From the Guidelines
Tacrolimus is a potent immunosuppressive drug that should be used with caution due to its potential for nephrotoxicity, neurotoxicity, and increased risk of malignancies, but its benefits in preventing organ rejection in transplant recipients and treating certain autoimmune conditions make it a valuable treatment option. The main uses of tacrolimus include preventing organ rejection in kidney, liver, heart, and other solid organ transplants, as well as treating severe atopic dermatitis, severe ulcerative colitis, and refractory rheumatoid arthritis 1.
Key Points on Main Uses
- Preventing organ rejection in transplant recipients, particularly for kidney, liver, heart, and other solid organ transplants
- Treating certain autoimmune conditions like severe atopic dermatitis, severe ulcerative colitis, and refractory rheumatoid arthritis
- Available in oral forms (immediate and extended-release) and topical formulations, with dosing individualized based on blood level monitoring
Adverse Effects
- Nephrotoxicity (kidney damage)
- Neurotoxicity (tremors, headaches, seizures)
- Hypertension
- Hyperglycemia (which may lead to new-onset diabetes)
- Electrolyte abnormalities (particularly hyperkalemia)
- Increased susceptibility to infections
- Long-term use is associated with an increased risk of certain malignancies, particularly skin cancers and lymphomas
According to the most recent and highest quality study, tacrolimus is associated with better patient and graft survival rates than cyclosporine 1. Regular monitoring of tacrolimus blood levels, kidney function, blood pressure, blood glucose, and electrolytes is essential for patients on this medication to minimize toxicity while maintaining therapeutic immunosuppression. Additionally, the choice of immunosuppressive regimen should consider medication adherence, as this is one of the most important risks for acute rejection 1.
From the FDA Drug Label
The most common adverse reactions (≥30%) observed in tacrolimus-treated kidney transplant patients are: infection, tremor, hypertension, abnormal renal function, constipation, diarrhea, headache, abdominal pain, insomnia, nausea, hypomagnesemia, urinary tract infection, hypophosphatemia, peripheral edema, asthenia, pain, hyperlipidemia, hyperkalemia, and anemia Adverse reactions that occurred in ≥15% of kidney transplant patients treated with tacrolimus in conjunction with azathioprine are presented below: Adverse reactions that occurred in ≥10% of kidney transplant patients treated with tacrolimus in conjunction with MMF in Study 1 are presented below: The following serious and otherwise important adverse drug reactions are discussed in greater detail in other sections of labeling: Lymphoma and Other Malignancies, Serious Infections, New Onset Diabetes After Transplant, Nephrotoxicity, Neurotoxicity, Hyperkalemia, Hypertension, Anaphylactic Reactions with Tacrolimus Injection, Myocardial Hypertrophy, Pure Red Cell Aplasia, Thrombotic Microangiopathy, Including Hemolytic Uremic Syndrome and Thrombotic Thrombocytopenic Purpura
The main uses of tacrolimus are not explicitly stated in the provided text, but based on the context, it appears to be used as an immunosuppressive drug for kidney transplant patients. The adverse effects of tacrolimus include:
- Common adverse reactions: infection, tremor, hypertension, abnormal renal function, constipation, diarrhea, headache, abdominal pain, insomnia, nausea, hypomagnesemia, urinary tract infection, hypophosphatemia, peripheral edema, asthenia, pain, hyperlipidemia, hyperkalemia, and anemia
- Serious adverse reactions: Lymphoma and Other Malignancies, Serious Infections, New Onset Diabetes After Transplant, Nephrotoxicity, Neurotoxicity, Hyperkalemia, Hypertension, Anaphylactic Reactions with Tacrolimus Injection, Myocardial Hypertrophy, Pure Red Cell Aplasia, Thrombotic Microangiopathy, Including Hemolytic Uremic Syndrome and Thrombotic Thrombocytopenic Purpura 2 2
From the Research
Main Uses of Tacrolimus
- Tacrolimus is an immunosuppressant agent used as a therapeutic alternative to cyclosporin in organ transplant recipients 3, 4.
- It is used for primary immunosuppression in liver and kidney transplantation, and has experience in other types of solid organ transplantation, including heart, lung, pancreas, and intestinal transplantation 3.
- Tacrolimus is also used for the prevention of graft-versus-host disease in allogeneic bone marrow transplantation (BMT) 3.
- It has demonstrated efficacy in various types of transplantation as rescue therapy in patients who experience persistent acute rejection with cyclosporin-based therapy 3, 4.
Adverse Effects of Tacrolimus
- The most common adverse effects of tacrolimus include nephrotoxicity, neurotoxicity, and diabetes mellitus 3, 4, 5, 6.
- Other adverse effects include diarrhea, alopecia, and some types of neurotoxicity (e.g. tremor, paraesthesia) 3, 4.
- Tacrolimus has a higher incidence of adverse events requiring withdrawal from the study, primarily nephrotoxicity and neurotoxicity, compared to cyclosporine 6.
- Monitoring of tacrolimus levels is essential to avoid organ rejection and other complications related to tacrolimus over-exposure 7.
Comparison with Cyclosporin
- Tacrolimus has a similar degree of nephrotoxicity to cyclosporin, but has a higher incidence of diabetes mellitus and some types of neurotoxicity 3, 4.
- Cyclosporin has a higher incidence of significant hypertension, hypercholesterolaemia, hirsutism, and gingival hyperplasia compared to tacrolimus 3, 4.
- Tacrolimus has demonstrated a consistent statistically significant advantage over cyclosporin with respect to acute rejection rate in liver and kidney transplantation 3, 4.