Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Subcutaneous [preservative free]:
Firazyr: 30 mg/3 mL (3 mL)
Generic: 30 mg/3 mL (3 mL)
Pharmacology
Mechanism of Action
Icatibant is a selective competitive antagonist for the bradykinin B2 receptor. Patients with HAE have an absence or dysfunction of C1-esterase-inhibitor which leads to the production of bradykinin. The presence of bradykinin may cause symptoms of localized swelling, inflammation, and pain. Icatibant inhibits bradykinin from binding at the B2 receptor, thereby treating the symptoms associated with acute attack.
Pharmacokinetics/Pharmacodynamics
Distribution
Vdss:
Children ≥2 years: 0.39 ± 0.11 L/kg (Farkas 2017)
Adolescents: 0.44 ± 0.18 L/kg (Farkas 2017)
Adults: 29 ± 8.7 L
Metabolism
Metabolized by proteolytic enzymes to metabolites (inactive)
Excretion
Urine (<10% unchanged)
Onset of Action
Median time to 50% decrease of symptoms: ~2 hours
Time to Peak
Children ≥2 years: 0.42 ± 0.13 hours (Farkas 2017)
Adolescents: 0.55 ± 0.19 hours (Farkas 2017)
Adults: ~0.75 hours
Duration of Action
Inhibits symptoms caused by bradykinin for ~6 hours
Half-Life Elimination
Children ≥2 years: 0.8 ± 0.04 hours (Farkas 2017)
Adolescents: 1.34 ± 0.96 hours (Farkas 2017)
Adults: 1.4 ± 0.4 hours
Use in Specific Populations
Special Populations: Elderly
Elderly subjects had a 2-fold higher AUC compared with younger subjects. Only minor differences (12% to 14%) in Cmax were observed.
Special Populations: Gender
Women have a 2-fold higher AUC and Cmax compared with men because of differences in body weight.
Use: Labeled Indications
Hereditary angioedema: Treatment of acute attacks of hereditary angioedema (HAE)
Use: Off Label
Angiotensin-converting enzyme inhibitor–induced angioedema, severe or life-threateningb
Data regarding the efficacy of icatibant for the treatment of angiotensin-converting enzyme (ACE) inhibitor-induced angioedema involving the upper aerodigestive tract (ie, face, lips, cheeks, tongue, soft palate or uvula, pharynx, larynx) are conflicting. In 2 randomized, double-blind, placebo-controlled studies, no difference in time for meeting discharge criteria or resolution of symptoms was found between icatibant and placebo
Contraindications
There are no contraindications listed in the manufacturer’s labeling.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to icatibant acetate or any component of the formulation.
Dosage and Administration
Dosing: Adult
Hereditary angioedema: SubQ: 30 mg; may repeat every 6 hours if response is inadequate or symptoms recur (maximum dose: 90 mg/day).
Angiotensin-converting enzyme inhibitor–induced angioedema, severe or life-threatening (off-label use): SubQ: 30 mg; a second 30 mg injection may be administered if symptoms of angioedema continue to worsen after 6 hours (Baş 2015; Hirschy 2018). Note: Most likely to be effective if administered within the first few hours of angioedema attack (ie, ≤6 hours) when swelling is increasing and has not yet peaked and/or stabilized (Baş 2015; Guyer 2019). IV prednisolone (not available in the US) was administered with the second dose of icatibant (Baş 2015).
Dosing: Geriatric
Refer to adult dosing.
Dosing: Pediatric
Hereditary angioedema (HAE): Limited data available: Children ≥2 years and Adolescents: SubQ: 0.4 mg/kg once; maximum dose: 30 mg/dose. Dosing based on an open-label study of 32 patients (mean age: 12.3 ± 3.5 years) with HAE (Farkas 2017).
Administration
SubQ: For SubQ injection only. Patients may self-administer upon recognition of an HAE attack. Inject into the abdomen over ≥30 seconds, using the 25 gauge needle provided. Inject 2 to 4 inches below belly button and away from any scars; do not inject into an area that is bruised, swollen, or painful.
Storage
Store between 2°C to 25°C (36°F to 77°F); do not freeze. Store in original container until time of administration.
Drug Interactions
Angiotensin-Converting Enzyme Inhibitors: Icatibant may diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors. Monitor therapy
Adverse Reactions
>10%: Local: Injection site reaction (97%)
1% to 10%:
Central nervous system: Dizziness (3%)
Hepatic: Increased serum transaminase (4%)
Miscellaneous: Fever (4%)
<1%: Antibody development (anti-icatibant, no association with efficacy observed), chest pain, headache, myocardial infarction, nausea, skin rash
Warnings/Precautions
Concerns related to adverse effects:
- Airway obstruction: Airway obstruction may occur during acute laryngeal attacks of HAE. Patients with laryngeal attacks should be instructed to seek medical attention immediately in addition to treatment with icatibant.
- CNS effects: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).
Monitoring Parameters
Symptom relief; laryngeal symptoms or airway obstruction (immediate medical attention required in addition to icatibant therapy)
Pregnancy
Pregnancy Risk Factor
C
Pregnancy Considerations
Adverse events were observed in some animal reproduction studies.
Information related to the use of icatibant in pregnancy is limited (Boufleur 2014; Farkas 2016; Kaminsky 2017; Tran 2013; Zanichelli 2015). When treatment for hereditary angioedema (HAE) in pregnancy is needed, other agents are recommended (WAO/EEACI [Maurer 2018]).
Patient Education
What is this drug used for?
- It is used to treat swelling attacks in people with hereditary angioedema (HAE).
Frequently reported side effects of this drug
- Dizziness
- Nausea
- Headache
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Severe injection site irritation
- Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
