Cyclosporine
Cyclosporine (Sandimmune)
Cyclosporine
(sye-kloh- SPOR-een)
Pregnancy Category: C Neoral Sandimmune Sandimmune I.V. Sandimmune Neoral SangCya (Rx)

Classification: Immunosuppressant

Action/Kinetics: Thought to act by inhibiting the immunocompetent lymphocytes in the G ₀ or G ₁ phase of the cell cycle. T-lymphocytes are specifically inhibited; both the T-helper cell and the T-suppressor cell may be affected. Also inhibits interleukin 2 or T-cell growth factor production and release. Absorption from the GI tract is incomplete and variable. Children often require larger PO doses than adults, which may be due to the smaller absorptive surface area of their intestines. Peak plasma levels: 3.5 hr. Food may both delay and impair drug absorption. t 1/2: Approximately 19 hr for adults and 7 hr in children. Metabolized by the liver; inactive metabolites are excreted mainly through the bile.
Neoral immediately forms a microemulsion in an aqueous environment. This product has better bioequivalency; thus, Sandimmune and Neoral are not bioequivalent and cannot be used interchangeably without medical supervision. Time to peak blood levels: 1.5-2 hr. Food decreases the amount of drug absorbed.

Uses: Prophylaxis of rejection in kidney, liver, and heart allogeneic transplants. Sandimmune is always to be taken with adrenal corticosteroids while Neoral has been used in combination with azathioprine and corticosteroids. Neoral microemulsion: Alone or in combination with methotrexate for severe, active rheumatoid arthritis which has not responded to methotrexate alone. Neoral microemulsion: Severe recalcitrant plaque psoriasis. Sandimmune: Treatment of chronic rejection in clients previously treated with other immunosuppressants. Sandimmune has been used in children as young as 6 months with no unusual side effects. Investigational: Aplastic anemia, myasthenia gravis, atopic dermatitis, Crohn's disease, Graves ophthalmology, severe psoriasis, multiple sclerosis, polymyositis, Behcet's disease, biliary cirrhosis, corneal transplantation (or other diseases of the eye which have an autoimmune component), dermatomyositis, insulin-dependent diabetes mellitus, lichen planus, lupus nephritis, nephrotic syndrome, pemphigus and pemphigoid, psoriatic arthritis, pulmonary sarcoidosis, pyoderma gangrenosum, alopecia areata, ulcerative colitis, uveitis.

Contraindications: Hypersensitivity to cyclosporine or polyoxyethylated castor oil. Lactation. Use of potassium-sparing diuretics. Neoral in psoriasis or rheumatoid arthritis with abnormal renal function, uncontrolled hypertension, or malignancies. Neoral together with PUVA or UVB in psoriasis.

Special Concerns: Use with caution in clients with impaired renal or hepatic function. Safety and efficacy have not been established in children. Clients with malabsorption may not achieve therapeutic levels following PO use.

Side Effects: GI: N&V;, diarrhea, gum hyperplasia, anorexia, gastritis, hiccoughs, peptic ulcer, abdominal discomfort, upper GI bleeding, pancreatitis, constipation, mouth sores, difficulty in swallowing. Hematologic: Leukopenia, lymphoma, thrombocytopenia, anemia, microangiopathic hemolytic anemia syndrome. Allergic: Anaphylaxis (rare). CV: Hypertension, edema, chest pain, cramps, MI (rare). CNS: Headache, tremor, confusion, fever, seizures anxiety, depression, weakness, lethargy, ataxia. GU: Renal dysfunction, glomerular capillary thrombosis, nephrotoxicity. Dermatologic: Acne, hirsutism, brittle finger nails, hair breaking, pruritus. Miscellaneous: Hepatotoxicity, flushing, paresthesia, sinusitis, gynecomastia, conjunctivitis, hearing loss, tinnitus, muscle pain, infections (including fungal, viral), Pneumocystis carinii pneumonia, hematuria, blurred vision, weight loss, joint pain, night sweats, tingling, hypomagnesemia in some clients with seizures, infectious complications, increased risk of cancer.

Laboratory Test Alterations: Serum creatinine, BUN, total bilirubin, alkaline phosphatase, serum potassium. Possibly cholesterol, LDL, and apolipoprotein B. Hyperglycemia, hyperkalemia, hyperuricemia.

Overdose Management: Symptoms: Transient hepatotoxicity and nephrotoxicity. Treatment: Induction of vomiting (up to 2 hr after ingestion). General supportive measures.

Drug Interactions: Aminoglycosides / Risk of nephrotoxicity Amiodarone / Blood levels of cyclosporine risk of nephrotoxicity Amphotericin B / Risk of nephrotoxicity Azathioprine / Immunosuppression due to suppression of lymphocytes possible infection and malignancy Bromocriptine / Plasma level of cyclosporine R/T liver breakdown Calcium channel blockers / / Plasma levels of cyclosporine R/T liver breakdown; risk of toxicity Carbamazepine / Plasma level of cyclosporine R/T liver breakdown Carvedilol / Carvedilol blood levels due to liver breakdown Chloramphencil / Cyclosporine blood levels in renal transplant clients Cimetidine / Risk of nephrotoxicity Clarithromycin / Plasma levels of cyclosporine R/T liver breakdown; risk of nephro-/neurotoxicity Clindamycin / Cyclosporine serum levels Colchicine / Severe side effects, including GI, hepatic, renal, and neuromuscular toxicity Corticosteroids / Immunosuppression R/T suppression of lymphocytes possible infection and malignancy Cyclophosphamide / Immunosuppression R/T suppression of lymphocytes possible infection and malignancy Danazol / Plasma level of cyclosporine R/T liver breakdown Diclofenac / Risk of nephrotoxicity Digoxin / Digoxin levels R/T clearance; also, volume of distribution of digoxin toxicity Diltiazem / Cyclosporine plasma level R/T liver breakdown possible nephrotoxicity Echinacea / Do not give with cyclosporine Erythromycin / Plasma level of cyclosporine R/T liver breakdown and biliary excretion possible nephrotoxicity Etoposide / Etoposide renal clearance increased toxicity Fluconazole / Plasma level of cyclosporine R/T gut and liver metabolism possible nephrotoxicity Foscarnet Risk of renal failure Grapefruit juice / Cyclosporine blood levels due to liver breakdown HIV Protease Inhibitors / Plasma levels of cyclosporine R/T liver breakdown toxicity Imipenem-cilastatin / Blood levels of cyclosporine CNS toxicity Isoniazid / Plasma level of cyclosporine R/T liver breakdown Itraconazole / Plasma level of cyclosporine R/T liver breakdown Ketoconazole / Plasma level of cyclosporine R/T breakdown by gut and liver metabolism possible nephrotoxicity Lovastatin / Risk of myopathy and rhabdomyolysis due to breakdown of cyclosporine Melphalan / Risk of nephrotoxicity Methylprednisolone / Blood levels of cyclosporine R/T liver breakdown toxicity Metoclopramide / Plasma level of cyclosporine R/T liver breakdown toxicity Naproxen / Risk of nephrotoxicity Nephrotoxic drugs / Additive nephrotoxicity Nicardipine / Plasma level of cyclosporine R/T liver breakdown possible nephrotoxicity Nifedipine / Risk of gingival hyperplasia Octreotide / Plasma level of cyclosporine R/T liver breakdown Oral contraceptives / Plasma level of cyclosporine R/T liver breakdown; possible severe hepatotoxicity Phenobarbital / Plasma level of cyclosporine R/T liver breakdown Phenytoin / Plasma level of cyclosporine R/T liver breakdown Probucol / Bioavailability of cyclosporine clinical effect Ranitidine / Risk of nephrotoxicity Rifabutin/Rifampin / Plasma level of cyclosporine R/T liver breakdown Saquinavir / Cyclosporine blood levels Simvastatin / Risk of myopathy and rhabdomyolysis due to breakdown of cyclosporine Sulfamethoxazole and/or trimethoprim / Risk of nephrotoxicity; also, serum levels of cyclosporine possible organ rejection Sulindac / Risk of nephrotoxicity Tacrolimus / Risk of nephrotoxicity Terbenafine / Serum levels of cyclosporine R/T liver breakdown Vancomycin / Risk of nephrotoxicity Verapamil / Immunosuppression

How Supplied: Capsule: 25 mg, 100 mg, 250 mg; Injection: 50 mg/mL; Oral Solution: 100 mg/mL

Dosage
?Capsules, Oral Solution Allogenic transplants.
Adults and children, initial: A single 15 mg/kg dose given 4-12 hr before transplantation; there is a trend to use lower initial doses of 10-14 mg/kg/day. The dose should be continued postoperatively for 1-2 weeks followed by 5% decrease in dose per week to maintenance dose of 5-10 mg/kg/day (some have used a dose of 3 mg/kg/day successfully). Compared with Sandimmune, lower maintenance doses of Neoral may be sufficient.
If converting from Sandimmune to Neoral, start with a 1:1 conversion. Then, adjust the Neoral dose to reach the pre-conversion cyclosporine blood trough levels. Until this level is reached, monitor the cyclosporine trough level q 4-7 days.
Rheumatoid arthritis (Neoral only).
Initial: 1.25 mg/kg b.i.d. PO. Salicylates, NSAIDs, and PO corticosteroids may be continued. If sufficient beneficial effect is not seen and the client is tolerating the medication, the dose may be increased by 0.5-0.75 mg/kg/day after 8 weeks and again after 12 weeks to a maximum dose of 4 mg/kg/day. If no benefit is seen after 16 weeks, discontinue therapy. If Neoral is combined with methotrexate, the same initial dose and dose range of Neoral can be used.
Psoriasis (Neoral only).
Initial: 1.25 mg/kg b.i.d. PO. Maintain this dose for 4 weeks if tolerated. If significant improvement is not seen, increase the dose at 2-week intervals. Based on client response, make dose increases of about 0.5 mg/kg/day to a maximum of 4 mg/kg/day. Discontinue treatment if beneficial effects can not be achieved after 6 weeks at 4 mg/kg/day. Once beneficial effects are seen, decrease the dose (doses less than 2.5 mg/kg/day may be effective). To control side effects, make dose decreases by 25% to 50% at any time.
?IV (only in clients unable to take PO medication) Allogenic transplants.
Adults: 5-6 mg/kg/day 4-12 hr prior to transplantation and postoperatively until client can be switched to PO dosage. NOTE: Steroid therapy must be used concomitantly.
Investigational uses.
Oral doses ranging from 1 to 10 mg/kg/day.