Ecallantide

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Subcutaneous [preservative free]:

Kalbitor: 10 mg/mL (1 mL)

Pharmacology

Mechanism of Action

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.

Pharmacokinetics/Pharmacodynamics

Distribution

V_d: 26.4 ± 7.8 L

Excretion

Primarily urine

Onset of Action

30 minutes to 4 hours (Epstein 2008)

Time to Peak

~2 to 3 hours

Half-Life Elimination

2 ± 0.5 hours

Use: Labeled Indications

Hereditary angioedema: Treatment of acute attacks of hereditary angioedema (HAE) in patients 12 years and older

Contraindications

Hypersensitivity to ecallantide or any component of the formulation

Dosage and Administration

Dosing: Adult

Hereditary angioedema (HAE) treatment: SubQ: 30 mg (as three 10 mg [1 mL] injections); if attack persists, may repeat an additional 30 mg within 24 hours

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

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.

Administration

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.

Storage

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).

Drug Interactions

There are no known significant interactions.

Adverse Reactions

>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)

Warnings/Precautions

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).

Monitoring Parameters

Monitor for hypersensitivity reaction

Pregnancy

Pregnancy Risk Factor

C

Pregnancy Considerations

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]).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience headache, loss of strength and energy, nausea, vomiting, common cold symptoms, sore throat, throat irritation, diarrhea, or abdominal pain. Have patient report immediately to prescriber severe injection site irritation, difficulty swallowing, shortness of breath, dizziness, passing out, fast heartbeat, abnormal heartbeat, anxiety, flushing, runny nose, stuffy nose, or sneezing (HCAHPS).
• Educate patient about signs of a significant reaction (eg, 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. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.