How Do Kallikrein Inhibitors Work?


Kallikrein inhibitors are a class of drugs used to prevent and treat attacks due to an inherited immune disease “hereditary angioedema” (HAE) in adults and children aged 12 years and older. HAE is a rare, hereditary (passed down through families) autosomal dominant disease associated with a deficiency or dysfunction of C1-esterase-inhibitor (C1-INH) activity. C1-INH is a protein found in the fluid part of the blood that controls a protein called C1, which is a part of the complement system. The complement system is a group of nearly 60 proteins (consisting of nine major proteins labeled as C1 through C9) in the blood plasma or on the surface of some cells. This complement system along with the immune system helps to protect the body from infections and remove dead cells and foreign materials. Rarely, few people may inherit deficiency of some complement proteins making them prone to infections and autoimmune disorders.

HAE causes repeated episodes of severe swelling of the skin, airway, and gastrointestinal system and is characterized by symptoms such as:

  • Swelling of the skin
  • Swelling of hands and feet
  • Headache
  • Fatigue (feeling of tiredness or lack of energy)
  • Skin tingling
  • Muscle aches
  • Abdominal pain
  • Nausea and vomiting
  • Hoarseness of voice
  • Shortness of breath
  • Mood changes

Laryngeal edema (swelling in the upper airway, a medical emergency)

HAE may be triggered by situations such as stress, anxiety, injuries, surgical procedures, medications, menstrual periods, and pregnancy.

Kallikrein inhibitors are prescription-only medicines and are administered via oral and subcutaneous injection (under the skin) routes.

Kallikrein inhibitors work in the following ways:

  • They work by binding to a natural substance “kallikrein” made by the body and by inhibiting its activity.
  • This binding lowers the amount of another natural substance “bradykinin,” the major biologic peptide that promotes swelling and pain associated with attacks of HAE.
  • They obstruct the proteolytic active site of plasma kallikrein, preventing the splitting of kininogen (a coagulation protein) into bradykinin.
  • During HAE attacks, the levels of plasma kallikrein fall, leading to the cleavage of high-molecular-weight kininogen and the release of bradykinin, a potent vasodilator that increases vascular permeability.
  • Patients with HAE cannot properly regulate plasma kallikrein activity because of the deficiency or dysfunction of a C1-INH, leading to uncontrolled increases in plasma kallikrein activity and recurrent angioedema attacks.


Kallikrein inhibitors are used in the prevention and treatment of HAE, a rare genetic disorder associated with severe swelling of the skin and upper airway.


Common side effects include:

  • Diarrhea
  • Nausea
  • Vomiting
  • Stomach upset
  • Abdominal pain
  • Heartburn
  • Back pain
  • Headache
  • Flatulence (gas)
  • Upper respiratory tract infection
  • Bruising/itching/redness/swelling of the skin at the injection site

Other rare side effects include:

  • Myalgia (chronic pain, stiffness, and tenderness of muscles)
  • Increased alanine transferase and aspartate transferase liver enzymes
  • Pyrexia (fever)
  • Sneezing, runny or stuffy nose
  • Hoarse voice, tight feeling in the throat
  • Hypersensitivity
    • Urticaria (an outbreak of pale red bumps or welts on the skin that appear suddenly)
    • Itching
    • Swelling of the face/tongue/throat
    • Dizziness (feeling faint, weak or unsteady)
    • Difficulty breathing

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.


Generic and brand names of kallikrein inhibitors include:

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