heres some of the side effectsof tacrolimus in transplant situations. now i can understand why they had to use something...the alternative in these patients was most likely death, but there has to be a better drug out there and ISA247 is it.
The most common adverse effects associated with tacrolimus include: tremor (48-56% from pooled data), headache (37-64%), insomnia (32-64%), hypertension (38-50%), nausea and/or abdominal pain (32-59%), diarrhea (37-44%), constipation (23-35%), hyperkalemia (13-45%), hypomagnesemia (16-48%), asthenia (11-52%), atelectasis and pleural effusion (5-36%), and rash and/or pruritus (15-36%).In addition, hyperglycemia occurs in 33 to 47% of patients receiving tacrolimus. Insulin-dependent diabetes occurs in approximately 11 to 20% of patients post-transplant. The median time to onset in one study of adult liver transplant patients was 68 days. Insulin dependence was reversible in 15% of kidney transplants and 31 to 45% of liver transplants after one year. The development of hyperglycemia and diabetes with tacrolimus appears to be more common in blacks, in patients receiving high-dose steroids, and in patients with elevated tacrolimus concentrations.[2, 3]
Children may be at greater risk from this adverse effect, as symptoms of hyperglycemia may be more difficult to recognize and delay diagnosis. Diabetic ketoacidosis requiring hospitalization was recently reported in a 14-year-old girl after one year of tacrolimus post-transplantation.[11]
Nephrotoxicity has been reported in up to 52% of kidney transplantation patients and 40% of liver transplantation patients taking tacrolimus. Renal dysfunction is typically seen early in therapy, with an increase in serum creatinine and decrease in urine output. Dosage adjustment is often adequate to reverse this effect, but some patients may require discontinuation of therapy.[2, 3]
Tacrolimus-induced neurotoxicity may be manifest in a wide range of symptoms, from tremor and headache in up to 50% of patients to more severe symptoms including seizures, coma, and delirium. Neurotoxicity appears more commonly in patients with elevated tacrolimus concentrations or hepatic dysfunction leading to impaired metabolism.[2, 3] It has recently been suggested that some patients may possess a genetic predisposition to tacrolimus neurotoxicity.[12] Mutation of the ABCB1 gene may cause an alteration of P-glycoprotein function, decreasing its ability to restrict distribution of tacrolimus into the brain.
Although rare, severe myocardial hypertrophy has been reported in infants, children, and adults receiving tacrolimus. Hypertrophy is seen on echocardiography as an increase in left ventricular posterior wall and intraventricular septum thickness. These changes are often associated with elevated tacrolimus concentrations and typically reverse after dose reduction or discontinuation of therapy. A recent study has suggested that this adverse effect may be more common than previously thought and occurs with both tacrolimus and cyclosporine.[13]
An increased risk of malignancy is a known complication of long-term immunosuppressive therapy. Lymphomas, carcinomas of the skin, and lymphoproliferative disease associated with Epstein-Barr virus infections have been reported in patients taking tacrolimus, and may be more common in children than adults. In a retrospective evaluation of 326 pediatric liver transplant patients from the University of Pittsburgh, two of the 47 patients who died had post-transplant lymphoproliferative disease.[14]
Rare hypersensitivity reactions, including anaphylaxis, have been reported with IV tacrolimus. The castor oil derivative used in this formulation is believed to be the cause.[2, 3]
While the overall tolerability of tacrolimus and cyclosporine is similar, there are differences which may guide drug selection. In comparison with cyclosporine, the incidence of headache, insomnia, tremor, diarrhea, nephrotoxicity, and hyperglycemia appear to be greater with tacrolimus. Conversely, cyclosporine has been more frequently associated with hirsutism, gingival hyperplasia, constipation, hypertension, and dyslipidemias.[1]