Monograph: |
Glibenclamide
A white or almost white, crystalline powder. Practically
insoluble in water and in ether, slightly soluble in alcohol and
in methyl alcohol: sparingly soluble in dichloromethane: dis-
solves in dilute solutions of alkali hydroxides. Store in air-
tight containers.
Adverse Effects, Treatment, and Precau-
tions
As for sulphonylureas in general like glimepiride.
Hypoglycaemia. Severe hypoglycaemia may occur in any
patient treated with any sulphonylurea ,this poten-
tially life-threatening complication requires prolonged and
energetic treatment. Glibenclamide has a relatively pro-
longed duration of action and appears to cause severe hy-
poglycaemia more often than shorter-acting sulphonylureas
such as tolbutamide.
Asplund and colleagues reviewed 57 instances of hypogly-
caemia associated with glibenclamide.2 The median age of
patients affected was 70 years; only one was less than 60
years old. Median daily dosage was 10 mg Coma or dis-
turbed consciousness was observed in 46 patients. Ten of
these remained comatose despite alleviation of their hypogly-
caemia and died up to 20 days after presentation. In discuss-
ing their review, the authors reported that, including the
present series of 57 cases, there had been published reports on
101 severe hypoglycaemias with glibenclamide. 14 with a fa-
tal outcome.
There has been a more recent report of hypoglycaemic coma
associated with the inhalation of glibenclamide by a worker
at a pharmaceutical plant.
Interactions
As for sulphonylureas In general, like glimepiride.
Pharmacokinetics
Glibenclamide is readily absorbed from the gastro-
intestinal tract, peak plasma concentrations usually
occurring within 2 to 4 hours, and is extensively
bound to plasma proteins. Absorption may be slow-
er in hyperglycaemic patients and may differ ac-
cording to the particle size of the preparation used.
It is metabolised, almost completely, in the liver, the
principal metabolite being only very weakly active.
Approximately 50% of a dose is excreted in the
urine and 50% via the bile into the faeces.
Uses and Administration
Glibenclamide is a sulphonylurea hypoglycaemic.
It is given by mouth in the treatment of type
2 diabetes mellitus and has a duration of ac-
tion of up to 24 hours.
The usual initial-dose of conventional formulations
in type 2 diabetes mellitus is 2.5 to 5 mg daily with
breakfast, adjusted every 7 days by increments of
2.5 mg daily up to 15 mg daily. Although increasing
the dose above 15 mg is unlikely to produce further
benefit, doses of up to 20 mg daily have been given.
Doses greater than 10 mg daily may be given in 2
divided doses. Because of the relatively long dura-
tion of action of glibenclamide, it is best avoided in
the elderly.
In some countries micronised preparations of glib-
enclamide are available, in which the drug is formu-
lated with a smaller particle size. and which have
enhanced bioavailability. The usual initial dose of
one such preparation (Glynase) is 1.5 to 3 mg daily.
adjusted every 7 days by increments of 1.5 mg, up to
a usual maximum of 12 mg daily. Doses greater than
6 mg daily may be given in 2 divided doses.
Action. Proceedings of a symposium on the mechanism of
action of glibenclamide.
EFFECTS ON THE HEART. A reduced incidence of ventricular fi-
brillation has been reported in diabetics treated with gliben-
clamide who develop myocardial infarction, compared with
those receiving other treatments or with nondiabetic patients
with myocardial infarction. However, it should be borne in
mind that some evidence has also suggested that sulphonylu-
reas may impair the adaptive responses of the heart to ischae-
mia .
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