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Toxic serum levels of tacrolimus after topical administration in an infant with severe cutaneous graft-versus-host disease

Bone Marrow Transplantation volume 40, pages 295–296 (2007)Cite this article

Previous reports have been published of increased cutaneous absorption of tacrolimus in children with concomitant conditions associated with a skin-barrier dysfunction. Our case is the first report on toxic levels of tacrolimus after topical administration in a child with severe cutaneous acute GVHD. An 11-month-old boy who underwent unrelated umbilical cord blood stem cell transplantation for a SCID received topical tacrolimus for severe cutaneous GVHD. After only two applications restricted to the upper extremities, tacrolimus serum levels reached 23.4 ng/ml. Serum levels rapidly decreased following discontinuation of the topical tacrolimus. No adverse effects related to tacrolimus toxic levels were observed. This case report suggests that significant topical tacrolimus absorption may occur in some children with concomitant conditions displaying skin-barrier dysfunction. Drug monitoring of tacrolimus should be considered in children with extensive skin lesions treated with topical tacrolimus to adjust appropriately dosage.

A child was diagnosed at 5 months of age with SCID. At 7 months, he underwent unrelated umbilical cord blood hematopoietic stem cell transplantation (HSCT) for the treatment of this condition. He presented 30 days later with gastrointestinal and cutaneous involvement resulting in a global grade 3 acute GVHD. More than 10 stools per day were reported (600 ml/m2/day) corresponding to grade 2 gastrointestinal GVHD. The cutaneous condition covered more than 50% of his body surface (cutaneous GVHD grade 3). The lesions were very erythematous with superficial desquamation but were not denuded and there were no apparent vesicles or ulcerations. As part of the HSCT protocol, he had received cyclosporine with steroids as GVHD prophylaxis. The GVHD was treated initially with cyclosporine and high-dose corticosteroids. Cyclosporine was switched 2 months after his HSCT to tacrolimus owing to intolerance to intravenous cyclosporine and variable therapeutic levels with the oral formulation. Several drugs were used in combination to treat his GVHD such as mycophenolate mofetil, infliximab, daclizumab and thymoglobulin. The response to these treatments was very limited, with some treatments showing only short-term efficacy.

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References

  1. Hochleitner BW, Bosmuller C, Nehoda H, Fruhwirt M, Simma B, Ellemunter H et al. Increased tacrolimus levels during diarrhea. Transpl Int 2001; 14: 230–233.

    Article  CAS  Google Scholar 

  2. Harper J, Smith C, Rubins A, Green A, Jackson K, Zigure S et al. A multicenter study of the pharmacokinetics of tacrolimus ointment after first and repeated application to children with atopic dermatitis. J Invest Dermatol 2005; 124: 695–699.

    Article  CAS  Google Scholar 

  3. Food and Drug Administration. Protopic® (tacrolimus) Ointment 0.03% Ointment 0.1% Monography. http://www.fda.gov/cder/foi/label/2006/050777s012lbl.pdf.

  4. Simpson D, Noble S . Tacrolimus ointment: a review of its use in atopic dermatitis and its clinical potential in other inflammatory skin conditions. Drugs 2005; 65: 827–858.

    Article  CAS  Google Scholar 

  5. Allen A, Siegfried E, Silverman R, Williams ML, Elias PM, Szabo SK et al. Significant absorption of topical tacrolimus in 3 patients with Netherton syndrome. Arch Dermatol 2001; 137: 747–750.

    CAS  PubMed  Google Scholar 

  6. Allen DM, Esterly NB . Significant systemic absorption of tacrolimus after topical application in a patient with lamellar ichthyosis. Arch Dermatol 2002; 138: 1259–1260.

    Article  Google Scholar 

  7. Russell RK, Richardson N, Wilson DC . Systemic absorption with complications during topical tacrolimus treatment for orofacial Crohn disease. J Pediatr Gastroenterol Nutr 2001; 32: 207–208.

    Article  CAS  Google Scholar 

  8. Shah KN, Yan AC . Low but detectable serum levels of tacrolimus seen with the use of very dilute, extemporaneously compounded formulations of tacrolimus ointment in the treatment of patients with Netherton syndrome. Arch Dermatol 2006; 142: 1362–1363.

    Article  Google Scholar 

Download references

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Authors and Affiliations

  1. Pharmacy Department, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada

    S Prot-Labarthe & R Therrien

  2. Division of Hematology, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada

    M A Champagne, M Duval & C Joubert

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  1. S Prot-Labarthe
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  2. R Therrien
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  3. M A Champagne
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  4. M Duval
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  5. C Joubert
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Correspondence to R Therrien.

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Prot-Labarthe, S., Therrien, R., Champagne, M. et al. Toxic serum levels of tacrolimus after topical administration in an infant with severe cutaneous graft-versus-host disease. Bone Marrow Transplant 40, 295–296 (2007). https://doi.org/10.1038/sj.bmt.1705726

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