TOLBUTAMIDE

TOLBUTAMIDE (tole-byoo'ta-mide) Mobenol , Novobutamide , Orinase TOLBUTAMIDE SODIUM Orinase Diagnostic Classifications: hormone; sulfonylurea antidiabetic; Therapeutic: antidiabetic, sulfonylurea Prototype: Glyburide Pregnancy Category: C

Availability

500 mg tablets; 1 g vial

Action

Short-acting sulfonylurea that lowers blood glucose concentration by stimulating pancreatic beta cells to synthesize and release insulin. No action demonstrated if functional beta cells are absent.

Therapeutic Effect

Lowers blood glucose concentration by stimulating pancreatic beta cells to synthesize and release insulin.

Uses

Management of mild to moderately severe, stable type 2 diabetes that is not controlled by diet and weight reduction alone. Also used in treatment of patients who are unresponsive to other sulfonylureas and adjunctively with insulin to stabilize certain cases of labile diabetes. Used as diagnostic agent to rule out pancreatic islet cell adenoma or diabetes.

Contraindications

Hypersensitivity to sulfonylureas or to sulfonamides; history of repeated episodes of diabetic ketoacidosis (with or without coma); type 1 diabetes as sole therapy; diabetic coma; severe stress, infection, trauma, or major surgery; severe renal insufficiency, liver or endocrine disease; pregnancy (category C). Safe use in children is not established.

Cautious Use

Cardiac, thyroid, pituitary, or adrenal dysfunction; severe hepatic disease, renal disease, renal impairment, renal failure; history of peptic ulcer; alcoholism; infection; older adults, debilitated, malnourished, or uncooperative patient; lactation.

Route & Dosage

Type 2 Diabetes Adult: PO 250 mg to 3 g/d in 1–2 divided doses Diagnosis of Functioning Insulinoma Adult: IV 1 g over 2–3 min

Administration

Oral

• Give total dose before breakfast but preferably in divided doses after meals.
• Crush tablet and give with full glass of water if patient desires.
• Do not give at bedtime because of danger of nocturnal hypoglycemia, unless specifically prescribed.
• Discontinue at least 2 wk before the expected delivery date to prevent prolonged severe hypoglycemia (4–10 d) in the neonate if used during pregnancy.
• Store below 40° C (104° F), preferably between 15°–30° C (59°–86° F) in well-closed container. Avoid freezing.

Adverse Effects (≥1%)

GI: Nausea, epigastric fullness, heartburn, anorexia, constipation, diarrhea, cholestatic jaundice (rare). Hematologic: Agranulocytosis, thrombocytopenia, leukopenia, hemolytic anemia, aplastic anemia, pancytopenia. Metabolic: Hepatic porphyria, disulfiram-like reactions, SIADH, hypoglycemia without loss of consciousness or neurologic symptoms (unusual fatigue, tremulousness, hunger, drowsiness, GI distress, sweating, anxiety, headache) severe hypoglycemia (visual disturbances, ataxia, paresthesias, confusion, tachycardia, seizures, coma). Skin: Allergic skin reactions: pruritus, erythema, urticaria, morbilliform or maculopapular eruptions; porphyria cutanea tarda, photosensitivity. Special Senses: Taste alterations. CNS: Headache.

Diagnostic Test Interference

The sulfonylureas may produce abnormal thyroid function test results and reduced RAI uptake (after long-term administration). A tolbutamide metabolite may cause false-positive urinary protein values when turbidity procedures are used (such as heat and acetic acid or sulfosalicylic acid); Ames reagent strips reportedly not affected.

Interactions

Drug: Phenylbutazone increases hypoglycemic effects; thiazide diuretics may attenuate hypoglycemic effects; alcohol may produce disulfiram reaction; beta blockers may mask symptoms of a hypoglycemic reaction. Herbal: Ginseng, karela may potentiate hypoglycemic effects.

Pharmacokinetics

Absorption: Readily from GI tract. Peak: 3–5 h. Distribution: Into extracellular fluids. Metabolism: Principally in liver. Elimination: 75–85% in urine; some in feces. Half-Life: 7 h.

Nursing Implications

Assessment & Drug Effects

• Supervise closely during initial period of therapy until dosage is established. One or 2 wk of therapy may be required before full therapeutic effect is achieved.
• Give low initial dose before breakfast to older adults, who may be hyperresponsive to oral antidiabetic therapy. If blood and urine glucose tests are negative during first 24 h of therapy, initial dose may be continued on a daily basis.
• Monitor closely during adjustment period, watching for S&S of impending hypoglycemia (see Appendix F). Detection of a hypoglycemic reaction in a diabetic patient also receiving a beta blocker, especially older adults, is difficult.
• Evaluate nondefinitive vague complaints; hypoglycemic symptoms may be especially vague in older adults. Observe patient carefully, especially 2–3 h after eating, check urine for sugar and ketone bodies and capillary blood glucose.
• Lab tests: Baseline liver and kidney function tests; periodic HbA_1C, serum electrolytes, CBC with differential, and platelet counts.
• Report repetitive complaints of headache and weakness a few hours after eating; may signal incipient hypoglycemia.
• Be aware that pruritus and rash, frequently reported adverse effects, may clear spontaneously; if these persist, drug will be discontinued.

Patient & Family Education

• Understand need to inform physician promptly of symptoms of hyperglycemia and ketoacidosis: flushed, dry skin, weight loss, fatigue, Kussmaul respiration, double or blurred vision, soft eyeballs, irritability, fruity-smelling breath, abdominal cramps, nausea, vomiting, diarrhea, dyspnea, polydipsia, polyphagia, polyuria, headache, hypotension, weak and rapid pulse, positive ketonuria and glycosuria.
• Hypoglycemia is frequently caused by overdosage of hypoglycemic drug, inadequate or irregular food intake, nausea, vomiting, diarrhea, and added exercise without caloric supplement or dose adjustment. Its occurrence indicates need for immediate reevaluation of patient's diet, medication regimen, and compliance. It is most likely to appear in patients >50 y of age.
• Report any illness promptly. Physician may want to evaluate need for insulin.
• Do not self-medicate with OTC drugs unless approved or prescribed by physician.
• Be aware that alcohol, even in moderate amounts, can precipitate a disulfiram-type reaction (see Appendix F). A hypoglycemic response after ingesting alcohol requires emergency treatment.
• Protect exposed skin areas from the sun with a sunscreen lotion (SPF 12–15) because of potential photosensitivity (especially in the alcoholic).
• Weigh at least weekly and report a progressive gain, especially if edema is present. These signs indicate the necessity to discontinue tolbutamide.
• Be alert to added danger of loss of control (hyperglycemia) when a drug that affects the hypoglycemic action of sulfonylureas (see DRUG INTERACTIONS) is withdrawn or added to the tolbutamide regimen. Monitor blood glucose carefully.
• Use or add barrier contraceptive if using hormonal contraceptives.
• Carry medical identification at all times. It needs to indicate medical diagnosis, medication(s) and doses, patient's and physician's names, addresses, and telephone numbers.
• Potential for hypoglycemia in breast fed infants presents the necessity to decide whether to discontinue breast feeding or temporarily transfer to insulin (if diet alone is inadequate for blood sugar control).

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Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug