ADVERSE REACTIONS
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 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:
| Randomized Kidney Patients | All Sandimmune ® (cyclosporine) Patients |
| Sandimmune ® | Azathioprine | Kidney | Heart | Liver |
| Body System/ | (N=227) | (N=228) | (N=705) | (N=112) | (N=75) |
| Adverse Reactions | % | % | % | % | % |
| Genitourinary | | | | | |
| Renal Dysfunction | 32 | 6 | 25 | 38 | 37 |
| Cardiovascular | | | | | |
| Hypertension | 26 | 18 | 13 | 53 | 27 |
| Cramps | 4 | < 1 | 2 | < 1 | 0 |
| Skin | | | | | |
| Hirsutism | 21 | < 1 | 21 | 28 | 45 |
| Acne | 6 | 8 | 2 | 2 | 1 |
| Central Nervous System | | | | | |
| Tremor | 12 | 0 | 21 | 31 | 55 |
| Convulsions | 3 | 1 | 1 | 4 | 5 |
| Headache | 2 | < 1 | 2 | 15 | 4 |
| Gastrointestinal | | | | | |
| Gum Hyperplasia | 4 | 0 | 9 | 5 | 16 |
| Diarrhea | 3 | < 1 | 3 | 4 | 8 |
| Nausea/Vomiting | 2 | < 1 | 4 | 10 | 4 |
| Hepatotoxicity | < 1 | < 1 | 4 | 7 | 4 |
| Abdominal Discomfort | < 1 | 0 | < 1 | 7 | 0 |
| Autonomic Nervous System | | | | | |
| Paresthesia | 3 | 0 | 1 | 2 | 1 |
| Flushing | < 1 | 0 | 4 | 0 | 4 |
| Hematopoietic | | | | | |
| Leukopenia | 2 | 19 | < 1 | 6 | 0 |
| Lymphoma | < 1 | 0 | 1 | 6 | 1 |
| Respiratory | | | | | |
| Sinusitis | < 1 | 0 | 4 | 3 | 7 |
| Miscellaneous | | | | | |
| 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 |
| Randomized Patients | All Sandimmune ® Patients |
| Sandimmune ® | Azathioprine | |
| (N=227) | (N=228) | (N=705) |
| Reason for Discontinuation | % | % | % |
| Renal Toxicity | 5.7 | 0 | 5.4 |
| Infection | 0 | 0.4 | 0.9 |
| Lack of Efficacy | 2.6 | 0.9 | 1.4 |
| Acute Tubular Necrosis | 2.6 | 0 | 1.0 |
| Lymphoma/Lymphoproliferative Disease | 0.4 | 0 | 0.3 |
| Hypertension | 0 | 0 | 0.3 |
| Hematological Abnormalities | 0 | 0.4 | 0 |
| Other | 0 | 0 | 0.7 |
| Sandimmune® (cyclosporine) was discontinued on a temporary basis and then restarted in 18 additional patients. |
| Infectious Complications in the Randomized Renal Transplant Patients |
| Sandimmune ® Treatment | Standard Treatment* |
| (N=227) | (N=228) |
| Complication | % of Complications | % of Complications |
| Septicemia | 5.3 | 4.8 |
| Abscesses | 4.4 | 5.3 |
| Systemic Fungal Infection | 2.2 | 3.9 |
| Local Fungal Infection | 7.5 | 9.6 |
| Cytomegalovirus | 4.8 | 12.3 |
| Other Viral Infections | 15.9 | 18.4 |
| Urinary Tract Infections | 21.1 | 20.2 |
| Wound and Skin Infections | 7.0 | 10.1 |
| Pneumonia | 6.2 | 9.2 |
*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.
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REPORTS OF SUSPECTED SANDIMMUNE SIDE EFFECTS / ADVERSE REACTIONS
Below is a sample of reports where side effects / adverse reactions may be related to Sandimmune. The information is not vetted and should not be considered as verified clinical evidence.
Possible Sandimmune side effects / adverse reactions in 33 year old female
Reported by a health professional (non-physician/pharmacist) from Iran (Islamic Republic OF) on 2011-10-10
Patient: 33 year old female
Reactions: Lymphadenopathy, Central Nervous System Lesion, Tuberculosis, CSF Polymorphonuclear Cell Count Increased, Encephalitis, Pyrexia, Hemiparesis, Haemoglobin Decreased, CSF Protein Increased, C-Reactive Protein Increased, CSF White Blood Cell Count Increased, Aspergillosis, Depressed Level of Consciousness, CSF Pressure Increased, Hydrocephalus, Splenomegaly
Adverse event resulted in: death, hospitalization
Suspect drug(s):
Sandimmune
Other drugs received by patient: Mycophenolate Mofetil; Prednisolone
Possible Sandimmune side effects / adverse reactions in 47 year old male
Reported by a individual with unspecified qualification from United States on 2011-10-12
Patient: 47 year old male weighing 74.0 kg (162.8 pounds)
Reactions: Bipolar Disorder, Skin Cancer, Insomnia
Suspect drug(s):
Sandimmune
Other drugs received by patient: Atenolol; Prednisone; Temazepam; Lamictal
Possible Sandimmune side effects / adverse reactions in 63 year old male
Reported by a health professional (non-physician/pharmacist) from Japan on 2011-10-31
Patient: 63 year old male
Reactions: Rash Pustular, Squamous Cell Carcinoma, Skin Disorder, Erythrodermic Psoriasis, Erythema, C-Reactive Protein Increased, Oedema, Leukocytosis, Hypertension
Suspect drug(s):
Sandimmune
Dosage: 6 mg/kg
Administration route: Oral
Indication: Pustular Psoriasis
Start date: 1995-01-01
End date: 2000-12-01
Neoral
Dosage: 50 mg, daily
Administration route: Oral
End date: 2010-10-14
Neoral
Dosage: 75 mg, daily
Administration route: Oral
Neoral
Dosage: 250 mg, daily
Administration route: Oral
Indication: Pustular Psoriasis
Start date: 2000-12-01
Neoral
Dosage: 100 mg, daily
Administration route: Oral
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