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Pronunciation(tole AZ a mide)
U.S. Brand NamesTolinase®
Generic AvailableYes
Canadian Brand NamesTolinase®
UseAdjunct to diet for the management of mild to moderately severe, stable, type 2 diabetes mellitus (noninsulin dependent, NIDDM)
Pregnancy Risk FactorD
Pregnancy ImplicationsAbnormal blood glucose levels are associated with a higher incidence of congenital abnormalities. Insulin is the drug of choice for the control of diabetes mellitus during pregnancy.
LactationExcretion in breast milk unknown
ContraindicationsHypersensitivity to tolazamide, sulfonylureas, or any component of the formulation; type 1 diabetes mellitus (insulin dependent, IDDM) therapy; diabetes complicated by ketoacidosis; pregnancy
Warnings/PrecautionsFalse-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. Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with sulfonylurea allergy is specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe.
Product labeling states oral hypoglycemic drugs may be associated with an increased cardiovascular mortality as compared to treatment with diet alone or diet plus insulin. Data to support this association are limited, and several studies, including a large prospective trial (UKPDS) have not supported an association.
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Adverse ReactionsFrequency not defined. Central nervous system: Headache, dizziness
Dermatologic: Rash, urticaria, photosensitivity
Endocrine & metabolic: Hypoglycemia, SIADH
Gastrointestinal: Anorexia, nausea, vomiting, diarrhea, constipation, heartburn, epigastric fullness
Hematologic: Aplastic anemia, hemolytic anemia, bone marrow suppression, thrombocytopenia, agranulocytosis
Hepatic: Cholestatic jaundice
Renal: Diuretic effect
Overdosage/ToxicologySymptoms 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)
Drug InteractionsIncreased toxicity: Monitor patient closely; large number of drugs interact with sulfonylureas including salicylates, anticoagulants, H2 antagonists, TCAs, MAO inhibitors, beta-blockers, thiazides
Ethanol/Nutrition/Herb InteractionsEthanol: Avoid ethanol (possible disulfiram-like reaction).
Mechanism of ActionStimulates insulin release from the pancreatic beta cells; reduces glucose output from the liver; insulin sensitivity is increased at peripheral target sites
Pharmacodynamics/KineticsOnset of action: 4-6 hours
Duration: 10-24 hours
Protein binding: >98%
Metabolism: Extensively hepatic to one active and three inactive metabolites
Half-life elimination: 7 hours
Excretion: Urine
DosageOral (doses >1000 mg/day normally do not improve diabetic control): Adults:
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 to 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
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
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Monitoring ParametersSigns and symptoms of hypoglycemia (fatigue, sweating, numbness of extremities); urine for glucose and ketones; fasting blood glucose; hemoglobin A1c or fructosamine
Reference RangeTarget range: Fasting blood glucose:
Adults: 80-140 mg/dL
Geriatrics: 100-150 mg/dL
Glycosylated hemoglobin: <7%
Patient EducationThis 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 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.
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Nursing ImplicationsPatients who are anorexic or NPO may need to have their dose held to avoid hypoglycemia
Cardiovascular ConsiderationsThe possibility of higher doses of sulfonylureas eliciting an increase in cardiovascular events, because of their effects on blocking potassium sensitive ATP channels, has been raised. However, there are presently only limited data to support this premise, particularly with newer generation agents. An early study suggested poor cardiovascular outcomes in diabetic patients treated with tolbutamide. Retrospective studies evaluating cardiovascular outcomes following angioplasty and acute myocardial infarction in diabetic patients receiving newer sulfonylureas are inconsistent. Longer-term prospective trials of sulfonylurea therapy, such as the UKPDS, do not reveal any increased cardiovascular mortality.
Dental Health: Effects on Dental TreatmentUse salicylates with caution in patients taking tolazamide due to 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.
Dental Health: Vasoconstrictor/Local Anesthetic PrecautionsNo information available to require special precautions
Mental Health: Effects on Mental StatusDizziness is common
Mental Health: Effects on Psychiatric TreatmentMay 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
Dosage Forms[DSC] = Discontinued product Tablet: 100 mg, 250 mg, 500 mg
Tolinase®: 100 mg [DSC], 250 mg
ReferencesAlexander RW, "Prolonged Hypoglycemia Following Acetohexamide Administration,"Diabetes, 1966, 15(5):362-4.
"A Study of the Effects of Hypoglycemia Agents on Vascular Complications in Patients With Adult-onset Diabetes. VI. Supplementary Report on Nonfatal Events in Patients Treated With Tolbutamide. The University Group Diabetes Program,"Diabetes, 1976, 25(12):1129-53.
Cowen DL, Burtis B, and Youmans J, "Prolonged Coma After Acetohexamide Ingestion,"JAMA, 1967, 201(2):141-2.
"Effect of Intensive Blood-Glucose Control With Metformin on Complications in Overweight Patients With Type 2 Diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group,"Lancet, 1998, 352(9131):854-65.
Garratt KN, Brady PA, Hassinger NL, et al, "Sulfonylurea Drugs Increase Early Mortality in Patients With Diabetes Mellitus After Direct Angioplasty for Acute Myocardial Infarction,"J Am Coll Cardiol, 1999, 33(1):119-24.
"Intensive Blood-Glucose Control With Sulphonylureas or Insulin Compared With Conventional Treatment and Risk of Complications in Patients With Type 2 Diabetes (UKPDS 33) UK Prospective Diabetes Study (UKPDS) Group,"Lancet, 1998, 352(9131):837-53.
Klamann A, Sarfert P, Launhardt V, et al, "Myocardial Infarction in Diabetic vs Nondiabetic Subjects. Survival and Infarct Size Following Therapy With Sulfonylureas (Glibenclamide), Eur Heart J, 2000, 21(3):220-9.
Meinert CL, Knatterud GL, Prout TE, et al, "A Study of the Effects of Hypoglycemic Agents on Vascular Complications in Patients With Adult-Onset Diabetes. II. Mortality Results,"Diabetes, 1970, 19:789-830.
O'Keefe JH, Blackstone EH, Sergeant P, et al, "The Optimal Mode of Coronary Revascularization for Diabetics. A Risk-Adjusted Long-Term Study Comparing Coronary Angioplasty and Coronary Bypass Surgery,"Eur Heart J, 1998, 19(11):1696-703.
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.
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International Brand NamesTolinase® (CA)
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