Immunosuppression‐induced leukoencephalopathy from tacrolimus (FK506)

Small, Steven L.; Fukui, Melanie B.; Bramblett, Gregory T.; Eidelman, Benjamin H.

doi:10.1002/ana.410400406

Cited by 117 publications

(61 citation statements)

References 16 publications

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“…25 The major adverse effects previously reported with tacrolimus have included nephrotoxicity, neurotoxicity, hyperglycemia, and hypertension. [29][30][31][32] Other commonly reported side-effects include microangiopathic hemolytic anemias, 33 hyperkalemia, 34 hypomagnesemia, 35 and hypercholesterolemia. 36 Unlike cyclosporine, tacrolimus rarely causes gingival hyperplasia or hirsutism.…”

Section: Discussionmentioning

confidence: 99%

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Tacrolimus (FK506) and methotrexate as prophylaxis for acute graft-versus-host disease in pediatric allogeneic stem cell transplantation

Yanik

Levine

Ratanatharathorn

et al. 2000

Bone Marrow Transplant

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Summary:Currently, limited data exist on the role of tacrolimus (FK506) in pediatric allogeneic marrow transplantation. Forty-one patients who received tacrolimus as prophylaxis were reviewed, with a median age of 9 years (range 0.2-16 years). Twenty-one patients underwent related donor transplants and 20 underwent unrelated donor transplants. All patients received tacrolimus beginning the day prior to transplant at a dose of 0.03 mg/kg/day by continuous i.v. infusion. When clinically possible, patients were switched to oral therapy in two divided doses, at four times the intravenous dose. Tacrolimus levels were monitored twice a week, and dosages adjusted to maintain serum levels 5-15 ng/ml. Common adverse effects included hypomagnesemia (98%), hypertension (49%), nephrotoxicity (34%), and tremors (32%). Less common side-effects (Ͻ10% cases) included seizures and hyperglycemia. The median time to ANC recovery (ANC Ͼ500 × 10 6 /l) was 15 days. For the related donor group, the incidence of grade II-IV acute GVHD was 33%, and grade III-IV GVHD 19%. For the unrelated donor group, the incidence of grade II-IV acute GVHD was 55%, and grade III-IV GVHD 30%. Overall, tacrolimus therapy was well tolerated as prophylaxis for acute GVHD in pediatric patients undergoing allogeneic transplantation. Bone Marrow Transplantation (2000) 26, 161-167.

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Section: Discussionmentioning

confidence: 99%

“…[30][31][32] Clinical manifestations have ranged from mild tremors, headaches, or mild paresthesias to more severe manifestations such as aphasia, paralysis, or seizures. The neurotoxicity noted in our pediatric trial was generally mild, manifested mainly as tremors in 32% of the patients.…”

Section: Discussionmentioning

confidence: 99%

Tacrolimus (FK506) and methotrexate as prophylaxis for acute graft-versus-host disease in pediatric allogeneic stem cell transplantation

Yanik

Levine

Ratanatharathorn

et al. 2000

Bone Marrow Transplant

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“…Initially Hepatic enchephalopathy due to graft dysfunction was suspected, but the Hepatic flow parameters and liver function tests were normal. Suspected neurotoxincity [28] was ruled out, since no improvement after switching over to cyclosporine [29] And the suspected azotemia(urea 230mg%) was also ruled out since the patient deteriorated even when urea came down (60mg%), after SLED. As per literature, even if there is subtle behavioural changes or muscle power weakness after transplant, possibility of ODS must be kept in mind [10] [14] Long duration of surgery is also a predisposing factor [13].…”

Section: Discussionmentioning

confidence: 99%

An Interesting Case of Osmotic Demyelination Syndrome, with two Cerebrovascular Accidents in a Post Liver Transplant Patient

Kanimozhi¹

2017

jmscr

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Though ODS is perceived to be a dreadful complication classically occurring after aggressive therapy for hyponatremia, it is important to recognise that osmotic demyelination can develop in patients with any levels of sodium, indicating the contribution of other factors [1] . Alcohol abuse, liver transplantation, malnutrition [2,3] are strong independent risk factors for the development of ODS. We present the events in a case of an Ethanol related Decompensated Liver Disease(DCLD), who developed ODS after liver transplantation, with normal sodium levels, who eventually suffered an embolic stroke later and a cerebral hemorrhage towards discharge.

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“…The major adverse effects associated with tacrolimus consist of nephrotoxicity, 32,33,51,55,60,61 neurotoxicity, [62][63][64][65][66][67][68] hyperglycemia [69][70][71][72] and hypertension. 73,74 Other less prevalent adverse effects include infectious complications, [75][76][77][78][79] lymphoproliferative disorders, 80-83 microangiopathic hemolytic anemia, 84 electrolyte abnormalities such as hyperkalemia, 85 hypomagnesemia, 86 and hypercholesterolemia.…”

Section: Adverse Effectsmentioning

confidence: 99%

Tacrolimus: a new agent for the prevention of graft-versus-host disease in hematopoietic stem cell transplantation

Jacobson

Uberti

Davis

et al. 1998

Bone Marrow Transplant

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Summary:Tacrolimus (FK506) is a macrolide lactone with potent immunosuppressive activity 100 times that of cyclosporine by weight. The molecular mechanism of action is mediated via an inhibition of the phosphorylase activity of calcineurin by drug-immunophilin complex, resulting in the inhibition of IL-2 gene expression. There are emerging studies now showing significant efficacy of tacrolimus in GVHD prevention in both related and unrelated donor transplantation. Three multicenter randomized studies comparing tacrolimus to cyclosporine have been completed, one each in related and unrelated donor transplantation; the remaining study involved both related and unrelated donor transplantation. All three studies showed a significantly lower incidence of grade II-IV acute GVHD in patients who received tacrolimus. One study in sibling donor transplantation showed that patients with advanced disease who received tacrolimus had a poorer survival than patients who received cyclosporine, but the survival was similar in patients with non-advanced disease. The remaining two studies, one in unrelated donors and the other combining both related and unrelated donors did not show any survival difference between the tacrolimus and cyclosporine groups. In addition, this review also highlights some of the critical questions regarding the role of this agent in allogeneic stem cell transplantation: (1) the contribution of methotrexate in combination with tacrolimus; (2) the starting i.v. dose of tacrolimus; (3) the suggested whole blood level of tacrolimus and its effect on nephrotoxicity; and (4) whether tacrolimus should be used in patients with advanced malignancy. Future studies using tacrolimus in combination with other immunosuppressants, and its use in patients with advanced malignancy will be warranted.

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Immunosuppression‐induced leukoencephalopathy from tacrolimus (FK506)

Cited by 117 publications

References 16 publications

Tacrolimus (FK506) and methotrexate as prophylaxis for acute graft-versus-host disease in pediatric allogeneic stem cell transplantation

Tacrolimus (FK506) and methotrexate as prophylaxis for acute graft-versus-host disease in pediatric allogeneic stem cell transplantation

An Interesting Case of Osmotic Demyelination Syndrome, with two Cerebrovascular Accidents in a Post Liver Transplant Patient

Tacrolimus: a new agent for the prevention of graft-versus-host disease in hematopoietic stem cell transplantation

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