GVOKE HYPOPEN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for GVOKE HYPOPEN (GVOKE HYPOPEN).
Glucagon is a polypeptide hormone that increases blood glucose by promoting hepatic glycogenolysis and gluconeogenesis. It also relaxes smooth muscle of the gastrointestinal tract.
| Metabolism | Metabolized in the liver by proteolytic enzymes, primarily by cathepsin B and other proteases. |
| Excretion | Glucagon is primarily eliminated by hepatic metabolism and renal excretion. Approximately 30-40% of a dose is excreted in urine as metabolites, with the remainder cleared via biliary/fecal pathways. Less than 10% is excreted unchanged in urine. |
| Half-life | The terminal elimination half-life of glucagon following subcutaneous administration is approximately 18-25 minutes. In patients with hepatic or renal impairment, the half-life may be prolonged. The short half-life supports rapid offset of action. |
| Protein binding | Glucagon is not significantly bound to plasma proteins; protein binding is negligible (<1%). |
| Volume of Distribution | The volume of distribution (Vd) of glucagon is approximately 0.2-0.3 L/kg, indicating distribution primarily in extracellular fluid. The relatively small Vd reflects negligible tissue binding and rapid clearance. |
| Bioavailability | Subcutaneous administration: Bioavailability is approximately 80-100% compared to IV. Intranasal administration: Bioavailability is approximately 30-50% relative to IV injection. The lower IN bioavailability is due to limited nasal absorption and some degradation. |
| Onset of Action | Subcutaneous (SC) injection: Onset of effect occurs within 10 minutes, with clinical response (increase in blood glucose) typically seen within 5-10 minutes. Intranasal (IN) administration: Onset within 10 minutes, similar to SC. Intravenous (IV) administration: Onset within 1 minute. |
| Duration of Action | The glycemic effect after SC or IN administration lasts approximately 30-90 minutes, depending on dose and patient factors. For treatment of severe hypoglycemia, a single dose provides sufficient effect for clinical management; repeat dosing may be required if no response in 15 minutes. The duration is limited by rapid hepatic metabolism. |
1 mg subcutaneously as a single dose.
| Dosage form | SOLUTION |
| Renal impairment | No adjustment required. |
| Liver impairment | No adjustment required. |
| Pediatric use | Weight-based dosing for severe hypoglycemia: <25 kg: 0.5 mg subcutaneously; ≥25 kg: 1 mg subcutaneously. |
| Geriatric use | No specific adjustment required; use caution in patients with cardiovascular disease. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for GVOKE HYPOPEN (GVOKE HYPOPEN).
| Breastfeeding | Glucagon is not orally bioavailable; maternal doses are unlikely to affect breastfed infant. M/P ratio not available. Use caution if maternal hypoglycemia occurs. |
| Teratogenic Risk | Animal studies have not shown fetal harm at clinically relevant doses. No adequate controlled studies in pregnant women. First trimester: not associated with major malformations. Second/third trimesters: potential for maternal hypoglycemia, which can cause fetal distress; consider risk-benefit. |
| Fetal Monitoring |
■ FDA Black Box Warning
None.
| Serious Effects |
["Known hypersensitivity to glucagon or any component of the formulation","Patients with pheochromocytoma (risk of hypertensive crisis)","Patients with insulinoma (risk of rebound hypoglycemia)","Patients with glucagonoma (risk of paradoxical hyperglycemia)"]
| Precautions | ["Should not be used in patients with suspected pheochromocytoma or insulinoma, as it can cause catecholamine release and hyperglycemia respectively.","Use with caution in patients with cardiac disease, as it may increase myocardial oxygen demand.","May cause nausea and vomiting; ensure patient is protected from aspiration if vomiting occurs.","Hypersensitivity reactions including anaphylaxis may occur.","Reconstituted solution should be used immediately if stored at room temperature; discard any unused portion."] |
Loading safety data…
| Monitor maternal blood glucose closely during administration and for resolution of hypoglycemia. Fetal heart rate monitoring if severe maternal hypoglycemia or distress. |
| Fertility Effects | No known adverse effects on fertility in animal studies. No human data. |