What are the complications of Cyclosporine (Cyclosporin) use?

From the Guidelines

Cyclosporine use is associated with significant complications, including nephrotoxicity, hypertension, and increased risk of infections, which can impact morbidity, mortality, and quality of life. The most common adverse effects of cyclosporine are nephrotoxicity and hypertension, with reversible nephrotoxicity developing in 19% to 24% of patients during short-term treatment 1. Long-term use of cyclosporine can lead to irreversible kidney damage, with 71% of patients treated for an average of 4.5 years experiencing serum creatinine levels 30% above baseline 1.

Some of the key complications of cyclosporine use include:

• Nephrotoxicity, which can be dose-dependent and potentially irreversible with long-term use
• Hypertension, which affects approximately 50% of patients and requires monitoring and often antihypertensive therapy
• Increased risk of infections due to immunosuppression
• Metabolic complications, such as hyperglycemia, hyperlipidemia, hyperkalemia, and hypomagnesemia
• Cosmetic side effects, such as hirsutism and gingival hyperplasia
• Gastrointestinal disturbances, such as nausea, vomiting, and diarrhea
• Neurotoxicity, which can present as tremors, headaches, seizures, or posterior reversible encephalopathy syndrome

Regular monitoring of cyclosporine blood levels, renal function, blood pressure, and electrolytes is essential for early detection of these complications. Dose adjustments or alternative immunosuppressants may be necessary if severe adverse effects develop 1. It is also important to note that cyclosporine can increase the risk of malignancies, particularly with long-term use, and can cause hepatotoxicity 1.

In terms of management, patients should be closely monitored for signs of nephrotoxicity, hypertension, and infections, and dose adjustments should be made as needed to minimize the risk of these complications. Alternative immunosuppressants may be considered if cyclosporine is not tolerated or if severe adverse effects develop. Overall, the use of cyclosporine requires careful consideration of the potential risks and benefits, and close monitoring to minimize the risk of complications.

From the FDA Drug Label

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 Manifestations include impaired consciousness, convulsions, visual disturbances (including blindness), loss of motor function, movement disorders and psychiatric disturbances. 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 Cyclosporine nephropathy was detected in renal biopsies of 6 out of 60 (10%) rheumatoid arthritis patients after the average treatment duration of 19 months. There is a potential, as with other immunosuppressive agents, for an increase in the occurrence of malignant lymphomas with cyclosporine Patients receiving immunosuppressive therapies, including cyclosporine and cyclosporine -containing regimens, are at increased risk of infections (viral, bacterial, fungal, parasitic). Cases of hepatotoxicity and liver injury including cholestasis, jaundice, hepatitis and liver failure; serious and/or fatal outcomes have been reported

The complications of cyclosporine use include:

• Neurotoxicity: convulsions, encephalopathy, impaired consciousness, visual disturbances, loss of motor function, movement disorders, and psychiatric disturbances
• Nephrotoxicity: renal dysfunction, thrombosis of the renal microvasculature, microangiopathic hemolytic anemia, thrombocytopenia, and decreased renal function
• Malignancies: increased risk of malignant lymphomas
• Infections: increased risk of viral, bacterial, fungal, and parasitic infections
• Hepatotoxicity: liver injury, including cholestasis, jaundice, hepatitis, and liver failure
• Other complications: hypertension, gastrointestinal disturbances, hirsutism/hypertrichosis, and headache 2, 2

From the Research

Complications of Cyclosporine Use

• Nephrotoxicity: a major concern in current immunosuppression regimens, causing abnormal kidney function while treating kidney disease 3
• Hepatotoxicity: a significant adverse effect of cyclosporine, as reported in studies 4, 5
• Malignancies: a potential complication of cyclosporine use, as mentioned in a study 4
• Hirsutism: a common adverse event in cyclosporine recipients, usually mild to moderate and resolving on dosage reduction 6
• Minor neurologic complications: reported as reversible adverse effects of cyclosporine 4
• Hypertension: a significant increase in blood pressure, correlated with cyclosporine trough levels 7
• Hypertrichosis: an adverse event in cyclosporine recipients, usually mild to moderate and resolving on dosage reduction 6
• Gingival hyperplasia: a common adverse event in cyclosporine recipients, usually mild to moderate and resolving on dosage reduction 6
• Neurological and gastrointestinal effects: common adverse events in cyclosporine recipients, usually mild to moderate and resolving on dosage reduction 6
• Changes in laboratory variables indicating renal dysfunction: relatively common, although serious irreversible damage is rare 6
• Electrolyte imbalances: significant changes in serum potassium, magnesium, and urate levels, correlated with cyclosporine trough levels 7