How Do Calcineurin Inhibitors Work?

Calcineurin inhibitors are a class of drugs used in the chronic management of patients with allografts (transplant of an organ or tissue from one individual to another of the same species with a different genotype) and inflammatory conditions such as atopic dermatitis, rheumatoid arthritis, and postoperative immunosuppression. Calcineurin inhibitors are “immunosuppressants” as they work by inhibiting calcineurin, an enzyme that activates T-cells of the immune system. T-cell, also called T lymphocyte, is a type of leukocyte (white blood cell) essential for cell-mediated immunity. 

Calcineurin inhibitors are prescription-only medicines and are administered via oral, intravenous, topical, and ophthalmic routes.

Calcineurin inhibitors work in the following ways:

• They inhibit the action of calcineurin, an enzyme that plays a key role in cell-mediated immunity.
• They bind to the proteins in the cells called "immunophilins."
• This reduces the release of the cytokine interleukin-2 from T-cells and T-cell proliferation.
• This leads to inhibition of a key signaling phosphatase “calcineurin”; thus, they are known as “calcineurin inhibitors.”
• In addition, they suppress the immune system so that the body can accept the new organ, thus preventing the rejection reaction.
• They work by weakening the skin’s defense system, thereby decreasing the allergic reaction and relieving the skin irritation and inflammation.
• They increase eyes’ natural ability to produce tears, which reduces swelling of the eyes.

Calcineurin inhibitors are used for the prevention and treatment of conditions such as:

• Organ transplant rejection prophylaxis in:
  • Heart transplant
  • Liver transplant
  • Kidney transplant
  • Corneal graft (replaces diseased or scarred corneal tissue with healthy tissue from an organ donor)
• Ophthalmic conditions such as:
  • Keratoconjunctivitis (a group of inflammatory eye conditions involving the cornea and the conjunctiva)
  • Keratoconjunctivitis sicca (also known as dry eye syndrome, a condition characterized by the inability of the eye to produce sufficient tears to keep it moist)
  • Vernal keratoconjunctivitis (an allergic eye disease that especially affects young males)
  • Corneal melting (a devastating complication of end stage corneal disease)
• Inflammatory conditions such as:
  • Rheumatoid arthritis (a chronic disease marked by symptoms of inflammation and pain in the joints)
  • Lupus nephritis (inflammation of the kidney that is caused by systemic lupus erythematous)
• Skin conditions such as:
  • Atopic dermatitis (a chronic skin condition characterized by dry, itchy skin)
  • Psoriasis (a skin disease that causes red, itchy scaly patches, most commonly on the knees, elbows, trunk, and scalp)
  • Eczema (an allergic-type condition that causes red, irritated, and itchy skin)
  • Graft versus host disease (a syndrome characterized by inflammation in different organs which occurs after an allogeneic transplant)
  • Postoperative immunosuppression

Common side effects include:

Tremors (an involuntary, rhythmic shaking movement in one or more parts of body)

• Headache
• Diarrhea
• Nausea
• Vomiting
• Stinging/burning/soreness/itching of the affected skin
• Stomach upset
• Acne
• Muscle or back pain
• Eye redness/pain
• Watery eyes

Other rare side effects include:

• Folliculitis (a common skin condition in which hair follicles become inflamed)
• Trouble sleeping
• Hypertension (high blood pressure)
• Blurred vision
• Anemia (low number of red blood cells)
• Hypophosphatemia (abnormally low level of phosphate in the blood)
• Asthenia (abnormal physical weakness or lack of energy)
• Foreign body sensation in the eyes
• Upper respiratory tract infection
• Nephrotoxicity (rapid deterioration in the kidney function because of the toxic effect of medications and chemicals)
• Conjunctival hyperemia (dilation and redness of conjunctival vessels that can be a symptom of various ocular disorders)
• Cough

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 calcineurin inhibitors include:

• Astagraf XL
• Cequa
• Cyclosporine
• Cyclosporine ophthalmic
• Elidel
• Envarsus XR
• Gengraf
• Hecoria
• Lupkynis
• Neoral
• Pimecrolimus
• Prograf
• Protopic
• Restasis
• Sandimmune
• Tacrolimus
• Tacrolimus ointment
• Voclosporin