Kalbitor

Agents for Acute Treatment of Hereditary Angioedema (HAE)
Inhibitors of The Kallikrein-kinin-system

 
Ecallantide should only be administered by a health care professional with appropriate medical support to manage anaphylaxis and hereditary angioedema.

Using aseptic technique, withdraw 1 mL (10 mg) of ecallantide from the vial using a large bore needle. Change the needle on the syringe to a needle suitable for subcutaneous injection (27 gauge recommended).
Inject ecallantide into the skin of the abdomen, thigh, or upper arm.
Repeat the procedure for each of the three vials of ecallantide (30 mg total dose). The injection site for each of the three injections may be in the same or different anatomic location (abdomen, thigh, or upper arm). There is no need for site rotation. Individual injections should be separated by at least 2 inches and away from the anatomical site of attack.
The same directions for administration apply if an additional dose of ecallantide is required within 24 hours. Different injection sites or the same anatomical location as used for the first dose may be used.
Ecallantide is a clear, colorless solution. Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. If there is particulate matter or discoloration, the vial should not be used.

serious hypersensitivity reactions or anaphylaxis / Rapid / Incidence not known

antibody formation / Delayed / 20.2-20.2
wheezing / Rapid / Incidence not known
erythema / Early / Incidence not known
chest pain (unspecified) / Early / Incidence not known
hypotension / Rapid / Incidence not known

headache / Early / 16.0-16.0
nausea / Early / 13.0-13.0
fatigue / Early / 12.0-12.0
diarrhea / Early / 11.0-11.0
infection / Delayed / 8.0-8.0
injection site reaction / Rapid / 7.0-7.0
vomiting / Early / 6.0-6.0
pharyngitis / Delayed / 6.0-6.0
pruritus / Rapid / 5.0-5.0
abdominal pain / Early / 5.0-5.0
fever / Early / 5.0-5.0
rash / Early / 3.0-3.0
urticaria / Rapid / 2.0-2.0
nasal congestion / Early / Incidence not known
flushing / Rapid / Incidence not known
sneezing / Early / Incidence not known
throat irritation / Early / Incidence not known
rhinorrhea / Early / Incidence not known

Kalbitor

Rx

Recombinant protein kallikrein inhibitor
Used for treatment of acute attacks of hereditary angioedema
Only administer in settings with appropriate medical support/supplies readily available to treat anaphylaxis

30 mg subcutaneously administered as three 10-mg (1 mL) injections. If the attack persists, an additional 30 mg dose may be administered within a 24-hour period. The efficacy of ecallantide in children and adolescents 12 to 15 years of age is extrapolated from efficacy in patients 16 years of age or older and from pharmacokinetic data demonstrating similar drug exposure in adolescents and adults.

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

There are no drug interactions associated with Ecallantide products.

Kalbitor Subcutaneous Inj Sol: 1mL, 10mg

30 mg/dose subcutaneously. May repeat once within 24 hour period.

30 mg/dose subcutaneously. May repeat once within 24 hour period.

30 mg/dose subcutaneously. May repeat once within 24 hour period.

12 years: 30 mg/dose subcutaneously. May repeat once within 24 hour period.
< 12 years: Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Ecallantide is a potent, selective, reversible inhibitor of kallikrein that blocks the production of kallikrein, a precursor to bradykinin. Ecallantide binds to the protease plasma kallikrein and blocks its binding site, preventing the conversion of high molecular weight kininogen to bradykinin. People with hereditary angioedema (HAE) have mutations to C1-esterase inhibitor (C1-INH) located on chromosome 11q. C1-INH, a serine protease, is the primary regulator of the kallikrein-kinin cascade, but is also involved in complement and intrinsic coagulation, fibrinolysis, hypotension, and pain and inflammation pathways. A deficiency in C1-INH causes an increase in the production of kallikrein, and thus, bradykinin. The edema and swelling of HAE attacks are thought to be due to the excessive production of bradykinin. Because ecallantide is selective for the kallikrein-kinin pathway, ecallantide should not affect other pathways regulated by C1-INH.
 
In regard to the investigational use of ecallantide for the prevention of blood loss during cardiothoracic surgery, ecallantide's inhibition of kallikrein production may be very beneficial. Kallikrein liberates bradykinin, which causes local leakage of fluid from the blood vessels into the tissues. Ecallantide helps reduce bradykinin liberation and may reduce both blood transfusions associated with on-pump cardiothoracic surgery and systemic inflammatory effects. Contact activation of the inflammatory cascade is one of the inherent risks of on-pump cardiothoracic surgery. Blood loss and the systemic inflammatory response syndrome may occur when the patient's blood comes into contact with the artificial surface of the cardiopulmonary bypass machine and tubing.

Ecallantide is administered subcutaneously. After administration, the mean elimination half-life of ecallantide was approximately 2 hours. Plasma clearance was 153 +/- 20 mL/min and the volume of distribution was 26.4 +/- 7.8 L. Ecallantide is a small protein with a molecular weight of 7054 Da. Renal elimination of ecallantide has been observed in treated subjects.

After the subcutaneous administration of a single 30 mg dose of ecallantide to healthy subjects, the maximum plasma concentration, 586 +/- 106 ng/mL, was observed 2—3 hours after the dose.

The available data from the pharmacovigilance database for ecallantide have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes with use during pregnancy. In an animal reproductive study, increased early fetal deaths resulting in decreased live fetuses were observed after 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 other animal studies after treatment during the period of organogenesis with intravenous doses up to approximately 1.1 and 6 times the MRHD or with subcutaneous doses up to 2.4 times the MRHD. In a pre- and post-natal development animal study, there were no effects on pup survival and development with subcutaneous doses up to approximately 2.7 times the MRHD.

There are no data on the presence of ecallantide in human breast milk, the effects on the breast-fed infant, or the effects on milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for ecallantide and any potential adverse effects on the breast-fed child from ecallantide or the underlying maternal condition.