Drug Action
Ciclosporin inhibits production and release of lymphokines, thereby suppressing cell-mediated immune response.
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Drug reference
Ciclosporin inhibits production and release of lymphokines, thereby suppressing cell-mediated immune response.
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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 (administered on expert advice) ▶BY MOUTH ▶Adult: Initially 1.5 mg/kg twice daily, increased if necessary up to 2.5 mg/kg twice daily after 6 weeks, dose increases should be made gradually, for maintenance treatment, titrate dose individually to the lowest effective dose according to tolerability, treatment may be required for up to 12 weeks Severe active rheumatoid arthritis [in combination with low-dose methotrexate, when methotrexate monotherapy has been ineffective] (administered on expert advice) ▶BY MOUTH ▶Adult: Initially 1.25 mg/kg twice daily, increased if necessary up to 2.5 mg/kg twice daily after 6 weeks, dose increases should be made gradually, for maintenance treatment, titrate dose individually to the lowest effective dose according to tolerability, treatment may be required for up to 12 weeks 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 Immune system and malignant disease 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 creatinine measurements; discontinue after 3 months if no improvement in glomerulonephritis or glomerulosclerosis (after 6 months in membranous glomerulonephritis)
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DUE TO INTERACTIONS ▶With oral use Manufacturer advises increase dose by 50% or switch to intravenous administration with concurrent use of octreotide. l UNLICENSED USE Not licensed for use in severe acute ulcerative colitis refractory to corticosteroid treatment.
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Malignancy (in non-transplant indications). uncontrolled hypertension (in non- transplant indications). uncontrolled infections (in non- transplant indications)
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Elderly—monitor renal function. hyperuricaemia. in atopic dermatitis, active herpes simplex infections—allow infection to clear before starting (if they occur during treatment withdraw if severe). in atopic dermatitis, Staphylococcus aureus skin infections— not absolute contra-indication providing controlled (but avoid erythromycin unless no other alternative). in psoriasis treat, patients with malignant or pre-malignant conditions of skin only after appropriate treatment (and if no other option). in uveitis, Behcet’s syndrome (monitor neurological status). lymphoproliferative disorders (discontinue treatment). malignancy CAUTIONS, FURTHER INFORMATION ▶Malignancy In psoriasis, exclude malignancies (including those of skin and cervix) before starting (biopsy any lesions not typical of psoriasis) and treat patients with malignant or pre-malignant conditions of skin only after appropriate treatment (and if no other option); discontinue if lymphoproliferative disorder develops.
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Brand name prescribing Prescribing and dispensing of ciclosporin should be by brand name to avoid inadvertent switching. If it is necessary to switch a patient to a different brand of ciclosporin, the patient should be monitored closely for changes in blood-ciclosporin concentration, serum creatinine, blood pressure, and transplant function (for transplant indications). Sandimmun ® capsules and oral solution are available direct from Novartis for patients who cannot be transferred to a different oral preparation.
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MHRA/CHM ADVICE: CICLOSPORIN MUST BE PRESCRIBED AND DISPENSED BY BRAND NAME (DECEMBER 2009) Patients should be stabilised on a particular brand of oral ciclosporin because switching between formulations without close monitoring may lead to clinically important changes in blood-ciclosporin concentration.
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→Appendix 1: ciclosporin
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GENERAL SIDE-EFFECTS ▶Common or very common Eye inflammation SPECIFIC SIDE-EFFECTS ▶Common or very common Appetite decreased. diarrhoea. electrolyte imbalance. fatigue. fever. flushing. gastrointestinal discomfort. gingival hyperplasia. hair changes. headaches. hepatic disorders. hyperglycaemia. hyperlipidaemia. hypertension. hyperuricaemia. leucopenia. muscle complaints. nausea. paraesthesia. peptic ulcer. renal impairment (renal structural changes on long-term administration). seizure. skin reactions. tremor. vomiting ▶Uncommon Anaemia. encephalopathy. oedema. thrombocytopenia. weight increased ▶Rare or very rare Gynaecomastia. haemolytic anaemia. idiopathic intracranial hypertension. menstrual disorder. multifocal motor neuropathy. muscle weakness. myopathy. pancreatitis ▶Frequency not known Pain in extremity. thrombotic microangiopathy Immune system and malignant disease
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Crosses placenta; manufacturer advises avoid unless potential benefit outweighs risk—toxicity in animal studies.
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Manufacturer advises avoid—present in milk.
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Manufacturer advises caution in severe impairment (risk of increased exposure). Dose adjustments Manufacturer advises consider dose reduction in severe impairment to maintain blood- ciclosporin concentration in target range—monitor until concentration stable.
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Dose adjustments In non-transplant indications, manufacturer advises establishing baseline renal function before initiation of treatment; if baseline function is impaired in non-transplant indications, except nephrotic syndrome—avoid. In nephrotic syndrome, manufacturer advises initial dose should not exceed 2.5 mg/kg daily in patients with baseline renal impairment. During treatment for non-transplant indications, manufacturer recommends if eGFR decreases by more than 25% below baseline on more than one measurement, reduce dose by 25–50%. If the eGFR decrease from baseline exceeds 35%, further dose reduction should be considered (even if within normal range); discontinue if reduction not successful within 1 month.
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Monitor whole blood ciclosporin concentration (trough level dependent on indication—consult local treatment protocol for details). Dermatological and physical examination, including blood pressure and renal function measurements required at least twice before starting treatment for psoriasis or atopic dermatitis. Monitor liver function. Monitor serum potassium, especially in renal dysfunction (risk of hyperkalaemia). Monitor serum magnesium. Measure blood lipids before treatment and after the first month of treatment. In psoriasis and atopic dermatitis monitor serum creatinine every 2 weeks for first 3 months then every month. Investigate lymphadenopathy that persists despite improvement in atopic dermatitis. Monitor kidney function—dose dependent increase in serum creatinine and urea during first few weeks may necessitate dose reduction in transplant patients (exclude rejection if kidney transplant) or discontinuation in non-transplant patients. Monitor blood pressure—discontinue if hypertension develops that cannot be controlled by antihypertensives. In long-term management of nephrotic syndrome, perform renal biopsies at yearly intervals. In rheumatoid arthritis measure serum creatinine at least twice before treatment. During treatment, monitor serum creatinine every 2 weeks for first 3 months, then every month for a further 3 months, then every 4–8 weeks depending on the stability of the disease, concomitant medication, and concomitant diseases (or more frequently if dose increased or concomitant NSAIDs introduced or increased). Monitor hepatic function if concomitant NSAIDs given.
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▶With oral use Mix solution with orange or apple juice, or other soft drink (to improve taste) immediately before taking (and rinse with more to ensure total dose). Do not mix with grapefruit juice. Total daily dose should be taken in 2 divided doses. ▶With intravenous use For intravenous infusion (Sandimmun ®), give intermittently or continously in Glucose 5% or Sodium Chloride 0.9%; dilute to a concentration of 50 mg in 20–100 mL; give intermittent infusion over 2–6 hours; not to be used with PVC equipment. Observe patient for signs of anaphylaxis for at least 30 minutes after starting infusion and at frequent intervals thereafter.
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There can be variation in the licensing of different medicines containing the same drug. Solution for infusion CAUTIONARY AND ADVISORY LABELS 11 EXCIPIENTS: May contain Alcohol, polyoxyl castor oils ▶Sandimmun (Novartis Pharmaceuticals UK Ltd) Ciclosporin 50 mg per 1 ml Sandimmun 250mg/5ml concentrate for solution for infusion ampoules | 10 ampoule P £110.05 Sandimmun 50mg/1ml concentrate for solution for infusion ampoules | 10 ampoule P £23.23 Oral solution CAUTIONARY AND ADVISORY LABELS 11 EXCIPIENTS: May contain Alcohol, propylene glycol ▶Capsorin (Morningside Healthcare Ltd) Ciclosporin 100 mg per 1 ml Capsorin 100mg/ml oral solution sugar- free | 50 ml P £86.96 DT = £164.72 ▶Neoral (Novartis Pharmaceuticals UK Ltd) Ciclosporin 100 mg per 1 ml Neoral 100mg/ml oral solution sugar- free | 50 ml P £102.30 DT = £164.72 ▶Sandimmun (Novartis Pharmaceuticals UK Ltd) Ciclosporin 100 mg per 1 ml Sandimmun 100mg/ml oral solution sugar-free | 50 ml P £164.72 DT = £164.72 Capsule CAUTIONARY AND ADVISORY LABELS 11 EXCIPIENTS: May contain Ethanol, ethyl lactate, propylene glycol ▶Ciclosporin (Non-proprietary) Ciclosporin 25 mg Ciclosporin 25mg capsules | 30 capsule P s DT = £18.37 Ciclosporin 50 mg Ciclosporin 50mg capsules | 30 capsule P s DT = £35.97 Ciclosporin 100 mg Ciclosporin 100mg capsules | 30 capsule P s DT = £68.28 ▶Capimune (Mylan) Ciclosporin 25 mg Capimune 25mg capsules | 30 capsule P £13.05 DT = £18.37 Ciclosporin 50 mg Capimune 50mg capsules | 30 capsule P £25.50 DT = £35.97 Ciclosporin 100 mg Capimune 100mg capsules | 30 capsule P £48.50 DT = £68.28 ▶Capsorin (Morningside Healthcare Ltd) Ciclosporin 25 mg Capsorin 25mg capsules | 30 capsule P £11.14 DT = £18.37 Ciclosporin 50 mg Capsorin 50mg capsules | 30 capsule P £21.80 DT = £35.97 Ciclosporin 100 mg Capsorin 100mg capsules | 30 capsule P £41.59 DT = £68.28 ▶Deximune (Dexcel-Pharma Ltd) Ciclosporin 25 mg Deximune 25mg capsules | 30 capsule P £13.06 DT = £18.37 Ciclosporin 50 mg Deximune 50mg capsules | 30 capsule P £25.60 DT = £35.97 Ciclosporin 100 mg Deximune 100mg capsules | 30 capsule P £48.90 DT = £68.28 ▶Neoral (Novartis Pharmaceuticals UK Ltd) Ciclosporin 10 mg Neoral 10mg capsules | 60 capsule P £18.25 DT = £18.25 Ciclosporin 25 mg Neoral 25mg capsules | 30 capsule P £18.37 DT = £18.37 Ciclosporin 50 mg Neoral 50mg capsules | 30 capsule P £35.97 DT = £35.97 Ciclosporin 100 mg Neoral 100mg capsules | 30 capsule P £68.28 DT = £68.28 ▶Sandimmun (Novartis Pharmaceuticals UK Ltd) Ciclosporin 25 mg Sandimmun 25mg capsules | 30 capsule P £29.58 DT = £18.37 Ciclosporin 50 mg Sandimmun 50mg capsules | 30 capsule P £57.92 DT = £35.97 Ciclosporin 100 mg Sandimmun 100mg capsules | 30 capsule P £109.93 DT = £68.28 ▶Vanquoral (Teva UK Ltd) Ciclosporin 10 mg Vanquoral 10mg capsules | 60 capsule P £12.75 DT = £18.25 Ciclosporin 25 mg Vanquoral 25mg capsules | 30 capsule P £13.05 DT = £18.37 Ciclosporin 50 mg Vanquoral 50mg capsules | 30 capsule P £25.59 DT = £35.97 Ciclosporin 100 mg Vanquoral 100mg capsules | 30 capsule P £48.89 DT = £68.28
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Patients and carers should be counselled on the administration of different formulations of ciclosporin. Manufacturer advises avoid excessive exposure to UV light, including sunlight. In psoriasis and atopic dermatitis, avoid use of UVB or PUVA.
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2 mg/kg, to be given over 24 hours, dose
First-line fragment. Read the complete Indications and Dose section above.
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Initially 1.5 mg/kg twice daily, increased if
First-line fragment. Read the complete Indications and Dose section above.
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Initially 1.25 mg/kg twice daily, increased if
First-line fragment. Read the complete Indications and Dose section above.
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Initially 1.25 mg/kg twice daily (max. per dose
First-line fragment. Read the complete Indications and Dose section above.
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2.5 mg/kg twice daily usual maximum duration
First-line fragment. Read the complete Indications and Dose section above.
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Initially 1.25 mg/kg twice daily (max. per dose
First-line fragment. Read the complete Indications and Dose section above.
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10–15 mg/kg, to be administered 4–12 hours
First-line fragment. Read the complete Indications and Dose section above.
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3–5 mg/kg daily, to be administered over
First-line fragment. Read the complete Indications and Dose section above.
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5 mg/kg daily in 2 divided doses, for
First-line fragment. Read the complete Indications and Dose section above.
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