Panfor SR 750

Panfor SR 750 Sustained Release Tablets

Panfor SR 750

Each sustained release tablet contains Metformin hydrochloride 750 mg corresponding to 585 mg metformin base.

Therapeutic indications

Metformin Hydrochloride is indicated as an adjunct to diet and exercise to improve glycaemic control in adults with type 2 diabetes mellitus.

Posology and method of administration

Adults with normal renal function (GFR ≥ 90 mL/min)

Reduction in the risk or delay of the onset of type 2 diabetes

  • Metformin should only be considered where intensive lifestyle modifications for 3 to 6 months have not resulted in adequate glycaemic control.
  • The therapy should be initiated with one tablet Panfor SR 500 mg once daily with the evening meal.
  • After 10 to 15 days dose adjustment on the basis of blood glucose measurements is recommended (OGTT and/or FPG and/or HbA1C values to be within the normal range). A slow increase of dose may improve gastro-intestinal tolerability. The maximum recommended dose is 4 tablets (2000 mg) once daily with the evening meal.
  • It is recommended to regularly monitor (every 3-6 months) the glycaemic status (OGTT and/or FPG and/or HbA1c value) as well as the risk factors to evaluate whether treatment needs to be continued, modified or discontinued.
  • A decision to re-evaluate therapy is also required if the patient subsequently implements improvements to diet and/or exercise, or if changes to the medical condition will allow increased lifestyle interventions to be possible.

Monotherapy in Type 2 diabetes mellitus and combination with other oral antidiabetic agents:

  • The usual starting dose is one tablet of Panfor SR 500 mg once daily.
  • After 10 to 15 days the dose should be adjusted on the basis of blood glucose measurements. A slow increase of dose may improve gastro-intestinal tolerability. The maximum recommended dose is 4 tablets daily.
  • Dosage increases should be made in increments of 500mg every 10-15 days, up to a maximum of 2000mg once daily with the evening meal. If glycaemic control is not achieved on Metformin SR 2000mg once daily, Panfor SR 1000mg twice daily should be considered, with both doses being given with food. If glycaemic control is still not achieved, patients may be switched to standard metformin tablets to a maximum dose of 3000 mg daily.
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  • In patients already treated with metformin tablets, the starting dose of Panfor SR should be equivalent to the daily dose of metformin immediate release tablets. In patients treated with metformin at a dose above 2000 mg daily, switching to Panfor SR is not recommended.
  • If transfer from another oral antidiabetic agent is intended: discontinue the other agent and initiate Panfor SR at the dose indicated above.
  • Panfor SR 750 mg and Panfor SR 1000 mg are intended for patients who are already treated with metformin tablets (prolonged or immediate release).
  • The dose of Panfor SR 750 mg or Panfor SR 1000 mg should be equivalent to the daily dose of metformin tablets (prolonged or immediate release), up to a maximum dose of 1500 mg or 2000 mg respectively, given with the evening meal.

Combination with insulin

Metformin and insulin may be used in combination therapy to achieve better blood glucose control. The usual starting dose Panfor SR is one 500 mg tablet once daily, while insulin dosage is adjusted on the basis of blood glucose measurements.

For patients already treated with metformin and insulin in combination therapy, the dose of Panfor SR 750 mg or Panfor SR 1000 mg should be equivalent to the daily dose of metformin tablets up to a maximum of 1500 mg or 2000 mg respectively, given with the evening meal, 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 metformin dosage should be adjusted based on renal function. Regular assessment of renal function is necessary.

Benefit in the reduction of risk or delay of the onset of type 2 diabetes mellitus has not been established in patients 75 years and older  and metformin initiation is therefore not recommended in these patients.

Renal impairment: A GFR should be assessed before initiation of treatment with metformin containing products and at least annually thereafter. In patients at an increased risk of further progression of renal impairment and in the elderly, renal function should be assessed more frequently, e.g. every 3-6 months.

Paediatric population: In the absence of available data, Panfor SR should not be used in children.

Contraindications

  • Hypersensitivity to metformin or to any of the excipients
  • Any type of acute metabolic acidosis (such as lactic acidosis, diabetic ketoacidosis)
  • Diabetic pre-coma
  • Severe renal failure (GFR < 30 mL/min).
  • Acute conditions with the potential to alter renal function such as: dehydration, severe infection, shock
  • Disease which may cause tissue hypoxia (especially acute disease, or worsening of chronic disease) such as: decompensated heart failure, respiratory failure, recent myocardial infarction, shock
  • Hepatic insufficiency, acute alcohol intoxication, alcoholism

Special warnings and precautions for use

Lactic acidosis: Lactic acidosis, a very rare, but serious metabolic complication, most often occurs at acute worsening of renal function or cardiorespiratory illness or sepsis. Metformin accumulation occurs at acute worsening of renal function and increases the risk of lactic acidosis.

In case of dehydration (severe diarrhoea or vomiting, fever or reduced fluid intake), metformin should be temporarily discontinued and contact with a health care professional is recommended.

Medicinal products that can acutely impair renal function (such as antihypertensives, diuretics and NSAIDs) should be initiated with caution in metformin-treated patients. Other risk factors for lactic acidosis are excessive alcohol intake, hepatic insufficiency, inadequately controlled diabetes, ketosis, prolonged fasting and any conditions associated with hypoxia, as well as concomitant use of medicinal products that may cause lactic acidosis.

Patients and/or care-givers should be informed of the risk of lactic acidosis. Lactic acidosis is characterised by acidotic dyspnoea, abdominal pain, muscle cramps, asthenia and hypothermia followed by coma. In case of suspected symptoms, the patient should stop taking metformin and seek immediate medical attention. Diagnostic laboratory findings are decreased blood pH (< 7.35), increased plasma lactate levels (>5 mmol/L) and an increased anion gap and lactate/pyruvate ratio.

Renal function: GFR should be assessed before treatment initiation and regularly thereafter. Metformin is contraindicated in patients with GFR<30 mL/min and should be temporarily discontinued in the presence of conditions that alter renal function.

Cardiac function: Patients with heart failure are more at risk of hypoxia and renal insufficiency. In patients with stable chronic heart failure, metformin may be used with a regular monitoring of cardiac and renal function.

Surgery: Metformin must be discontinued at the time of surgery under general, spinal or epidural anaesthesia. Therapy may be restarted no earlier than 48 hours following surgery or resumption of oral nutrition and provided that renal function has been re-evaluated and found to be stable.

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.

Interaction with other medicinal products and other forms of interaction

Concomitant use not recommended

Alcohol: Alcohol intoxication is associated with an increased risk of lactic acidosis, particularly in case of fasting, malnutrition or hepatic impairment.

Iodinated contrast agents: Metformin must be discontinued prior to or at the time of the imaging procedure and not restarted until at least 48 hours after, provided that renal function has been re-evaluated and found to be stable.

Combinations requiring precautions for use

Some medicinal products can adversely affect renal function which may increase the risk of lactic acidosis, e.g. NSAIDs, including selective cyclo-oxygenase (COX) II inhibitors, ACE inhibitors, angiotensin II receptor antagonists and diuretics, especially loop diuretics. When starting or using such products in combination with metformin, close monitoring of renal function is necessary.

Medicinal products with intrinsic hyperglycaemic 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 respective medicinal product and upon its discontinuation.

Fertility, pregnancy and lactation

Pregnancy: Uncontrolled diabetes during pregnancy (gestational or permanent) is associated with increased risk of congenital abnormalities and perinatal mortality.

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A limited amount of data from the use of metformin in pregnant women does not indicate an increased risk of congenital abnormalities. Animal studies do not indicate harmful effects with respect to pregnancy, embryonic or foetal development, parturition or postnatal development.

When the patient plans to become pregnant and during pregnancy, it is recommended that diabetes is not treated with metformin but insulin be used to maintain blood glucose levels as close to normal as possible, to reduce the risk of malformations of the foetus.

Breast-feeding: Metformin is excreted into human breast milk. No adverse effects were observed in breastfed newborns/infants. However, as only limited data are available, breast-feeding is not recommended during metformin treatment. A decision on whether to discontinue breast-feeding should be made, taking into account the benefit of breast-feeding and the potential risk to adverse effects on the child.

Fertility: Fertility of male or female rats was unaffected by metformin when administered at doses as high as 600 mg/kg/day, which is approximately three times the maximum recommended human daily dose based on body surface area comparisons.

Effects on ability to drive and use machines

Metformin monotherapy does not cause hypoglycaemia and therefore has no effect on the ability to drive or to use machines.

However, patients should be alerted to the risk of hypoglycaemia when metformin is used in combination with other antidiabetic agents (e.g. sulfonylureas, insulin or meglitinides).

Overdose

Hypoglycaemia has not been seen with metformin hydrochloride doses of up to 85 g, although lactic acidosis has occurred in such circumstances. High overdose of metformin or concomitant risks 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.

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