GLUCAGON
Clinical safety rating: safe
Animal studies have demonstrated safety
Glucagon is a polypeptide hormone that raises blood glucose by stimulating glycogenolysis in the liver, increasing gluconeogenesis, and inhibiting glycogen synthesis and glycolysis. It also relaxes smooth muscle of the gastrointestinal tract.
| Metabolism | Primarily hepatic degradation by proteolysis; also degraded in kidneys and plasma. Major site: liver via cleavage by enzymes including dipeptidyl peptidase-4 (DPP-4). |
| Excretion | Primarily hepatic and renal degradation; renal excretion of intact glucagon is minimal (<5%). |
| Half-life | 3–6 minutes (intravenous); 8–18 minutes (subcutaneous/intramuscular). |
| Protein binding | Negligible (<5%), primarily albumin. |
| Volume of Distribution | 0.25–0.4 L/kg; distributes into extracellular space. |
| Bioavailability | Subcutaneous/Intramuscular: >90%. |
| Onset of Action | Intravenous: <1 minute; Intramuscular: ~5–10 minutes; Subcutaneous: ~5–10 minutes. |
| Duration of Action | Intravenous: 5–15 minutes; Intramuscular/Subcutaneous: 10–30 minutes. Clinical effect in severe hypoglycemia is typically brief. |
Severe hypoglycemia: 1 mg IM, SC, or IV; may repeat every 15 minutes. Diagnostic aid: 0.5-2 mg IV/IM. Continuous infusion: 1 mg/h IV.
| Dosage form | POWDER |
| Renal impairment | No dose adjustment required for any GFR. |
| Liver impairment | No dose adjustment required for any Child-Pugh class. |
| Pediatric use | Hypoglycemia: <20 kg: 0.5 mg IM/SC/IV; ≥20 kg or >6-8 years: 1 mg IM/SC/IV; may repeat every 15 minutes. Diagnostic: 0.03 mg/kg IV/IM (max 0.5-1 mg). |
| Geriatric use | Same as adult dosing; monitor blood glucose and cardiovascular status due to potential increased sensitivity or concurrent conditions. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
No significant drug interactions Administer glucose upon recovery to prevent rebound hypoglycemia.
| Breastfeeding | Glucagon is a polypeptide that is not expected to be excreted significantly into breast milk. M/P ratio not determined; due to high molecular weight and poor oral bioavailability, infant exposure is likely negligible. Compatible with breastfeeding. |
| Teratogenic Risk | Glucagon has not been associated with teratogenic effects in animal studies. There are no adequate and well-controlled studies in pregnant women. Use during pregnancy should be limited to acute management of severe hypoglycemia; risk is low due to brief exposure and peptide nature. |
■ FDA Black Box Warning
None
| Common Effects | Nausea |
| Serious Effects |
["Hypersensitivity to glucagon or any component of the formulation","Patients with pheochromocytoma (risk of hypertensive crisis)","Patients with insulinoma (may cause rebound hypoglycemia)"]
| Precautions | ["May cause nausea and vomiting; ensure airway if vomiting occurs","Use with caution in patients with insulinoma or pheochromocytoma (may cause hypertensive crisis)","May cause hypoglycemia in patients with glycogen storage disease or starvation","Large doses may cause hypokalemia","Cardiac effects: may cause tachycardia, hypertension, and in overdose, paradoxical bradycardia or hypotension"] |
| Food/Dietary | No direct food interactions. However, after glucagon administration, consume oral carbohydrates as soon as safely possible to replenish glycogen stores and prevent recurrent hypoglycemia. |
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| Fetal Monitoring |
| Monitor maternal blood glucose levels frequently during and after administration. In hypoglycemia emergency, monitor for signs of hypoglycemia rebound; fetal heart rate monitoring not routinely required unless maternal hypoglycemia is severe or prolonged. |
| Fertility Effects | No known adverse effects on fertility from available data. Glucagon is used acutely and does not interfere with reproductive function. |
| Clinical Pearls | Glucagon is used for severe hypoglycemia when IV glucose is unavailable or difficult to administer. It can be given IM, SC, or IV. Onset is 1-2 minutes for IV, 5-15 minutes for IM/SC. Failure to respond within 15 minutes suggests need for IV glucose. Glucagon may cause nausea/vomiting; protect airway. It is ineffective in patients with depleted glycogen stores (e.g., starvation, adrenal insufficiency). In beta-blocker overdose, glucagon can be used as inotrope due to direct cAMP activation. |
| Patient Advice | Glucagon is a rescue medication for severe hypoglycemia when you are unable to take sugar by mouth. · Ensure family members/caregivers know how to prepare and inject glucagon using the provided kit. · After glucagon injection, you may experience nausea or vomiting; lie on your side to prevent choking. · As soon as you are conscious and able to swallow, eat a fast-acting carbohydrate (e.g., juice, glucose tablets) followed by a snack with protein/long-acting carbs. · Glucagon is not for routine hypoglycemia; only for emergencies when you cannot safely swallow. · This medication does not treat hyperglycemia; it raises blood sugar dangerously high in healthy individuals. |