SAJAZIR (icatibant)—a bradykinin B2-receptor antagonist1

Schematic diagram of the contact system, which controls clotting and inflammation (swelling) in the body. The contact system is regulated by a protein called a C1 inhibitor. In HAE the C1 inhibitor protein is faulty, leading to unpredictable swellings (HAE attacks) . These swellings are caused by the contact system when a peptide called bradykinin binds to B2 receptors and triggers an attack. SAJAZIR (icatibant) controls attacks in HAE by blocking the binding between bradykinin and B2 receptors.

Adapted from Zuraw BL, 2008 and Kaplan AP, 2010.7,8
HMWK = high-molecular-weight kininogen.

A Icon Bradykinin binding to the B2 receptor.

B Icon SAJAZIR inhibiting bradykinin from binding to the B2 receptor, preventing vascular leakage.

Most patients with hereditary angioedema (HAE) have an underlying deficiency of functional C1 esterase inhibitor that leads to an increase in plasma kallikrein activity, triggering an overproduction of bradykinin.2–6 This causes an increase in blood vessel permeability, which allows fluid to pass through the blood vessel walls causing subcutaneous or submucosal swelling.3,5

​SAJAZIR inhibits bradykinin from binding to the B2 receptor and thereby treats the clinical symptoms of an acute, episodic attack of HAE.1​

Most patients with hereditary angioedema (HAE) have an underlying deficiency of functional C1 esterase inhibitor that leads to an increase in plasma kallikrein activity, triggering an overproduction of bradykinin.2-6 This causes an increase in blood vessel permeability, which allows fluid to pass through the blood vessel walls causing subcutaneous or submucosal swelling.3,5

​SAJAZIR inhibits bradykinin from binding to the B2 receptor and thereby treats the clinical symptoms of an acute, episodic attack of HAE.1​

Schematic diagram of the contact system, which controls clotting and inflammation (swelling) in the body. The contact system is regulated by a protein called a C1 inhibitor. In HAE the C1 inhibitor protein is faulty, leading to unpredictable swellings (HAE attacks) . These swellings are caused by the contact system when a peptide called bradykinin binds to B2 receptors and triggers an attack. SAJAZIR (icatibant) controls attacks in HAE by blocking the binding between bradykinin and B2 receptors.

Adapted from Zuraw BL, 2008 and Kaplan AP, 2010.7,8
HMWK = high-molecular-weight kininogen.

Bradykinin binding to the B2 receptor.

SAJAZIR inhibiting bradykinin from binding to the B2 receptor, preventing vascular leakage.




References

  1. SAJAZIR™ (icatibant) Injection. Prescribing Information. Cycle Pharmaceuticals Limited.
  2. Zuraw BL, et al. J Allergy Clin Immunol Pract. 2013;1(5):458–467.
  3. Ghazi A, Grant JA. Biologics. 2013;7:103–113.
  4. Lumry W, et al. Journal of Infusion Nursing. 2020;43(3):134–145.
  5. Maurer M, et al. Allergy. 2018;73(8):1575–1596.
  6. El-Shanawany T. Hereditary Angioedema. British Society for Immunology. https://www.immunology.org/public-information/bitesized-immunology/immune-dysfunction/hereditary-angioedema (accessed October 2021). ​
  7. Zuraw BL. N Engl J Med. 2008;359(10):1027–1036.
  8. Kaplan AP, Joseph K. Ann Allergy Asthma Immunol. 2010;104(3):193–204.
View

Indication and Important Safety Information

SAJAZIR™ (Icatibant) injection is indicated for the treatment of acute attacks of hereditary angioedema (HAE) in adults 18 years of age and older.

Warnings and precautions: Given the potential for airway obstruction during acute laryngeal HAE attacks, patients should be advised to seek medical attention in an appropriate healthcare facility immediately in addition to treatment with SAJAZIR.

Adverse reactions: The most commonly reported adverse reactions were injection-site reactions, which occurred in almost all patients (97%) in clinical trials. These injection-site reactions included bruising, hematoma, burning, erythema, hypoesthesia, irritation, numbness, edema, pain, pressure sensation, pruritus, swelling, urticaria, and warmth.

Other common adverse reactions included pyrexia (4%), transaminase increase (4%), and dizziness (3%), as well as rash, nausea, and headache.

Drug interactions: Icatibant is a bradykinin B2 receptor antagonist and thereby has the potential to have a pharmacodynamic interaction with ACE inhibitors where SAJAZIR may attenuate the antihypertensive effect of ACE inhibitors. Clinical trials to date have excluded subjects taking ACE inhibitors.

Use in specific populations: Clinical studies of Icatibant included a limited number of subjects aged 65 and over. Elderly patients are likely to have increased systemic exposure. Reported clinical experience has not identified differences in efficacy and safety between elderly and younger patients.

Safety and effectiveness in patients below 18 years of age have not been established.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.

For more detailed information, please refer to the Full Prescribing Information.

To report SUSPECTED ADVERSE REACTIONS contact Cycle Pharmaceuticals at 1-800-836-4380, or the FDA at: 1-800-FDA-1088 or www.fda.gov/medwatch.

x

Indication

SAJAZIRTM (icatibant) injection is indicated for the treatment of acute attacks of hereditary angioedema (HAE) in adults 18 years of age and older.

Important Safety Information
Warnings and Precautions

Laryngeal Attacks. Given the potential for airway obstruction during acute laryngeal HAE attacks, patients should be advised to seek medical attention in an appropriate healthcare facility immediately in addition to treatment with SAJAZIR.

Adverse Reactions

The most commonly reported adverse reactions were injection site reactions, which occurred in almost all patients (97%) in clinical trials. Other common adverse reactions occurring in greater than 1% of patients included pyrexia (4%), transaminase increase (4%), dizziness (3%), and rash.

Postmarketing Experience

The following adverse reactions have been identified during post approval use of icatibant: urticaria.

Drug Interactions:

ACE Inhibitors. Icatibant is a bradykinin B2 receptor antagonist and thereby has the potential to have a pharmacodynamic interaction with ACE inhibitors where icatibant may attenuate the antihypertensive effect of ACE inhibitors. Clinical trials to date have excluded subjects taking ACE inhibitors.

Use in Specific Populations

Pregnancy: Available data from published literature and the pharmacovigilance database with icatibant use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes.

Lactation: The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for icatibant and any potential adverse effects on the breastfed child from icatibant or from the underlying maternal condition.

Pediatric Use: Safety and effectiveness in pediatric patients below the age of 18 years have not been established.

Geriatric Use: Elderly patients are likely to have increased systemic exposure to icatibant injection compared to younger (18-45 years) patients. No dose adjustment is recommended.

For more detailed information, please refer to the full Prescribing Information

To report SUSPECTED ADVERSE REACTIONS contact Cycle Pharmaceuticals at 1-800-836-4380, or the FDA at: 1-800-FDA-1088 or www.fda.gov/medwatch.