BIORAL

*Severe acute ulcerative colitis refractory to corticosteroid treatment:* BY IV INF: Adult: 2 mg/kg, to be given over 24 hours, dose adjusted according to blood-ciclosporin concentration and response. *Severe active rheumatoid arthritis when conventional second-line therapy inappropriate or ineffective:* Adult: Initially 2.5 mg/kg daily in 2 divided doses, increased gradually if necessary up to 4 mg/kg daily after 6 weeks, discontinue if response insufficient after 3 months, dose adjusted according to response for maintenance and treatment reviewed after 6 months. *Short-term treatment of severe atopic dermatitis, Severe psoriasis (where conventional therapy ineffective or inappropriate):* Adult: Initially 1.25 mg/kg twice daily (max. per dose2.5 mg/kg twice daily) usual max. duration of8 weeks but may be used for longer under specialist supervision, discontinue if inadequate response after 3 months at the optimum dose; max duration of treatment usually 1 year. *Organ transplantation (used alone):* Adult: 10-15 mg/kg, to be administered 4-12 hours before transplantation, followed by 10-15 mg/kg daily for 1-2 weeks postoperatively, then maintenance 2-6 mg/kg daily, reduce dose gradually to maintenance. Dose should be adjusted according to blood-ciclosporin concentration and renal function; dose is lower if given concomitantly with other immunosuppressant therapy (e.g. corticosteroids). *Bone-marrow transplantation, Prevention and treatment of graft-versus-host disease:* BY IV INF: Adult: 3-5 mg/kg daily, to be administered over 2-6 hours from day before transplantation to 2 weeks postoperatively, alternatively; oral, initially12.5-15 mg/kg daily, then 12.5 mg/kg daily for 3-6 months and then tailed off (may take up to a year after transplantation). *Nephrotic syndrome:* Adult: 5 mg/kg daily in 2 divided doses, for maintenance reduce to lowest effective dose according to proteinuria and serum creatinine measurements; discontinue after 3 months if no improvement in glomerulonephritis or glomerulosclerosis (after 6 months in membranous glomerulonephritis).

Pregnancy, lactation. In non-transplant indications: abnormal baseline renal function, malignancy, uncontrolled hypertension and uncontrolled infections

Hyperkalaemia, hyper-uricaemia, hypomagnesaemia, elderly. Avoid excess exposure to UV light. Closely monitor renal, liver functions, BP and serum lipids, uveitis, Behcets syndrome (monitor neurological status), lymphoproliferative disorders (discontinue treatment), malignancy. Allow infection to clear before starting (if they occur during treatment withdraw if severe)

Tacrolimus, other immunosuppressants, barbiturates, carbamazepine, oxcarbazepine, primidone, phenytoin, griseofulvin, trimethoprim, rifampicin, octreotide, orlistat, St. Johns Wort, macrolides, azole antifungals, calcium channel blockers, metoclopramide, oral contraceptives, danazol, allopurinol, amiodarone, ursodeoxycholic acid, protease inhibitors, imatinib, nephrotoxic drugs, NSAIDs, vaccines, digoxin, corticosteroids, statins, etoposide, colchicine, K+-sparing diuretics, K+ supplement, ACE inhibitors, angiotensin II antagonists, grapefruit juice, methotrexate, H2 blockers, propafenone, bromocriptine, doxycycline, chloroquine, sulfinpyrazortb, terbinafine, bosentan, substrates of CYP3A4 and/or P-qlycoprotein, repaglinide.

Acne, anorexia, convulsion, fatigue, flushing, gingival hyperplasia, headache, hepatic dysfunction, hirsutism, hyperglycaemia, hyperkalaemia, hyperlipidaemia, hypertension, hypertrichosis, hyperuricaemia, hypomagnesaemia, leucopenia, muscle cramps, myalgia, GI upset, paraesthesia, peptic ulcer, pyrexia, renal dysfunction (renal structural changes on long-term administration), tremor, anaemia, oedema, signs of encephalopathy, thrombocytopenia, weight gain, gynaecomastia, haemolytic uraemic syndrome, menstrual disturbances, micro-angiopathic haemolytic anaemia, motor polyneuropathy, muscle weakness, myopathy, pancreatitis, visual disturbances. Rare: Secondary to benign intracranial hypertension, lymphoproliferative disorder