NSAIDS, MTX, LEFLUNOMIDE, CICLOSPORIN THERAPEUTICS

Oral - 100 mg OD for 3 days (loading dose) * Then, DECREASE to 10-20 mg OD

• The effect starts after 4-6 weeks and may further improve up to 4-6 months

Liver function tests (LFT), full blood count (FBC) and BP * Prior to initiation * Every 2 weeks for the first 6 months * Then, every 8 weeks

• GI • Alopecia • Skin reactions • Dizziness

• Hepatic impairment • Bone marrow suppression – leucopoenia, anaemia, thrombocytopenia, pancytopenia • Increased BP (Common)

• Hepatic impairment – accumulation • Severe immunodeficiency • Severe infection • Severe hypoproteinaemia • Moderate to severe renal impairment – no data • Pregnancy • Breastfeeding

• Haematotoxic or hepatotoxic drugs • People with History of TB • Bone marrow suppression – anaemia, leucopenia, thrombocytopenia

• Avoid live vaccines • Avoid alcohol (increase risk of hepatic impairment) • Can be taken with or without food

• Monitoring after discontinuation is required • Washout procedure – • Stop treatment • Give colestyramine 8 g TDS or activated charcoal 50g QDS • Treat for 11 days • The active metabolite has a long half life – 1-4 weeks

Calcineurin inhibitor

• Inflammatory bowel disease • Immunosuppressive therapy in transplant patients (SOT and bone marrow) • Psoriasis • Severe atopic dermatitis • Rheumatoid arthritis

PO, IV • Doses vary greatly for the different conditions - Doses are often titrated • Balance between effective treatment and tolerability/adverse effects

• GI, fatigue, convulsions, headache, muscle cramps, tremor, hyperG, hyperL, hyperK, hyperuricaemia hypoM, HP, hirtsutism, Hypertrichosis, hepatic impairment, renal impairment, leucopenia • Other important side effects – • Immunosuppression • Immunosuppression – lymphomas and malignancies (esp. skin)

• Abnormal Renal function • Malignancy • Uncontrolled hypertension • Uncontrolled infection

• Elderly • Gout • Hepatic impairment

• Renal function • Hepatic function • BP • Lipids • Electrolytes – potassium, magnesium, • Uric acid

• CYP450 inhibitors – macrolides, diltiazem, verapamil, lercanidipine, fluconazole, itraconazole, ketoconazole, grapefruit juice → ↑blood ciclosporin levels • CYP450 inducers – rifampicin, carbamazepine, phenobarbital, phenytoin, St. John Wort → ↓ blood ciclosporin levels • Statins – avoid or dose reductions • Nephrotoxic drugs – NSAIDs, MTX • Any drugs causing effects as seen with ciclosporin • i.e. K+ sparing diuretics

• The oral dose of ciclosporin is approximately 3 times that of the IV formulation Specific information relating to the oral solution - * Required dose should be mixed with orange or apple juice immediately before administration

• Twice a day preparation • Should be maintained on the same brand of ciclosporin • Consistency of administration – time of day and proximity to food • Avoid live vaccines

Once a week • On the same day of the week – documented in full on the prescription • Patient should be appropriately educated about the dosing schedule • Dose and frequency should be clear on the label

The strength of tablet should be prescribed as a single strength of tablet, only 2.5mg should be used – low dose MTX

Oral (Po), intramuscular (IM), subcutaneous (SC) • There are slight differences in dosing for different immune diseases and when using different routes

Generally it will take some time for MTX to start to have it’s effect and for that effect to be at a maximum * i.e. for RA it can take 6 weeks to begin to work and 12 weeks to feel the maximum effect • In RA, dose escalation is required to reach the optimal dose • 2.5mg to 5mg increases every 1-3 weeks • Aim for optimal dose in 4-6 weeks

• Full blood count (FBC) • Liver function test (LFT) • Renal function (creatinine, Cr or estimated glomerular filtration rate, eGFR) = every 1-2 weeks until therapy stabilised • Once stabilised – every 2-3 months • Urea and electrolytes (U&E) • Chest x-ray