Norizec Special Precautions

Allergic reaction to glimepiride may be experienced by persons allergic to other sulfonamide derivatives.
Increased Risk of Cardiovascular Mortality: Based on a long-term prospective study conducted by the University Group Diabetes Program (UGDP), it has been reported that diabetic patients treated for 5-8 years with diet plus a fixed dose of tolbutamide (1.5 g/day), a sulfonylurea, had a risk of cardiovascular mortality approximately 2 ½ times that of patients treated with diet alone.
In the United Kingdom Prospective Diabetes Study (UKPDS), however, intensive glycemic control with either sulfonylurea or insulin did not have an adverse effect on cardiovascular outcomes. Despite questions regarding the design of these studies and interpretation of the results, these studies provide a basis for caution especially in high-risk patients with cardiovascular disease.
More patients receiving glimepiride and insulin reported an increase in peripheral edema in clinical trials compared with patients receiving insulin alone. Patients using this combination therapy should be asked to report any edema or weight gain.
Hypoglycemia: Sulfonylureas, including glimepiride, are capable of producing severe hypoglycemia. Proper patient selection, dosage and instructions are important to avoid hypoglycemic episodes.
Symptoms of hypoglycemia may be characterized by headache, ravenous hunger, nausea, vomiting, lassitude, sleepiness, disordered sleep, restlessness, aggressiveness, impaired concentration, alertness and reaction time, depression, confusion, speech and visual disorders, aphasia, tremor paresis, sensory disturbances, dizziness, helplessness, loss of self-control, delirium, cerebral convulsions, somnolence, and loss of consciousness including coma, shallow respiration and bradycardia. Signs of adrenergic counter-regulation (i.e., sweating, clammy skin, anxiety, tachycardia, hypertension, palpitations, angina pectoris and cardiac arrhythmias) may also be present. A severe hypoglycemic attack may resemble that of a stroke.
Hypoglycemia may occur when caloric intake is deficient and therefore, glimepiride should be taken shortly before or during a meal to prevent hypoglycemia. These symptoms can almost always be promptly controlled by immediate intake of carbohydrates (sugar). Artificial sweeteners have no effect.
Other factors which contribute to the risk of hypoglycemia include: unwillingness of patients to cooperate with therapy, undernutrition, irregular mealtimes or missed meals or periods of fasting, alterations in diet, strenuous exercise not compensated by caloric supplementation, alcohol consumption, concomitant use with other glucose-lowering agents (such as other sulfonylureas and insulin) or overdosage with glimepiride.
Elderly, debilitated or malnourished patients, those with renal or hepatic dysfunction, and those with adrenal or pituitary insufficiency are particularly susceptible to hypoglycemia. It may be difficult to recognize hypoglycemic states in the elderly, in patients with autonomic neuropathy and in people who are taking beta-adrenergic blocking drugs or other sympatholytic agents.
Loss of Control of Blood Glucose: Loss of control of blood glucose may occur in patients stabilized on any antidiabetic regimen exposed to stress (e.g., fever, trauma, infection, or surgery). In such cases, insulin may be added to glimepiride therapy or monotherapy with insulin be used.
The efficacy of any oral hypoglycemic drug may be reduced in many patients over a period of time due to progression of severity of the diabetes or to diminished responsiveness to the drug (secondary failure). In patients who experience secondary failure with glimepiride or metformin monotherapy, combination therapy with glimepiride and metformin or glimepiride with insulin may be beneficial. Insulin therapy should be initiated in patients who experience secondary failure after combination therapy.
Hypersensitivity Reactions: Hypersensitivity reactions, including serious reactions such as anaphylaxis, angioedema, and Stevens-Johnson Syndrome (SJS) have been reported in postmarketing studies. Glimepiride should be immediately discontinued if hypersensitivity reaction is suspected. The patient should be assessed for other potential causes for the reaction, and institute alternative treatment for diabetes.
Hemolytic Anemia: Sulfonylureas may cause hemolytic anemia in patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency. Use sulfonylureas with caution and consider a non-sulfonylurea alternative in these patients. Hemolytic anemia has also been observed in patients who did not have known G6PD deficiency in postmarketing reports.
Spontaneous reports of severe thrombocytopenia with platelet count less than 10,000/microL and thrombocytopenic purpura were reported.
Renal and Hepatic Insufficiency: Treatment with glimepiride (i.e., starting dose, dose increments and maintenance dose) in patients with renal and hepatic insufficiency should be conservative to avoid hypoglycemic reactions.
Renal Insufficiency: Glimepiride is substantially excreted by the kidneys. The recommended starting dose of 1 mg daily for all patients with type 2 diabetes and renal impairment is recommended to minimize the risk of hypoglycemia in these patients.
Effects on Ability to Drive or Use Machines: Glimepiride may cause visual abnormalities due to changes in blood glucose (hypoglycemia/hyperglycemia). Patients receiving glimepiride should be advised to take precautions while performing activities requiring mental alertness or physical coordination especially if diabetes is not satisfactorily controlled (usually at the beginning of treatment). It should be carefully considered whether it is advisable to drive or operate machinery under these circumstances.
Use in Children: The pharmacokinetics, safety and efficacy of glimepiride in children have not been established in pediatric patients. Glimepiride use is not recommended in this age group.
Use in Elderly: There are no significant differences in glimepiride pharmacokinetics, safety and efficacy in patients with type 2 diabetes ≤65 years old and those >65 years. Although no dosage adjustment is necessary, elderly patients are more susceptible to the hypoglycemic action of glucose-lowering agents. To avoid hypoglycemia, carefully adjust the starting dose, dose increments and maintenance dose based on blood glucose levels.