Monograph: |
Glycopyrronium Bromide
A white odourless crystalline powder. Soluble I in 4.2 of wa-
ter. I in 30 of alcohol, I in 260 of chloroform, and I in 35 000
of ether. Incompatible with alkalis. Store in airtight contain-
ers.
Stablllty. Investigation of the compatibility of glycopyrro-
nium bromide with infusion solutions and additives showed
that the stability of glycopyrronium bromide is questionable
above a pH of 6. owing to ester hydrolysis.
Adverse Effects, Treatment, and Precautions
As for Atropine Sulphate.
Renal Impairment. A comparison of the pharmacokinet-
ics of intravenous glycopyrronium in 1 uraemic and 7 con-
trol patients indicated that the renal elimination of
glycopyrronium is considerably prolonged in patients with
uraemia. The mean amount of a dose excreted in the urine
within 3 hours of administration was 0.7% in the uraemic pa-
tients and 50% in the control patients: 24-hour excretion was
7% and 65% respectively. The authors of the study concluded
that repeated or large doses of glycopyrronium should be
avoided or perhaps the drug should not be used in patients
with uraemia.
Interactions
As for antimuscarinics in general (see Atropine Sul-
phate.
Pharmacokinetics
Glycopyrronium bromide is poorly absorbed from
the gastro-intestinal tract; about 10 to 25% has been
stated to be absorbed following a dose by mouth.
Glycopyrronium bromide penetrates the blood-
brain barrier only poorly. Glycopyrronium is excret-
ed in bile and urine.
Uses and Administration
Glycopyrronium bromide is a quaternary ammoni-
um antimuscarinic with peripheral effects similar to
those of atropine . Following intramuscular
administration, onset of effects is within 15 to 30
minutes; vagal blocking effects last for 2 to 3 hours
and antisialagogue effects persist for up to 7 hours.
Following intravenous administration, onset of ac-
tion occurs within one minute.
Glycopyrronium bromide is used similarly to atro-
pine in anaesthetic practice. It is also used in the ion-
tophoretic treatment of hyperhidrosis and has been
used as an adjunct in the treatment of peptic ulcer
disease.
See below for details on dosage and administration
of glycopyrronium.
Anesthesia. Glycopyrronium bromide is given as a pre-
medicant before general anaesthesia to diminish
the risk of vagal inhibition of the heart and to reduce salivary
and bronchial secretions. It is given in doses of 200 to 400 mcg
intravenously or intramuscularly before the induction of an-
aesthesia; alternatively, it may be given in a dose of 4 to 5
mcgper kg body-weight to a maximum of 400 mcg. If necessary,
similar or lower doses may be given intravenously during the
operation and repeated if required. A suggested dosage for
premedication in children is 4 to 8 mcg per kg intravenously or
intramuscularly to a maximum of 200 mcg.
Glycopyrronium bromide is given before or with anti-
cholinesterases to counteract their muscarinic effects when
they are used to reverse the effects of competitive muscle re-
laxants (see Neostigmine Methylsulphate. The dose
is glycopyrronium bromide 200 mcg intravenously per I mg of
neostigmine (or the equivalent dose of pyridostigmine ); alter-
natively, it may be given in a dose of 10 to 15 mcg per kg intra
venously with neostigmine 50 mcg per kg. A suggested dosage
for children is 10 mcg per kg intravenously with neostigmine
50 mcg per kg. Glycopyrronium bromide can be administered
mixed in the same syringe with the anticholinesterase, and it
has been suggested that greater cardiovascular stability re-
sults from this method of administration.
Gastro-inteitinal disorders. Antimuscarinics, including
glycopyrronium bromide, may be used in the treatment of
gastro-intestinal spasms and as an adjunct in the treatment of
peptic ulcer disease, but they have only a limited role .
As an adjunct in the treatment of peptic ulcer disease the usual
initial dose of glycopyrronium bromide is 3 to 6 mg daily by
mouth in divided doses adjusted according to response to a
maximum of 8 mg daily; a maintenance dose of I mg twice
daily is often adequate. Doses of 100 to 200 mcg have been giv-
en by intramuscular or intravenous injection.
Hyperhidrosis. Adverse effects of antimuscarinics given
orally generally preclude their use by this route for the man-
agement of hyperhidrosis , but some, such as glyco-
pyrronium, have been applied topically as alternatives to
aluminium salts.
In studies involving 22 patients with the Prey syndrome (lo-
calised flushing and sweating on eating) glycopyrronium bro-
mide as I and 2% cream or roll-on solution gave good control
of symptoms;' patients tended to prefer the roll-on lotion as it
was easier to apply. Topical hyoscine as 0.25, 1. or 3% solu-
tion or cream also gave control of sweating, but was associat-
ed with a much higher incidence of side-effects. Patients with
frequency and severity of episodes after applying glycopyrro-
nium 0.5% cream.
Glycopyrronium bromide has also been used as a 0.05% so-
lution in the iontophoretic treatment of hyperhidrosis.
Respiratory-tract disorders. Antimuscarinics have po-
tent bronchodilatory activity and may be used in the manage-
ment of reversible airways obstruction,
although glycopyrronium is not one of the main ones used.
|