TOLINASE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TOLINASE (TOLINASE).
Sulfonylurea that stimulates insulin secretion from pancreatic beta cells by binding to SUR1 subunit of ATP-sensitive potassium channels, causing membrane depolarization and calcium influx.
| Metabolism | Primarily hepatic metabolism via CYP2C9; metabolites are excreted in urine (85%) and feces (15%). |
| Excretion | Renal: 85% as unchanged drug and metabolites; biliary/fecal: 15%. |
| Half-life | Terminal elimination half-life is 7 hours (range 4–10 hours) in normal renal function; clinically, dosing interval adjustments are needed in renal impairment, with half-life prolonged to 20–30 hours in severe renal disease. |
| Protein binding | 99% bound primarily to serum albumin; binding is reversible and saturable at high concentrations. |
| Volume of Distribution | Vd is 0.2 L/kg (approximately 14 L in 70 kg patient); indicates limited extravascular distribution, primarily confined to extracellular fluid. |
| Bioavailability | Oral bioavailability: 85–100%; food does not significantly affect absorption. |
| Onset of Action | Oral: Onset of glucose lowering is 1 hour after a single dose; peak effect at 4–6 hours. |
| Duration of Action | Duration of action is 12–24 hours; clinically, once-daily dosing is sufficient, but duration may be extended in hepatic or renal impairment due to reduced clearance. |
Initial dose 100-250 mg orally once daily with breakfast or first main meal; increase by 250 mg at weekly intervals based on glycemic response. Maximum 1 g daily. Doses above 500 mg should be divided twice daily.
| Dosage form | TABLET |
| Renal impairment | Contraindicated if eGFR <30 mL/min. For eGFR 30-59 mL/min: start at 100 mg daily, max 500 mg daily; for eGFR 60-89 mL/min: start at 100 mg daily, max 750 mg daily. |
| Liver impairment | Contraindicated in Child-Pugh class C. For Child-Pugh class A: reduce dose by 50%; for class B: reduce dose by 75% from usual starting dose. |
| Pediatric use | Not recommended for pediatric patients; safety and efficacy not established. |
| Geriatric use | Start at 50 mg daily with first main meal; titrate slowly every 2 weeks; avoid doses >500 mg daily. Monitor renal function closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TOLINASE (TOLINASE).
| Breastfeeding | TOLINASE is excreted in human milk. The milk-to-plasma ratio is approximately 0.3. Potential for hypoglycemia in nursing infants. Caution is advised. Consider alternatives, especially for preterm or sick infants. |
| Teratogenic Risk | TOLINASE (tolazamide) is a sulfonylurea. In animal studies, sulfonylureas have been associated with teratogenic effects at high doses. In humans, first trimester exposure is not strongly associated with major malformations but may increase risk of hypoglycemia. Second and third trimester exposure can cause neonatal hypoglycemia and macrosomia. Overall, FDA Pregnancy Category C. |
■ FDA Black Box Warning
Increased risk of cardiovascular mortality compared to diet alone or diet plus insulin (based on University Group Diabetes Program study).
| Serious Effects |
["Type 1 diabetes mellitus","Diabetic ketoacidosis","Hypersensitivity to tolazamide or sulfonylureas"]
| Precautions | ["Hypoglycemia","Hepatic impairment","Renal impairment","Hemolytic anemia in patients with G6PD deficiency","Weight gain","Disulfiram-like reaction with alcohol"] |
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| Fetal Monitoring | Monitor maternal blood glucose, HbA1c, and signs of hypoglycemia. Fetal monitoring includes ultrasound for growth assessment and amniotic fluid index, and nonstress test or biophysical profile in third trimester. Monitor neonatal blood glucose for 24-48 hours after delivery. |
| Fertility Effects | No direct effects on fertility reported. Poor glycemic control may impair fertility due to anovulation. Improved glycemic control can restore fertility. |