Metformin oral standard release
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations containing metformin hydrochloride.
Drugs List
Therapeutic Indications
Uses
Type 2 diabetes (NIDDM) not controlled by diet,weight loss & exercise alone
Treatment of type 2 (non-insulin dependent diabetes mellitus), particularly in overweight patients, when dietary management and exercise alone does not result in adequate glycaemic control. Metformin may be used as monotherapy or in combination therapy with other oral antidiabetics or insulin.
Unlicensed Uses
Polycystic ovary syndrome
Treatment of polycystic ovary syndrome.
Dosage
Adults
Monotherapy and combination with other oral antidiabetic agents
Initiation regime
500mg or 850mg two to three times a day.
To improve gastrointestinal tolerability take the dose with food and increase the dose slowly.
Adjust dose after ten to fifteen days according to blood glucose measurements.
The maximum recommended dose is 3g daily.
When transferring from another oral antidiabetic agent, discontinue the other agent and initiate metformin at the monotherapy dose given above.
Combination with insulin
Initially 500mg or 850mg of metformin two to three times a day, while adjusting insulin dosage on the basis of blood glucose measurements.
Treatment of polycystic ovary syndrome (unlicensed)
500mg once daily (with breakfast) for one week. Then 500mg with breakfast and 500mg with an evening meal for one week. Then 1.5g to 1.7g daily in two to three divided doses.
Children
Children aged over 10 years of age
Initially, 500mg or 850mg of metformin once daily given during or after meals.
After ten to fifteen days, the dose should be adjusted on the basis of blood glucose measurements. The maximum dose of metformin is 2g daily, taken as two or three divided doses.
Children aged 8 to 10 years (unlicensed)
200mg once daily titrated to response at intervals of at least one week. The maximum dose of metformin is 2g daily, taken as two or three divided doses.
Patients with Renal Impairment
The dosage for renally impaired patients should be based on glomerular filtration rate (GFR).
GFR of 60 to 89ml/minute
Total maximum daily dose in two or three divided doses: 3000mg. Dose reduction may be considered in relation to declining renal function.
GFR of 45 to 59ml/minute
Total maximum daily dose in two or three divided doses: 2000mg. The starting dose is at most half of the maximum dose.
Factors that may increase the risk of lactic acidosis should be reviewed before considering initiation of metformin.
GFR of 30 to 44ml/minute
Total maximum daily dose in two or three divided doses: 1000mg. The starting dose is at most half of the maximum dose.
Factors that may increase the risk of lactic acidosis should be reviewed before considering initiation of metformin.
The Renal Drug Handbook contains additional information, and suggests the following:
GFR 45 to 59ml/minute
Reduce dose to 25 to 50% of the normal dose.
GFR 10 to 45ml/minute
Reduce dose to 25% of the normal dose.
GFR less than 10ml/minute
Avoid.
Contraindications
Acute alcohol intoxication
Children under 8 years
Severe infection
Shock
Within 48 hours of using iodinated contrast media
Alcoholism
Decompensated cardiac failure
Dehydration
Diabetic ketoacidosis
Diabetic pre-coma
Hepatic impairment
Hypoxia
Lactic acidosis
Recent myocardial infarction
Renal impairment - glomerular filtration rate below 30ml/minute
Respiratory failure
Precautions and Warnings
Children under 10 years
Elderly
Breastfeeding
Hereditary fructose intolerance
Pregnancy
Renal impairment - glomerular filtration rate 30 to 59 ml/minute
Stable cardiac failure
Reduce dose in patients with moderate renal impairment
Sodium content of oral solution may be significant
Test vit B12 levels if deficiency is suspected or risk factors are present
Oral solution with maltitol unsuitable in hereditary fructose intolerance
Monitor renal function prior to initiating treatment
Monitor for development of lactic acidosis
Monitor renal function 3 to 6 monthly in elderly patients
Monitor renal function 3- 6 monthly if renal function is borderline normal
Monitor renal function annually in patients with normal renal function
Advise patient to report symptoms of low vitamin B12 levels
Advise patient/carer to report immediately symptoms of lactic acidosis
Withhold until at least 48hrs after general, spinal or epidural anaesthesia
Discontinue if lactic acidosis is suspected
If dehydration occurs, discontinue treatment until patient has recovered
Pregnancy confirmed: Change patient to insulin treatment
Advise patient to avoid alcohol during treatment
Dietary restrictions should be maintained
Patient to inform DVLA if fitness to drive impaired or hypoglycaemic risk
Lactic acidosis can occur due to metformin accumulation. To reduce the incidence of this occurring, patients should be assessed for risk factors associated with the development of lactic acidosis and monitored regularly. Symptoms of lactic acidosis include acidotic dyspnoea, abdominal pain, hypothermia and coma. Risk factors associated with lactic acidosis include poorly controlled diabetes, ketosis, prolonged fasting, excessive alcohol intake, hepatic impairment and any condition associated with hypoxia.
A diagnosis of lactic acidosis should be considered in the presence of non-specific symptoms such as muscle cramps, digestive disorders, abdominal pain or severe asthenia. Lactic acidosis is also indicated by decreased blood pH, plasma lactate levels above 5mmol/L and an increased anion gap and lactate pyruvate ratio. If lactic acidosis is suspected, discontinue metformin and hospitalise the patient immediately.
Special caution should be exercised in situations where renal function may become impaired, e.g. when starting therapy with a non-steroidal anti-inflammatory drug (NSAID).
Patients with heart failure are at an increased risk of hypoxia and renal insufficiency. Treatment is contraindicated in patients with acute or unstable heart failure but may be used in patients with stable chronic heart failure provided cardiac and renal function is regularly monitored.
Pregnancy and Lactation
Pregnancy
Use metformin with caution during pregnancy.
The manufacturer states that metformin is not recommended for the treatment of diabetes during pregnancy, insulin is preferred. With limited data, the use of metformin in pregnant women did not show an increased risk of congenital abnormalities. Animal studies also indicated no harmful effects to pregnancy, embryonic or foetal development, parturition or postnatal development. Metformin is known to cross the placenta.
Metformin is generally considered to present a low risk when used during pregnancy. Rare cases of neural tube defects and malformations of the heart and eye have been seen in animals though studies in pregnant women indicate a low risk to the foetus (Briggs, 2015).
Metformin is also used in the treatment of polycystic ovary syndrome (unlicensed indication) and may have a role in improving poor conception rates and reducing high rates of pregnancy loss during the first trimester in such patients.
Detailed guidance on the treatment of diabetes during pregnancy is available from the National Institute for Health and Clinical Excellence (NICE) at https://www.nice.org.uk/guidance/ng3.
Lactation
Use metformin with caution during breastfeeding.
The manufacturer does not recommend breastfeeding during metformin treatment. As metformin is excreted into human breast milk, a decision should be made on whether to discontinue breastfeeding considering the benefits of breastfeeding and potential risks to the child.
Counselling
Advise patient to avoid alcohol and alcohol containing medications.
When metformin is used in combination with other antidiabetics, patients should be advised of the potential risk of hypoglycaemia.
Patients should be advised against taking NSAIDs or aspirin without consulting their doctor.
Advise patients that their ability to drive or operate machinery may be impaired.
Advise patients to report symptoms of lactic acidosis such as acidotic dyspnoea, abdominal pain, muscle cramps, asthenia and hypothermia.
Advise patient to report symptoms of low vitamin B12 levels.
Advise patients to temporarily discontinue treatment in case of dehydration (severe diarrhoea or vomiting, fever or reduced fluid intake) and to contact a healthcare professional for advice.
Advise patient to report to DVLA if there is a risk of hypoglycaemia, or if fitness to drive may be impaired due to diabetes complications. Guidance can be found by accessing Gov.uk website.
Side Effects
Abdominal pain
Abnormal liver function tests
Anorexia
Decreased appetite
Decreased vitamin-B12 absorption
Diarrhoea
Erythema
Hepatitis
Lactic acidosis
Nausea
Pruritus
Taste disturbances
Urticaria
Vomiting
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: July 2015
Reference Sources
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.
The Renal Drug Handbook. Fifth Edition (2019) ed. Ashley, C. and Dunleavy, A. Radcliffe Publishing Ltd, London.
Summary of Product Characteristics: Axpinet 500mg and 850mg tablets. Medley Pharma Limited. Revised March 2021.
Summary of Product Characteristics: Glucophage 500 mg and 850 mg tablets. Merck Serono. Revised December 2016.
Summary of Product Characteristics: Metformin Colonis 850 mg/5ml Oral Solution. Colonis Pharm Limited. Revised August 2016.
Summary of Product Characteristics: Metformin Colonis 1000 mg/5ml Oral Solution. Colonis Pharm Limited. Revised August 2016.
Summary of Product Characteristics: Metformin hydrochloride 100 mg/ml oral solution. Focus Pharmaceuticals Limited. Revised December 2014.
Summary of Product Characteristics: Metformin hydrochloride 500 mg/5 ml oral solution. Rosemont Pharmaceuticals Limited. Revised December 2013.
Summary of Product Characteristics: Metformin hydrochloride 500mg Powder for Oral Solution. Morningside Healthcare Ltd. Revised June 2020.
Summary of Product Characteristics: Metformin 1000mg F/C Tablets (Caplet Shape). Sigma Pharmaceuticals PLC (Special Concept Development/RxFarma). Revised October 2019.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 15 November 2021
MHRA Drug Safety Update June 2022
Available at: https://www.mhra.gov.uk
Last accessed: 21 July 2022
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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