What are the effects of Cyclosporin (Cyclosporine) toxicity?

From the Guidelines

Cyclosporine toxicity necessitates prompt dose reduction or discontinuation to mitigate the risk of irreversible kidney damage, with nephrotoxicity and hypertension being the most common adverse effects, as evident in a study published in the Journal of the American Academy of Dermatology in 2020 1. The primary concern with cyclosporine toxicity is its impact on renal function, with reversible nephrotoxicity developing in 19% to 24% of patients during short-term treatment, and the risk of fibrosis and irreversible kidney damage increasing substantially with treatment duration exceeding 2 years 1. Key aspects of cyclosporine toxicity management include:

• Monitoring serum creatinine levels and adjusting the dose accordingly to prevent irreversible kidney damage
• Being aware of the potential for GI adverse effects, such as abdominal pain, diarrhea, nausea, and vomiting, although these tend to be mild and short-lived
• Recognizing the possibility of respiratory effects, including dyspnea, cough, and rhinitis, in approximately 5% of patients
• Considering the potential for hyperuricemia and hypomagnesemia as part of the toxicity profile
• Regularly monitoring cyclosporine trough levels to ensure therapeutic ranges are maintained, typically between 100-400 ng/mL, depending on the condition being treated. Given the potential for severe and irreversible toxicity, it is crucial to prioritize dose reduction or discontinuation in cases of suspected cyclosporine toxicity, particularly when nephrotoxicity or hypertension is evident, as supported by the 2020 guidelines from the Journal of the American Academy of Dermatology 1.

From the FDA Drug Label

Cyclosporine, the active ingredient in cyclosporine capsules [MODIFIED] and cyclosporine oral solution [MODIFIED], can cause nephrotoxicity and hepatotoxicity. The risk increases with increasing doses of cyclosporine Renal dysfunction including structural kidney damage is a potential consequence of cyclosporine [MODIFIED] and therefore renal function must be monitored during therapy. Neurotoxicity There have been reports of convulsions in adult and pediatric patients receiving cyclosporine, particularly in combination with high dose methylprednisolone. Encephalopathy, including Posterior Reversible Encephalopathy Syndrome (PRES), has been described both in post-marketing reports and in the literature OVERDOSAGE There is a minimal experience with cyclosporine overdosage. Forced emesis can be of value up to 2 hours after administration of cyclosporine [MODIFIED]. Transient hepatotoxicity and nephrotoxicity may occur which should resolve following drug withdrawal

Cyclosporine toxicity can cause:

• Nephrotoxicity: renal dysfunction, structural kidney damage
• Hepatotoxicity: liver damage
• Neurotoxicity: convulsions, encephalopathy, including Posterior Reversible Encephalopathy Syndrome (PRES) The risk of toxicity increases with:
• Increasing doses of cyclosporine
• Combination with other nephrotoxic or high-dose medications
• Prolonged use of cyclosporine
• Pre-existing renal or liver dysfunction
• Elderly patients It is essential to monitor patients closely for signs of toxicity and adjust the dose or discontinue the medication as needed 2, 2, 2.

From the Research

Cyclosporine Toxicity

• Cyclosporine is an immunosuppressive agent that can cause nephrotoxicity and hypertension in patients, particularly those undergoing organ transplantation 3, 4, 5, 6, 7.
• The mechanisms underlying cyclosporine nephrotoxicity are complex and involve oxidative stress, autophagy, and various signaling pathways, including the p38, ERK, and JNK MAPK subfamilies, as well as NF-κB and TGF-β1 7.
• Cyclosporine can cause acute and chronic nephrotoxicity, with chronic nephrotoxicity leading to structural lesions in the kidney, such as arteriolar hyalinosis, stripped interstitial fibrosis, and tubular atrophy 4.
• The use of cyclosporine can also lead to arterial hypertension, which can contribute to long-term renal graft failure and cardiovascular morbidity in transplant recipients 3, 4, 5, 6.
• Reducing the dose of cyclosporine and adding other immunosuppressive agents, such as azathioprine, can help to minimize nephrotoxicity and hypertension while maintaining effective immunosuppression 3.
• Alternative immunosuppressive agents, such as tacrolimus and rapamycin, may have fewer nephrotoxic effects than cyclosporine and could be considered as alternatives in certain patients 4, 5.
• Calcium channel blockers may also be useful in controlling blood pressure and minimizing nephrotoxicity in patients treated with cyclosporine 6.