The principal adverse reactions of Sandimmune® (cyclosporine) therapy are renal dysfunction, tremor, hirsutism, hypertension, and gum hyperplasia.
Hypertension, which is usually mild to moderate, may occur in approximately 50% of patients following renal transplantation and in most cardiac transplant patients.
Glomerular Capillary Thrombosis
Glomerular capillary thrombosis has been found in patients treated with cyclosporine and may progress to graft failure. The pathologic changes resemble those seen in the hemolytic-uremic syndrome and include 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 posttransplantation.
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 following reactions occurred in 3% or greater of 892 patients involved in clinical trials of kidney, heart, and liver transplants:
|Body System/Adverse Reactions||Randomized Kidney Patients||All Sandimmune® (cyclosporine) Patients|
|Cramps||4||< 1||2||< 1||0|
|Central Nervous System|
|Hepatotoxicity||< 1||< 1||4||7||4|
|Abdominal Discomfort||< 1||0||< 1||7||0|
|Autonomic Nervous System|
|Gynecomastia||< 1||0||< 1||4||3|
The following reactions occurred in 2% or less of patients: allergic reactions, anemia, anorexia, confusion, conjunctivitis, edema, fever, brittle fingernails, gastritis, hearing loss, hiccups, hyperglycemia, muscle pain, peptic ulcer, thrombocytopenia, tinnitus.
The following reactions occurred rarely: anxiety, chest pain, constipation, depression, hair breaking, hematuria, joint pain, lethargy, mouth sores, myocardial infarction, night sweats, pancreatitis, pruritus, swallowing difficulty, tingling, upper GI bleeding, visual disturbance, weakness, weight loss.
Renal Transplant Patients in Whom Therapy Was Discontinued
|Reason for Discontinuation||Randomized Patients||All Sandimmune® Patients
|Lack of Efficacy||2.6||0.9||1.4|
|Acute Tubular Necrosis||2.6||0||1.0|
|Sandimmune® (cyclosporine) was discontinued on a temporary basis and then restarted in 18 additional patients.|
Patients receiving immunosuppressive therapies, including cyclosporine and cyclosporine -containing regimens, are at increased risk of infections (viral, bacterial, fungal, parasitic). Both generalized and localized infections can occur. Pre-existing infections may also be aggravated. Fatal outcomes have been reported. (See WARNINGS)
Infectious Complications in the Randomized Renal Transplant Patients
% of Complications
% of Complications
|Systemic Fungal Infection||2.2||3.9|
|Local Fungal Infection||7.5||9.6|
|Other Viral Infections||15.9||18.4|
|Urinary Tract Infections||21.1||20.2|
|Wound and Skin Infections||7.0||10.1|
|*Some patients also received ALG.|
Cremophor® EL (polyoxyethylated castor oil) is known to cause hyperlipemia and electrophoretic abnormalities of lipoproteins. These effects are reversible upon discontinuation of treatment but are usually not a reason to stop treatment.
Cases of hepatotoxicity and liver injury including cholestasis, jaundice, hepatitis and liver failure; serious and/or fatal outcomes have been reported. [See WARNINGS, Hepatotoxicity]
Increased Risk of Infections
Cases of JC virus-associated progressive multifocal leukoencephalopathy (PML), sometimes fatal; and polyoma virus-associated nephropathy (PVAN), especially BK virus resulting in graft loss have been reported. [See WARNINGS, Polyoma Virus Infection]
Headache, including Migraine
Cases of migraine have been reported. In some cases, patients have been unable to continue cyclosporine, however, the final decision on treatment discontinuation should be made by the treating physician following the careful assessment of benefits versus risks.