Generic Name: Glycopyrrolate
Class: Antimuscarinics/Antispasmodics
VA Class: AU350
CAS Number: 596-51-0

Introduction

Antimuscarinic; a synthetic quaternary ammonium compound.a b c

Uses for Robinul

Peptic Ulcer Disease

Has been used as an adjunct in the treatment of peptic ulcer disease;a b however, no conclusive data that it aids in the healing, decreases the rate of recurrence, or prevents complications of peptic ulcers.c d

With the advent of more effective therapies for the treatment of peptic ulcer disease, antimuscarinics have only limited usefulness in this condition.c d

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Surgery

To inhibit salivation and excessive secretions of the respiratory tract (antisialogue).b c d However, current surgical practice (e.g., using general anesthetics that do not stimulate salivary and tracheobronchial secretions) has reduced the need to control excessive respiratory secretions during surgery.c d

To prevent other cholinergic effects during surgery (e.g., cardiac arrhythmias, hypotension, bradycardia) secondary to visceral traction (resultant vagal stimulation), carotid sinus stimulation, or concomitant drugs (e.g., succinylcholine).b c d

To block adverse muscarinic effects of anticholinesterase agents that are used after surgery to terminate curarization.b c d

Ineffective for preventing acid-aspiration pneumonitis during surgery.c d

Robinul Dosage and Administration

General

  • Administer lowest effective dosage to minimize risk and occurrence of adverse effects.a

  • Adjust dosage carefully according to individual requirements and response.a c

Administration

Administer orally or by IM or IV injection.a b c

Oral Administration

Administer orally 2 or 3 times daily.a c

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by direct IV injection;b c alternatively, administer via the tubing of a running IV infusion of a compatible solution.b c

IM Administration

May administer in the same syringe with other compatible preoperative medications.c (See Compatibility in Syringe under Stability.)

Dosage

Pediatric Patients

Surgery
Preoperatively to Decrease Secretions and Block Cardiac Vagal Reflexes
IM

0.004 mg/kg given 30–60 minutes prior to the anticipated time of induction of anesthesia or at the time other preanesthetic medications (e.g., opiates, sedatives) are administered.b c

Children 1 month to 2 years of age may require dose of up to 0.009 mg/kg.b c

Intraoperatively to Prevent Cholinergic Effects
IV

0.004 mg/kg (maximum 0.1 mg); may repeat as needed at intervals of 2–3 minutes.b c However, intraoperative doses rarely are needed in children because of long duration of antimuscarinic effects of preoperative dose.b c

Muscarinic Blockade during Anticholinesterase Reversal of Curariform Neuromuscular Blockade
IV

0.2 mg for each 1 mg of neostigmine methylsulfate or 5 mg of pyridostigmine bromide.b c

To minimize the appearance of adverse cardiac effects, administer glycopyrrolate simultaneously (e.g., mixed in the same syringe) with or a few minutes before the anticholinesterase agent.b c

If bradycardia is present, administer before the anticholinesterase agent to increase pulse to 80 bpm.c

Adults

Peptic Ulcer Disease
Oral

Initially, 1 mg 3 times daily (morning, early afternoon, and bedtime); may increase bedtime dose to 2 mg if needed to control overnight symptoms.a c

Alternatively, 2 mg given 2 or 3 times daily at equally spaced intervals.a c

Maintenance dosage of 1 mg twice daily is adequate in most adults.a c

IV or IM

0.1 mg administered at 4-hour intervals 3 or 4 times daily.b c

0.2 mg may be given when a more profound antimuscarinic effect is desired.b c

Some patients may need only a single dose; patient response dictates frequency of administration, up to a maximum of 4 times daily.b c

Surgery
Preoperatively to Decrease Secretions and Block Cardiac Vagal Reflexes
IM

0.004 mg/kg given 30–60 minutes prior to the anticipated time of induction of anesthesia or at the time other preanesthetic medications (e.g., opiates, sedatives) are administered.b c

Intraoperatively to Prevent Cholinergic Effects
IV

Usual dose is 0.1 mg; may repeat as needed at intervals of 2–3 minutes.b c

Muscarinic Blockade during Anticholinesterase Reversal of Curariform Neuromuscular Blockade
IV

0.2 mg for each 1 mg of neostigmine methylsulfate or 5 mg of pyridostigmine bromide.b c

To minimize the appearance of adverse cardiac effects, administer glycopyrrolate simultaneously (e.g., mixed in the same syringe) with or a few minutes before the anticholinesterase agent.b c

If bradycardia is present, administer before the anticholinesterase agent to increase pulse to 80 bpm.c

Prescribing Limits

Adults

Peptic Ulcer Disease
Oral

Maximum 8 mg daily.a c

IV or IM

Maximum 4 doses daily.c

Special Populations

Renal Impairment

Dosage reduction may be necessary.b

Geriatric Patients

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.b

Cautions for Robinul

Contraindications

  • Known hypersensitivity to glycopyrrolate or any ingredient in the formulation.a b d

  • Angle-closure glaucoma.a b d

  • Tachycardia secondary to cardiac insufficiency or thyrotoxicosis.d

  • Oral Therapy and Longer-duration Parenteral Therapy (e.g., for Treatment of Peptic Ulcer)
  • Obstructive uropathy (e.g., bladder neck obstruction secondary to prostatic hypertrophy).a b d

  • Obstructive GI disease (e.g., pyloroduodenal stenosis, achalasia).a b d

  • Paralytic ileus.a b d

  • Intestinal atony (especially in geriatric and debilitated patients).a b d

  • Severe ulcerative colitis.a b d

  • Toxic megacolon complicating ulcerative colitis.a b d

  • Acute hemorrhage when cardiovascular status is unstable.a b d

  • Myasthenia gravisa b (unless used to reduce adverse muscarinic effects of an anticholinesterase agent such as neostigmined ).

Warnings/Precautions

Warnings

Overdosage

Avoid overdosage.d Potential risk of curariform neuromuscular blockade resulting in muscle weakness or paralysis with overdosage.a b d

Thermoregulatory Effects

Presence of fever, exposure to high environmental temperatures, and/or physical exertion may result in heat prostration due to decreased sweating, particularly in children and geriatric patients.a b d

CNS Effects

Risk of drowsiness.a b d Performance of activities requiring mental alertness (e.g., operating machinery, driving a motor vehicle) may be impaired.a b d

Intestinal Obstruction

Extreme caution in diarrhea (especially in patients with ileostomy or colostomy) because diarrhea may be an early sign of intestinal obstruction.a b d

Major Toxicities

Cardiovascular Effects

Caution in cardiac arrhythmias (including tachyarrhythmia), CHF, or CADa b since antimuscarinics block vagal inhibition of the SA nodal pacemaker.d Investigate cause of tachycardia before administering glycopyrrolate injection, since an increase in heart rate may occur.b

GI Disorders

Extreme caution in known or suspected GI infections because of decreased GI motility and retention of causative organism and/or toxins.d

Extreme caution in mild to moderate ulcerative colitis; large doses may suppress intestinal motility, resulting in paralytic ileus and toxic megacolon.a b d

Caution in gastric ulcer because of delayed gastric emptying and possible antral stenosis.b d

Caution in esophageal reflux and hiatal hernia because of decreased gastric motility and lower esophageal sphincter pressure leading to gastric retention and reflux aggravation.a b d

GU Disorders

Extreme caution in patients with partial obstructive uropathy because of decreased tone and amplitude of contractions of ureters and bladder and resultant urinary retention.a d (See Contraindications under Cautions.)

General Precautions

Neuropathy

Caution in patients with autonomic neuropathy.a b d

Down’s Syndrome, Spastic Paralysis, and Brain Damage

Increased sensitivity to antimuscarinic effects (e.g., mydriasis, positive chronotropic effect).b d

Hypertension

Caution in hypertensive patients.a b d

Hyperthyroidism

Caution in hyperthyroid patients.a b d

Ocular Effects

Blurred vision or sensitivity of the eyes to light may occur.b

Specific Populations

Pregnancy

Category B.b

Lactation

Not known whether glycopyrrolate is distributed into milk.a b Caution if used in nursing women.b

Pediatric Use

Manufacturers state that safety and efficacy in pediatric patients (including safety and efficacy for treatment of peptic ulcer disease in pediatric patients) are not established.a b

Use with caution; infants and children may be more susceptible to the effects of antimuscarinics.b d Patients with Down’s syndrome and children with spastic paralysis or brain damage may be hypersensitive to antimuscarinic effects (e.g., mydriasis, positive chronotropic effect).b d

Dysrhythmias have been reported in pediatric patients receiving IV glycopyrrolate preoperatively or during anesthesia.b

Large amounts of benzyl alcohol (i.e., 100–400 mg/kg daily) have been associated with toxicity in neonates;359 360 361 362 363 364 each mL of glycopyrrolate injection contains 9 mg of benzyl alcohol.b Manufacturer does not recommend use in neonates;b AAP states that the presence of small amounts of this preservative in a commercially available injection should not proscribe its use when indicated in neonates.359

Geriatric Use

Use with caution;a b d possible increased susceptibility to the adverse effects of antimuscarinics.d

Hepatic Impairment

Use with caution.a b d

Renal Impairment

Use with caution.a b d Elimination may be severely impaired.b Dosage reduction may be necessary.b

Common Adverse Effects

Xerostomia, decreased sweating, urinary hesitancy and retention, blurred vision, tachycardia, palpitations, dilatation of the pupil, cycloplegia, increased ocular tension, loss of taste, headaches, nervousness, mental confusion, drowsiness, weakness, dizziness, insomnia, constipation, nausea, vomiting, bloated feeling.a b d Ocular and CNS effects are less common with glycopyrrolate than with tertiary amine antimuscarinics.d

Interactions for Robinul

Orally Administered Drugs

Potential pharmacokinetic interaction (altered GI absorption of various drugs); antimuscarinics may inhibit GI motility, delay gastric emptying, and prolong GI transit time.d

Specific Drugs

Drug

Interaction

Comments

Amantadine

Possible additive anticholinergic effectsd

Use concomitantly with cautiond

Antacids

Possible decreased absorption of antimuscarinicd

Administer oral glycopyrrolate at least 1 hour before antacidsd

Antiarrhythmic agents (quinidine, disopyramide, procainamide)

Possible additive anticholinergic effectsd

Use concomitantly with cautiond

Antidepressants, tricyclic

Possible additive anticholinergic effectsb d

Use concomitantly with cautiond

Antihistamines (meclizine)

Possible additive anticholinergic effectsd

Use concomitantly with cautiond

Antiparkinsonian agents

Possible additive anticholinergic effectsb d

Use concomitantly with cautiond

Corticosteroids

Possible increased intraocular pressured

Cyclopropane anesthesia

Increased risk of ventricular arrhythmiasb

Use with caution; administer IV glycopyrrolate in incremental doses of ≤1 mg to reduce risk of ventricular arrhythmiasb

Glutethimide

Possible additive anticholinergic effectsd

Use concomitantly with cautiond

Ketoconazole

Possible decreased ketoconazole absorption d

If concomitant therapy is necessary, give antimuscarinic at least 2 hours after ketoconazoled

Levodopa

Possible increased gastric metabolism of levodopa and decreased levodopa absorption in the small intestined

Toxicity may result from increased levodopa absorption if antimuscarinic is discontinued without a concomitant reduction in levodopa dosaged

Meperidine

Possible additive anticholinergic effectsd

Use concomitantly with cautiond

Phenothiazines

Possible additive anticholinergic effectsb d

Use concomitantly with cautiond

Potassium chloride

Glycopyrrolate may potentiate potassium chloride’s local GI mucosal effectsb d

Use glycopyrrolate cautiously with potassium chloride preparations (especially wax-matrix preparations); monitor carefully for evidence of GI mucosal lesionsd

Skeletal muscle relaxants

Possible additive anticholinergic effectsd

Use concomitantly with cautiond

Robinul Pharmacokinetics

Absorption

Bioavailability

Incompletely absorbed from the GI tract.c d

Rapidly absorbed following IM injection.d

Onset

Following IV administration, onset of action generally occurs within 1 minute.b c

Following IM or sub-Q injection, effects are evident within 15–30 minutes and peak within 30–45 minutes.b c

Duration

Following oral administration, anticholinergic effects may persist for up to 8–12 hours.c

Following parenteral administration, vagal blocking effects persist for 2–3 hours and the antisialogue effects persist up to 7 hours.b c

Distribution

Extent

Rapidly distributed throughout the body with highest concentrations in the stomach and intestine following IV administration in animals.c d

Distributed into bile.c d

Does not readily cross lipid membranes;b c does not readily cross the blood-brain barrier or penetrate the eye.c d

Glycopyrrolate crosses the placenta to a limited extent; not known whether distributed into milk.a b c

Elimination

Metabolism

Small amounts are metabolized to several metabolites.c

Elimination Route

Excreted principally as unchanged drug in feces via biliary excretion and in urine.b c

Half-life

Adults: about 30–75 minutes;b infants: 22–130 minutes; children: 19–99 minutes.b

Special Populations

In patients undergoing renal transplantation, half-life is prolonged to 47 minutes compared with 19 minutes in healthy individuals.b

Stability

Storage

Oral

Tablets

20–25°C.a

Parenteral

Injection

20–25°C.b

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility

If the pH of the admixture is >6, rapid ester hydrolysis of glycopyrrolate generally occurs.b c

CompatibleHID

Dextrose 5% in sodium chloride 0.45%

Dextrose 5 or 10%b in water

Ringer’s injection

Sodium chloride 0.9%

Incompatible

Ringer’s injection, lactatedb

Drug Compatibility

Generally incompatible with drugs that have a pH >6.b c If the pH of the admixture is >6, rapid ester hydrolysis of glycopyrrolate generally occurs.b c

Admixture CompatibilityHID

Compatible

Buprenorphine HCl with haloperidol lactate

Incompatible

Methylprednisolone sodium succinate

Y-Site CompatibilityHID

Compatible

Dexmedetomidine HCl

Propofol

Palonosetron HCl

Compatibility in SyringeHID

Compatible

Atropine sulfate

Buprenorphine HCl with haloperidol lactate

Butorphanol tartrateb

Chlorpromazine HCl

Diphenhydramine HCl

Droperidol

Fentanyl citrateb

Hydromorphone HCl

Hydroxyzine HCl

Lidocaine HCl

Meperidine HCl

Midazolam HCl

Morphine sulfate

Nalbuphine HCl

Neostigmine methylsulfate

Ondansetron HCl

Physostigmine salicylateb

Prochlorperazine edisylate

Promethazine HCl

Ranitidine HCl

Scopolamine HBr

Trimethobenzamide HCl

Incompatible

Chloramphenicol sodium succinate

Dexamethasone sodium phosphate

Diazepam

Dimenhydrinate

Methohexital sodium

Pentazocine lactate

Pentobarbital sodium

Sodium bicarbonate

Actions

  • Competitively inhibits acetylcholine or other cholinergic stimuli at autonomic effectors innervated by postganglionic cholinergic nerves and, to a lesser extent, on smooth muscles that lack cholinergic innervation.a b d

  • At usual doses, principally antagonizes cholinergic stimuli at muscarinic receptors and has little or no effect on cholinergic stimuli at nicotinic receptors.d

  • At high doses, may produce substantial ganglionic blockade with resultant adverse effects (e.g., impotence, postural hypotension); in overdosage, may cause curariform neuromuscular blockade.d

  • Antimuscarinics also have been referred to as anticholinergics (cholinergic blocking agents), but this term is appropriate only when it describes the antagonism of cholinergic stimuli at any cholinergic receptor, whether muscarinic or nicotinic.d

  • Also have been referred to as parasympatholytics since the antagonized functions principally are under the parasympathetic division of the nervous system.d

  • Receptors at various sites are not equally sensitive to inhibition of muscarinic effects.d Relative sensitivity of physiologic functions (proceeding from the most sensitive) is as follows: secretions of the salivary, bronchial, and sweat glands; pupillary dilation; ocular accommodation, and heart rate; contraction of the detrusor muscle of the bladder and smooth muscle of the GI tract; and gastric secretion and motility.d Doses used to decrease gastric secretions are likely to cause dryness of the mouth (xerostomia) and interfere with visual accommodation, and possibly cause difficulty in urinating.d

Advice to Patients

  • Importance of promptly notifying clinician if urinary hesitancy or retention occurs.e

  • Advise that dry mouthd or sensitivity of eyes to lightb may occur.

  • Risk of hyperthermia and heat prostration;a b d avoid exposure to high environmental temperatures and avoid use when febrile.c d

  • Risk of dizziness, drowsiness, or blurred vision;a b d avoid activities requiring mental alertness and/or visual acuity (e.g., driving, operating machinery, hazardous work) until effects on individual are known.d

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.a b d

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.a b

  • Importance of informing patients of other important precautionary information.a b (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Glycopyrrolate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

1 mg

Robinul (scored)

First Horizon

2 mg

Robinul Forte (scored)

First Horizon

Parenteral

Injection

0.2 mg/mL*

Robinul

Baxter

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Glycopyrrolate 1MG Tablets (PAR): 100/$104.99 or 300/$314.96

Glycopyrrolate 2MG Tablets (WEST-WARD): 90/$135.98 or 270/$369.99

Robinul 1MG Tablets (SHIONOGI PHARMA): 90/$359.99 or 270/$1,010.34

Robinul-Forte 2MG Tablets (SHIONOGI PHARMA): 60/$628.79 or 180/$1,798.76

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions July 9, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

Only references cited for selected revisions after 1984 are available electronically.

359. American Academy of Pediatrics Committee on Fetus and Newborn and Committee on Drugs. Benzyl alcohol: toxic agent in neonatal units. Pediatrics. 1983; 72:356-8. [IDIS 175725] [PubMed 6889041]

360. Anon. Benzyl alcohol may be toxic to newborns. FDA Drug Bull. 1982; 12(2):10-1.

361. Centers for Disease Control. Neonatal deaths associated with use of benzyl alcohol. MMWR Morb Mortal Wkly Rep. 1982; 31:290-1. [IDIS 150868] [PubMed 6810084]

362. Gershanik J, Boecler B, Ensley H et al. The gasping syndrome and benzyl alcohol poisoning. N Engl J Med. 1982; 307:1384-8. [IDIS 160823] [PubMed 7133084]

363. Menon PA, Thach BT, Smith CH et al. Benzyl alcohol toxicity in a neonatal intensive care unit: incidence, symptomatology, and mortality. Am J Perinatol. 1984; 1:288-92. [PubMed 6440575]

364. Anderson CW, Ng KJ, Andresen B et al. Benzyl alcohol poisoning in a premature newborn infant. Am J Obstet Gynecol. 1984; 148:344-6. [IDIS 181207] [PubMed 6695984]

a. First Horizon Pharmaceutical Corporation. Robinul (glycopyrrolate) and Robinul Forte (glycopyrrolate) tablets prescribing information. Alpharetta, GA; 2003 Jan.

b. Baxter. Robinul (glycopyrrolate) injection prescribing information. Deerfield, IL; 2005 Aug.

c. AHFS drug information 2006. McEvoy GK, ed. Glycopyrrolate. Bethesda, MD: American Society of Health-System Pharmacists; 2006:1272-73.

d. AHFS drug information 2006. McEvoy GK, ed. Antimuscarinics/antispasmodics general statement. Bethesda, MD: American Society of Health-System Pharmacists; 2006:1257-1264.

e. Schilling McCann JA, Publisher. AHFS drug handbook. 2nd ed. Glycopyrrolate. Philadelphia, PA: Lippincott Williams and Wilkins and American Society of Health-System Pharmacists; 2003:585-7.

HID. Trissel LA. Handbook on injectable drugs. 17th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2013:568-73.

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