Posology : מינונים

4.2   Posology and method of administration

Posology

In transplant patients routine monitoring of ciclosporin blood levels is required to avoid adverse effects due to high levels and to prevent organ rejection due to low levels (see section 4.4 Special warnings and precautions for use).

Transplantation
Solid organ transplantation
Treatment with Sandimmun concentrate for infusion should be initiated within 12 hours before surgery at a dose of 3 to 5 mg/kg. This dose should be maintained as the daily dose for 1 to 2 weeks post- operatively before being gradually reduced in accordance with blood levels until a maintenance dose of about 0.7 to 2 mg/kg given in 2 divided doses is reached.
When Sandimmun concentrate for infusion is given with other immunosuppressants (e.g., with corticosteroids or as part of a triple or quadruple drug therapy), lower doses (e.g., 1 to 2 mg/kg given in 2 divided doses for the initial treatment) may be used.
The recommended dose of Sandimmun concentrate for infusion is approximately one third of the appropriate oral dose. It is recommended that patients be put on oral therapy as soon as possible.



SAN CON API Oct23 V5   ;   Ref: UK PI 15Sep23
Bone marrow transplantation
The initial dose should be given on the day before transplantation. For the initiation of Sandimmun therapy the preferred route of administration is by intravenous infusion. The recommended i.v. dose is 3 to 5 mg/kg per day. Infusion is continued at this dose level during the immediate post-transplant period of up to 2 weeks, before a change is made to oral maintenance therapy.
Maintenance treatment should be continued for at least 3 months (and preferably for 6 months) before the dose is gradually decreased to zero by 1 year after transplantation. Continuation of ciclosporin treatment via i.v. therapy may be necessary in the presence of oral ciclosporin induced gastrointestinal disturbances which might decrease drug absorption.
In some patients, GVHD occurs after discontinuation of ciclosporin treatment, but usually responds favorably to re-introduction of therapy. In such cases, an initial oral loading dose of 10 to 12.5 mg/kg should be given, followed by daily oral administration of the maintenance dose previously found to be satisfactory. Low doses of ciclosporin should be used to treat mild, chronic GVHD.

Special populations

Patients with renal impairment
Ciclosporin undergoes minimal renal elimination and its pharmacokinetics is not affected by renal impairment (see section 5.2). However, due to its nephrotoxic potential (see section 4.8), a careful monitoring of renal function is recommended (see section 4.4).

Patients with hepatic impairment
Ciclosporin is extensively metabolised by the liver. The terminal half-life varied between 6.3 hours in healthy volunteers to 20.4 hours in severe liver patients (see section 5.2). Dose reduction may be necessary in patients with severe liver impairment to maintain blood levels within the recommended target range (see sections 4.4 and 5.2).

Paediatric population
Experience with ciclosporin in children is still limited. However, children from 1 year of age have received Sandimmun in standard dosage with no particular problems. In several studies, pediatric patients required and tolerated higher doses of ciclosporin per kg body weight than those used in adults.

Elderly population (age 65 years and above)
Experience with ciclosporin in the elderly is limited, but no particular problems have been reported following the use of the drug at the recommended dose.

In rheumatoid arthritis clinical trials with oral ciclosporin, 17.5% of patients were aged 65 or older.
These patients were more likely to develop systolic hypertension on therapy, and more likely to show serum creatinine rises ≥ 50% above the baseline after 3-4 months of therapy.

Clinical studies of Neoral in transplant and psoriasis patients did not include a sufficient number of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experiences have not identified differences in response between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Method of administration
Intravenous administration.

Because of the risk of anaphylaxis (see section 4.4) the use of Sandimmun concentrate for infusion should be reserved for organ transplant patients who are unable to take the medicinal product orally (e.g., shortly after surgery), or in whom absorption of the oral forms might be impaired during episodes of gastrointestinal disorders. In such cases, it is recommended to switch to oral administration as soon as 

feasible. Another well-established use of the concentrate for infusion is the initial treatment of patients undergoing bone marrow transplantation.

Precautions to be taken before handling or administering the medicinal product For instructions on dilution of the medicinal product before administration, see section 6.6.