ORINASE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ORINASE (ORINASE).
Stimulates insulin secretion from pancreatic beta cells by binding to sulfonylurea receptor 1 (SUR1) on ATP-sensitive potassium channels, causing membrane depolarization, calcium influx, and exocytosis of insulin granules.
| Metabolism | Primarily hepatic via CYP2C9; metabolites are eliminated renally and in feces. |
| Excretion | Renal: approximately 85-90% as metabolites and unchanged drug; biliary/fecal: <10% |
| Half-life | Terminal elimination half-life: 4-7 hours; clinical context: due to active metabolites, hypoglycemic effect may persist up to 24 hours |
| Protein binding | 88-99% bound, primarily to albumin |
| Volume of Distribution | 0.1-0.2 L/kg; low Vd indicates limited extravascular distribution |
| Bioavailability | Oral: approximately 85-90% |
| Onset of Action | Oral: 30-60 minutes |
| Duration of Action | 6-12 hours, but may extend up to 24 hours due to active metabolites; caution in elderly and renal impairment |
Initial dose 250 mg to 500 mg orally once daily with breakfast, titrated up to a maximum of 3 g/day in divided doses.
| Dosage form | TABLET |
| Renal impairment | Contraindicated if GFR <50 mL/min/1.73 m². For GFR 50-80 mL/min/1.73 m², reduce dose by 50%. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh class C). For Child-Pugh class A or B, reduce dose by 50% and monitor glucose closely. |
| Pediatric use | Not recommended for pediatric use due to lack of safety data. |
| Geriatric use | Initiate with 250 mg orally once daily; titrate slowly to avoid hypoglycemia. Avoid use in patients >80 years unless GFR >50 mL/min/1.73 m². |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ORINASE (ORINASE).
| Breastfeeding | Orinase is excreted in breast milk in low concentrations. The M/P ratio is not well established. Potential for hypoglycemia in nursing infants. American Academy of Pediatrics considers it compatible with breastfeeding, but caution is advised. Monitor infant for hypoglycemia symptoms. |
| Teratogenic Risk | Orinase (tolbutamide) is a sulfonylurea. Data on teratogenicity in humans are limited. First trimester exposure: some studies suggest a possible increased risk of congenital malformations, but evidence is inconclusive. Second and third trimester exposure: may cause neonatal hypoglycemia if used near term. Avoid use in pregnancy; insulin is preferred. |
■ FDA Black Box Warning
No FDA boxed warning.
| Serious Effects |
["Type 1 diabetes mellitus","Diabetic ketoacidosis","Hypersensitivity to tolbutamide or any excipient"]
| Precautions | ["Hypoglycemia: risk increased with caloric restriction, hepatic/renal impairment, or use of multiple glucose-lowering drugs","Cardiovascular mortality: possible increased risk compared to diet or insulin (based on UGDP study)","Hematologic reactions: rare but include agranulocytosis, hemolytic anemia, aplastic anemia, and pancytopenia","Hepatic porphyria: may exacerbate porphyria cutanea tarda"] |
Loading safety data…
| Fetal Monitoring | Monitor maternal blood glucose levels regularly. For the fetus: ultrasound monitoring for growth and anomalies if exposed in first trimester. Neonatal monitoring for hypoglycemia if drug used near term. |
| Fertility Effects | No known adverse effects on fertility in humans. Animal studies show no significant reproductive toxicity. |