LIVER TRANSPLANTATION, STARTING 12 HOURS AFTER TRANSPLANTATION, BY MOUTH, 100-200 MICROGRAMS/KG DAILY IN 2 DIVIDED DOSES OR BY INTRAVENOUS INFUSION OVER 24 HOURS, 10-50 MICROGRAMS/KG DAILY FOR UP TO MAX. 7 DAYS (THEN TRANSFER TO ORAL THERAPY); CHILD BY MOUTH, 300 MICROGRAMS/KG DAILY IN 2 DIVIDED DOSES OR BY INTRAVENOUS INFUSION OVER 24 HOURS, 50 MICROGRAMS/KG DAILY FOR UP TO MAX. 7 DAYS (THEN TRANSFER TO ORAL THERAPY)
RENAL TRANSPLANTATION, STARTING WITHIN 24 HOURS OF TRANSPLANTATION, BY MOUTH, 200-300 MICROGRAMS/KG DAILY IN 2 DIVIDED DOSES OR BY INTRAVENOUS INFUSION OVER 24 HOURS, 50-100 MICROGRAMS/KG DAILY FOR UP TO MAX. 7 DAYS (THEN TRANSFER TO ORAL THERAPY); CHILD BY MOUTH, 300 MICROGRAMS/KG DAILY IN 2 DIVIDED DOSES OR BY INTRAVENOUS INFUSION OVER 24 HOURS, 75-100 MICROGRAMS/KG DAILY FOR UP TO MAX. 7 DAYS (THEN TRANSFER TO ORAL THERAPY)
HEART TRANSPLANTATION (WITH OR WITHOUT ANTIBODY INDUCTION) STARTING WITHIN 5 DAYS OF TRANSPLANTATION, BY MOUTH, 75 MICROGRAMS/KG DAILY IN 2 DIVIDED DOSES OR BY INTRAVENOUS INFUSION OVER 24 HOURS, 10-20 MICROGRAMS/KG DAILY FOR UP TO MAX. 7 DAYS (THEN TRANSFER TO ORAL THERAPY); CHILD, WITHOUT ANTIBODY INDUCTION, INITIALLY BY INTRAVENOUS INFUSION OVER 24 HOURS, 30-50 MICROGRAMS/KG DAILY, THEN BY MOUTH, 300 MICROGRAMS/KG DAILY IN 2 DIVIDED DOSES AS SOON AS CLINICALLY POSSIBLE (GIVE 8-12 HOURS AFTER DISCONTINUING INTRAVENOUS INFUSION); FOLLOWING ANTIBODY INDUCTION, BY MOUTH, 100-300 MICROGRAMS/KG DAILY IN 2 DIVIDED DOSES
MAINTENANCE TREATMENT, DOSE ADJUSTED ACCORDING TO RESPONSE .
FOR THE TREATMENT OF ATOPIC ECZEMA, WHERE CONVENTIONAL THERAPIES ARE INEFFECTIVE OR UNSUITABLE, TACROLIMUS MAY BE APPLIED TWICE DAILY AS A 0.03 OR 0.1% OINTMENT; AN ATTEMPT SHOULD BE MADE TO USE THE LOWER STRENGTH OR REDUCE THE FREQUENCY OF APPLICATION WHEN POSSIBLE. EITHER STRENGTH MAY BE USED IN ADULTS, BUT CHILDREN AGED 2 TO 15 YEARS OF AGE SHOULD ONLY BE TREATED WITH 0.03% TACROLIMUS OINTMENT; USE SHOULD BE AVOIDED IN CHILDREN LESS THAN 2 YEARS OLD. IN THE UK, CHILDREN MAY BE TREATED TWICE DAILY FOR UP TO 3 WEEKS; THEREAFTER TREATMENT SHOULD BE REDUCED TO ONCE-DAILY APPLICATION. TREATMENT IN ADULTS AND CHILDREN SHOULD BE CONTINUED ONLY UNTIL RESOLUTION OF SIGNS AND SYMPTOMS. UK LICENSED PRODUCT INFORMATION RECOMMENDS THAT IF NO SIGNS OF IMPROVEMENT ARE SEEN AFTER 2 WEEKS OF TREATMENT, FURTHER TREATMENT OPTIONS SHOULD BE CONSIDERED; IN THE USA, IF CLINICAL MANIFESTATIONS DO NOT IMPROVE WITHIN 6 WEEKS, DIAGNOSIS OF ATOPIC ECZEMA SHOULD BE CONFIRMED THROUGH RE-EXAMINATION.
THERE IS LIMITED EVIDENCE THAT CHILDREN WITH HEPATITIS C REQUIRED ON AVERAGE ONE-THIRD OF THE DOSE OF TACROLIMUS NEEDED BY CHILDREN WITHOUT THE VIRUS.
TOPICAL TACROLIMUS HAS BEEN FOUND TO BE SAFE AND EFFECTIVE FOR SHORT-TERM USE IN THE TREATMENT OF MODERATE TO SEVERE ATOPIC ECZEMA. IN ADULT PATIENTS, THE EFFICACY OF 0.1% TACROLIMUS OINTMENT WAS SIMILAR TO THAT OF 0.1% HYDROCORTISONE BUTYRATE OINTMENT IN ONE STUDY AND MORE EFFECTIVE THAN A COMBINATION OF 0.1% HYDROCORTISONE BUTYRATE OINTMENT (APPLIED TO THE TRUNK AND EXTREMITIES) AND 1% HYDROCORTISONE ACETATE OINTMENT (APPLIED TO THE HEAD AND NECK) IN ANOTHER STUDY. IN PAEDIATRIC PATIENTS, BOTH 0.03 AND 0.1% TACROLIMUS WERE SIGNIFICANTLY MORE EFFECTIVE THAN 1% HYDROCORTISONE ACETATE OINTMENT. IN 18 OF 19 PATIENTS WITH FACIAL ATOPIC ECZEMA RESISTANT TO 0.03% TACROLIMUS OINTMENT, THERE WAS SIGNIFICANT IMPROVEMENT UPON APPLICATION OF A 0.03% LOTION FORMULATION, AND 6 PATIENTS WERE POSITIVE TO A PATCH TEST FOR WHITE PETROLATUM, AN INGREDIENT OF THE COMMERCIAL OINTMENT. A META-ANALYSIS CONCLUDED THAT TOPICAL TACROLIMUS 0.1% WAS AS EFFECTIVE AS POTENT TOPICAL CORTICOSTEROIDS AND MORE EFFECTIVE THAN MILD TOPICAL CORTICOSTEROIDS FOR THE TREATMENT OF ECZEMA; HOWEVER, TACROLIMUS WAS SIGNIFICANTLY MORE LIKELY TO CAUSE SKIN BURNING THAN CORTICOSTEROIDS. RESULTS FROM A SMALL, OPEN-LABEL STUDY SUGGEST THAT LONG-TERM INTERMITTENT USE OF TACROLIMUS OINTMENT MAY REVERSE THE SKIN ATROPHY INDUCED BY TOPICAL CORTICOSTEROIDS. IN GENERAL, HOWEVER, LONG-TERM USE OF TOPICAL TACROLIMUS SHOULD BE AVOIDED BECAUSE OF CONCERNS ABOUT POTENTIAL CARCINOGENICITY (SEE UNDER ADVERSE EFFECTS).
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
THERE ARE REPORTS OF RESPONSE TO TACROLIMUS, GIVEN ORALLY OR TOPICALLY, IN PATIENTS WITH PYODERMA GANGRENOSUM . A SMALL STUDY FOUND TOPICAL TACROLIMUS 0.3% IN CARMELLOSE SODIUM PASTE TO BE MORE EFFECTIVE THAN CLOBETASOL PROPIONATE 0.05% FOR PERISTOMAL PYODERMA GANGRENOSUM.