Sandimmun/Sandimmun Neoral

Ciclosporin

Prevention of rejection of kidney, liver, heart, combined heart-lung, lung & pancreas allografts. Treatment of transplant rejection in patients previously treated w/ other immunosuppressive agents. Prevention of bone marrow graft rejection. Prevention & treatment of graft-versus-host disease (GVHD). Sandimmun Neoral Non-transplantation indications: Active sight-threatening intermediate or posterior uveitis of non-infectious aetiology in which alternative therapy is ineffective or inappropriate. Uveitis in Behçet's disease, w/ recurrent inflammatory attacks involving the retina, in patients 7-70 yr w/ normal renal function. Treatment of severe cases of psoriasis in which alternative therapies are ineffective or inappropriate. Treatment of severe cases of atopic dermatitis in which alternative therapies are ineffective or inappropriate. Treatment of severe cases of RA in which standard basic therapies are ineffective or inappropriate. Idiopathic steroid-dependent or steroid-resistant nephrotic syndrome (biopsy shows minimal-change disease or focal segmental glomerulosclerosis in most cases) in adults or childn, which has failed to respond to conventional cytostatic therapy, but only if renal function indices are at least 50% below normal values. Maintenance of steroid-induced remission, in order to enable corticosteroids to be w/drawn.

Sandimmun Organ transplantation 3-5 mg/kg. In conjunction w/ other immunosuppressants: Lower doses (eg, 1-2 mg/kg daily IV followed initially by 3-6 mg/kg daily orally) may be given. Bone marrow transplantation Starting dose should be given on the day before transplantation. 3-5 mg/kg daily IV infusion, repeated daily in the immediate post-op period for a max of 2 wk before switching to oral maintenance. Sandimmun Neoral Organ transplantation Initially 10-15 mg/kg in 2 divided doses w/in 12 hr before transplantation, maintain for 1-2 wk post-surgery, then gradually reduce to maintenance dose of 2-6 mg/kg daily in 2 divided doses. In conjunction w/ other immunosuppressants: Lower doses (eg, 3-6 mg/kg daily as starting dose) may be given. Bone marrow transplantation Initially 12.5-15 mg/kg daily on the day before transplantation. Maintenance dose: Approx 12.5 mg/kg daily in 2 divided doses for at least 3-6 mth, then gradually taper off completely w/in a period of 1 yr after transplantation. Reinstitution therapy in case of GVHD following treatment w/drawal: Initially 10-12.5 mg/kg, followed by daily oral maintenance dose. Endogenous uveitis Initially 5 mg/kg daily in 2 divided doses until uveitis subsides & visual acuity improves, may be temporarily increased to 7 mg/kg daily in resistant cases. Maintenance: Gradually reduce to lowest effective dose & do not exceed 5 mg/kg daily during periods of remission. Psoriasis Induction of remission: Initially 2.5 mg/kg daily in 2 divided doses, increasing gradually by 0.5-1 mg/kg mthly up to max 5 mg/kg daily if no improvement after 1 mth. Initially 5 mg/kg daily in 2 divided doses if rapid improvement is required. Maintenance: Adjust to lowest effective dose & do not exceed 5 mg/kg daily. Atopic dermatitis Adult & adolescent >16 yr 2.5-5 mg/kg daily in 2 divided doses, may be rapidly increased to max of 5 mg/kg after 2 wk of unsatisfactory response. Initially 5 mg/kg daily in very severe cases. RA 3 mg/kg daily in 2 divided doses for the 1st 6 wk, may be gradually increased to max 5 mg/kg if effect is considered insufficient. Nephrotic syndrome Induction of remission: Adult 5 mg/kg daily in 2 divided doses. Childn 6 mg/kg daily in 2 divided doses. Patient w/ abnormal renal function at baseline Do not exceed 2.5 mg/kg daily as starting dose. Maintenance: Gradually reduce to lowest effective dose.

May be taken with or without food: Cap: Swallow whole. Oral soln: Dilute w/ orange/apple juice. Other drinks (eg, soft drinks) may be used according to individual taste. Stir soln well & drink immediately. Do not use grapefruit juice.

Sandimmun Hypersensitivity to ciclosporin or polyoxyethylated castor oil. Sandimmun Neoral Hypersensitivity. Non-transplantation indications: Renal impairment, except in patients w/ nephrotic syndrome & moderately increased baseline serum creatinine values of max 200 micromol/L in adults & 140 micromol/L in childn. Inadequately controlled HTN &/or infection. History of known or diagnosed malignancy of any kind, except premalignant or malignant skin lesions following curative treatment.

Increased risk of lymphomas & other malignancies, particularly of the skin. W/draw treatment if premalignancy or malignancy is determined. Avoid excessive sun exposure w/o adequate protection. Do not receive concomitant UVB irradiation or PUVA photochemotherapy. Susceptibility to bacterial, fungal, parasitic & viral infections, often w/ opportunistic pathogens. Activation of latent polyomavirus infections that may lead to polyomavirus-associated nephropathy, especially BK virus nephropathy or JC-virus-associated progressive multifocal leucoencephalopathy. Increases in serum creatinine & urea levels; serum bilirubin & liver enzyme levels. Regularly monitor appropriate hepatic & renal parameters. Monitor ciclosporin blood levels preferably by measuring the proportion of parent drug using a specific monoclonal Ab or a HPLC-based analysis method. Regularly check BP during therapy. Measure blood lipid levels prior to & 1 mth after the start of treatment. Increased risk of hyperkalaemia, particularly in patients w/ renal dysfunction. Enhanced clearance of Mg. Monitor serum Mg levels during the peri-transplantation period, particularly in the presence of neurological symptoms. Caution in treating patients w/ hyperuricaemia. Avoid w/ live vaccines; aliskiren, dabigatran or bosentan. Caution w/ lercanidipine. Pregnancy. Do not breastfeed during treatment. Sandimmun Contains polyoxyethylated castor oil. Sandimmun Neoral Absorption of calcineurin inhibitors may be impaired in patients w/ cystic fibrosis. Reports of possible connection w/ neurological manifestations of Behçet's syndrome. Carefully monitor neurological status. Do not give concomitantly w/ β-blockers or diuretics in psoriasis patients. Contains ethanol (oral soln only). Not recommended in paed patients <16 yr in non-transplantation indications other than nephrotic syndrome.

Hyperlipidaemia; tremor, headache including migraine; HTN; nausea, vomiting, abdominal pain, diarrhoea, gingival hyperplasia; hypertrichosis; renal dysfunction. Leukopenia; anorexia, hyperuricaemia, hyperkalaemia, hypomagnesaemia; paraesthesia; peptic ulcer; liver injury; acne, rash; muscle cramps, myalgia; fatigue, pyrexia, oedema.

Increased bioavailability w/ grapefruit juice. Reduced levels w/ barbiturates, carbamazepine, oxcarbazepine, phenytoin, nafcillin, sulfadimidine IV, rifampicin, octreotide, probucol, orlistat, Hypericum (St. John's wort) prep, ticlopidine, sulfinpyrazone, terbinafine, bosentan. Increased levels w/ chloroquine, macrolide antibiotics (eg, erythromycin, azithromycin & clarithromycin), ketoconazole, fluconazole, itraconazole, voriconazole, diltiazem, nicardipine, verapamil, metoclopramide, OCs, danazol, high-dose methylprednisolone, allopurinol, amiodarone, cholic acid & derivatives, PIs, imatinib, colchicine, nefazodone. Synergistic interaction w/ other medicines causing nephrotoxicity eg, aminoglycosides (including gentamicin & tobramycin), amphotericin B, ciprofloxacin, vancomycin, trimethoprim (+ sulfamethoxazole), NSAIDs (including diclofenac, indometacin, naproxen & sulindac), melphalan, histamine H₂-receptor antagonists (eg, cimetidine, ranitidine), MTX, tacrolimus. Increased incidence of gingival hyperplasia w/ nifedipine. Increased AUC of ciclosporin & lercanidipine following co-administration. Significantly increased bioavailability of diclofenac. May reduce clearance of digoxin, colchicine, prednisolone, HMG-CoA reductase inhibitors (statins), etoposide, aliskiren, bosentan or dabigatran. Severe digitalis intoxication w/ digoxin. Potential to potentiate toxic effects of colchicine. Significantly increased exposure to anthracycline antibiotics (eg, doxorubicine, mitoxanthrone, daunorubicine). Cases of myotoxicity, myositis & rhabdomyolysis w/ lovastatin, simvastatin, atorvastatin, pravastatin & fluvastatin. Elevated serum creatinine w/ everolimus or sirolimus. Significantly increased blood levels of everolimus & sirolimus. Significantly increased serum K w/ K-sparing drugs (eg, K-sparing diuretics, ACE inhibitors, AIIAs) or K-containing medicines. May raise plasma levels of repaglinide. Decreased levels w/ bosentan. Increased exposure of bosentan. Increased C_max & AUC of aliskiren. Increased plasma conc of dabigatran. Increased exposure of ciclosporin & ambrisentan following co-administration.

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

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

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