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Brought to you by Xeris Pharmaceuticals
As experts, diabetes care and education specialists know that hypoglycemia can quickly evolve from a mild event to an emergency, so prompt and reliable intervention is critically important for people with type 1 or type 2 diabetes. In recent years, the only glucagon treatment available for a severe hypoglycemia event has been an emergency kit requiring a complex series of preparation and administration steps that can be difficult in these emergency situations.
In an effort to simplify the administration process and ensure reliable delivery of a full dose of glucagon, Xeris Pharmaceuticals developed and obtained FDA approval for the Gvoke™ (glucagon injection). Gvoke is the first-ever premixed, pre-filled, and pre-measured liquid stable glucagon product available for the treatment of severe hypoglycemic events in adults and pediatrics with diabetes, age 2 years and older. Gvoke is available in two product designs: Gvoke™ PFS (Prefilled Syringe) and Gvoke HypoPen™ (auto-injector).
“We regularly educate people with diabetes and their caregivers to recognize the signs of hypoglycemia so they can promptly intervene using the most appropriate treatment including glucagon for severe hypoglycemia. However, we know that in this crisis, caregivers become frustrated and fearful of a complex process and often don't give the glucagon properly. This tool will help instill confidence that anyone who may be present when hypoglycemia occurs – parents, friends, coaches or colleagues – can quickly and easily administer the correct dose of this important medicine with less hesitation” said Belinda Childs, APRN, BC-ADM, CDE.
Product Specific Information:
- Efficacy profile: Gvoke demonstrated its ability to effectively resolve severe hypoglycemic events over multiple Phase 3 studies, showing 99% of adults and 100% of children achieved treatment success.1* In clinical studies with adults, it took on average less than 14 minutes to achieve treatment success.1
- Pre-measured dosing: Gvoke will have two pre-measured dosing options: one for adults (1 mg/0.2 mL) and one for children (0.5 mg/0.1 mL), and both product designs will be made available in one or two-device packages.
- Usability: In usability studies, 99% of trained and untrained people were able to successfully administer a full dose of Gvoke in a simulated emergency setting. 2,3
Designed to be both effective and user-friendly, Gvoke HypoPen and Gvoke PFS are valuable additions to the diabetes management toolkit for your patients. Gvoke PFS is now available and Gvoke HypoPen will be available in 2020. To learn more, stay connected, and talk with a Gvoke representative, visit gvokeglucagonpro.com.
Indication and Important Safety Information
GVOKE is indicated for the treatment of severe hypoglycemia in adult and pediatric patients with diabetes ages 2 years and above.
Important Safety Information
Contraindications
GVOKE is contraindicated in patients with pheochromocytoma, insulinoma, and known hypersensitivity to glucagon or to any of the excipients in GVOKE. Allergic reactions have been reported with glucagon and include anaphylactic shock with breathing difficulties and hypotension.
Warnings and Precautions
GVOKE is contraindicated in patients with pheochromocytoma because glucagon may stimulate the release of catecholamines from the tumor. If the patient develops a dramatic increase in blood pressure and a previously undiagnosed pheochromocytoma is suspected, 5 to 10 mg of phentolamine mesylate, administered intravenously, has been shown to be effective in lowering blood pressure.
In patients with insulinoma, administration of glucagon may produce an initial increase in blood glucose; however, GVOKE administration may directly or indirectly (through an initial rise in blood glucose) stimulate exaggerated insulin release from an insulinoma and cause hypoglycemia. GVOKE is contraindicated in patients with insulinoma. If a patient develops symptoms of hypoglycemia after a dose of GVOKE, give glucose orally or intravenously.
Allergic reactions have been reported with glucagon. These include generalized rash, and in some cases, anaphylactic shock with breathing difficulties and hypotension. GVOKE is contraindicated in patients with a prior hypersensitivity reaction.
GVOKE is effective in treating hypoglycemia only if sufficient hepatic glycogen is present. Patients in states of starvation, with adrenal insufficiency or chronic hypoglycemia, may not have adequate levels of hepatic glycogen for GVOKE administration to be effective. Patients with these conditions should be treated with glucose.
Necrolytic migratory erythema (NME), a skin rash commonly associated with glucagonomas has been reported postmarketing following continuous glucagon infusion and resolved with discontinuation of the glucagon. Should NME occur, consider whether the benefits of continuous glucagon infusion outweigh the risks. Glucagon administered to patients with glucagonoma may cause secondary hypoglycemia.
Adverse Reactions
Most common (≥5%) adverse reactions associated with GVOKE are nausea, vomiting, injection site edema (raised 1 mm or greater) and hypoglycemia.
Drug Interactions
Patients taking beta-blockers may have a transient increase in pulse and blood pressure when given GVOKE. In patients taking indomethacin, GVOKE may lose its ability to raise blood glucose or may even produce hypoglycemia. GVOKE may increase the anticoagulant effect of warfarin.
A BRIEF SUMMARY OF PRESCRIBING INFORMATION
GVOKE is indicated for the treatment of severe hypoglycemia in adult and pediatric patients with diabetes ages 2 years and above. GVOKE is administered by subcutaneous injection.
CONTRAINDICATIONS
GVOKE PFS is contraindicated in patients with:
WARNINGS AND PRECAUTIONS
Catecholamine Release in Patients with Pheochromocytoma
GVOKE is contraindicated in patients with pheochromocytoma because glucagon may stimulate the release of catecholamines from the tumor. If the patient develops a dramatic increase in blood pressure and a previously undiagnosed pheochromocytoma is suspected, 5 to 10 mg of phentolamine mesylate, administered intravenously, has been shown to be effective in lowering blood pressure.
Hypoglycemia in Patients with Insulinoma
In patients with insulinoma, administration of glucagon may produce an initial increase in blood glucose; however, glucagon administration may directly or indirectly (through an initial rise in blood glucose) stimulate exaggerated insulin release from an insulinoma and cause hypoglycemia. GVOKE is contraindicated in patients with insulinoma. If a patient develops symptoms of hypoglycemia after a dose of GVOKE, give glucose orally or intravenously.
Hypersensitivity and Allergic Reactions
Allergic reactions have been reported with glucagon, these include generalized rash, and in some cases anaphylactic shock with breathing difficulties and hypotension. GVOKE is contraindicated in patients with a prior hypersensitivity reaction.
Lack of Efficacy in Patients with Decreased Hepatic Glycogen
GVOKE is effective in treating hypoglycemia only if sufficient hepatic glycogen is present. Patients in states of starvation, with adrenal insufficiency or chronic hypoglycemia may not have adequate levels of hepatic glycogen for GVOKE administration to be effective. Patients with these conditions should be treated with glucose.
Necrolytic Migratory Erythema
Necrolytic migratory erythema (NME), a skin rash commonly associated with glucagonomas (glucagon-producing tumors) and characterized by scaly, pruritic erythematous plaques, bullae, and erosions, has been reported postmarketing following continuous glucagon infusion. NME lesions may affect the face, groin, perineum and legs or be more widespread. In the reported cases NME resolved with discontinuation of the glucagon, and treatment with corticosteroids was not effective. Should NME occur, consider whether the benefits of continuous glucagon infusion outweigh the risks.
Hypoglycemia in Patients with Glucagonoma
Glucagon administered to patients with glucagonoma may cause secondary hypoglycemia. Test patients suspected of having glucagonoma for blood levels of glucagon prior to treatment and monitor for changes in blood glucose levels during treatment. If a patient develops symptoms of hypoglycemia after a dose of glucagon for injection, give glucose orally or intravenously.
ADVERSE REACTIONS
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of GVOKE cannot be directly compared to rates in the clinical trials of other drugs and may not reflect the rates observed in practice.
Adverse Reactions in Adult Patients
The safety of GVOKE was evaluated in two randomized, blinded, 2-way crossover studies conducted in adults with type 1 diabetes mellitus. In total, 154 patients received an injection of GVOKE. The most common adverse reactions occurring in 2% or more of adult subjects treated with GVOKE during clinical trials within 12 hours of treatment are: nausea (30%), vomiting (16%), injection site edema raised 1 mm or greater (7%), and headache (5%). Injection site pain was reported by 1% of patients with GVOKE. Hypertension and tachycardia have occurred with glucagon treatment.
Adverse Reactions in Pediatric Patients Aged 2 Years and Older
The safety of GVOKE was evaluated in one single-arm, open-label, study in 31 pediatric patients with type 1 diabetes mellitus. The data in Table 1 reflect the exposure of 31 pediatric patients to 0.5 mg or 1 mg of GVOKE. The most common adverse reactions occurring in 2% or greater of pediatric patients treated with GVOKE are listed in Table 1.
Table 1: Adverse Reactions Occurring ≥ 2% in Pediatric Patients with Type 1 Diabetes Treated with GVOKEa
| | Ages 2 to < 6 years (0.5 mg dose) N =7 | Ages 6 to < 12 years (0.5 mg dose) N = 13 | Ages 12 to < 18 years (1 mg dose) N = 11 | Total N = 31 |
| Nausea | 43% | 54% | 36% | 45% |
| Hypoglycemia | 29% | 54% | 27% | 39% |
| Vomiting | 14% | 23% | 18% | 19% |
| Headache | 0% | 15% | 0% | 7% |
| Abdominal pain | 0% | 8% | 0% | 3% |
| Hyperglycemia | 14% | 8% | 0% | 7% |
| Injection site discomfort | 0% | 8% | 0% | 3% |
| Injection site reaction | 0% | 0% | 9% | 3% |
| Urticaria | 0% | 8% | 0% | 3% |
aAdverse Reactions occurring within 12 hours.
Postmarketing Experience
NME cases have been reported postmarketing in patients receiving continuous infusion of glucagon.
DRUG INTERACTIONS
Beta-Blockers:Patients taking beta-blockers may have a transient increase in pulse and blood pressure when given GVOKE.
Indomethacin: In patients taking indomethacin, GVOKE may lose its ability to raise blood glucose or may even produce hypoglycemia.
Warfarin: GVOKE may increase the anticoagulant effect of warfarin.
- Gvoke Prescribing Information, 09/2019.
- Virginia Valentine, Brett Newswanger, Steve Prestrelski, Anthony D. Andre, and Mark Garibaldi. (2019). Human Factors Usability and Validation Studies of a Glucagon Autoinjector in a Simulated Severe Hypoglycemia Rescue Situation, Diabetes Technology & Therapeutics. Vol. 21, No.9, https://doi.org/10.1089/dia.2019.0148
- Brett Newswanger, Steven Prestrelski & Anthony D. Andre (2019) Human factors studies of a prefilled syringe with stable liquid glucagon in a simulated severe hypoglycemia rescue situation, Expert Opinion on Drug Delivery, 16:9, 1015-1025, DOI: 10.1080/17425247.2019.1653278
* Treatment success in adults: blood glucose > 70 mg/dL or increase in blood glucose ≥ 20 mg/dL change at 30 minutes; treatment success in pediatrics: increase in blood glucose >25 mg/dL over 30 minutes
Gvoke™ and Gvoke HypoPen™ are trademarks of Xeris Pharmaceuticals, Inc.
©2019 Xeris Pharmaceuticals, Inc. All Rights Reserved. US-GVK-19-00164 10/19