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Increased Topical Tacrolimus Absorption in Generalized Leukemic Erythroderma

Clinical Pharmacist, Department of Pharmacy, Kyushu University Hospital, Fukuoka, Japan

Hiroaki Ikesue, BS

Clinical Pharmacist, Department of Pharmacy, Kyushu University Hospital

Yoshinori Itoh, PhD

Associate Professor, Department of Pharmacy, Kyushu University Hospital

Kazunori Urabe, MD

Dermatologist, Department of Dermatology, Kyushu University Hospital

Masutaka Furue, MD

Professor, Department of Dermatology, Kyushu University Hospital

Ryozo Oishi, PhD

Professor, Department of Pharmacy, Kyushu University Hospital

Reprints: Daisuke Teshima PhD, Department of Hospital Pharmacy, Faculty of Medicine, Kyushu University, 3-1-1, Higashi-ku, Maidashi, Fukuoka 812-8582, Japan, FAX 81-92-642-5937, dteshima{at}st.hosp.kyushu-u.ac.jp

OBJECTIVE: To report a case of elevated blood tacrolimus concentration after application of topical tacrolimus ointment in an erythrodermic patient.

CASE SUMMARY: A 44-year-old man developed generalized erythroderma and itching due to infection with human T-cell lymphotropic virus. Despite application of strong glucocorticosteroid ointments, the symptoms and area of erythroderma were not alleviated. Daily topical application of tacrolimus 0.1% ointment was added and therapeutic drug monitoring was started. The dose and applied area of tacrolimus were gradually increased from 2.5 to 12.5 g/d and from 10% to 90% of body surface area, respectively. Because the trough concentration of tacrolimus in whole blood increased from 7.5 ng/mL on treatment day 9 to 15.4 ng/mL on day 13, the dose was reduced to 10 g/d. However, the concentration further elevated to 16.5 ng/mL. Therefore, the applied area was reduced to 20% of body surface area, and the tacrolimus concentration decreased gradually thereafter. Although the transient increase of blood tacrolimus concentration was observed on day 23, treatment with 20% applied area and 5 g/d were maintained.

DISCUSSION: Topically applied tacrolimus was substantially absorbed with the expansion of its applied area and dose. Increased tacrolimus concentrations may have a tendency to depend on the increase of the percent of body surface area per dose. Our findings showing the elevation of blood tacrolimus concentration after application of the ointment to a large area of the body suggest that the applied area should be as narrow as possible in a barrier-disrupted condition such as erythroderma. However, the safety of tacrolimus ointment has not been established in patients with generalized erythroderma.

CONCLUSIONS: Tacrolimus concentrations in whole blood should be carefully monitored to prevent nephrotoxicity. Based on the results of that monitoring, the application area and dose of tacrolimus ointment should be closely adjusted, especially in generalized erythrodermic cases.

Key Words: erythroderma, human T-cell lymphotropic virus infection, tacrolimus ointment, transcutaneous absorption

Published Online, August 1, 2003. www.theannals.com, DOI 10.1345/aph.1D082