DYMELOR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DYMELOR (DYMELOR).
Sulfonylurea that stimulates insulin secretion from pancreatic beta cells by blocking ATP-sensitive potassium channels, leading to membrane depolarization and calcium influx.
| Metabolism | Extensively metabolized in the liver to hydroxyhexamide, which has hypoglycemic activity. Metabolites are excreted primarily in urine. |
| Excretion | Primarily renal excretion of metabolites and unchanged drug (approximately 70-80%), with biliary/fecal excretion accounting for 10-20%. |
| Half-life | Terminal elimination half-life is 6-10 hours; clinically significant as it supports once-daily dosing. |
| Protein binding | Highly protein-bound (80-90%) to albumin. |
| Volume of Distribution | Vd is 0.1-0.2 L/kg, indicating limited distribution primarily to extracellular fluid. |
| Bioavailability | Oral bioavailability is 80-100%. |
| Onset of Action | Oral: Onset of hypoglycemic effect occurs within 1-2 hours. |
| Duration of Action | Duration is approximately 12-24 hours, with clinical note that sustained effects allow once-daily dosing. |
Initial dose: 250 mg orally once daily with breakfast; maintenance dose: 250-500 mg orally once daily; maximum dose: 1000 mg per day.
| Dosage form | TABLET |
| Renal impairment | GFR 50-80 mL/min: no adjustment; GFR 30-49 mL/min: reduce dose by 50%; GFR <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 for pediatric patients due to lack of safety and efficacy data. |
| Geriatric use | Start at 125 mg once daily; increase slowly to avoid hypoglycemia; monitor renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DYMELOR (DYMELOR).
| Breastfeeding | Excreted in breast milk; M/P ratio unknown. Potential for neonatal hypoglycemia. Contraindicated in breastfeeding; alternatives such as insulin recommended. |
| Teratogenic Risk | First trimester: Crosses placenta; associated with increased risk of congenital anomalies (neural tube defects, cardiovascular malformations) based on sulfonylurea class effects. Second/third trimester: Risk of neonatal hypoglycemia, macrosomia, and perinatal complications due to maternal glycemic control. Avoid use; insulin preferred. |
■ FDA Black Box Warning
Increased risk of cardiovascular mortality compared to diet alone or diet plus insulin. The University Group Diabetes Program (UGDP) trial reported increased cardiovascular mortality with tolbutamide, a sulfonylurea of similar class. DYMELOR (acetohexamide) should be prescribed with caution and patients should be informed of this risk.
| Serious Effects |
Hypersensitivity to acetohexamide or any sulfonylurea. Type 1 diabetes mellitus. Diabetic ketoacidosis, with or without coma. Severe renal or hepatic impairment.
| Precautions | Hypoglycemia: May cause severe hypoglycemia, especially in elderly, debilitated, or malnourished patients, and those with renal or hepatic insufficiency. Cardiovascular mortality: Possible increased risk as per UGDP study. Hepatic impairment: Use with caution; may prolong drug effects. Renal impairment: Excretion of active metabolites may be reduced, increasing risk of hypoglycemia. |
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| Fetal Monitoring |
| Maternal: Blood glucose, HbA1c, renal function, hepatic function. Fetal: Ultrasound for growth and anomalies, fetal echocardiography if first trimester exposure, neonatal blood glucose monitoring after delivery. |
| Fertility Effects | No direct evidence of impaired fertility in humans; sulfonylureas may affect ovulation via metabolic improvements. Animal studies show no significant reproductive toxicity. |