Cyclosporin

Indications & Dose:

Severe acute ulcerative colitis refractory to corticosteroid treatment

• BY CONTINUOUS INTRAVENOUS INFUSION

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

• BY MOUTH

Adult: Initially 2.5 mg/kg daily in 2 divided doses, increased if necessary up to 4 mg/kg daily after 6 weeks, if dose increases are necessary they should be made gradually, 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 where conventional therapy ineffective or inappropriate (administered on expert advice) 

• BY MOUTH

Adult: Initially 1.25 mg/kg twice daily (max. per dose 2.5 mg/kg twice daily) usual maximum duration of 8 weeks but may be used for longer under specialist supervision, if good initial response not achieved within 2 weeks, increase dose rapidly up to maximum

Short-term treatment of very severe atopic dermatitis where conventional therapy ineffective or inappropriate (administered on expert advice) 

• BY MOUTH

Adult: 2.5 mg/kg twice daily usual maximum duration of 8 weeks but may be used for longer under specialist supervision

Severe psoriasis where conventional therapy ineffective or inappropriate (administered on expert advice)

• BY MOUTH

Adult: Initially 1.25 mg/kg twice daily (max. per dose 2.5 mg/kg twice daily), increased gradually to maximum if no improvement within 1 month, initial dose of 2.5 mg/kg twice daily justified if condition requires rapid improvement; discontinue if inadequate response after 3 months at the optimum dose; max. duration of treatment usually 1 year unless other treatments cannot be used

Organ transplantation (used alone)

• BY MOUTH

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); if necessary one-third corresponding oral dose can be given by intravenous infusion over 2–6 hours

Bone-marrow transplantation | Prevention and treatment of graft-versus-host disease 

• INITIALLY BY INTRAVENOUS INFUSION

Adult: 3–5 mg/kg daily, to be administered over 2–6 hours from day before transplantation to 2 weeks postoperatively, alternatively (by mouth) initially 12.5–15 mg/kg daily, then (by mouth) 12.5 mg/kg daily for 3-6 months and then tailed off (may take up to a year after transplantation)

Nephrotic syndrome 

• BY MOUTH

Adult: 5 mg/kg daily in 2 divided doses, for maintenance reduce to lowest effective dose according to proteinuria and serum creatininemeasurements; discontinue after 3 months if no improvement in glomerulonephritis or glomerulosclerosis (after 6 months in membranous glomerulonephritis)

Contraindications:

Hypersensitivity to Cremophor EL (Sandimmune dosage forms) 

Side Effects:

CNS: Headache, tremors

CV: Hypertension (50% of renal transplants; most cardiac transplants) 
GI: Diarrhea, gum hyperplasia, hepatotoxicity, nausea, oral Candida, pancreatitis, vomiting 
GU: Albuminuria, hematuria, proteinuria, renal failure
HEME: Leukopenia 
METAB: Hypomagnesemia (related to neurotoxicity) 
SKIN: Acne, hirsutism, rash

Cautions:

Precautions:

Renal disease, hepatic disease, concurrent nephrotoxic drugs; anaphylaxis possible with 1st IV dose; malabsorption syndromes

Interaction:

Drugs

Allopurinol, amiodarone, chloroquine, clarithromycin, clonidine, clotrimazole, oral contraceptives, erythromycin, fluconazole, griseofulvin, itraconazole, ketoconazole, miconazole, roxithromycin, ticlopidine: Increased cyclosporine levels, potential for toxicity

Aminoglycosides, amphotericin B, , enalapril, melphalan, sulfonamides: Additive nephrotoxicity with cyclosporine

Anabolic steroids: Increased cyclosporine levels, potential for toxicity

Barbiturates, carbamazepine, nafcillin, pyrazinamide, phenytoin, sulfonamides: Reduced cyclosporine levels, potential for therapeutic failure

Calcium channel blockers: Diltiazem, verapamil, increase cyclosporine levels; israpidine, nifedipine, nitrendipine do not interact

Cisapride, metoclopramide: Increased bioBrands Available with Cost and serum levels of single-dose cyclosporine

Digitalis glycosides: Cyclosporine in patients stabilized on digitalis leads to increased levels and potential toxicity

Doxorubicin,imipenem: CNS toxicity

HMG-CoA reductase inhibitors: Increased risk of reversible myopathy

Methotrexate: increased toxicity of both agents

NSAIDs: Increased risk of cyclosporine nephrotoxicity

Rifampin: Reduced cyclopsorine levels, potential for therapeutic failure

Warnings:

Adverse Effects:

Lactations:

Pregnancy category C; excreted into breast milk, avoid nursing.

Special Precautions:

Counselling:

Side Effects Or Adverse Reactions:

Patient And Carer Advice: