Baqsimi - Drug Monograph

Introduction

Baqsimi (glucagon nasal powder) is a novel intranasal formulation of glucagon indicated for the treatment of severe hypoglycemia. Developed as an alternative to traditional injectable glucagon formulations, Baqsimi represents a significant advancement in hypoglycemia management by providing a needle-free, ready-to-use option that can be administered rapidly during emergency situations.

Mechanism of Action

Baqsimi contains glucagon, a polypeptide hormone that acts as a counter-regulatory hormone to insulin. Its primary mechanism involves:

• Hepatic glycogenolysis: Stimulating hepatic adenylate cyclase to increase cyclic AMP production, which activates phosphorylase and promotes glycogen breakdown to glucose
• Gluconeogenesis: Enhancing hepatic glucose production from non-carbohydrate substrates
• Inhibiting hepatic glucose uptake and glycogen synthesis
• Delaying gastric emptying and reducing gastrointestinal motility

These actions collectively result in a rapid increase in blood glucose levels, typically within 10-15 minutes of administration.

Indications

FDA-approved indications:

• Treatment of severe hypoglycemia in patients with diabetes ages 4 years and older
• Use in individuals who require assistance from another person due to their hypoglycemia

Off-label uses (limited evidence):

• Diagnostic aid in radiologic examinations to temporarily inhibit gastrointestinal motility
• Management of beta-blocker or calcium channel blocker overdose (though injectable forms are typically preferred)

Dosage and Administration

• Adults and pediatric patients ≥4 years: 3 mg (1 nasal device) administered intranasally once
• Repeat dosing: If no response within 15 minutes, may administer a second dose

1. Remove device from case 2. Hold device between fingers and thumb 3. Insert tip into nostril until fingers touch nose 4. Push plunger completely in with one firm motion 5. Remove device from nose after administration

• Renal impairment: No dosage adjustment required
• Hepatic impairment: Use with caution; limited data available
• Geriatric patients: No specific dosage adjustment recommended
• Pediatric: Approved for ages 4 years and older; safety and effectiveness not established in children <4 years

Pharmacokinetics

• Rapid systemic absorption through nasal mucosa
• Tmax: Approximately 15-30 minutes
• Bioavailability: Approximately 40-50% compared to intramuscular glucagon

• Does not significantly bind to plasma proteins
• Volume of distribution: Approximately 0.25 L/kg

• Primarily metabolized in liver, kidneys, and plasma
• Undergoes proteolytic degradation

• Half-life: Approximately 8-18 minutes
• Clearance: Primarily hepatic
• No active metabolites identified

Contraindications

• Known hypersensitivity to glucagon or any component of the formulation
• Pheochromocytoma (due to risk of catecholamine release)
• Insulinoma (may stimulate initial insulin release)
• Glucagonoma

Warnings and Precautions

• Hepatic impairment: Use with caution in patients with hepatic insufficiency; may have reduced response
• Gastrointestinal effects: May cause nausea and vomiting, creating aspiration risk in unconscious patients
• Hypersensitivity reactions: Although rare, anaphylactic reactions have been reported with glucagon products
• rebound hypoglycemia: Monitor for recurrent hypoglycemia after initial recovery
• Nasal conditions: Effectiveness may be reduced in patients with severe nasal congestion, nasal discharge, or nasal deformities

Drug Interactions

• Beta-blockers: May blunt hyperglycemic response
• Indomethacin: May attenuate glucagon's effects
• Anticholinergic agents: May potentiate gastrointestinal effects
• Insulin: Glucagon antagonizes insulin effects
• Warfarin: Glucagon may enhance anticoagulant effect

Adverse Effects

• Nausea (36%)
• Vomiting (16%)
• Headache (15%)
• Upper respiratory tract irritation (8%)
• Nasal congestion (6%)
• Lacrimation increased (5%)
• Rhinitis (5%)

• Anaphylactic reactions
• Severe hypotension
• Hypertension (particularly in patients with pheochromocytoma)
• Hypokalemia

Monitoring Parameters

• Blood glucose: Monitor before and every 15 minutes after administration until patient recovers
• Neurological status: Assess consciousness level and cognitive function
• Vital signs: Monitor blood pressure, heart rate, respiratory status
• Signs of hypersensitivity: Observe for rash, respiratory distress
• Recurrent hypoglycemia: Monitor for several hours after recovery
• Nasal examination: In repeated use cases, assess nasal mucosa integrity

Patient Education

• Baqsimi is for emergency use only during severe hypoglycemia when the patient cannot treat themselves
• Administer when the patient is unconscious, having a seizure, or unable to swallow
• Practice proper administration technique before an emergency occurs
• Always call for emergency medical help after administration
• After recovery, consume a fast-acting carbohydrate followed by a snack or meal
• Check expiration date regularly and replace as needed
• Store at room temperature (20-25°C); avoid freezing
• Each device is single-use only
• Common side effects include nausea, vomiting, and headache
• Inform healthcare providers about all medications being taken

• Keep in sealed tube until ready to use
• Protect from moisture
• Do not test or prime the device before use
• Discard properly after single use

References

1. FDA Prescribing Information: Baqsimi (glucagon nasal powder). 2019. 2. Rickels MR, et al. Intranasal glucagon for treatment of insulin-induced hypoglycemia in adults with type 1 diabetes: A randomized crossover noninferiority study. Diabetes Care. 2016;39(2):264-270. 3. Yale JF, et al. Efficacy and safety of nasal glucagon for treatment of hypoglycemia in adults with type 1 diabetes. Diabetes Care. 2019;42(8):1509-1515. 4. Sherr JL, et al. Glucagon nasal powder: A promising alternative to intramuscular glucagon in youth with type 1 diabetes. Diabetes Care. 2018;41(2):246-250. 5. Pieber TR, et al. Efficacy and safety of nasal glucagon in treatment of moderate hypoglycemia in adults with type 1 diabetes. J Clin Endocrinol Metab. 2020;105(3):dgz041. 6. American Diabetes Association. 6. Glycemic targets: Standards of Medical Care in Diabetes-2021. Diabetes Care. 2021;44(Suppl 1):S73-S84. 7. Seaquist ER, et al. Hypoglycemia and diabetes: A report of a workgroup of the American Diabetes Association and The Endocrine Society. Diabetes Care. 2013;36(5):1384-1395.