Adverse reactions : תופעות לוואי

4.8 Undesirable effects
- Hypoglycaemia

Hypoglycaemia, sometimes prolonged and even life-threatening, may occur as a result of the blood glucose lowering action of GLUBEN. Possible symptoms of hypoglycaemia include headache, ravenous hunger, nausea, vomiting, lassitude, sleepiness, disordered sleep, restlessness, aggressiveness, impaired concentration, alertness, and reactions, depression, confusion, speech disorders, aphasia, visual disorders, tremor, pareses, sensory disturbances, dizziness, helplessness, loss of self control, delirium, cerebral convulsions, somnolence and loss of consciousness up to and including coma, shallow respiration and bradycardia.

Signs of adrenergic counter-regulation may be present such as sweating, clammy skin, anxiety, tachycardia, hypertension, palpitations, angina pectoris and cardiac arrhythmias. The clinical picture of a severe hypoglycaemic attack may resemble that of a stroke. The symptoms of hypoglycaemia nearly always subside when hypoglycaemia is corrected.

- Eyes

Temporary visual impairment, changes in accommodation and/or blurred vision.
These are thought to be related to fluctuation in glucose levels.
- Digestive tract

Gastrointestinal symptoms such as nausea, vomiting, sensations of pressure or fullness in the epigastrium, abdominal pain, heartburn, and diarrhoea are the most common reactions and may occur in 1.8% of treated patients. They tend to be dose-related and may disappear when dosage is reduced. In isolated cases, there may be elevation of liver enzyme levels and even impairment of liver function (e.g. with cholestasis and jaundice and hepatitis which can regress after withdrawal of GLUBEN, although they may lead to life-threatening liver failure). GLUBEN should be discontinued if this occurs. Treatment with sulphonylureas has been associated with occasional disturbances of liver function and cholestatic jaundice.

- Metabolic Reactions

Hepatic porphyria reactions have been reported with sulfonylureas; however, these have not been reported with glibenclamide. Disulfiram-like reactions have been reported very rarely with glibenclamide. Cases of hyponatremia have been reported with glibenclamide and all other sulfonylureas, most often in patients who are on other medications or have medical conditions known to cause hyponatremia or increase release of antidiuretic hormone. The syndrome of inappropriate antidiuretic hormone (SIADH) secretion has been reported with certain other sulfonylureas, and it has been suggested that these sulfonylureas may augment the peripheral (antidiuretic) action of ADH and/or increase release of ADH.

- Blood

Potentially life-threatening changes in the blood picture may occur. They may include – rarely – mild to severe thrombopenia (e.g. presenting as purpura), - isolated cases – haemolytic anaemia, aplastic anemia, erythrocytopenia, leucopenia, granulocytopenia, agranulocytosis and (e.g. due to myelosupression) pancytopenia have been reported with sulfonylureas.

- General disorders

Occasionally, allergic or pseudoallergic reactions may occur, e.g. in the form of itching or rashes. Allergic skin reactions, e.g., pruritus, erythema, urticaria, and morbilliform or maculopapular eruptions, occur in 1.5% of treated patients.
These may be transient and may disappear despite continued use of GLUBEN; if skin reactions persist, the drug should be discontinued.

In isolated cases, mild reactions in the form of urticaria may develop into serious and even life-threatening reactions with dyspnoea and fall in blood pressure, sometimes progressing to shock. In the event of urticaria, a physician must therefore be notified immediately.

Porphyria cutanea tarda and photosensitivity reactions have been reported with sulfonylureas.

A hypersensitivity reaction may be directed against glibenclamide itself, but may alternatively be triggered by excipients. Allergy to sulphonamide derivatives may also be responsible for an allergic reaction to glibenclamide.

In addition to dermatologic reactions, allergic reactions such as angioedema, arthralgia, myalgia and vasculitis have been reported.

In isolated cases, allergic vasculitis may arise and, in some circumstance, may be life threatening.