Metformin oral modified release
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Modified release tablets containing metformin hydrochloride.
Drugs List
Therapeutic Indications
Uses
Type 2 diabetes (NIDDM) not controlled by diet,weight loss & exercise alone
Type 2 diabetes: Risk reduction or delay of onset
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. In adults metformin may be used as monotherapy or in combination therapy with other oral antidiabetics or insulin.
Reduction in the risk or delay of the onset of type 2 diabetes mellitus in adult, overweight patients with impaired glucose tolerance and/or impaired fasting glucose and/or increased HbA1C who are: At high risk for developing overt type 2 diabetes mellitus or still progressing towards type 2 diabetes mellitus despite implementation of intensive lifestyle change for 3 to 6 months.
Such treatment with metformin should be based on a risk score which incorporates appropriate measures of glycaemic control and includes evidence of high cardiovascular risk.
Dosage
Increases in dosage should be made gradually to improve gastrointestinal tolerability.
Dose should be taken with an evening meal.
Adults
Treatment of type 2 (non-insulin dependent) diabetes mellitus, either as monotherapy or in combination with other oral antidiabetic agents
Initial dose: 500mg once daily with the evening meal.
Adjust dose after 10 to 15 days according to blood glucose measurements.
Maximum dose: 2000mg once daily with the evening meal.
Dosage increases should be made in increments of 500mg every 10 to 15 days up to a maximum of 2000mg daily with the evening meal. If glycaemic control is not achieved on 2000mg once daily, consider 1000mg twice daily with a meal (morning and evening).
If glycaemic control is still not achieved, consider switching the patient to standard release metformin tablets up to a maximum dose of 3000mg daily.
Transfer from standard release metformin tablets
The starting dose of metformin modified release tablets should be equivalent to the daily dose of standard release metformin tablets. Transfer is not recommended in patients receiving more than 2000mg of metformin daily.
The 750mg tablets are intended for use in patients already treated with metformin tablets, either prolonged or standard release. The dose of the 750mg tablets should be equivalent to the daily dose of metformin up to a maximum dose of 1500mg. The dosage should be checked after 10 to 15 days to ensure that it is adequate.
Transfer from another antidiabetic agent
Discontinue the other agent and initiate metformin at the monotherapy initiation dose given above.
Combination with insulin
Initially, 500mg of prolonged release metformin once daily, while adjusting insulin dosage on the basis of blood glucose measurements. After titration, switch to either 750mg or 1000mg tablets may be considered.
For patients already treated with metformin and insulin combination therapy, the 750mg or 1000mg tablets may be used with the dosage equivalent to the daily dose of metformin, up to a maximum of 1500mg or 2000mg, respectively. The insulin dosage should be adjusted on the basis of blood glucose measurements.
Reduction in the risk or delay of the onset of type 2 diabetes mellitus
Initially, 500mg of prolonged release metformin once daily with the evening meal. After 10 to 15 days, a dose adjustment (based on blood glucose measurements) is recommended. Slowly increasing the dose may improve gastrointestinal tolerability. The maximum recommended dose is 2000mg once daily with the evening meal. It is recommended to monitor the glycaemic status every 3 to 6 months, as well as the risk factors to evaluate whether treatment needs to be continued, modified or discontinued.
Patients with Renal Impairment
The dosage for renally impaired patients should be based on glomerular filtration rate (GFR).
GFR of 60 to 89ml/minute
Maximum daily dose of 2000mg. Dose reduction may be considered in relation to declining renal function.
GFR of 45 to 59ml/minute
Maximum daily dose of 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
Maximum daily dose of 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.
GFR less than 30ml/minute
Contraindicated.
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 18 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
Elderly
Breastfeeding
Pregnancy
Renal impairment - glomerular filtration rate 30 to 59 ml/minute
Stable cardiac failure
Reduce dose in patients with moderate renal impairment
Not all available brands are licensed for all indications
Test vit B12 levels if deficiency is suspected or risk factors are present
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
Advise patients that empty tablet/capsule may be observed in stools
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 for 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.
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 or glycaemic control during pregnancy, insulin therapy is preferred. Limited data from the use of metformin in pregnant women did not indicate an increase risk of congenital abnormalities. Metformin is known to cross the placenta.
Metformin is generally considered to present a low risk when used during pregnancy (Briggs, 2015) and animal data generally do not indicate harmful effects on pregnancy, embryonal or foetal development, parturition or postnatal development. 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.
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. Metformin is known to be excreted into human breast milk, no adverse effects were observed in breast-fed infants or newborns. A decision should be made on whether to discontinue breastfeeding considering the benefit of breastfeeding and risk of adverse effect the child.
Counselling
Patients should be advised that tablet shells may be present in the faeces and this is normal.
Advise patient to avoid excessive consumption of alcohol.
When metformin is used in combination with other antidiabetics, patients should be advised of the potential risk of hypoglycaemia.
Advise patients taking metformin in combination with other antidiabetics, 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: August 2020
Reference Sources
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
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: Bolamyn SR 500mg prolonged-release tablets. TEVA UK Ltd. Revised March 2014.
Summary of Product Characteristics: Bolamyn SR 1000mg prolonged-release tablets. TEVA UK Ltd. Revised March 2014.
Summary of Product Characteristics: Diagemet XL 500mg prolonged release tablets. Genus Pharmaceuticals. Revised April 2017.
Summary of Product Characteristics: Glucient SR 500mg prolonged-release tablets. Consilient Health Ltd. Revised March 2011.
Summary of Product Characteristics: Glucient SR 750mg prolonged-release tablets. Consilient Health Ltd. Revised August 2014.
Summary of Product Characteristics: Glucient SR 1000mg prolonged-release tablets. Consilient Health Ltd. Revised December 2014.
Summary of Product Characteristics: Glucophage SR tablets 500mg, 750 mg and 1000 mg prolonged release tablets. Merck. Revised May 2017.
Summary of Product Characteristics: Glucorex SR 500mg, prolonged release tablets. Somex Pharma. Revised October 2019.
Summary of Product Characteristics: Jesacrin 750mg prolonged release tablets. Key Pharmaceuticals Ltd. Revised August 2020.
Summary of Product Characteristics: Jesacrin 1000mg prolonged release tablets. Key Pharmaceuticals Ltd. Revised August 2020.
Summary of Product Characteristics: Metabet SR 500mg. Morningside Healthcare Ltd. Revised March 2014.
Summary of Product Characteristics: Metabet SR 1000mg. Morningside Healthcare Ltd. Revised March 2014.
Summary of Product Characteristics: Meijumet 500mg prolonged release tablets. Medreich PLC. Revised June 2016.
Summary of Product Characteristics: Meijumet 750mg prolonged release tablets. Medreich PLC. Revised June 2016.
Summary of Product Characteristics: Meijumet 1000mg prolonged release tablets. Medreich PLC. Revised June 2016.
Summary of Product Characteristics: Metuxtan SR 500mg prolonged release tablets. Accord Healthcare Limited. Revised January 2018.
Summary of Product Characteristics: Sukkarto SR 500mg. Morningside Healthcare Ltd. Revised July 2013.
Summary of Product Characteristics: Sukkarto SR 750mg. Morningside Healthcare Ltd. Revised August 2019.
Summary of Product Characteristics: Sukkarto SR 1000mg. Morningside Healthcare Ltd. Revised July 2013.
Summary of Product Characteristics: Yaltormin SR 500mg prolonged-release tablets. Wockhardt UK Ltd. Revised December 2017.
Summary of Product Characteristics: Yaltormin SR 750mg prolonged-release tablets. Wockhardt UK Ltd. Revised December 2017.
Summary of Product Characteristics: Yaltormin SR 1000mg prolonged-release tablets. Wockhardt UK Ltd. Revised December 2017.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 11 August 2020
MHRA Drug Safety Update June 2022
Available at: https://www.mhra.gov.uk
Last accessed: 21 July 2022
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