Tacrolimus (FK506): immunosuppressant in transplantation and autoimmune diseases | Clinique Omicron<\/title>\n<meta name=\"description\" content=\"Le tacrolimus est un immunosuppresseur inhibiteur de la calcineurine utilis\u00e9 en transplantation d'organes et dans les maladies auto-immunes. Surveillance des taux r\u00e9siduels, n\u00e9phrotoxicit\u00e9, diab\u00e8te post-transplantation et interactions m\u00e9dicamenteuses au Qu\u00e9bec.\">\n<meta name=\"keywords\" content=\"tacrolimus, FK506, Prograf tacrolimus, tacrolimus transplantation, tacrolimus taux r\u00e9siduel, tacrolimus n\u00e9phrotoxicit\u00e9, tacrolimus diab\u00e8te, tacrolimus interactions, tacrolimus dermite atopique, tacrolimus Qu\u00e9bec\">\n<link rel=\"preconnect\" href=\"https:\/\/fonts.googleapis.com\">\n<link href=\"https:\/\/fonts.googleapis.com\/css2?family=Cinzel:wght@600&family=Poppins:wght@400;500;600;700&display=swap\" rel=\"stylesheet\">\n<style>\n@import url('https:\/\/fonts.googleapis.com\/css2?family=Cinzel:wght@600&family=Poppins:wght@400;500;600;700&display=dump');\n\n.co-wrap * {\n font-family: 'Poppins', sans-serif;\n box-sizing: border-box;\n}\n.co-wrap {\n max-width: 1100px;\n margin: 0 auto;\n padding: 30px 0 60px;\n margin-top: 10px;\n}\n.co-label {\n font-family: 'Cinzel', 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(FK506)<\/h1>\n<style>.oc-fiche-cta{margin:8px 0 34px;padding:22px 24px;border:1.5px solid rgba(50,60,82,.15);border-left:4px solid #FF611C;border-radius:12px;background:#F4F6F8;font-family:Poppins,sans-serif}.oc-fiche-cta-t{font-size:18px;font-weight:600;color:#323C52;margin:0 0 4px;line-height:1.35}.oc-fiche-cta-x{font-size:15px;color:#4D6577;margin:0 0 14px;line-height:1.55}.oc-fiche-cta-b{display:flex;flex-wrap:wrap;gap:10px}.oc-fiche-cta-b a{display:inline-flex;align-items:center;justify-content:center;min-height:44px;padding:10px 18px;border-radius:8px;font-size:14px;font-weight:600;text-decoration:none;box-sizing:border-box}.oc-fiche-cta-b .oc-p{background:#FF611C;color:#fff}.oc-fiche-cta-b .oc-p:hover{background:#E04E0C}.oc-fiche-cta-b .oc-s{background:#fff;color:#323C52;border:1.5px solid rgba(50,60,82,.25)}@media (max-width:600px){.co-wrap h1{font-size:24px;line-height:1.25;text-transform:none}.oc-fiche-cta{padding:18px 16px}.oc-fiche-cta-b a{flex:1 1 100%}body .co-wrap > .co-table,body .co-wrap > .co-table tbody,body .co-wrap > .co-table tr,body .co-wrap > .co-table td{display:block;width:100%;box-sizing:border-box}body .co-wrap > .co-table{min-width:0;table-layout:auto}body .co-wrap > .co-table thead{display:none}body .co-wrap > .co-table tr{margin:0 0 10px;border:1px solid rgba(77,101,119,.18);border-radius:8px;overflow:hidden}body .co-wrap > .co-table td{padding:9px 12px;border:0}body .co-wrap > .co-table td:first-child{font-weight:600;color:#323C52;background:rgba(77,101,119,.07)}#ocw{transform:scale(.8);transform-origin:bottom right}}<\/style><div class=\"oc-fiche-cta\" data-oc-cta=\"fiche-haut-lab\"><p class=\"oc-fiche-cta-t\">Faire cette analyse<\/p><p class=\"oc-fiche-cta-x\">Pr\u00e9l\u00e8vements sanguins dans nos points de service au Qu\u00e9bec. Un professionnel peut aussi interpr\u00e9ter vos r\u00e9sultats avec vous.<\/p><div class=\"oc-fiche-cta-b\"><a class=\"oc-p\" href=\"https:\/\/cliniqueomicron.ca\/prelevements-medicaux\/\">Blood sampling<\/a><a class=\"oc-s\" href=\"https:\/\/cliniqueomicron.ca\/rendez-vous\/\">Make an appointment<\/a><a class=\"oc-s\" href=\"tel:+15146063350\">514 606-3350<\/a><\/div><\/div>\n\n\n <div class=\"co-intro\">\n Le tacrolimus \u2014 d\u00e9sign\u00e9 FK506 (pour Fujisawa Pharmaceutical compound K506 \u2014 isol\u00e9 en 1984 de <em>Streptomyces tsukubaensis<\/em>) + marketed as Prograf\u00ae (immediate-release form) + Advagraf\u00ae or Astagraf\u00ae (extended-release forms - LP) - is an immunosuppressive macrolide of the calcineurin inhibitor (CNI) family, which, since the 1990s, has been the cornerstone of immunosuppressive therapy in solid organ transplantation (kidney + liver + heart + lung + pancreas + intestine) + due to its immunosuppressive potency + its efficacy in preventing acute allograft rejection + and its overall superior safety profile to ciclosporin (the historical CNI). Its mechanism of action is based on binding to FKBP-12 (FK506 Binding Protein 12) \u2192 the tacrolimus-FKBP12 complex inhibits calcineurin (a calcium phosphatase) \u2192 blocks dephosphorylation of nuclear factor of activated T cells (NFAT) \u2192 NFAT cannot migrate into the nucleus \u2192 inhibits transcription of cytokine genes (IL-2 + IL-4 + TNF-\u03b1 + interferon-\u03b3) \u2192 block activation and proliferation of CD4+ and CD8+ T lymphocytes \u2192 powerful, selective immunosuppression. Tacrolimus is 10 to 100 times more potent than ciclosporin at equimolar concentration, enabling it to be used at much lower doses. Its clinical efficacy and safety depend critically on the maintenance of residual blood levels (C0 - residual level before morning intake - measured in whole blood on EDTA tube) within narrow therapeutic windows defined according to the type of organ transplanted + the post-transplant timeframe + and the recipient's level of immunological risk. Outside transplantation, tacrolimus is used topically (Protopic\u00ae - ointment 0.03 % and 0.1 %) in the treatment of moderate to severe atopic dermatitis + and systemically in certain refractory autoimmune diseases (cortico-resistant nephrotic syndrome + severe PCOS + autoimmune uveitis + dermatomyositis).\n <\/div>\n\n <h2>Clinical indications<\/h2>\n <ul class=\"co-list\">\n <li><strong>Transplantation r\u00e9nale :<\/strong> prevention of acute rejection + treatment of cortico-resistant acute rejection + in combination with mycophenolate mofetil (MMF) + corticosteroids + induction with monoclonal antibodies (basiliximab or thymoglobulin) \u2192 tacrolimus + MMF + corticosteroids = standard reference triple therapy in kidney transplantation<\/li>\n <li><strong>Transplantation h\u00e9patique :<\/strong> prevention and treatment of rejection \u2192 tacrolimus superior to cyclosporine + improved graft survival results<\/li>\n <li><strong>Heart + lung transplant:<\/strong> long-term immunosuppressive maintenance + in combination with MMF + corticoids + or everolimus<\/li>\n <li><strong>Syndrome n\u00e9phrotique cortico-r\u00e9sistant :<\/strong> GSFS + or refractory LGM + tacrolimus 0.1-0.2 mg\/kg\/d \u2192 target level 4-8 ng\/mL<\/li>\n <li><strong>Dermite atopique (forme topique \u2014 Protopic\u00ae) :<\/strong> 0.03 % (children 2-15 years) + 0.1 % (adults) \u2192 2 applications\/d until resolution + then proactive maintenance treatment (2\u00d7\/week) \u2192 efficacy comparable to moderate dermocorticoids + without skin atrophy + without significant topical systemic risk<\/li>\n <li><strong>Maladies auto-immunes r\u00e9fractaires :<\/strong> non-infectious uveitis + dermatomyositis + renal lupus \u2192 in combination with other immunosuppressants under specialized supervision<\/li>\n <\/ul>\n\n <h2>Taux r\u00e9siduels cibles selon le type de greffe<\/h2>\n\n <table class=\"co-table\">\n <thead>\n <tr>\n <th>Type of graft \/ Indication<\/th>\n <th>Phase pr\u00e9coce (0\u20133 mois)<\/th>\n <th>Late phase (>12 months)<\/th>\n <th>Remarks<\/th>\n <\/tr>\n <\/thead>\n <tbody>\n <tr>\n <td>Transplantation r\u00e9nale<\/td>\n <td>8\u201312 ng\/mL<\/td>\n <td>5\u20138 ng\/mL<\/td>\n <td>Cibles r\u00e9duites progressivement avec le temps + risque de rejet chronique si sous-exposition + n\u00e9phrotoxicit\u00e9 si sur-exposition<\/td>\n <\/tr>\n <tr>\n <td>Transplantation h\u00e9patique<\/td>\n <td>8\u201312 ng\/mL<\/td>\n <td>4\u20138 ng\/mL<\/td>\n <td>Descente plus rapide possible \u2192 le foie m\u00e9tabolise lui-m\u00eame le tacrolimus + risque de sous-immunosuppression si descente trop rapide<\/td>\n <\/tr>\n <tr>\n <td>Heart transplantation<\/td>\n <td>10\u201315 ng\/mL<\/td>\n <td>5\u201310 ng\/mL<\/td>\n <td>Cibles plus \u00e9lev\u00e9es en raison du risque \u00e9lev\u00e9 de rejet cardiaque + biopsie endomyocardique de surveillance<\/td>\n <\/tr>\n <tr>\n <td>Lung transplantation<\/td>\n <td>10\u201315 ng\/mL<\/td>\n <td>8\u201312 ng\/mL<\/td>\n <td>Cibles \u00e9lev\u00e9es maintenues longtemps \u2192 risque \u00e9lev\u00e9 de rejet chronique (syndrome de bronchiolite oblit\u00e9rante)<\/td>\n <\/tr>\n <tr>\n <td>Syndrome n\u00e9phrotique cortico-r\u00e9sistant<\/td>\n <td>4\u20138 ng\/mL<\/td>\n <td>4\u20136 ng\/mL<\/td>\n <td>Cibles plus basses \u2192 efficacit\u00e9 sur les podocytes + risque de n\u00e9phrotoxicit\u00e9 si taux trop \u00e9lev\u00e9s<\/td>\n <\/tr>\n <\/tbody>\n <\/table>\n\n <h2>Effets ind\u00e9sirables et toxicit\u00e9s<\/h2>\n <ul class=\"co-list\">\n <li><strong>N\u00e9phrotoxicit\u00e9 (la plus fr\u00e9quente et la plus importante) :<\/strong> renal afferent vasoconstriction \u2192 reduced GFR \u2192 acute renal failure (dose-dependent + reversible on dose reduction) + chronic calcineurin nephropathy (long-term irreversible interstitial fibrosis) \u2192 monitor creatinine + GFR regularly + keep levels within targets + avoid associated nephrotoxic drugs (NSAIDs + aminoglycosides + iodinated contrast media)<\/li>\n <li><strong>Diab\u00e8te post-transplantation (NODAT \u2014 New-Onset Diabetes After Transplantation) :<\/strong> inhibition of insulin secretion by pancreatic \u03b2-cells \u2192 hyperglycemia + post-transplant type 2 diabetes in 10-20 % recipients + particularly at-risk patients (obesity + advanced age + family history + HCV infection) \u2192 blood glucose monitoring + HbA1c + treatment if necessary<\/li>\n <li><strong>Neurotoxicit\u00e9 :<\/strong> fine hand tremors (frequent + dose-dependent) + headaches + insomnia + paresthesias + high-dose encephalopathy (PRES - Posterior Reversible Encephalopathy Syndrome) + convulsions<\/li>\n <li><strong>Opportunistic infections :<\/strong> CMV + BK virus (BK polyomavirus nephropathy - a frequent complication of renal transplantation) + Pneumocystis jirovecii + cryptococcosis + bacterial infections + systematic prophylaxis (valganciclovir + trimethoprim-sulfamethoxazole)<\/li>\n <li><strong>Post-transplant cancers :<\/strong> skin carcinomas (epidermoid +++ - mandatory sun protection) + EBV-associated post-transplant lymphoproliferative disease (PTLD) + Kaposi's disease<\/li>\n <li><strong>Hypertension art\u00e9rielle :<\/strong> by renal vasoconstriction + less pronounced than with cyclosporine<\/li>\n <li><strong>Hyperkali\u00e9mie :<\/strong> by impaired tubular excretion of potassium + avoid ACE inhibitors + high-dose ARB II if hyperkalemia<\/li>\n <li><strong>Hypertrichose + alop\u00e9cie :<\/strong> unlike ciclosporin (which causes hirsutism) + tacrolimus can cause alopecia<\/li>\n <\/ul>\n\n <h2>Interactions m\u00e9dicamenteuses majeures \u2014 m\u00e9tabolisme CYP3A4<\/h2>\n <ul class=\"co-list\">\n <li><strong>Le tacrolimus est un substrat du CYP3A4 et de la P-glycoprot\u00e9ine \u2192 nombreuses interactions :<\/strong><\/li>\n <li><strong>Inhibiteurs du CYP3A4 (augmentent les taux de tacrolimus \u2192 toxicit\u00e9) :<\/strong> azole antifungals (fluconazole + voriconazole + itraconazole + ketoconazole) - tacrolimus levels increased \u00d7 2 to 5 times ++ + macrolides (erythromycin + clarithromycin) + protease inhibitors (HIV) + diltiazem + verapamil + grapefruit juice (absolutely avoid)<\/li>\n <li><strong>Inducteurs du CYP3A4 (diminuent les taux de tacrolimus \u2192 risque de rejet) :<\/strong> rifampicin +++ (80-90 % reduction) + antiepileptics (phenytoin + carbamazepine + phenobarbital) + St. John's wort (Hypericum perforatum - over-the-counter) + nevirapine + efavirenz<\/li>\n <li><strong>M\u00e9dicaments n\u00e9phrotoxiques (risque de toxicit\u00e9 r\u00e9nale additive) :<\/strong> NSAIDs + aminoglycosides + amphotericin B + vancomycin + iodinated contrast media \u2192 prefer IV hydration + temporarily reduce dose if exposure necessary<\/li>\n <li><strong>Vaccins vivants att\u00e9nu\u00e9s :<\/strong> CONTRAINDICATED in transplant recipients on tacrolimus (immunosuppression) \u2192 MMR + varicella + yellow fever + BCG + rotavirus \u2192 inactivated vaccines permitted (inactivated influenza + pneumococcus + HBV)<\/li>\n <\/ul>\n\n <div class=\"co-infobox\">\n <span class=\"ico\">\u2119\ufe0f<\/span>\n <span>Le jus de pamplemousse contient des furanocoumarines qui inhibent le CYP3A4 intestinal \u2192 augmentation significative et impr\u00e9visible de la biodisponibilit\u00e9 du tacrolimus (+ 35\u2013100 %) \u2192 risque de toxicit\u00e9 aigu\u00eb (n\u00e9phrotoxicit\u00e9 + neurotoxicit\u00e9). Les patients sous tacrolimus doivent \u00eatre explicitement avertis d'\u00e9viter absolument le jus de pamplemousse + le pamplemousse entier + et les produits d\u00e9riv\u00e9s. Cette interaction s'applique \u00e9galement aux oranges de S\u00e9ville (marmelade) et aux pomelos.<\/span>\n <\/div>\n\n <div class=\"co-urgence\">\n <div class=\"co-urgence-titre\">Medical consultation recommended<\/div>\n <p>Consulter un m\u00e9decin ou un n\u00e9phrologue-transplantologue rapidement si un patient transplant\u00e9 sous tacrolimus pr\u00e9sente une augmentation de la cr\u00e9atinine + une hausse inexpliqu\u00e9e des taux r\u00e9siduels + une fi\u00e8vre + une confusion + ou des convulsions \u2014 ces signes peuvent indiquer une toxicit\u00e9 au tacrolimus + un rejet aigu + ou une infection opportuniste n\u00e9cessitant une prise en charge urgente. Pour la gestion des interactions m\u00e9dicamenteuses avec le tacrolimus et la surveillance r\u00e9guli\u00e8re des taux r\u00e9siduels, Clinique Omicron offre des consultations m\u00e9dicales dans ses points de service au Qu\u00e9bec et en t\u00e9l\u00e9m\u00e9decine. Pour prendre rendez-vous, visitez <a href=\"https:\/\/cliniqueomicron.ca\" style=\"color:#c0392b;font-weight:600;text-decoration:none;\">cliniqueomicron.ca<\/a>.<\/p>\n <\/div>\n\n <h2>Consult at Clinique Omicron<\/h2>\n <p>Les m\u00e9decins et infirmiers praticiens sp\u00e9cialis\u00e9s (IPS) de Clinique Omicron assurent le suivi ambulatoire des patients transplant\u00e9s sous tacrolimus (cr\u00e9atinine + taux r\u00e9siduels + glyc\u00e9mie + pression art\u00e9rielle + NFS + bilan h\u00e9patique), identifient et g\u00e8rent les interactions m\u00e9dicamenteuses avec le tacrolimus (antifoniques azol\u00e9s + macrolides + rifampicine + millepertuis), prescrivent le tacrolimus topique (Protopic\u00ae) dans les dermites atopiques mod\u00e9r\u00e9es \u00e0 s\u00e9v\u00e8res, rappellent les contre-indications aux vaccins vivants, et orientent imm\u00e9diatement vers le centre de transplantation en cas de suspicion de rejet ou de toxicit\u00e9. Des consultations sont disponibles dans plusieurs points de service au Qu\u00e9bec et en t\u00e9l\u00e9m\u00e9decine. Pour prendre rendez-vous, visitez <a href=\"https:\/\/cliniqueomicron.ca\" style=\"color:#4D6577;font-weight:600;text-decoration:none;\">cliniqueomicron.ca<\/a>.<\/p>\n\n <p class=\"co-disclaimer\">Le contenu de cette page est fourni \u00e0 titre informatif uniquement et ne remplace pas l'avis d'un m\u00e9decin ou d'un n\u00e9phrologue-transplantologue. Le tacrolimus est un m\u00e9dicament \u00e0 index th\u00e9rapeutique \u00e9troit n\u00e9cessitant une surveillance r\u00e9guli\u00e8re des taux r\u00e9siduels. Ne jamais modifier la dose de tacrolimus sans l'accord de l'\u00e9quipe de transplantation. Les vaccins vivants att\u00e9nu\u00e9s sont formellement contre-indiqu\u00e9s chez les patients immunosupprim\u00e9s sous tacrolimus.<\/p>\n\n<\/div>\n<\/body>\n<\/html>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>","protected":false},"excerpt":{"rendered":"<p>Tacrolimus (FK506) : immunosuppresseur en transplantation et maladies auto-immunes | Clinique Omicron Transplantation & Pharmacologie clinique & M\u00e9decine de famille Tacrolimus (FK506) Le tacrolimus \u2014 d\u00e9sign\u00e9 FK506 (pour Fujisawa Pharmaceutical compound K506 \u2014 isol\u00e9 en 1984 de Streptomyces tsukubaensis) + commercialis\u00e9 sous le nom de Prograf\u00ae (forme \u00e0 lib\u00e9ration imm\u00e9diate) + Advagraf\u00ae ou Astagraf\u00ae (formes… <a href=\"https:\/\/cliniqueomicron.ca\/en\/tacrolimus-fk506\/\" rel=\"bookmark\">Read More \"<span class=\"screen-reader-text\">Tacrolimus (FK506): immunosuppressant in transplantation and autoimmune diseases | Clinique Omicron<\/span><\/a><\/p>","protected":false},"author":1,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"om_disable_all_campaigns":false,"neve_meta_sidebar":"","neve_meta_container":"","neve_meta_enable_content_width":"off","neve_meta_content_width":100,"neve_meta_title_alignment":"","neve_meta_author_avatar":"","neve_post_elements_order":"","neve_meta_disable_header":"","neve_meta_disable_footer":"","neve_meta_disable_title":"","_themeisle_gutenberg_block_has_review":false,"_metasync_otto_title":"Tacrolimus (FK506) | Brossard | Clinique Omicron","_metasync_otto_description":"Tacrolimus (FK506) Tacrolimus (FK506) est un test de laboratoire qui permet d'\u00e9valuer certains aspects de votre \u00e9tat de sant\u00e9. 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(FK506)<\/h1>\n<style>.oc-fiche-cta{margin:8px 0 34px;padding:22px 24px;border:1.5px solid rgba(50,60,82,.15);border-left:4px solid #FF611C;border-radius:12px;background:#F4F6F8;font-family:Poppins,sans-serif}.oc-fiche-cta-t{font-size:18px;font-weight:600;color:#323C52;margin:0 0 4px;line-height:1.35}.oc-fiche-cta-x{font-size:15px;color:#4D6577;margin:0 0 14px;line-height:1.55}.oc-fiche-cta-b{display:flex;flex-wrap:wrap;gap:10px}.oc-fiche-cta-b a{display:inline-flex;align-items:center;justify-content:center;min-height:44px;padding:10px 18px;border-radius:8px;font-size:14px;font-weight:600;text-decoration:none;box-sizing:border-box}.oc-fiche-cta-b .oc-p{background:#FF611C;color:#fff}.oc-fiche-cta-b .oc-p:hover{background:#E04E0C}.oc-fiche-cta-b .oc-s{background:#fff;color:#323C52;border:1.5px solid rgba(50,60,82,.25)}@media (max-width:600px){.co-wrap h1{font-size:24px;line-height:1.25;text-transform:none}.oc-fiche-cta{padding:18px 16px}.oc-fiche-cta-b a{flex:1 1 100%}body .co-wrap > .co-table,body .co-wrap > .co-table tbody,body .co-wrap > .co-table tr,body .co-wrap > .co-table td{display:block;width:100%;box-sizing:border-box}body .co-wrap > .co-table{min-width:0;table-layout:auto}body .co-wrap > .co-table thead{display:none}body .co-wrap > .co-table tr{margin:0 0 10px;border:1px solid rgba(77,101,119,.18);border-radius:8px;overflow:hidden}body .co-wrap > .co-table td{padding:9px 12px;border:0}body .co-wrap > .co-table td:first-child{font-weight:600;color:#323C52;background:rgba(77,101,119,.07)}#ocw{transform:scale(.8);transform-origin:bottom right}}<\/style><div class=\"oc-fiche-cta\" data-oc-cta=\"fiche-haut-lab\"><p class=\"oc-fiche-cta-t\">Faire cette analyse<\/p><p class=\"oc-fiche-cta-x\">Pr\u00e9l\u00e8vements sanguins dans nos points de service au Qu\u00e9bec. Un professionnel peut aussi interpr\u00e9ter vos r\u00e9sultats avec vous.<\/p><div class=\"oc-fiche-cta-b\"><a class=\"oc-p\" href=\"https:\/\/cliniqueomicron.ca\/prelevements-medicaux\/\">Blood sampling<\/a><a class=\"oc-s\" href=\"https:\/\/cliniqueomicron.ca\/rendez-vous\/\">Make an appointment<\/a><a class=\"oc-s\" href=\"tel:+15146063350\">514 606-3350<\/a><\/div><\/div>\n\n\n <div class=\"co-intro\">\n Le tacrolimus \u2014 d\u00e9sign\u00e9 FK506 (pour Fujisawa Pharmaceutical compound K506 \u2014 isol\u00e9 en 1984 de <em>Streptomyces tsukubaensis<\/em>) + marketed as Prograf\u00ae (immediate-release form) + Advagraf\u00ae or Astagraf\u00ae (extended-release forms - LP) - is an immunosuppressive macrolide of the calcineurin inhibitor (CNI) family, which, since the 1990s, has been the cornerstone of immunosuppressive therapy in solid organ transplantation (kidney + liver + heart + lung + pancreas + intestine) + due to its immunosuppressive potency + its efficacy in preventing acute allograft rejection + and its overall superior safety profile to ciclosporin (the historical CNI). Its mechanism of action is based on binding to FKBP-12 (FK506 Binding Protein 12) \u2192 the tacrolimus-FKBP12 complex inhibits calcineurin (a calcium phosphatase) \u2192 blocks dephosphorylation of nuclear factor of activated T cells (NFAT) \u2192 NFAT cannot migrate into the nucleus \u2192 inhibits transcription of cytokine genes (IL-2 + IL-4 + TNF-\u03b1 + interferon-\u03b3) \u2192 block activation and proliferation of CD4+ and CD8+ T lymphocytes \u2192 powerful, selective immunosuppression. Tacrolimus is 10 to 100 times more potent than ciclosporin at equimolar concentration, enabling it to be used at much lower doses. Its clinical efficacy and safety depend critically on the maintenance of residual blood levels (C0 - residual level before morning intake - measured in whole blood on EDTA tube) within narrow therapeutic windows defined according to the type of organ transplanted + the post-transplant timeframe + and the recipient's level of immunological risk. Outside transplantation, tacrolimus is used topically (Protopic\u00ae - ointment 0.03 % and 0.1 %) in the treatment of moderate to severe atopic dermatitis + and systemically in certain refractory autoimmune diseases (cortico-resistant nephrotic syndrome + severe PCOS + autoimmune uveitis + dermatomyositis).\n <\/div>\n\n <h2>Clinical indications<\/h2>\n <ul class=\"co-list\">\n <li><strong>Transplantation r\u00e9nale :<\/strong> prevention of acute rejection + treatment of cortico-resistant acute rejection + in combination with mycophenolate mofetil (MMF) + corticosteroids + induction with monoclonal antibodies (basiliximab or thymoglobulin) \u2192 tacrolimus + MMF + corticosteroids = standard reference triple therapy in kidney transplantation<\/li>\n <li><strong>Transplantation h\u00e9patique :<\/strong> prevention and treatment of rejection \u2192 tacrolimus superior to cyclosporine + improved graft survival results<\/li>\n <li><strong>Heart + lung transplant:<\/strong> long-term immunosuppressive maintenance + in combination with MMF + corticoids + or everolimus<\/li>\n <li><strong>Syndrome n\u00e9phrotique cortico-r\u00e9sistant :<\/strong> GSFS + or refractory LGM + tacrolimus 0.1-0.2 mg\/kg\/d \u2192 target level 4-8 ng\/mL<\/li>\n <li><strong>Dermite atopique (forme topique \u2014 Protopic\u00ae) :<\/strong> 0.03 % (children 2-15 years) + 0.1 % (adults) \u2192 2 applications\/d until resolution + then proactive maintenance treatment (2\u00d7\/week) \u2192 efficacy comparable to moderate dermocorticoids + without skin atrophy + without significant topical systemic risk<\/li>\n <li><strong>Maladies auto-immunes r\u00e9fractaires :<\/strong> non-infectious uveitis + dermatomyositis + renal lupus \u2192 in combination with other immunosuppressants under specialized supervision<\/li>\n <\/ul>\n\n <h2>Taux r\u00e9siduels cibles selon le type de greffe<\/h2>\n\n <table class=\"co-table\">\n <thead>\n <tr>\n <th>Type of graft \/ Indication<\/th>\n <th>Phase pr\u00e9coce (0\u20133 mois)<\/th>\n <th>Late phase (>12 months)<\/th>\n <th>Remarks<\/th>\n <\/tr>\n <\/thead>\n <tbody>\n <tr>\n <td>Transplantation r\u00e9nale<\/td>\n <td>8\u201312 ng\/mL<\/td>\n <td>5\u20138 ng\/mL<\/td>\n <td>Cibles r\u00e9duites progressivement avec le temps + risque de rejet chronique si sous-exposition + n\u00e9phrotoxicit\u00e9 si sur-exposition<\/td>\n <\/tr>\n <tr>\n <td>Transplantation h\u00e9patique<\/td>\n <td>8\u201312 ng\/mL<\/td>\n <td>4\u20138 ng\/mL<\/td>\n <td>Descente plus rapide possible \u2192 le foie m\u00e9tabolise lui-m\u00eame le tacrolimus + risque de sous-immunosuppression si descente trop rapide<\/td>\n <\/tr>\n <tr>\n <td>Heart transplantation<\/td>\n <td>10\u201315 ng\/mL<\/td>\n <td>5\u201310 ng\/mL<\/td>\n <td>Cibles plus \u00e9lev\u00e9es en raison du risque \u00e9lev\u00e9 de rejet cardiaque + biopsie endomyocardique de surveillance<\/td>\n <\/tr>\n <tr>\n <td>Lung transplantation<\/td>\n <td>10\u201315 ng\/mL<\/td>\n <td>8\u201312 ng\/mL<\/td>\n <td>Cibles \u00e9lev\u00e9es maintenues longtemps \u2192 risque \u00e9lev\u00e9 de rejet chronique (syndrome de bronchiolite oblit\u00e9rante)<\/td>\n <\/tr>\n <tr>\n <td>Syndrome n\u00e9phrotique cortico-r\u00e9sistant<\/td>\n <td>4\u20138 ng\/mL<\/td>\n <td>4\u20136 ng\/mL<\/td>\n <td>Cibles plus basses \u2192 efficacit\u00e9 sur les podocytes + risque de n\u00e9phrotoxicit\u00e9 si taux trop \u00e9lev\u00e9s<\/td>\n <\/tr>\n <\/tbody>\n <\/table>\n\n <h2>Effets ind\u00e9sirables et toxicit\u00e9s<\/h2>\n <ul class=\"co-list\">\n <li><strong>N\u00e9phrotoxicit\u00e9 (la plus fr\u00e9quente et la plus importante) :<\/strong> renal afferent vasoconstriction \u2192 reduced GFR \u2192 acute renal failure (dose-dependent + reversible on dose reduction) + chronic calcineurin nephropathy (long-term irreversible interstitial fibrosis) \u2192 monitor creatinine + GFR regularly + keep levels within targets + avoid associated nephrotoxic drugs (NSAIDs + aminoglycosides + iodinated contrast media)<\/li>\n <li><strong>Diab\u00e8te post-transplantation (NODAT \u2014 New-Onset Diabetes After Transplantation) :<\/strong> inhibition of insulin secretion by pancreatic \u03b2-cells \u2192 hyperglycemia + post-transplant type 2 diabetes in 10-20 % recipients + particularly at-risk patients (obesity + advanced age + family history + HCV infection) \u2192 blood glucose monitoring + HbA1c + treatment if necessary<\/li>\n <li><strong>Neurotoxicit\u00e9 :<\/strong> fine hand tremors (frequent + dose-dependent) + headaches + insomnia + paresthesias + high-dose encephalopathy (PRES - Posterior Reversible Encephalopathy Syndrome) + convulsions<\/li>\n <li><strong>Opportunistic infections :<\/strong> CMV + BK virus (BK polyomavirus nephropathy - a frequent complication of renal transplantation) + Pneumocystis jirovecii + cryptococcosis + bacterial infections + systematic prophylaxis (valganciclovir + trimethoprim-sulfamethoxazole)<\/li>\n <li><strong>Post-transplant cancers :<\/strong> skin carcinomas (epidermoid +++ - mandatory sun protection) + EBV-associated post-transplant lymphoproliferative disease (PTLD) + Kaposi's disease<\/li>\n <li><strong>Hypertension art\u00e9rielle :<\/strong> by renal vasoconstriction + less pronounced than with cyclosporine<\/li>\n <li><strong>Hyperkali\u00e9mie :<\/strong> by impaired tubular excretion of potassium + avoid ACE inhibitors + high-dose ARB II if hyperkalemia<\/li>\n <li><strong>Hypertrichose + alop\u00e9cie :<\/strong> unlike ciclosporin (which causes hirsutism) + tacrolimus can cause alopecia<\/li>\n <\/ul>\n\n <h2>Interactions m\u00e9dicamenteuses majeures \u2014 m\u00e9tabolisme CYP3A4<\/h2>\n <ul class=\"co-list\">\n <li><strong>Le tacrolimus est un substrat du CYP3A4 et de la P-glycoprot\u00e9ine \u2192 nombreuses interactions :<\/strong><\/li>\n <li><strong>Inhibiteurs du CYP3A4 (augmentent les taux de tacrolimus \u2192 toxicit\u00e9) :<\/strong> azole antifungals (fluconazole + voriconazole + itraconazole + ketoconazole) - tacrolimus levels increased \u00d7 2 to 5 times ++ + macrolides (erythromycin + clarithromycin) + protease inhibitors (HIV) + diltiazem + verapamil + grapefruit juice (absolutely avoid)<\/li>\n <li><strong>Inducteurs du CYP3A4 (diminuent les taux de tacrolimus \u2192 risque de rejet) :<\/strong> rifampicin +++ (80-90 % reduction) + antiepileptics (phenytoin + carbamazepine + phenobarbital) + St. John's wort (Hypericum perforatum - over-the-counter) + nevirapine + efavirenz<\/li>\n <li><strong>M\u00e9dicaments n\u00e9phrotoxiques (risque de toxicit\u00e9 r\u00e9nale additive) :<\/strong> NSAIDs + aminoglycosides + amphotericin B + vancomycin + iodinated contrast media \u2192 prefer IV hydration + temporarily reduce dose if exposure necessary<\/li>\n <li><strong>Vaccins vivants att\u00e9nu\u00e9s :<\/strong> CONTRAINDICATED in transplant recipients on tacrolimus (immunosuppression) \u2192 MMR + varicella + yellow fever + BCG + rotavirus \u2192 inactivated vaccines permitted (inactivated influenza + pneumococcus + HBV)<\/li>\n <\/ul>\n\n <div class=\"co-infobox\">\n <span class=\"ico\">\u2119\ufe0f<\/span>\n <span>Le jus de pamplemousse contient des furanocoumarines qui inhibent le CYP3A4 intestinal \u2192 augmentation significative et impr\u00e9visible de la biodisponibilit\u00e9 du tacrolimus (+ 35\u2013100 %) \u2192 risque de toxicit\u00e9 aigu\u00eb (n\u00e9phrotoxicit\u00e9 + neurotoxicit\u00e9). Les patients sous tacrolimus doivent \u00eatre explicitement avertis d'\u00e9viter absolument le jus de pamplemousse + le pamplemousse entier + et les produits d\u00e9riv\u00e9s. Cette interaction s'applique \u00e9galement aux oranges de S\u00e9ville (marmelade) et aux pomelos.<\/span>\n <\/div>\n\n <div class=\"co-urgence\">\n <div class=\"co-urgence-titre\">Medical consultation recommended<\/div>\n <p>Consulter un m\u00e9decin ou un n\u00e9phrologue-transplantologue rapidement si un patient transplant\u00e9 sous tacrolimus pr\u00e9sente une augmentation de la cr\u00e9atinine + une hausse inexpliqu\u00e9e des taux r\u00e9siduels + une fi\u00e8vre + une confusion + ou des convulsions \u2014 ces signes peuvent indiquer une toxicit\u00e9 au tacrolimus + un rejet aigu + ou une infection opportuniste n\u00e9cessitant une prise en charge urgente. Pour la gestion des interactions m\u00e9dicamenteuses avec le tacrolimus et la surveillance r\u00e9guli\u00e8re des taux r\u00e9siduels, Clinique Omicron offre des consultations m\u00e9dicales dans ses points de service au Qu\u00e9bec et en t\u00e9l\u00e9m\u00e9decine. Pour prendre rendez-vous, visitez <a href=\"https:\/\/cliniqueomicron.ca\" style=\"color:#c0392b;font-weight:600;text-decoration:none;\">cliniqueomicron.ca<\/a>.<\/p>\n <\/div>\n\n <h2>Consult at Clinique Omicron<\/h2>\n <p>Les m\u00e9decins et infirmiers praticiens sp\u00e9cialis\u00e9s (IPS) de Clinique Omicron assurent le suivi ambulatoire des patients transplant\u00e9s sous tacrolimus (cr\u00e9atinine + taux r\u00e9siduels + glyc\u00e9mie + pression art\u00e9rielle + NFS + bilan h\u00e9patique), identifient et g\u00e8rent les interactions m\u00e9dicamenteuses avec le tacrolimus (antifoniques azol\u00e9s + macrolides + rifampicine + millepertuis), prescrivent le tacrolimus topique (Protopic\u00ae) dans les dermites atopiques mod\u00e9r\u00e9es \u00e0 s\u00e9v\u00e8res, rappellent les contre-indications aux vaccins vivants, et orientent imm\u00e9diatement vers le centre de transplantation en cas de suspicion de rejet ou de toxicit\u00e9. Des consultations sont disponibles dans plusieurs points de service au Qu\u00e9bec et en t\u00e9l\u00e9m\u00e9decine. Pour prendre rendez-vous, visitez <a href=\"https:\/\/cliniqueomicron.ca\" style=\"color:#4D6577;font-weight:600;text-decoration:none;\">cliniqueomicron.ca<\/a>.<\/p>\n\n <p class=\"co-disclaimer\">Le contenu de cette page est fourni \u00e0 titre informatif uniquement et ne remplace pas l'avis d'un m\u00e9decin ou d'un n\u00e9phrologue-transplantologue. Le tacrolimus est un m\u00e9dicament \u00e0 index th\u00e9rapeutique \u00e9troit n\u00e9cessitant une surveillance r\u00e9guli\u00e8re des taux r\u00e9siduels. Ne jamais modifier la dose de tacrolimus sans l'accord de l'\u00e9quipe de transplantation. Les vaccins vivants att\u00e9nu\u00e9s sont formellement contre-indiqu\u00e9s chez les patients immunosupprim\u00e9s sous tacrolimus.<\/p>\n\n<\/div>\n<\/body>\n<\/html>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>","protected":false},"excerpt":{"rendered":"<p>Tacrolimus (FK506) : immunosuppresseur en transplantation et maladies auto-immunes | Clinique Omicron Transplantation & Pharmacologie clinique & M\u00e9decine de famille Tacrolimus (FK506) Le tacrolimus \u2014 d\u00e9sign\u00e9 FK506 (pour Fujisawa Pharmaceutical compound K506 \u2014 isol\u00e9 en 1984 de Streptomyces tsukubaensis) + commercialis\u00e9 sous le nom de Prograf\u00ae (forme \u00e0 lib\u00e9ration imm\u00e9diate) + Advagraf\u00ae ou Astagraf\u00ae (formes… <a href=\"https:\/\/cliniqueomicron.ca\/en\/tacrolimus-fk506\/\" rel=\"bookmark\">Read More \"<span class=\"screen-reader-text\">Tacrolimus (FK506): immunosuppressant in transplantation and autoimmune diseases | Clinique Omicron<\/span><\/a><\/p>","protected":false},"author":1,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"om_disable_all_campaigns":false,"neve_meta_sidebar":"","neve_meta_container":"","neve_meta_enable_content_width":"off","neve_meta_content_width":100,"neve_meta_title_alignment":"","neve_meta_author_avatar":"","neve_post_elements_order":"","neve_meta_disable_header":"","neve_meta_disable_footer":"","neve_meta_disable_title":"","_themeisle_gutenberg_block_has_review":false,"_metasync_otto_title":"Tacrolimus (FK506) | Brossard | Clinique Omicron","_metasync_otto_description":"Tacrolimus (FK506) Tacrolimus (FK506) est un test de laboratoire qui permet d'\u00e9valuer certains aspects de votre \u00e9tat de sant\u00e9. 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