What is Ciclosporin used for?

Ciclosporin is evaluated for the following indications with varying evidence strength: Maintenance immunosuppression after organ transplantation (evidence tier A), Severe plaque psoriasis (evidence tier A), Severe atopic dermatitis (evidence tier A). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Ciclosporin?

Common side effects of Ciclosporin (≥ 1 in 100): Arterial hypertension, Decreased eGFR, raised creatinine, Hypertrichosis, Gingival hyperplasia, Tremor, Paresthesias. See the Safety section for uncommon and serious reactions.

Who should not take Ciclosporin?

Ciclosporin is contraindicated in: Hypersensitivity to cyclosporine; Uncontrolled arterial hypertension; Active untreated infections; Malignancy (except post-transplant use); Severe renal impairment outside transplantation. Full list in the Safety section.

Does Ciclosporin carry an FDA boxed warning?

FDA boxed warning: cyclosporine therapy is delivered only by physicians experienced in immunosuppression and transplantation. The drug increases risk of severe infections and lymphoproliferative disorders. Oral Sandimmune and microemulsion (Neoral, Gengraf) are not bioequivalent and not interchangeable without dose recalculation and concentration monitoring.

FDA category C. FDA category C. In transplant patients, pregnancy on cyclosporine is feasible – data on thousands of live births are available. Risks: prematurity, low birth weight, hypertension. In pregnant patients with other indications, use is strictly individualized by a team including a transplantation specialist or rheumatologist.

Maintenance immunosuppression after organ transplantation

First line

Cyclosporine is one of the cornerstone maintenance immunosuppressants after kidney, liver, heart, lung and bone marrow transplantation. Standard regimens combine it with an antimetabolite (mycophenolate mofetil, azathioprine) and a glucocorticoid. In recent years tacrolimus has gradually replaced cyclosporine in most protocols due to better graft survival, but cyclosporine remains an alternative when tacrolimus is not tolerated or specific adverse effects develop.

Therapy is led by a transplantation specialist with serum concentration monitoring. Target range depends on the type of transplant and time after surgery (typically 100–300 ng/mL by C0 or 600–1400 ng/mL by C2).

Severe atopic dermatitis

Second line

In severe atopic dermatitis not controlled by topical glucocorticoids and calcineurin inhibitors, cyclosporine reduces itch severity and lesion extent within 2–6 weeks. Course is limited to 6–12 months. Since the advent of dupilumab and other biologics, cyclosporine has moved to the second line in adults but remains an option when biologics are unavailable or when a rapid effect is needed.

Sources

Минздрав РФ: Атопический дерматит. Клинические рекомендации (ID 265) (2021)

Severe plaque psoriasis

Second line

Cyclosporine is used in severe psoriasis when topical therapy and phototherapy are insufficient. The effect develops in 4–8 weeks, achieving PASI 50 in 70–80% of patients. Course is limited to 1–2 years due to cumulative nephrotoxicity; after that, retinoids, methotrexate or biologics are used. and the Russian Ministry of Health classify cyclosporine as a standard systemic option for severe psoriasis.

Sources

Non-infectious uveitis

Second line

In non-infectious uveitis, cyclosporine is used as a steroid-sparing immunosuppressant when systemic glucocorticoids alone are insufficient or when dose reduction is needed. Efficacy is established in Behcet disease and severe chronic non-infectious uveitis. Usually combined with methotrexate or mycophenolate mofetil.

Sources

UpToDate: Cyclosporine: Drug information (2024)

Steroid-refractory nephrotic syndrome

Second line

In steroid-refractory nephrotic syndrome, including focal segmental glomerulosclerosis and membranous nephropathy, cyclosporine induces remission in 50–60% of patients. Duration is 12–24 months with gradual withdrawal once stable remission is achieved. Target concentrations are lower than in transplantation (100–175 ng/mL).

Sources

UpToDate: Cyclosporine: Drug information (2024)

Timing and administration

Taken at the same time each day, split into two doses 12 hours apart. Sandimmune Neoral capsules and oral solution are bioequivalent and interchangeable 1:1; conventional Sandimmune (oil-based) has different bioavailability – switching requires dose recalculation. Not co-administered with grapefruit juice (raises concentration via CYP3A4 and P-glycoprotein inhibition).

Monitoring

Cyclosporine concentration is measured fasting (C0) or 2 hours after dose (C2). Creatinine, urea and eGFR are checked every 2 weeks in the first 3 months, monthly thereafter. Potassium, magnesium, uric acid and lipids – monthly. Home blood pressure weekly. If creatinine rises more than 30% above baseline, the dose is reduced by 25–50% or discontinued.

Special situations

Cyclosporine is a CYP3A4 substrate. Concentration rises with concomitant erythromycin, clarithromycin, ketoconazole, fluconazole, diltiazem, verapamil and grapefruit juice. Concentration falls with rifampin, phenytoin, carbamazepine and St. John's wort. Combinations with other nephrotoxic drugs (NSAIDs, aminoglycosides, amphotericin B) are avoided.

Drug interactions

With statins, risk of myopathy and rhabdomyolysis rises. Simvastatin and lovastatin are not used. Atorvastatin – maximum 10 mg daily. Rosuvastatin – maximum 5 mg daily. Combination with potassium-sparing diuretics is avoided due to hyperkalemia risk.

Common myths

Myth: «cyclosporine can be stopped on adverse effects». Fact: in transplant patients, abrupt withdrawal causes acute rejection. Only gradual tapering by the transplantation team.

Myth: «cyclosporine works the same at any dose». Fact: individual bioavailability varies, and therapeutic drug monitoring with C0 or C2 dose adjustment is required.

Myth: «cyclosporine can be taken for years for psoriasis». Fact: course is limited to 1–2 years due to cumulative nephrotoxicity and lymphoma risk.

Grapefruit juice

Grapefruit raises cyclosporine exposure 30–60% via intestinal CYP3A4 inhibition. Nephrotoxicity and hypertension risk. Monitor blood levels and exclude grapefruit from diet.

Source: FDA: Sandimmune (cyclosporine) prescribing information (2021)

Magnesium

Cyclosporine increases renal magnesium excretion and often causes hypomagnesemia. Monthly serum magnesium monitoring. Hypomagnesemia is treated with oral or IV magnesium.

Source: UpToDate: Cyclosporine: Drug information (2024)

Potassium

Cyclosporine raises serum potassium via distal tubular effects. Large dietary potassium intake or supplements may cause hyperkalemia. Combinations with potassium-sparing diuretics and ACE inhibitors require potassium monitoring.

Source: UpToDate: Cyclosporine: Drug information (2024)

Grapefruit

Grapefruit and grapefruit juice inhibit intestinal CYP3A4 and P-glycoprotein, raising cyclosporine bioavailability and serum levels by 1.5–2 fold. This increases nephrotoxicity and other adverse effect risks. Grapefruit and grapefruit juice are eliminated entirely during cyclosporine therapy.

Source: UpToDate: Cyclosporine: Drug information (2024)

Major

clarithromycin

Macrolide antibiotic

Mechanism

Кларитромицин ингибирует CYP3A4 и P-gp, концентрация циклоспорина может удвоиться. Риск нефротоксичности.

Management

Контроль уровня циклоспорина через 3–5 дней. Снизить дозу на 25–50% или заменить антибиотик на азитромицин.

Sources

FDA: Sandimmune (cyclosporine) prescribing information (2021)

Pair details →

Contraindications

Hypersensitivity to cyclosporine
Uncontrolled arterial hypertension
Active untreated infections
Malignancy (except post-transplant use)
Severe renal impairment outside transplantation
Active gout
Concomitant rifampin in dermatologic indications

Serious adverse effects

Chronic nephrotoxicity, progressive CKD
Thrombotic microangiopathy
Lymphoproliferative disorders and other malignancies
Opportunistic infections (CMV, PJP, aspergillosis)
PRES (posterior reversible encephalopathy syndrome)
Hepatotoxicity

Common adverse effects

Arterial hypertension
Decreased eGFR, raised creatinine
Hypertrichosis
Gingival hyperplasia
Tremor
Paresthesias
Nausea, dyspepsia

Uncommon adverse effects

Hyperkalemia
Hypomagnesemia
Hyperuricemia and gout attacks
Hyperlipidemia
Hyperglycemia

PregnancyFDA C

FDA category C. In transplant patients, pregnancy on cyclosporine is feasible – data on thousands of live births are available. Risks: prematurity, low birth weight, hypertension. In pregnant patients with other indications, use is strictly individualized by a team including a transplantation specialist or rheumatologist.

Breastfeeding

Transfers into breast milk. LactMed notes conflicting data: milk levels are low, but a few reports document measurable infant levels. The decision to breastfeed is individualized with the pediatrician and transplantation team.

Ciclosporin

Mechanism of action

Indications

Maintenance immunosuppression after organ transplantation

Severe atopic dermatitis

Severe plaque psoriasis

Non-infectious uveitis

Steroid-refractory nephrotic syndrome

Practical notes

Timing and administration

Monitoring

Special situations

Drug interactions

Common myths

Drug–nutrient interactions

Grapefruit juice

Magnesium

Potassium

Grapefruit

Drug–drug interactions

clarithromycin

Safety

Contraindications

Serious adverse effects

Common adverse effects

Uncommon adverse effects

PregnancyFDA C

Breastfeeding

Frequently asked