Introduction
Kalbitor (ecallantide) is a plasma kallikrein inhibitor approved for the treatment of acute attacks of hereditary angioedema (HAE) in patients 12 years and older. HAE is a rare genetic disorder characterized by recurrent episodes of swelling in various body parts, including the extremities, face, larynx, abdomen, and genitals. Kalbitor represents a targeted therapeutic approach for managing these potentially life-threatening acute attacks.
Mechanism of Action
Ecallantide is a potent, selective, and reversible inhibitor of plasma kallikrein. In HAE, deficient or dysfunctional C1 esterase inhibitor leads to uncontrolled activation of the contact system, resulting in excessive plasma kallikrein activity. Plasma kallikrein cleaves high-molecular-weight kininogen to produce bradykinin, the primary mediator of vascular permeability and edema formation in HAE attacks. By inhibiting plasma kallikrein, ecallantide reduces bradykinin generation, thereby decreasing vascular permeability and alleviating HAE symptoms.
Indications
Kalbitor is indicated for:
- Treatment of acute attacks of hereditary angioedema in patients 12 years of age and older
Dosage and Administration
Standard dosing: 30 mg administered subcutaneously as three 10 mg injections- Administer in the abdominal area, thigh, or upper arm
- Injection sites should be at least 2 inches apart and away from the anatomical site of the attack
- Dosing is not weight-based
- Should be administered by a healthcare professional
- Observe patients for at least 1 hour following administration due to risk of anaphylaxis
- No dosage adjustment required for renal or hepatic impairment
- Safety and effectiveness in pediatric patients below 12 years have not been established
Pharmacokinetics
Absorption: Following subcutaneous administration, ecallantide reaches maximum plasma concentrations within 2-3 hours Distribution: Volume of distribution is approximately 35.8 L, suggesting limited extravascular distribution Metabolism: Primarily metabolized via proteolytic degradation pathways Elimination: Terminal half-life is approximately 2 hours; cleared primarily through proteolytic pathways Excretion: Not primarily excreted renally; specific elimination pathways not fully characterizedContraindications
- Known hypersensitivity to ecallantide or any component of the formulation
- Patients with known clinical hypersensitivity to Kalbitor, including anaphylaxis
Warnings and Precautions
Anaphylaxis: Serious hypersensitivity reactions, including anaphylaxis, have occurred. Reactions typically manifest within 1 hour of administration and may include urticaria, dyspnea, flushing, chest discomfort, and throat tightness. Healthcare professionals should be prepared to manage anaphylaxis, and patients should be observed for at least 1 hour after injection. Hypersensitivity reactions: Monitor patients for signs and symptoms of hypersensitivity reactions during and after treatment. Administration site reactions: Local injection site reactions may occur, including erythema, pruritus, and pain.Drug Interactions
No formal drug interaction studies have been conducted. However, based on its mechanism of action and metabolic pathway:
- Theoretical potential for interactions with other agents affecting the kallikrein-kinin system
- No known interactions with cytochrome P450 substrates, inhibitors, or inducers
- Clinical experience has not revealed significant interactions with concomitant medications
Adverse Effects
Most common adverse reactions (≥3%):- Headache (14%)
- Nausea (12%)
- Fatigue (8%)
- Diarrhea (7%)
- Pyrexia (5%)
- Injection site reactions (including erythema, pruritus, pain) (5%)
- Anaphylaxis (<1%)
- Hypersensitivity reactions
Monitoring Parameters
- Monitor for signs and symptoms of HAE attack resolution
- Observe for hypersensitivity reactions for at least 1 hour post-administration
- Assess injection sites for local reactions
- Monitor vital signs during and after administration
- Evaluate response to treatment and need for additional interventions
Patient Education
- Understand that Kalbitor is used to treat acute HAE attacks, not for prevention
- Be aware of the risk of serious allergic reactions, including anaphylaxis
- Recognize symptoms of hypersensitivity reactions: hives, difficulty breathing, chest tightness, swelling of face or throat
- Report any side effects or concerns to healthcare provider promptly
- Understand that administration must be performed by a healthcare professional
- Keep all follow-up appointments as recommended
References
1. Kalbitor® (ecallantide) [prescribing information]. Dyax Corp.; 2021. 2. Zuraw BL, Christiansen SC. HAE pathophysiology and underlying mechanisms. Clin Rev Allergy Immunol. 2016;51(2):216-229. 3. Bernstein JA, Qazi M. Ecallantide: its pharmacology, pharmacokinetics, clinical efficacy and tolerability. Expert Rev Clin Immunol. 2012;8(1):17-27. 4. Lumry WR, Castaldo AJ, Vernon MK, et al. The humanistic burden of hereditary angioedema: Impact on health-related quality of life, productivity, and depression. Allergy Asthma Proc. 2010;31(5):407-414. 5. Cicardi M, Banerji A, Bracho F, et al. Icat