Anaphylaxis has been reported after administration of ecallantide. Because of the risk of anaphylaxis, ecallantide should only be administered by a health care provider with appropriate medical support to manage anaphylaxis and hereditary angioedema. Health care providers should be aware of the similarity of symptoms between hypersensitivity reactions and hereditary angioedema, and patients should be monitored closely. Do not administer ecallantide to patients with known clinical hypersensitivity to ecallantide.
Hereditary angioedema (HAE), treatment:
Children 8 to <12 years of age: Limited data available (Frank 2016): SubQ: 30 mg (as three 10 mg [1 mL] injections); dosing based on data pooled from 4 clinical studies (n=29, ages 9 to 17 years including 25 who received at least 1 dose of ecallantide) (MacGinnitie 2013) and a single case report in an 8-year-old (Dy 2013); efficacy was observed with no adverse events reported.
Children ≥12 years and Adolescents: SubQ: 30 mg (as three 10 mg [1 mL] injections); if attack persists, may repeat an additional 30 mg within 24 hours.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
(For additional information see "Ecallantide: Drug information")
Hereditary angioedema attacks, treatment:
Note: Because of the risk of anaphylaxis, self-administration at home is not recommended; however, may be administered at home by a trained health care professional. Shortening the time between symptom onset and drug administration helps minimize morbidity and mortality (US HAEA [Busse 2021]).
SUBQ: 30 mg once, administered as three 10 mg (1 mL) injections into skin of the abdomen, upper arm, or thigh, ≥2 inches apart, and away from the location of angioedema; if attack persists after ≥1 hour, may repeat 1 additional 30 mg dose within 24 hours (Zuraw 2022; manufacturer's labeling).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Subcutaneous [preservative free]:
Kalbitor: 10 mg/mL (1 mL)
No
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/125277s081lbl.pdf#page=13, must be dispensed with this medication.
Note: Administer only by a health care provider in presence of appropriate medical support to manage anaphylaxis and hereditary angioedema.
Parenteral: SubQ: Administer as 3 (10 mg/mL each) injections subcutaneously into skin of abdomen, upper arm, or thigh (do not administer at site of attack). Recommended needle size is 27 gauge. Separate injections by 2 inches (5 cm). May inject all doses in same or different location; rotation of sites is not necessary. Do not self-administer. Monitor/observe for hypersensitivity.
SubQ: Administer as 3 (10 mg/mL each) injections subcutaneously into skin of abdomen, upper arm, or thigh (do not administer at site of attack). Recommended needle size is 27 gauge. Separate injections by 2 inches (5 cm). May inject all doses in same or different location; rotation of sites is not necessary. Monitor/observe for hypersensitivity. Should only be administered by a health care professional; not for self-administration.
Store at 2°C to 8°C (36°F to 46°F). Protect from light. May be stored for up to 14 days at <30°C (<86°F).
Treatment of acute attacks of hereditary angioedema (HAE) (FDA approved in ages ≥12 years and adults)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Central nervous system: Headache (8% to 16%), fatigue (12%)
Gastrointestinal: Nausea (5% to 13%), diarrhea (4% to 11%)
Immunologic: Antibody development (IgE: 5% to 20%; neutralizing: 9%)
1% to 10%:
Dermatologic: Pruritus (5%), skin rash (3%), urticaria (2%)
Gastrointestinal: Vomiting (6%), upper abdominal pain (5%)
Hypersensitivity: Anaphylaxis (4%)
Local: Injection site reaction (3% to 7%; includes bruising, erythema, irritation, pain, pruritus, urticaria)
Respiratory: Upper respiratory tract infection (8%), nasopharyngitis (3% to 6%)
Miscellaneous: Fever (4% to 5%)
<1%, postmarketing, and/or case reports: Hypersensitivity reaction (chest discomfort, flushing, pharyngeal edema, rhinorrhea, sneezing, nasal congestion, throat irritation, wheezing, hypotension)
Hypersensitivity to ecallantide or any component of the formulation
Concerns related to adverse effects:
• Hypersensitivity reactions: [US Boxed Warning]: Serious hypersensitivity reactions, including anaphylaxis have been reported; administer only by health care provider in presence of appropriate medical support to manage anaphylaxis and hereditary angioedema. Do not administer to patients with known hypersensitivity to ecallantide. Reactions usually occur within 1 hour and may include chest discomfort, flushing, hypotension, nasal congestion, pharyngeal edema, pruritus, rash, rhinorrhea, sneezing, throat irritation, urticaria, and wheezing. Signs/symptoms of hypersensitivity reactions may be similar to those associated with hereditary angioedema attacks; therefore, consideration should be given to treatment methods; monitor patients closely.
• Immunogenicity: Some patients may develop antibodies to ecallantide during therapy; seroconversion may increase the risk of hypersensitivity reaction.
Other warnings/precautions:
• Appropriate use: The role of ecallantide in the management of patients with ACEI-induced angioedema is controversial (Bernstein 2015; Lewis 2015).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program
There are no known significant interactions.
Adverse effects were observed in animal reproduction studies. If treatment for hereditary angioedema (HAE) is needed during pregnancy, other agents are recommended (WAO/EEACI [Maurer 2018]).
Monitor for hypersensitivity reaction
Ecallantide is a recombinant protein which inhibits the conversion of high molecular weight kininogen to bradykinin by selectively and reversibly inhibiting plasma kallikrein. Unregulated bradykinin production is thought to contribute to the increased vascular permeability and angioedema observed in HAE.
Onset: 30 minutes to 4 hours (Epstein 2008)
Distribution: Vd: 26.4 ± 7.8 L
Half-life elimination: 2 ± 0.5 hours
Time to peak: ~2 to 3 hours
Excretion: Primarily urine
Solution (Kalbitor Subcutaneous)
10 mg/mL (per mL): $6,266.79
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