GLYCOPYRROLATE
DESCRIPTION:
PYROLATE (glycopyrrolate) is a synthetic anticholinergic agent. Each 1 mL
contains:
Glycopyrrolate, USP............... 0.2 mg
Water for Injection, USP.............q.s.
Benzyl Alcohol, NF (preservative)....0.9%
pH adjusted, when necessary, with hydrochloric acid and/or sodium hydroxide.
FOR INTRAMUSCULAR OR INTRAVENOUS ADMINISTRATION.
Glycopyrrolate is a quaternary ammonium compound with the following chemical
name:
3((cyclopentylhydroxyphenylacetyl)oxy)-1,1-dimeth yl pyrrolidinium bromide.
Unlike atropine, glycopyrrolate is completely ionized at physiological pH
values.
PYROLATE Injectable is a clear, colorless, sterile liquid; pH 2.0-3.0.
ACTIONS/CLINICAL PHARMACOLOGY:
Glycopyrrolate, like other anticholinergic (antimuscarinic) agents, inhibits the
action of acetylcholine on structures innervated by postganglionic cholinergic
nerves and on smooth muscles that respond to acetylcholine but lack cholinergic
innervation. These peripheral cholinergic receptors are present in the autonomic
effector cells of smooth muscle, cardiac muscle, the sinoatrial node, the
atrioventricular node, exocrine glands, and, to a limited degree, in the
autonomic ganglia. Thus, it diminishes the volume and free acidity of gastric
secretions and controls excessive pharyngeal, tracheal, and bronchial
secretions.
Glycopyrrolate antagonizes muscarinic symptoms (e.g., bronchorrhea,
bronchospasm, bradycardia, and intestinal hypermotility) induced by cholinergic
drugs such as the anticholinesterases.
The highly polar quaternary ammonium group of glycopyrrolate limits its passage
across lipid membranes, such as the blood-brain barrier, in contrast to atropine
sulfate and scopolamine hydrobromide, which are non-polar tertiary amines which
penetrate lipid barriers easily.
Peak effects occur approximately 30 to 45 minutes after intramuscular
administration. The vagal blocking effects persist for 2 to 3 hours and the
antisialagogue effects persist up to 7 hours, periods longer than for atropine.
With intravenous injection, the onset of action is generally evident within one
minute.
INDICATIONS AND USAGE:
IN ANESTHESIA: PYROLATE (glycopyrrolate) Injectable is indicated for use as a
preoperative antimuscarinic to reduce salivary, tracheobronchial, and pharyngeal
secretions; to reduce the volume and free acidity of gastric secretions; and, to
block cardiac vagal inhibitory reflexes during induction of anesthesia and
intubation. When indicated, PYROLATE Injectable may be used intraoperatively to
counteract drug-induced or vagal traction reflexes with the associated
arrhythmias. Glycopyrrolate protects against the peripheral muscarinic effects
(e.g., bradycardia and excessive secretions) of cholinergic agents such as
neostigmine and pyridostigmine given to reverse the neuromuscular blockade due
to nondepolarizing muscle relaxants.
IN PEPTIC ULCER: For use in adults as adjunctive therapy for the treatment of
peptic ulcer when rapid anticholinergic effect is desired or when oral
medication is not tolerated.
CONTRAINDICATIONS:
Known hypersensitivity to glycopyrrolate.
Due to its benzyl alcohol content, PYROLATE Injectable should not be used in
newborns (children less than 1 month of age).
In addition, in the management of PEPTIC ULCER patients, because of the longer
duration of therapy, PYROLATE Injectable may be contraindicated in patients with
concurrent 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.
WARNINGS:
This drug should be used with great caution, if at all, in patients with
glaucoma or asthma.
IN THE AMBULATORY PATIENT. PYROLATE (glycopyrrolate) may produce drowsiness or
blurred vision. The patient should be cautioned regarding activities requiring
mental alertness such as operating a motor vehicle or other machinery or
performing hazardous work while taking this drug.
In addition, in the presence of a high environmental temperature, heat
prostration (fever and heat stroke due to decreased sweating) can occur with use
of PYROLATE (glycopyrrolate).
Diarrhea may be an early symptom of incomplete intestinal obstruction,
especially in patients with ileostomy or colostomy. In this instance treatment
with PYROLATE (glycopyrrolate) would be inappropriate and possibly harmful.
PRECAUTIONS:
GENERAL.
Investigate any tachycardia before giving glycopyrrolate since an increase in
the heart rate may occur.
Use with caution in patients with: coronary artery disease; congestive heart
failure; cardiac arrhythmias; hypertension; hyperthyroidism.
In managing ulcer patients, use PYROLATE with caution in the elderly and in all
patients with autonomic neuropathy, hepatic or renal disease, ulcerative colitis
or hiatal hernia, since anticholinergic drugs may aggravate these conditions.
With overdosage, a curare-like action may occur.
DRUG INTERACTIONS. The intravenous administration of any anticholinergic in the
presence of cyclopropane anesthesia can result in ventricular arrhythmias;
therefore, caution should be observed if PYROLATE (glycopyrrolate) Injectable is
used during cyclopropane anesthesia. If the drug is given in small incremental
doses of 0.1 mg or less, the likelihood of producing ventricular arrhythmias is
reduced.
CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY. Long-term studies in
animals have not been performed to evaluate carcinogenic potential. In the
teratology studies, diminished rates of conception and of survival at weaning
were observed in rats, in a dose-related manner. Studies in dogs suggest that
this may be due to diminished seminal secretion which is evident at high doses
of glycopyrrolate.
PREGNANCY CATEGORY B. Reproduction studies have been performed in rats and
rabbits up to 1000 times the human dose and have revealed no teratogenic effects
from glycopyrrolate. There are, however, no adequate and well-controlled studies
in pregnant women. Because animal reproduction studies are not always predictive
of human response, this drug should be used during pregnancy only if clearly
needed.
NURSING MOTHERS. It is not known whether this drug is excreted in human milk.
Because many drugs are excreted in human milk, caution should be exercised when
PYROLATE is administered to a nursing woman.
PEDIATRIC USE. Safety and effectiveness in children below the age of 12 years
have not been established for the management of peptic ulcer.
DRUG INTERACTIONS:
The intravenous administration of any anticholinergic in the presence of
cyclopropane anesthesia can result in ventricular arrhythmias; therefore,
caution should be observed if PYROLATE (glycopyrrolate) Injectable is used during
cyclopropane anesthesia. If the drug is given in small incremental doses of 0.1
mg or less, the likelihood of producing ventricular arrhythmias is reduced.
(See Also PRECAUTIONS)
ADVERSE REACTIONS:
Anticholinergics produce certain effects, most of which are extensions of their
pharmacologic actions. Adverse reactions to anticholinergics in general may
include dry mouth; urinary hesitancy and retention; blurred vision due to
mydriasis; increased ocular tension; tachycardia; palpitation; decreased
sweating; loss of taste; headache; nervousness; drowsiness; weakness; dizziness;
insomnia; nausea; vomiting; impotence; suppression of lactation; constipation;
bloated feeling; severe allergic reaction or drug idiosyncrasies including
anaphylaxis; urticaria and other dermal manifestations; some degree of mental
confusion and/or excitement, especially in elderly persons.
PYROLATE is chemically a quaternary ammonium compound; hence, its passage across
lipid membranes, such as the blood-brain barrier is limited in contrast to
atropine sulfate and scopolamine hydrobromide. For this reason the occurrence of
CNS related side effects is lower, in comparison to their incidence following
administration of anticholinergics which are chemically tertiary amines that can
cross this barrier readily.
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 children. Indication for
repetitive doses of neostigmine should be based on close monitoring of the
decrease in heart rate and the return of bowel sounds.
In the unlikely event that CNS symptoms (excitement, restlessness, convulsions,
psychotic behavior) occur, physostigmine (which does cross the blood-brain
barrier) should 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 children.
Fever should be treated symptomatically. In the event of a curare-like effect on
respiratory muscles, artificial respiration should be instituted and maintained
until effective respiratory action returns.
DOSAGE AND ADMINISTRATION:
PYROLATE (glycopyrrolate) Injectable may be administered intramuscularly, or
intravenously, without dilution, in the following indications:
ADULTS: PREANESTHETIC MEDICATION. The recommended dose of PYROLATE
(glycopyrrolate) Injectable is 0.002 mg (0.01 mL) per pound of body weight 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. PYROLATE (glycopyrrolate) Injectable may be used
during surgery to counteract drug induced or vagal traction reflexes with the
associated arrhythmias (e.g., bradycardia). It should be administered
intravenously as single doses of 0.1 mg (0.5 mL) and repeated, as needed, at
intervals of 2-3 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 PYROLATE
(glycopyrrolate) Injectable is 0.2 mg (1.0 mL) 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.
CHILDREN: (Read Contraindications). PREANESTHETIC MEDICATION. The recommended
dose of PYROLATE (glycopyrrolate) Injectable in children 1 month to 12 years of
age is 0.002 mg (0.01 mL) per pound of body weight 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.
Children 1 month to 2 years of age may require up to 0.004 mg (0.02 mL) per
pound of body weight.
INTRAOPERATIVE MEDICATION. Because of the long duration of action of PYROLATE
(glycopyrrolate) if used as preanesthetic medication, additional PYROLATE
(glycopyrrolate) Injectable for anticholinergic effect intraoperatively is
rarely needed; in the event it is required the recommended pediatric dose is
0.002 mg (0.01 mL) per pound of body weight intravenously, not to exceed 0.1 mg
(0.5 mL) in a single dose which may be repeated, as needed, at intervals of 2-3
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 PYROLATE
(glycopyrrolate) Injectable is 0.2 mg (1.0 mL) 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.
ADULTS: PEPTIC ULCER. The usual recommended dose of PYROLATE Injectable is 0.1 mg
(0.5 mL) administered at 4-hour intervals, 3 or 4 times daily intravenously or
intramuscularly. Where more profound effect is required, 0.2 mg (1.0 mL) 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.
PYROLATE Injectable is not recommended for peptic ulcers in children under 12
years of age. (See Precautions.)
NOTE: Parenteral drug products should be inspected visually for particulate
matter and discoloration prior to administration whenever solution and container
permit.
ADMIXTURE COMPATIBILITIES. PYROLATE (glycopyrrolate) Injectable is compatible for
mixing and injection with the following injectable dosage forms: 5% and 10%
glucose in water or saline; atropine sulfate, USP; Antilirium(R) (physostigmine
salicylate); Benadryl(R) (diphenhydramine HCl); codeine phosphate, USP; Emete-
Con(R) (benzquinamide HCl); hydromorphone HCl, USP; Inapsine(R) (droperidol);
Innovar(R) (droperidol and fentanyl citrate); Largon(R) (propiomazine HCl);
Levo-Dromoran(R) (levorphanol tartrate); lidocaine, USP; Mepergan(R) (meperidine
and promethazine HCls); meperidine HCl, USP; Mestinon(R)/Regonol(R)
(pyridostigmine bromide); morphine sulfate, USP; Nisentil(R) (alphaprodine HCl);
Nubain(R) (nalbuphine HCl); Numorphan(R) (oxymorphone HCl); Pantopon(R) (opium
alkaloids HCls); procaine HCl, USP; promethazine HCl, USP; Prostigmin(R)
(neostigmine methylsulfate, USP); scopolamine HBr, USP; Sparine(R) (promazine
HCl); Stadol(R) (butorphanol tartrate); Sublimaze(R) (fentanyl citrate);
Talwin(R) (pentazocine lactate); Tigan(R) (trimethobenzamide HCl); Vesprin(R)
(triflupromazine HCl); and Vistaril(R) (hydroxyzine HCl). PYROLATE Injectable may
be administered via the tubing of a running infusion of physiological saline or
lactated Ringer's solution.
Since the stability of glycopyrrolate is questionable above a pH of 6.0, do Not
combine PYROLATE Injectable in the same syringe with Brevital(R) (methohexital
Na); Chloromycetin(R) (chloramphenicol Na succinate); Dramamine(R)
(dimenhydrinate); Nembutal(R) (pentobarbital Na); Pentothal(R) (thiopental Na);
Seconal(R) (secobarbital Na); sodium bicarbonate (Abbott); or Valium(R)
(diazepam). A gas will evolve or a precipitate may form. Mixing with Decadron(R)
(dexamethasone Na phosphate) or a buffered solution of lactated Ringer's
solution will result in a pH higher than 6.0. Mixing chlorpromazine HCl, USP, or
Compazine(R) (prochlorperazine) with other agents in a syringe is not
recommended by the manufacturer, although the mixture with PYROLATE Injectable is
physically compatible.
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