These Highlights Do Not Include All The Information Needed To Use Baqsimi Safely And Effectively. See Full Prescribing Information For Baqsimi.

Adverse Reactions in Adult Patients

Two similarly designed comparator-controlled trials, Study 1 and Study 2, evaluated the safety of a single intranasal dose of BAQSIMI compared to a 1 mg dose of intra-muscular glucagon (IMG) in adult patients with diabetes [see Clinical Studies (14.1)].

Table 1 presents adverse reactions that occurred with BAQSIMI at an incidence of ≥2% in a pool of Study 1 and Study 2.

Nasal and ocular symptoms with BAQSIMI were solicited through a patient questionnaire in Study 1 and 2 and these adverse reactions are presented in Table 2.

698351AMD

INSTRUCTIONS FOR USE

BAQSIMI^®

(glucagon) nasal powder

3 mg

Read the Instructions for Use for BAQSIMI before using it. BAQSIMI is used to treat very low blood sugar (severe hypoglycemia) that will cause you to need help from others. You should make sure you show your caregivers, family and friends where you keep BAQSIMI and explain how to use it by sharing these instructions. They need to know how to use BAQSIMI before an emergency happens.

Important Information to Know

• Do not remove the Shrink Wrap or open the Tube until you are ready to use it.
• If the Tube has been opened, BAQSIMI could be exposed to moisture. This could cause BAQSIMI not to not work as expected.
• Do not push the plunger or test BAQSIMI before you are ready to use it.
• BAQSIMI contains 1 dose of glucagon nasal powder and cannot be reused.
• BAQSIMI is for nasal (nose) use only.
• BAQSIMI will work even if you have a cold or are taking cold medicine.

Preparing the Dose

Giving the Dose

After giving BAQSIMI

• Call for emergency medical help right away.
• If the person is passed out (unconscious) turn the person on their side.
• Encourage the person to eat as soon as possible. When they can safely swallow, give the person a fast-acting source of sugar such as juice. Then encourage the person to eat a snack such as crackers with cheese or peanut butter.
• If the person does not respond after 15 minutes, another dose may be given, if available.

Storage and Handling

• Do not remove the Shrink Wrap or open the Tube until you are ready to use it.
• Store BAQSIMI in the shrink wrapped Tube at temperatures up to 86º F (30ºC ).
• Throw away (discard) BAQSIMI and Tube after use. Used BAQSIMI may be placed in household trash.
• Caution: Replace the used BAQSIMI right away so you will have a new BAQSIMI in case you need it.
• Replace BAQSIMI before the expiration date printed on the Tube or carton.

• Keep BAQSIMI and all medicines out of the reach of children.

For Questions or More Information about BAQSIMI

• Call your healthcare provider
• Call Amphastar Pharmaceuticals, Inc. at 1-800-423-4136
• Visit www.baqsimi.com

BAQSIMI is a registered trademark of Amphastar Pharmaceuticals, Inc.

Marketed by: Amphastar Pharmaceuticals, Inc. Rancho Cucamonga, CA 91730, U.S.A

Copyright © 2025, Amphastar Pharmaceuticals, Inc.

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

Revised: March, 2025

678351AMC/3-25

BAQSIMI may increase the anticoagulant effect of warfarin.

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 levels 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. In the event of an overdose of BAQSIMI, consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendation.

BAQSIMI contains glucagon, an antihypoglycemic agent used to treat severe hypoglycemia. Glucagon is a single-chain polypeptide containing 29 amino acid residues and has a molecular weight of 3483, and is identical to human glucagon.

Its molecular formula is C₁₅₃H₂₂₅N₄₃O₄₉S, with the following molecular structure:

BAQSIMI is a preservative-free, white powder for intranasal administration in an intranasal device containing one dose of 3 mg glucagon. BAQSIMI contains glucagon as the active ingredient and betadex, and dodecylphosphocholine as the excipients.

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

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

The safety and effectiveness of BAQSIMI for the treatment of severe hypoglycemia in patients with diabetes have been established in pediatric patients aged 1 year and older. Use of BAQSIMI for this indication is supported by evidence from an adequate and well-controlled study in adults with type 1 diabetes mellitus [see Clinical Studies (14.1)], a study in 48 pediatric patients aged 4 to less than 17 years with type 1 diabetes mellitus [see Clinical Studies (14.2)], and additional pharmacokinetic and safety data from a study of seven pediatric patients aged 1 to less than 4 years with type 1 diabetes mellitus [see Adverse Reactions (6.1),Clinical Pharmacology (12.2, 12.3), and  Clinical Studies (14.2)].

The safety and effectiveness of BAQSIMI have not been established in pediatric patients younger than 1 year of age.

Clinical studies of BAQSIMI did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger adult patients.

BAQSIMI 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)]
• Prior hypersensitivity reaction to glucagon or to any of the excipients in BAQSIMI. Allergic reactions have been reported with glucagon and include anaphylactic shock with breathing difficulties and hypotension [see Warnings and Precautions (5.3)]

The following clinically significant adverse reactions are described 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 in Patients with Decreased Hepatic Glycogen [see Warnings and Precautions (5.4)].

• Beta-blockers: Patients taking beta-blockers may have a transient increase in pulse and blood pressure. (7.1)
• Indomethacin: In patients taking indomethacin BAQSIMI may lose its ability to raise glucose or may produce hypoglycemia. (7.2)
• Warfarin: BAQSIMI may increase the anticoagulant effect of warfarin. (7.3)

After administration of BAQSIMI in adult patients with diabetes, the mean maximum glucose increase from baseline was 140 mg/dL (Figure 1).

In pediatric patients aged 1 to less than 17 years with type 1 diabetes, the mean maximum glucose increase from baseline was 132 mg/dL (1 to less than 4 years), 138 mg/dL (4 to less than 8 years), 133 mg/dL (8 to less than 12 years), and 102 mg/dL (12 to less than 17 years) (Figure 2).

Sex and body weight had no clinically meaningful effects on the pharmacodynamics of BAQSIMI.

Common cold with nasal congestion tested with or without use of decongestant did not impact pharmacodynamics of BAQSIMI.

Figure 1 Mean glucose concentration over time after glucagon dose in adult Type 1 Diabetes patients with insulin-induced hypoglycemia.

Fi gure 2 Mean glucose concentration over time in pediatric Type 1 Diabetes patients administered BAQSIMI

BAQSIMI™ is indicated for the treatment of severe hypoglycemia in adults and pediatric patients aged 1 year and older with diabetes.

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.

• Substantial Increase in Blood Pressure in Patients with Pheochromocytoma: Contraindicated in patients with pheochromocytoma because BAQSIMI 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, BAQSIMI may stimulate exaggerated insulin release from an insulinoma and cause hypoglycemia. If a patient develops symptoms of hypoglycemia after a dose of BAQSIMI, give glucose orally or intravenously. (5.2)
• Serious Hypersensitivity Reactions: Serious hypersensitivity reactions have been reported and include generalized rash, and in some cases anaphylactic shock with breathing difficulties, and hypotension. (5.3)
• Lack of Efficacy in Patients with Decreased Hepatic Glycogen: BAQSIMI 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 BAQSIMI to be effective. Patients with these conditions should be treated with glucose. (5.4)

• BAQSIMI is for intranasal use only. (2.1)
• The recommended dose of BAQSIMI is 3 mg administered as one actuation of the intranasal device into one nostril. (2.2)
• Administer BAQSIMI according to the printed instructions on the shrink-wrapped tube label and the Instructions for Use. (2.1)
• Administer the dose by inserting the tip into one nostril and pressing the device plunger all the way in until the green line is no longer showing. The dose does not need to be inhaled. (2.1)
• Call for emergency assistance immediately after administering the dose. (2.1)
• When the patient responds to treatment, give oral carbohydrates. (2.1)
• Do not attempt to reuse BAQSIMI. Each BAQSIMI device contains one dose of glucagon and cannot be reused. Discard any unused portion. (2.1)
• If there has been no response after 15 minutes, an additional 3 mg dose may be administered while waiting for emergency assistance. (2.2)

Nasal Powder:

• 3 mg glucagon: as a white powder in an intranasal device containing one dose of glucagon

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of BAQSIMI cannot be directly compared with rates in clinical trials of other drugs and may not reflect the rates observed in practice.

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

BAQSIMI is supplied as an intranasal device containing one 3 mg dose of glucagon as a preservative free, white powder.

• BAQSIMI One Pack carton contains 1 intranasal device (NDC 0548-8351-01)
• BAQSIMI Two Pack carton contains 2 intranasal devices (NDC 0548-8352-02)
• Store at temperatures up to 86°F (30°C) in the shrink wrapped tube provided.
• Keep BAQSIMI in the shrink wrapped tube until ready to use. If the tube has been opened, BAQSIMI may have been exposed to moisture and may not work as expected.
• Discard BAQSIMI and tube after use.

Serious hypersensitivity reactions have been reported with glucagon products, including generalized rash, and in some cases anaphylactic shock with breathing difficulties and hypotension. Discontinue BAQSIMI if symptoms of serious hypersensitivity reactions occur. Advise patients and/or caregivers to seek immediate medical attention if the patient experiences any symptoms of serious hypersensitivity reactions. BAQSIMI is contraindicated in patients with a prior hypersensitivity reaction [see Contraindications (4)].

BAQSIMI is for intranasal use only.

Instruct patients and their caregivers on the signs and symptoms of severe hypoglycemia. Because severe hypoglycemia requires help of others to recover, instruct the patient to inform those around them about BAQSIMI and its Instructions for Use. Administer BAQSIMI 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 BAQSIMI. Emphasize the following instructions to the patient or caregiver:

• Do not push the plunger or test the device prior to administration.
• Administer BAQSIMI according to the printed instructions on the shrink-wrapped tube label and the Instructions for Use.
• Administer the dose by inserting the tip into one nostril and pressing the device plunger all the way in until the green line is no longer showing. The dose does not need to be inhaled.
• Call for emergency assistance immediately after administering the dose.
• If there has been no response after 15 minutes, an additional dose of BAQSIMI may be administered while waiting for emergency assistance.
• When the patient responds to treatment, give oral carbohydrates to restore the liver glycogen and prevent recurrence of hypoglycemia.
• Do not attempt to reuse BAQSIMI. Each BAQSIMI device contains one dose of glucagon and cannot be reused. Discard any unused portion.

In patients with insulinoma, administration of glucagon may produce an initial increase in blood glucose; however, BAQSIMI administration may directly or indirectly (through an initial rise in blood glucose) stimulate exaggerated insulin release from an insulinoma and cause hypoglycemia. BAQSIMI is contraindicated in patients with insulinoma [see Contraindications (4)]. If a patient develops symptoms of hypoglycemia after a dose of BAQSIMI, give glucose orally or intravenously.

NDC 0548-8351-01

baqsimi^®

(glucagon) nasal powder

3 mg

For Treatment of Severe Low Blood Sugar

For Nasal Use Only

Contains 1 nasal device.

Keep tube sealed until ready to use.

Rx only

BAQSIMI One Pack^®

www.baqsimi.com

568351AMA/5-23

NDC 0548-8352-02

baqsimi^®

(glucagon) nasal powder

3 mg

For Treatment of Severe Low Blood Sugar

For Nasal Use Only

Contains 2 nasal devices.

Keep tubes sealed until ready to use.

Rx only

BAQSIMI Two Pack^®

www.baqsimi.com

528352AMA/5-23

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.

Study 1 (NCT03339453) was a randomized, multicenter, open-label, 2-period, crossover study in adult patients with type 1 diabetes. The efficacy of a single 3 mg dose of BAQSIMI was compared to a 1 mg dose of intra-muscular glucagon (IMG). Insulin was used to reduce blood glucose levels to <60 mg/dL. Seventy patients were enrolled, with a mean age of 41.7 years and a mean diabetes duration of 20.1 years. Twenty-seven (39%) were female.

The primary efficacy outcome measure was the proportion of patients achieving treatment success, which was defined as either an increase in blood glucose to ≥70 mg/dL or an increase of ≥20 mg/dL from glucose nadir within 30 minutes after receiving study glucagon, without receiving additional actions to increase the blood glucose level. Glucose nadir was defined as the minimum glucose measurement at the time of, or within 10 minutes, following glucagon administration.

The mean nadir blood glucose was 54.5 mg/dL for BAQSIMI and 55.8 mg/dL for IMG. BAQSIMI demonstrated non-inferiority to IMG in reversing insulin-induced hypoglycemia with 100% of BAQSIMI-treated patients and 100% of IMG-treated patients achieving treatment success. The mean time to treatment success was 11.6 and 9.9 minutes in the BAQSIMI and IMG 1 mg treatment groups, respectively.

Table 5: Adult Patients with Type 1 Diabetes Meeting Treatment Success and Other Glucose Criteria in Study 1

Study 2 (NCT01994746) was a randomized, multicenter, open-label, 2-period, crossover study in adult patients with type 1 diabetes or type 2 diabetes. The efficacy of a single 3 mg dose of BAQSIMI was compared to a 1 mg dose of intra-muscular glucagon (IMG). Insulin was used to reduce blood glucose levels to the hypoglycemic range with a target blood glucose nadir of <50 mg/dL.

Study 2 enrolled 83 patients 18 to <65 years of age. The mean age of patients with type 1 diabetes (N=77) was 32.9 years and a mean diabetes duration of 18.1 years, and 45 (58%) patients were female. The mean age of patients with type 2 diabetes (N=6) was 47.8 years, with a mean diabetes duration of 18.8 years, and 4 (67%) patients were female.

The mean nadir blood glucose was 44.2 mg/dL for BAQSIMI and 47.2 mg/dL for IMG. BAQSIMI demonstrated non-inferiority to IMG in reversing insulin-induced hypoglycemia with 98.8% of BAQSIMI-treated patients and 100% of IMG-treated patients achieving treatment success within 30 minutes.

The mean time to treatment success was 15.9 and 12.1 minutes in the BAQSIMI and IMG 1 mg treatment groups, respectively.

Patients with insufficient hepatic stores of glycogen may not respond to BAQSIMI for the treatment of severe hypoglycemia [see Clinical Pharmacology (12.2)]. Insufficient hepatic stores of glycogen may be present in conditions such as states of starvation or in patients with adrenal insufficiency or chronic hypoglycemia.

The recommended dose of BAQSIMI is 3 mg administered as one actuation of the intranasal device into one nostril.

If there has been no response after 15 minutes, an additional 3 mg dose of BAQSIMI from a new device may be administered while waiting for emergency assistance.

BAQSIMI is contraindicated in patients with pheochromocytoma because glucagon may stimulate 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.

Study 3 (NCT01997411) was a randomized, multicenter, clinical study that assessed BAQSIMI compared to intra-muscular glucagon (IMG) in pediatric patients aged 4 to less than 17 years with type 1 diabetes. Insulin was used to reduce blood glucose levels, and glucagon was administered after glucose reached <80 mg/dL. Efficacy was assessed based on percentage of patients with a glucose increase of ≥20 mg/dL from glucose nadir within 30 minutes following BAQSIMI administration.

Forty-eight patients were enrolled and received at least one dose of study drug. The mean age in the Young Children cohort (4 to <8 years) was 6.5 years. In the Children cohort (8 to <12 years), mean age was 11.1 years and in the Adolescents cohort (12 to <17 years) mean age was 14.6 years. In all age cohorts, the population was predominantly male and white.

Across all age groups, all (100%) patients in both treatment arms achieved an increase in glucose ≥20 mg/dL from glucose nadir within 20 minutes of glucagon administration. The mean time to reach a glucose increase of ≥20 mg/dL for BAQSIMI and IMG for all age groups is shown in Table 7.

Study 4 (NCT04992312) was a phase 1, open-label, multi-center study with a primary objective of assessing the safety and tolerability of a single 3 mg dose of BAQSIMI in pediatric participants aged 1 to less than 4 years with type 1 diabetes mellitus. Patients were recommended to fast overnight before the dosing visit on Day 1, to achieve the target range glucose of 70 to 140 mg/dL (3.9 to 7.8 mmol/L) at baseline. Efficacy was assessed based on the percentage of patients with a glucose increase of ≥20 mg/dL from baseline within 30 minutes following BAQSIMI administration.

Seven patients were enrolled in the study, all received the planned 3 mg dose of BAQSIMI and completed the study. The mean age of the patients enrolled in the study was 2.98 years, with ages ranging from 1.8 to 4 years old. There were 4 males and 3 females enrolled in the study, all who were white.

All (100%) patients achieved an increase in glucose ≥20 mg/dL from baseline within 30 minutes of BAQSIMI administration.

Adverse Reactions in Adult Patients

Two similarly designed comparator-controlled trials, Study 1 and Study 2, evaluated the safety of a single intranasal dose of BAQSIMI compared to a 1 mg dose of intra-muscular glucagon (IMG) in adult patients with diabetes [see Clinical Studies (14.1)].

Table 1 presents adverse reactions that occurred with BAQSIMI at an incidence of ≥2% in a pool of Study 1 and Study 2.

Nasal and ocular symptoms with BAQSIMI were solicited through a patient questionnaire in Study 1 and 2 and these adverse reactions are presented in Table 2.

698351AMD

INSTRUCTIONS FOR USE

BAQSIMI^®

(glucagon) nasal powder

3 mg

Read the Instructions for Use for BAQSIMI before using it. BAQSIMI is used to treat very low blood sugar (severe hypoglycemia) that will cause you to need help from others. You should make sure you show your caregivers, family and friends where you keep BAQSIMI and explain how to use it by sharing these instructions. They need to know how to use BAQSIMI before an emergency happens.

Important Information to Know

• Do not remove the Shrink Wrap or open the Tube until you are ready to use it.
• If the Tube has been opened, BAQSIMI could be exposed to moisture. This could cause BAQSIMI not to not work as expected.
• Do not push the plunger or test BAQSIMI before you are ready to use it.
• BAQSIMI contains 1 dose of glucagon nasal powder and cannot be reused.
• BAQSIMI is for nasal (nose) use only.
• BAQSIMI will work even if you have a cold or are taking cold medicine.

Preparing the Dose

Giving the Dose

After giving BAQSIMI

• Call for emergency medical help right away.
• If the person is passed out (unconscious) turn the person on their side.
• Encourage the person to eat as soon as possible. When they can safely swallow, give the person a fast-acting source of sugar such as juice. Then encourage the person to eat a snack such as crackers with cheese or peanut butter.
• If the person does not respond after 15 minutes, another dose may be given, if available.

Storage and Handling

• Do not remove the Shrink Wrap or open the Tube until you are ready to use it.
• Store BAQSIMI in the shrink wrapped Tube at temperatures up to 86º F (30ºC ).
• Throw away (discard) BAQSIMI and Tube after use. Used BAQSIMI may be placed in household trash.
• Caution: Replace the used BAQSIMI right away so you will have a new BAQSIMI in case you need it.
• Replace BAQSIMI before the expiration date printed on the Tube or carton.

• Keep BAQSIMI and all medicines out of the reach of children.

For Questions or More Information about BAQSIMI

• Call your healthcare provider
• Call Amphastar Pharmaceuticals, Inc. at 1-800-423-4136
• Visit www.baqsimi.com

BAQSIMI is a registered trademark of Amphastar Pharmaceuticals, Inc.

Marketed by: Amphastar Pharmaceuticals, Inc. Rancho Cucamonga, CA 91730, U.S.A

Copyright © 2025, Amphastar Pharmaceuticals, Inc.

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

Revised: March, 2025

678351AMC/3-25

BAQSIMI may increase the anticoagulant effect of warfarin.

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 levels 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. In the event of an overdose of BAQSIMI, consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendation.

BAQSIMI contains glucagon, an antihypoglycemic agent used to treat severe hypoglycemia. Glucagon is a single-chain polypeptide containing 29 amino acid residues and has a molecular weight of 3483, and is identical to human glucagon.

Its molecular formula is C₁₅₃H₂₂₅N₄₃O₄₉S, with the following molecular structure:

BAQSIMI is a preservative-free, white powder for intranasal administration in an intranasal device containing one dose of 3 mg glucagon. BAQSIMI contains glucagon as the active ingredient and betadex, and dodecylphosphocholine as the excipients.

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

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

The safety and effectiveness of BAQSIMI for the treatment of severe hypoglycemia in patients with diabetes have been established in pediatric patients aged 1 year and older. Use of BAQSIMI for this indication is supported by evidence from an adequate and well-controlled study in adults with type 1 diabetes mellitus [see Clinical Studies (14.1)], a study in 48 pediatric patients aged 4 to less than 17 years with type 1 diabetes mellitus [see Clinical Studies (14.2)], and additional pharmacokinetic and safety data from a study of seven pediatric patients aged 1 to less than 4 years with type 1 diabetes mellitus [see Adverse Reactions (6.1),Clinical Pharmacology (12.2, 12.3), and  Clinical Studies (14.2)].

The safety and effectiveness of BAQSIMI have not been established in pediatric patients younger than 1 year of age.

Clinical studies of BAQSIMI did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger adult patients.

BAQSIMI 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)]
• Prior hypersensitivity reaction to glucagon or to any of the excipients in BAQSIMI. Allergic reactions have been reported with glucagon and include anaphylactic shock with breathing difficulties and hypotension [see Warnings and Precautions (5.3)]

The following clinically significant adverse reactions are described 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 in Patients with Decreased Hepatic Glycogen [see Warnings and Precautions (5.4)].

• Beta-blockers: Patients taking beta-blockers may have a transient increase in pulse and blood pressure. (7.1)
• Indomethacin: In patients taking indomethacin BAQSIMI may lose its ability to raise glucose or may produce hypoglycemia. (7.2)
• Warfarin: BAQSIMI may increase the anticoagulant effect of warfarin. (7.3)

After administration of BAQSIMI in adult patients with diabetes, the mean maximum glucose increase from baseline was 140 mg/dL (Figure 1).

In pediatric patients aged 1 to less than 17 years with type 1 diabetes, the mean maximum glucose increase from baseline was 132 mg/dL (1 to less than 4 years), 138 mg/dL (4 to less than 8 years), 133 mg/dL (8 to less than 12 years), and 102 mg/dL (12 to less than 17 years) (Figure 2).

Sex and body weight had no clinically meaningful effects on the pharmacodynamics of BAQSIMI.

Common cold with nasal congestion tested with or without use of decongestant did not impact pharmacodynamics of BAQSIMI.

Figure 1 Mean glucose concentration over time after glucagon dose in adult Type 1 Diabetes patients with insulin-induced hypoglycemia.

Fi gure 2 Mean glucose concentration over time in pediatric Type 1 Diabetes patients administered BAQSIMI

BAQSIMI™ is indicated for the treatment of severe hypoglycemia in adults and pediatric patients aged 1 year and older with diabetes.

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.

• Substantial Increase in Blood Pressure in Patients with Pheochromocytoma: Contraindicated in patients with pheochromocytoma because BAQSIMI 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, BAQSIMI may stimulate exaggerated insulin release from an insulinoma and cause hypoglycemia. If a patient develops symptoms of hypoglycemia after a dose of BAQSIMI, give glucose orally or intravenously. (5.2)
• Serious Hypersensitivity Reactions: Serious hypersensitivity reactions have been reported and include generalized rash, and in some cases anaphylactic shock with breathing difficulties, and hypotension. (5.3)
• Lack of Efficacy in Patients with Decreased Hepatic Glycogen: BAQSIMI 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 BAQSIMI to be effective. Patients with these conditions should be treated with glucose. (5.4)

• BAQSIMI is for intranasal use only. (2.1)
• The recommended dose of BAQSIMI is 3 mg administered as one actuation of the intranasal device into one nostril. (2.2)
• Administer BAQSIMI according to the printed instructions on the shrink-wrapped tube label and the Instructions for Use. (2.1)
• Administer the dose by inserting the tip into one nostril and pressing the device plunger all the way in until the green line is no longer showing. The dose does not need to be inhaled. (2.1)
• Call for emergency assistance immediately after administering the dose. (2.1)
• When the patient responds to treatment, give oral carbohydrates. (2.1)
• Do not attempt to reuse BAQSIMI. Each BAQSIMI device contains one dose of glucagon and cannot be reused. Discard any unused portion. (2.1)
• If there has been no response after 15 minutes, an additional 3 mg dose may be administered while waiting for emergency assistance. (2.2)

Nasal Powder:

• 3 mg glucagon: as a white powder in an intranasal device containing one dose of glucagon

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of BAQSIMI cannot be directly compared with rates in clinical trials of other drugs and may not reflect the rates observed in practice.

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

BAQSIMI is supplied as an intranasal device containing one 3 mg dose of glucagon as a preservative free, white powder.

• BAQSIMI One Pack carton contains 1 intranasal device (NDC 0548-8351-01)
• BAQSIMI Two Pack carton contains 2 intranasal devices (NDC 0548-8352-02)
• Store at temperatures up to 86°F (30°C) in the shrink wrapped tube provided.
• Keep BAQSIMI in the shrink wrapped tube until ready to use. If the tube has been opened, BAQSIMI may have been exposed to moisture and may not work as expected.
• Discard BAQSIMI and tube after use.

Serious hypersensitivity reactions have been reported with glucagon products, including generalized rash, and in some cases anaphylactic shock with breathing difficulties and hypotension. Discontinue BAQSIMI if symptoms of serious hypersensitivity reactions occur. Advise patients and/or caregivers to seek immediate medical attention if the patient experiences any symptoms of serious hypersensitivity reactions. BAQSIMI is contraindicated in patients with a prior hypersensitivity reaction [see Contraindications (4)].

BAQSIMI is for intranasal use only.

Instruct patients and their caregivers on the signs and symptoms of severe hypoglycemia. Because severe hypoglycemia requires help of others to recover, instruct the patient to inform those around them about BAQSIMI and its Instructions for Use. Administer BAQSIMI 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 BAQSIMI. Emphasize the following instructions to the patient or caregiver:

• Do not push the plunger or test the device prior to administration.
• Administer BAQSIMI according to the printed instructions on the shrink-wrapped tube label and the Instructions for Use.
• Administer the dose by inserting the tip into one nostril and pressing the device plunger all the way in until the green line is no longer showing. The dose does not need to be inhaled.
• Call for emergency assistance immediately after administering the dose.
• If there has been no response after 15 minutes, an additional dose of BAQSIMI may be administered while waiting for emergency assistance.
• When the patient responds to treatment, give oral carbohydrates to restore the liver glycogen and prevent recurrence of hypoglycemia.
• Do not attempt to reuse BAQSIMI. Each BAQSIMI device contains one dose of glucagon and cannot be reused. Discard any unused portion.

In patients with insulinoma, administration of glucagon may produce an initial increase in blood glucose; however, BAQSIMI administration may directly or indirectly (through an initial rise in blood glucose) stimulate exaggerated insulin release from an insulinoma and cause hypoglycemia. BAQSIMI is contraindicated in patients with insulinoma [see Contraindications (4)]. If a patient develops symptoms of hypoglycemia after a dose of BAQSIMI, give glucose orally or intravenously.

NDC 0548-8351-01

baqsimi^®

(glucagon) nasal powder

3 mg

For Treatment of Severe Low Blood Sugar

For Nasal Use Only

Contains 1 nasal device.

Keep tube sealed until ready to use.

Rx only

BAQSIMI One Pack^®

www.baqsimi.com

568351AMA/5-23

NDC 0548-8352-02

baqsimi^®

(glucagon) nasal powder

3 mg

For Treatment of Severe Low Blood Sugar

For Nasal Use Only

Contains 2 nasal devices.

Keep tubes sealed until ready to use.

Rx only

BAQSIMI Two Pack^®

www.baqsimi.com

528352AMA/5-23

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.

Study 1 (NCT03339453) was a randomized, multicenter, open-label, 2-period, crossover study in adult patients with type 1 diabetes. The efficacy of a single 3 mg dose of BAQSIMI was compared to a 1 mg dose of intra-muscular glucagon (IMG). Insulin was used to reduce blood glucose levels to <60 mg/dL. Seventy patients were enrolled, with a mean age of 41.7 years and a mean diabetes duration of 20.1 years. Twenty-seven (39%) were female.

The primary efficacy outcome measure was the proportion of patients achieving treatment success, which was defined as either an increase in blood glucose to ≥70 mg/dL or an increase of ≥20 mg/dL from glucose nadir within 30 minutes after receiving study glucagon, without receiving additional actions to increase the blood glucose level. Glucose nadir was defined as the minimum glucose measurement at the time of, or within 10 minutes, following glucagon administration.

The mean nadir blood glucose was 54.5 mg/dL for BAQSIMI and 55.8 mg/dL for IMG. BAQSIMI demonstrated non-inferiority to IMG in reversing insulin-induced hypoglycemia with 100% of BAQSIMI-treated patients and 100% of IMG-treated patients achieving treatment success. The mean time to treatment success was 11.6 and 9.9 minutes in the BAQSIMI and IMG 1 mg treatment groups, respectively.

Table 5: Adult Patients with Type 1 Diabetes Meeting Treatment Success and Other Glucose Criteria in Study 1

Study 2 (NCT01994746) was a randomized, multicenter, open-label, 2-period, crossover study in adult patients with type 1 diabetes or type 2 diabetes. The efficacy of a single 3 mg dose of BAQSIMI was compared to a 1 mg dose of intra-muscular glucagon (IMG). Insulin was used to reduce blood glucose levels to the hypoglycemic range with a target blood glucose nadir of <50 mg/dL.

Study 2 enrolled 83 patients 18 to <65 years of age. The mean age of patients with type 1 diabetes (N=77) was 32.9 years and a mean diabetes duration of 18.1 years, and 45 (58%) patients were female. The mean age of patients with type 2 diabetes (N=6) was 47.8 years, with a mean diabetes duration of 18.8 years, and 4 (67%) patients were female.

The mean nadir blood glucose was 44.2 mg/dL for BAQSIMI and 47.2 mg/dL for IMG. BAQSIMI demonstrated non-inferiority to IMG in reversing insulin-induced hypoglycemia with 98.8% of BAQSIMI-treated patients and 100% of IMG-treated patients achieving treatment success within 30 minutes.

The mean time to treatment success was 15.9 and 12.1 minutes in the BAQSIMI and IMG 1 mg treatment groups, respectively.

Patients with insufficient hepatic stores of glycogen may not respond to BAQSIMI for the treatment of severe hypoglycemia [see Clinical Pharmacology (12.2)]. Insufficient hepatic stores of glycogen may be present in conditions such as states of starvation or in patients with adrenal insufficiency or chronic hypoglycemia.

The recommended dose of BAQSIMI is 3 mg administered as one actuation of the intranasal device into one nostril.

If there has been no response after 15 minutes, an additional 3 mg dose of BAQSIMI from a new device may be administered while waiting for emergency assistance.

BAQSIMI is contraindicated in patients with pheochromocytoma because glucagon may stimulate 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.

Study 3 (NCT01997411) was a randomized, multicenter, clinical study that assessed BAQSIMI compared to intra-muscular glucagon (IMG) in pediatric patients aged 4 to less than 17 years with type 1 diabetes. Insulin was used to reduce blood glucose levels, and glucagon was administered after glucose reached <80 mg/dL. Efficacy was assessed based on percentage of patients with a glucose increase of ≥20 mg/dL from glucose nadir within 30 minutes following BAQSIMI administration.

Forty-eight patients were enrolled and received at least one dose of study drug. The mean age in the Young Children cohort (4 to <8 years) was 6.5 years. In the Children cohort (8 to <12 years), mean age was 11.1 years and in the Adolescents cohort (12 to <17 years) mean age was 14.6 years. In all age cohorts, the population was predominantly male and white.

Across all age groups, all (100%) patients in both treatment arms achieved an increase in glucose ≥20 mg/dL from glucose nadir within 20 minutes of glucagon administration. The mean time to reach a glucose increase of ≥20 mg/dL for BAQSIMI and IMG for all age groups is shown in Table 7.

Study 4 (NCT04992312) was a phase 1, open-label, multi-center study with a primary objective of assessing the safety and tolerability of a single 3 mg dose of BAQSIMI in pediatric participants aged 1 to less than 4 years with type 1 diabetes mellitus. Patients were recommended to fast overnight before the dosing visit on Day 1, to achieve the target range glucose of 70 to 140 mg/dL (3.9 to 7.8 mmol/L) at baseline. Efficacy was assessed based on the percentage of patients with a glucose increase of ≥20 mg/dL from baseline within 30 minutes following BAQSIMI administration.

Seven patients were enrolled in the study, all received the planned 3 mg dose of BAQSIMI and completed the study. The mean age of the patients enrolled in the study was 2.98 years, with ages ranging from 1.8 to 4 years old. There were 4 males and 3 females enrolled in the study, all who were white.

All (100%) patients achieved an increase in glucose ≥20 mg/dL from baseline within 30 minutes of BAQSIMI administration.