Calcineurin Inhibitors: Uses, most common brand names, and safety information
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Calcineurin inhibitors (CNIs) such as cyclosporine and tacrolimus, have transformed the way we prevent organ rejections from transplantation surgery. Cyclosporine was the first CNI approved in 1983 by the U.S. Food and Drug Administration (FDA) for immunosuppression following solid organ transplantation (allograft). A new formulation of cyclosporine, which had a higher absorption rate, was approved 12 years later. Tacrolimus was initially approved in 1994 and currently is the first-line treatment for immunosuppression for over 85% of kidney transplant recipients. This is largely due to tacrolimus being associated with less incidence of organ rejection and nephrotoxicity (kidney damage) than cyclosporine. Today CNIs are also used to treat autoimmune and other inflammatory conditions.
The list below includes calcineurin inhibitors approved by the U.S. Food and Drug Administration (FDA) and their pricing:
List of calcineurin inhibitors
Prograf is indicated for the prophylaxis of organ rejection.
Envarsus XR (tacrolimus)
Envarsus XR is indicated for the prophylaxis of organ rejection.
Advagraf is indicated for the prophylaxis of organ rejection.
Advagraf XL (tacrolimus)
Advagraf XL is indicated for the prophylaxis of organ rejection.
Astagraf XL (tacrolimus)
Astagraf XL is indicated for the prophylaxis of organ rejection.
Protopic (tacrolimus ointment)
Protopic is indicated to treat atopic dermatitis.
Sandimmune is indicated for the prophylaxis of organ rejection and the treatment of rheumatoid arthritis, and psoriasis.
Neoral is indicated for the prophylaxis of organ rejection and the treatment of rheumatoid arthritis, and psoriasis.
Gengraf is indicated for the prophylaxis of organ rejection and the treatment of rheumatoid arthritis, and psoriasis.
Restasis (cyclosporine ophthalmic)
Restasis is indicated to treat dry eyes.
Restasis MultiDose (cyclosporine ophthalmic)
Restasis MultiDose is indicated to treat dry eyes.
Cequa (cyclosporine ophthalmic)
Cequa is indicated to treat dry eyes.
Verkazia (cyclosporine ophthalmic)
Verkazia is indicated to treat vernal keratoconjunctivitis.
Elidel (pimecrolimus cream)
Elidel is indicated to treat atopic dermatitis.
Lupkynis is indicated to treat lupus nephritis.
What are calcineurin inhibitors?
Calcineurin is an enzyme that activates the T-lymphocytes (T-cells) of your immune system. T-cells are a type of white blood cell (leukocyte) that plays an essential role in cell-mediated immunity. When your immune system is overactive, it can attack healthy tissue and cause inflammation. After organ transplants, your immune system can also attack the new organ because it recognizes it as a foreign body. Because of the way CNIs alter your immune response, they are classified as immunosuppressant drugs.
Oral CNIs are used in adult and pediatric patients following organ transplants to help prevent damage from your immune system. They are also used to treat autoimmune diseases such as rheumatoid arthritis. Topical CNIs are typically used for inflammatory skin conditions such as plaque psoriasis when you have failed other treatments. CNIs can be used alone but are often used in combination with corticosteroids or other immunosuppressants such as Imuran (azathioprine).
What is the mechanism of action of calcineurin inhibitors?
Calcineurin is a protein that is found inside T-lymphocytes (T-cells). Stimulating T-cell receptors causes them to produce antibodies that work with other immune cells in response to foreign antigens. Sometimes your immune system can overreact and start attacking healthy cells. CNIs bind to proteins called immunophilins: cyclophilins in the case of cyclosporine A, and the FK-binding proteins in the case of tacrolimus. This complex then binds to calcineurin, leading to an inhibition of its activity. By blocking the calcium-dependent phosphatase activity of calcineurin, CNIs block T-cells from producing the cytokine interleukin-2 (IL-2). This suppresses the response of your immune system to foreign antigens, reducing inflammation and tissue damage.
What conditions are calcineurin inhibitors used to treat?
Calcineurin inhibitors are used alone or in combination with steroids or other immunosuppressants for a variety of conditions, including:
- Prevention of organ rejection following kidney, heart, or liver transplants
- Atopic dermatitis
- Rheumatoid arthritis
- Plaque psoriasis
- Lupus nephritis
- Vernal keratoconjunctivitis
CNIs are often used off-label for conditions such as:
- Allergic conjunctivitis
- Ulcerative colitis
- Systemic lupus erythematosus
- Sjogren’s syndrome
- Crohn’s disease
- Myasthenia gravis
- Aplastic anemia
- Interstitial cystitis
Are calcineurin inhibitors safe?
The use of calcineurin inhibitors is relatively safe and effective when taken as prescribed. Before beginning treatment with calcineurin inhibitors, tell your doctor if you have any of the following medical conditions:
- Hypersensitivity to any ingredient in the CNI formulation
- Active infection
- History of cancer
- Liver dysfunction
- Kidney dysfunction
- Pregnant, plan on becoming pregnant or are breastfeeding
What are some common side effects of calcineurin inhibitors?
The adverse effects you experience from calcineurin inhibitors will depend on several factors including the medication and dose. The most common adverse effects in clinical trials when compared to placebo include:
- Kidney toxicity
- Increased risk of infections
- Increased risk of cancer
- Liver toxicity
- High blood pressure
- Increased liver enzymes
- Increased potassium levels
- Hair loss
- Excessive hair growth
- Increased blood sugar, especially after renal transplants
- Burning and redness at the application site
- Itching at the application site
- Flu-like symptoms
- Common cold symptoms
- Eye pain, stinging, and burning
- Blurred vision
- Increased tears
- Foreign body sensation
This is not a complete list of side effects and we encourage you to consult with your healthcare provider or pharmacist for medical advice about any possible side effects.
Who should not take calcineurin inhibitors?
If you have the following conditions you should not take calcineurin inhibitors:
- Active infection
- Cancer or malignancy
- Severely impaired renal function
- Liver impairment
- Known hypersensitivity to any ingredient in the CNI product
- Uncontrolled hypertension
- Uncontrolled diabetes
- Patients taking strong CYP3A inhibitors or other medications that can cause severe drug interactions
Why are calcineurin inhibitors toxic to your kidneys?
Calcineurin inhibitors are thought to cause kidney damage through acute arteriolopathy. Arteriolopathy is typically due to calcium deposits in your arterioles, which leads to the death of tissue around it.
How much do calcineurin inhibitors cost?
Calcineurin inhibitors are very expensive with an average cost at least $5,000 per year.
You can purchase calcineurin inhibitors for $49 per month from NiceRx if eligible for assistance. Prices at the pharmacy vary by location, strength, and quantity, as well as your insurance status.
Related resources for calcineurin inhibitors
The content on this website is intended for information purposes only. It does not constitute medical advice. The information on this website should not be relied upon and is not a substitute for professional medical advice. You should always speak to your doctor regarding the risks and benefits of any treatment.