FIRAZYR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FIRAZYR (FIRAZYR).
Icatibant is a selective antagonist of the bradykinin B2 receptor, blocking the binding of bradykinin and thereby inhibiting the increased vascular permeability and vasodilation that underlie acute attacks of hereditary angioedema (HAE).
| Metabolism | Icatibant is not significantly metabolized; it is primarily eliminated by the kidney via glomerular filtration and proteolytic degradation. |
| Excretion | Primarily metabolized in the liver (hydrolysis by peptidases); renal excretion of metabolites (approximately 25% unchanged drug in urine). Less than 10% excreted in feces. |
| Half-life | Terminal half-life approximately 1.5 hours; clinically, effects last longer due to receptor binding kinetics. |
| Protein binding | Approximately 90–95% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution approximately 0.3 L/kg, indicating limited extravascular distribution. |
| Bioavailability | Subcutaneous administration: bioavailability approximately 97% (nearly complete). No oral formulation. |
| Onset of Action | Subcutaneous injection: rapid onset within 15–30 minutes, with peak effect at 2 hours. |
| Duration of Action | Duration of action approximately 4–6 hours; may persist up to 8 hours for some patients. Single injection provides symptomatic relief during an acute attack. |
30 mg subcutaneously every 3 days. For acute attacks, 30 mg subcutaneously as needed, not to exceed 3 doses in 24 hours.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not studied in severe renal impairment (CrCl <30 mL/min) or end-stage renal disease; use with caution. |
| Liver impairment | No dose adjustment required for mild hepatic impairment (Child-Pugh class A). Not studied in moderate to severe hepatic impairment (Child-Pugh class B or C); use with caution. |
| Pediatric use | Not approved for pediatric use. Safety and efficacy not established in patients <18 years. |
| Geriatric use | No specific dose adjustment recommended; however, clinical studies did not include sufficient numbers of patients aged ≥65 years to determine whether they respond differently. Use with caution due to potential age-related renal or hepatic function decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for FIRAZYR (FIRAZYR).
| Breastfeeding | It is not known whether icatibant is excreted in human milk. In lactating rats, icatibant was detected in milk at concentrations approximately 0.5% of maternal plasma levels, yielding a milk-to-plasma (M/P) ratio of approximately 0.005. Because many drugs are excreted in human milk, caution should be exercised when FIRAZYR is administered to a breastfeeding woman. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for FIRAZYR and any potential adverse effects on the breastfed child from the drug or underlying maternal condition. |
| Teratogenic Risk | FIRAZYR (icatibant) is a bradykinin B2 receptor antagonist. There are no adequate and well-controlled studies in pregnant women. In animal reproduction studies, no evidence of fetal harm was observed at doses up to 2.2 times the maximum recommended human dose (MRHD) in rats and 1.5 times the MRHD in rabbits. However, because animal studies are not always predictive of human response, FIRAZYR should be used during pregnancy only if clearly needed. The risk of teratogenicity in the first trimester is unknown but considered low based on limited data. No specific fetal risks have been identified for any trimester. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Hypersensitivity to icatibant or any of its excipients"]
| Precautions | ["Laryngeal attacks: Promptly treat with icatibant; seek immediate medical attention due to risk of airway obstruction.","Hypersensitivity reactions: Including anaphylaxis, have been reported; discontinue if severe reaction occurs.","Not for prophylaxis: Icatibant is not approved for routine prophylactic use to prevent HAE attacks.","Administration: For subcutaneous use only; do not administer intravenously or intramuscularly."] |
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| Fetal Monitoring | There are no specific monitoring requirements for FIRAZYR during pregnancy beyond standard obstetric care. However, because FIRAZYR is used for acute attacks of hereditary angioedema (HAE), maternal respiratory and hemodynamic status should be monitored during and after administration. Fetal monitoring (e.g., fetal heart rate) may be considered if clinically indicated, especially in cases of maternal hypoxia or hypotension. No specific laboratory monitoring is required. |
| Fertility Effects | In animal studies, there was no evidence of impaired fertility in male or female rats at doses up to 2.2 times the MRHD. Human data are lacking. However, since HAE itself may have effects on reproductive health due to hormonal influences, it is difficult to attribute any fertility changes directly to FIRAZYR. Overall, FIRAZYR is not expected to adversely affect fertility in humans. |