Icatibant (Firazyr) inhibits the binding of bradykinin to its receptors alleviating the acute symptoms of angioedema such as facial and lips swelling and airway edema. C-1 esterase is deficient or dysfunctional in patients with hereditary angioedema that results in the production of uncontrolled release of bradykinin.

Icatibant Uses:

• Hereditary angioedema:

  • It is indicated for aborting the acute attacks of hereditary angioedema (HAE).

• Off Label Use of Icatibant in Adults:

  • It may be used in the treatment of severe or life-threatening angioedema induced by an angiotensin-converting enzyme inhibitor.

Icatibant (Firazyr) Dose in Adults:

Icatibant (Firazyr) Dose in the treatment of hereditary angioedema:

• SubQ: 30 mg;
• The dose may be repeated every 6 hours if the symptoms recur or the response is not adequate until a maximum dose of 90 mg/day is reached.

Icatibant (Firazyr) Dose in the treatment of severe or life-threatening Angiotensin-converting enzyme inhibitor–induced angioedema:

• SubQ: 30 mg.
• A second dose of 30 mg subQ injection may be administered after 6 hours if the symptoms persist or worsen.

Note:

• It should best be administered within the first few hours of the angioedema attack (usually within six hours) when the swelling is noted, or increasing but not yet peaked.
• In some studies, intravenous prednisolone was administered with the second dose.

Icatibant (Firazyr) Dose in Childrens:

Icatibant (Firazyr) Dose in the treatment of Hereditary angioedema (HAE): 

• Children older than 2 years and Adolescents:

  • SubQ: 0.4 mg/kg once;
  • The maximum dose is 30 mg/dose.

Pregnancy Risk Factor C

• Its use in pregnancy is not known. Some studies on animal reproduction have shown adverse pregnancy outcomes.
• Pregnancy is a good time to try other therapies.

Icatibant use during breastfeeding:

• It is unknown if the drug will be excreted into breastmilk. 
• It is recommended that breastfeeding mothers avoid using the drug. 
• It is recommended that you use other safer agents during breastfeeding if they are available.

Dose in Kidney Disease:

• Adjustments in the dose are not recommended in patients with kidney disease.
• Since the drug is cleared by non-renal mechanisms, drug accumulation is less likely in patients with renal impairment.

Dose in Liver disease:

Adjustment in the dose is not necessary for patients with liver disease.

Common Side Effects of Icatibant:

• Local:

  • Injection site reaction

Less Common Side Effects of Icatibant:

• Central nervous system:

  • Dizziness

• Hepatic:

  • Increased serum transaminase

• Miscellaneous:

  • Fever

Contraindication to Icatibant (Firazyr):

The manufacturer's labeling does not contain any contraindications.

Canadian labeling: Allergies to icatibant Acetyl or any component of formulation

Warnings and precautions

• Obstructing the airway:

  • Acute airway obstruction may occur in patients who experience laryngeal attacks due to HAE. 
  • In the event of laryngeal attacks, patients should seek immediate medical attention.

• CNS effects

  • CNS depression may result. It can cause impairment of physical and mental capabilities, especially for those who operate heavy machinery or do tasks that require mental alertness like driving.

Icatibant: Drug Interaction

Monitoring parameters:

Monitor for the response to the treatment. Observe for laryngeal symptoms and airway obstruction. Patients must seek immediate medical attention in addition to the injection.

How to administer Icatibant (Firazyr)?

SubQ:

• It is administered as a SubQ injection only. It is best administered into the anterior abdomen over 30 seconds or more using a 25 gauge needle.
• The patients may self administer the injection as soon as the symptoms are noticed.
• The medicine is injected 2 to 4 inches below the belly button. It should not be injected into bruised areas, scars, swollen, or painful and erythematous areas.

Mechanism of action of Icatibant (Firazyr):

• It selectively inhibits bradykinin-receptor activation in patients with hereditary angiopathy. 
• Patients with hereditary angioedema have dysfunction of or lack C1-esterase-inhibitor. 
• This results in an increase in bradykinin.
• Bradykinin excess can cause swelling, inflammation, pain, and pain at specific sites (primarily the lips, airways and face). Icatibant blocks bradykinin binding to its receptors, which can alleviate the symptoms of the disease.

Initial:

• In less than 2 hours, symptoms can improve by up to 50%.

Duration:

• Inhibits symptoms caused by bradykinin for ~6 hours

Metabolism:

• It is metabolized to inactive metabolites by proteolytic enzymes.

Bioavailability:

• About 97%

Half-life elimination:

• Children ≥2 years: 0.8 ± 0.04 hours.
• Adolescents: 1.34 ± 0.96 hours.
• Adults: 1.4 ± 0.4 hours

Time to peak:

• Children 2 years of age or older: 0.42 ± 0.13 hours.
• Adolescents: 0.55 ± 0.19 hours.
• Adults: about 0.75 hours

Excretion:

• Urine (<10% unchanged)

International Brand Names of Icatibant:

• Firazyr

Icatibant Brand Names in Pakistan:

No Brands Available in Pakistan.