Generic Name: Ecallantide
Class: Complement Inhibitors
Molecular Formula: C305H442O91S8
CAS Number: 460738-39-9
Potential for severe hypersensitivity reactions (e.g., anaphylaxis).1 (See Sensitivity Reactions under Cautions.)
Clinicians should be aware of the similarity between symptoms of a hypersensitivity reaction and a hereditary angioedema (HAE) attack; administer only in a setting equipped to monitor and treat hypersensitivity reactions and HAE attacks.1
Do not administer to patients with known hypersensitivity to ecallantide.1
FDA approved a REMS for ecallantide to ensure that the benefits outweigh the risks. The REMS may apply to one or more preparations of ecallantide and consists of the following: communication plan. See the FDA REMS page () or the ASHP REMS Resource Center ().
Uses for Kalbitor
Designated an orphan drug by FDA for this use.7
Kalbitor Dosage and Administration
Administer only under supervision of qualified clinicians experienced in management of anaphylaxis and HAE and in a setting with appropriate and readily available medical support (e.g., antihistamines, epinephrine, corticosteroids) to manage such conditions.1 3 4 8 9 10 15
If persistent HAE attack symptoms are present, assess patient carefully prior to administration of second dose of ecallantide to determine whether symptoms represent HAE attack or hypersensitivity reaction.1 10 (See Sensitivity Reactions under Cautions.)
Vials are for single use only.1
To prepare a 30-mg dose: Withdraw 1 mL of ecallantide injection from a vial containing 10 mg/mL of the drug into an appropriately sized syringe using a large-bore needle.1 Perform procedure with each of 3 vials to prepare total dose (3 syringes each containing ecallantide 10 mg). 1
Prior to administration, replace large-bore needle on each syringe with a 27-gauge needle for sub-Q injection.1
Observe strict aseptic technique; drug vials contain no preservative.1
Inject sub-Q into abdomen, thigh, or upper arm.1 Use same anatomic site for all 3 injections or select different sites; separate injections administered at same site by 2 inches (5 cm) and inject away from site of HAE attack.1 Rotation of injection sites not necessary.1
If a second 30 mg-dose is required, may use same anatomic site as for initial dose or select different site.1
Patients ≥16 years of age: Maximum 60 mg (i.e., two 30-mg doses) in 24-hour period.1
No specific dosage recommendations.1
No specific dosage recommendations.1
Select dosage with caution; usually initiate therapy at low end of dosage range.1 (See Geriatric Use under Cautions.)
Cautions for Kalbitor
Risk of severe hypersensitivity reactions (e.g., chest discomfort, flushing, pharyngeal edema, pruritus, rhinorrhea, sneezing, nasal congestion, throat irritation, urticaria, wheezing, hypotension), including anaphylaxis.1 2 5 6 15 Monitor patient; such reactions usually occur within first hour following drug administration.9 10 15 (See General under Dosage and Administration.)
Because symptoms of hypersensitivity can resemble those of acute HAE attacks, carefully consider treatment method.1 9 10 15 Use of medical support for anaphylaxis (e.g., epinephrine, antihistamines, corticosteroids) may be required.1 2
Response to antihistamine and sympathomimetic therapy may distinguish between hypersensitivity reaction (a histamine-mediated event) and acute HAE attack (bradykinin-mediated event); hypersensitivity reactions likely to respond to this type of medical intervention, while HAE attack symptoms likely to be resistant.1 2
Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults; use with caution due to greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy in the elderly.1
Safety and efficacy not established.1
Safety and efficacy not established.1
Common Adverse Effects
Interactions for Kalbitor
No formal drug interaction studies to date.1
Not known whether distributed into milk.1
Pharmacokinetics not studied in patients with hepatic or renal impairment.1
Vials removed from refrigerator should be stored below 30°C and used within 14 days or returned to refrigeration until use.1
Prolongation of thrombin time (>30 seconds) reported rarely; however, no clinically important effects on coagulation parameters (i.e., aPTT, PT) in patients with HAE receiving the drug by sub-Q injection.2 5 14 No abnormal patterns or increased risk of bleeding or thrombosis.2 5 14 15
Advice to Patients
Importance of providing a medication guide to the patient each time the drug is administered.1 Importance of discussing potential risks and benefits of therapy with the patient; importance of the patient reading the medication guide prior to initiation of therapy and before subsequent treatment.1 11
Risk of hypersensitivity reactions, including anaphylaxis.1 Importance of immediately informing clinician of possible hypersensitivity symptoms (e.g., shortness of breath, cough, chest tightness, trouble breathing, dizziness, fainting, irregular heartbeat, anxiety, reddening of the face, itching, hives, feeling of warmth, swelling of the throat or tongue, throat tightness, hoarse voice, trouble swallowing, runny nose, sneezing).1 10 Inform patients that most reactions occur within 1 hour following sub-Q injection of ecallantide.10 Importance of not administering ecallantide to patients with a history of hypersensitivity to the drug.1 9 10
Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.1
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements.1
Importance of informing patients of other important precautionary information.1 (See Cautions.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Injection, for subcutaneous use
AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions June 1, 2012. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
1. Dyax. Kalbitor (ecallantide) prescribing information. Cambridge, MA; 2009 Dec.
2. Bernstein JA, Qazi M. Ecallantide: its pharmacology, pharmacokinetics, clinical efficacy and tolerability. Expert Rev Clin Immunol.2010;6:29-39
3. Schneider L, Lumry W, Vegh A et al. Critical role of kallikrein in hereditary angioedema pathogenesis: a clinical trial of ecallantide, a novel kallikrein inhibitor. J Allergy Clin Immunol. 2007; 120:416-22. [PubMed 17559913]
4. Lehmann A. Ecallantide (DX-88), a plasma kallikrein inhibitor for the treatment of hereditary angioedema and the prevention of blood loss in on-pump cardiothoracic surgery. Expert Opin Biol Ther. 2008; 8:1187-99. [PubMed 18613770]
5. Food and Drug Administration. Center for Drug Evaluation and Research: Application number 125277 summary review. From FDA website
6. Christiansen SC, Zuraw BL. Update on therapeutic developments for hereditary angioedema. Allergy Asthma Proc. 2009 Sep-Oct; 30:500-5.
7. Food and Drug Administration. Orphan designation pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act. (P.L. 97-414). Rockville, MD; From FDA website). Accessed 2010 May 3.
8. Epstein TG, Bernstein JA. Current and emerging management options for hereditary angioedema in the US. Drugs. 2008; 68:2561-73. [PubMed 19093699]
9. Dyax. Important safety information for healthcare professionals. Risk evaluation mitigation strategy (REMS) for Kalbitor (ecallantide) injection. Cambridge, MA Accessed 2010 Apr 23..
10. Dyax. Dear healthcare professional letter regarding important drug warning for Kalbitor (ecallantide) injection. Cambridge MA; Accessed 2010 Apr 23.
11. Dyax. Kalbitor (ecallantide) injection medication guide. Available from manufacturer website. Cambridge, MA; 2009 Dec.
12. Cicardi M, Levy RJ, McNeil DL et al. Ecallantide for the treatment of acute attacks in hereditary angioedema. N Engl J Med. 2010; 363:523-31. [PubMed 20818887]
13. Levy RJ, Lumry WR, McNeil DL et al. EDEMA4: a phase 3, double-blind study of subcutaneous ecallantide treatment for acute attacks of hereditary angioedema. Ann Allergy Asthma Immunol. 2010; 104:523-9. [PubMed 20568386]
14. Dyax. FDA advisory committee briefing document on Kalbitor (ecallantide) for acute attacks of hereditary angioedema. BLA 125277. 2009 Jan 2. From FDA website.
15. Garnock-Jones KP. Ecallantide in acute hereditary angioedema. Drugs. 2010; 70:1423-31. [PubMed 20614949]
16. Dyax, Cambridge, MA: Personal communication.