glycopyrrolate (systemic)

General

Pronunciation:
glye-koe-pye-roe-late

Trade Name(s)

• Cuvposa
• Glyrx-PF
• Robinul

Ther. Class.
antispasmodics

Pharm. Class.
anticholinergics

Indications

• Inhibits salivation and excessive respiratory secretions when given preoperatively.
• Reverses some of the secretory and vagal actions of cholinesterase inhibitors used to treat nondepolarizing neuromuscular blockade (cholinergic adjunct).
• Adjunctive management of peptic ulcer disease.
• Oral solution: Reduce chronic severe drooling in children with neurologic conditions associated with drooling.

Action

• Inhibits the action of acetylcholine at postganglionic sites located in smooth muscle, secretory glands, and the CNS (antimuscarinic activity).
• Low doses decrease sweating, salivation, and respiratory secretions.
• Intermediate doses result in increased heart rate.
• Larger doses decrease GI and GU tract motility.

Therapeutic Effect(s):

Decreased GI and respiratory secretions.

Pharmacokinetics

Absorption: Incompletely absorbed (<10%) after oral administration. Well absorbed after IM administration.

Distribution: Distribution not fully known. Does not significantly cross the blood-brain barrier or eye. Crosses the placenta.

Metabolism and Excretion: Eliminated primarily unchanged in the urine and bile.

Half-life: 1.7 hr (0.6–4.6 hr).

TIME/ACTION PROFILE (anticholinergic effects)

Contraindication/Precautions

Contraindicated in:

• Hypersensitivity;
• Angle-closure glaucoma;
• Acute hemorrhage;
• Tachycardia secondary to cardiac insufficiency or thyrotoxicosis;
• Severe ulcerative colitis;
• Toxic megacolon;
• Myasthenia gravis;
• Obstructive uropathy;
• Paralytic ileus;
• Concurrent use of oral potassium chloride dosage forms (oral solution only).

Use Cautiously in:

• Patients who may have intra-abdominal infections;
• Prostatic hyperplasia;
• Chronic renal, hepatic, pulmonary, or cardiac disease;
• Hyperthyroidism;
• Down syndrome and children with spastic paralysis or brain damage (may be hypersensitive to antimuscarinic effects);
• OB:  Lactation: Safety not established;
• Pedi:  ↑ sensitivity to anticholinergic effects and adverse reactions;
• Geri:   ↑ sensitivity to anticholinergic effects and adverse reactions.

Adverse Reactions/Side Effects

CV: tachycardia, orthostatic hypotension, palpitations

Derm: flushing

EENT: nasal congestion, blurred vision, cycloplegia, dry eyes, mydriasis

GI: dry mouth, vomiting, constipation

GU: urinary hesitancy, urinary retention

Neuro: headache, confusion, drowsiness.

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

• May ↑ GI mucosal lesions in patients taking oral  potassium chloride  tablets; concurrent use with oral glycopyrrolate solution contraindicated.
• Additive anticholinergic effects with other  anticholinergics, including  antihistamines,  phenothiazines,  meperidine,  amantadine,  tricyclic antidepressants,  quinidine, and  disopyramide.
• May alter the absorption of other  orally administered drugs  by slowing motility of the GI tract.
• May ↑ GI transit time of oral  digoxin  and ↑ digoxin levels.
•  Antacids  or  adsorbent   antidiarrheal agents  ↓ absorption of anticholinergics.
• May ↑ GI mucosal lesions in patients taking oral  potassium chloride  tablets.
• May ↑  atenolol  and  metformin  levels.
• May ↓ levels of  haloperidol  and  levodopa.
• Concurrent use may ↓ absorption of  ketoconazole  (administer 2 hr after ketoconazole).

Route/Dosage

Control of Secretions during Surgery

IM (Adults): 4.4 mcg/kg 30–60 min preop (not to exceed 0.1 mg).

IM (Children >2 yr): 4.4 mcg/kg 30–60 min preop.

IM (Children <2 yr): 4.4–8.8 mcg/kg 30–60 min preop.

Control of Secretions (chronic)

IM IV Children: 4–10 mcg/kg/dose every 3–4 hr.

PO Children: 40–100 mcg/kg/dose 3–4 times/day.

Cholinergic Adjunct

IV (Adults and Children): 200 mcg for each 1 mg of neostigmine or 5 mg of pyridostigmine given at the same time.

Antiarrhythmic

IV (Adults): 100 mcg, may be repeated every 2–3 min.

IV Children: 4.4 mcg/kg (up to 100 mcg); may be repeated every 2–3 min.

Peptic Ulcer

PO (Adults): 1–2 mg 2–3 times daily. An additional 2 mg may be given at bedtime; may be ↓ to 1 mg twice daily (not to exceed 8 mg/day).

IM IV (Adults): 100–200 mcg every 4 hr up to 4 times daily.

Chronic Severe Drooling

PO (Children 3–16 yr): Oral solution– 0.02 mg/kg 3 times daily; may ↑ by 0.02 mg/kg 3 times daily every 5–7 days (not to exceed 0.1 mg/kg 3 times daily or 1.5–3 mg/dose).

Availability (generic available)

Oral solution (cherry-flavor): 1 mg/5 mL

Solution for injection: 200 mcg (0.2 mg)/mL

Tablets: 1 mg, 1.5 mg, 2 mg

Assessment

• Assess heart rate, BP, and respiratory rate before and periodically during parenteral therapy.
• Monitor intake and output ratios in geriatric or surgical patients; glycopyrrolate may cause urinary retention. Instruct patient to void before parenteral administration.
• Assess patient routinely for abdominal distention and auscultate for bowel sounds. If constipation becomes a problem, increasing fluids and adding bulk to the diet may help alleviate the constipating effects of the drug.
• Periodic intraocular pressure determinations should be made for patients receiving long-term therapy.

• Pedi:   Monitor amount and frequency of drooling periodically during therapy.

  • Assess for hyperexcitability, a paradoxical response that may occur in children.

Lab Test Considerations:

Antagonizes effects of pentagastrin and histamine during the gastric acid secretion test. Avoid administration for 24 hr preceding the test.

• May cause ↓ uric acid levels in patients with gout or hyperuricemia.

Toxicity Overdose:

If overdose occurs, neostigmine is the antidote.

Implementation

• Do not administer cloudy or discolored solution.
• PO 

  Administer 30–60 min before meals to maximize absorption.

  • For drooling: Administer at least 1 hr before or 2 hr after meals.
  • Do not administer within 1 hr of antacids or antidiarrheal medications.
  • Oral dose is 10 times the parenteral dose.
• IM May be administered undiluted (200 mcg/mL).

Patient/Family Teaching

• Instruct patient to take glycopyrrolate as directed and not to take more than the prescribed amount. Take missed doses as soon as remembered if not just before next dose.
• Medication may cause drowsiness and blurred vision. Caution patient to avoid driving or other activities requiring alertness until response to the medication is known.
• Inform patient that frequent oral rinses, sugarless gum or candy, and good oral hygiene may help relieve dry mouth. Consult health care professional regarding use of saliva substitute if dry mouth persists for more than 2 wk.
• Advise patient to change positions slowly to minimize the effects of drug-induced orthostatic hypotension.
• Caution patient to avoid extremes of temperature. This medication decreases the ability to sweat and may increase the risk of heat stroke.
• Advise patient to notify health care professional immediately if eye pain or increased sensitivity to light occurs. Emphasize the importance of routine eye exams throughout therapy.
• Advise patient to consult health care professional before taking any OTC medications concurrently with this therapy.
• Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected, or if breast feeding.
• Geri:  Advise geriatric patients about increased susceptibility to side effects and to call health care professional immediately if they occur.

• Pedi:  Instruct parents to use a calibrated measuring device with solution for accurate dosing.

  • Advise parents to stop glycopyrrolate and notify health care professional if constipation; signs of urinary retention (inability to urinate, dry diapers or undergarments, irritability, or crying); or rash, hives, or an allergic reaction occurs.
  • Glycopyrrolate reduces sweating. Advise parents to avoid exposure of the patient to hot or very warm environmental temperatures to avoid overheating and heat exhaustion or heat stroke.

Evaluation/Desired Outcomes

• Mouth dryness preoperatively.
• Reversal of cholinergic medications.
• Decrease in GI motility and pain in patients with peptic ulcer disease.
• Reduce chronic severe drooling in children with neurologic conditions associated with drooling.