Diarrhea tacrolimus

Tacrolimus, an immunosuppressant that inhibits T-cell activation, is a useful alternative in severe recalcitrant psoriasis. Although it is not FDA approved for this indication, patients have received oral doses of 0.05 mg/kg daily, with increases up to 0.15 mg/kg daily, depending on results. Adverse effects include diarrhea, nausea, paresthesias, hypertension, tremor, and insomnia. 

The principal adverse reactions of tacrolimus are tremor, headache, diarrhea, hypertension, nausea, and renal dysfunction. Other reactions may include insomnia, paresthesia, constipation, anorexia, vomiting, anemia, leukocytosis, thrombocytopenia, hyperglycemia, dyspnea, pruritus, rash, abdominal pain, fever, asthenia, back pain,... 

Toxicities of the PSIs can include profound myelosuppression (especially thrombocytopenia), hepatotoxicity, diarrhea, hypertriglyceridemia, pneumonitis, and headache. Because nephrotoxicity is of major concern when administering calcineurin inhibitors, there is interest in increased early use of PSIs since renal toxicity is less common with these agents. However, increased use in stem cell transplantation regimens as graft-versus-host disease prophylaxis, particularly when combined with tacrolimus, has revealed an increased incidence of hemolytic-uremic syndrome. 

Adverse Effects. Common side effects of tacrolimus include gastrointestinal disturbances (cramps, nausea, diarrhea, constipation), weakness, fever, and skin rashes and itching. More serious problems include renal and central nervous system (CNS) toxicity (headache, anxiety, nervousness, seizures).41 Tacrolimus is also associated with problems with glucose metabolism (hyperglycemia, glucose intolerance), and can cause diabetes mellitus in certain individuals.73... 

Tacrolimus, an immunosuppressant that inhibits T-cell activation, is a useful alternative in severe recalcitrant psoriasis. Although it is not FDA approved for this indication, patients have received oral doses of 0.05 mg/kg daily, with increases up to 0.15 mg/kg daily, depending on results. Adverse effects include diarrhea, nausea, paresthesias, hypertension, tremor, and insomnia. Methotrexate, an antimetabolite, is indicated for moderate to severe psoriasis. It is particularly beneficial for psoriatic arthritis. It is also indicated for patients refractory to topical or UV therapy. Methotrexate can he administered orally, subcutaneously, or intramuscularly. The starting dose is 7.5 to 15 mg per week, increased incrementally by 2.5 mg every 2 to 4 weeks until response maximal doses are approximately 25 mg/wk. Adverse effects include nausea, vomiting, mucosal ulceration, stomatitis, malaise, headache, macrocytic anemia, and hepatic and pulmonary toxicity. Nausea and macrocytic anemia can be ameliorated by giving oral fohc acid 1 to 5 mg/day. Methotrexate should be avoided in patients with active infections and in those with liver disease. It is contraindicated in pregnancy because it is teratogenic. 

A 68-year-old man developed diarrhea, dehydration, and atrial fibrillation 4 months after liver transplantation. He was taking tacrolimus (blood concentration 13 ng/ml) and was given a continuous infusion of diltiazem for 1 day followed by oral therapy. Three days later he became delirious, confused, and agitated, and the blood concentration of tacrolimus was 55 ng/ml. His mental statns gradnally improved after withdrawal of both dmgs. 

A 49-year-old woman taking ciclosporin, prednisolone, and mycophenolate developed acute refractory rejection 4 days after renal transplantation. After an unsuccessful glucocorticoid pulse, her immunosuppressive regimen was successively changed to muromonab and tacrolimus with mycophenolate maintenance. Twelve days after transplantation she had abdominal pain and watery/bloody diarrhea. Colonoscopy showed multiple ulcers with mucosal injection and colon edema. A biopsy suggested ischemic cohtis and cytomegalovirus infection was ruled out. Her sjmptoms persisted until mycophenolate was withdrawn and further colonoscopy showed complete resolution. 

A 29-year-old man was given mycophenolate and tacrolimus for an episode of renal transplant rejection that occurred 6.5 years after transplantation. Four weeks after tacrolimus was begun, he had diarrhea, nausea, and malaise. There was C. difficile toxin in the stools, and his symptoms abated with metronidazole. About 1 month later, he developed diarrhea, fever, and severe dehydration. Clostridium difficile toxin was again detected in the stools, and his symptoms completely resolved with oral vancomycin and withdrawal of tacrolimus. 

Sharma AK, Holder FE. Clostridium difficile diarrhea after use of tacrolimus following renal transplantation. Clin Infect Dis 1998 27(6) 1540-1. 

Adverse effects include diarrhea, nausea, paresthesias, hypertension, tremor, and insomnia. Other toxicities with topical tacrolimus— including renal insufficiency and immunosuppression—have been rarely reported. ... 

The principal toxicities of mycophenolate are gastrointestinal and hematologic. These include leukopenia, diarrhea, and vomiting. There also is an increased incidence of some infections, especially sepsis associated with cytomegalovirus. Tacrolimus in combination with mycophenolate mofetil has been associated with devastating viral infections including polyoma nephritis. 

In liver transplant patients taking tacrolimus, a dose dependent increase in blood levels of tacrolimus was observed after treatment with two capsules of schisandra (each containing 11.25 mg deoxyschizandrin) extract along with one of two doses of tacrolimus, 0.1 to 0.15 mg/kg daily or 0.5 to 3 mg/person daily. Increases in the maximum plasma concentration of tacrolimus were 339% for the 0.1 to 0.15 mg/kg dose and 262% for the 0.5 to 3 mg/person dose. A decrease in diarrhea and agitation, two side effects typically observed with tacrolimus treatment, was noted along with improvement in liver function (Jiang et al. 2010). 

A renal transplant recipient developed severe nephrotoxicity related to a toxic tacrolimus trough concentration associated with diarrhea and use of a calcium channel blocker. 

Gastrointestinal Severe new-onset colitis occurred in two kidney transplant recipients shortly after the introduction of a mod-ified-release formulation of tacrolimus instead of standard twice-daily tacrolimus in one case and ciclosporin in the other [85 ]. Both developed severe, intermittent bloody diarrhea, with abdominal pain, weight loss, dehydration, and worsening graft function. The symptoms did not abate after dosage reduction or withdrawal of mycophenolate. 

---