Baqsimi

BAQSIMI- glucagon powder
Eli Lilly and Company

1 INDICATIONS AND USAGE

BAQSIMI™ is indicated for the treatment of severe hypoglycemia in adult and pediatric patients with diabetes ages 4 years and above.

2 DOSAGE AND ADMINISTRATION

2.1 Important Administration Instructions

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.
• 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.

2.2 Dosage in Adults and Pediatric Patients Aged 4 Years and Above

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.

3 DOSAGE FORMS AND STRENGTHS

Nasal Powder:

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

4 CONTRAINDICATIONS

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)]
• Known hypersensitivity 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)]

5 WARNINGS AND PRECAUTIONS

5.1 Substantial Increase in Blood Pressure in Patients with Pheochromocytoma

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.

5.2 Hypoglycemia in Patients with Insulinoma

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.

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. BAQSIMI is contraindicated in patients with a prior hypersensitivity reaction [see Contraindications (4)].

5.4 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 administration to be effective. Patients with these conditions should be treated with glucose.

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)].

6.1 Clinical Trial Data

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.

Adverse Reactions in Adult Patients

Two similarly designed comparator-controlled trials, Study 1 and Study 2, evaluated the safety of a single dose of BAQSIMI compared to a 1 mg dose of intra-muscular glucagon (IMG) in adult patients with diabetes [see Clinical Studies (14)].

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

Table 1: Pooled Adverse Reactions (≥2%) in Adult Patients with Type 1 and Type 2 Diabetes in Study 1 and Study 2

a Upper Respiratory Tract Irritation: rhinorrhea, nasal discomfort, nasal congestion, cough, and epistaxis.
Adverse Reaction	BAQSIMI 3 mg (N=153) %
Nausea	26.1
Headache	18.3
Vomiting	15.0
Upper Respiratory Tract Irritationa	12.4

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.

Table 2: Solicited Nasal and Non-Nasal Adverse Reactions in Adult Patients with Type 1 and Type 2 Diabetes Pooled from Study 1 and 2

a Subjects were asked to report whether they have the symptom, as well as severity (mild, moderate, severe) at baseline, and after glucagon administration.
Adverse Reaction a	BAQSIMI 3 mg (n=153) %
	Any increase in symptom severity a
Watery eyes	58.8
Nasal congestion	42.5
Nasal itching	39.2
Runny nose	34.6
Redness of eyes	24.8
Itchy eyes	21.6
Sneezing	19.6
Itching of throat	12.4
Itching of ears	3.3

Adverse Reactions in Pediatric Patients Aged 4 Years and Above

A single dose of BAQSIMI was compared to weight-based doses of 0.5 mg or 1 mg of IMG in pediatric patients with type 1 diabetes in Study 3 [see Clinical Studies (14)].

Table 3 presents adverse reactions that occurred with BAQSIMI in pediatric patients at an incidence of ≥2% in Study 3.

Table 3: Adverse Reactions (≥2%) Occurring in Pediatric Patients with Type 1 Diabetes in Study 3

a Upper Respiratory Tract Irritation: nasal discomfort, nasal congestion, sneezing.
Adverse Reaction	BAQSIMI 3 mg (n=36) %
Vomiting	30.6
Headache	25.0
Nausea	16.7
Upper Respiratory Tract Irritationa	16.7

Nasal and ocular symptoms with BAQSIMI were solicited through a patient questionnaire in pediatric patients in Study 3 and these adverse reactions are presented in Table 4.

Table 4: Solicited Nasal and Non-Nasal Adverse Reactions in Pediatric Patients with Type 1 Diabetes in Study 3

a Subjects were asked to report whether they have the symptom, as well as severity (mild, moderate, severe) at baseline, and after glucagon administration.
Adverse Reaction a	BAQSIMI 3 mg (n=36) %
	Any increase in symptom severity a
Watery eyes	47.2
Nasal congestion	41.7
Nasal itching	27.8
Runny nose	25.0
Sneezing	19.4
Itchy eyes	16.7
Redness of eyes	13.9
Itching of throat	2.8
Itching of ears	2.8

Other Adverse Reactions in Adult and Pediatric Patients

Other observed adverse reactions with BAQSIMI-treated patients across clinical trials were, dysgeusia, pruritus, tachycardia, hypertension, and additional upper respiratory tract irritation events (nasal pruritus, throat irritation, and parosmia).