Formulary
Ciclosporin: Indications, Dosing, Side Effects and Interactions
Ciclosporin inhibits production and release of lymphokines, thereby suppressing cell-mediated immune response.
MedNext Academy | 9 min read
Ciclosporin: Indications, Dosing, Side Effects and Interactions
Ciclosporin inhibits production and release of lymphokines, thereby suppressing cell-mediated immune response.
Drug action
Ciclosporin inhibits production and release of lymphokines, thereby suppressing cell-mediated immune response.
Indications and dose
**Severe active rheumatoid arthritis (administered on expert advice)**
- **Adult** (By Mouth): 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)**
- **Adult** (By Mouth): 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)**
- **Adult** (By Mouth): 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)**
- **Adult** (By Mouth): 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)**
- **Adult** (By Mouth): 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)**
- **Adult** (By Mouth): 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.
**Nephrotic syndrome**
- **Adult** (By Mouth): 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).
**Moderate to severe dry eye disease that has not responded adequately to treatment with tear substitutes (initiated by a specialist)**
- **Adult** (To The Eye): Apply 1 drop twice daily, to be applied to the affected eye(s), review treatment at least every 3 months.
**Severe keratitis in dry eye disease that has not responded to treatment with tear substitutes (initiated by a specialist)**
- **Adult** (To The Eye): Apply 1 drop once daily, to be applied to the affected eye(s) at bedtime, review treatment at least every 6 months.
**Refractory ulcerative colitis for ciclosporin**
- **Child 2-17 years** (By mouth): Initially 2 mg/kg twice daily (max. per dose 5 mg/kg twice daily), dose adjusted according to blood-ciclosporin concentration and response.
- **Child 3-17 years** (By intravenous infusion): Initially 0.5-1 mg/kg twice daily, dose adjusted according to blood-ciclosporin concentration and response.
**Short-term treatment of severe atopic dermatitis where conventional therapy ineffective or inappropriate (administered on expert advice) for ciclosporin**
- **Child** (By mouth): 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) for ciclosporin**
- **Child** (By mouth): 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) for ciclosporin**
- **Child** (By mouth): 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.
**Prevention of graft rejection following bone-marrow, kidney, liver, pancreas, heart, lung, and heart-lung transplantation, Prevention and treatment of graft-versus-host disease for ciclosporin**
- **Child** (By mouth, or by intravenous infusion): (consult local protocol).
**Nephrotic syndrome for ciclosporin**
- **Child** (By mouth): 3 mg/kg twice daily, dose can be increased if necessary in corticosteroid-resistant disease; for maintenance reduce to lowest effective dose according to whole blood-ciclosporin concentrations, proteinuria, and renal function.
**Severe vernal keratoconjunctivitis (initiated by a specialist) for Verkazia**
- **Child 4-17 years** (To the eye): Apply 1 drop 4 times a day, to be applied to the affected eye(s) during the vernal keratoconjunctivitis season, if signs and symptoms persist after the end of the season, treatment may be continued at the recommended dose or decreased to 1 drop twice daily once adequate control is achieved. Once resolved, treatment should be discontinued, and re-initiated upon recurrence.
Cautions
When used by eye Contact lens wearers-consult product literature; glaucoma-limited information available; history of ocular herpes-no information available With systemic use 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 With systemic use: 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.
Contraindications
When used by eye Active or suspected ocular or peri-ocular infection; ocular or peri-ocular malignancies or premalignant conditions With systemic use Malignancy (in non-transplant indications); uncontrolled hypertension (in non-transplant indications); uncontrolled infections (in non-transplant indications)
Side effects
General side-effects: Common or very common Eye inflammation Specific side-effects: Common or very common When used by eye (topical) Eye discomfort; eye disorders; vision blurred With oral use 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 With parenteral use 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 When used by eye (topical) Eye deposit; increased risk of infection With oral use Anaemia; encephalopathy; oedema; thrombocytopenia; weight increased With parenteral use Anaemia; encephalopathy; oedema; thrombocytopenia; weight increased Rare or very rare With oral use Gynaecomastia; haemolytic anaemia; idiopathic intracranial hypertension; menstrual disorder; multifocal motor neuropathy; muscle weakness; myopathy; pancreatitis With parenteral use Gynaecomastia; haemolytic anaemia; idiopathic intracranial hypertension; menstrual disorder; multifocal motor neuropathy; muscle weakness; myopathy; pancreatitis Frequency not known With oral use Pain in extremity; thrombotic microangiopathy With parenteral use Pain in extremity; thrombotic microangiopathy
Interactions
**Severe interactions:**
- However, the pharmacokinetic profile of ciclosporin was not significantly altered.
- The concomitant use of diclofenac and ciclosporin has been found to result in a significant increase in the bioavailability of diclofenac, with the possible consequence of reversible renal function...
- Coadministration of ciclosporin significantly increases blood levels of everolimus and sirolimus.
- Caution is required with concomitant use of potassium sparing medicinal products (e.g.
- A significantly increased exposure to anthracycline antibiotics (e.g.
**Other interactions (59):**
- Drug interactions Of the many medicinal products reported to interact with ciclosporin, those for which the interactions are adequately substantiated and considered to have clinical implications are...
- Various agents are known to either increase or decrease plasma or whole blood ciclosporin levels usually by inhibition or induction of enzymes involved in the metabolism of ciclosporin, in...
- Ciclosporin is also an inhibitor of CYP3A4, the multidrug efflux transporter P-glycoprotein (P-gp) and organic anion transporter proteins (OATP) and may increase plasma levels of co-medications that...
- Medicinal products known to reduce or increase the bioavailability of ciclosporin In transplant patients, frequent measurement of ciclosporin levels and, if necessary, ciclosporin dosage adjustment...
- If medicinal products known to increase ciclosporin levels are given concomitantly, frequent assessment of renal function and careful monitoring for ciclosporin-related side effects may be more...
- Medicinal products that decrease ciclosporin levels All inducers of CYP3A4 and/or P-glycoprotein (P-gp) are expected to decrease ciclosporin levels.
Pregnancy
With systemic use: Crosses placenta; manufacturer advises avoid unless potential benefit outweighs risk-toxicity in animal studies. When used by eye: Manufacturer advises avoid unless potential benefit outweighs risk-no information available.
Breast feeding
With systemic use: Manufacturer advises avoid-present in milk. When used by eye: Manufacturer advises avoid-limited information.
Hepatic impairment
With systemic use: Manufacturer advises caution in severe impairment (risk of increased exposure). Dose adjustments With systemic use: Manufacturer advises consider dose reduction in severe impairment to maintain blood-ciclosporin concentration in target range-monitor until concentration stable.
Renal impairment
With systemic use: 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. Dose adjustments See Prescribing in renal impairment . With systemic use: 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.
Medicinal forms
Ointment,Capsule,Solution,Solution,Drops
Clinical governance
**Author:** MedNext Clinical Team. **Clinical reviewer:** Dr Shameer Deen, MBBS, MS, MRCS. **Sources:** BNF, Indian Pharmacopoeia, CIMS India. **Correction:** Report errors at support@mednext.academy.
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