Consumer medicine information

Metformin Generichealth

Metformin hydrochloride

BRAND INFORMATION

Brand name

Metformin Generichealth

Active ingredient

Metformin hydrochloride

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Metformin Generichealth.

What is in this leaflet

This leaflet answers some common questions about Metformin generichealth.

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits.

Your doctor has weighed the risk of you taking Metformin generichealth against the benefits it is expected to have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may want to read it again.

What Metformin generichealth is used for

The name of your medicine is Metformin generichealth. It contains the active ingredient metformin.

Metformin is used to control blood glucose in patients with diabetes mellitus, when diet and exercise are not enough to control blood glucose.

There are two types of diabetes mellitus:

  • Type I, also called insulin dependent diabetes
  • Type II, also called non-insulin dependent diabetes mellitus (NIDDM) or maturity onset diabetes.

Metformin can be used in patients with Type I diabetes mellitus where insulin alone is not enough to control blood glucose levels.

Metformin can also be used in patients with Type II diabetes mellitus. It can be used alone or in combination with other medicines for treating diabetes.

Your doctor may have prescribed Metformin generichealth tablets for another reason.

Ask your doctor if you have any questions about why Metformin Generic Health was prescribed for you.

How Metformin generic healthworks

Metformin belongs to a group of medicines called biguanides. Metformin lowers high blood glucose by helping your body make better use of the insulin produced by your pancreas.

If your blood glucose is not properly controlled, you may experience hypoglycaemia (low blood glucose) or hyperglycaemia (high blood glucose).

High blood glucose can lead to serious problems with your heart, eyes, circulation or kidneys.

Low blood glucose can occur suddenly. Signs may include:

  • weakness, trembling or shaking
  • sweating
  • lightheadedness, dizziness, headache or lack of concentration
  • tearfulness or crying
  • irritability
  • hunger
  • numbness around the lips and tongue.

If not treated promptly, these may progress to:

  • loss of co-ordination
  • slurred speech
  • confusion
  • loss of consciousness or fitting.

High blood glucose usually occurs more slowly than low blood glucose. Signs of high blood glucose may include:

  • lethargy or tiredness
  • headache
  • thirst
  • passing large amounts of urine
  • blurred vision.

There is no evidence that Metformin generichealth is addictive.

Before you take Metformin generichealth

When you must not take Metformin generichealth

Do not take metformin if you have had an allergic reaction to medicines containing metformin or any of the ingredients listed at the end of this leaflet.

Symptoms of an allergic reaction to these medicines may include:

  • shortness of breath, wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin.

If you are not sure if you have an allergy to metformin check with your doctor.

Do not take metformin if you have any of the following medical conditions:

  • Type I diabetes mellitus that is well controlled by insulin alone
  • diabetic acidosis
  • diabetic coma
  • kidney disease
  • severe liver disease
  • high blood pressure or other heart or blood vessel problems
  • gangrene
  • blood clots in the lungs
  • inflammation of the pancreas.

If you are not sure if you have any of the above, ask your doctor.

Do not take Metformin generic health if you are pregnant or intend becoming pregnant. Insulin is more suitable for controlling blood glucose during pregnancy. Your doctor will replace Metformin Generic Health with insulin.

Do not take Metformin generic health after the expiry date (EXP) printed on the pack. If you take this medicine after the expiry date has passed, it may not work (as well).

Do not take Metformin generichealth if the packaging is torn or shows signs of tampering.

If you are not sure whether you should start taking Metformin Generic Health, talk to your doctor or pharmacist.

Before you start to take it

Tell your doctor if you have allergies to:

  • any other medicines
  • any other substances, such as foods, preservatives or dyes.

Tell your doctor if you are breast-feeding or plan to breast-feed. It is not known whether metformin passes into breast milk. Metformin is usually not recommended while you are breastfeeding. Your doctor will discuss the risks and benefits of taking metformin when breast-feeding.

Tell your doctor if you have or have had any medical conditions, especially the following:

  • kidney disease
  • heart failure
  • high blood pressure
  • recent heart attacks
  • liver disease
  • clots in the lung.

Tell your doctor if:

  • you ever drink alcohol
  • you do not eat regular meals
  • you do heavy exercise or work
  • you are ill or feeling unwell.

Alcohol, diet, exercise and your general health all strongly affect the control of your diabetes. Discuss these things with your doctor. If you have not told your doctor, pharmacist or diabetes educator about any of the above, tell them before you start taking metformin.

Taking other medicines

Tell your doctor, pharmacist or diabetes educator if you are taking any other medicines, including any that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines may hide the symptoms of low blood sugar (hypoglycaemia). These include:

  • alcohol
  • certain medicines used to treat high blood pressure e.g. betablockers.

Some medicines and Metformin generichealth may interfere with each other. These include:

  • alcohol
  • cimetidine, a medicine used to treat reflux and ulcers
  • other medicines used to treat diabetes e.g. glibenclamide and insulin
  • beta blockers, medicines used to treat high blood pressure and angina
  • nifedipine, a medicine used to treat high blood pressure and angina
  • medicines used to prevent blood clots, also known as anticoagulants
  • diuretics, also known as fluid tablets e.g. thiazides, frusemide
  • medicines used to treat thyroid gland problems
  • corticosteroids such as prednisolone and cortisone
  • oestrogen and progesterone in oral contraceptives
  • diazoxide, a medicine used to treat glaucoma
  • (high dose) nicotinic acid used for the lowering of blood fats.

You may need different amounts of your medicine or you may need to take different medicines. Your doctor, pharmacist or diabetes educator can tell you what to do if you are taking any of these medicines. They also have a more complete list of medicines to be careful with or avoid while taking metformin.

Ask your doctor or pharmacist if you are not sure if you are taking any of these medicines.

How to take Metformin Generic Health

Follow all directions given to you by your doctor, pharmacist or diabetes educator carefully. They may differ from the information contained in this leaflet.

If you do not understand the instructions on the box, ask your doctor or pharmacist for help.

Your doctor will tell you how much to take and when to take it.

Take Metformin generichealth exactly as directed by your doctor.

How much to take

The dose varies from patient to patient. Your doctor will decide the right dose for you.

The usual dose of metformin for adults is 500 mg one to three times a day, up to a maximum of 1 g three times a day.

Your doctor may increase or decrease the dose, depending on your blood glucose levels.

Metformin generichealth can be taken by children with diabetes that cannot be controlled with insulin and who are being treated in hospital. Your child's doctor will decide the dose.

How to take it

Swallow the tablets with a glass of water.

When to take it

Take Metformin generichealth during or immediately after a meal, at about the same time each day.

This will reduce the chance of a stomach upset.

Do not skip meals while taking metformin.

How long to take it

Continue taking Metformin generichealth for as long as your doctor recommends.

Make sure you keep enough Metformin generichealth to last over weekends and holidays.

Metformin generichealth will help control your diabetes but will not cure it. Therefore, you may have to take it for a long time.

If you forget to take it

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

Otherwise, take it as soon as you remember (with food), and then go back to taking your medicine as you would normally.

Do not take a double dose to make up for the dose that you missed. If you double a dose, this may cause low blood sugar (hypoglycaemia).

If you are not sure what to do, ask your doctor or pharmacist.

If you take too much (overdose)

Immediately telephone your doctor or the Poisons Information Centre (telephone 13 11 26), or go to Accident & Emergency at your nearest hospital, if you think that you or anyone else may have taken too much Metformin generichealth. Do this even if there are no signs of discomfort or poisoning.

If you take too much metformin together with other medicines for diabetes or alcohol, you may experience symptoms of low blood sugar (hypoglycaemia).

At the first signs of hypoglycaemia, raise your blood glucose quickly by eating jelly beans, sugar or honey, drinking non-diet soft drink or taking glucose tablets.

If not treated quickly, these symptoms may progress to loss of co-ordination, slurred speech, confusion, fits or loss of consciousness.

If you take too much metformin, you may feel sick, vomit, have trouble breathing and have stomach pain or diarrhoea. These may be the early signs of a serious condition called lactic acidosis.

If you experience any of these symptoms, immediately get medical help.

While you are using Metformin generichealth

Things you must do

Tell your doctor if:

  • you become pregnant while you are taking metformin,
  • you are about to start taking any new medicines.

Tell all doctors, dentists and pharmacists who are treating you that you are taking metformin.

Make sure that you, your friends, family and work colleagues can recognise the symptoms of low blood sugar and high blood sugar and know how to treat them.

If you experience any of the symptoms of low blood sugar, you need to raise your blood glucose immediately. You can do this by doing one of the following:

  • eating 5 to 7 jelly beans
  • eating 3 teaspoons of sugar or honey
  • drinking half a can of ordinary (non-diet) soft drink
  • taking 2 to 3 concentrated glucose tablets.

Unless you are within 10 to 15 minutes of your next meal or snack, follow up with extra carbohydrates such as plain biscuits, fruit or milk. Taking this extra carbohydrate will prevent a second drop in your blood glucose level.

Metformin does not normally cause low blood sugar (hypoglycaemia) unless you are also taking other medicines for diabetes such as insulin or sulfonylureas.

If you experience any of the signs of high blood sugar (hyperglycaemia), contact your doctor immediately.

The risk of high blood sugar is increased in the following situations:

  • undiagnosed or uncontrolled diabetes
  • illness, infection or stress
  • taking too little metformin
  • taking certain other medicines
  • too little exercise
  • eating more carbohydrates than normal.

Tell your doctor if you become ill, seriously dehydrated (have lost a large amount of body fluids) or experience injury, fever, extra stress, infection or need surgery.

You are more at risk of developing a serious condition called lactic acidosis at these times. Your doctor may decide to change your treatment and use insulin instead of metformin.

Make sure you check your blood glucose levels regularly.

This is the best way to tell if your diabetes is being controlled properly. Your doctor or diabetes educator will show you how and when to do this.

Tell your doctor, dentist or anaesthetist that you are taking metformin before you have any surgery or X-ray procedures that require injection of contrast agents.

Your doctor may decide that metformin should be stopped prior to these procedures.

Visit your doctor for regular checks of your eyes/feet/ kidneys/heart/circulation/blood/ blood pressure.

See your doctor once a year for a check on your body's level of vitamin B12.

Carefully follow your doctor's and/or dietician's advice on diet, drinking alcohol and exercise.

Tell your doctor immediately if you notice the return of any symptoms you had before starting metformin. These may include lethargy or tiredness, headache, thirst, passing large amounts of urine and blurred vision.

These may be signs that metformin is no longer working, even though you may have been taking it successfully for some time.

Things you must not do

Do not give metformin to anyone else, even if they have the same condition as you.

Do not skip meals while taking metformin.

Do not let yourself run out of medicine over the weekend or on holidays

Things to be careful of

If you have to be alert, for example when driving, be especially careful not to let your blood glucose levels fall too low.

Low blood glucose levels may slow your reaction time and affect your ability to drive or operate machinery. Drinking alcohol can make this worse. However, metformin by itself is unlikely to affect how you drive or operate machinery.

If you are travelling, it is a good idea to:

  • wear some form of identification showing you have diabetes
  • carry some form of sugar to treat hypoglycaemia if it occurs, for example, sugar sachets or jelly beans
  • carry emergency food rations in case of a delay, for example, dried fruit, biscuits or muesli bars
  • keep Metformin generichealth readily available.

If you become sick with a cold, fever or flu, it is very important to continue taking metformin, even if you feel unable to eat your normal meal. If you have trouble eating solid food, use sugar-sweetened drinks as a carbohydrate substitute or eat small amounts of bland food.

Your diabetes educator or dietician can give you a list of foods to use for sick days.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking Metformin generichealth.

Metformin generichealth helps most people with diabetes, but it may have unwanted side effects in a few people.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects. If you are over 65 years of age you may have an increased chance of getting side effects.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor if you notice any of the following and they worry you:

  • stomach upset such as feeling sick (nausea)
  • diarrhoea
  • skin rash.

These are generally mild side effects which usually occur during the first few weeks. Taking Metformin generichealth with meals can help reduce nausea and diarrhoea. Skin rash is rare; it is usually not serious and should go away in a few days.

Tell your doctor immediately or go to the accident and emergency department at your nearest hospital if you notice any of the following symptoms of lactic acidosis (high lactic acid in the blood):

  • loss of appetite
  • unexplained weight loss
  • nausea (feeling sick)
  • vomiting
  • stomach pain
  • trouble breathing
  • rapid, shallow breathing
  • feeling weak, tired, or uncomfortable
  • sleepiness
  • unusual muscle pain
  • dizziness or lightheadedness
  • slow heart beat.

You may need urgent medical attention if these symptoms occur. Lactic acidosis with metformin is rare and mostly happens to people who are ill or whose kidneys are not working properly.

Tell your doctor if you notice any other effects.

Other side effects not listed above may also occur in some patients.

Do not be alarmed by this list of possible side effects.

You may not experience any of them.

After using Metformin generichealth

Storage

Keep your tablets in the pack until it is time to take them.

If you take the tablets out of the pack they will not keep well.

Keep your tablets in a cool dry place where the temperature stays below 30°C.

Do not store metformin or any other medicine in the bathroom or near a sink.

Do not leave it in the car on hot days or on window sills.

Heat and dampness can destroy some medicines.

Keep it where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop using the tablets, or the tablets have passed their expiry date, ask your pharmacist what to do with any that are left over.

Product description

What Metformin generichealth looks like

Metformin generichealth-Tablets 500 mg: white to off-white circular, biconvex, bevel-edged, film-coated tablets debossed with '500' on one side. Available in blister packs of 100 tablets

Metformin generichealth- Tablets 850 mg: white to off-white circular, biconvex, bevel-edged, film-coated tablets debossed with '850' on one side. Available in blister packs of 60 tablets

Tablet Ingredients

Active Ingredient:
Metformin hydrochloride

Excipients:
sodium starch glycollate type A
povidone
maize starch
magnesium stearate
colloidal anhydrous silica
hypromellose
macrogol 6000
purified talc
titanium dioxide
propylene glycol

Sponsor

Generic Health Pty Ltd
Level 1,1102 Toorak Road
CAMBERWELL
VIC 3124
Australia

Australian Registration Numbers

Metformin generichealth 500mg blister
AUST R 142882

Metformin generichealth 850 mg blister
AUST R 142885

Metformin generichealth 500mg bottle
AUST R 164952

Metformin generichealth 850 mg bottle
AUST R 164953

This leaflet was prepared on: July 2015

Published by MIMS June 2017

BRAND INFORMATION

Brand name

Metformin Generichealth

Active ingredient

Metformin hydrochloride

Schedule

S4

 

Name of the medicine

Metformin hydrochloride.

Excipients

Sodium starch glycollate type A, povidone, maize starch, magnesium stearate, anhydrous colloidal silica, hypromellose, macrogol 6000, purified talc, titanium dioxide and propylene glycol. The tablets are gluten free.

Description

Chemical name: 1,1-dimethylbiguanide hydrochloride. Molecular formula: C4H11N5.HCl. MW: 165.6. CAS: 1115-70-4.
Metformin hydrochloride is a white, crystalline powder which is odourless or almost odourless and hygroscopic. It is freely soluble in water, slightly soluble in ethanol (96%), and practically insoluble in chloroform and ether.
Metformin Generichealth tablets are available in two strengths and contain either 500 mg or 850 mg of metformin hydrochloride. The tablets also contain the following excipients: sodium starch glycollate type A, povidone, maize starch, magnesium stearate, colloidal anhydrous silica, hypromellose, macrogol 6000, purified talc, titanium dioxide and propylene glycol. The tablets are gluten free.

Pharmacology

Metformin is an oral biguanide hypoglycaemic agent. It causes an increased peripheral uptake of glucose by increasing the biological efficiency of available exogenous or endogenous insulin.
The mode of action of metformin may be linked to an increase of insulin sensitivity. It does not stimulate insulin release but does require the presence of insulin to exert its hypoglycaemic effect. Possible mechanisms of action include inhibition of gluconeogenesis in the liver, delay in glucose absorption from the gastrointestinal tract and an increase in peripheral uptake of glucose.
Metformin has an antiketogenic activity which is comparable, though somewhat inferior, to insulin itself.
Metformin lowers both basal and postprandial blood glucose in diabetic patients but does not cause hypoglycaemia in either diabetics or normal individuals.

Pharmacokinetics.

Absorption.

After oral administration, metformin hydrochloride is absorbed along the entire gastrointestinal mucosa. Studies using single oral doses of metformin tablets indicate that there is a lack of dose proportionality with increasing doses, which is due to decreased absorption rather than an increase in elimination.
At usual clinical doses and dosing schedules of metformin tablets, steady-state plasma concentrations are reached in 24 to 48 hours and are generally less than 1 microgram/mL. During controlled clinical trials, maximum metformin plasma levels did not generally exceed 5 microgram/mL, even at maximum doses.

Distribution.

Metformin is not bound to plasma proteins.

Metabolism.

Metformin is excreted unchanged in the urine and does not undergo hepatic metabolism.

Excretion.

In patients with decreased renal function (based on measured creatinine clearance), the plasma half-life of metformin is prolonged and renal clearance is decreased in proportion to the decrease in creatinine clearance, e.g. if creatinine clearance is 10-30 mL/min, renal clearance is reduced to 20% of normal.

Indications

Metformin is indicated in the treatment of type 2 diabetes mellitus not satisfactorily controlled by diet, where the risk of lactic acidosis is minimised by excluding predisposing factors, especially impaired renal, hepatic or cardiovascular function.
Metformin may be used as initial therapy or in sulphonylurea failure, either alone or in combination with a sulphonylurea or as adjuvant therapy in insulin dependent diabetes.

Contraindications

Juvenile diabetes mellitus that is uncomplicated and well regulated on insulin.
Diabetes mellitus regulated by diet alone.
Hypersensitivity to metformin hydrochloride or to any of the excipients in Metformin Generichealth tablets.
During or immediately following surgery where insulin is essential.
Diabetic ketoacidosis, diabetic precoma.
Renal failure or renal dysfunction (creatinine clearance < 60 mL/min).
Acute conditions with the potential to alter renal function such as dehydration, severe infection, shock and intravascular administration of iodinated contrast materials (see Precautions).
Acute or chronic disease which may cause tissue hypoxia such as cardiac failure, recent myocardial infarction, respiratory failure, gangrene, shock, acute significant blood loss, pulmonary embolism, pancreatitis and sepsis.
Severe hepatic insufficiency, acute alcohol intake, alcoholism.
Lactation.

Precautions

Lactic acidosis is a rare but serious metabolic complication which can occur due to metformin accumulation during treatment with Metformin Generichealth tablets. When it occurs, it is fatal in approximately 50% of cases. Lactic acidosis is a medical emergency and must be treated in hospital immediately. The risk of lactic acidosis increases with the degree of renal dysfunction and the patient's age. Reported cases have occurred primarily in diabetic patients with significant renal insufficiency, often in the setting of multiple concomitant medical/ surgical problems and multiple concomitant medications. Special caution should be taken in the elderly due to the decrease of renal function with age.
The reported incidence of lactic acidosis in patients receiving metformin is very low (approximately 0.03 cases per 1,000 patient years, with approximately 0.015 fatal cases per 1,000 patient years). The onset is often subtle and accompanied by nonspecific symptoms such as malaise, myalgia, respiratory distress, increasing somnolence and nonspecific abdominal distress. Lactic acidosis may also occur in association with a number of pathophysiological conditions, including diabetes mellitus, and when there is significant tissue hypoperfusion and hypoxaemia. Lactic acidosis is characterised by acidosis (decreased blood pH), elevated lactate levels with increased lactate/ pyruvate ratio and electrolyte disturbances with an increased anion gap.

Heart failure.

Type II diabetic patients with heart failure are at an increased risk of hypoperfusion and possible renal insufficiency. Renal insufficiency is a risk factor for systemic accumulation of metformin and consequently lactic acidosis. Careful monitoring of renal function is recommended when Metformin Generichealth tablets are used in patients with cardiac failure. The major risk of cardiac insufficiency is hypoxia.
When metformin is implicated as the cause of lactic acidosis, metformin plasma levels greater than 5 microgram/mL are generally found (see Pharmacokinetics). Underlying renal disease, or a deterioration in renal function, result in reduced clearance of metformin and drug accumulation and are therefore major risk factors in lactic acidosis. The risk of lactic acidosis may therefore be significantly decreased by regular monitoring of renal function in patients taking metformin and those patients on concomitant diuretics. The use of the minimum effective dose of metformin is recommended. In addition, metformin therapy should be temporarily stopped in the presence of any condition associated with hypoxaemia or dehydration, in patients suffering from serious infections or trauma (particularly if gastrointestinal disturbances are noted or acidosis is suspected) and in those undergoing surgery.
Radiological studies involving the use of intravascular iodinated contrast materials (for example intravenous urogram, intravenous cholangiography, angiography, any computed tomography scans with intravascular contrast materials) can lead to acute alteration of renal function and have been associated with lactic acidosis in patients receiving metformin. Therefore, in patients with normal renal function, Metformin Generichealth tablets should be stopped at the time of the study and not recommenced for 48 hours and only after renal function has been re-evaluated and found to be normal.
Alcohol is known to potentiate the effect of metformin on lactate metabolism. Patients should therefore be warned against excessive alcohol intake, acute or chronic, while taking metformin.
Periodic assessment of renal, hepatic and cardiovascular function is recommended during prolonged periods of treatment with metformin.
Patients receiving continuous metformin therapy should have an annual estimation of vitamin B12 levels because of reports of decreased vitamin B12 absorption.

Carcinogenicity/ mutagenicity.

Long-term carcinogenicity studies have been performed in rats (dosing duration of 104 weeks) and mice (dosing duration of 91 weeks) at doses up to and including 900 mg/kg/day and 1500 mg/kg/day, respectively. These doses are both approximately two to three times the recommended human daily dose on a body surface area basis. No evidence of carcinogenicity with metformin was found in either male or female mice. Similarly, there was no tumourigenic potential observed with metformin in male rats. However, an increased incidence of benign stromal uterine polyps was seen in female rats treated with 900 mg/kg/day.
No evidence of a mutagenic potential of metformin was found in the Ames test (S. typhimurium), gene mutation test (mouse lymphoma cells), chromosomal aberrations test (human lymphocytes), or in vivo micronuclei formation test (mouse bone marrow).
Fertility of male or female rats was unaffected by metformin administration at doses up to 600 mg/kg/day, or approximately twice the maximum recommended human daily dose on a body surface area basis.

Use in pregnancy.

(Category C)
Oral hypoglycaemics may enter the fetal circulation and cause neonatal hypoglycaemia. Since it is important to achieve strict normoglycaemia during pregnancy, metformin should be replaced by insulin.
Metformin was not teratogenic in rats and rabbits at doses up to 600 mg/kg/day, or about two times the maximum recommended human daily dose on a body surface area basis. Determination of fetal concentrations demonstrated a partial placental barrier to metformin. Because animal reproduction studies are not always predictive of human response, any decision to use this drug should be balanced against the benefits and risks. The safety of metformin in pregnant women has not been established.
Because information available suggests that abnormal blood glucose levels during pregnancy are associated with a higher incidence of congenital abnormalities, there is a consensus among experts that insulin be used during pregnancy to maintain blood glucose levels as close to normal as possible.

Australian categorisation definition of Category C.

Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human foetus or neonate without causing malformations. These effects maybe reversible. Accompanying text above should be consulted for further details.

Use in lactation.

Studies on lactating rats show that metformin is excreted into milk and reaches levels comparable to those in plasma. Similar studies have not been conducted in nursing mothers, but caution should be exercised in such patients, and a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Use in children.

Metformin Generichealth tablets are not recommended for use in children, except those with insulin resistant diabetes who are being treated in hospital.

Use in the elderly.

The risk of lactic acidosis, in association with metformin, is increased in elderly patients on long-term therapy due to the physiological alteration of the renal function and the possible accumulation of metformin. Metformin may be used in the elderly if contraindications and precautions are respected, the dosage is frequently reviewed and renal function monitored.
Decreased renal function in elderly subjects is frequent and asymptomatic. Special caution should be exercised in situations where renal function may become impaired.

Interactions

Pharmacokinetic interactions.

Cimetidine.

Reduced clearance of metformin has been reported during cimetidine therapy, so a dose reduction should be considered.

Anticoagulants.

Metformin increases the elimination rate of vitamin K antagonists. Consequently, the prothrombin time should be closely monitored in patients in whom metformin and vitamin K antagonists are being coadministered. Cessation of metformin in patients receiving vitamin K antagonists can cause marked increases in the prothrombin time.

Nifedipine.

A single dose, metformin/ nifedipine drug interaction study in normal healthy volunteers demonstrated that coadministration of metformin and nifedipine increased plasma metformin Cmax and AUC by 20% and 9%, respectively, and increased the amount of metformin excreted in the urine. Tmax and half-life of metformin were unaffected. Nifedipine appears to enhance the absorption of metformin. Metformin had minimal effects on the pharmacokinetics of nifedipine.

Pharmacodynamic interactions.

Sulfonylureas.

During concomitant therapy with sulfonylureas, blood glucose should be monitored because combined therapy may cause hypoglycaemia.

Beta-blockers.

Coadministration of metformin and beta-blockers may result in a potentiation of the hypoglycaemic action. In addition, some of the premonitory signs of hypoglycaemia, in particular tachycardia, may be masked. Monitoring of blood glucose should be undertaken during dosage adjustment of either agent.

ACE inhibitors.

Coadministration of metformin and ACE inhibitors may result in a potentiation of the hypoglycaemic action. Monitoring of blood glucose should be undertaken during dosage adjustment of either agent.

Calcium channel blockers.

Calcium channel blockers may affect glucose control in diabetic patients; regular monitoring of glycaemic control is recommended.

Thyroid products.

Thyroid products tend to produce hyperglycaemia and may therefore lead to loss of control.

Corticosteroids.

Corticosteroids tend to produce hypoglycaemia and may lead to loss of control.

Alcohol.

The risk of lactic acidosis increases with acute alcohol intoxication, particularly in cases of fasting or malnutrition and hepatic insufficiency. Alcohol may make the signs of hypoglycaemia less clear, and delayed hypoglycaemia can occur.
The CNS depressant effects of alcohol plus hypoglycaemia can make driving or the operation of dangerous machinery much more hazardous.

Thiazide diuretics.

Thiazide therapy may impair glucose tolerance. Dosage adjustment of metformin may be required.

Iodinated contrast media.

Metformin Generichealth tablets should be temporarily withheld in patients undergoing radiological studies involving intravascular administration of iodinated contrast materials, because use of such products may result in acute alteration of renal function (see Precautions).

Effect on laboratory tests.

No information is available.

Adverse Effects

Gastrointestinal.

Very common.

Mild gastrointestinal symptoms (such as diarrhoea, nausea, vomiting) are the most frequent reactions to metformin (> 1/10), especially during the initial treatment period. These symptoms are generally transient and resolve spontaneously during continued treatment.
Gastrointestinal side effects can possibly be avoided if metformin is taken with meals and if the dose is increased slowly. Occasionally, a temporary dose reduction can be considered. Occurrence of gastrointestinal symptoms, once a patient is stabilised on any dose of metformin, could be due to lactic acidosis or other serious disease.

Systemic/ metabolic.

Very rare.

Lactic acidosis (see Precautions) is a very rare (< 1/10,000) but serious metabolic complication that can occur due to metformin accumulation during treatment with Metformin Generichealth tablets.
The onset of lactic acidosis is often subtle and accompanied only by nonspecific symptoms such as malaise, myalgia, respiratory distress, increasing somnolence and nonspecific abdominal distress. There may be associated hypothermia, hypotension and resistant bradyarrhythmias with more marked acidosis. The patient and the patient's doctor must be aware of the possible importance of such symptoms and the patient should be instructed to notify the doctor immediately if they occur. Lactic acidosis should be suspected in any diabetic patient with metabolic acidosis lacking evidence of ketoacidosis (ketonuria and ketonaemia).
Lactic acidosis is a medical emergency that must be treated in hospital. In a patient with lactic acidosis who is taking Metformin Generichealth tablets, the drug should be discontinued immediately and general supportive measures should be instituted promptly.

Common.

Taste disturbance is common.

Dermatological.

Very rare.

Skin reactions such as erythema, pruritus and urticaria have been reported, but the incidence is very rare (< 1/10,000).

Haematological.

Very rare.

A decrease of vitamin B12 absorption with a decrease in serum levels has been observed in patients treated long-term with metformin (< 1/10,000). Consideration of such an aetiology is recommended if a patient presents with megaloblastic anaemia. Therefore, serum B12 levels should be appropriately monitored or periodic parenteral B12 supplementation considered.

Hepatobiliary disorders.

Isolated reports.

Liver function tests abnormalities or hepatitis resolving upon metformin discontinuation, have been reported.

Dosage and Administration

Life threatening lactic acidosis can occur due to accumulation of metformin. Risk factors include renal impairment, old age and high doses of metformin above 2 g per day.
It is important that the tablets are taken in divided doses with meals.
Initially 500 mg should be taken once or twice a day and, if necessary, increased over a few weeks up to 1 g three times per day. The dose should be titrated with gradual dose increments until the desired effect is obtained. 500 mg three times a day is often sufficient to obtain diabetic control. If necessary, the dose can be increased to 1 g three times daily, which is the maximum recommended daily dose. Control may be attained within a few days but occasionally requires up to two weeks. Once control has been obtained, the dosage should be reviewed and reduced to the lowest maintenance level consistent with good diabetic control.
Metformin dosage should be frequently reviewed in patients stabilised on metformin, especially if they develop an illness, as they may tolerate the drug less well, particularly if the illness is accompanied by a decrease in renal function. If necessary, metformin should be ceased for a few days during an illness and then restarted at low dosage, as for initial therapy.
The action of metformin is progressive and no final assessment of the patient's real response should be made before the 21st day of treatment; blood sugar estimations are recommended during the initial 15 days of stabilisation. Metformin will not produce a hypoglycaemic state when used alone; however, due to its action in increasing insulin effectiveness, care must be taken when metformin is initially administered with parenteral doses of insulin.

Elderly.

The initial and maintenance dosing of metformin should be conservative in elderly patients, due to the potential for decreased renal function in this population. Any dosage adjustment should be based on a careful assessment of renal function. Generally, elderly patients should not be titrated to the maximum dose of metformin.
In debilitated or malnourished patients, the dosing should be conservative and based on a careful assessment of renal function.

Overdosage

Symptoms.

Hypoglycaemia has not been seen with ingestion of up to 85 g of metformin alone, although lactic acidosis has occurred in such circumstances. The onset of lactic acidosis is often subtle and accompanied only by nonspecific symptoms such as malaise, myalgia, respiratory distress, increasing somnolence and nonspecific abdominal distress. There may be associated hypothermia, hypotension and resistant bradyarrhythmias with more marked acidosis. Lactic acidosis should be suspected in any diabetic patient with metabolic acidosis lacking evidence of ketoacidosis (ketonuria and ketonaemia).

Treatment.

Lactic acidosis should be feared in diabetic metformin treated patients with overdose. Lactic acidosis is diagnosed and monitored by measurement of serum electrolytes, arterial pH and pCO2 and arterial lactate plasma level.
The aim of treatment is to manage any underlying disorder and in some cases this will be sufficient to enable the body's homeostatic mechanism to correct the acid-base imbalance. The advantages of more active treatment of the acidosis must be balanced against the risks, including over alkalinisation with sodium bicarbonate. Because metformin hydrochloride is dialysable (with a clearance of up to 170 mL/min under good haemodynamic conditions), prompt haemodialysis is recommended to correct the acidosis and remove the accumulated metformin.

Presentation

Tablets (white to off white, circular, biconvex, bevel edged, film coated), 500 mg (marked 500 on one side): 100's (blister pack, AUST R 142882), 100's*, 250's*, 500's* (bottle, AUST R 164952); 850 mg (marked 850 on one side): 60's (blister pack, AUST R 142885), 100's*, 250's*, 500's* (bottle, AUST R 164953).
*Not currently marketed in Australia.

Storage

Store below 30°C.

Poison Schedule

S4.