Cipol-N Dosage/Direction for Use

Recommended Dose: The daily doses of Cipol-N should always be given in two divided doses.
Because of considerable inter- and intraindividual variations in absorption and elimination and the possibility of pharmacokinetic drug interactions, doses should be titrated individually according to clinical response and tolerability.
In transplant patients, routine monitoring of cyclosporine trough blood levels is required to avoid adverse effects due to high levels and to prevent organ rejection due to low levels.
In patients treated for non-transplant indications, monitoring of cyclosporine blood levels is of limited value except in the case of unexpected treatment failure or relapse, where it may be appropriate to establish the possibility of very low levels caused by non-compliance, impaired gastrointestinal absorption, or pharmacokinetic interactions.
General target population: Transplantation indications: Solid organ transplantation: Treatment with this drug should be initiated 12 hours before surgery at a dose of 10 to 15 mg/kg given in two divided doses. This dose should be maintained as the daily dose for 1 to 2 weeks postoperatively before being gradually reduced in accordance with blood levels until a maintenance dose of about 2 to 6 mg/kg given in two divided doses is reached. When this drug is given with other immunosuppressants (e.g. with corticosteroids or as part of a triple or quadruple drug therapy) lower doses (e.g. 3 to 6 mg/kg given in two divided doses for the initial treatment) may be used.
Bone marrow transplantation: The initial dose should be given on the day before transplantation. If this drug is used to initiate therapy, the recommended daily dose is 12.5 to 15 mg/kg given in two divided doses, starting on the day before transplantation. Maintenance treatment at daily doses of about 12.5 mg/kg should be continued for at least 3 months (and preferably for 6 months) before the dose is gradually decreased zero by 1 year after transplantation. Higher doses of this drug, or the use of IV therapy, may be necessary in the presence of gastrointestinal disturbances which might decrease drug absorption. In some patients, GVHD occurs after discontinuation of this drug treatment, but usually responds favourably to reintroduction of therapy. Low doses of this drug should be used to treat mild, chronic GVHD.
Non-transplantation indications: When using Cipol-N in any of the established non-transplant indications, the following general rules should be adhered to: Before initiation of treatment a reliable baseline level of serum creatinine should be established by at least two measurements, and renal function must be assessed regularly throughout therapy to allow dosage adjustment.
The only accepted route of administration is by mouth (the concentrate for intravenous infusion must not be used), and the daily dose should be given in two divided doses.
Except in patients with sight-threatening endogenous uveitis and in children with nephrotic syndrome, the total daily dose must never exceed 5 mg/kg.
For maintenance treatment the lowest effective and well tolerated dosage should be determined individually.
In patients in whom within a given time no adequate response is achieved or the effective dose is not compatible with the established safety guidelines, treatment with this drug should be discontinued.
Endogenous uveitis: For inducing remission, initially 5 mg/kg per day orally given in two divided doses are recommended until remission of active uveal inflammation and improvement in visual acuity are achieved. In refractory cases, the dose can be increased to 7 mg/kg per day for a limited period.
To achieve initial remission, or to counteract inflammatory ocular attacks, systemic corticosteroid treatment with daily doses of 0.2 to 0.6 mg/kg prednisolone or an equivalent may be added if this drug alone does not control the situation sufficiently.
For maintenance treatment, the dose should be slowly reduced to the lowest effective level, which, during the remission phases, should not exceed 5 mg/kg per day.
Nephrotic syndrome: For inducing remission, the recommended daily dose, given in 2 divided oral doses, is 5 mg/kg for adults and 6 mg/kg for children if, except for proteinuria, renal function is normal. In patients with impaired renal function, the initial dose should not exceed 2.5 mg/kg per day. The combination of Cipol-N with low doses of oral corticosteroids is recommended if the effect of Cipol-N alone is not satisfactory, especially in steroid-resistant patients. If no improvement has been observed after 3 months' treatment, Cipol-N therapy should be discontinued. The doses need to be adjusted individually according to efficacy (proteinuria) and safety (primarily serum creatinine), but should not exceed 5 mg/kg per day in adults and 6 mg/kg per day in children.
For maintenance treatment, the dose should be slowly reduced to the lowest effective level.
Rheumatoid arthritis: For the first 6 weeks of treatment the recommended dose is 3 mg/kg per day orally given in two divided doses. If the effect is insufficient, the daily dose may then be increased gradually as tolerability permits, but should not exceed 5 mg/kg. To achieve full effectiveness, up to 12 weeks of this drug may be required.
For maintenance treatment the dose has to be titrated individually to the lowest effective level according to tolerability. This drug can be given in combination with low-dose corticosteroids and/or non-steroidal anti-inflammatory drugs. This drug can also be combined with low-dose weekly methotrexate in patients who have insufficient response to methotrexate alone, by using initially 2.5 mg/kg in two divided doses per day, with the option to increase the dose as tolerability permits.
Psoriasis: Due to the variability of this condition, treatment must be individualized.
For inducing remission, the recommended initial dose is 2.5 mg/kg per day orally given in two divided doses. If there is no improvement after 1 month, the daily dose may be gradually increased, but should not exceed 5 mg/kg. Treatment should be discontinued in patients in whom sufficient response of psoriatic lesions cannot be achieved within 6 weeks on 5 mg/kg per day, or in whom the effective dose is not compatible with the established safety guidelines.
Initial doses of 5 mg/kg per day are justified in patients whose condition requires rapid improvement. Once satisfactory response is achieved, this drug may be discontinued and subsequent relapse managed with re-introduction of this drug at the previous effective dose. In some patients, continuous maintenance therapy may be necessary.
For maintenance treatment, doses have to be titrated individually to the lowest effective level, and should not exceed 5 mg/kg per day.
Atopic dermatitis: Due to the variablility of this condition, treatment must be individualized. The recommended dose range is 2.5 to 5 mg/kg per day given in 2 divided oral doses. If a starting dose of 2.5 mg/kg per day does not achieve a satisfactory response within two weeks of therapy, the daily dose may be rapidly increased to a maximum of 5 mg/kg. In very severe cases, rapid and adequate control of the disease is more likely to occur with a starting dose of 5 mg/kg per day. Once satisfactory response is achieved, the dose should be reduced gradually and, if possible, Cipol-N should be discontinued. Subsequent relapse may be managed with a further course of Cipol-N.
Although a course of 8 weeks' therapy may be sufficient to achieve clearing, up to 1 year's therapy has been shown to be effective and well tolerated, provided the monitoring guidelines are followed.
Special population: Renal impairment all indications: Cyclosporine undergoes minimal renal elimination and its pharmacokinetics is not affected by renal impairment. However, due to its nephrotoxic potential, a careful monitoring of the renal function is recommended.
Non-transplant indications: Patients with impaired renal function, except nephrotic syndrome patients, should not receive cyclosporine. In nephrotic syndrome patients with impaired renal function, the initial dose should not exceed 2.5 mg/kg per day.
Hepatic impairment: Dose reduction may be necessary in patients with severe liver impairment to maintain blood levels within the recommended target range.
Pediatrics: Experience with cyclosporine in children is still limited. Clinical studies have included children from 1 year of age using standard cyclosporine dosage with no particular problems. In several studies, pediatric patients required and tolerated higher doses of cyclosporine per kg body weight than those used in adults.
This drug use in children for non-transplant indications other than nephrotic syndrome cannot be recommended.
Geriatrics (65 years old and above): Experience with cyclosporine in the elderly is limited, but no particular problems have been reported following the use of the drug at the recommended dose.
Mode of Administration: This drug should always be given in two divided doses. Capsules should be swallowed whole.