Topical Calcineurin Inhibitors for Psoriasis Treatment

Off-Label Uses of Protopic and Elidel

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Topical calcineurin inhibitors (TCIs) are a relatively new class of immunosuppressant drugs approved by the U.S. Food and Drug Administration (FDA) for the treatment of moderate to severe eczema (atopic dermatitis). In recent years, two of these drugs—Protopic (tacrolimus ointment) and Elidel (1.0% pimecrolimus cream)—have been used off-label to treat psoriasis and have proven beneficial in reducing the red, scaly plaques characteristics of the disease. While effective, both drugs have significant side effects that should be considered.

Calcineurin inhibitors revolutionized the field of organ transplantation when they were introduced in the 1980s by suppressing the immune system and preventing organ rejection. The first such drug, known as cyclosporine, continues to be used to treat today a variety of medical conditions, including many autoimmune diseases.

How They Work

Topical calcineurin inhibitors work by blocking a protein called calcineurin, which is responsible for activating a type of white blood cell known as a T-cell. T-cells help instigate the immune response by stimulating the release of inflammatory compounds called cytokines. While this response is considered normal and beneficial, it can be problematic if it is too robust.

Eczema is characterized by an overactive immune response that leads to the development of skin dryness, flakiness, fissures, bumps, peeling, redness, and rash. By reducing inflammation at the source, TCIs have proven effective in relieving these symptoms.

Rationale for Off-Label Use

Psoriasis is an inflammatory autoimmune disease. It starts when the immune system suddenly regards normal skin cells as a threat and sends an army of T-cells to "control" what it presumes to be an infection. The ensuing inflammation triggers the hyperproduction of skin cells that proliferate faster than they can be shed. What results is the dry, red, scaly skin recognized as psoriasis.

It is largely presumed that Protopic and Elidel can benefit people with psoriasis by tempering local inflammation and slowing the hyperproduction of skin cells.

According to a 2014 review of studies from Canada, TCIs were not only effective in treating psoriasis but were able to do so without many of the side effects of more commonly prescribed topical drugs.

This includes irreversible skin atrophy (thinning) caused by the prolonged use of topical corticosteroids, as well as the irritation that Dovonex (calcipotriene) and Psoriatec (anthralin) can cause to delicate tissues. By contrast, both Protopic and Elidel appear safe to use on the face, ears, and groin.

While it may seem strange to prescribe an approved drug for an unapproved use, such "off-label" use is not only legal but quite common in the field of dermatology.

Protopic

Protopic (tacrolimus) was approved for use by the FDA in 2000 for the second-line treatment of moderate to severe atopic dermatitis in adults and children.

Protopic comes in two strengths: 0.03% for children ages 2 to 15 and 0.1% for adults and children 16 years and older. It can be used twice daily and applied directly to affected skin. Many prefer one of these applications to be timed just before bed, given the ointment's greasy consistency.

Common side effects include:

  • Itching
  • Acne
  • Skin redness
  • Burning, stinging, or tingling sensations
  • Local sensitivity to hot or cold temperatures
  • Folliculitis (hair follicle infection)
  • Headache
  • Back of muscle pain
  • Runny or stuffy nose
  • Flu-like symptoms
  • Nausea

When used concurrent with alcohol consumption, Protopic can cause the skin to become hot and red at the application site.

If you experience any of these serious side effects when taking Protopic, call your doctor immediately:

Elidel

Elidel (pimecrolimus) is another TCI that works like Protopic, but its cream base makes it far less greasy than Protopic. It is available in a 1.0% strength and is approved for the second-line treatment of mild to moderate atopic dermatitis.

Elidel is used twice daily until symptoms improve and once daily to prevent a recurrence. Like Proptic, it can also cause the treated areas to become red or hot when you drink alcohol.

According to the aforementioned Canadian review, pimecrolimus was beneficial but far less effective than tacrolimus in treating psoriasis symptoms.

Common side effects of Elidel include:

  • Itching
  • Burning, stinging, or tingling sensations
  • Skin redness
  • Acne or warts
  • Eye irritation (if applied in the area)
  • Headache
  • Joint pain
  • Cough
  • Ear congestion
  • Stuffy or runny nose
  • Flu-like symptoms
  • Nosebleeds
  • Upset stomach
  • Diarrhea
  • Folliculitis
  • Swollen glands

If any of the side effects are severe or persist for more than a week or worsen, call your doctor. The same applies if you experience a worsening of symptoms or develop cold sores, chickenpox, or shingles.

When to Call 911

Seek emergency care if you experience:

  • Skin rashes or hives
  • Swelling of the lips, tongue, or throat
  • Shortness of breath
  • Trouble breathing
  • Wheezing
  • Dizziness and/or fainting
  • Vomiting or diarrhea
  • A feeling of impending doom

These could be signs a potentially life-threatening, whole-body allergy known as anaphylaxis. While uncommon, several cases have been reported with Elidel use.

Black Box Warning

In 2006, Protopic and Elidel both received a black box warning from the FDA after it was reported that several users developed skin cancer or lymphoma (a type of blood cancer). It was assumed by some that the TCI agents were to blame.

To date, there is little evidence of such an association. According to a 2013 review in the Journal of Clinical Dermatology, the rate of malignancies in users of TCI were no different than that of the general population.

Moreover, of the six studies reviewed, two could find no association between Protopic and cancer, while the other four suggested that TCIs may increase the risk of lymphoma, but that the risk was minimal at best.

For its part, the American Academy of Dermatology has adamantly stated that there is no proof of a causal link between TCIs and cancer and that Protopic and Elidel are both safe and effective when used as directed.

A Word From Verywell

Whether the off-label use of Protopic or Elidel is right for you is something you and your dermatologist have to decide. Be advised, however, that some insurance companies are reluctant to cover the costs of these drugs when cheaper steroids are available. (The retail price of Protopic is around $200 for a 30-gram tube, while the price of Elidel is around $300 for the same. Less costly generics of both are now available.) However, if your doctor can show that your condition has not improved after using a topical steroid, most insurers will grant approval.

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