Based on the experience with Gliclazide and with other sulfonylureas, the following undesirable effects have to be mentioned. Hypoglycaemia: As for othersulfonylureas, treatment with Gliclazide can cause hypoglycaemia, if mealtimes are irregular and, in particular if meals are skipped. Possible symptoms of hypoglycaemia are: headache, intense hunger, nausea, vomiting, lassitude, sleep disorders, agitation, aggression, poor concentration, reduced awareness and slowed reactions, depression, confusion, visual and speech disorders, aphasia, tremor, paresis, sensory disorders, dizziness, feeling of powerlessness, loss of self-control, delirium, convulsions, shallow respiration, bradycardia, drowsiness and loss of consciousness, possibly resulting in coma and lethal outcome. In addition, signs of adrenergic counter-regulation may be observed: sweating, clammy skin, anxiety, tachycardia, hypertension, palpitations, angina pectoris and cardiac arrhythmia. Usually, symptoms disappear after intake of carbohydrates (sugar). However, artificial sweeteners have no effect. Experience with other sulfonylureas shows that hypoglycaemia can recur even when measures prove effective initially. If a hypoglycaemic episode is severe or prolonged, and even if it is temporarily controlled by intake of sugar, immediate medical treatment or even hospitalisation is required. Gastrointestinal disturbances, including abdominal pain, nausea, vomiting, dyspepsia, diarrhoea and constipation have been reported. These can be avoided or minimised if Gliclazide is taken with a meal.
The following undesirable effects have been more rarely reported: Blood and lymphatic system disorders: Changes in haematology are rare. They may include anaemia, leukopenia, thrombocytopenia, granulocytopenia. These are in general reversible upon discontinuation of Gliclazide.
Skin and subcutaneous tissue disorders: Rash, pruritus, urticaria, erythema, maculo-papular rashes, bullous reactions, photosensitivity skin reactions.
Hepatobiliary disorders: Raised hepatic enzyme levels (ASAT, ALAT, alkaline phosphatase), hepatitis (isolated reports). Discontinue treatment if cholestatic jaundice appears.
These symptoms usually disappear after discontinuation of treatment.
Eye disorders: Transient visual disturbances may occur, especially on initiation of treatment, due to changes in blood glucose levels.
Metformin: During treatment initiation, the most common adverse reactions are nausea, vomiting, diarrhoea, abdominal pain and loss of appetite which resolve spontaneously in most cases. To prevent them, it is recommended to take metformin in 2 or 3 daily doses and to increase slowly the doses.
Metabolism and nutrition disorders: Lactic acidosis. Decrease of vitamin B12 absorption with decrease of serum levels during long-term use of metformin. Consideration of such aetiology is recommended if a patient presents with megaloblastic anaemia.
Nervous system disorders: Taste disturbance.
Gastrointestinal disorders: Gastrointestinal disorders such as nausea, vomiting, diarrhoea, abdominal pain and loss of appetite. These undesirable effects occur most frequently during initiation of therapy and resolve spontaneously in most cases. To prevent them, it is recommended that metformin be taken in 2 or 3 daily doses during or after meals. A slow increase of the dose may also improve gastrointestinal tolerability.
Hepatobiliary disorders: Isolated reports of liver function tests abnormalities or hepatitis resolving upon metformin discontinuation.
Skin and subcutaneous tissue disorders: Skin reactions such as erythema, pruritus, urticaria.