Sandimmun Neoral

Prevention of graft rejection in kidney, liver, heart, combined heart-lung, lung or pancreas allogenic transplant. Treatment of transplant rejection in patients previously receiving other immunosuppressive agents. Prevention of graft rejection following bone marrow transplantation. Prevention or treatment of graft-vs-host disease (GVHD). Non-transplantation conditions eg, endogenous uveitis; nephrotic syndrome; severe active RA; severe psoriasis; severe atopic dermatitis.

Transplantation: Solid organ transplantation Initially 10-15 mg/kg in 2 divided doses, w/in 12 hr before surgery. Maintain as daily dose for 1-2 wk post-op before gradually reducing in accordance w/ blood levels until maintenance of about 2-6 mg/kg in 2 divided doses is reached. Bone marrow transplantation Initially 12.5-15 mg/kg in 2 divided doses, starting on the day before transplantation. Maintenance dose: 12.5 mg/kg daily in 2 divided doses. Continue for at least 3 mth (& preferably for 6 mth) before the dose is gradually decreased to 0 by 1 yr after transplantation. GVHD after discontinuation Loading dose: Initially 10-12.5 mg/kg followed by daily maintenance dose previously found to be satisfactory. Nontransplant: Endogenous uveitis Inducing remission: Initially 5 mg/kg/day in 2 divided doses. May be increased to 7 mg/kg/day for a limited period for refractory cases. Max maintenance: 5 mg/kg/day. Nephrotic syndrome Adult Inducing remission: 5 mg/kg/day in 2 divided doses. Maintenance: Slowly reduce to lowest effective level. Childn Inducing remission: 6 mg/kg/day in 2 divided doses. Maintenance: Slowly reduce to lowest effective level. Patient w/ renal impairment Max initial dose: 2.5 mg/kg/day. RA 3 mg/kg/day in 2 divided doses for 1st 6 wk. May be increased gradually as tolerability permits, but max 5 mg/kg & may be extended up to 12 wk. Maintenance: Titrate individually to lowest effective level according to tolerability. Psoriasis Individualized dose. Inducing remission: Initially 2.5 mg/kg/day in 2 divided doses. May be gradually increased if no improvement after 1 mth, but max 5 mg/kg. Maintenance: Titrate individually to lowest effective level. Atopic dermatitis Individualized dose. 2.5-5 mg/kg/day in 2 divided doses. If no satisfactory response w/in 2 wk, daily dose may be rapidly increased to max 5 mg/kg.

May be taken with or without food: Cap: Swallow whole. Oral soln: Dilute w/ preferably orange or apple juice; however, other drinks eg, soft drinks can be used according to individual taste. Avoid grapefruit juice. Stir well immediately before taking the oral soln.

Hypersensitivity to ciclosporin.

Risk of developing lymphomas & other malignancies particularly skin; bacterial, fungal, parasitic & viral infections; increases in serum bilirubin & liver enzymes; hepatotoxicity & liver injury; hyperkalemia especially in patients w/ renal dysfunction; hypomagnesemia especially in peri-transplant period; hyperuricemia; renal impairment. Increase in serum creatinine & urea may occur during the 1st few wk of therapy. Long-term treatment may cause structural changes in the kidney. Close monitoring of parameters that assess renal & hepatic function is required. Regularly monitor BP during therapy; institute appropriate antihypertensive treatment if HTN develops. Reports of reversible slight increase in blood lipids; perform lipid determinations before treatment & after the 1st mth of therapy. Avoid excess UV light exposure. Caution w/ concomitant K-sparing drugs (eg, K-sparing diuretics, ACE inhibitors, AIIA) & K-containing drugs; K-rich diets; lercanidipine. Not recommended w/ aliskiren. Avoid live attenuated vaccines; dabigatran or bosentan. Contains ethanol. May cause neurological & visual disturbances; caution when driving a motor vehicle or operating machines. Dose adjustment may be necessary in patients w/ severe liver impairment. Should not be used during pregnancy unless expected benefit to the mother outweighs potential risk to the fetus. Abstain from breastfeeding during therapy or abstain from using the drug during breastfeeding. Monitor renal function in elderly. Non-transplant indications: Patients w/ renal impairment, except nephrotic syndrome patients, uncontrolled HTN/infection, or any kind of malignancy should not receive ciclosporin. Use in childn for non-transplant indications other than nephrotic syndrome cannot be recommended. Endogenous uveitis: Caution in patients w/ neurological Behcet's syndrome. Nephrotic syndrome: Consider renal biopsy for patients w/ steroid-dependent minimal-change nephropathy, in whom therapy has been maintained for >1 yr. RA: Caution w/ concomitant MTX. Psoriasis/atopic dermatitis: Not to be used concomitantly w/ UVB irradiation or PUVA photochemotherapy. Use in elderly only in the presence of disabling psoriasis/atopic dermatitis. Atopic dermatitis: Lymphadenopathy observed on treatment should be regularly monitored. Clear active herpes simplex infections prior to treatment initiation. Control Staph aureus skin infection w/ appropriate antibacterial agents; avoid oral erythromycin.

Anorexia, hyperglycemia; tremor, headache; HTN; nausea, vomiting, abdominal discomfort, diarrhea, gingival hyperplasia; hirsutism; renal dysfunction. Leucopenia; convulsions, paraesthesia; flushing; peptic ulcer; hepatotoxicity; acne, rash; pyrexia, oedema.

Vaccination may be less effective. Increases in serum K w/ K-sparing & K-containing drugs. Increased AUC of ciclosporin & lercanidipine when co-administered. Risk of nephrotoxic synergy w/ MTX. Increased/decreased plasma or whole blood levels w/ CYP3A4 inhibitors/inducers or P-gp inhibitors/inducers. Decreased levels w/ barbiturates, carbamazepine, oxcarbazepine, phenytoin, nafcillin, sulfadimidine IV, rifampicin, octreotide, probucol, orlistat, St. John's wort, ticlopidine, sulfinpyrazone, terbinafine, bosentan. Increased levels w/ macrolides (eg, erythromycin, azithromycin, clarithromycin), ketoconazole, fluconazole, itraconazole, voriconazole, diltiazem, nicardipine, verapamil, metoclopramide, OCs, danazol, methylprednisolone (high dose), allopurinol, amiodarone, cholic acid & derivatives, PIs, imatinib, colchicine, nefazodone. Increased bioavailability w/ grapefruit juice. Potential increased nephrotoxicity w/ aminoglycosides (including gentamycin, tobramycin), amphotericin B, ciprofloxacin, vancomycin, trimethoprim (+ sulfamethoxazole), NSAIDs (including diclofenac, naproxen, sulindac), melphalan, H₂-receptor antagonists (eg, cimetidine, ranitidine), tacrolimus. Reports of considerable but reversible kidney impairment w/ fibric acid derivatives (eg, bezafibrate, fenofibrate). Increased risk of gingival hyperplasia w/ nifedipine. May increase plasma levels of substrates of CYP3A4 & P-gp. May reduce clearance of digoxin, colchicine, prednisolone, HMG-CoA reductase inhibitors (statins), etoposide, aliskiren, bosentan or dabigatran. Enhanced toxicity of digoxin, colchicine, statins. Increased blood levels of everolimus & sirolimus. Increased plasma conc of repaglinide. Increased exposure of ambrisentan & anthracyclines (eg, doxorubicin, mitoxanthrone, daunorubicine). Decreased mean exposure of mycophenolic acid.

Disease-Modifying Anti-Rheumatic Drugs (DMARDs) / Immunosuppressants

L04AD01 - ciclosporin ; Belongs to the class of calcineurin inhibitors. Used as immunosuppressants.

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