ROMIDAB Film-coated tablet Ref.[115215] Active ingredients: Metformin

Lactic acidosis

Lactic acidosis is a rare, but serious (high mortality in the absence of prompt treatment) metabolic complication that can occur due to ROMIDAB accumulation. The incidence of lactic acidosis may be reduced by assessing other associated risk factors such as poorly controlled diabetes mellitus type 2, ketosis, prolonged fasting, excessive alcohol intake, hepatic insufficiency and any condition associated with hypoxia.

Lactic acidosis is characterised by acidotic dyspnoea, abdominal pain and hypothermia followed by coma. Diagnostic laboratory findings include decreased blood pH, plasma lactate levels above 5 mmol/l, and an increased anion gap and lactate/pyruvate ratio. If metabolic acidosis is suspected, ROMIDAB should be discontinued and the patient should be hospitalised immediately.

Renal function

As ROMIDAB is excreted by the kidneys, serum creatinine levels should be determined before initiating treatment and regularly thereafter:

• At least annually in patients with normal renal function.
• At least two to four times a year in patients with serum creatinine levels at the upper limit of normal and in elderly subjects.

Decreased renal function in elderly subjects is frequent and may be asymptomatic. Special caution should be exercised in situations where renal function may become impaired, for example when initiating antihypertensive therapy or diuretic therapy and when starting therapy with a NSAID.

Administration of iodinated contrast agent

As the intravascular administration of iodinated contrast materials in radiological studies can lead to renal failure, ROMIDAB should be discontinued prior to, or at the time of the test and not re-instituted until 48 hours afterwards, and only after renal function has been re-evaluated and found to be normal.

Surgery

ROMIDAB should be discontinued 48 hours before elective surgery with general anaesthesia and should not be resumed earlier than 48 hours afterwards or only after control of renal function has been regained. Lactic acidosis associated with the use of ROMIDAB. In patients presenting with metabolic acidosis and not having evidence of ketoacidosis (ketonuria and ketonaemia), lactic acidosis should be suspected and ROMIDAB therapy stopped. Lactic acidosis is a medical emergency, which must be treated in hospital. ROMIDAB is excreted by the kidney and regular monitoring of renal function is advised in all diabetic patients with type 2 diabetes mellitus.

The use of ROMIDAB is not advised in conditions which may cause dehydration, or in patients suffering from serious infections, trauma or on a low calorie intake. Patients on long-term treatment with ROMIDAB should have an annual estimation of Vitamin B12 levels, since ROMIDAB may cause mal-absorption of Vitamin B12 and folic acid, which may result in megaloblastic anaemia. During concomitant treatment with sulphonylureas, blood glucose should be monitored because combined therapy may cause hypoglycaemia. Stabilisation of diabetic patients with ROMIDAB and insulin should be carried out in hospital because of the possibility of hypoglycaemia until the ratio of the two medicines has been obtained. Contra-indications should be carefully observed.

All patients should continue their diet with a regular distribution of carbohydrate intake during the day.

Overweight patients should continue their energy-restricted diet. The usual laboratory tests for diabetes monitoring should be performed regularly.

Due to possible gastrointestinal intolerance it is recommended that treatment in the elderly be initiated with low doses, gradually adjusting based on renal clearance. Maximum doses should not be used.

Inadvisable combinations

Alcohol:

Increased risk of lactic acidosis in acute alcohol intoxication, particularly in case of:

• fasting or malnutrition,
• hepatic insufficiency.

Avoid consumption of alcohol and alcohol-containing medications.

Iodinated contrast agents:

Intravascular administration of iodinated contrast agents may lead to renal failure, resulting in ROMIDAB accumulation and a risk of lactic acidosis.

ROMIDAB should be discontinued prior to, or at the time of the test and not reinstituted until 48 hours afterwards, and only after renal function has been re-evaluated and found to be normal.

Glucocorticoids (systemic and local routes), beta-2-agonists, and diuretics: have intrinsic hyperglycaemic activity. Medical practitioners should inform the patient and perform more frequent blood glucose monitoring, especially at the beginning of treatment. If necessary, adjust the dosage of ROMIDAB during therapy with the other medicines and upon its discontinuation.

ACE-inhibitors may decrease the blood glucose levels. If necessary, adjust the dosage of ROMIDAB during therapy with the other medicine and upon its discontinuation.

Cimetidine: Reduced renal clearance of ROMIDAB has been reported during cimetidine therapy, so a dose reduction should be considered.

Anticoagulants: ROMIDAB has been reported to diminish the activity of warfarin, and so dose adjustment of warfarin should be considered.

Sulphonylurea: Concomitant therapy of ROMIDAB with sulphonylurea may cause hypoglycaemia.

Vitamins: Long-term treatment with ROMIDAB may cause vitamin B12 mal-absorption in the gastrointestinal tract (see “WARNINGS AND SPECIAL PRECAUTIONS”).

The use of ROMIDAB during pregnancy and lactation is contraindicated as the safety has not been established. Metformin (contained in ROMIDAB) crosses the placenta and is distributed into breast milk in small amounts. Patients using ROMIDAB should not breastfeed their infants.

There is no data to suggest that the ability to drive and operate heavy machinery may be impaired.

Blood and the lymphatic system disorders

Less frequent: Megaloblastic anaemia.

Gastrointestinal disorders

Frequent: Anorexia, nausea, vomiting, constipation, diarrhoea, metallic taste.

Less frequent: Abdominal pain.

Hepato-biliary disorders

The following side effects have been reported but the frequencies are unknown:

Severe cholestatic hepatitis, liver function abnormalities.

Immune system disorders

The following side effects have been reported but the frequencies are unknown:

Hypersensitivity

Investigations

Less frequent: Hypoglycaemia

Metabolic and nutrition disorders

Less frequent: Hypoglycaemia and lactic acidosis (see “WARNINGS AND SPECIAL PRECAUTIONS”)

Unknown frequency: Decreased absorption of Vitamin B12 and folic acid (see “WARNINGS AND SPECIAL PRECAUTIONS”)