Dasiglucagon (Monograph)

Brand name: Zegalogue
Drug class: Glycogenolytic Agents
Chemical name: (4S)-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S,3R)-2-[[2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-amino-3-(1H-imidazol-4-yl)propanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]acetyl]amino]-3-hydroxybutanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxypropanoyl]amino]hexanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]-3-carboxypropanoyl]amino]-2-methylpropanoyl]amino]propanoyl]amino]-5-carbamimidamidopentanoyl]amino]propanoyl]amino]-5-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-4-carboxy-1-[[(2S)-1-[[(1S,2R)-1-carboxy-2-hydroxypropyl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-5-oxopentanoic acid
Molecular formula: C₁₅₂H₂₂₂N₃₈O₅₀
CAS number: 1544300-84-6

Medically reviewed by Drugs.com on Aug 9, 2024. Written by ASHP.

Introduction

Antihypoglycemic agent; glucagon analog that increases blood glucose concentration by stimulating hepatic glycogenolysis.^{1 5 6 7 8 9}

Uses for Dasiglucagon

Hypoglycemia

Treatment of severe hypoglycemia in patients with diabetes mellitus;^{1 2 3 4} effective only if liver glycogen is available.¹

May be of little or no value in patients with chronic hypoglycemia or in those with hypoglycemia associated with starvation or adrenal insufficiency.¹

Dasiglucagon Dosage and Administration

General

• Inform patients and their caregivers of the signs and symptoms of severe hypoglycemia; effective only if liver glycogen available.¹

• Effective treatment of severe hypoglycemia requires assistance from other individuals; patients should inform family members and friends about the availability of dasiglucagon and provide them with instructions for use of the drug.¹

Administration

Sub-Q Administration

For sub-Q injection only.¹ Injection sites include lower abdomen, buttocks, thigh, and outer upper arm.¹

Available in single-use auto-injectors and prefilled syringes.¹ Solution should appear clear, colorless, and free from particles; discard if it is discolored or contains particulate matter.¹

Administer as soon as possible after severe hypoglycemia is recognized.¹ Immediately following administration, summon emergency assistance.¹ If patient has not responded within 15 minutes after the initial dose, may administer an additional dose using a new auto-injector or prefilled syringe while awaiting emergency assistance.¹ Once patient has responded, administer oral carbohydrates to restore liver glycogen stores and prevent recurrence of hypoglycemia.¹

Dosage

Available as dasiglucagon hydrochloride; dosage expressed in terms of dasiglucagon.¹

Pediatric Patients

Hypoglycemia

Sub-Q

Pediatric patients ≥6 years of age: 0.6 mg; may administer a second 0.6-mg dose if no response after 15 minutes.¹

Adults

Hypoglycemia

Sub-Q

0.6 mg; may administer a second 0.6-mg dose if no response after 15 minutes.¹

Special Populations

Manufacturer makes no special population dosage recommendations at this time.¹

Cautions for Dasiglucagon

Contraindications

• Pheochromocytoma because of the risk of a substantial increase in BP.¹ (See Pheochromocytoma under Cautions.)

• Insulinoma because of the risk of hypoglycemia.¹ (See Insulinoma under Cautions.)

Warnings/Precautions

Pheochromocytoma

Glucagon may stimulate tumor release of catecholamines in patients with pheochromocytoma.¹ If patient's BP increases substantially after dasiglucagon administration and a previously undiagnosed pheochromocytoma is suspected, IV administration of 5–10 mg of phentolamine mesylate may effectively lower BP.¹ (See Contraindications under Cautions.)

Insulinoma

Glucagon preparations may produce an initial increase in blood glucose concentration in patients with insulinoma; however, dasiglucagon may directly or indirectly (through initial rise in blood glucose concentration) stimulate exaggerated insulin release from an insulinoma and cause hypoglycemia.¹ (See Contraindications under Cautions.) If patient experiences symptoms of hypoglycemia after receiving dasiglucagon, administer IV or oral glucose.¹

Hypersensitivity Reactions

Allergic reactions (including generalized rash and, occasionally, anaphylactic shock with respiratory distress and hypotension) reported in patients receiving glucagon preparations.¹

Decreased Hepatic Glycogen Stores

Dasiglucagon is effective in treating hypoglycemia only if hepatic glycogen stores are sufficient.¹ Patients in states of starvation and those with adrenal insufficiency or chronic hypoglycemia may not have adequate hepatic glycogen stores; use glucose rather than dasiglucagon to treat severe hypoglycemia in these patients.¹

Immunogenicity

Potential for immunogenicity.¹ Treatment-emergent antidrug antibodies reported in clinical trials in <1% of patients receiving dasiglucagon; no safety or efficacy concerns observed.¹ However, not known whether antibody development can affect the pharmacokinetics, pharmacodynamics, safety, or efficacy of dasiglucagon.¹

Specific Populations

Pregnancy

No available data regarding use of dasiglucagon in pregnant women by which to establish a drug-associated risk of major birth defects, spontaneous abortion, or adverse maternal or fetal outcomes.¹ Untreated hypoglycemia during pregnancy can cause complications and can be fatal.¹

In animal reproduction studies, no adverse developmental effects reported in rats; fetal skeletal and visceral malformations reported in rabbits receiving higher doses.¹

Lactation

Not known whether dasiglucagon distributes into human or animal milk, affects breast-fed infants, or affects milk production.¹ Unlikely to harm breast-fed infants since dasiglucagon is a peptide and would be expected to be broken down to its constituent amino acids in an infant's digestive tract.¹

Pediatric Use

Safety and efficacy for treatment of severe hypoglycemia in pediatric patients ≥6 years of age with diabetes mellitus are supported by a controlled study in 42 pediatric patients with type 1 diabetes mellitus.¹ Safety and efficacy not established in pediatric patients <6 years of age.¹

Geriatric Use

Clinical studies did not include sufficient numbers of patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.¹

Common Adverse Effects

Nausea, vomiting, headache, and injection site pain reported in ≥2% of adults or pediatric patients.¹ Diarrhea also reported in ≥2% of adults.¹

Drug Interactions

Specific Drugs

Dasiglucagon Pharmacokinetics

Absorption

Bioavailability

Following sub-Q administration in patients with type 1 diabetes mellitus, mean peak plasma concentration attained in approximately 35 minutes in adults^{1 9} and 21 minutes in pediatric patients.¹

Mean increase in glucose concentration from baseline to 90 minutes was 168 mg/dL in adults;¹ mean increase in glucose concentration from baseline to 60 minutes was 162 mg/dL in pediatric patients.¹

Onset

In adults with controlled insulin-induced hypoglycemia (mean baseline glucose concentration of 55–58.8 mg/dL), median time to plasma glucose recovery (increase of ≥20 mg/dL) was 10 minutes (numerically similar to 12-minute recovery time with glucagon).^{1 2 3}

In pediatric patients with controlled insulin-induced hypoglycemia (mean baseline glucose concentration of 72 mg/dL), median time to plasma glucose recovery (increase of ≥20 mg/dL) was 10 minutes (numerically similar to 10-minute recovery time with glucagon).^{1 4}

Elimination

Metabolism

Undergoes proteolytic degradation.¹

Elimination Route

Eliminated via proteolytic degradation in the blood, liver, and kidneys (similar to endogenous glucagon).¹

Half-life

Approximately 30 minutes.^{1 9}

Stability

Storage

Parenteral

Injection

2–8°C (store away from the refrigerator cooling element).¹ Do not freeze.¹ May store at 20–25°C for up to 12 months but not beyond the expiration date stated on the package.¹ Record the date when the product was removed from refrigerated storage.¹ Do not return to refrigerator after room temperature storage.¹ Store in the protective case provided by manufacturer; protect from light.¹

Actions

• Antihypoglycemic agent that increases blood glucose concentration by activating hepatic glucagon receptors, thereby stimulating hepatic glycogenolysis and release of glucose from the liver.^{1 7}

• Peptide analog of human glucagon, a hormone synthesized and secreted by the α₂ cells of the pancreatic islets of Langerhans.^{1 5} Dasiglucagon consists of 29 amino acids with 7 amino acid substitutions relative to glucagon that increase stability of the drug in aqueous solution at physiologic pH.^{1 6 8 9}

• Potency at the human glucagon receptor is similar to that of glucagon.⁷

• Availability of dasiglucagon injection and more stable parenteral and intranasal formulations of glucagon provide opportunities to expand use of this hormone in managing insulin-induced hypoglycemia in nonhospital settings.^{5 6 8}

Advice to Patients

• Importance of advising patients and their family members or caregivers to read the manufacturer's patient information and instructions for use of dasiglucagon.¹

• Importance of instructing patients and their family members or caregivers on how to recognize severe hypoglycemia, the risks of prolonged hypoglycemia, appropriate use of dasiglucagon, and proper use of the auto-injectors and/or prefilled syringes.¹

• Risk of allergic reactions.¹ Importance of advising patients to seek immediate medical attention if they experience any symptoms of serious hypersensitivity reactions.¹

• Inform patients that the inside of the auto-injector cap and the inside of the needle cover of the prefilled syringe contain dry natural rubber, which may cause allergic reactions in patients with latex allergy.¹

• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.¹

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.¹

• Importance of informing patients of other important precautionary information.¹ (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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