DRUG INTERACTIONS(summary)

 • Beta-blockers: Patients taking beta-blockers may have a transient increase in pulse and blood pressure.

 • Indomethacin: In patients taking indomethacin, ZEGALOGUE may lose its ability to raise blood glucose or may produce hypoglycemia.

 • Warfarin: ZEGALOGUE may increase the anticoagulant effect of warfarin. 

 DRUG INTERACTIONS-(details)

 Clinically Significant Drug Interactions with ZEGALOGUE                                 

• Beta-Blockers Clinical Impact:                                                                                           Patients taking beta-blockers may have a transient increase in pulse and blood pressure when given ZEGALOGUE

• Indomethacin Clinical Impact:                                                                                        In patients taking indomethacin, ZEGALOGUE may lose its ability to raise blood glucose or may even produce hypoglycemia.

• Warfarin Clinical Impact:                                                                                       ZEGALOGUE may increase the anticoagulant effect of warfarin.

BRIEF SUMMARY

DASIGLUCAGON-(Mar 2021)

Indn-   To treat severe hypoglycemia   

Comp-    Injection:                                                                                                                              • 0.6 mg/0.6 mL single-dose autoinjector

             • 0.6 mg/0.6 mL single-dose prefilled syringe                                                                      autoinjector and prefilled syringe are for subcutaneous injection only.     

           • The dose in adults and pediatric patients aged 6 years and older is 0.6 mg.                                                                  

ADR-   Most common adverse reactions are: Adults: nausea, vomiting, headache, diarrhea, and injection site pain Pediatrics: nausea, vomiting, headache, and injection site pain

CI- Pheochromocytoma ,Insulinoma 

WARNINGS-

 • Substantial Increase in Blood Pressure in Patients with Pheochromocytoma: Contraindicated in patients with pheochromocytoma because  may stimulate the release of catecholamines from the tumor.

Pat Inform-

Recognition of Severe Hypoglycemia-                                                                           Inform patient and family members or caregivers on how to recognize the signs and symptoms of severe hypoglycemia and the risks of prolonged hypoglycemia.

Serious Hypersensitivity-                                                                                         Inform patients that allergic reactions can occur with glucagon products like 

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U.S. FDA APPROVED DRUGS SURING 2021                                          

Serial No 14

Name of the Drug-    ZEGALOGUE

Active Ingredient -   Dasiglucon

Pharmacological Classification-   To treat severe hypoglycemia                                                                                                                                                                                       

Date of Approval-          3/22/2021

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use                              ZEGALOGUE® safely and effectively.                                                                              See full prescribing information for ZEGALOGUE. ZEGALOGUE (dasiglucagon) injection, for subcutaneous use

Initial U.S. Approval: 2021

 INDICATIONS AND USAGE -                                          

ZEGALOGUE is an antihypoglycemic agent indicated for the treatment of severe hypoglycemia in pediatric and adult patients with diabetes aged 6 years and above. 

ADVERSE REACTIONS

 Most common adverse reactions (=2%) associated with ZEGALOGUE are: Adults: nausea, vomiting, headache, diarrhea, and injection site pain Pediatrics: nausea, vomiting, headache, and injection site pain

.

 CONTRAINDICATIONS-

Pheochromocytoma ,Insulinoma 

WARNINGS AND PRECAUTIONS

 • Substantial Increase in Blood Pressure in Patients with Pheochromocytoma: Contraindicated in patients with pheochromocytoma because ZEGALOGUE may stimulate the release of catecholamines from the tumor.

 • Hypoglycemia in Patients with Insulinoma: In patients with insulinoma, administration may produce an initial increase in blood glucose, but ZEGALOGUE may stimulate exaggerated insulin release from an insulinoma and cause subsequent hypoglycemia.

If a patient develops symptoms of hypoglycemia after a dose of ZEGALOGUE, give glucose orally or intravenously.

 • Hypersensitivity and Allergic Reactions: Allergic reactions have been reported with glucagon products and may include generalized rash, and in some cases anaphylactic shock with breathing difficulties and hypotension.

 • Lack of Efficacy in Patients with Decreased Hepatic Glycogen: ZEGALOGUE 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 ZEGALOGUE to be effective. Patients with these conditions should be treated with glucose. 

DOSAGE AND ADMINISTRATION

• ZEGALOGUE autoinjector and prefilled syringe are for subcutaneous injection only.     

• The dose in adults and pediatric patients aged 6 years and older is 0.6 mg.               

 • Administer ZEGALOGUE according to the printed instructions on the protective case label and the Instructions For Use.

 • Visually inspect ZEGALOGUE prior to administration. The solution should appear clear, colorless, and free from particles. If the solution is discolored or contains particulate matter, do not use.

 • Administer the injection into the lower abdomen, buttocks, thigh, or outer upper arm.

 • Call for emergency assistance immediately after administering the d

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

 • When the patient has responded to treatment, give oral carbohydrates.

 • Do not attempt to reuse ZEGALOGUE. Each device contains a single dose of dasiglucagon and cannot be reused.

DOSAGE FORMS AND STRENGTHS-                                                                        Injection:                                                                                                                              • 0.6 mg/0.6 mL single-dose autoinjector

 • 0.6 mg/0.6 mL single-dose prefilled syringe

 PATIENT COUNSELING INFORMATION

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

Recognition of Severe Hypoglycemia-                                                                           Inform patient and family members or caregivers on how to recognize the signs and symptoms of severe hypoglycemia and the risks of prolonged hypoglycemia.

Administration-                                                                                                              Review the Patient Information and Instructions For Use with the patient and family members or caregivers.

Serious Hypersensitivity-                                                                                         Inform patients that allergic reactions can occur with glucagon products like ZEGALOGUE.

Advise patients to seek immediate medical attention if they experience any symptoms of serious hypersensitivity reaction

Manufactured by: Zealand Pharma A/S, 2860 Søborg, Denmark

 CLINICAL PHARMACOLOGY

1. Mechanism of Action-                                                                                         Dasiglucagon is a glucagon receptor agonist, which 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 dasiglucagon to produce an antihypoglycemic effect.

2. Pharmacodynamics-                                                                                                 After administration of ZEGALOGUE in adult patients with type 1 diabetes, the mean glucose increase from baseline at 90 minutes was 168 mg/dL

 Mean Glucose (mg/dL) ZEGALOGUE 230 210 190 170 150 130 110 90 70 50 250 0 10 20 30 40 50 60 70 80 90 Time (minutes) 

Mean plasma glucose over time in adults with type 1 diabetes administered 0.6 mg dasiglucagon In pediatric patients (7 to 17 years) with type 1 diabetes, the mean glucose increase at 60 minutes after administration of ZEGALOGUE was 162 mg/dL

Mean Glucose (mg/dL) 250 230 210 190 170 150 130 110 90 70 50 6-11 years 12-17 years 0 10 20 30 40 50 60 70 80 90 Time (minutes) 

Mean plasma glucose over time in pediatric patients with type 1 diabetes administered 0.6 mg dasiglucagon

Cardiac Electrophysiology -                                                                                           At a dose resulting in more than 5 times the concentration achieved with the recommended therapeutic dose, ZEGALOGUE does not prolong the QT interval to any clinically relevant extent.

3 Pharmacokinetics-                                                                                                Absorption -                                                                                                             ZEGALOGUE absorption following subcutaneous injection of 0.6 mg resulted in a mean peak plasma concentration of 5110 pg/mL (1510 pmol/L) at around 35 minutes.

Distribution-                                                                                                                  The mean apparent volume of distribution was 47 L to 57 L following subcutaneous administration. Elimination The half-life was approximately 30 minutes.

Metabolism -                                                                                                                Metabolism data indicated that dasiglucagon is cleared like native glucagon through proteolytic degradation pathways in blood, liver, and kidney.

Specific Populations -                                                                                                        After administration of ZEGALOGUE in pediatric patients with type 1 diabetes, the mean peak plasma concentration of 3920 pg/mL occurred at around 21 minutes. 

USE IN SPECIFIC POPULATIONS

1 Pregnancy Risk Summary -                                                                                   There are no available data on dasiglucagon use in pregnant women to evaluate for a drugassociated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes.

Untreated hypoglycemia in pregnancy can cause complications and may be fatal. In animal reproduction studies, daily subcutaneous administration of dasiglucagon to pregnant rabbits and rats during the period of organogenesis did not cause adverse developmental effects at exposures 7 and 709 times the human dose of 0.6 mg based on AUC, respectively

2. Lactation Risk Summary- There is no information on the presence of dasiglucagon in either human or animal milk, or the effects of the drug on the breastfed infant or milk production.

Dasiglucagon is a peptide and would be expected to be broken down to its constituent amino acids in the infant's digestive tract and is therefore unlikely to cause harm to an exposed infant.

3. Pediatric Use-                                                                                                            The safety and effectiveness of ZEGALOGUE for the treatment of severe hypoglycemia in patients with diabetes have been established in pediatric patients aged 6 years and above.

Use of ZEGALOGUE for this indication is supported by evidence from a study in 42 pediatric patients with type 1 diabetes 

The safety and effectiveness of ZEGALOGUE have not been established in pediatric patients younger than 6 years of age.

4. Geriatric Use-                                                                                                      Clinical studies of ZEGALOGUE included too few patients 65 years of age and older to determine whether these patients respond differently from younger adult patients.

 OVERDOSAGE-

If overdosage occurs, the patient may experience nausea, vomiting, inhibition of GI tract motility, and/or increases in blood pressure and heart rate.

In case of suspected overdosing, serum potassium may decrease and should be monitored and corrected if needed.

If the patient develops a marked 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.

Appropriate supportive treatment should be initiated according to the patient’s clinical signs and symptoms