GLYCOPYRROLATE
Brand names: Glycopyrrolate, GLYCOPYRROLATE, Cuvposa, glycopyrrolate, GLYRX-PF, Glycate, Glycopyrrolate Oral Solution, GLYCOPYRROLATE 1ML
Warnings
5 WARNINGS AND PRECAUTIONS • Constipation or intestinal pseudo-obstruction: May present as abdominal distention, pain, nausea, or vomiting. Assess patients for constipation, particularly within 4 to 5 days of initial dosing or after a dose increase. ( 5.1 ) • Incomplete mechanical intestinal obstruction: May present as diarrhea. If obstruction is suspected, discontinue glycopyrrolate and evaluate. ( 5.2 ) • High ambient temperature: To reduce the risk of heat prostration, avoid high temperatures. ( 5.3 ) 5.1 Constipation or Intestinal Pseudo-obstruction Constipation is a common dose-limiting adverse reaction which sometimes leads to glycopyrrolate discontinuation [see Adverse Reactions ( 6.1 )]. Assess patients for constipation, particularly within 4 to 5 days of initial dosing or after a dose increase. Intestinal pseudo-obstruction has been reported and may present as abdominal distention, pain, nausea or vomiting. 5.2 Incomplete Mechanical Intestinal Obstruction Diarrhea may be an early symptom of incomplete mechanical intestinal obstruction, especially in patients with ileostomy or colostomy. If incomplete mechanical intestinal obstruction is suspected, discontinue treatment with glycopyrrolate and evaluate for intestinal obstruction. 5.3 High Ambient Temperatures In the presence of high ambient temperature, heat prostration (fever and heat stroke due to decreased sweating) can occur with the use of anticholinergic drugs such as glycopyrrolate. Advise patients/caregivers to avoid exposure of the patient to hot or very warm environmental temperatures. 5.4 Operating Machinery or an Automobile Glycopyrrolate may produce drowsiness or blurred vision. As appropriate for a given age, warn the patient not to engage in activities requiring mental alertness such as operating a motor vehicle or other machinery, or performing hazardous work while taking glycopyrrolate. 5.5 Anticholinergic Drug Effects Use glycopyrrolate with caution in patients with conditions that are exacerbated by anticholinergic drug effects including: • Autonomic neuropathy • Renal disease • Ulcerative colitis – Large doses may suppress intestinal motility to the point of producing a paralytic ileus and for this reason may precipitate or aggravate “toxic megacolon”, a serious complication of the disease • Hyperthyroidism • Coronary heart disease, congestive heart failure, cardiac tachyarrhythmias, tachycardia, and hypertension • Hiatal hernia associated with reflux esophagitis, since anticholinergic drugs may aggravate this condition
Contraindications
CONTRAINDICATIONS Known hypersensitivity to glycopyrrolate or any of its inactive ingredients. In addition, in the management of peptic ulcer patients, because of the longer duration of therapy, glycopyrrolate injection may be contraindicated in patients with the following concurrent conditions: glaucoma; obstructive uropathy (for example, bladder neck obstruction due to prostatic hypertrophy); obstructive disease of the gastrointestinal tract (as in achalasia, pyloroduodenal stenosis, etc.); paralytic ileus, intestinal atony of the elderly or debilitated patient; unstable cardiovascular status in acute hemorrhage; severe ulcerative colitis; toxic megacolon complicating ulcerative colitis; myasthenia gravis.
Overdose
OVERDOSAGE To combat peripheral anticholinergic effects, a quaternary ammonium anticholinesterase such as neostigmine methylsulfate (which does not cross the blood-brain barrier) may be given intravenously in increments of 0.25 mg in adults. This dosage may be repeated every five to ten minutes until anticholinergic overactivity is reversed or up to a maximum of 2.5 mg. Proportionately smaller doses should be used in pediatric patients. Indication for repetitive doses of neostigmine should be based on close monitoring of the decrease in heart rate and the return of bowel sounds. If CNS symptoms (e.g., excitement, restlessness, convulsions, psychotic behavior) occur, physostigmine (which does cross the blood–brain barrier) may be used. Physostigmine 0.5 to 2 mg should be slowly administered intravenously and repeated as necessary up to a total of 5 mg in adults. Proportionately smaller doses should be used in pediatric patients. To combat hypotension, administer IV fluids and/or pressor agents along with supportive care. Fever should be treated symptomatically. Following overdosage, a curare-like action may occur, i.e., neuromuscular blockade leading to muscular weakness and possible paralysis. In the event of a curare-like effect on respiratory muscles, artificial respiration should be instituted and maintained until effective respiratory action returns.
Drug interactions
7 DRUG INTERACTIONS Drugs Affected by Reduced GI Transit Time Glycopyrrolate reduces GI transit time, which may result in altered release of certain drugs when formulated in delayed- or controlled-release dosage forms. • The passage of potassium chloride tablets through the GI tract may be arrested or delayed with coadministration of glycopyrrolate. Solid dosage forms of potassium chloride are contraindicated [see Contraindications ( 4 )]. • Digoxin administered as slow dissolution oral tablets may have increased serum levels and enhanced action when administered with glycopyrrolate. Monitor patients receiving slow dissolution digoxin for increased action if glycopyrrolate is coadministered regularly. Consider the use of other oral dosage forms of digoxin (e.g., elixir or capsules). Amantadine The anticholinergic effects of glycopyrrolate may be increased with concomitant administration of amantadine. Consider decreasing the dose of glycopyrrolate during coadministration of amantadine. Drugs Whose Plasma Levels May be Increased by Glycopyrrolate Coadministration of glycopyrrolate may result in increased levels of certain drugs. • Atenolol’s bioavailability may be increased with coadministration of glycopyrrolate. A reduction in the atenolol dose may be needed. • Metformin plasma levels may be elevated with coadministration of glycopyrrolate, increasing metformin’s pharmacologic and toxic effects. Monitor clinical response to metformin with concomitant glycopyrrolate administration; consider a dose reduction of metformin if warranted. Drugs Whose Plasma Levels May be Decreased by Glycopyrrolate Coadministration of glycopyrrolate may result in decreased levels of certain drugs. • Haloperidol’s serum level may be decreased when coadministered with glycopyrrolate, resulting in worsening of schizophrenic symptoms, and development of tardive dyskinesia. Closely monitor patients if coadministration cannot be avoided. • Levodopa’s therapeutic effect may be reduced with glycopyrrolate administration. Consider increasing the dose of levodopa. • Digoxin tablets: Use with glycopyrrolate can increase digoxin serum levels. Monitor patients and consider use of alternative dosage forms of digoxin. ( 7 ) • Amantadine: Effects of glycopyrrolate may be increased with concomitant administration of amantadine. Consider decreasing the dose of glycopyrrolate during concomitant use. ( 7 ) • Atenolol or metformin: Glycopyrrolate may increase serum levels of atenolol or metformin. Consider dose reduction when used with glycopyrrolate. ( 7 ) • Haloperidol or levodopa: Glycopyrrolate may decrease serum levels of haloperidol or levodopa. Consider a dose increase when used with glycopyrrolate. ( 7 )
Uses
1 INDICATIONS AND USAGE Glycopyrrolate oral solution is indicated to reduce chronic severe drooling in patients aged 3 to 16 years with neurologic conditions associated with problem drooling (e.g., cerebral palsy). Glycopyrrolate is an anticholinergic indicated to reduce chronic severe drooling in patients aged 3 to 16 years with neurologic conditions associated with problem drooling (e.g., cerebral palsy). ( 1 )
Dosage forms & strengths
DOSAGE & ADMINISTRATIN NOTE: CONTAINS BENZYL ALCOHOL (see PRECAUTIONS ). Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Glycopyrrolate injection may be administered intramuscularly, or intravenously, without dilution, in the following indications. Adults Preanesthetic Medication The recommended dose of glycopyrrolate injection is 0.004 mg/kg by intramuscular injection, given 30 to 60 minutes prior to the anticipated time of induction of anesthesia or at the time the preanesthetic narcotic and/or sedative are administered. Intraoperative Medication Glycopyrrolate injection may be used during surgery to counteract drug-induced or vagal reflexes and their associated arrhythmias (e.g., bradycardia). It should be administered intravenously as single doses of 0.1 mg and repeated, as needed, at intervals of 2 to 3 minutes. The usual attempts should be made to determine the etiology of the arrhythmia, and the surgical or anesthetic manipulations necessary to correct parasympathetic imbalance should be performed. Reversal of Neuromuscular Blockade The recommended dose of glycopyrrolate injection is 0.2 mg for each 1.0 mg of neostigmine or 5.0 mg of pyridostigmine. In order to minimize the appearance of cardiac side effects, the drugs may be administered simultaneously by intravenous injection and may be mixed in the same syringe. Peptic Ulcer The usual recommended dose of glycopyrrolate injection is 0.1 mg administered at 4-hour intervals, 3 or 4 times daily intravenously or intramuscularly. Where more profound effect is required, 0.2 mg may be given. Some patients may need only a single dose, and frequency of administration should be dictated by patient response up to a maximum of four times daily. Glycopyrrolate injection is not recommended for the treatment of peptic ulcer in pediatric patients (see PRECAUTIONS, PEDIATRIC USE ). Pediatric Patients (see PRECAUTIONS, PEDIATRIC USE ) Preanesthetic Medication The recommended dose of glycopyrrolate injection in pediatric patients is 0.004 mg/kg intramuscularly, given 30 to 60 minutes prior to the anticipated time of induction of anesthesia or at the time the preanesthetic narcotic and/or sedative are administered. Infants (1 month to 2 years of age) may require up to 0.009 mg/kg. Intraoperative Medication Because of the long duration of action of glycopyrrolate injection if used as preanesthetic medication, additional glycopyrrolate injection for anticholinergic effect intraoperatively is rarely needed; in the event it is required the recommended pediatric dose is 0.004 mg/kg intravenously, not to exceed 0.1 mg in a single dose which may be repeated, as needed, at intervals of 2 to 3 minutes. The usual attempts should be made to determine the etiology of the arrhythmia, and the surgical or anesthetic manipulations necessary to correct parasympathetic imbalance should be performed. Reversal of Neuromuscular Blockade The recommended pediatric dose of glycopyrrolate injection is 0.2 mg for each 1.0 mg of neostigmine or 5.0 mg of pyridostigmine. In order to minimize the appearance of cardiac side effects, the drugs may be administered simultaneously by intravenous injection and may be mixed in the same syringe. Peptic Ulcer Glycopyrrolate injection is not recommended for the treatment of peptic ulcer in pediatric patients (see PRECAUTIONS, PEDIATRIC USE ). Diluent Compatibilities Dextrose 5% and 10% in water, or saline, dextrose 5% in sodium chloride 0.45%, sodium chloride 0.9%, and Ringer’s Injection. Diluent Incompatibilities Lactated Ringer’s solution. Admixture Compatibilities Physical Compatibility This list does not constitute an endorsement of the clinical utility or safety of co‑administration of glycopyrrolate with these drugs. Glycopyrrolate injection is compatible for mixing and injection with the following injectable dosage forms: atropine sulfate, USP; physostigmine salicylate; diphenhydramine HCl; codeine phosphate, USP; benz-quinamide HCl; hydromorphone HCl, USP; droperidol; levorphanol tartrate; lidocaine, USP; meperidine HCl, USP; pyridostigmine bromide; morphine sulfate, USP; nalbuphine HCl; oxymorphone HCl; procaine HCl, USP; promethazine HCl, USP; neostigmine methylsulfate, USP; scopolamine HBr, USP; butorphanol tartrate; fentanyl citrate; trimethobenzamide HCl; and hydroxyzine HCl. Glycopyrrolate injection may be administered via the tubing of a running infusion of normal saline. Admixture Incompatibilities Physical Incompatibility Since the stability of glycopyrrolate is questionable above a pH of 6.0 do not combine glycopyrrolate injection in the same syringe with methohexital Na; chloramphenicol Na succinate; dimenhydrinate; pentobarbital Na; thiopental Na; secobarbital Na; sodium bicarbonate; diazepam; dexamethasone Na phosphate; or pentazocine lactate. These mixtures will result in a pH higher than 6.0 and may result in gas production or precipitation.