Does pimacrolimus (Pimacrolimus) have a black box warning like tacrolimus (Tacrolimus)?

From the Guidelines

Both pimacrolimus and tacrolimus carry black box warnings due to concerns about a theoretical risk of malignancy, particularly lymphoma and skin cancer, with long-term use. The FDA required black box warnings for both these topical calcineurin inhibitors in 2005 due to concerns about a theoretical risk of malignancy, particularly lymphoma and skin cancer, with long-term use, as stated in the guidelines of care for the management of psoriasis and psoriatic arthritis 1. The warning states that these medications should be used only as second-line agents for short-term and intermittent treatment of atopic dermatitis in patients who have failed to respond to other therapies, and should be avoided in children under 2 years of age.

The black box warning was based on animal studies and case reports, though subsequent long-term safety data has not demonstrated a clear causal relationship between these medications and cancer in humans, as reported in the joint AAD-NPF guidelines of care for the management and treatment of psoriasis with topical therapy and alternative medicine modalities for psoriasis severity measures 2. Despite this, the warning remains in place for both medications. Healthcare providers typically weigh the benefits against potential risks when prescribing either medication, particularly for chronic use or in young children.

Some key points to consider when prescribing these medications include:

• The potential risk of malignancy, particularly lymphoma and skin cancer, with long-term use
• The lack of clear causal relationship between these medications and cancer in humans
• The importance of weighing the benefits against potential risks when prescribing either medication
• The recommendation to use these medications only as second-line agents for short-term and intermittent treatment of atopic dermatitis in patients who have failed to respond to other therapies
• The recommendation to avoid these medications in children under 2 years of age, as stated in the guidelines of care for the management of atopic dermatitis: section 3. management and treatment with phototherapy and systemic agents 3.

Overall, the decision to prescribe pimacrolimus or tacrolimus should be made on a case-by-case basis, taking into account the individual patient's needs and medical history, as recommended by the report of the topical calcineurin inhibitor task force of the American College of Allergy, Asthma and Immunology and the American Academy of Allergy, Asthma and Immunology 4, 5.

From the FDA Drug Label

Elidel® (pimecrolimus) Cream 1% FOR DERMATOLOGIC USE ONLY NOT FOR OPHTHALMIC USE Rx only Prescribing Information See WARNINGS, boxed WARNING concerning long-term safety of topical calcineurin inhibitors. The FDA drug label does mention a boxed WARNING for pimacrolimus, which is similar to a black box warning, concerning the long-term safety of topical calcineurin inhibitors 6.

• Key point: Pimacrolimus has a boxed warning.
• Main idea: The warning is related to the long-term safety of the drug.

From the Research

Comparison of Pimacrolimus and Tacrolimus

• Pimacrolimus and tacrolimus are both topical calcineurin inhibitors (TCIs) used to treat atopic dermatitis 7, 8, 9.
• Tacrolimus has been shown to be effective in treating moderate to severe atopic dermatitis, with a higher potency than pimecrolimus 7.
• Pimecrolimus is primarily used to treat mild to moderate atopic dermatitis, with a lower potency than tacrolimus 8, 9.

Safety and Efficacy

• Both pimecrolimus and tacrolimus have been shown to be safe and effective in treating atopic dermatitis, with minimal systemic absorption and no evidence of skin atrophy 7, 8, 10, 9.
• Tacrolimus has been associated with a higher risk of local irritation, such as burning, compared to pimecrolimus 7.
• There is no evidence to suggest that either pimecrolimus or tacrolimus increases the risk of malignancies or skin atrophy 7, 9.

Black Box Warning

• Tacrolimus and pimecrolimus were both approved with a "black box" warning by the US FDA in 2006 due to concerns about a possible link to malignancy 11.
• However, the warning was based on animal studies and case reports, and there is no conclusive evidence to support a causal link between the use of these medications and an increased risk of cancer 11.
• Pimecrolimus does not have the same level of warning as tacrolimus, suggesting that it may be considered a safer alternative for some patients 11.