Ikervis 1mg/1mL eye drops, emulsion

Medical supervision Ciclosporin Viatris should only be prescribed by physicians experienced in immunosuppressive therapy who are able to provide adequate follow-up, including regular complete physical examinations, blood pressure measurements, and monitoring of laboratory safety parameters. Transplant patients should be managed at facilities with appropriate laboratory and supportive medical resources. The physician responsible for maintenance therapy must receive all information necessary for patient follow-up. Lymphomas and other malignancies As with other immunosuppressants, ciclosporin increases the risk of developing lymphomas and other malignancies, particularly those of the skin. The increased risk appears to relate to the degree and duration of immunosuppression rather than to any specific agent. For this reason, regimens combining multiple immunosuppressants (including ciclosporin) should be used cautiously, as they may give rise to lymphoproliferative disorders or solid organ malignancies, some of which have been reported to be fatal. In view of the potential risk of skin malignancies, patients treated with Ciclosporin Viatris, particularly those treated for psoriasis or atopic dermatitis, should be advised to avoid direct sunlight exposure and must not receive concomitant UVB irradiation or PUVA photochemotherapy. Infections As with other immunosuppressants, ciclosporin therapy predisposes patients to the development of various bacterial, fungal, parasitic, and viral infections, often with opportunistic pathogens. Activation of latent polyomavirus infections has been observed in patients receiving ciclosporin and may lead to polyomavirus-associated nephropathy (PVAN), particularly BK virus nephropathy (BKVN), or to JC virus-associated progressive multifocal leukoencephalopathy (PML). These conditions are often associated with a high overall immunosuppressive burden and should be considered in the differential diagnosis of immunosuppressed patients with deteriorating renal function or neurological symptoms. Serious and/or fatal outcomes have been reported. Effective preventive and therapeutic measures must therefore be undertaken, particularly in patients on long-term combined immunosuppressive therapy. Renal toxicity A frequent and potentially serious complication of Ciclosporin Viatris therapy is increases in serum creatinine and urea. These functional changes are dose-dependent and initially reversible, usually responding to dose reduction. During long-term therapy, structural changes in the kidney (e.g. interstitial fibrosis) may develop in some patients, which in renal transplant recipients must be distinguished from changes due to chronic rejection. Renal function should therefore be monitored regularly in this context, in accordance with local guidelines (see sections 4.2 and 4.8). Hepatotoxicity Ciclosporin Viatris may also cause dose-dependent reversible increases in serum bilirubin and liver enzymes (see section 4.8). Solicited and spontaneous post-marketing reports in patients treated with ciclosporin have included hepatotoxicity and liver injury comprising cholestasis, jaundice, hepatitis, and hepatic failure. Most cases occurred in patients with significant comorbidities, underlying conditions, and other contributing factors, including infectious complications and concomitant therapy with potentially hepatotoxic medicinal products. In some cases, mainly in transplant recipients, fatal outcomes have been reported (see section 4.8). Liver function tests should be carefully monitored. If abnormal values occur, dose reduction may be necessary (see sections 4.2 and 5.2). Elderly patients (65 years and over) Renal function should be monitored with particular care in elderly patients. Monitoring of ciclosporin levels (see section 4.2) Routine monitoring of ciclosporin blood levels is an important safety measure in transplant patients receiving Ciclosporin Viatris. Specific monoclonal antibody methods (measuring parent drug) are preferred for monitoring whole-blood ciclosporin concentrations. High-performance liquid chromatography (HPLC) methods, which also measure the parent compound, may be used. When plasma or serum is used, a standardised separation protocol (time and temperature) must be followed. Initial monitoring of liver transplant patients may be carried out using either specific monoclonal antibodies or concurrent assessment with both specific and non-specific monoclonal antibodies, in order to determine a dose that ensures adequate immunosuppression. For non-transplant indications, occasional monitoring of ciclosporin blood levels is recommended, e.g. when Ciclosporin Viatris is co-administered with substances that may affect ciclosporin pharmacokinetics, or in cases of unusual clinical response (such as poor efficacy or increased intolerance during renal dysfunction). Ciclosporin concentrations in blood, plasma, and serum are only one of several factors determining the patient's clinical status; results should therefore serve as a guide to dose adjustment in conjunction with other clinical and laboratory parameters. Hypertension Blood pressure should be monitored regularly during Ciclosporin Viatris therapy; if hypertension develops, appropriate antihypertensive treatment should be initiated. Antihypertensives that do not interfere with ciclosporin pharmacokinetics, e.g. isradipine, are preferred (see section 4.5). Increased blood lipids Since Ciclosporin Viatris has occasionally been reported to cause slight, reversible increases in blood lipids, lipid levels should be measured before treatment and after the first month of therapy. If elevations occur, a low-fat diet should be considered and, where appropriate, a reduction in ciclosporin dose. Hyperkalaemia Ciclosporin increases the risk of hyperkalaemia, particularly in patients with renal impairment. Caution is required when ciclosporin is co-administered with potassium-sparing agents (e.g. potassium-sparing diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists), potassium-containing products, or in patients on a high-potassium diet. In such situations, monitoring of serum potassium is recommended. Hypomagnesaemia Ciclosporin increases magnesium excretion. This may lead to symptomatic hypomagnesaemia, particularly in the peri-transplant period. Serum magnesium levels should therefore be monitored peri-transplantation, especially in patients with neurological symptoms. Magnesium supplementation should be administered if considered necessary. Hyperuricaemia Caution is required when treating patients with hyperuricaemia. Live attenuated vaccines Vaccination may be less effective during ciclosporin therapy. Vaccination with live attenuated vaccines should be avoided (see section 4.5). Interactions Caution is required when ciclosporin is co-administered with medicinal products that substantially increase or decrease ciclosporin plasma levels by inhibiting or inducing CYP3A4 and/or P-glycoprotein (P-gp) (see section 4.5). The patient's clinical status should be monitored carefully. Monitoring of ciclosporin blood levels and dose adjustment may be necessary. When co-administering ciclosporin with active substances that increase ciclosporin levels or with substances having synergistic nephrotoxic effects, renal toxicity must be monitored (see section 4.5). Ciclosporin and tacrolimus should not be administered concomitantly (see section 4.5). Ciclosporin is an inhibitor of CYP3A4, of the multidrug efflux transporter P-gp, and of organic anion transporting polypeptides (OATP), and may increase the plasma levels of co-administered medicinal products that are substrates of this enzyme and/or transporters. Caution is therefore required when co-administering ciclosporin with such products, or such combinations should be avoided (see section 4.5). Ciclosporin increases the exposure to HMG-CoA reductase inhibitors (statins). When statins are co-administered with ciclosporin, the statin dose should be reduced, or co-administration with certain statins should be avoided in accordance with the recommendations in their respective product information. In patients with signs or symptoms of myopathy, or with risk factors predisposing to severe renal injury, including renal failure secondary to rhabdomyolysis, statin therapy should be temporarily withheld or discontinued (see section 4.5). Concomitant use of ciclosporin and lercanidipine resulted in a 3-fold increase in lercanidipine AUC, while ciclosporin AUC increased by 21 %. Therefore, ciclosporin should not be administered at the same time as lercanidipine. Administration of ciclosporin 3 hours after lercanidipine did not alter lercanidipine AUC, but ciclosporin AUC increased by 27 %. This combination should therefore be administered with caution, with an interval of at least 3 hours between lercanidipine and ciclosporin dosing. Additional precautions for non-transplant indications Patients with impaired renal function (other than nephrotic syndrome with an acceptable degree of renal impairment), uncontrolled hypertension, uncontrolled infections, or any malignancies must not receive ciclosporin. Before starting therapy, a reliable baseline of renal function must be established using at least two measurements of eGFR. Renal function must be monitored repeatedly during therapy to allow dose adjustment (see section 4.2). Additional precautions in endogenous uveitis Ciclosporin Viatris should be administered with caution in patients with neurological manifestations of Behçet's syndrome. Their neurological status must be carefully monitored. Experience with Ciclosporin Viatris in children with endogenous uveitis is limited. Additional precautions in nephrotic syndrome In patients with abnormal renal function before starting therapy, the initial dose should be 2.5 mg/kg/day. These patients must be very closely monitored. In some patients, it may be difficult to distinguish renal dysfunction induced by Ciclosporin Viatris from changes related to the underlying nephrotic syndrome. This explains why structural changes in the kidney have, in rare cases, been observed during Ciclosporin Viatris therapy without an accompanying rise in serum creatinine. In patients with steroid-dependent minimal change nephropathy receiving Ciclosporin Viatris for more than one year, a renal biopsy should be considered. Cases of malignancies (including Hodgkin's lymphoma) have been reported in isolation in patients with nephrotic syndrome treated with immunosuppressants (including ciclosporin). Additional precautions in rheumatoid arthritis After 6 months of treatment, renal function should be monitored every 4–8 weeks, depending on disease stability, comorbidities, and concomitant medications. More frequent monitoring is required if the dose of Ciclosporin Viatris is increased, or when concomitant non-steroidal anti-inflammatory drugs are introduced or their dose is increased. Discontinuation of treatment may also be necessary if hypertension developing during Ciclosporin Viatris therapy cannot be controlled with appropriate antihypertensive treatment. As with other long-term immunosuppressive therapies, the increased risk of lymphoproliferative disorders should be borne in mind. Particular caution is advised when combining Ciclosporin Viatris with methotrexate, owing to the synergistic nephrotoxic potential. Additional precautions in psoriasis Discontinuation of treatment is recommended if hypertension developing during Ciclosporin Viatris therapy cannot be controlled with appropriate treatment. Elderly patients should be treated only for disabling psoriasis, and renal function should be monitored with particular care. Experience with Ciclosporin Viatris in children with psoriasis is limited. As with conventional immunosuppressive therapy, malignancies (especially of the skin) have been reported in psoriasis patients treated with ciclosporin. Skin lesions atypical for psoriasis but suspected of being malignant or premalignant should undergo biopsy before Ciclosporin Viatris therapy is initiated. Patients with malignant or premalignant skin changes may be treated with Ciclosporin Viatris only after appropriate management of these lesions, and only when no other effective treatment option for psoriasis is available. A few psoriasis patients treated with Ciclosporin Viatris have developed lymphoproliferative disorders, which responded promptly to discontinuation of therapy. Patients receiving Ciclosporin Viatris must not undergo concomitant UVB irradiation or PUVA photochemotherapy. Additional precautions in atopic dermatitis Discontinuation of treatment is recommended if hypertension developing during Ciclosporin Viatris therapy cannot be controlled with appropriate antihypertensive treatment. Experience with Ciclosporin Viatris in children with atopic dermatitis is limited. Elderly patients should be treated only for disabling atopic dermatitis, with particularly careful monitoring of renal function. Exacerbations of atopic dermatitis are often accompanied by benign lymphadenopathy, which always resolves spontaneously or with overall improvement of the disease. Lymphadenopathy observed during ciclosporin therapy should be monitored regularly. Lymphadenopathy that persists despite resolution of disease activity should be biopsied as a precaution to exclude lymphoma. Active herpes simplex infection should be allowed to resolve before initiating Ciclosporin Viatris therapy. If it occurs during treatment and is not severe, it does not necessarily require discontinuation of therapy. Skin infection with Staphylococcus aureus is not an absolute contraindication to Ciclosporin Viatris therapy but should be controlled with an appropriate antibiotic. Oral erythromycin is not suitable, as it may increase ciclosporin blood concentrations (see section 4.5). If no alternative is available, careful monitoring of ciclosporin blood levels, renal function, and adverse reactions is recommended. Patients receiving Ciclosporin Viatris must not undergo concomitant UVB irradiation or PUVA photochemotherapy. Paediatric use in non-transplant indications Adequate experience with Ciclosporin Viatris is not available except for the treatment of nephrotic syndrome. Use in children and adolescents under 16 years of age in non-transplant indications other than nephrotic syndrome cannot be recommended. Excipients with known effect Ethanol Ciclosporin Viatris 25 mg contains 25 mg of alcohol (ethanol) per capsule. The amount of alcohol in one capsule is equivalent to less than 1 mL of beer or 1 mL of wine. Such a small amount of alcohol in this medicinal product has no perceptible effects. Ciclosporin Viatris 50 mg contains 50 mg of alcohol (ethanol) per capsule. The amount of alcohol in one capsule is equivalent to less than 2 mL of beer or 1 mL of wine. Such a small amount of alcohol in this medicinal product has no perceptible effects. Ciclosporin Viatris 100 mg contains 100 mg of alcohol (ethanol) per capsule. The amount of alcohol in one capsule is equivalent to less than 3 mL of beer or 1 mL of wine. Such a small amount of alcohol in this medicinal product has no perceptible effects. Propylene glycol Ciclosporin Viatris 25 mg contains 26 mg of propylene glycol per capsule. Ciclosporin Viatris 50 mg contains 43 mg of propylene glycol per capsule. Ciclosporin Viatris 100 mg contains 70 mg of propylene glycol per capsule. Macrogolglycerol hydroxystearate Ciclosporin Viatris contains macrogolglycerol hydroxystearate, which may cause stomach upset and diarrhoea.