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Diamitex
COMPOSITION
Each tablet contains Gliclazide 80 mg.
DESCRIPTION
A 10 mm oblong tablet, white in colour with 'DUO 861' and 'DUO' markings.
ACTIONS
Gliclazide stimulates insulin secretion from functional pancreatic
beta-cells to a glucose stimulus (Some residual beta-cell function is
therefore necessary) Gliclazide restores the diminished first-phase of
insulin secretion noted in non-insulin dependent diabetes mellitus. Any
long-term hypoglycaemic activity of Gliclazide can be attributed lo an
ability to maintain its effects on insulin secretion. Extrapancreatic
effects may also be involved in the long-term efficacy of Gliclazide
Extrapancreatic effects demonstrated for Gliclazide include improvement in
insulin-mediated glucose utilisation and potentiation of post-receptor
insulin sensitive pathways At normal therapeutic doses in man, Gliclazide
reduces platelet adhesiveness aggregation.
PHARMACOLOGY
Absorption: Gliclazide is absorbed in the gastrointestinal tract
reaching peak plasma concentrations within 4-6 hours Single dose studies
have demonstrated that maximal falls in blood glucose levels (23% - 80 mg
dose; 30% - 160 mg dose) occur approximately 5 hours after drug
administration, nine hours after a dose of 160 mg, a reduction of 20% was
still in evidence The half life of Gliclazide is approximately 12 hours
INDICATIONS
Diabetes mellitus of the maturity onset type, which cannot be controlled by
diet alone
CONTRAINDICATIONS
Gliclazide should not be used in diabetes complicated by acidosis, ketosis
or coma, or in patients with a history of repeated episodes of ketoacidosis
or coma.
Juvenile onset diabetes and unstable or brittle diabetes: As
sulphonylurea hypoglycaemic agents are not effective in juvenile onset.
unstable or brittle diabetes, Gliclazide should not be used in these
conditions.
Severe renal and liver disease: Gliclazide is contraindicated in
severe hepatic or renal insufficiency Caution should be exercised and dosage
reduction may be required.
Hypersensitivity: Gliclazide should not be used in patients with
known sensitivity to sulphonylureas.
Pregnancy: Gliclazide should not be used in pregnant women. Whilst,
animal studies of Gliclazide have not shown any teratogenic effect,
Gliclazide should only be used in women who are likely lo become pregnant if
the expected benefits outweigh any potential risk.
Use during lactation: Gliclazide should not be used during lactation.
SIDE EFFECTS/ADVERSE REACTIONS
Adverse reactions have occurred in some 12% of cases in clinical studies.
However, approximately 2% of patients were withdrawn from therapy because of
adverse reactions notably hypoglycaemia, gastro-intestinal disturbances
(constipation, nausea, epigastric discomfort and heartburn), dermatological
reactions (rash and transient itching), and biochemical abnormalities
(elevated serum creatinine, increased serum alkaline phosphatase, raised
serum SGOT, elevated BUN and raised serum bilirubin). Headache, slight
disulfiram-like reactions and lassitude have also been reported. Serious
reactions which have been reported with other sulphonylureas are leukopenia,
thrombocytopenia, agranulocytosis, pancytopenia, haemolytic anaemia,
cholestatic jaundice and gastrointestinal haemorrhage. These reactions have
not been reported with Gliclazide. As in the case with all forms of
antidiabetic therapy, hypoglycaemic reactions have occasionally been
reported following Gliclazide administration Severe hypoglycaemia, though
very rarely reported, may occur in patients receiving Gliclazide.
PRECAUTIONS/WARNINGS
Warnings:
Acute complications such as severe trauma, fever, infection or
surgery: These acute complications provoke additional metabolic
stress which accentuate the predisposition to hyperglycaemia and ketosis.
Patients presenting with such conditions may require insulin to maintain
control. It is not appropriate to increase the dosage of Gliclazide.
Hypoglycaemia: Close observation and careful initiation and
adjustment of dosage, is mandatory in patients who are elderly, debilitated,
malnourished, semi-starved or simply neglecting dietary restrictions. In
such patients severe hypoglycaemia may occur and may require corrective
therapy over a period of several days Certain conditions such as alcoholism,
insulinoma, adrenal thyroid and pituitary insufficiency increase the
sensitivity to sulphonylureas and may dispose to hypoglycaemia
Precautions:
Monitoring of diabetic state: As with other anti-diabetic
therapies, patients must be under constant medical supervision. Particular
care must be taken during the initial period of stabilisation. Patients
treated with Gliclazide must be monitored regularly to ensure the optimal
control of the diabetic state and where necessary, for the adjustment of
dosage
Disturbances of blood sugar control: As with all
hypoglycaemics, caution should be observed in administering thiazide to
patients on Gliclazide therapy, since thiazides have been reported to
aggravate the diabetic state Other drugs which may adversely affect blood
sugar control with hypoglycaemic agents in some patients, include
barbiturates, glucocorticoids and oestrogens.
Potentiation of hypoglycaemic effect: Certain drugs may
potentiate the effect of Gliclazide and thereby increase the risk of
hypoglycaemia. These include insulin, biguanides. sulphonamides,
oxyphenbutazone, phenylbutazone, clofibrate, salicylates, coumarin
derivatives, chloramphenicol, M. A.O inhibitors, beta blockers and ethanol.
Alcohol: Acute alcohol intoxication potentiates the
hypoglycaemic action of all sulphonylurea agents Furthermore, ingestion of
alcohol may cause a disulfiram-like reaction with characteristic flushing of
the face, throbbing headache, giddiness, tachyponea, tachycardia or angina
pectoris. Chronic alcohol abuse may, as a result of liver enzyme induction,
stimulate the metabolism of sulphonylurea drugs and shorten plasma half-life
and duration of action.
As in Chlorpropamide - DRUG INTERACTIONS: Enhanced Effect - In 5
diabetics poorly controlled with sulphonylurea treatment, tolerance to
glucose was improved when mebanazine 20 mg daily was given for 5 weeks.
Since salicylic acid, phenylbutazone, ethionamide, and aminosalicylic acid
lowered blood-sugar concentrations they were associated with severe
hypoglycaemic reactions in patients being treated with sulphonylureas
including chlorpropamide. Enhancement of the effect of phenformin with a
sulphonylurea during treatment with halofenate. Two of thirteen patients
taking chlorpropamide had hypoglycaemic episodes when halofenate 1 g daily
was added to their treatment.
RECOMMENDED DOSAGE, DOSAGE SCHEDULE & ROUTE OF ADMINISTRATION
The dosage of Gliclazide should be carefully titrated to maintain optimal
control at the various possible dose levels. Dosage should be initiated at
40 mg (½ tablet) daily and may be increased if necessary to 320 mg (4
tablets daily). Doses up to 160 mg daily may be taken in a single daily dose
but preferably at the same time each morning. Doses in excess of 160 mg
should be taken in divided doses in the morning and evening. In general, the
dosage will depend on the severity of the glycaemia with ongoing adjustments
made in order to obtain the optimal response at the lowest dosage Treatment
with Gliclazide does not obviate the necessity for maintaining standard
dietary regulations.
Transferring to Gliclazlde: Patients who have been previously treated
with sulphonylureas or biguanides alone or in combination may be transferred
to Gliclazide When Gliclazide is administered as sole therapy (e.g.
biguanides and sulphonylureas), careful observation is essential during the
transitional phase It is not generally recommended that insulin treated
patients be transferred to Gliclazide.
SYMPTOMS AND TREATMENT FOR OVERDOSAGE AND ANTIDOTE
Clinical Features: Manifestations of severe hypoglycaemia result from
overdosage. Hypoglycaemia caused by sulphonylurea agents differs in several
aspects from insulin coma. Warning symptoms are often absent, neurological
syndromes are frequent and coma is often prolonged.
Management - Consciousness should be restored by the
administration of intravenous glucose or glucagon injection. care being
taken to ensure against the return of hypoglycaemia by constant monitoring
of the blood sugar level
PACKING/PACK SIZES:
Containers of 100's, 250's, 500's and 1000's.
Strip packing of 10 x 10's, 25 x 10's, 50 x 10's and 100 x 10's
STORAGE CONDITION:
Store in a cool place below 25°C.
Protect from light
KEEP OUT OF REACH OF CHILDREN
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