Yes

Antidiabetic Agent (Sulfonylurea)

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

D

Diabetes complicated by ketoacidosis, therapy of IDDM, hypersensitivity to sulfonylureas

False-positive response has been reported in patients with liver disease, idiopathic hypoglycemia of infancy, severe malnutrition, acute pancreatitis. Because of its low potency and short duration, it is a useful agent in the elderly if drug interactions can be avoided. 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: Constipation, diarrhea, heartburn, anorexia, epigastric fullness

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

<1%: Venospasm, SIADH, disulfiram-type reactions, thrombocytopenia, agranulocytosis, hypoglycemia, leukopenia, aplastic anemia, hemolytic anemia, bone marrow suppression, cholestatic jaundice, thrombophlebitis, tinnitus, hypersensitivity reaction

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

Treatment: I.V. glucose (12.5-25 g), epinephrine for anaphylaxis

CYP2C8, 2C9, 2C18, and 2C19 enzyme substrate; CYP2C19 enzyme inhibitor

Decreased effects:

Hypoglycemic effects may be decreased by beta-blockers, cholestyramine, hydantoins, thiazides, rifampin, and others

Ethanol may decrease the half-life of tolbutamide

Use parenteral formulation within 1 hour following reconstitution

Stimulates insulin release from the pancreatic beta cells; reduces glucose output from the liver; insulin sensitivity is increased at peripheral target sites, suppression of glucagon may also contribute

Peak hypoglycemic action: Oral: 1-3 hours; I.V.: 30 minutes

Duration: Oral: 6-24 hours; I.V.: 3 hours

Time to peak serum concentration: 3-5 hours

Absorption: Oral: Rapid

Distribution: V_d: 6-10 L

Protein binding: 95% to 97% (principally to albumin) ionic/nonionic

Metabolism/Elimination: Hepatic metabolism to hydroxymethyltolbutamide (mildly active) and carboxytolbutamide (inactive) both rapidly excreted renally, less 2% excreted in the urine unchanged; metabolism does not appear to be affected by age

Increased plasma concentrations and volume of distribution secondary to decreased albumin concentrations and less protein binding have been reported.

Half-life: Plasma: 4-25 hours; Elimination: 4-9 hours

Divided doses may increase gastrointestinal side effects

Oral: Initial: 1-2 g/day as a single dose in the morning or in divided doses throughout the day. Total doses may be taken in the morning; however, divided doses may allow increased gastrointestinal tolerance. Maintenance dose: 0.25-3 g/day; however, a maintenance dose >2 g/day is seldom required.

I.V. bolus: 1 g over 2-3 minutes

Elderly: Oral: Initial: 250 mg 1-3 times/day; usual: 500-2000 mg; maximum: 3 g/day

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: Adjustment is not necessary

Hemodialysis: Not dialyzable (0% to 5%)

Dosing adjustment in hepatic impairment: Reduction of dose may be necessary in patients with impaired liver function

Alcohol: Avoid use

Entire dose can be given in AM, divided doses may improve GI tolerance

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. Tolbutamide-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 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 is 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 precautions: Do not get pregnant; use appropriate contraceptive measures to prevent possible harm to the fetus.

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

Injection, diagnostic, as sodium: 1 g (20 mL)

Tablet: 250 mg, 500 mg

Huupponen R, "Adverse Cardiovascular Effects of Sulphonylurea Drugs. Clinical Significance," Med Toxicol, 1987, 2(3):190-209.

Miller AK, Adir J, and Vestal RE, "Tolbutamide Binding to Plasma Proteins of Young and Old Human Subjects," J Pharm Sci, 1978, 67(8):1192-3.

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

Seltzer HS, "Drug-Induced Hypoglycemia: A Review Based on 473 Cases," Diabetes, 1972, 21(9):955-66.

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