PROGLYCEM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PROGLYCEM (PROGLYCEM).
Diazoxide is a benzothiadiazine derivative that inhibits insulin release from pancreatic beta cells by opening ATP-sensitive potassium channels (K_ATP channels), leading to hyperpolarization of the cell membrane and reduced calcium influx. It also has peripheral hyperglycemic effects by inhibiting glucose uptake and enhancing hepatic glucose output.
| Metabolism | Primarily hepatic metabolized via oxidation and conjugation, with renal excretion of metabolites and unchanged drug. |
| Excretion | Primarily renal (about 80% as unchanged drug), with the remainder metabolized hepatically and eliminated via bile/feces. |
| Half-life | Approximately 20-30 hours; may be prolonged in hepatic or renal impairment, requiring dose adjustment. |
| Protein binding | Approximately 90% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | 0.2-0.5 L/kg; indicates distribution mainly in extracellular fluid. |
| Bioavailability | Oral: ~100%; well-absorbed with no significant first-pass metabolism. |
| Onset of Action | Oral: 30-60 minutes for reduction of blood glucose; peak effect at 2-4 hours. |
| Duration of Action | 8-12 hours for oral administration; may be extended in renal or hepatic impairment. |
Initial: 50-100 mg orally three times daily; maintenance: 50-100 mg orally three times daily; maximum single dose: 100 mg, maximum daily dose: 300 mg.
| Dosage form | SUSPENSION |
| Renal impairment | No specific guidelines available; use with caution in renal impairment due to risk of hypoglycemia. Monitor blood glucose closely. |
| Liver impairment | No specific guidelines available; use with caution in hepatic impairment. Dose reduction may be necessary if adverse effects occur. |
| Pediatric use | Initial: 3-5 mg/kg/day orally in two to three divided doses; maintenance: 3-8 mg/kg/day orally in two to three divided doses; maximum: 10 mg/kg/day or 300 mg/day. |
| Geriatric use | Use with caution; start at low end of dosing range due to potential for altered drug clearance and increased sensitivity to hypoglycemic effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PROGLYCEM (PROGLYCEM).
| Breastfeeding | Diazoxide is excreted in human breast milk. The milk-to-plasma ratio (M/P) is approximately 0.2–0.8. Potential for infant serum diazoxide levels and hypoglycemia exists. Breastfeeding is not recommended during PROGLYCEM therapy due to the risk of neonatal hypoglycemia and other adverse effects. If used, monitor infant for signs of hypoglycemia and hyperbilirubinemia. |
| Teratogenic Risk | In animal studies, diazoxide (PROGLYCEM) has been associated with fetal pancreatic, cardiac, and skeletal abnormalities at high doses. There are limited human data; however, potential risks include fetal hyperglycemia, delayed lung maturation, and possible teratogenic effects. Use during first trimester should be avoided unless benefit outweighs risk. During second and third trimesters, may cause fetal or neonatal hyperbilirubinemia, thrombocytopenia, and fetal/neonatal hyperglycemia. Also associated with fetal pancreatic beta-cell agenesis or hypoplasia if used near term. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to diazoxide","Hypoglycemia due to causes other than hyperinsulinism","Functional hypoglycemia","Pregnancy (unless potential benefit outweighs risk)","Lactation (discontinue nursing or drug)"]
| Precautions | ["Fluid retention and heart failure (risk increased in patients with compromised cardiac function)","Hyperglycemia and diabetic ketoacidosis","Hypotension (due to vasodilation)","Increased risk of thrombosis and embolism","Neutropenia and other hematologic effects","Sodium and fluid retention may cause edema"] |
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| Fetal Monitoring | Maternal: Monitor blood glucose, blood pressure, heart rate, and electrolytes regularly. Monitor for signs of fluid retention, heart failure, and ketoacidosis. Fetal/neonatal: Monitor growth, amniotic fluid index, fetal heart rate. Neonatal: Monitor for hypoglycemia, hyperbilirubinemia, thrombocytopenia, and panting respiration within the first 24 hours. Postnatal: Long-term follow-up for pancreatic function and growth. |
| Fertility Effects | No specific human studies on fertility effects. In animal studies, high doses of diazoxide have been associated with impaired fertility and reproductive performance. Effects on libido or menstrual cycle have not been systematically evaluated. May cause hormonal alterations due to hyperglycemic effects. |