Ecallantide

Hereditary angioedema (HAE) is a rare genetic disorder caused by mutations to C1-esterase-inhibitor (C1-INH) located on Chromosome 11q and inherited as an autosomal dominant trait. HAE is characterized by low levels of C1-INH activity and low levels of C4.

• KALBITOR ® (ecallantide) is indicated for treatment of acute attacks of hereditary angioedema (HAE) in patients 12 years of age and older. KALBITOR is a plasma kallikrein inhibitor indicated for treatment of acute attacks of hereditary angioedema (HAE) in patients 12 years of age and older.

• Do not administer KALBITOR to a patient who has known clinical hypersensitivity to KALBITOR. [ see Warnings and Precautions (5.1) ].contraindicated

30 mg (3 mL), administered subcutaneously in three 10 mg (1 mL) injections. If an attack persists, an additional dose of 30 mg may be administered within a 24 hour period. ( 2.1 ) KALBITOR should only be administered by a healthcare professional with appropriate medical support to manage anaphylaxis and hereditary angioedema. ( 2.2 ). 2.1 Recommended Dosing The recommended dose of KALBITOR is 30 mg (3 mL), administered subcutaneously in three 10 mg (1 mL) injections. If the attack persists, an additional dose of 30 mg may be administered within a 24 hour period. 2.2 Administration Instructions KALBITOR should only be administered by a healthcare professional with appropriate medical support to manage anaphylaxis and hereditary angioedema. KALBITOR should be refrigerated and protected from the light. KALBITOR is a clear, colorless liquid; visually inspect each vial for particulate matter and discoloration prior to administration. If there is particulate matter or discoloration, the vial should not be used. Using aseptic technique, withdraw 1 mL (10 mg) of KALBITOR from the vial using a large bore needle. Change the needle on the syringe to a needle suitable for subcutaneous injection. The recommended needle size is 27 gauge. Inject KALBITOR into the skin of the abdomen, thigh, or upper arm. Repeat the procedure for each of the 3 vials comprising the KALBITOR dose. The injection site for each of the injections may be in the same or in different anatomic locations (abdomen, thigh, upper arm). There is no need for site rotation.

Hypersensitivity Reactions Including Anaphylaxis: Anaphylaxis has occurred in 4% of treated patients. Administer KALBITOR in a setting equipped to manage anaphylaxis and hereditary angioedema. Given the similarity in hypersensitivity symptoms and acute HAE symptoms, monitor patients closely for hypersensitivity reactions ( 5 ). 5.1 Hypersensitivity Reactions, Including Anaphylaxis Potentially serious hypersensitivity reactions, including anaphylaxis, have occurred in patients treated with KALBITOR. In 255 HAE patients treated with intravenous or subcutaneous KALBITOR in clinical studies, 10 patients (4%) experienced anaphylaxis. For the subgroup of 187 patients treated with subcutaneous KALBITOR, 5 patients (3%) experienced anaphylaxis. Symptoms associated with these reactions have included chest discomfort, flushing, pharyngeal edema, pruritus, rhinorrhea, sneezing, nasal congestion, throat irritation, urticaria, wheezing, and hypotension. These reactions occurred within the first hour after dosing. Other adverse reactions indicative of hypersensitivity reactions included the following: pruritus (5%), rash (3%), and urticaria (2%). Patients should be observed for an appropriate period of time after administration of KALBITOR, taking into account the time to onset of anaphylaxis seen in clinical trials. Given the similarity in hypersensitivity symptoms and acute HAE symptoms, patients should be monitored closely in the event of a hypersensitivity reaction.

Hypersensitivity reactions, including anaphylaxis, have occurred in patients treated with KALBITOR [ see Contraindications (4) and Warnings and Precautions (5.1) ]. The most common adverse reactions occurring in ≥3% of KALBITOR-treated patients and greater than placebo are headache, nausea, diarrhea, pyrexia, injection site reactions, and nasopharyngitis. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals U.S.A., Inc. at 1-877-TAKEDA-7 (1-877-825-3327) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety data described below reflect exposure to KALBITOR in 255 patients with HAE treated with either intravenous or subcutaneous KALBITOR. Of the 255 patients, 66% of patients were female and 86% were Caucasian. Patients treated with KALBITOR were between the ages of 10 and 78 years. Overall, the most common adverse reactions in 255 patients with HAE were headache (16%), nausea (13%), fatigue (12%), diarrhea (11%), upper respiratory tract infection (8%), injection site reactions (7%), nasopharyngitis (6%), vomiting (6%), pruritus (5%), upper abdominal pain (5%), and pyrexia (5%). Anaphylaxis was reported in 4% of patients with HAE. Injection site reactions were characterized by local pruritus, erythema, pain, irritation, urticaria, and/or bruising.

8.1 Pregnancy Risk Summary The available data from the pharmacovigilance database for KALBITOR have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. In an animal reproduction study, increased early fetal deaths resulting in decreased live fetuses were observed in rats following treatment during the period of organogenesis at an intravenous dose approximately 1.6 times the maximum recommended human dose (MRHD) in the presence of maternal toxicity. There were no effects on embryofetal survival or structural abnormalities in rats and rabbits following treatment during the period of organogenesis with intravenous doses up to approximately 1.1 and 6 times the MRHD, respectively, or rats treated with subcutaneous doses up to 2.4 times the MRHD. In a pre- and post-natal development study with rats, there were no effects on pup survival and development with subcutaneous doses up to approximately 2.7 times the MRHD. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Metabolism

Following the administration of a single 30 mg subcutaneous dose of KALBITOR to healthy subjects, a mean (± standard deviation) maximum plasma concentration of 586 ± 106 ng/mL was observed approximately 2 to 3 hours post-dose. The mean area under the concentration-time curve was 3017 ± 402 ng*hr/mL.

There have been no reports of overdose with KALBITOR. HAE patients have received single doses up to 90 mg intravenously without evidence of dose-related toxicity.

• Dec 1, 2009BLABLA125277Dyax Corp.

1. 1Hereditary Angioedema76942%
2. 2Off Label Use1699.1%
3. 3Drug Ineffective1457.9%
4. 4Headache844.5%
5. 5Malaise824.4%
6. 6Product Dose Omission Issue713.8%
7. 7Pain693.7%
8. 8Weight Decreased673.6%
9. 9Hypersensitivity663.6%
10. 10Nausea663.6%
11. 11Anaphylactic Reaction623.4%
12. 12Weight Increased593.2%
13. 13Therapeutic Response Decreased542.9%
14. 14Pneumonia522.8%
15. 15Vomiting522.8%

The 10 most recently updated of 13 ClinicalTrials.gov registrations naming Ecallantide as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Study to Assess the Tolerability and Safety of Ecallantide in Children and Adolescents With Hereditary Angioedema
  Withdrawn · Phase 2 · Interventional · 0 enrolled · NYU Langone Health
  NCT01832896updated 2023-03-31
• Efficacy and Safety Study of DX-88 to Treat Acute Attacks of Hereditary Angioedema (HAE)
  Completed · Phase 3 · Interventional · 91 enrolled · Shire
  NCT00262080updated 2021-06-11
• Evaluation of Ecallantide for Treatment of Angiotensin Converting Enzyme (ACE) Inhibitor Induced Angioedema
  Terminated · Phase 2 · Interventional · 79 enrolled · Shire
  NCT01343823updated 2021-06-11
• Efficacy Study of DX-88 (Ecallantide) to Treat Acute Attacks of Hereditary Angioedema (HAE)
  Completed · Phase 3 · Interventional · 96 enrolled · Shire
  NCT00457015updated 2021-06-08
• Observational Safety Study for KALBITOR (Ecallantide) in the Treatment of Acute Attacks of Hereditary Angioedema
  Completed · Observational · 81 enrolled · Shire
  NCT01059526updated 2021-06-08
• Safety and Efficacy Study of Repeated Doses of DX-88 (Ecallantide) to Treat Attacks of Hereditary Angioedema (HAE)
  Completed · Phase 3 · Interventional · 147 enrolled · Shire
  NCT00456508updated 2021-06-08
• EDEMA2: Evaluation of DX-88's Effect in Mitigating Angioedema
  Completed · Phase 2 · Interventional · 77 enrolled · Shire
  NCT01826916updated 2021-05-18
• Study to Evaluate Ecallantide in Paediatric Patients With Acute Attacks of Hereditary Angioedema
  Withdrawn · Phase 2 · Phase 3 · Interventional · 0 enrolled · Shire
  NCT01253382updated 2021-05-18
• Efficacy Study of Recombinant Protein (Ecallantide) to Reduce Blood Loss During Primary Coronary Bypass Grafting or Valve Repair/Replacement
  Terminated · Phase 2 · Interventional · 75 enrolled · Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
  NCT00448864updated 2019-06-25
• A Dose-ranging Safety and Efficacy Study of Ecallantide to Reduce Surgical Blood Loss Volume
  Completed · Phase 2 · Interventional · 276 enrolled · Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
  NCT00816023updated 2015-08-11

Frequently asked questions

How does Ecallantide work?

Hereditary angioedema (HAE) is a rare genetic disorder caused by mutations to C1-esterase-inhibitor (C1-INH) located on Chromosome 11q and inherited as an autosomal dominant trait. HAE is characterized by low levels of C1-INH activity and low levels of C4.

What is Ecallantide used for?

According to FDA labeling, Ecallantide carries indications including: KALBITOR ® (ecallantide) is indicated for treatment of acute attacks of hereditary angioedema (HAE) in patients 12 years of age and older. KALBITOR is a plasma kallikrein inhibitor indicated for treatment of acute attacks of hereditary angioedema (HAE) in patients 12 years of age and older.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Ecallantide?

Ecallantide is classified as Drugs used in hereditary angioedema, Plasma Kallikrein Inhibitor, Kallikrein Inhibitors, Decreased Coagulation Activity, Decreased Immunologic Activity, Vasoconstriction.

What are the brand names for Ecallantide?

Ecallantide is marketed under brand names including Kalbitor.

What are the contraindications for Ecallantide?

Ecallantide labeling lists contraindications including: Do not administer KALBITOR to a patient who has known clinical hypersensitivity to KALBITOR. [ see Warnings and Precautions (5.1) ].. Always consult the full prescribing information and a clinician.