TOLAZAMIDE
Clinical safety rating: safe
Animal studies have demonstrated safety
Tolazamide is a sulfonylurea that stimulates insulin secretion from pancreatic beta cells by binding to the sulfonylurea receptor (SUR1) on ATP-sensitive potassium channels, leading to channel closure, membrane depolarization, calcium influx, and insulin exocytosis.
| Metabolism | Primarily hepatic metabolism via CYP2C9 and other pathways; metabolites are excreted renally. |
| Excretion | Primarily renal (85% as metabolites, <1% unchanged); biliary/fecal (7%) |
| Half-life | Terminal half-life 7 hours (range 4–10 hours); prolonged in renal impairment. |
| Protein binding | 92–98% bound to serum albumin. |
| Volume of Distribution | 0.12–0.20 L/kg; low Vd indicates minimal extravascular distribution. |
| Bioavailability | Oral: ~100% (well absorbed) |
| Onset of Action | Oral: 4–6 hours |
| Duration of Action | 12–24 hours; up to 36 hours in impaired renal function. |
Initial: 100-250 mg orally once daily with breakfast. Maintenance: 250-500 mg orally once or twice daily. Maximum: 1 g daily.
| Dosage form | TABLET |
| Renal impairment | eGFR 30-60 mL/min: Reduce dose by 50%. eGFR <30 mL/min: Contraindicated. |
| Liver impairment | Child-Pugh Class A: No adjustment. Child-Pugh Class B: Reduce dose by 50%. Child-Pugh Class C: Contraindicated. |
| Pediatric use | Not recommended in pediatric patients due to risk of severe hypoglycemia and lack of safety data. |
| Geriatric use | Start at 100 mg orally once daily; monitor renal function and adjust accordingly. Avoid use in frail elderly or those with irregular eating patterns. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Drugs that increase hypoglycemia risk (eg beta-blockers) Can cause severe and prolonged hypoglycemia.
| Breastfeeding | Tolazamide is excreted into breast milk in low concentrations; M/P ratio not reported. Theoretical risk of neonatal hypoglycemia. Caution advised; monitor infant for hypoglycemia. Consider alternative agents. |
| Teratogenic Risk | FDA pregnancy category C. Tolazamide is a sulfonylurea that crosses the placenta. First trimester: Limited human data; animal studies show no teratogenicity but fetal toxicity at high doses. Second/third trimester: Risk of neonatal hypoglycemia if used near term. Inadequate studies, use only if benefit outweighs risk. |
■ FDA Black Box Warning
Increased risk of cardiovascular mortality based on the University Group Diabetes Program (UGDP) study; treatment with oral hypoglycemics may be associated with increased cardiovascular mortality compared to diet alone or diet plus insulin.
| Common Effects | Dizziness Sleepiness Orthostatic hypotension sudden lowering of blood pressure on standing Dryness in mouth Weight gain Increased prolactin level in blood Constipation Muscle stiffness Restlessness Tremors |
| Serious Effects |
["Type 1 diabetes mellitus or diabetic ketoacidosis","Hypersensitivity to tolazamide or any sulfonylurea","Severe renal or hepatic impairment"]
| Precautions | ["Hypoglycemia: may be severe and prolonged, especially in elderly, debilitated, or malnourished patients; renal or hepatic impairment may increase risk.","Cardiovascular mortality: see black box warning.","Hematologic reactions: agranulocytosis, aplastic anemia, hemolytic anemia, thrombocytopenia.","Hepatic porphyria: may precipitate porphyria attacks.","Disulfiram-like reaction: with alcohol consumption may cause flushing, headache, nausea."] |
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| Fetal Monitoring |
| Monitor maternal blood glucose and HbA1c. Fetal monitoring: ultrasound for growth and amniotic fluid index, nonstress test or biophysical profile in third trimester. Monitor neonate for hypoglycemia after delivery. |
| Fertility Effects | No known adverse effects on fertility. Limited data; sulfonylureas not associated with fertility impairment in humans. |