GLUCOTROL XL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for GLUCOTROL XL (GLUCOTROL XL).
Stimulates insulin secretion from pancreatic beta cells by binding to ATP-sensitive potassium channels, causing depolarization and calcium influx, leading to insulin release.
| Metabolism | Hepatic metabolism via cytochrome P450 (CYP2C9) to inactive metabolites. |
| Excretion | Renal: ~70% as metabolites (primarily hydroxylated and conjugated metabolites), unchanged drug <10%; Fecal: ~20% via bile. |
| Half-life | Terminal elimination half-life 2-5 hours; however, due to extended-release formulation, therapeutic effects persist up to 24 hours. |
| Protein binding | ~97-99% bound primarily to albumin. |
| Volume of Distribution | 0.11-0.16 L/kg; low Vd indicates limited extravascular distribution, consistent with high protein binding. |
| Bioavailability | Oral: ~100% (complete absorption); relative bioavailability of XL formulation compared to immediate-release is approximately 90-100%. |
| Onset of Action | Oral: 2-3 hours (initial reduction in plasma glucose); maximum effect at 6-12 hours. |
| Duration of Action | 24 hours (once-daily dosing); extended-release formulation maintains glucose control over 24 hours with once-daily administration. |
Initial dose: 5 mg orally once daily with breakfast. Titrate by 2.5-5 mg increments at weekly intervals based on glycemic response. Maximum dose: 20 mg once daily.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | For eGFR 30-60 mL/min: use with caution, initial dose 2.5 mg daily. For eGFR <30 mL/min: contraindicated. |
| Liver impairment | Mild to moderate hepatic impairment (Child-Pugh A or B): start at 2.5 mg daily; titrate cautiously. Severe impairment (Child-Pugh C): contraindicated. |
| Pediatric use | Not indicated for pediatric patients under 18 years; safety and efficacy not established. |
| Geriatric use | Initial dose 2.5 mg orally once daily to avoid hypoglycemia; titrate slowly every 2-3 weeks. Maximum 20 mg daily. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for GLUCOTROL XL (GLUCOTROL XL).
| Breastfeeding | Glipizide is excreted in human milk. M/P ratio not reported. Breastfeeding is generally not recommended due to risk of neonatal hypoglycemia. If used, monitor infant blood glucose. |
| Teratogenic Risk | Glipizide (Glucotrol XL) is classified as FDA Pregnancy Category C. First trimester: Animal studies have shown embryotoxicity with no adequate human studies, but available data do not suggest a major increase in congenital anomalies. Second and third trimesters: Potential neonatal hypoglycemia and macrosomia due to poor glycemic control. Use only if insulin is not feasible. |
■ FDA Black Box Warning
Increased risk of cardiovascular mortality based on the University Group Diabetes Program (UGDP) study.
| Serious Effects |
["Type 1 diabetes mellitus","Diabetic ketoacidosis, with or without coma","Known hypersensitivity to glipizide or sulfonylureas","Severe renal or hepatic impairment"]
| Precautions | ["Hypoglycemia risk, especially in elderly, debilitated, or malnourished patients; renal or hepatic impairment; and with use of other hypoglycemic agents","May cause hemolytic anemia in patients with G6PD deficiency","Increased cardiovascular mortality risk (black box warning)"] |
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| Fetal Monitoring | Monitor maternal blood glucose and HbA1c regularly. Fetal monitoring includes ultrasound for growth and amniotic fluid volume, and nonstress test or biophysical profile in third trimester. Monitor neonate for hypoglycemia after delivery. |
| Fertility Effects | No specific adverse effects on fertility reported in humans. In animal studies, no impairment of fertility was observed. |