CICLOSPORIN

Immunosuppressive medicine

Dosage Forms

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Tablet

25 mg

Capsules

100 mg

Concentrate for intravenous infusion

50mg/ml

Uses

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  • Prevention of graft rejection
  • Prophylaxis of graft-versus-host disease
  • Nephrotic syndrome
  • Inflammatory bowel disease
  • Rheumatoid arthritis
  • Psoriasis
  • Atopic dermatitis

Dose and Duration

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Adjust dose according to plasma ciclosporin concentration and renal function. Lower doses are required when ciclosporin is used with other immunosuppressants
Organ transplantation
Adult and child over 3 months: by mouth, 10–15 mg/kg 4–12 hours before surgery given in 2 divided doses, then 10–15 mg/kg in 2 divided doses for 1–2 weeks and reducing it gradually to a maintenance dose of 2–6 mg/kg daily in 2 divided doses

By IV infusion: if using concentrated solution, give 1/3rd of the corresponding dose by mouth over 2–6 hours. Same dose as for oral administration when diluted

Bone marrow transplantation, graft-versus-host disease
Adult and child over 3 months:by mouth, 12.5–15 mg/kg daily in 2 divided doses for 2 weeks, starting on the day before surgery, followed by 12.5 mg/kg daily in 2 divided doses for 3–6 months, then gradually reduced to zero by 1 year after transplantation.

By IV infusion over 2–6 hours, 3–5 mg/kg daily for 2 weeks, starting on the day before surgery, followed by maintenance doses by mouth

Intractable hiccups
Adult:25–50 mg every 6–8 hours
Nephrotic syndrome
Adult:by mouth, initially 2.5 mg/kg every 12 hours slowly reduced to lowest effective dose according to proteinuria and serum creatinine measurements. Discontinue after 3 months if no improvement is observed (after 6 months in membranous glomerulonephritis)
Child:by mouth, initially 3 mg/kg every 12 hours and titrated as in the adult
Inflammatory bowel disease
Adult:by continuous IV infusion, 2 mg/kg daily over 24 hours adjusted according to blood ciclosporin concentration and response
Rheumatoid arthritis
Adult: 1.5 mg/kg every 12 hours for 6 weeks increased gradually according to response and tolerability up to a maximum 2.5 mg/kg every 12 hours for 6 more weeks
Psoriasis, atopic dermatitis
Adult: initially 1.25 mg/kg (2.5 mg/kg if rapid improvement is needed) every 12 hours gradually increased if there is no improvement after 1 month (2 weeks in dermatitis) to a maximum dose of 2.5 mg/kg every 12 hours. Treat for 8 weeks to 1 year in dermatitis Discontinue if there is no improvement after 6 weeks of treatment in psoriasis

Preparation

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  • Dilute according to manufacturer’s directions

Contraindications

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  • Porphyria
  • Malignancy
  • Uncontrolled infections

Side Effects

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  • Nutrition disorders such as hyperlipidaemia, anorexia
  • Metabolism disorders e.g. hyperglycaemia, hyperuricaemia, hyperkalaemia and hypomagnesaemia
  • Leucopoenia
  • Tremor, paraesthesia, headache, convulsions, fever
  • Hypertension, flushing
  • Fatigue
  • Nausea, vomiting, abdominal pain, diarrhea
  • Gingival hyperplasia and peptic ulcer
  • Abnormal hepatic function
  • Hirsutism, acne, hypertrichosis (excessive body and/or facial hair growth)
  • Hirsutism, acne, hypertrichosis (excessive body and/or facial hair growth)
  • Renal dysfunction

Interactions

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  • Amikacin, amphotericin B, ciprofloxacin, gentamicin, ibuprofen, levofloxacin, ofloxacin, silver sulfadiazine, streptomycin, sulfadiazine, sulfadoxine + pyrimethamine, vancomycin (increased risk of nephrotoxicity)
  • Silver sulfadiazine, sulfadiazine, sulfamethoxazole + trimethoprim, trimethoprim (plasma ciclosporin concentration possibly increased)
  • Amiloride (increased risk of hyperkalaemia)
  • Azithromycin, chloramphenicol, doxycycline, ritonavir (plasma concentration of ciclosporin possibly increased)
  • Carbamazepine, Phenobarbital, phenytoin, rifampicin ( reduced plasma ciclosporin concentration)
  • Chloroquine, erythromycin, fluconazole, grape fruit juice, levonogestrel, medroxyprogesterone, metoclopramide, norethisterone, verapamil (increased plasma concentration and toxicity of ciclosporin)
  • Oral contraceptives (Plasma ciclosporin concentration in creased)
  • Digoxin (increased concentration and toxicity of digoxin)
  • Doxorubicin (increased risk of neurotoxicity)
  • Enalapril, potassium salts, spironolactone (increased risk of hyperkalaemia)
  • Methotrexate (increased toxicity)
  • Simvastatin (increased risk of myopathy)

Pregnancy

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  • Do not use

Breastfeeding

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  • Do not use

⚠️ Caution

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  • Monitor renal function. Reduce dose if dose-related in creases in serum creatinine and blood urea nitrogen oc cur during the first few weeks; exclude kidney transplant rejection
  • Monitor hepatic function. Adjust dose according to bilirubin and liver enzymes levels
  • Monitor blood pressure and discontinue if hypertension cannot be controlled by antihypertensives .
  • Monitor serum magnesium and potassium especially in renal impairment due to risk of hyperkalaemia
  • Monitor blood lipids before and during treatment
  • In patients with nephritic syndrome, reduce dose by 25-50% if serum creatinine is more than 30% above baseline at more than one measurement. Perform renal biopsies at yearly intervals
  • Monitor patients receiving the IV infusion for 30 minutes after starting the infusion since the polyethoxylated castor oil may cause anaphylaxis in some patients
  • When changing from IV to oral dose, start with similar dose as for IV and monitor ciclosporin plasma concentration for 4–7 days
  • Use in pregnancy may cause premature delivery