Glycopyrrolate is used as an adjunct in the treatment of peptic ulcer disease. Glycopyrrolate injection is used in patients with peptic ulcer disease when rapid antimuscarinic effect is desired or oral therapy is not tolerated. As with other antimuscarinics, there are no conclusive data from well-controlled studies which indicate that, in usually recommended dosage, glycopyrrolate aids in the healing, decreases the rate of recurrence, or prevents complications of peptic ulcers. In addition, in patients with gastric ulcer, antimuscarinics may delay gastric emptying and result in antral stasis. With the advent of more effective therapies for the treatment of peptic ulcer disease, antimuscarinics have only limited usefulness in this condition. Current epidemiologic and clinical evidence supports a strong association between gastric infection with Helicobacter pylori and the pathogenesis of duodenal and gastric ulcers, and the American College of Gastroenterology (ACG), the National Institutes of Health (NIH), and most clinicians currently recommend that all patients with initial or recurrent duodenal or gastric ulcer and documented H. pylori infection receive anti-infective therapy for treatment of the infection. For a more complete discussion of H. pylori infection, including details about the efficacy of various regimens and rationale for drug selection,
Glycopyrrolate injection has been used as a preoperative medication to inhibit salivation and excessive secretions of the respiratory tract; however, the current practice of using thiopental (no longer commercially available in the US), halothane, or similar general anesthetics that do not stimulate the production of salivary or tracheobronchial secretions has reduced the need to control excessive respiratory secretions during surgery. Although glycopyrrolate injection has been used prophylactically to prevent acid-aspiration pneumonitis during surgery, antimuscarinics, including glycopyrrolate, have not been shown to be effective for this use. Glycopyrrolate injection may be used to prevent cholinergic effects during surgery, such as cardiac arrhythmias, hypotension, and bradycardia, which may result from traction on viscera (with resultant vagal stimulation), stimulation of the carotid sinus, or administration of drugs (e.g., succinylcholine). Glycopyrrolate injection is administered concurrently with anticholinesterase agents (e.g., neostigmine, pyridostigmine) to block the adverse muscarinic effects of these latter agents when they are used after surgery to terminate curarization. Unlike atropine or hyoscyamine (tertiary amine antimuscarinics), glycopyrrolate (quaternary ammonium antimuscarinic) does not readily penetrate the CNS and therefore will not reverse the central effects of physostigmine. Because glycopyrrolate does not have appreciable CNS effects, it may be preferred in some patients. For further discussion on the use of glycopyrrolate injection in surgery, .
Dosage and Administration
Glycopyrrolate is administered orally or by IM or direct IV injection. For IV administration, glycopyrrolate may also be administered via the tubing of a running IV infusion of a compatible solution. For preoperative IM administration, glycopyrrolate is often administered in the same syringe with other compatible preoperative medications. When used concomitantly with neostigmine or physostigmine, glycopyrrolate may be administered IV simultaneously with the anticholinesterase agent via the same syringe. (See Chemistry and Stability: Stability.)
Because glycopyrrolate injection contains benzyl alcohol as a preservative, the manufacturer recommends that the drug not be used in neonates younger than 1 month of age. Although a causal relationship has not been established, administration of injections preserved with benzyl alcohol has been associated with toxicity in neonates. Toxicity appears to have resulted from administration of large amounts (i.e., 100-400 mg/kg daily) of benzyl alcohol in these neonates. Although use of drugs preserved with benzyl alcohol should be avoided in neonates whenever possible, the American Academy of Pediatrics (AAP) states that the presence of small amounts of the preservative in a commercially available injection should not proscribe its use when indicated in neonates.
Peptic Ulcer Disease
The usual initial oral dosage of glycopyrrolate for the adjunctive treatment of peptic ulcer disease in adults is 1 mg 3 times daily, in the morning, early afternoon, and at bedtime. Some patients may require 2 mg at bedtime to ensure overnight control of symptoms. Alternatively, an oral dosage for adults of 2 mg 2 or 3 times daily, given at equally spaced intervals, may be used. A maintenance dosage of 1 mg twice daily is adequate in most adults. The maximum adult oral dosage is 8 mg daily.
The usual adult IM or IV dosage of glycopyrrolate for the adjunctive treatment of peptic ulcer disease is 0.1 mg, administered every 4 hours, 3 or 4 times daily. When a more profound antimuscarinic effect is desired, 0.2 mg may be given IM or IV. Some patients may only require a single dose, and frequency of parenteral administration should be determined by the patient's response up to a maximum of 4 doses daily.
As with other antimuscarinics, higher than recommended dosage may be required for therapeutic effect in patients with peptic ulcer disease. Dosage should be carefully titrated until therapeutic effect is achieved or adverse effects become intolerable, using the lowest possible effective dosage.
Safety and efficacy of glycopyrrolate for the treatment of peptic ulcer disease in children younger than 12 years of age have not been established.
As a preoperative medication in adults or children 2 years of age and older, the usual dose of glycopyrrolate is 0.004 mg/kg, administered IM 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. Children 1-24 months of age may require a preoperative dose up to 0.009 mg/kg.
When intraoperative use of glycopyrrolate is necessary to prevent cholinergic effects during surgery in adults or children, the usual IV dose is 0.1 mg or 0.004 mg/kg (not to exceed 0.1 mg), respectively; if necessary, the dose may be repeated at 2- to 3-minute intervals. Because of the long duration of antimuscarinic effects of the preoperative dose, intraoperative doses of glycopyrrolate are rarely needed in children.
To block adverse muscarinic effects of anticholinesterase agents (i.e., neostigmine, pyridostigmine) when these agents are used to reverse the neuromuscular blockade produced by curariform agents in adults or children, the usual IV dose of glycopyrrolate is 0.2 mg for each 1 mg of neostigmine or 5 mg of pyridostigmine administered; glycopyrrolate is administered concurrently in the same syringe with or a few minutes before the anticholinesterase agent. Some clinicians recommend that, in the presence of bradycardia, antimuscarinics be administered IV before the anticholinesterase agent to increase the pulse rate to about 80 beats/minute.
Glycopyrrolate, like other quaternary ammonium drugs, is incompletely absorbed from the GI tract since it is completely ionized; however, the rate and extent of absorption of glycopyrrolate following oral administration has not been fully characterized.
Following IV administration of glycopyrrolate, the drug has an onset of action of about 1 minute. Following IM or subcutaneous injection, pharmacologic effects are evident within 15-30 minutes and peak within 30-45 minutes. The vagal blocking effects of the drug persist for 2-3 hours and inhibition of salivation persists for up to 7 hours after parenteral administration of the drug. Following oral administration, the anticholinergic effects of glycopyrrolate may persist for up to 8-12 hours.
Little information is available on the distribution of glycopyrrolate. Quaternary ammonium antimuscarinics are completely ionized and possess poor lipid solubility. Accordingly they do not readily penetrate the CNS or eye. Following IV administration of glycopyrrolate in animals, the drug is rapidly distributed throughout the body with highest concentrations appearing in the stomach and intestine. Following IV administration of a single 0.1 mg/kg dose of radiolabeled glycopyrrolate in dogs, peak CSF concentrations of the drug were 0.9 ng/mL, about 10% of the peak serum concentration. Glycopyrrolate is distributed into bile. Following surgery for cholelithiasis in patients who had T-tube drains placed into the common bile duct, peak biliary concentrations of drug were reached within 30-60 minutes after IV administration and persisted for up to 48 hours in some patients.
Glycopyrrolate crosses the placental barrier to a limited extent. Following IV administration of a single 0.1 mg/kg dose of radiolabeled drug in pregnant dogs, peak fetal concentrations were 0.63 ng/mL, about 4% of the peak maternal serum concentration. It is not known if glycopyrrolate distributes into milk.
Following IV administration of glycopyrrolate, serum concentrations of the drug decline rapidly, with less than 10% of the dose remaining in serum after 5 minutes and essentially no drug remaining during the period of 0.5-3 hours after administration. The elimination half-life of glycopyrrolate has not been determined.
Small amounts of glycopyrrolate are metabolized to several metabolites. Glycopyrrolate is excreted mainly as unchanged drug in feces via biliary elimination and in urine. In animals, 70-90% of a dose was eliminated in feces. Following IV administration of the drug in patients who had undergone surgery for cholelithiasis, about 85% of the dose was excreted in urine within 48 hours and less than 5% of the dose was distributed into T-tube drainage of bile, principally as unchanged drug.