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COMPOSITION :
Gliclazide MR
............................ 30 mg
Gliclazide MR
............................ 80 mg
USE:
Management of type 2 diabetes mellitus.
PREGNANCY IMPLICATIONS:
Clinical effects on the fetus: Crosses the placenta. Hypoglycemia;
ear defects reported with sulfonylureas; other malformations
reported but may have been secondary to poor maternal glucose
control/diabetes. Insulin is the drug of choice for the control of
diabetes mellitus during pregnancy.
LACTATION:
Excretion in breast milk unknown/contraindicated
CONTRAINDICATIONS :
Hypersensitivity to gliclazide, sulfonylureas, or any component of
the formulation; type 1 diabetes mellitus (insulin dependent, IDDM),
diabetic ketoacidosis with or without coma; renal or hepatic
impairment; pregnancy (per manufacturer); breast-feeding
WARNINGS / PREAUTIONS :
All sulfonylurea drugs are capable of producing severe
hypoglycemia. Hypoglycemia is more likely to occur when caloric
intake is deficient, after severe or prolonged exercise, when
ethanol is ingested, or when more than one glucose-lowering drug
is used. Hypoglycemia is also more likely in elderly patients, or
in impaired renal or hepatic function.
Chemical similarities are present among sulfonamides,
sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop
diuretics (except ethacrynic acid). Use in patients with
sulfonamide allergy is specifically contraindicated in product
labeling, however, a risk of cross-reaction exists in patients
with allergy to any of these compounds; avoid use when previous
reaction has been severe. Safety and efficacy have not been
established in pediatric patients.
Product labeling of sulfonylureas (in U.S.) states oral
hypoglycemic drugs may be associated with an increased
cardiovascular mortality as compared to treatment with diet alone
or diet plus insulin. Data to support this association are
limited, and several studies, including a large prospective trial
(UKPDS), have not supported an association.
ADVERSE REACTIONS :
Frequency not defined.
Central nervous system: Headache, nervousness, dizziness
Dermatologic: Rash, erythema, pruritus, urticaria. Sulfonylureas
have also been associated with rare photosensitivity and porphyria
cutanea tarda
Endocrine & metabolic: Hypoglycemia (dose dependent), hyponatremia
(rare)
Gastrointestinal: Nausea, vomiting, diarrhea, epigastric fullness,
gastritis
Hematologic: Agranulocytosis, leukopenia, thrombocytopenia, anemia
Hepatic: Jaundice, LDH increased, transaminases increased
Miscellaneous: Disulfiram reaction (very low potential)
OVERDOSAGE / TOXICOLOGY :
Symptoms of overdose include severe hypoglycemia, seizures,
cerebral damage, tingling of lips and tongue, nausea, yawning,
confusion, agitation, tachycardia, sweating, convulsions, stupor,
and coma. Intoxication with sulfonylureas can cause hypoglycemia
and is best managed with glucose administration (oral for milder
hypoglycemia or by injection in more severe forms).
DRUG INTERACTIONS :
ACE inhibitors: May increase the hypoglycemic effect of gliclazide;
monitor
Anabolic steroids: May increase hypoglycemic effect of gliclazide;
monitor
Beta-blockers: Decrease hypoglycemic effect, mask most
hypoglycemic symptoms, decrease glycogenolysis; avoid use in
diabetics with frequent hypoglycemic episodes.
Corticosteroids: May cause hyperglycemia; adjustment of
hypoglycemic agent may be necessary.
Cyclosporine: Gliclazide may increase serum concentrations of
cyclosporine.
Fluoroquinolones: A possible interaction between sulfonylureas and
fluoroquinolone antibiotics has been reported resulting in a
potentiation of hypoglycemic action of sulfonylureas.
H2 antagonists, antacids, oral sodium bicarbonate: May increase
the hypoglycemic effect; monitor glucose response.
Rifampin: May increase metabolism of gliclazide, decreasing its
effects.
Salicylates: May increase hypoglycemic effect of gliclazide.
Sulfonamides: May increase hypoglycemic effect of gliclazide.
Thiazide diuretics: Hypoglycemic effect of gliclazide may be
decreased by thiazide diuretics.
Warfarin: Anticoagulant effects may be increased by sulfonylureas.
Ethanol/Nutrition/Herb Interactions:
Ethanol: Avoid ethanol (may cause hypoglycemia and/or rare
disulfiram reactions).
Herb/Nutraceutical: Avoid chromium, garlic, gymnema (may cause
hypoglycemia).
Stability:
Store at 20°C to 30°C (68°F to 86°F).
Mechanism of Action:
Stimulates insulin release from the pancreatic beta cells; reduces
glucose output from the liver; lowers plasma glucose
concentrations. Gliclazide has also been shown to decrease
platelet aggregation at therapeutic doses.
PHARMACODYNAMICS / KINETICS :
Absorption: Rapid
Protein binding: 94%
Metabolism: Hepatic, to inactive metabolites
Half-life elimination: 10 hours
Time to peak: 4-6 hours
Excretion: Urine (60% to 70%) and feces (10% to 20%) as
metabolites
Dosage:
Oral: Adults:
Immediate release tablet: Initial: 80-160 mg/day; typical dose
range 80-320 mg/day; dosage of 160 mg should be divided into 2
equal parts for twice-daily administration; maximum dose: 320
mg/day; should be taken with meals
Sustained release tablet: 30-120 mg once daily
NOTE: There is no fixed dosage regimen for the management of
diabetes mellitus with gliclazide or any other hypoglycemic agent.
Dose must be individualized based on frequent determinations of
blood glucose during dose titration and throughout maintenance.
Dosage adjustment in renal/hepatic impairment: Contraindicated in
severe impairment
Administration:
Patients who are anorexic or NPO, may need to have their dose held
to avoid hypoglycemia. Should be administered with meals.
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