Cyclosporine

Indications

Cyclosporine is used for: Ulcerative colitis, Rheumatoid arthritis, Psoriasis, Missed abortion, Nephrotic syndrome ,Urticaria, Bone marrow transplantation, Organ transplantation, atopic dermatitis

Adult Dose

Oral Immunosuppression in organ transplantation Adult: Initially, 10-15 mg/kg/day, starting 4-12 hr before procedure and continued for 1-2 wk; usual maintenance: 2-6 mg/kg/day. Lower doses may be used when combined with other immunosuppressants. Severe atopic dermatitis Adult: Initially, 2.5 mg/kg/day, in 2 divided doses. Reduce to lowest effective dose once remission is achieved. Stop treatment if there is no sufficient improvement to max dose within 6 wk. Max: 5 mg/kg/day. Psoriasis Adult: Initially, 2.5 mg/kg/day, in 2 divided doses. Reduce to lowest effective dose once remission is achieved. Stop treatment if there is no sufficient improvement to max dose within 6 wk. Max: 5 mg/kg/day. Rheumatoid arthritis Adult: 2.5 mg/kg/day, in 2 divided doses. Treatment should continue for 6-8 wk. If response is insufficient, may increase dose gradually. Max: 4 mg/kg/day. Nephrotic syndrome Adult: 5 mg/kg daily, given in 2 divided doses. Intravenous Prophylaxis of graft rejection in bone marrow transplantation Adult: Intially, 3-5 mg/kg/day starting on the day before transplantation and continue for up to 2 wk or until oral therapy can be initiated at a maintenance of 12.5 mg/kg/day. Continue maintenance dose for at least 3-6 mth. Immunosuppression in organ transplantation Adult: Initially: 5-6 mg/kg/day as a single dose, infuse dose over 2-6 hr. Switch to an oral dosage form as soon as possible.

Child Dose

Oral Nephrotic syndrome Child: 6 mg/kg daily, given in 2 divided doses.

Renal Dose

Administration

May be taken with or without food. Take consistently w/ regard to time of day & relation to meals. Avoid grapefruit juice. IV Preparation Dilute 1 mL (50 mg) of concentrated inj soln in 20-100 mL of D5W or NS Stability of injection of parenteral admixture at room temp (25°C) is 6 hr in PVC; 24 hr in Excel, PAB containers, or glass Polyoxyethylated castor oil surfactant in cyclosporine injection may leach phthalate from PVC containers such as bags and tubing Actual amount of DEHP plasticizer leached from PVC containers and administration sets may vary in clinical situations, depending on surfactant concentration, bag size, & contact time IV Administration Following dilution, infuse over 2-6 hr Continuously monitor for at least the first 30 min of the infusion, and then frequently thereafter Anaphylaxis possible with IV use; reserve only for patients unable to take oral form Maintain airway; other supportive measures & agents for treating anaphylaxis should be present

Contra Indications

Hypersensitivity; malignant neoplasms; uncontrolled hypertension; psoriasis; lactation.

Precautions

Cyclosporine increases the risk of developing lymphomas and other malignancies, particularly those of the skin. So patients should be warned to avoid excess ultraviolet light exposure. Cyclosporine may develop bacterial, fungal, parasitic and viral infections. So therapeutic strategies should be employed for long-term immunosuppressive therapy. A reversible increase in serum creatinine and urea may occur during the first few weeks of Cyclosporine therapy and usually responding to dose reduction. In elderly patients, renal function should be monitored with particular care. Regular monitoring of blood pressure is required during Cyclosporine therapy; if hypertension develops, appropriate antihypertensive treatment must be instituted. Cyclosporine enhances the risk of hyperkalaemia, especially in patients with renal dysfunction. Caution is also required when Cyclosporine is co-administered with potassium sparing drugs. Cyclosporine enhances the clearance of magnesium. If considered necessary, magnesium supplementation should be given. Caution should be observed in treating patients with hyperuricaemia. During treatment with Cyclosporine, vaccination may be less effective; the use of live-attenuated vaccines should be avoided. Non-transplant patients with impaired renal function, uncontrolled hypertension, uncontrolled infections, or any kind of malignancy should not receive Cyclosporine. Renal and hepatic impairment; hyperuricaemia; anaphylaxis; history of allergic reactions; pregnancy; monitor BP, serum electrolytes, renal and hepatic function. Lactation: excreted in breast milk, do not nurse

Pregnancy-Lactation

Pregnancy Category: C; take into consideration alcohol content of various cyclosporine formulations Lactation: excreted in breast milk, do not nurse

Interactions

Increased ciclosporin level by diltiazem, doxycycline, erythromycin, ketoconazole, methylprednisolone (high doses), nicardipine, verapamil, oral contraceptives. Drugs which reduce ciclosporin level are carbamazepine, isoniazid, phenobarbitone, phenytoin and rifampicin. Increased risk of convulsion when used concurrently with high-dose methylprednisolone. Potentially Fatal: Additive nephrotoxicity when used with aminoglycosides, amphotericin B, ciprofloxacin, colchicine, melphalan, co-trimoxazole and NSAIDs.

Adverse Effects

Side effects of Cyclosporine : >10% Tremor (12-55%), Nephrotoxicity (32%), Hypertension (26%), Infection (3-25%), Headache (2-25%), Nausea (23%), Hirsutism (21%), Hypertrichosis (5-19%), Female reproductive disorder (5-19%), Gum hyperplasia (2-16%), Triglycerides increased (15%), Abdominal discomfort (1-15%), URI (1-14%), Diarrhea (3-13%), Dyspepsia (2-12%), Leg cramps (2-12%), Parathesia (1-11%) 1-10% Acne, Convulsions, Pruitus, Hyperkalemia, hypomagnesemia, Pancreatitis, , Hepatotoxicity, Flu-like syndrome Frequency Not Defined Leukopenia, Thrombocytopenia, Anaphylaxis, Glomerular capillary thrombosis, Hypomagnesemia, Migraine, Hyponatremia

Mechanism of Action

Ciclosporin is a strong immunosuppressant that acts mainly on the helper T-cells. It inhibits the activation of calcineurin and production of interleukin-2, thus reducing cell-mediated immune response.