Metnova 500/1000 SR

Metnova 500SR/Metnova 1000 SR

METFORMIN HYDROCHLORIDE

SUSTAINED RELEASE TABLETS

Composition:

Each film coated sustained release tablet contains:

Metformin Hydrochloride BP 500 mg/1000 mg

Excipients: q.s.

Colour: Titanium Dioxide BP

 

Pharmacologlcal action:

Metformin is a biguanide with antihyperglycaemic effects,

lowering both basal and postprandial plasma glucose. It does not

stimulate insulin secretion and therefore does not produce

hypoglycemia.

 

Itmay act via 3 mechanisms:

(1) Reduction of hepatic glucose production by inhibiting

gluconeogenesis and glycogenolysis

(2) In muscle, by increasing insulin sensitivity, improving

peripheral glucose uptake and utilization

(3) And delay of intestinal glucose absorption.

Metformin stimulates intracellular glycogen synthesis by acting on

glycogen synthase. It increases the transport capacity of all types

of membrane glucose transporters (GLUT).

In clinical studies, the major non glycemic effect of Metformin is

either weight stability or modest weight loss.

In humans, independently of its action on glycaemia, immediate

release Metformin has favourable effects on lipid metabolism.

This has been shown at therapeutic doses in controlled, medium-

term or long-term clinical studies: immediate release Metformin

reduces total cholesterol, LDL cholesterol and triglyceride levels.

A similar action has not been demonstrated with the prolonged

release formulation, possibly due to the evening administration,

and an increase in triglycerides may occur.

 

Therapeutic category: Blood glucose lowering drug

Therapeutic Indications:

i) Treatment of type 2 diabetes mellitus, particularly in

overweight patients, when dietary management and exercise

alone does not result in adequate glycemic control.

ii) In adults, Metformin film-coated tablets may be used as

monotherapy or in combination with other oral anti-diabetic

agents or with insulin.

iii) In children from 10 years of age and adolescents, Metformin

hydrochloride film-coated tablats may be used as

monotherapy or in combination with insulin.

iv) A reduction of diabetic complications has been shown in

overweight type 2 diabetic adult patients treated with

metformin hydrochloride as first-line therapy after diet failure.

 

Posology and Method of Administration:

Route of Administration: Oral

Adults:

Monotherapy and combination with other oral antidiabetic

agents:

The usual starting dose is 500 mg or 850 mg Metformin

hydrochloride 2 or 3 times daily given during or after meals.

After 10 to 15 days the dose should be adjusted on the basis of

blood glucose measurements. A slow increase of dose may

improve gastrointestinal tolerability.

The maximum recommended dose of is 3 g daily, taken as 3

divided doses.

Combination with insulin:

Metformin hydrochloride and insulin may be used in combination

therapy to achieve better blood glucose control. Metformin

hydrochloride is given at the usual starting dose of 500mg or

850mg metformin hydrochloride 2 or 3 times daily, while insulin

dosage is adjusted on the basis of blood glucose measurements.

Elderly:

Due to the potential for decreased renal function in elderly

subjects, the dosage should be adjusted based on renal function.

Regular assessment of renal function is necessary.

Children and adolescents:

Monotherapy and combination with insulin

* Metformin hydrochloride film-coated tablets can be used in

children from 10 years of age and adolescents.

* The usual starting dose is 500 mg or 850 mg metformin

hydrochloride once daily, given during meals or after meals.

After 10 to 15 days the dose should be adjusted on the basis of

blood glucose measurements. A slow increase of dose may

improve gastrointestinal tolerability. The maximum recommended

dose of metformin hydrochloride is 2 g daily, taken as 2 or 3

divided doses.

 

Contraindications:

i) Hypersensitivity to Metformin or to any of the excipients.

ii) Diabetic ketoacidosis, diabetic pre-coma.

iii) Renal failure or renal dysfunction (creatinine clearance < 60

ml/min)

iv) Acute conditions with the potential to alter renal function such

as:

– Dehydration,

– Severe infection,

– Shock,

v) Acute or chronic disease which may cause tissue hypoxia

such as:

–  Cardiac or respiratory failure,

– Recent myocardial infarction,

– Shock

vi) Hepatic insufficiency, acute alcohol intoxication, alcoholism

vii) Lactation

 

 

Warning & Precautions:

Lactic acidosis:

Lactic acidosis is a rare, but serious (high mortality in the absence

of prompt treatment), metabolic complication that can occur due

to Metformin accumulation. Reported cases of lactic acidosis in

patients on Metformin have occurred primarily in diabetic patients

with significant renal failure. The incidence of lactic acidosis can

and should be reduced by assessing also other associated risk

factors such as poorly controlled diabetes, ketosis, prolonged

fasting, excessive alcohol intake, hepatic insufficiency and any

condition associated with hypoxia.

 

Renal function:

As Metformin is excreted by the kidney, creatinine clearance (this

can be estimated from serum creatinine levels using the

Cockcroft-Gault formula} should be determined before initiating

treatment and regularly thereafter:

* Atleast annually in patients with normal renal function,

* At least two to four times a year in patients with creatinine

clearance levels at the limit of normal and in elderly subjects.

Decreased renal function in elderly subjects is frequent and

asymptomatic. Special caution should be exercised in situations

where renal function may become impaired, for example when

initiating antihypertensive therapy or diuretic therapy and when

starting therapy with an non-steroidal anti-inflammatory drug

(NSAID).

 

Administration of iodinated contrast media:

The intravascular administration of iodinated contrast media in

radiological studies can lead to renal failure. This may lead to

Metformin accumulation and risk of lactic acidosis. Metformin

must be discontinued prior to, or at the time of the test and not

reinstituted until 48 hours afterwards, and only after renal function

has been re-evaluated and found to be normal.

 

Surgery:

Metformin should be discontinued 48 hours before elective

surgery with general spinal or peridural anaesthesia. Therapy

may be restarted no earlier than 48 hours following surgery or

resumption of oral nutrition provided normal renal function has

been established.

 

Children and adolescents:

The diagnosis of type 2 diabetes mellitus should be confirmed

before treatment with metformin hydrochloride is initiated.

No effect of metformin hydrochloride on growth and puberty has

been detected during controlled clinical studies of one-year

duration but no long-term data on these specific points are

available. Therefore, a careful follow-up of the effect of metformin

hydrochloride on these parameters in metformin hydrochloride-

treated children, especially pre-pubescent children, is

recommended.

 

Children aged between 10 and 12 years:

Only 15 subjects aged between 10 and 12 years were included in

the controlled clinical studies conducted in children and

adolescents. Although efficacy and safety of metformin

hydrochloride in these children did not differ from efficacy and

safety in older children and adolescents, particular caution is

recommended when prescribing to children aged between 10 and

12 years.

 

Other precautions:

All patients should continue their diet with a regular distribution of

carbohydrate intake during the day. Overweight patients should

continue their energy-restricted diet.

The usual laboratory tests for diabetes monitoring should be

performed regularly.

 

Adverse effects:

In post marketing data and in controlled clinical studies, adverse

event reporting in patients treated with Metformin SR was similar

in nature and severity to that reported in patients treated with

Metformin immediate release.

During treatment initiation, the most common adverse reactions

are nausea, vomiting, diarrhoea, abdominal pain and loss of

appetite, which resolve spontaneously in most cases.

 

Frequencies are defined as follows:

very common >1/100

common >1/100to < 1/10

uncommon >1/1000 to <1/100

rare >1/10000 to<1/1000

very rare <1/10000.

 

a) Metabolism and nutrition disorders

Very rare: Lactic acidosis Decrease of vitamin B,, absorption

with decrease of serum levels during long-term use of

metformin. Consideration of such an etiology is recommended

if a patient presents with megaloblastic anaemia.

 

b) Nervous system disorders.

Common: Taste disturbance

 

c) Gastrointestinal disorders.

Very common: Gastrointestinal disorders such as nausea,

vomiting, diarrhoea, abdominal pain and loss of appetite.

These undesirable effects occur most frequently during

initiation of therapy and resolve spontaneously in most cases.

As low increase of the dose may also improve gastrointestinal

tolerability.

 

d) Hepatobiliary disorders

Isolated reports: Liver function tests abnormalities or hepatitis

resolving upon metformin discontinuation.

 

e) Skin and subcutaneous tissue disorders

Very rare: Skin reactions such as erythema, pruritus, urticaria.

 

Drug interactions:

A) Concomitant use not recommended

a) Alcohol

Acute alcohol intoxication is associated with an increased risk

of lactic acidosis, particularly in case of:

* Fasting or malnutrition,

* Hepatic insufficiency

b) lodinated contrast media

Intravascular administration of iodinated contrast media may lead

to renal failure, resulting in Metformin accumulation and a risk of

lactic acidosis.

Metformin hydrochloride must be discontinued prior to, or at the

time of the test and not reinstituted until 48 hours afterwards, and

only after renal function has been re-evaluated and found to be

normal.

 

B) Combinations requiring precautions for use

Medicinal products with intrinsic hyperglycemic activity (e.g.

glucocorticoids (systemic and local routes) and

Sympathomimetics. More frequent blood glucose monitoring may

be required, especially at the beginning of treatment. If necessary,

adjust the Metformin dosage during therapy with the other drug

and upon its discontinuation.

 

C) Diuretics, especially loop diuretics

They may increase the risk of lactic acidosis due to their potential

to decrease renal function

 

Over dosage:

Hypoglycemia has not been seen with Metformin doses of up to 85

g, although lactic acidosis has occurred in such circumstances.

High overdose or concomitant risks of Metformin may lead to lactic

acidosis. Lactic acidosis is a medical emergency and must be

treated in hospital. The most effective method to remove lactate

and Metformin is haemodialysis.

Pharmaceutical information:

Storage conditions:

Store in a cold and dry place below 30°C.

Protect from light and moisture.

Keep medicine away from children.

 

Shelf Life: 36 months

Pack size: Blister pack of 10 tablets