These highlights do not include all the information needed to use GVOKE safely and effectively. See full prescribing information for GVOKE. GVOKE (glucagon) injection, for subcutaneous use Initial U.S. Approval: 1960

1 INDICATIONS AND USAGE

GVOKE is indicated for the treatment of severe hypoglycemia in pediatric and adult patients with diabetes ages 2 years and above.

2 DOSAGE AND ADMINISTRATION

2.1 Important Administration Instructions

GVOKE auto-injector (HypoPen), pre-filled syringe, and vial and syringe kit are for subcutaneous injection only.

Instruct patients and their caregivers on the signs and symptoms of severe hypoglycemia. Because severe hypoglycemia requires the help of others to recover, instruct the patient to inform those around them about GVOKE and its Instructions for Use. Administer GVOKE as soon as possible when severe hypoglycemia is recognized.

Instruct the patient or caregiver to read the Instructions for Use at the time they receive a prescription for GVOKE. Emphasize the following instructions to the patient or caregiver:

• •For the HypoPen or pre-filled syringe: Do not open foil pouch until ready to administer.
• •For the vial and syringe kit: Store in original carton until ready to administer.
• •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 and be free of particles. If the solution is discolored or contains particulate matter, do not use.
• •Administer the injection in the lower abdomen, outer thigh, or outer upper arm.
• •Withdraw the correct dose.
• •Call for emergency assistance immediately after administering the dose.
• •If there has been no response after 15 minutes, an additional dose from a new device or vial and syringe kit may be administered while waiting for emergency assistance.
• •When the patient has responded to treatment, give oral carbohydrates to restore the liver glycogen and prevent recurrence of hypoglycemia.
• •Do not attempt to reuse GVOKE. Each GVOKE device or vial contains a single dose of glucagon and cannot be reused. Discard any unused portion.

2.2 Dosage in Adults and Pediatric Patients Aged 2 Years and Above

Adults and Pediatric Patients Aged 12 and Older

Pediatric Patients Aged 2 to Under 12 Years of Age

• •The recommended dose of GVOKE is 1 mg administered by subcutaneous injection into lower abdomen, outer thigh, or outer upper arm.
• •If there has been no response after 15 minutes, an additional 1 mg dose of GVOKE from a new device or vial and syringe kit may be administered while waiting for emergency assistance.

3 DOSAGE FORMS AND STRENGTHS

GVOKE injection is a clear, colorless to pale yellow solution available as follows:

• •0.5 mg/0.1 mL single-dose pre-filled HypoPen auto-injector
• •1 mg/0.2 mL single-dose pre-filled HypoPen auto-injector
• •1 mg/0.2 mL single-dose pre-filled syringe
• •1 mg/0.2 mL single-dose vial and syringe kit

4 CONTRAINDICATIONS

GVOKE is 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)]
• •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 [see Warnings and Precautions (5.3)].

5 WARNINGS AND PRECAUTIONS

5.1 Substantial Increase in Blood Pressure in Patients Pheochromocytoma

GVOKE is contraindicated in patients with pheochromocytoma because glucagon may stimulate the release of catecholamines from the tumor [see Contraindications (4)]. If the patient develops a substantial 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.

5.2 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 [see Contraindications (4)]. If a patient develops symptoms of hypoglycemia after a dose of GVOKE, give glucose orally or intravenously.

5.3 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 [see Contraindications (4)].

5.4 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.

5.5 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.

6 ADVERSE REACTIONS

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

• •Hypersensitivity and Allergic Reactions [see Warnings and Precautions (5.3)].
• •Necrolytic Migratory Erythema [see Warnings and Precautions (5.5)].

6.1 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 [see Clinical Studies (14.1)].

The most common adverse reactions occurring in 2% or more of adult subjects treated with GVOKE during clinical trials are listed in Table 1.

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 [see Clinical Studies (14.2)].

The data in Table 2 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 2.

6.2 Postmarketing Experience

Additional adverse reactions have been identified during post-approval use of glucagon. Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

• •Necrolytic migratory erythema (NME) cases have been reported postmarketing in patients receiving continuous infusion of glucagon.
• •Hypoglycemia and hypoglycemic coma. Patients taking indomethacin may be more likely to experience hypoglycemia following glucagon administration [see Drug Interactions (7)].

7 DRUG INTERACTIONS

7.1 Beta-Blockers

Patients taking beta-blockers may have a transient increase in pulse and blood pressure when given GVOKE.

7.2 Indomethacin

In patients taking indomethacin, GVOKE may lose its ability to raise blood glucose or may even produce hypoglycemia.

7.3 Warfarin

GVOKE may increase the anticoagulant effect of warfarin.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

Available data from case reports and a small number of observational studies with glucagon use in pregnant women over decades of use have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Multiple small studies have demonstrated a lack of transfer of pancreatic glucagon across the human placental barrier during early gestation. In a rat reproduction study, no embryofetal toxicity was observed with glucagon administered by injection during the period of organogenesis at doses representing up to 40 times the human dose, based on body surface area (mg/m2) (see Data).

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Data

Animal Data

In pregnant rats given animal sourced glucagon twice-daily by injection at doses up to 2 mg/kg (up to 40 times the human dose based on body surface area extrapolation, mg/m2) during the period of organogenesis, there was no evidence of increased malformations or embryofetal lethality.

8.2 Lactation

Risk Summary

There is no information available on the presence of glucagon in human or animal milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production. However, glucagon is a peptide and would be expected to be broken down to its constituent amino acids in the infant's digestive tract and is therefore, unlikely to cause harm to an exposed infant.

8.4 Pediatric Use

The safety and effectiveness of GVOKE for the treatment of severe hypoglycemia in patients with diabetes have been established in pediatric patients ages 2 years and above. Use of GVOKE for this indication is supported by evidence from a study in 31 pediatric patients ages 2 and older with type 1 diabetes mellitus [see Clinical Studies (14.2)].

The safety and effectiveness of GVOKE have not been established in pediatric patients younger than 2 years of age.

8.5 Geriatric Use

Clinical studies of GVOKE did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Limited clinical trial experience has not identified differences in responses between the elderly and younger patients.

10 OVERDOSAGE

If overdosage occurs, the patient may experience nausea, vomiting, inhibition of GI tract motility, increase in blood pressure, and pulse rate. In case of suspected overdosing, serum potassium may decrease and should be monitored and corrected if needed. If the patient develops a dramatic increase in blood pressure, phentolamine mesylate has been shown to be effective in lowering blood pressure for the short time that control would be needed.

11 DESCRIPTION

GVOKE contains glucagon, an antihypoglycemic agent used to treat severe hypoglycemia. 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 produced by solid phase synthesis with subsequent purification.

Its molecular formula is C153H225N43O49S with the following structure:

GVOKE is a clear, colorless to pale yellow, sterile solution for subcutaneous injection available in 0.5 mg per 0.1 mL (auto-injector) or 1 mg per 0.2 mL (auto-injector, pre-filled syringe, and vial and syringe kit).

GVOKE Auto-Injector (HypoPen) and GVOKE Pre-Filled Syringe

Each 0.2 mL of GVOKE 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.

Each 0.1 mL of GVOKE 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 Vial and Syringe Kit

Each 0.2 mL of GVOKE 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.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Glucagon increases blood glucose concentration by activating hepatic glucagon receptors, thereby stimulating glycogen breakdown and release of glucose from the liver. Hepatic stores of glycogen are necessary for glucagon to produce an antihypoglycemic effect.

12.2 Pharmacodynamics

After administration of 1 mg GVOKE in adult patients with diabetes, the mean maximum glucose increase from baseline was 176 mg/dL.

Figure 1: Mean ± Standard Error of the Mean (SEM) Plasma Glucose vs. Time from 1 mg GVOKE Injection in Adult Subjects with Type 1 Diabetes Mellitus

In pediatric patients with type 1 diabetes (2 to less than 18 years), the mean maximum glucose increase from baseline was 134 mg/dL (2 to less than 6 years), 145 mg/dL (6 to less than 12 years), and 123 mg/dL (12 to less than 18 years).

Figure 2: Mean (± SEM) Plasma Glucose vs. Time from GVOKE Injection in Pediatric Subjects with Type 1 Diabetes Mellitus

12.3 Pharmacokinetics

Absorption

Subcutaneous injection of 1 mg GVOKE in adult type 1 diabetes mellitus subjects resulted in a mean glucagon Cmax of 2481.3 pg/mL, tmax of 50 minutes and AUC0‑240min of 3454.6 pg*min/mL.

Figure 3: Mean (± SEM) Plasma Glucagon Concentration vs. Time for 1 mg GVOKE Injection in Adults with Type 1 Diabetes Mellitus

Distribution

The apparent volume of distribution was in the range of 137-2425 L.

Elimination

The half-life of GVOKE was determined to be 32 minutes.

Metabolism

Glucagon is extensively degraded in liver, kidney, and plasma.

Excretion

Urinary excretion of intact glucagon has not been measured.

Specific Populations

Pediatrics

Subcutaneous injection of 0.5 mg GVOKE in subjects ages 2 to under 6 years resulted in a mean glucagon Cmax of 2300 pg/mL, tmax of 41 minutes, and AUC0‑180min of 138900 pg/mL*min. Subcutaneous injection of 0.5 mg GVOKE in subjects ages 6 to under 12 years resulted in a mean Cmax of 1600 pg/mL, median tmax of 34 minutes and AUC0‑180min of 104700 pg/mL*min. Subcutaneous injection of 1 mg GVOKE in subjects ages 12 to less than 18 years resulted in a mean Cmax of 1900 pg/mL, tmax of 51 minutes AUC0‑180min of 134300 pg/mL*min. Mean plasma glucagon levels were similar across the age groups following age appropriate doses of GVOKE.

Figure 4: Mean (± SEM) Plasma Glucagon Concentration vs. Time from GVOKE Injection in Pediatric Patients with Type 1 Diabetes Mellitus

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Long term studies in animals to evaluate carcinogenic potential have not been performed. Recombinant glucagon was positive in the bacterial Ames assay. It was determined that an increase in colony counts was related to technical difficulties in running this assay with peptides. Studies in rats have shown that glucagon does not cause impaired fertility.

14 CLINICAL STUDIES

14.1 Adult Patients with Type 1 Diabetes Mellitus

GVOKE was evaluated in adult patients aged 18 to 74 years with type 1 diabetes in two multi-center 2-way crossover studies, Study A was double-blinded with 80 patients, and Study B was single-blinded with 81 patients. Both studies involved 2 clinic visits 7 to 28 days apart, with random assignment to receive GVOKE 1 mg during one session and GEK 1 mg during the other. 154 subjects received an injection of GVOKE and 157 subjects received an injection of GEK. A total of 152 subjects received both GVOKE and GEK.

The efficacy of GVOKE was compared to GEK in subjects who were in a state of insulin‑induced hypoglycemia via insulin infusion with target plasma glucose less than 50 mg/dL. In Study A, mean plasma glucose at time of glucagon administration was 44.8 mg/dL and 45.2 mg/dL for GVOKE and GEK, respectively. In Study B, mean plasma glucose at time of glucagon administration was 47.7 mg/dL and 48.7 mg/dL for GVOKE and GEK, respectively.

Treatment ‘success’ was defined as plasma glucose increase from mean value at time of glucagon administration to absolute value greater than 70 mg/dL or relative increase of 20 mg/dL or greater, at 30 minutes after glucagon administration. In a pooled analysis of Study A and Study B, the proportion of patients who achieved treatment ‘success’ was 98.7 % in the GVOKE group and 100% in the GEK group and the comparison between groups met the pre-specified non-inferiority margin. A summary of treatment ‘success’ rates is shown in Table 3.

The mean time to treatment ‘success’ was 13.8 minutes in the GVOKE group and 10 minutes in the GEK group.

14.2 Pediatric Patients with Type 1 Diabetes Mellitus

GVOKE was evaluated in a study in 31 pediatric patients with type 1 diabetes mellitus. Patients were administered insulin to induce a plasma glucose of less than 80 mg/dL. Patients ages 2 to under 6 years and 6 to under 12 years of age then received a 0.5 mg dose of GVOKE. Patients ages 12 and older received a 0.5 mg or 1 mg dose of GVOKE.

All evaluable pediatric patients (30/30) achieved a target glucose increase of at least 25 mg/dL. Following administration, plasma glucose levels over time showed similar glucose responses for patients in each age group. A summary of plasma glucose results are shown in Table 4.

16 HOW SUPPLIED/STORAGE AND HANDLING

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

Store GVOKE at 20° to 25°C (68° to 77°F); excursions permitted between 15° and 30°C (59° and 86°F). Do not refrigerate or freeze. Do not expose to extreme temperatures.

Store the GVOKE HypoPen and pre-filled syringe in the original sealed foil pouch until time of use. Store the vial and pouched syringe together in original carton until time of use. Discard any unused portion.

17 PATIENT COUNSELING INFORMATION

Advise the patient and family members or caregivers to read the FDA-approved patient labeling (Patient Information and Instructions for Use).

Recognition of Severe Hypoglycemia

Inform patient and family members or caregivers on how to recognize the signs and symptoms of severe hypoglycemia and the risks of prolonged hypoglycemia.

Administration

Review the Patient Information and Instructions for Use with the patient and family members or caregivers.

Serious Hypersensitivity

Inform patients that allergic reactions can occur with GVOKE. Advise patients to seek immediate medical attention if they experience any symptoms of serious hypersensitivity reactions [see Warnings and Precautions (5.3)].

SPL UNCLASSIFIED SECTION

GVOKE® is a trademark of Xeris Pharmaceuticals, Inc.

Distributed by Xeris Pharmaceuticals, Inc.

For information contact:

Xeris Pharmaceuticals, Inc.

1375 W Fulton St., Suite 1300, Chicago IL 60607

1-877-XERIS-37 (1-877-937-4737)

www.xerispharma.com

© 2023 Xeris Pharmaceuticals, Inc.

INSTRUCTIONS FOR USE

GVOKE HypoPen® [GEE-voke hypo-pen] (glucagon injection) Auto-injector for subcutaneous use

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

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 HYPOPEN® VISUAL

Understanding GVOKE HypoPen

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

Adult GVOKE HypoPen (1 mg dose)

Pediatric GVOKE HypoPen contains a 0.5 mg dose of glucagon and is in a foil pouch. Below is a picture of the pouch. See the GVOKE HypoPen package for a full view of the Quick-use guide.

Pediatric GVOKE HypoPen (0.5 mg dose)

HypoPen Device

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

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

Make sure that relatives, close friends, or caregivers know that if you become unconscious, they should call for emergency medical help right away. GVOKE HypoPen 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 HypoPen can be given while awaiting medical assistance.

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

Indications for Use

GVOKE HypoPen 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 HypoPen if:

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 HypoPen 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:

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 HypoPen® should be given or the patient should be treated with intravenous glucose by a medical professional.

Possible Problems with GVOKE HypoPen 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 HypoPen or may experience fast heart-beat for a short while.

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

Important:

Important Warnings

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

3. PREPARING TO INJECT GVOKE HYPOPEN

Step 1. Remove GVOKE HypoPen from Foil Pouch

Figure 1

Step 2. Check the Expiration Date

Figure 2

Step 3. Inspect the Solution

Figure 3

4. INJECTING GVOKE HYPOPEN

Step 4. Pull Off Red Cap

Figure 4

Step 5. Choose Injection Site and Expose Bare Skin

Figure 5

Figure 6

Step 6. Push and Hold to Start Injection

Figure 7

Figure 8

Step 7. Lift Away from Skin

Lift the device straight up from the injection site (see Figure 9).

Figure 9

Step 8. Turn Patient onto Side

Figure 10

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

5. STORING GVOKE HYPOPEN

Storage Information

6. DISPOSING OF GVOKE HYPOPEN®

Re-cap and Dispose of GVOKE HypoPen in an FDA Cleared Sharps Disposal Container

If a puncture-resistant sharps container is not available, carefully re-cap and store GVOKE HypoPen in a safe place until it can be disposed of into a FDA cleared sharps container (see Figure 11).

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 HypoPen.

Figure 11

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.

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

INSTRUCTIONS FOR USE

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

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:

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:

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:

Important Warnings

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

Figure 1

Step 2. Check the Expiration Date

Figure 2

Step 3. Inspect the Solution

Figure 3

4. INJECTING GVOKE® PFS

Step 4. Choose Injection Site and Expose Bare Skin

Figure 4

Figure 5

Step 5. Pull off the Needle Cap

Figure 6

Step 6. Pinch, Insert and Push to Start Injection

Figure 7

Figure 8

Figure 9

Step 7. Lift Away from Skin

Figure 10

Step 8. Turn Patient onto Side

Figure 11

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

5. STORING GVOKE® PFS

Storage Information

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:

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.

• •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.

INSTRUCTIONS FOR USE

GVOKE KIT [GEE-voke k-it] glucagon injection Subcutaneous InjectionThis Instructions for Use contains information on how to inject GVOKE® KIT.

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 artwork/patient-facing IFU files.

GVOKE ® KIT VISUAL

Understanding GVOKE KIT

GVOKE KIT contains one (1) single-dose sterile syringe (29 G x ½” needle) with markings for 0.1 mL (0.5 mg pediatric dose) and 0.2 mL (1 mg adult dose), and one single-dose vial containing 0.2 mL of solution.

STORING GVOKE KIT

Storage Information

IMPORTANT INFORMATION YOU NEED TO KNOW BEFORE INJECTING GVOKE KIT

Make sure that relatives, close friends, or caregivers know that if you become unconscious, they should call for emergency medical help right away. GVOKE KIT 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 KIT can be given while awaiting medical assistance.

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

Indications for Use

GVOKE KIT 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 KIT if:

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 KIT 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:

The occurrence of early symptoms of hypoglycemia 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 not possible, GVOKE® KIT should be used or the patient should be treated with intravenous glucose by a medical professional.

Possible Problems with GVOKE KIT 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 KIT or may experience fast heartbeat for a short while.

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

Important:

Important Warnings

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

PREPARING TO INJECT GVOKE KIT

Step 1. Remove GVOKE Vial and Syringe from Carton

Figure A

Step 2. Check the Expiration Date on GVOKE Vial

Figure B

Step 3. Inspect the Solution in GVOKE® Vial

Figure C

Step 4. Prepare

Figure D

Figure E

Figure F

Figure G

Figure H

Figure I

INJECTING GVOKE® KIT

Step 5. Choose Injection Site and Expose Bare Skin

Figure J

Figure K

Step 6. Pinch, Insert, and Push to Start Injection

Figure L

Figure M

Important: Do not aspirate (pull back on plunger rod) after inserting the needle. Do not lift up the syringe until the injection is complete.

Figure N

Step 7. Lift Away from Skin

Figure O

Step 8. Turn Patient onto Side

Figure P

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

DISPOSING OF GVOKE KIT

Disposing of GVOKE KIT

After the injection, discard vial with unused medicine and place the used syringe in a safe place until it can be disposed of in an FDA-cleared sharps container (see Figure Q). Do not throw away (dispose of) loose needles and syringes in your household trash.

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

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. Do not recycle your used sharps disposal container.

Always keep the sharps container out of the reach of children.

If needed, make sure to get a refill of your GVOKE KIT.

Figure Q

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 Original Approval 08/2021

©2023 by Xeris Pharmaceuticals, Inc.

• •Store vial and pouched syringe together in original carton until time of use. Do not remove syringe from pouch until time of use.
• •Store at room temperature, 68°F to 77°F (20°C to 25°C).
• •Do not refrigerate or freeze.
• •Protect vial from light exposure.

Gvoke Kit Patient Package Insert

This Patient Information has been approved by the U.S. Food and Drug Administration.                           Issued: 05/2023

1 mg Auto-Injector

0.5 mg Auto-Injector

1 mg Pre-Filled Syringe

1 mg Vial and Syringe Kit