BAQSIMI

1 Recommended Dose and Dosage Adjustment The recommended dose of BAQSIMI is 3 mg given intranasally in both adult and pediatric patients. Serious Warnings and Precautions BAQSIMI should be given only in patients where impaired consciousness precludes oral carbohydrates.

After intranasal administration the patient will normally respond within 15 minutes. If the patient does not respond within 15 minutes, intravenous (IV) glucose must be administered as soon as IV access can be established. Because glucagon is of little or no help in states of starvation, adrenal insufficiency, or chronic hypoglycemia, intravenous glucose should be used for the treatment of hypoglycemia in these conditions.

2 Administration Instruct the patient or caregiver to read the package leaflet at the time they receive BAQSIMI. Because BAQSIMI is designed to be administered in emergency situations to the patient by caregiver(s), where a high level of stress is likely, it is therefore important that the patient is instructed to make sure that family, friends and co-workers know where, when and how to use BAQSIMI.

Specific instructions on the use of BAQSIMI should be given to patients at risk of hypoglycemia unawareness, including elderly. Emphasize the following instructions to the patient and/or caregiver: • BAQSIMI is for intranasal use only.

The recommended dose of BAQSIMI is 3 mg administered as one actuation of the intranasal device into one nostril. • Read and follow the instructions on the package leaflet enclosed with BAQSIMI. • Do not push the plunger or test the device prior to administration.

• 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 medical help right away after giving the dose.

• Give oral carbohydrates when the patient responds to treatment. • If the patient does not respond within 15 minutes, intravenous glucose must be administered as soon as IV access can be established. Medical consultation is required for all patients with severe hypoglycemia so that the dose of insulin and oral antidiabetic medication may be adjusted more accurately.

• Each BAQSIMI device contains one dose of glucagon and cannot be reused.

1 Adverse Reaction Overview The safety profile of BAQSIMI has been assessed in 9 clinical studies in adult patients with and without diabetes mellitus, and 2 studies in pediatric patients (4 to <18 years of age) with diabetes mellitus.

The most common (≥10%) adverse reactions associated with BAQSIMI in adults were nausea, vomiting, headache, and upper respiratory tract irritation, which includes rhinorrhea, nasal discomfort, nasal congestion, cough, epistaxis and oropharyngeal pain.

Adverse reactions were typically mild to moderate in severity and none were serious. The adverse reactions were similar in adult and pediatric patients. 2 Clinical Trial Adverse Reactions (Adults) Because clinical trials are conducted under very specific conditions, the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.

Adverse reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates. Two similarly designed comparator-controlled trials (IGBC and IGBI) evaluated the safety of a single 3 mg dose of BAQSIMI compared to a 1 mg dose of intra-muscular glucagon (IMG) in adult patients with diabetes.

Table 2 provides a listing of the adverse reactions reported with a frequency of ≥2% in studies IGBC and IGBI. 5 mg or 1 mg of IMG in pediatric patients with type 1 diabetes. Table 3 presents adverse reactions that occurred in the pediatric study IGBB at an incidence of ≥2%.

4 Less Common Clinical Trial Adverse Reactions Other clinically relevant findings observed with BAQSIMI treated patients across clinical trials IGBC, IGBI and IGBB, were: Cardiac Disorders: tachycardia Eye Disorders: eye pain, ocular hyperemia Gastrointestinal Disorders: abdominal discomfort Metabolism and Nutrition Disorders: hyperglycemia, hypoglycemia Musculoskeletal and Connective Tissue Disorders: neck pain Nervous System Disorders: disturbance in attention Psychiatric Disorders: anxiety, confusional state Respiratory, Thoracic and Mediastinal Disorders: cough, epistaxis, nasal edema, upper-airway cough syndrome Skin and Subcutaneous Tissue Disorders: hyperhidrosis Clinically relevant findings observed across other clinical trials with BAQSIMI were: Dysgeusia, nasal pruritus, hypertension, throat irritation, and parosmia.

Please see the SERIOUS WARNINGS AND PRECAUTIONS BOX, Part I:

Health Professional Information. General BAQSIMI 3 mg by intranasal administration, is helpful in treating hypoglycemia only if sufficient liver glycogen is present. To prevent relapse of hypoglycemia, oral carbohydrates should be given to restore the liver glycogen when the patient has responded to the treatment.

Carcinogenesis and Mutagenesis (see NON-CLINICAL TOXICOLOGY) Cardiovascular In high concentrations, glucagon exerts positive inotropic and chronotropic effect and may therefore cause tachycardia and acute hypertensive reactions (see CONTRAINDICATIONS AND WARNINGS AND PRECAUTIONS, Endocrine and Metabolism).

Driving and Operating Machinery No studies on the effects of glucagon on the ability to drive and use machines have been performed. The patient’s ability to concentrate and react may be impaired as a result of hypoglycemia. This may present a risk in situations where these abilities are especially important, such as driving or operating machinery.

Endocrine and Metabolism Pheochromocytoma BAQSIMI is contraindicated in patients with pheochromocytoma (see CONTRAINDICATIONS). In the presence of pheochromocytoma, glucagon may stimulate the release of catecholamines from the tumor which results in a sudden and marked increase in blood pressure.

If the patient develops a dramatic increase in blood pressure, 5 to 10 mg of phentolamine mesylate, administered intravenously, has been shown to be effective in lowering blood pressure (see WARNINGS AND PRECAUTIONS, Cardiovascular).

Insulinoma BAQSIMI is contraindicated in patients with insulinoma (see CONTRAINDICATIONS). Glucagon 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: • Known hypersensitivity to glucagon or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.

• Pheochromocytoma • Insulinoma