From the Guidelines
Cyclosporine A should be used at a starting dose of 3 to 6 mg/kg per day, with a maximum of 200 mg, for the treatment of immune thrombocytopenia, as it has been shown to have a response rate of 37.8% to 56.7% at 1 month and a durable response rate of 23.3% to 44%. The dose of cyclosporine A needs to be adjusted based on trough drug levels, and patients should be monitored for major adverse effects such as gingival hyperplasia, hypertension, nephrotoxicity, and nausea 1. Some key points to consider when using cyclosporine A include:
- The response rate at 1 month can vary, but it has been reported to range from 37.8% to 56.7% 1
- The durable response rate can also vary, but it has been reported to range from 23.3% to 44% 1
- Major adverse effects of cyclosporine A include gingival hyperplasia, hypertension, nephrotoxicity, and nausea, which occur at rates of 6.6%, 11.6%, 6.7%, and an unspecified rate, respectively 1
- Cyclosporine A is not recommended for use during pregnancy or lactation 1. The mechanism of action of cyclosporine A involves binding to the protein cyclophilin, and the complex inhibits calcineurin, a protein vital for T-cell activation, which reduces T-cell activity and makes it a potent immunosuppressive agent 1.
From the FDA Drug Label
The pathologic changes resembled those seen in the hemolytic-uremic syndrome and included thrombosis of the renal microvasculature, with platelet-fibrin thrombi occluding glomerular capillaries and afferent arterioles, microangiopathic hemolytic anemia, thrombocytopenia, and decreased renal function Similar findings have been observed when other immunosuppressives have been employed post-transplantation. Hypomagnesemia has been reported in some, but not all, patients exhibiting convulsions while on cyclosporine therapy Although magnesium depletion studies in normal subjects suggest that hypomagnesemia is associated with neurologic disorders, multiple factors, including hypertension, high dose methylprednisolone, hypocholesterolemia, and nephrotoxicity associated with high plasma concentrations of cyclosporine appear to be related to the neurological manifestations of cyclosporine toxicity The FDA drug label does not answer the question.
From the Research
Cyclosporine Overview
- Cyclosporine is a potent immunosuppressive agent used in organ transplantation and various dermatological conditions 2, 3.
- It has a selective inhibitory effect on helper T cells, making it effective in treating diseases where these cells are involved in the pathogenesis 3.
Nephrotoxicity and Hypertension
- Cyclosporine can cause acute and chronic nephrotoxicity, leading to functional changes and structural lesions in the kidney 2.
- The risk of nephrotoxicity increases with age, preexisting hypertension, and high serum creatinine levels 4.
- Hypertension is also a common side effect of cyclosporine treatment, which can be reversible with discontinuation of the drug 2, 4, 3.
Dermatological Applications
- Cyclosporine has been used to treat various dermatological conditions, including psoriasis, pustular psoriasis, and erythrodermic psoriasis 5, 3.
- The starting dose of 5 mg/kg is associated with a higher degree of clearance, but the benefit-risk appears to be better for patients without risk factors for nephrotoxicity 5.
Toxicity and Side Effects
- Cyclosporine can cause a range of toxic effects, including nephrotoxic, hepatotoxic, neurotoxic, and cardiotoxic effects 6.
- The molecular pathways of toxicity induced by cyclosporine are complex and involve various mechanisms, including the inhibition of calcineurin 2, 6.
- Lymphoma is unlikely in an otherwise healthy patient who has received low-dose oral cyclosporine for limited periods, but the use of oral cyclosporine should be carefully considered in terms of the risk/benefit ratio 3.