Skip to Content

VAMJU 60 MG MODIFIED RELEASE TABLETS

Active substance(s): GLICLAZIDE / GLICLAZIDE / GLICLAZIDE

View full screen / Print PDF » Download PDF ⇩
Transcript
SUMMARY OF PRODUCT CHARACTERISTICS
1

NAME OF THE MEDICINAL PRODUCT
Vamju 60 mg modified-release tablets

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Vamju 60 mg: Each modified-release tablet contains 60 mg gliclazide.
Excipients with known effect: Lactose
Vamju 60 mg: Each 60 mg tablet contains 163.8 mg lactose (as monohydrate).
For the full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM
Modified-release tablet.
Vamju 60 mg
White, biconvex, oval-shaped tablet, with a deep break-line on both sides and
engraved with “GLI” and “60” on either side of the break-line on both sides, with
dimensions 15.0 x 7.0 mm.
The 60 mg tablet can be divided into equal doses.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
Vamju is indicated in adults for treatment of non-insulin dependent diabetes (type 2)
when dietary measures, physical exercise and weight loss alone are not sufficient to
control blood glucose.

4.2

Posology and method of administration
Posology
The daily dose may vary from 30 to 120 mg (i.e. 1 to 4 tablets of 30 mg per day or
one half to 2 tablets of 60 mg per day) taken orally in a single intake at breakfast
time.
It is recommended that the tablet(s) be swallowed whole, without crushing or
chewing.
If a dose is forgotten, there must be no increase in the dose taken the next day.
As with any hypoglycaemic medicinal product, the dose should be adjusted according
to the individual patient's metabolic response (blood glucose, HbA1c)
Initial dose
The recommended starting dose is 30 mg daily. If blood glucose is effectively
controlled, this dose may be used for maintenance treatment.
If blood glucose is not adequately controlled, the dose may be increased to 60, 90 or
120 mg daily, in successive steps. The interval between each dose increment should
be at least 1 month except in patients whose blood glucose has not reduced after two
weeks of treatment. In such cases, the dose may be increased at the end of the second
week of treatment.
The maximum recommended daily dose is 120 mg.
Switching from another oral antidiabetic medicinal product to Vamju
Vamju can be used to replace other oral antidiabetic medicinal products.
The dose and the half-life of the previous antidiabetic medicinal product should be
taken into account when switching to Vamju.
A transitional period is not generally necessary. A starting dose of 30 mg should be
used and this should be adjusted to suit the patient's blood glucose response, as
described above.
When switching from a hypoglycaemic sulphonylurea with a prolonged half-life, a
treatment free period of a few days may be necessary to avoid an additive effect of
the two products, which might cause hypoglycaemia. The procedure described for
initiating treatment should also be used when switching to treatment with Vamju,

i.e. a starting dose of 30 mg/day, followed by a stepwise increase in dose, depending
on the metabolic response.
Combination treatment with other antidiabetic medicinal products
Vamju can be given in combination with biguanides, alpha-glucosidase inhibitors or
insulin.
In patients not adequately controlled with Vamju, concomitant insulin therapy can be
initiated under close medical supervision.
Special populations
Elderly
Vamju should be prescribed using the same dosing regimen recommended for
patients under 65 years of age.
Patients with renal impairment
In patients with mild to moderate renal insufficiency the same dosing regimen can be
used as in patients with normal renal function with careful patient monitoring. These
data have been confirmed in clinical trials.
Patients at risk of hypoglycaemia:
-

Undernourished or malnourished.

Severe or poorly compensated endocrine disorders (hypopituitarism,
hypothyroidism, adrenocorticotrophic insufficiency).
-

Withdrawal of prolonged and/or high dose corticosteroid therapy.

Severe vascular disease (severe coronary heart disease, severe
carotid impairment, diffuse vascular disease).
It is recommended that the minimum daily starting dose of 30 mg is used.
Paediatric population
The safety and efficacy of gliclazide in children and adolescents have not been
established. No data are available in children.
Method of administration
Vamju is intended for oral use.
It is recommended that the tablet(s) be swallowed whole, without crushing or
chewing.

The breakability of the Vamju 60 mg modified release tablet enables flexibility of
dosing to be achieved.

4.3

4.4

Contraindications
-

Hypersensitivity to gliclazide or to any of the excipients listed in section 6.1,
other sulphonylureas, or sulphonamides,

-

type 1 diabetes,

-

diabetic pre-coma and coma, diabetic keto-acidosis,

-

severe renal or hepatic insufficiency: in these cases the use of insulin is
recommended,

-

treatment with miconazole (see section 4.5),

-

lactation (see section 4.6).

Special warnings and precautions for use
Hypoglycaemia
This treatment should be prescribed only if the patient is likely to have a regular food
intake (including breakfast). It is important to have a regular carbohydrate intake due
to the increased risk of hypoglycaemia if a meal is taken late, if an inadequate amount
of food is consumed or if the food is low in carbohydrate. Hypoglycaemia is more
likely to occur during low-calorie diets, following prolonged or strenuous exercise,
alcohol intake or if a combination of hypoglycaemic agents is being used.
Hypoglycaemia may occur following administration of sulphonylureas (see section
4.8). Some cases may be severe and prolonged. Hospitalisation may be necessary and
glucose administration may need to be continued for several days.
Careful selection of patients, of the dose used, and clear patient directions are
necessary to reduce the risk of hypoglycaemic episodes.
Factors which increase the risk of hypoglycaemia:
-

Patient refuses or (particularly in elderly subjects) is unable to co-operate.

-

Malnutrition, irregular mealtimes, skipping meals, periods of fasting or
dietary changes.

-

Imbalance between physical exercise and carbohydrate intake.

-

Renal insufficiency.

-

Severe hepatic insufficiency.

-

Overdose of Vamju.

-

Certain endocrine disorders: thyroid disorders, hypopituitarism and adrenal
insufficiency.

-

Concomitant administration of certain other medicines (see section 4.5).

Renal and hepatic insufficiency: the pharmacokinetics and/or pharmacodynamics of
gliclazide may be altered in patients with hepatic insufficiency or severe renal failure.
A hypoglycaemic episode occurring in these patients may be prolonged, so
appropriate management should be initiated.

Patient information
The risks of hypoglycaemia, together with its symptoms (see Section 4.8), treatment,
and conditions that predispose to its development, should be explained to the patient
and to family members.
The patient should be informed of the importance of following dietary advice, of
taking regular exercise, and of regular monitoring of blood glucose levels.
Poor blood glucose control: blood glucose control in a patient receiving antidiabetic
treatment may be affected by any of the following: fever, trauma, infection or surgical
intervention. In some cases, it may be necessary to administer insulin.
The hypoglycaemic efficacy of any oral antidiabetic agent, including gliclazide, is
attenuated over time in many patients: this may be due to progression in the severity
of the diabetes, or to a reduced response to treatment. This phenomenon is known as
secondary failure which is distinct from primary failure, when an active substance is
ineffective as first-line treatment. Adequate dose adjustment and dietary compliance
should be considered before classifying the patient as secondary failure.
Laboratory tests: measurement of glycated haemoglobin levels (or fasting venous
plasma glucose) is recommended in assessing blood glucose control. Blood glucose
self-monitoring may also be useful.
Treatment of patients with G6PD-deficiency with sulfonylurea agents can lead to
haemolytic anaemia. Since gliclazide belongs to the chemical class of sulfonylurea
drugs, caution should be used in patients with G6PD-deficiency and a nonsulfonylurea alternative should be considered.
Excipients
This medicinal product contains lactose monohydrate. Patients with rare hereditary
problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose
malabsorption should not take this medicine.

4.5

Interaction with other medicinal products and other forms of interaction
The following products are likely to increase the risk of hypoglycaemia:
Contra-indicated combination


Miconazole (systemic route, oromucosal gel): increases the hypoglycaemic effect
with possible onset of hypoglycaemic symptoms, or even coma.
Combinations which are not recommended



Phenylbutazone (systemic route): increases the hypoglycaemic effect of
sulphonylureas (displaces their binding to plasma proteins and/or reduces their
elimination).
It is preferable to use a different anti-inflammatory agent, or else to warn the patient
and emphasise the importance of self-monitoring. Where necessary, adjust the dose
during and after treatment with the anti-inflammatory agent.



Alcohol: increases the hypoglycaemic reaction (by inhibiting compensatory
reactions) that can lead to the onset of hypoglycaemic coma.
Alcohol or medicinal products containing alcohol should be avoided.

Combinations requiring precautions for use
Potentiation of the blood glucose lowering effect and thus, in some instances,
hypoglycaemia may occur when one of the following medicinal products is taken:
other antidiabetic agents (insulins, acarbose, metformin, thiazolidinediones,
dipeptidyl peptidase-4 inhibitors, GLP-1 receptor agonists), beta-blockers,
fluconazole, angiotensin converting enzyme inhibitors (captopril, enalapril), H2receptor antagonists, MAOIs, sulfonamides, clarithromycin and non-steroidal antiinflammatory agents.
The following products may cause an increase in blood glucose levels:
Combination which is not recommended
Danazol: diabetogenic effect of danazol.

If the use of this active substance cannot be avoided, warn the patient and emphasise
the importance of urine and blood glucose monitoring. It may be necessary to adjust
the dose of the antidiabetic agents during and after treatment with danazol.
Combinations requiring precautions during use
Chlorpromazine (neuroleptic agent): high doses (> 100 mg per day of
chlorpromazine) increase blood glucose levels (reduced insulin release).
Warn the patient and emphasise the importance of blood glucose monitoring. It may
be necessary to adjust the dose of the antidiabetic active substance during and after
treatment with the neuroleptic agent.
Glucocorticoids (systemic and local route: intra-articular, cutaneous and rectal
preparations) and tetracosactrin: increase in blood glucose levels with possible ketosis
(reduced tolerance to carbohydrates due to glucocorticoids).
Warn the patient and emphasise the importance of blood glucose monitoring,
particularly at the start of treatment. It may be necessary to adjust the dose of the
antidiabetic active substance during and after treatment with glucocorticoids.
Ritodrine, salbutamol, terbutaline: (I.V.)
Increased blood glucose levels due to beta-2 agonist effects.
Emphasise the importance of monitoring blood glucose levels. If necessary, switch to
insulin.
Combination which must be taken into account
Anticoagulant therapy (e.g. Warfarin):
Sulfonylureas may lead to potentiation of anticoagulation during concurrent
treatment.
Adjustment of the anticoagulant may be necessary.

4.6

Fertility, pregnancy and lactation
Pregnancy
There is no experience with the use of gliclazide during pregnancy in humans, even
though there are few data with other sulfonylurea.
In animal studies, gliclazide is not teratogenic.

Control of diabetes should be obtained before the time of conception to reduce the
risk of congenital abnormalities linked to uncontrolled diabetes.
Oral hypoglycaemic agents are not suitable, insulin is the drug of first choice for
treatment of diabetes during pregnancy. It is recommended that oral hypoglycaemic
therapy is changed to insulin before a pregnancy is attempted, or as soon as
pregnancy is discovered.
Breastfeeding
It is not known whether gliclazide or its metabolites are excreted in breast milk.
Given the risk of neonatal hypoglycaemia, the product is contra-indicated in breastfeeding mother.

4.7

Effects on ability to drive and use machines
Vamju has no known influence on the ability to drive and use machines. However,
patients should be made aware of the symptoms of hypoglycaemia and should be
careful if driving or operating machinery, especially at the beginning of treatment.

4.8

Undesirable effects
Based on the experience with gliclazide, the following undesirable effects have been
reported.
Hypoglycaemia
As for other sulfonylureas, treatment with gliclazide can cause hypoglycaemia, if
mealtimes are irregular and, in particular, if meals are skipped. Possible symptoms of
hypoglycaemia are: headache, intense hunger, nausea, vomiting, lassitude, sleep
disorders, agitation, aggression, poor concentration, reduced awareness and slowed
reactions, depression, confusion, visual and speech disorders, aphasia, tremor, paresis,
sensory disorders, dizziness, feeling of powerlessness, loss of self-control, delirium,
convulsions, shallow respiration, bradycardia, drowsiness and loss of consciousness,
possibly resulting in coma and lethal outcome.
In addition, signs of adrenergic counter-regulation may be observed: sweating,
clammy skin, anxiety, tachycardia, hypertension, palpitations, angina pectoris and
cardiac arrhythmia.

Usually, symptoms disappear after intake of carbohydrates (sugar). However,
artificial sweeteners have no effect. Experience with other sulphonylureas shows that
hypoglycaemia can recur even when measures prove effective initially.
If a hypoglycaemic episode is severe or prolonged, and even if it is temporarily
controlled by intake of sugar, immediate medical treatment or even hospitalisation are
required.

Other undesirable effects
Gastrointestinal disturbances, including abdominal pain, nausea, vomiting dyspepsia,
diarrhoea, and constipation have been reported: if these should occur they can be
avoided or minimised if gliclazide is taken with breakfast.
The following undesirable effects have been more rarely reported:
Skin and subcutaneous tissue disorders
Rash, pruritus, urticaria, angioedema, erythema, maculopapular rashes, bullous
reactions (such as Stevens-Johnson syndrome and toxic epidermal necrolysis).
Blood and lymphatic system disorders
Changes in haematology are rare. They may include anaemia, leucopenia,
thrombocytopenia, granulocytopenia. These are in general reversible upon
discontinuation of medication.
Hepatobiliary disorders
Raised hepatic enzyme levels (AST, ALT, alkaline phosphatase), hepatitis (isolated
reports). Discontinue treatment if cholestatic jaundice appears.
These symptoms usually disappear after discontinuation of treatment.
Eye disorders
Transient visual disturbances may occur especially on initiation of treatment, due to
changes in blood glucose levels.
Class attribution effects
As for other sulphonylureas, the following adverse events have been observed: cases
of erythrocytopenia, agranulocytosis, haemolytic anaemia, pancytopenia, allergic
vasculitis, hyponatraemia, elevated liver enzyme levels and even impairment of liver
function (e.g. with cholestasis and jaundice) and hepatitis which regressed after
withdrawal of the sulfonylurea or led to life-threatening liver failure in isolated cases.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is
important. It allows continued monitoring of the benefit/risk balance of the medicinal
product. Healthcare professionals are asked to report any suspected adverse reactions
via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

4.9

Overdose
An overdose of sulphonylureas may cause hypoglycaemia.
Moderate symptoms of hypoglycaemia, without any loss of consciousness or
neurological signs, must be corrected by carbohydrate intake, dose adjustment and/or
change of diet. Strict monitoring should be continued until the doctor is sure that the
patient is out of danger.
Severe hypoglycaemic reactions, with coma, convulsions or other neurological
disorders are possible and must be treated as a medical emergency, requiring
immediate hospitalisation.
If hypoglycaemic coma is diagnosed or suspected, the patient should be given a rapid
I.V. injection of 50 mL of concentrated glucose solution (20 to 30%). This should be
followed by continuous infusion of a more dilute glucose solution (10%) at a rate that
will maintain blood glucose levels above 1 g/L. Patients should be monitored closely
and, depending on the patient's condition after this time, the doctor will decide if
further monitoring is necessary.
Dialysis is of no benefit to patients due to the strong binding of gliclazide to proteins.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Pharmacotherapeutic group: sulphonamides, urea derivative, ATC code: A10BB09
Gliclazide is a hypoglycaemic sulphonylurea oral antidiabetic active substance
differing from other related compounds by an N-containing heterocyclic ring with an
endocyclic bond.

Mechanism of action
Gliclazide reduces blood glucose levels by stimulating insulin secretion from the βcells of the islets of Langerhans. Increase in postprandial insulin and C-peptide
secretion persists after two years of treatment.
In addition to these metabolic properties, gliclazide has haemovascular properties.
Pharmacodynamic effects
Effects on insulin release
In type 2 diabetics, gliclazide restores the first peak of insulin secretion in response to
glucose and increases the second phase of insulin secretion. A significant increase in
insulin response is seen in response to stimulation induced by a meal or glucose.
Haemovascular properties
Gliclazide decreases microthrombosis by two mechanisms which may be involved in
complications of diabetes:
A partial inhibition of platelet aggregation and adhesion, with a decrease in
the markers of platelet activation (beta thromboglobulin, thromboxane B2).
An action on the vascular endothelium fibrinolytic activity with an increase
in tPA activity.

5.2

Pharmacokinetic properties
Absorption
Plasma levels increase progressively during the first 6 hours, reaching a plateau
which is maintained from the sixth to the twelfth hour after administration.
Intra-individual variability is low.
Gliclazide is completely absorbed. Food intake does not affect the rate or degree of
absorption.
Distribution
Plasma protein binding is approximately 95%. The volume of distribution is around
30 litres. A single daily intake of gliclazide 30 mg and gliclazide 60 mg maintains
effective gliclazide plasma concentrations over 24 hours.
Biotransformation

Gliclazide is mainly metabolised in the liver and excreted in the urine: less than 1%
of the unchanged form is found in the urine. No active metabolites have been detected
in plasma.
Elimination
The elimination half-life of gliclazide varies between 12 and 20 hours.
Linearity/non-linearity
The relationship between the dose administered ranging up to 120 mg and the area
under the concentration time curve is linear.
Special populations
Elderly
No clinically significant changes in pharmacokinetic parameters have been observed
in elderly patients.

5.3

Preclinical safety data
Preclinical data reveal no special hazards for humans based on conventional studies
of repeated dose toxicity and genotoxicity. Long-term carcinogenicity studies have
not been done. No teratogenic changes have been shown in animal studies, but lower
foetal body weight was observed in animals receiving doses 25 fold higher than the
maximum recommended dose in humans.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Lactose monohydrate
Hypromellose
Magnesium stearate E572

6.2

Incompatibilities
Not applicable.

6.3

Shelf life
3 years.

6.4

Special precautions for storage
This medicinal product does not require any special storage conditions.

6.5

Nature and contents of container
60mg: PVC-PVDC/Al or PVC/Al foil blister packs of 28 modified-release tablets
The blisters are packed in carton boxes.
Not all pack sizes may be marketed.

6.6

Special precautions for disposal
No special requirements for disposal. Any unused medicinal product or waste
material should be disposed of in accordance with local requirements.

7

MARKETING AUTHORISATION HOLDER
Mercury Pharmaceuticals Limited
Capital House, 1st Floor,
85 King William Street,
London EC4N 7BL,
United Kingdom

8

MARKETING AUTHORISATION NUMBER(S)
PL 12762/0507

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
18/09/2014

10

DATE OF REVISION OF THE TEXT
18/09/2014

Expand view ⇕

Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

Hide