 mcg indacaterol and 31.2 mcg glycopyrrolate) by inhalation.

Geriatric

Contents of 2 capsules/day (total of 55 mcg indacaterol and 31.2 mcg glycopyrrolate) by inhalation.

Adolescents

Safety and efficacy have not been established.

Children

Safety and efficacy have not been established.

Infants

Not indicated.

Neonates

Not indicated.

Mechanism Of Action

Indacaterol is a long-acting, selective beta-2 agonist (LABA). Glycopyrrolate is an antimuscarinic anticholinergic agent.
Indacaterol: Indacaterol is a long-acting agonist at beta-2 receptors. These receptors are present in large numbers in the lungs and are located on bronchiolar smooth muscle. Stimulation of beta-2 receptors in the lung causes relaxation of bronchial smooth muscle, which produces bronchodilation and a resultant increase in bronchial airflow. These effects are believed to be mediated, in part, by increased activity of adenyl cyclase, an intracellular enzyme responsible for the formation of cyclic-3',5'-adenosine monophosphate (cAMP). Indacaterol has more than a 24-fold greater agonist activity at beta-2 receptors (primarily in the lung) than at beta-1 receptors (primarily in the heart). However, 10% to 50% of the beta receptors in the heart are beta-2 receptors. Even highly selective beta-2 receptor agonists may have adverse cardiovascular effects, such as tachycardia, palpitations, and ischemia. Other common adverse effects due to activation of beta-receptors include skeletal muscle tremors and cramps, insomnia, decreases in serum potassium, and increases in blood glucose.
Glycopyrrolate: Glycopyrrolate is a long-acting antagonist at muscarinic receptors. It 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.

Pharmacokinetics

Indacaterol; glycopyrrolate is administered by oral inhalation.
Indacaterol: Protein binding is approximately 94 to 96%. CYP3A4 is the predominant isoenzyme responsible for hydroxylation; CYP1A1, CYP2D6, and UGT1A1 enzymes are also involved in metabolism to a minor extent. In pharmacokinetic study of orally administered radiolabeled drug, unchanged indacaterol was the single largest form of the drug in serum, accounting for one-third of total drug-related AUC over 24 hours. A hydroxylated derivative was the most prominent metabolite in serum. Glucuronate and dealkylate products, among other metabolites, were also identified. Less than 2% of the administered dose is excreted unchanged in the urine. Renal elimination accounts for approximately 2 to 6% of systemic clearance (serum clearance 18 to 23 L/hour); after oral administration, 90% or more of the dose was recovered fecally. Elimination appears to be multi-phasic with an average terminal half-life ranging from 45.5 to 126 hours. Effective half life, calculated from indacaterol accumulation after repeated dosing, ranges from 40 to 56 hours, which is consistent with an observed steady state of approximately 12 to 15 days.
Glycopyrrolate: Protein binding is 38 to 41% (at concentrations of 1 to 10 ng/mL after intravenous administration). In vitro investigations suggest multiple CYP isoenzymes contribute to the oxidative biotransformation of glycopyrrolate. Hydrolysis to the carboxylic acid derivative (M9) is most likely catalyzed by members from the cholinesterase family pre-systemically and/or via first pass metabolism from the swallowed fraction of the orally inhaled dose. Glucuronate and sulfate products, among other metabolites, have also been identified. Renal elimination, including active tubular secretion, of the parent drug accounts for approximately 60 to 70% of total clearance of systemically available drug. Although biliary excretion contributes to the other 30 to 40% of clearance, metabolism is believed to be responsible for the majority of non-renal clearance. Mean clearance of orally inhaled glycopyrrolate is approximately 17 to 24 L/hour. Elimination appears to be multi-phasic with a mean terminal half-life ranging from 33 to 53 hours.
 
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, P-gp, OCT
 
Indacaterol; glycopyrrolate is not likely to inhibit or induce the transport or metabolism of other drugs.
Indacaterol: CYP3A4 is the predominant isoenzyme responsible for the hydroxylation of indacaterol; indacaterol also has a low affinity for the efflux pump P-glycoprotein (P-gp). Drug interaction studies suggest potent and specific dual inhibitors of CYP3A4 and P-gp (e.g., ketoconazole, erythromycin, verapamil, ritonavir) may increase indacaterol exposure; however, this inhibition does not result in a need for dose adjustment of the usual therapeutic inhalation doses (75 mcg/day) of indacaterol.
Glycopyrrolate: The organic cation transport (OCT) is thought to contribute to the renal excretion of glycopyrrolate. Studies suggest inhibitors of OCT (e.g., cimetidine) may slightly increase glycopyrrolate exposure. However, no dosage adjustment is warranted for inhalational glycopyrrolate when administered concomitantly with OCT inhibitors.

Inhalation Route

Peak plasma concentrations of indacaterol and glycopyrrolate are achieved rapidly, within 15 minutes and 5 minutes, respectively, after oral inhalation of indacaterol; glycopyrrolate. Median time to onset, defined as a 100-mL increase from baseline in FEV1, was 12 to 16 minutes on Day 1 of treatment in patients receiving indacaterol; glycopyrrolate during clinical trials. Systemic exposure of indacaterol and glycopyrrolate at steady state is similar after administration of twice-daily doses of the combination inhaler compared to the monotherapy products, when given at equivalent doses.
Indacaterol: Bioavailabillty of indacaterol after oral inhalation is approximately 45%, from both pulmonary and intestinal absorption. Indacaterol serum concentrations increase with repeated daily administration. Steady-state is achieved within 12 to 15 days.
Glycopyrrolate: Steady-state is achieved within 7 days. There is no indication that glycopyrrolate pharmacokinetics change over time.

Pregnancy And Lactation
Pregnancy

There are no data on the presence of indacaterol; glycopyrrolate or their metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. Indacaterol, glycopyrrolate, and their metabolites have been detected in the milk of lactating rat; concentrations of glycopyrrolate have been up to 10-fold higher 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.