GLUCOTROL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for GLUCOTROL (GLUCOTROL).
Stimulates insulin secretion from pancreatic beta cells by binding to sulfonylurea receptor 1 (SUR1) on ATP-sensitive potassium channels, causing depolarization and calcium influx. Also may increase peripheral insulin sensitivity.
| Metabolism | Extensively metabolized by CYP2C9 to inactive metabolites. |
| Excretion | Primarily renal: ~80% as metabolites (mainly 4-trans-hydroxyglipizide and 3-cis-hydroxyglipizide) and ~10% unchanged; fecal: ~10%. |
| Half-life | Terminal elimination half-life: 2-4 hours (mean 3.4 hours) in normal subjects; extended up to 8-12 hours in elderly or hepatic impairment due to reduced clearance. |
| Protein binding | 98-99% bound to albumin; slight displacement by acidic drugs (e.g., salicylates, sulfonamides) may occur. |
| Volume of Distribution | Approximately 0.16 L/kg (range 0.11-0.21 L/kg); indicates distribution primarily in extracellular fluid; low Vd consistent with high protein binding. |
| Bioavailability | Oral immediate-release: 100% (completely absorbed), but first-pass hepatic metabolism reduces systemic availability ~20-30%; absolute bioavailability ~80-90%. |
| Onset of Action | Oral immediate-release: peak serum concentration at 1-3 hours; glucose-lowering effect begins within 30 minutes; onset of insulin secretion: within 15-30 minutes. |
| Duration of Action | Duration of glucose lowering: 12-24 hours with immediate-release; extended-release (Glucotrol XL) provides 24-hour coverage due to controlled release. |
| Action Class | Sulfonylureas (Insulin Secretogogues) |
| Brand Substitutes | Glylup 5mg Tablet, Diacon 5mg Tablet, Glibetic 5mg Tablet, Glipitis 5mg Tablet, Glirum Tablet |
Initial dose 5 mg orally once daily, increased by 2.5-5 mg increments weekly based on glycemic response; maximum 20 mg daily as single or divided doses (for doses >15 mg, administer in divided doses).
| Dosage form | TABLET |
| Renal impairment | eGFR 30-60 mL/min: initiate at 2.5 mg daily with cautious titration; eGFR <30 mL/min: contraindicated. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B or C: contraindicated. |
| Pediatric use | Not recommended for pediatric patients due to insufficient safety and efficacy data. |
| Geriatric use | Start with 2.5 mg daily; titrate slowly to avoid hypoglycemia; monitor renal function closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for GLUCOTROL (GLUCOTROL).
| Breastfeeding | Excreted in breast milk; M/P ratio not established. Potential for infant hypoglycemia; contraindicated during breastfeeding. |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: No adequate studies; unknown risk. Second/Third trimester: Possible increased neonatal hypoglycemia if used near term; avoid use after 32 weeks gestation. |
| Fetal Monitoring | Maternal: Blood glucose, HbA1c. Fetal: Ultrasound for macrosomia, polyhydramnios; neonatal glucose monitoring for 24-48 hours postpartum. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Type 1 diabetes mellitus","Diabetic ketoacidosis","Hypersensitivity to glipizide or sulfonylureas"]
| Precautions | ["May cause hypoglycemia, especially in elderly, debilitated, or malnourished patients","Increased cardiovascular mortality risk based on University Group Diabetes Program (UGDP) study","Hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency","Hepatic impairment may prolong drug effects"] |
| Food/Dietary | Take with food to reduce GI side effects. Avoid alcohol. High-fiber meals may delay absorption; consistency in carbohydrate intake is advised to prevent hypoglycemia. Grapefruit juice may increase drug levels; avoid concurrent use. |
Loading safety data…
| Fertility Effects | No known adverse effects on fertility in humans; animal studies show no impairment. |
| Clinical Pearls | Initiate at 5 mg daily, taken with breakfast or first main meal. Titrate in 2.5–5 mg increments every 1–2 weeks. Max dose 40 mg/day. Use with caution in renal impairment; avoid in severe hepatic impairment. May cause disulfiram-like reaction with alcohol. Sulfonylurea hypersensitivity contraindicated. |
| Patient Advice | Take GLUCOTROL with breakfast or first main meal to reduce GI upset. · Monitor blood glucose regularly, especially during illness or stress. · Avoid alcohol to prevent disulfiram-like reaction (flushing, headache, nausea). · Report signs of hypoglycemia (sweating, tremor, confusion) immediately. · Maintain consistent meal schedule; skipping meals increases hypoglycemia risk. · Do not drive or operate machinery until you know how this drug affects you. · Wear medical alert ID for diabetes. · Do not crush or chew extended-release tablets. |