Tacrolimus

Author: Prof. Dr. med. Peter Altmeyer

Our authors

Last updated on: 29.10.2020

Dieser Artikel auf Deutsch

Definition
This section has been translated automatically.

Macrolide belonging to the group of calcineurin inhibitors, which is produced by the fungus Streptomyces tsukubaensis and is used as a systemic and topical immunosuppressive agent.

Pharmacodynamics (Effect)
This section has been translated automatically.

  • Tacrolimus inhibits the initial T cell activation, the differentiation and proliferation of cytotoxic T cells as well as specifically the expression of E-Selectin (adhesion molecule on endothelial cells).
  • Topically applied Tacrolimus binds to the cytoplasmic FK 506 binding protein-12 at the T-cell and thereby blocks the activity of the phosphatase calcineurin. Reduced activity of calcineurin inhibits the expression of the transcription factor NFAT (nuclear factor of activated T cells), the proinflammatory cytokines IL-2, -3, -4 and -5, GM-CSF and interferon gamma.

Indication
This section has been translated automatically.

Limited indication
This section has been translated automatically.

Systemic: pregnancy (risk of spina bifida).

Dosage and method of use
This section has been translated automatically.

  • Systemic: 0,1-0,2 mg/day/kg bw p.o. distributed over 2 single doses.

    Remember! Under the immunosuppression with Tacrolimus the ventricular wall and septum can thicken. Under therapy regular echocardiographic examinations are necessary. In women of childbearing age a pregnancy should be excluded before therapy and an effective contraception should be carried out under therapy!

  • Topical: 0.03% for children aged 2-16 years. 0.1% for adults/teenagers aged 16 years and older. The first three weeks: Apply thinly 2 times/day to the affected areas. From the 4th week: Apply thinly once/day to the eczema areas.

Undesirable effects
This section has been translated automatically.

Topical: Local irritation and burning, especially during the first two days of treatment. See table 1.

Interactions
This section has been translated automatically.

See Table 2.

Contraindication
This section has been translated automatically.

  • Systemic: Allergy to tacrolimus, pregnancy and lactation.
  • Topical: Known allergy to macrolides or other ingredients of the preparation Protopic. Pregnancy, lactation, Netherton syndrome, erythroderma. Bacterial, viral or mycotic skin infections (e.g. pyoderma, varicella, herpes simplex). In case of liver diseases, restraint with regard to the dosage. Caution! Avoid exposure to UV during ongoing therapy.

Recipe(s)
This section has been translated automatically.

  • To "stretch" finished dermatics with other vehicle systems is a practiced dermatological practice to achieve price advantages. This calculation mechanism however has to take into account the "auxiliary tax for pharmacies" according to which prescriptions have to be calculated. In case of a ready-to-use dermatological product the required package is not calculated grammatically but by the respective pack!
  • A standardized formulation is given in the new formulation form (NRF): Protopic ointment 0.1% (1 or 2 parts) + Lanette N 1 part/Aqua conservans 7 parts (1 part). The following formulation is a stable alternative not listed in the NRF: Protopic ointment 0,1% (1 part = 30,0 g) + low density polyethylene 2,5 + viscous paraffin ad 50,0 (vehicle type = lipophilic gel).

Preparations
This section has been translated automatically.

Prograf, Protopic 0.03% and 0.1%

Note(s)
This section has been translated automatically.

  • Remember! Caution is required for long-term application, as animal experiments have shown an increased risk of local carcinoma.

  • Since 2006, the US-American product information has carried a particularly highlighted warning notice (black box), in which the lack of knowledge about the long-term safety of the products with regard to the development of skin cancer and lymphoma is explicitly pointed out. S.a. Pimecrolimus.
  • After market launch of the drugs, the occurrence of lymphomas was observed in patients who were treated topically with calcineurin inhibitors and glucocorticoids. However, this could not be confirmed in a subsequent study.
  • In several case reports the successful application of Tacrolimus for the antipruritic therapy at diseases like lichen sclerosus et atrophicus, chronic hand eczema, scrotal eczema and graft-versus-host-disease has already been reported.
  • Also with the psoriasis inversa, clinical improvements after topical application of tacrolimus ( off-label-use) (see below calcineurin inhibitors) were shown in individual cases.

Literature
This section has been translated automatically.

  1. Arellano FM et al (2006) Risk of Lymphoma Following Exposure to Calcineurin Inhibitors and Topical Steroids in Patients with Atopic Dermatitis. J Invest Dermatol (epub)
  2. Bohm M (2003) Successful treatment of anogenital lichen sclerosus with topical tacrolimus. Arch Dermatol 139: 922-924
  3. Braza TJ et al (2003) Tacrolimus 0.1% ointment for seborrhoic dermatitis: an open-label pilot study. Br J Dermatol 148:1242-1244
  4. Clayton TH et al (2003) Topical tacrolimus for facial psoriasis. Br J Dermatol 149: 419-420
  5. Drake L, Prendergast M, Maher R et al (2001) The impact of tacrolimus ointment on health-related quality of life of adults and pediatric patients with atopic dermatitis. J Am Acad Dermatol 44: 65-72
  6. Freeman AK et al (2003) Tacrolimus ointment for the treatment of psoriasis on the face and intertriginous areas. J Am Acad Dermatol 48: 564-568
  7. Goldman D (2001) Tacrolimus ointment for the treatment of steroid-induced rosacea: a preliminary report. J Am Acad Dermatol 44: 995-998
  8. Kain S, Stephens CJ (2003) Successfull treatment of disseminated granuloma anulare with topical tacrolimus. Br J Dermatol 149(Suppl 64): 24
  9. Kunstfeld R (2003) Successful treatment of vulvar lichen sclerosus with topical tacrolimus. Arch Dermatol 139: 850-852
  10. Liu J Albers MW, Wandless TH et al (1992) Inhibition of T cell signaling by immunophilin-ligand complexes correlates with loss of calcineurin phosphatase activity. Biochemistry 31: 3896-3901
  11. Meshkinpour A (2003) An open pilot study using tacrolimus ointment in the treatment of seborrheic dermatitis. J Am Acad Dermatol 49: 145-147
  12. Niwa Y et al (2003) Topical application of the immunosuppressant tacrolimus accelerates carcinogenesis in mouse skin. Br J Dermatol 149: 960-967
  13. Plettenberg H et al (2003) Childhood vitiligo and tacrolimus: immunomodulating treatment for an autoimmune disease. Arch Dermatol 139: 651-654
  14. Ruzicka T et al (1997) A short-term trial of tacrolimus ointment for atopic dermatitis. European Tacrolimus Multicenter Atopic Dermatitis Study Group. New Engl J Med 337: 816-821
  15. Schroer B, Lockey R (2003) Oral tacrolimus for severe recalcitrant atopic eczema. J Allergy Clin Immunol 111: 1409-1410
  16. Ständer S et al (2006) Diagnostic and therapeutic procedures in chronic pruritis. J Dtsch Dermatol Ges 4: 350-370
  17. Soter NA et al (2001) Tacrolimus ointment for the treatment of atopic dermatitis in adult patients. J Am Acad Dermatol 44: 39-46
  18. Ständer S et al (2003) Antipruritic effects of pimecrolimus and tacrolimus. dermatologist 54: 413-417
  19. Tanghetti EA (2003) Tacrolimus ointment 0.1% produces repigmentation in patients with vitiligo: results of a prospective patient series. Cutis 71: 158-162
  20. Travis LB (2003) Successful treatment of vitiligo with 0.1% tacrolimus ointment. Arch Dermatol 139: 571-574
  21. Wohlrab J (2006) Calcineurin inhibitors for the topical therapy of psoriasis. dermatologist 57: 685-689
  22. Wolf G (2008) Recipe tip: Stability of Tacrolimus in different vehicle systems. dermatologist 59: 678-679
  23. Yamamoto T et al (2003) Deep dermatophytosis during topical tacrolimus therapy for psoriasis. Acta Derm Venereol 83: 291-292

Tables
This section has been translated automatically.

Essential side effects of Tacrolimus

Organ System

Side effects (UAW)

Airways

bronchial asthma, bronchospasm, dyspnoea, atelectasis, pulmonary oedema, pleural effusion, rhinitis, sinusitis

Blood Lymph

anaemia (haemolytic or aplastic anaemia), blood formation disorders, blood coagulation disorders, thrombocytopenia, pancytopenia, leucopenia, leucocytosis, eosinophilia, splenomegaly, non-Hodgkin's lymphomas

GIT

Abdominal pain, gastrointestinal disorders, eosinophilic enteritis, cholestasis, hepatitis, increase in AP, transaminases, bilirubin

Urinary tract

Haematuria, oliguria, anuria, renal dysfunction, hydronephrosis, urea and creatinine increase, acute renal failure

Skin

abscesses, herpes simplex, ecchymosis, hirsutism, hyperhidrosis, alopecia, photosensitization, pruritus, exanthema, epidermolysis, Lyell syndrome, anaphylactic reactions, erythema nodosum, spinocellular carcinoma, thrombocytopenic purpura

Cardiovascular

Hypertension, edema, tachycardia, cardiac arrhythmia, hypertrophic cardiomyopathy

Nervous System

Anxiety, depression, psychosis, aphasia, encephalopathy, seizures, tremor, neuropathy, myasthenia, headache, quadriplegia, apoplexy

Sensory Organs

Amblyopia, cataract, visual disturbances, glaucoma, conjunctivitis, dizziness, tinnitus, deafness

Metabolism, Endocrine

Alkalosis, acidosis, electrolyte disorders, desiccosis, diabetes mellitus, glucose tolerance disorder, gout attack, gynecomastia

Support apparatus

Arthralgia, myalgia, muscle spasms, osteoporosis, rhabdomyolysis, aseptic bone necrosis

System reactions

fever, chills, sepsis


Essential interactions of Tacrolimus

Aciclovir

CNS toxicity ↑

Aminoglycosides

Renal damage

Amoxicillin

Tacrolimus mirror ↑

amphotericin B

Renal damage

Ciclosporin A

Renal damage

Cisplatin

Renal damage

Clarithromycin

Tacrolimus mirror ↑

Clotrimazole

Tacrolimus mirror ↑

Danazol

Tacrolimus mirror ↑

diuretics, potassium-sparing

Hyperkalemia ↑, avoid combination

Erythromycin

Renal damage

Fluconazole

Renal damage

Ganciclovir

CNS toxicity ↑

Ibuprofen

Renal damage

Imipenem

Tacrolimus mirror ↓

Potassium preparations

Hyperkalemia ↑, avoid combination

Ketoconazole

Renal damage

Live virus vaccines

Avoid combination

Methylprednisolone

Tacrolimus mirror ↑

Rifampicin

Tacrolimus mirror ↓

Authors

Last updated on: 29.10.2020