Dosing and uses of Orinase (tolbutamide)
Adult dosage forms and strengths
tablet
- 500mg
Type 2 Diabetes
250 mg-2 g PO qDay or q8-12hr; not to exceed 3 g/day; maintenance dose >2 g/day seldom required
Divided doses may minimize gastrointestinal side effects
Renal Impairment
Dose adjustment not necessary
Hepatic Impairment
May require a lower dose (monitor)
Pediatric dosage forms and strengths
Safety and efficacy not established
Geriatric dosage forms and strengths
250 mg PO qDay or q8-12hr; not to exceed 3 g/day; maintenance dose >2 g/day seldom required
Divided doses may minimize gastrointestinal side effects
Orinase (tolbutamide) adverse (side) effects
Frequency not defined
Hypoglycemia
Dermatologic recations
Disulfiram-like reactions
Agranulocytosis
Hyponatremia
Aplastic anemia
Thrombocytopenia
Heartburn
Nausea/vomiting
Cholestatic jaundice and hepatitis may occur rarely which may progress to liver failure
Warnings
Contraindications
Hypersensitivity, sulfa allergy
Type I diabetes, diabetic ketoacidosis
Cautions
Patients with hypoglycemia, when caloric intake is decreased or there is increased stress due to infection, fever, trauma, or surgery (may need to discontinue treatment)
Risk of cardiovascular mortality increases with oral hypoglycemic drug treatments compared to treatment with diet alone or diet plus insulin
Risk of sulfonylurea-induced hemolytic anemia may increase in patients iwth glucose-6-phosphate dehydrogenase deficiency
Pregnancy and lactation
Pregnancy category: C
Lactation: Controversial, avoid
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Orinase (tolbutamide)
Mechanism of action
Initial effect is to increase beta-cell insulin secretion
May also decrease rate of hepatic glucose production, increases insulin receptor sensitivity, and increases number of insulin receptors
Pharmacokinetics
Half-Life: 4.5-6.5 hr
Duration: 6-24 hr
Onset: 1hr
Max Effect: 5-8 hr
Time to peak, serum: 3-4 hr
Protein Bound: 80-99%
Vd: 0.15 L/kg
Metabolism: extensively, in liver to inactive metabolites by hepatic P450 enzyme CYP2C9
Metabolites: carboxytolbutamide, hydroxymethyltolbutamide (inactive)
Excretion: mainly in urine 70-80%
Dialyzable
- Hemodialysis: No
- Peritoneal dialysis: No data
