Yes

Antidiabetic Agent (Sulfonylurea)

Adjunct to diet for the management of mild to moderately severe, stable, noninsulin-dependent (type 2) diabetes mellitus

D

Type 1 diabetes therapy (IDDM), hypersensitivity to sulfonylureas, diabetes complicated by ketoacidosis

False-positive response has been reported in patients with liver disease, idiopathic hypoglycemia of infancy, severe malnutrition, acute pancreatitis, renal dysfunction. Transferring a patient from one sulfonylurea to another does not require a priming dose; doses >1000 mg/day normally do not improve diabetic control. Has not been studied in older patients; however, except for drug interactions, it appears to have a safe profile and decline in renal function does not affect its pharmacokinetics. How "tightly" an elderly patient's blood glucose should be controlled is controversial; however, a fasting blood sugar <150 mg/dL is now an acceptable end point. Such a decision should be based on the patient's functional and cognitive status, how well they recognize hypoglycemic or hyperglycemic symptoms, and how to respond to them and their other disease states.

At higher dosages, sulfonylureas may block the ATP-sensitive potassium channels, which may correspond to an increased risk of cardiovascular events. In May, 2000, the National Diabetes Center issued a warning to avoid the use of sulfonylureas at higher dosages.

>10%:

Central nervous system: Headache, dizziness

Gastrointestinal: Anorexia, nausea, vomiting, diarrhea, constipation, heartburn, epigastric fullness

1% to 10%: Dermatologic: Rash, urticaria, photosensitivity

<1%: Hypoglycemia, aplastic anemia, hemolytic anemia, bone marrow suppression, thrombocytopenia, agranulocytosis, cholestatic jaundice, diuretic effect

Symptoms of overdose include low blood sugar, tingling of lips and tongue, nausea, yawning, confusion, agitation, tachycardia, sweating, convulsions, stupor, and coma

Intoxications with sulfonylureas can cause hypoglycemia and are best managed with glucose administration (oral for milder hypoglycemia or by injection in more severe forms)

Increased toxicity: Monitor patient closely; large number of drugs interact with sulfonylureas including salicylates, anticoagulants, H₂-antagonists, TCAs, MAO inhibitors, beta-blockers, thiazides

Stimulates insulin release from the pancreatic beta cells; reduces glucose output from the liver; insulin sensitivity is increased at peripheral target sites

Onset of action: Oral: Within 4-6 hours

Duration: 10-24 hours

Protein binding: >98% ionic/nonionic

Metabolism: Extensively in the liver to one active and three inactive metabolites

Half-life: 7 hours

Elimination: Renal

Oral (doses >1000 mg/day normally do not improve diabetic control):

Initial: 100-250 mg/day with breakfast or the first main meal of the day

Fasting blood sugar <200 mg/dL: 100 mg/day

Fasting blood sugar >200 mg/dL: 250 mg/day

Patient is malnourished, underweight, elderly, or not eating properly: 100 mg/day

Adjust dose in increments of 100-250 mg/day at weekly intervals to response. If >500 mg/day is required, give in divided doses twice daily; maximum daily dose: 1 g (doses >1 g/day are not likely to improve control)

Conversion from insulin tolazamide

10 units day = 100 mg/day

20-40 units/day = 250 mg/day

>40 units/day = 250 mg/day and 50% of insulin dose

Doses >500 mg/day should be given in 2 divided doses

At higher dosages, sulfonylureas may block the ATP-sensitive potassium channels, which may correspond to an increased risk of cardiovascular events. In May, 2000, the National Diabetes Center issued a warning to avoid the use of sulfonylureas at higher dosages; see Warnings/Precautions.

Dosing adjustment in renal impairment: Conservative initial and maintenance doses are recommended because tolazamide is metabolized to active metabolites, which are eliminated in the urine

Dosing comments in hepatic impairment: Conservative initial and maintenance doses and careful monitoring of blood glucose are recommended

Alcohol: Avoid use

Signs and symptoms of hypoglycemia, (fatigue, sweating, numbness of extremities); urine for glucose and ketones; fasting blood glucose; hemoglobin A_1c or fructosamine

Target range:

Adults: 80-140 mg/dL

Geriatrics: 100-150 mg/dL

Glycosylated hemoglobin: <7%

Dizziness is common

May cause agranulocytosis; use caution with clozapine and carbamazepine; concurrent use with psychotropics may produce alterations in serum glucose concentrations; monitor glucose; clinical manifestation of hypoglycemia may be blocked by beta-blockers

No information available to require special precautions

Use salicylates with caution in patients taking tolazamide because of potential increased hypoglycemia; NSAIDs such as ibuprofen and naproxen may be safely used. Tolazamide-dependent diabetics (noninsulin dependent, type 2) should be appointed for dental treatment in morning in order to minimize chance of stress-induced hypoglycemia.

This medication is used to control diabetes; it is not a cure. Other components of the treatment plan are important: follow prescribed diet, medication, and exercise regimen. Take exactly as directed; at the same time each day. Do not change dose or discontinue without consulting prescriber. Avoid alcohol while taking this medication; could cause severe reaction. Inform prescriber of all other prescription or OTC medications you are taking; do not introduce new medication without consulting prescriber. Do not take other medication within 2 hours of this medication unless so advised by prescriber. If you experience hypoglycemic reaction, contact prescriber immediately; maintain regular dietary intake and exercise routine and always carry quick source of sugar with you. You may be more sensitive to sunlight (use sunscreen, wear protective clothing and eyewear, and avoid direct sunlight). You may experience side effects during first weeks of therapy (headache, nausea, diarrhea, constipation, anorexia); consult prescriber if these persist. Report severe or persistent side effects, extended vomiting or flu-like symptoms, skin rash, easy bruising or bleeding, or change in color of urine or stool. Pregnancy/breast-feeding precautions: Do not get pregnant; use appropriate contraceptive measures to prevent possible harm to the fetus. Consult prescriber if breast-feeding.

Patients who are anorexic or NPO may need to have their dose held to avoid hypoglycemia

Tablet: 100 mg, 250 mg, 500 mg

Rull JH and Lennhoff M, "Prolonged and Recurrent Tolazamide-Induced Hypoglycemia," Diabetes, 1967, 16(5):352-3.

Seger D, "Toxic Emergencies of Endocrine and Metabolic Therapeutic Agents," J Emerg Med, 1988, 6(6):527-37.

"Standards of Medical Care for Patients With Diabetes Mellitus. American Diabetes Association," Diabetes Care, 1994, 17(6):616-23.