Metformin Hydrochloride Modified Release.
Modified release tablets in 500 mg and 1000 mg strengths. Unless specified by the brand modified released tablets should not be halved or crushed at any time. This form of Metformin has not been shown to have any increase in adverse effects compared to with the equivalent dose of the immediate release Metformin. There is data to suggest the modified release may cause less gastrointestinal side effects than the immediate release.
- Treatment of type 2 diabetes in adults where physical activity and dietary management has not resulted in adequate glycaemic targets.
- Maximum dose of Metformin modified release tablets is 2000mg per day.
- Metformin modified release tablet shells do not dissolve and may appear in the faeces. When people are commenced on this medicine, it is recommended to advised of this.
Due to the potential of changes in renal function, the dose should be adjusted based on renal function, with regular reviews undertaken.
- There is no data for the use of metformin modified release in children.
- Lactic acidosis. Life threatening lactic acidosis can occur due to metformin accumulating in susceptible individuals. Early warning symptoms include anorexia, nausea, vomiting, abdominal pain and cramps. metformin. Risks factors include renal dysfunction, old age, and doses of metformin >2g daily. It can also be associated with prolonged fasting, excessive alcohol, and hepatic dysfunction.
- Discontinue metformin 48 hours before surgery, if possible.
- It is common practice not to restart metformin for 2 days after surgery and once the individual is eating and drinking normally.
Metformin is entirely renally excreted and accumulates in those individuals with renal insufficiency. It is recommended creatinine clearance and/or serum creatinine levels are determined before initiating treatment and regularly thereafter (at least annually for those individuals with normal renal function). Renal function should be checked at least two to four times a year for those individuals whose serum creatinine levels are at the upper limit of normal and for elderly individuals. Current recommendations for metformin are CrCl 60-90 mL/min dose of metformin 2g daily, 30-60 mL/minute 1g daily. Metformin should be ceased if eGFR falls below 30 mL/min/1.73 m
- Gastrointestinal- diarrhoea, nausea, vomiting, abdominal pain, and loss of appetite. Starting with a low dose and increasing slowly can help with these side effects. Taking medicine with meals can also reduce the unwanted effects. Altered taste is also commonly reported with metformin.
- Dermatological -skin reactions including urticaria, erythema, and pruritus.
- Lactic acidosis reduced vitamin B12 absorption.
- Isolated reports of liver function test abnormalities or hepatitis. This has resolved after the metformin has ceased.
- Hypersensitivity to metformin or any of the excipients.
- Renal failure or dysfunction, any acute condition that has the potential to lower renal function (dehydration, severe infection, shock, contrast dye).
- Diabetic ketoacidosis, diabetic precoma.
- Renal failure or renal dysfunction.
- Any acute condition that has the potential to lower renal function (dehydration, severe infection, shock, contrast dye).
- Major surgery.
- Severe hepatic dysfunction.
- Acute or chronic disease that can cause tissue hypoxia (cardiac failure, MI, pancreatitis, sepsis).
Plasma protein binding of metformin is negligible.
Renal clearance of metformin is > 400 mL/min, indicating that metformin is eliminated by glomerular filtration and tubular secretion. Dosage adjustment should occur therefore in those with renal dysfunction and ceased in renal failure.
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