Icatibant (Monograph)

Brand name: Firazyr
Drug class: Bradykinin Receptor Antagonists
Chemical name: d-Arginyl-l-arginyl-l-prolyl-trans-4-hydroxy-l-prolylglycyl-3-(2-thienyl)-l-alanyl-l-seryl-d-1,2,3,4-tetrahydro-3-isoquinolinecarbonyl-l-(2α,3aβ,7aβ)-octahydro-1H-indole-2-carbonyl-l-arginine acetate (salt)
Molecular formula: C₅₉H₈₉N₁₉O₁₃S.xC₂H₄O₂
CAS number: 138614-30-9

Medically reviewed by Drugs.com on Jan 31, 2022. Written by ASHP.

Introduction

Synthetic decapeptide similar in structure to bradykinin; a selective bradykinin type 2 (B2) receptor antagonist.

Uses for Icatibant

Hereditary Angioedema

Treatment of acute attacks of hereditary angioedema (HAE); designated an orphan drug by FDA for this use.

Currently not FDA-labeled or recommended for prophylaxis of HAE attacks.

Icatibant Dosage and Administration

General

• Patients may self-administer drug after receiving training from healthcare provider.

Administration

Sub-Q Administration

Inject sub-Q into abdomen over at least 30 seconds until entire contents of syringe have been expelled; administer about 5–10 cm (2–4 inches) below the umbilicus and ≥5 cm (≥2 inches) from scars.

Use 25-gauge needle supplied by manufacturer; do not use any other needle.

Dosage

Available as icatibant acetate; dosage expressed in terms of icatibant.

Adults

Hereditary Angioedema

Sub-Q

Inject 30 mg at onset of acute attack. May repeat dose every 6 hours as needed for recurring symptoms or inadequate response, up to maximum of 3 doses (90 mg total) within a 24-hour period.

Prescribing Limits

Adults

Hereditary Angioedema

Sub-Q

Maximum 90 mg in 24-hour period.

Special Populations

Hepatic Impairment

No dosage adjustment required.

Renal Impairment

No dosage adjustment required.

Geriatric Patients

No dosage adjustment required.

Cautions for Icatibant

Contraindications

• No known contraindications.

Warnings/Precautions

Warnings

Laryngeal Attacks

Risk of airway obstruction during acute laryngeal HAE attack; immediately seek medical attention in appropriate healthcare facility in addition to treatment with icatibant.

Specific Populations

Pregnancy

Category C.

Lactation

Distributed into milk in rats; not known whether distributed into human milk. Use caution.

Pediatric Use

Safety and efficacy in patients <18 years of age not established.

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger patients.

Common Adverse Effects

Injection site reactions (e.g., bruising, hematoma, burning, erythema, hypoesthesia, irritation, numbness, edema, pain, pressure sensation, pruritus, swelling, urticaria, warmth), pyrexia, elevated serum aminotransferase concentrations, dizziness, rash.

Interactions for Icatibant

No formal drug interaction studies to date. However, icatibant is not metabolized by CYP isoenzymes.

Specific Drugs

Icatibant Pharmacokinetics

Absorption

Bioavailability

Mean absolute bioavailability of approximately 97% when given sub-Q dose.

Peak plasma concentrations achieved after approximately 0.75 hours after sub-Q dose.

Special Populations

Hepatorenal syndrome (Cl_cr 30–60 mL/minute): Plasma concentrations similar to those in patients with normal renal function.

Geriatric patients (male and female): AUC increased approximately twofold compared with young men and women.

Patients with low body weight: Increased systemic exposure.

Female patients (with typically lower body weight than males): AUC and peak plasma concentration increased approximately twofold compared with males.

Distribution

Extent

Distributed into milk in rats; not known whether distributed into human milk.

Elimination

Metabolism

Metabolized extensively by proteolytic enzymes.

Elimination Route

Excreted principally in urine as inactive metabolites.

Half-life

Approximately 1.4 hours.

Special Populations

Mild to moderate hepatic impairment (Child-Pugh score 5–8): Following continuous IV infusion^{† [off-label]}, pharmacokinetic parameters similar to those in healthy individuals.

Hepatic impairment (Child-Pugh score 7–15): Clearance similar to that in healthy individuals.

Geriatric patients: Reduced clearance, resulting in increased systemic exposure.

Patients with low body weight: Reduced clearance, resulting in increased systemic exposure.

Stability

Storage

Parenteral

Injection

2–25°C. Do not freeze. Protect from light.

Actions

• A synthetic decapeptide similar in structure to bradykinin; a selective bradykinin type 2 (B2) receptor antagonist.

• HAE is a rare autosomal-dominant genetic disorder characterized by a mutation in the complement 1 (C1)-inhibitor gene; deficiency in C1-esterase inhibitor results in unrestrained activity of plasma kallikrein and elevated bradykinin levels, which leads to increased vascular permeability and angioedema.

• Competitive inhibition of the bradykinin B2 receptor reduces the vasodilatory effects of excess bradykinin.

Advice to Patients

• Advise patients of maximum dosage; do not administer >3 doses of 30 mg each (total of 90 mg) within a 24-hour period.

• Advise patients to immediately seek medical attention after treating a laryngeal HAE attack with icatibant.

• Risk of injection site reactions. Importance of patients informing clinicians if any erythema, bruising, swelling, warmth, burning sensation, pruritus, irritation, urticaria, numbness, pressure, or pain occurs at injection site.

• Risk of pyrexia, elevated serum aminotransferases (ALT, AST), and rash.

• Risk of fatigue, drowsiness, and dizziness; do not perform hazardous activities requiring mental alertness or physical coordination (e.g., operating machinery, driving a motor vehicle) if such symptoms occur.

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

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

• Importance of informing patients of other important precautionary information. (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.

Reload page with references included

Frequently asked questions

• How long does Firazyr take to work?
• How do you administer/inject Firazyr?
• What is Firazyr used for?

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