Based on the experience with gliclazide, the following undesirable effects have been reported.
The most frequent adverse reaction with gliclazide is hypoglycemia.
As for other sulfonylureas, treatment with Gliclazide can cause hypoglycemia, if mealtimes are irregular and, in particular, if meals are skipped. Possible symptoms of hypoglycemia 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 hypoglycemia can recur even when measures prove effective initially.
If a hypoglycemic episode is severe or prolonged, and even if it is temporarily controlled by intake of sugar, immediate medical treatment or even hospitalization are required.
Gastrointestinal disturbances, including abdominal pain, nausea, vomiting dyspepsia, diarrhoea, and constipation have been reported: if these should occur they can be avoided or minimised if gliclazide is taken with breakfast.
The following undesirable effects have been more rarely reported.
Skin and subcutaneous tissue disorders:
rash, pruritus, urticaria, angioedema, erythema, maculopapular rashes, bullous reactions (such as Stevens-Johnson syndrome and toxic epidermal necrolysis), and exceptionally, drug rash with eosinophilia and systemic symptoms (DRESS).
Blood and lymphatic system disorders:
changes in haematology are rare. They may include anaemia, leucopenia, thrombocytopenia, granulocytopenia. These are in general reversible upon discontinuation of medication.
raised hepatic enzyme levels (AST, ALT, alkaline phosphatase), hepatitis (isolated reports).
Discontinue treatment if cholestatic jaundice appears. These symptoms usually disappear after discontinuation of treatment.
Transient visual disturbances may occur especially on initiation of treatment, due to changes in blood glucose levels.
Class attribution effects:
As for other sulfonylureas, the following adverse events have been observed: cases of erythrocytopenia, agranulocytosis, haemolytic anaemia, pancytopenia, allergic vasculitis, hyponatremia, elevated liver enzyme levels and even impairment of liver function (e.g. with cholestasis and jaundice) and hepatitis which regressed after withdrawal of the sulfonylurea or led to life-threatening liver failure in isolated cases.
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.
The following adverse reactions may occur under treatment with metformin. Frequencies are defined as follows: very common: >1/10; common >1/100, <1/10; uncommon >1/1,000, <1/100; rare >1/10,000, <1/1,000; very rare <1/10,000.
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Metabolism and nutrition disorders:
Very rare: 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:
Common: Taste disturbance.
Very common: 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.
Very rare: Isolated reports of liver function tests abnormalities or hepatitis resolving upon metformin discontinuation.
Skin and subcutaneous tissue disorders:
Very rare: Skin reactions such as erythema, pruritus, urticaria.