Get your patient on Gvoke Hypopen (Glucagon Injection, Solution)

Indications and Usage (1.1 , 1.2 )
Dosage and Administration (2.1 , 2.2 )
Contraindications (4 )
Warnings and Precautions (5.6 , 5.7 , 5.8 )

03/2025

• GVOKE is an antihypoglycemic agent indicated for subcutaneous use for the treatment of severe hypoglycemia in adult and pediatric patients aged two years and older with diabetes (1.1 )
• GVOKE VialDx is a gastrointestinal motility inhibitor indicated for intravenous use as a diagnostic aid during radiologic examinations to temporarily inhibit movement of the gastrointestinal tract in adult patients (1.2 )

Dosage and Administration of GVOKE for Subcutaneous Use to Treat Severe Hypoglycemia in Adult and Pediatric Patients Aged 2 Years and Older with Diabetes (2.1 )

• Important Administration Instructions
• Administer GVOKE HypoPen, GVOKE PFS, or GVOKE Kit subcutaneously. These three presentations are referred to as GVOKE in this labeling
• Administer GVOKE according to the printed instructions on the foil pouch label, carton, or the Instructions for Use.
• Visually inspect GVOKE prior to administration. The solution should appear clear and colorless to pale yellow.
• Administer GVOKE subcutaneously in the lower abdomen, outer thigh, or outer upper arm.
• Call for emergency assistance immediately after administering the dose.
• If there has been no response after 15 minutes, may administer an additional dose from a new HypoPen, GVOKE PFS, or GVOKE Kit while waiting for emergency assistance.
• When the patient has responded to GVOKE, give oral carbohydrates.
• Do not attempt to reuse GVOKE. Each GVOKE device or vial contains a single dose of glucagon. Do not reuse and discard any unused portion.
• Recommended Dosage
• Recommended dose for adult and pediatric patients aged 12 years of age and older is 1 mg.
• Recommended dose for adult and pediatric patients aged 12 years of age and older is 1 mg.
• The recommended dose for pediatric patients aged 2 to less than 12 years of age who weigh:
• Less than 45 kg, is 0.5 mg
• 45 kg or greater, is 1 mg

Dosage and Administration of GVOKE VialDx for Intravenous Use as a Diagnostic Aid in Adults (2.2 )

• GVOKE VialDx is only for intravenous use under medical supervision.
• The recommended diagnostic dose for relaxation of the stomach, duodenal bulb, duodenum, and small bulb is 0.2 mg to 0.5 mg; the recommended dose to relax the colon is 0.5 mg to 0.75 mg.
• See the Full Prescribing Information for administration instructions for GVOKE VialDx.

GVOKE HypoPen, GVOKE PFS, GVOKE Kit (these three presentations are also referred to as GVOKE in this labeling) , and GVOKE VialDx are clear, colorless to pale yellow solutions.

Subcutaneous Injection

• Injection: 0.5 mg/0.1 mL single-dose prefilled autoinjector (GVOKE HypoPen)
• Injection: 1 mg/0.2 mL single-dose prefilled autoinjector (GVOKE HypoPen)
• Injection: 1 mg/0.2 mL single-dose prefilled syringe (GVOKE PFS)
• Injection: 1 mg/0.2 mL single-dose vial and syringe kit (GVOKE Kit)

Intravenous Injection:

• Injection: 1 mg/0.2 mL single-dose vial (GVOKE VialDx)

GVOKE and GVOKE VialDx are contraindicated in patients with:

• Pheochromocytoma because of the risk of substantial increase in blood pressure [see Warnings and Precautions (5.1 )]
• Insulinoma because of the risk of hypoglycemia [see Warnings and Precautions (5.2 )]
• Prior hypersensitivity reaction to glucagon or to any of the excipients in GVOKE or GVOKE VialDx. Serious hypersensitivity reactions have been reported with glucagon and include anaphylactic shock with breathing difficulties and hypotension [see Warnings and Precautions (5.3 )] .

GVOKE VialDx for use as a diagnostic aid is also contraindicated in patients with glucagonoma because of risk of hypoglycemia [see Warnings and Precautions (5.8 )]

• Substantial Increase in Blood Pressure in Patients with Pheochromocytoma: Contraindicated in patients with pheochromocytoma because glucagon may stimulate the release of catecholamines from the tumor. (5.1 )
• Hypoglycemia in Patients with Insulinoma: In patients with insulinoma, administration may produce an initial increase in blood glucose; however, glucagon may stimulate exaggerated insulin release from an insulinoma and cause hypoglycemia. If a patient develops symptoms of hypoglycemia after a dose of GVOKE or GVOKE VialDx, give glucose orally or intravenously. (5.2 )
• Serious Hypersensitivity Reactions: Serious hypersensitivity reactions have been reported with glucagon products, including generalized rash, and in some cases anaphylactic shock with breathing difficulties, and hypotension.(5.3 )
• Lack of Efficacy with Subcutaneous Use for Severe Hypoglycemia in Patients with Decreased Hepatic Glycogen: Patients with insufficient hepatic stores of glycogen may not respond to GVOKE for subcutaneous use for the treatment of severe hypoglycemia. Insufficient hepatic stores of glycogen may be present in conditions such as states of starvation, or in patients with adrenal insufficiency or chronic hypoglycemia. (5.4 )
• Necrolytic Migratory Erythema (NME): a skin rash, has been reported postmarketing following continuous glucagon infusion and resolved with discontinuation of the glucagon. GVOKE and GVOKE VialDx are not approved for continuous infusion. Should NME occur, consider whether the benefits of continuous glucagon infusion outweigh the risks. (5.5 )
• Hyperglycemia with Intravenous Use as a Diagnostic Aid in Patients with Diabetes Mellitus: GVOKE VialDx in patients with diabetes mellitus may cause hyperglycemia. Monitor patients with diabetes for changes in blood glucose levels during treatment and treat hyperglycemia if indicated. (5.6 )
• Blood Pressure and Heart Rate Increases with Intravenous Use as a Diagnostic Aid in Patients with Cardiac Disease: GVOKE VialDx may increase myocardial oxygen demand, blood pressure, and pulse rate. Cardiac monitoring is recommended in patients with cardiac disease during use of GVOKE VialDx as a diagnostic aid, and an increase in blood pressure and pulse rate may require therapy. (5.7 )
• Hypoglycemia in Patients with Glucagonoma with Intravenous Use as a Diagnostic Aid: GVOKE VialDx 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. (5.8 )

The following serious adverse reactions are described below and elsewhere in labeling:

• Substantial Increase in Blood Pressure in Patients with Pheochromocytoma [see Warnings and Precautions (5.1 )] .
• Hypoglycemia in Patients with Insulinoma [see Warnings and Precautions (5.2 )] .
• Serious Hypersensitivity Reactions [see Warnings and Precautions (5.3 )]
• Lack of Efficacy With Subcutaneous Use for Severe Hypoglycemia in Patients with Decreased Hepatic Glycogen [see Warnings and Precautions (5.4 )]
• Necrolytic Migratory Erythema [see Warnings and Precautions (5.5 )] .
• Hyperglycemia with Intravenous Use as a Diagnostic Aid in Patients with Diabetes Mellitus [see Warnings and Precautions (5.6 )]
• Blood Pressure and Heart Rate Increases with Intravenous Use as a Diagnostic Aid in Patients with Cardiac Disease [see Warnings and Precautions (5.7 )]
• Hypoglycemia in Patients with Glucagonoma with Intravenous Use as a Diagnostic Aid [see Warnings and Precautions (5.8 )]

Glucagon is an antihypoglycemic agent and a gastrointestinal motility inhibitor. Glucagon is a single chain containing 29 amino acid residues and has a molecular weight of 3483 and is identical to human glucagon. Glucagon is of synthetic origin produced by solid phase synthesis.

Its molecular formula is C ₁₅₃ H ₂₂₅ N ₄₃ O ₄₉ S with the following structure:

GVOKE HypoPen, GVOKE PFS, and GVOKE Kit

GVOKE HypoPen (glucagon) injection, GVOKE PFS (glucagon) injection, and GVOKE Kit (glucagon) injection (these three presentations are also referred to as GVOKE (glucagon) injection in this labeling) are clear, colorless to pale yellow, sterile solutions for subcutaneous injection.

• GVOKE HypoPen and GVOKE PFS: Each 0.2 mL contains 1 mg of glucagon, 11.1 mg of trehalose dihydrate NF, and 1.2 mg of 1N sulfuric acid in 209 mg dimethyl sulfoxide diluent.
• GVOKE HypoPen: Each 0.1 mL contains 0.5 mg of glucagon, 5.6 mg of trehalose dihydrate NF, and 0.6 mg of 1N sulfuric acid in 104 mg dimethyl sulfoxide diluent.
• GVOKE Kit: Each 0.2 mL contains 1 mg of glucagon, 11.1 mg of trehalose dihydrate NF, 5.8 mg of mannitol USP, and 1.32 mg of 1N sulfuric acid in 205 mg dimethyl sulfoxide diluent.

GVOKE VialDx

GVOKE VialDx (glucagon) injection is a clear, colorless to pale yellow, sterile solution for intravenous injection available in 1 mg per 0.2 mL vial.

Each 0.2 mL of GVOKE VialDx contains 1 mg of glucagon, 11.1 mg of trehalose dihydrate NF, 5.8 mg of mannitol USP, and 1.32 mg of 1N sulfuric acid in 205 mg dimethyl sulfoxide diluent prior to dilution with 0.9% Sodium Chloride [for dilution instructions, see Dosage and Administration (2.2) ] .

The diluted solution contains 0.45 mg per mL glucagon, 5 mg per mL trehalose dihydrate, 93.2 mg per mL dimethyl sulfoxide, 2.6 mg per mL mannitol, and 0.60 mg per mL 1 N sulfuric acid.

GVOKE glucagon injection is supplied as a clear, colorless to pale yellow solution in the following configurations:

Store GVOKE HypoPen, GVOKE PFS, and GVOKE Kit (these three presentations are referred to as GVOKE in this labeling), and GVOKE VialDx at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F). Do not refrigerate or freeze. Do not expose to extreme temperatures.

• Store the GVOKE HypoPen and GVOKE PFS in the original sealed foil pouch until time of use
• Store the GVOKE Kit vial and pouched syringe together in original carton until time of use.
• Store GVOKE VialDx vials in original carton until time of use. Discard any unused portion

GVOKE® PFS
[GEE-voke P-F-S ]
(glucagon injection)
pre-filled syringe
for subcutaneous use

This “Instructions for Use” contains information on how to inject GVOKE® PFS

Section headings and other template-related items found in this IFU are for organization of the document only and are not intended for use in corresponding artwork/patient-facing IFU files. Figure numbers in this content document may not correspond to figure numbers in corresponding artwork/patient-facing IFU files.

Appropriate trademark symbol (™ or ®) should be used upon first use of a trademarked name on each page; usage may differ from this content file and final artwork based on page layout.

1. GVOKE® PFS VISUAL

Understanding GVOKE PFS

GVOKE PFS contains a 1 mg dose of glucagon and is in a foil pouch. Below is a picture of the pouch. See the GVOKE PFS package for a full view of the Quick-Use Guide.

GVOKE PFS (1 mg dose)

PFS Device

Note: GVOKE PFS should be used one time and then thrown away (discarded).

2. IMPORTANT INFORMATION YOU NEED TO KNOW BEFORE INJECTING GVOKE® PFS

• Become familiar with the following instructions before an emergency happens.
• Do not use this product past the expiration date printed on the device. Replace GVOKE PFS before the expiration date on the box.
• If you have questions regarding the use of this product, talk to a healthcare provider or pharmacist.

Make sure that relatives, close friends, or caregivers know that if you become unconscious, they should call for emergency medical help right away. GVOKE PFS may have been prescribed so that relatives, close friends, and caregivers can give the injection if you become hypoglycemic (severe low blood sugar) and are unable to take sugar by mouth. If you are unconscious, GVOKE PFS can be given while awaiting medical assistance.

Show your relatives, close friends, or caregivers where you store GVOKE PFS and how to use it. They need to know how to use GVOKE PFS before an emergency situation happens.

Indications for Use

GVOKE PFS is for the treatment of severe hypoglycemia in pediatric and adult patients with diabetes ages 2 years and above. Symptoms of severe hypoglycemia include unconsciousness, and seizures or convulsions.

Give GVOKE PFS if:

1. the patient is unconscious,
2. the patient is unable to eat sugar or a sugar-sweetened product,
3. the patient is having a seizure, or
4. you have tried to give the patient sugar or drinks that are high in sugar such as a regular soft drink (soda) or fruit juice and the patient does not get better.

Milder cases of hypoglycemia should be treated promptly by eating sugar or a sugar sweetened product. (See Information on Hypoglycemia for more information on the symptoms of low blood sugar.) GVOKE PFS will not work when taken by mouth (orally).

Information on Hypoglycemia

Early symptoms of hypoglycemia (low blood sugar) include:

If not treated, the patient may progress to severe hypoglycemia which can include:

• confusion
• seizures
• unconsciousness
• death

The occurrence of early symptoms calls for quick and, if necessary, repeated administration of some form of carbohydrate. Patients should always carry a quick source of sugar, such as candy mints or glucose tablets. The prompt treatment of mild hypoglycemic symptoms can prevent severe hypoglycemic reactions. If the patient does not improve or if administration of carbohydrate is impossible, GVOKE® PFS should be given or the patient should be treated with intravenous glucose by a medical professional.

Possible Problems with GVOKE PFS Treatment

Common side effects in adults and pediatric patients are nausea and vomiting. The product may cause serious side effects including serious allergic reactions, fast heart beat and high blood pressure.

People may be allergic to glucagon or to one of the inactive ingredients in GVOKE PFS, or may experience fast heart-beat for a short while.

If you experience any other reactions that may have been caused by GVOKE PFS, please contact your healthcare provider.

Important:

• Act quickly. Prolonged unconsciousness may be harmful.
• After the injection is complete, turn the unconscious patient on his or her side to prevent them from choking in case they throw up (vomit).
• Carefully read and follow these instructions. Have a healthcare provider show you the right way to use GVOKE PFS.

Important Warnings

• Do not open pouch until time of use.
• Do not use after the expiration date has passed.
• Do not use if the needle cap has been removed or is damaged.
• Do not remove the needle cap until you are ready to inject.
• Do not remove the finger flange from the syringe.
• Call a healthcare provider as soon as GVOKE® PFS has been injected.
• If the patient does not wake up within 15 minutes, give another dose of GVOKE PFS and call for emergency medical help right away.
• Feed the patient as soon as he or she wakes up and is able to swallow.

Read and become familiar with the following instructions before an emergency happens. If you have questions about using GVOKE PFS, talk with your healthcare provider or pharmacist.

3. PREPARING TO INJECT GVOKE® PFS

Step 1. Remove GVOKE PFS from Foil Pouch

• Tear open pouch at the dotted line and carefully remove GVOKE PFS (see Figure 1 ).

Figure 1

Step 2. Check the Expiration Date

• Check the expiration date printed on the label of GVOKE PFS (see Figure 2 ).
• Important: Do not use GVOKE PFS if the expiration date has passed. If GVOKE PFS is expired, throw it away in an FDA cleared sharps container and use a new GVOKE PFS.

Figure 2

Step 3. Inspect the Solution

• Look at the liquid medicine through the viewing window. It must be clear and colorless, or a pale yellow (see Figure 3 ).
• It is normal to see air bubbles in the medicine.
• Important: Do not try to remove air bubbles before injecting.
• Do not use GVOKE® PFS or inject if the liquid contains lumps, flakes, or particles.
• Do not inject if solution is not visible in the viewing window.
• If you do not have another GVOKE PFS to use, call for emergency help right away.

Figure 3

4. INJECTING GVOKE® PFS

Step 4. Choose Injection Site and Expose Bare Skin

• Choose the lower abdomen, outer thigh, or outer upper arm for your injection site (see Figure 4 ).
• Remove any clothing covering the injection site (see Figure 5 ). The injection must be performed straight into the skin.
• Important: Do not inject through clothing

Figure 4

Figure 5

Step 5. Pull off the Needle Cap

• Pull the needle cap straight off the syringe (see Figure 6 ).
• Important: Do not put your thumb, fingers, or hand on or near the needle to help prevent accidental needle sticks.

Figure 6

Step 6. Pinch, Insert and Push to Start Injection

• Pinch the skin directly around the chosen injection site and keep pinching for the entire injection (see Figure 7 ). This is recommended to make sure a subcutaneous (under the skin) injection is given and to prevent injection into the muscle.
• Without touching the plunger, insert the needle into the skin at the injection site at a 90-degree angle (see Figure 8 ).
• Push the plunger down as far as it will go to inject all of the liquid medicine into the skin (see Figure 9 ). You want to inject the medicine very fast to help decrease the pain.
• Important: Do not aspirate (pull back on plunger rod) after inserting the needle. Push the plunger down as far as it will go. Do not lift up GVOKE® PFS until the injection is complete.

Figure 7

Figure 8

Figure 9

Step 7. Lift Away from Skin

• Lift the syringe straight up from the injection site (see Figure 10 ).
• Important: Do not re-cap the syringe.

Figure 10

Step 8. Turn Patient onto Side

• When an unconscious person wakes up, he or she may throw up (vomit).
• Turn the unconscious patient on their side to prevent choking (see Figure 11 ).

Figure 11

Step 9. Make Sure Patient Receives Immediate Medical Attention After Use

• Call for emergency medical help right after GVOKE® PFS has been injected.
• Even if GVOKE PFS helps the patient to wake up, you should still call for emergency medical help right away.
• The patient’s healthcare provider should also be notified whenever a severe drop in blood sugar (hypoglycemic reactions) happens. Hypoglycemia may happen again after receiving an injection from GVOKE PFS. The patient’s diabetes medicine may need to be changed.
• Feed the patient as soon as he or she wakes up and is able to swallow. Give the patient a fast-acting source of sugar (such as a regular soft drink or fruit juice) and a long-acting source of sugar (such as crackers and cheese or a meat sandwich). If the patient does not wake up within 15 minutes, give another dose of glucagon if a second GVOKE PFS is available and notify emergency medical services right away.

5. STORING GVOKE® PFS

Storage Information

• Store in sealed original foil pouch until time of use.
• Store at room temperature, 68° to 77°F (20° to 25°C).
• Do not refrigerate or freeze.

6. DISPOSING OF GVOKE® PFS

Dispose of GVOKE PFS in an FDA Cleared Sharps Disposal Container

To prevent injury caused from contact with the used needle, put the used syringe in a safe place until it can be disposed of into a FDA cleared sharps container right away after use (see Figure 12 ). Do not throw away (dispose of) loose needles and syringes in your household trash.

If you do not have a FDA cleared sharps disposal container, you may use a household container that is:

• made of a heavy-duty plastic
• can be closed with a tight-fitting puncture-resistant lid, without sharps being able to come out
• upright and stable during use
• leak-resistant
• properly labeled to warn of hazardous waste inside the container.

When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA’s website at: http://www.fda.gov/safesharpsdisposal .

Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Always keep the sharps container out of the reach of children. If needed, make sure to get a refill of GVOKE PFS.

Figure 12

7. ADDITIONAL INFORMATION

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Distributed by:
Xeris Pharmaceuticals, Inc.
Chicago, IL 60607

Revised 04/2023

©2023 by Xeris Pharmaceuticals, Inc.