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Glycopyrrolate (Oral Inhalation)


General


Pronunciation

(glye koe PYE roe late)


Brand Names: U.S.

  • Seebri Neohaler

Indications


Use: Labeled Indications

Chronic obstructive pulmonary disease: Maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema.

Limitations of use: Not indicated for the relief of an acute deterioration of COPD.


Contraindications


Hypersensitivity to glycopyrrolate or any component of the formulation.

Canadian labeling: Additional contraindications (not in US labeling): Severe hypersensitivity to milk proteins.


Dosing and Administration


Dosing: Adult

Chronic obstructive pulmonary disease (COPD): Oral inhalation:

US labeling: One capsule (15.6 mcg) inhaled twice daily. If a dose is missed, administer the next capsule at the usual time; do not use 2 capsules at one time and do not use >2 capsules/day (maximum: 31.2 mcg/day).

Canadian labeling: One capsule (50 mcg) inhaled once daily. If a dose is missed, administer as soon as possible on that day; do not take 2 doses on the same day.


Dosing: Geriatric

Refer to adult dosing.


Dosing: Renal Impairment

Glomerular filtration rate (estimated) ≥30 mL/minute/1.73 m2: No dosage adjustment necessary.

Glomerular filtration rate (estimated) <30 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer 's labeling. Use with caution; systemic exposure may be increased.

End-stage renal disease (ESRD) requiring dialysis: There are no dosage adjustments provided in the manufacturer 's labeling. Use with caution; systemic exposure may be increased.


Dosing: Hepatic Impairment

No dosage adjustment necessary.


Administration

Oral inhalation: For oral inhalation only. Do not swallow capsules. Administer at the same time each day. Do not remove capsules from blister until immediately before use. Use the new inhaler included with each prescription. Discard any capsules that are exposed to air and not used immediately. Refer to manufacturer 's product labeling for additional administration instructions.


Storage

Store at 25 ‚ °C (77 ‚ °F); excursions permitted to 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F). Protect from moisture. Remove capsule from blister pack immediately before use; discard capsule if not used immediately.


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Inhalation:

Seebri Neohaler: 15.6 mcg [contains milk protein]


Drug Interactions

AbobotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of AbobotulinumtoxinA. Monitor therapy

Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Monitor therapy

Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Analgesics (Opioid): Anticholinergic Agents may enhance the adverse/toxic effect of Analgesics (Opioid). Specifically, the risk for constipation and urinary retention may be increased with this combination. Monitor therapy

Anticholinergic Agents: May enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Avoid combination

Cannabinoid-Containing Products: Anticholinergic Agents may enhance the tachycardic effect of Cannabinoid-Containing Products. Exceptions: Cannabidiol. Monitor therapy

Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Avoid combination

Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Avoid combination

Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Monitor therapy

Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Avoid combination

Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Monitor therapy

Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Avoid combination

Mianserin: May enhance the anticholinergic effect of Anticholinergic Agents. Monitor therapy

Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Monitor therapy

OnabotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of OnabotulinumtoxinA. Monitor therapy

Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Avoid combination

Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Consider therapy modification

Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Monitor therapy

RimabotulinumtoxinB: Anticholinergic Agents may enhance the anticholinergic effect of RimabotulinumtoxinB. Monitor therapy

Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid using drugs with substantial anticholinergic effects in patients receiving secretin whenever possible. If such agents must be used in combination, monitor closely for a diminished response to secretin. Consider therapy modification

Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Avoid combination

Topiramate: Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. Monitor therapy

Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination


Monitoring Parameters

FEV1, peak flow (or other pulmonary function studies)


Adverse Reactions


1% to 10%:

Central nervous system: Fatigue ( ≥2%)

Gastrointestinal: Diarrhea ( ≥2%), nausea ( ≥2%), upper abdominal pain ( ≥2%)

Neuromuscular & skeletal: Arthralgia ( ≥2%), back pain ( ≥2%)

Respiratory: Upper respiratory tract infection (2% to 3%), bronchitis ( ≥2%), dyspnea ( ≥2%), nasopharyngitis ( ≥2%), pneumonia ( ≥2%), rhinitis ( ≥2%), wheezing ( ≥2%), oropharyngeal pain (2%), sinusitis (1%)

<1% (Limited to important or life-threatening): Angioedema, atrial fibrillation, diabetes mellitus, dysuria, gastroenteritis, hypersensitivity reaction, insomnia, paradoxical bronchospasm, peripheral pain, productive cough, pruritus, vomiting


Warnings/Precautions


Special Populations: Renal Function Impairment

A moderate mean increase in total systemic exposure (AUClast) of up to 1.4-fold was seen in mild and moderate impairment estimated glomerular filtration rate (eGFR) ≥30 mL/minute/1.73m2) and up to 2.2-fold in subjects with severe impairment and ESRD (eGFR <30 mL/minute/1.73m2).


Warnings/Precautions

Concerns related to adverse effects:

- Bronchospasm: Rarely, paradoxical bronchospasm may occur with use of inhaled bronchodilating agents; discontinue use and consider other therapy if bronchospasm occurs.

- CNS effects: May cause drowsiness and/or blurred vision, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

- Hypersensitivity: Immediate hypersensitivity reactions have been reported; if signs suggesting allergic reactions occur, in particular, angioedema (including difficulties in breathing or swallowing, swelling of the tongue, lips, and face), urticaria, or skin rash, discontinue therapy immediately. Use with caution in patients with severe hypersensitivity to milk proteins (contraindicated in the Canadian labeling).

Disease-related concerns:

- Cardiovascular disease: Cardiovascular effects (eg, atrial fibrillation, tachycardia) may occur after administration. Use with caution in patients with unstable ischemic heart disease, left ventricular failure, history of myocardial infarction, arrhythmia (excluding chronic stable atrial fibrillation), a history of long QT syndrome or whose QTc was prolonged at screening. In some cases, treatment may need to be discontinued.

- Glaucoma: Use with caution in patients with narrow-angle glaucoma. Monitor for signs/symptoms of glaucoma.

- Renal impairment: Use with caution in patients with severe renal impairment, including end stage renal disease (ESRD) requiring dialysis; systemic exposure to glycopyrrolate may be increased.

- Urinary retention: Use with caution in patients with urinary retention. Monitor for signs and symptoms of urinary retention, especially in patients with prostatic hyperplasia or bladder-neck obstruction.

Concurrent drug therapy issues:

- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Dosage form specific issues:

- Appropriate use: Not indicated for the initial (rescue) treatment of acute episodes of bronchospasm or with acutely deteriorating or potentially life-threatening COPD; after initiation of therapy, patients should use short-acting bronchodilators only on an as needed basis for acute symptoms.

- Lactose: May contain lactose; Canadian labeling contraindicates use in patients with severe hypersensitivity to milk proteins.


Pregnancy Considerations

Adverse events have been observed in some animal reproduction studies. Small amounts of glycopyrrolate cross the human placenta following IM injection.


Actions


Pharmacology

Competitively and reversibly inhibits the action of acetylcholine at muscarinic receptor subtypes 1 to 3 (greater affinity for subtypes 1 and 3) in bronchial smooth muscle thereby causing bronchodilation


Absorption

Rapid


Distribution

Vd: Steady state: 83 L; Terminal phase: 376 L


Metabolism

Hepatic (minimal)


Excretion

Urine; bile

Clearance: Children (1 to 14 years): Mean range: 1 to 1.4 L/kg/hour; Adults: Mean range: 0.4 to 0.68 L/kg/hour


Time to Peak

Plasma: 5 minutes


Half-Life Elimination

33 to 53 hours


Protein Binding

38% to 41%


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience nasal irritation, rhinorrhea, or pharyngitis. Have patient report immediately to prescriber difficulty swallowing, severe nausea, severe vomiting, vision changes, eye pain, severe eye irritation, visual halos or bright colors around lights, eye redness, painful urination, difficult urination, polyuria, difficulty breathing, wheezing, or cough (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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