Posology : מינונים

4.2   Posology and method of administration

Posology
Adults
During each photopheresis treatment with methoxsalen, the dosage is calculated according to the treatment volume, using the formula below:

Treatment volume x 0.017 ml of Oxsoralen 20 mcg/ml for each treatment 
For example: Treatment volume = 240 ml x 0.017 = 4.1 ml of Oxsoralen 20 mcg/ml 
Paediatric population (under 18 years of age)
The safety and efficacy of Oxsoralen 20 mcg/ml in children and adolescents under the age of 18 years have not been established for this indication.

Hepatic or renal impairment
Oxsoralen 20 mcg/ml solution has not been clinically tested in patients with renal or hepatic impairment.
Liver enzymes should be monitored regularly before and during therapy (see section 4.4).

Method of administration
Extracorporeal use.

Note:
Extracorporeal photochemotherapy is to be carried out only by persons with special training and in institutions disposing of the suitable equipment for this treatment.
Psoralen and UV irradiation therapy should take place under constant supervision by a physician with the appropriate training.
The working instructions for the procedure (according to the company manufacturing the equipment in use and/or to recent guidelines) must be followed strictly.

The content of the ampoule must not be injected directly into the patient as there are no studies with direct injection of Oxsoralen 20 mcg/ml in humans.

In the photopheresis process the components of the whole-blood are separated. The erythrocytes and excess plasma are returned to the patient immediately, while the buffy coat (leucocyte-enriched blood) and some plasma are collected, Oxsoralen 20 mcg/ml is added, radiated with UV light and then reinfused into the patient.

The following basic rules should be observed:
-   The haematocrit of the separated blood fraction should not exceed 5%, in order not to block exposure to the UVA radiation and thus lower the efficacy of treatment.
-   Before radiation with UVA light (in the radiation bag) heparin, isotonic saline solution and the prescribed amount of Oxsoralen 20 mcg/ml are added to the leucocytes.
-   The quantities collected for therapy may vary (from 120 to 540 ml) depending on body weight, blood volume and therapy method used (on-line or off-line method).
-   During photoactivation the leucocyte-enriched blood is radiated with UVA light (1 to     2 J/cm2).
-   At the end of the photoactivation cycle, the photoactivated cells are reinfused via intravenous drip. The recommended duration of reinfusion is 15 to 20 minutes.
-   The buffy coat collection cycle is repeated up to six times, and the complete photopheresis procedure lasts approximately 3 to 4 hours.
-   During therapy blood pressure, heart rate and body temperature should be monitored.

Duration of treatment
During the first three months it is recommended to carry out treatment on two successive days every 2 to 4 weeks. After that, two-day treatment cycles every 3 to 4 weeks are recommended.
It has been shown that higher treatment frequencies do not lead to better treatment results.
As soon as maximum treatment response is achieved, intervals should be gradually extended to 4 to 8 weeks, and then continued as a maintenance therapy every 8 weeks.

The duration of photopheresis therapy should be at least 6 months. In patients who respond well to treatment or whose disease can be stabilised offering them good quality of life, photopheresis may be carried out for 2 years or more.

The above recommendations are a general guideline. Therapy cycles may be adapted individually to the specific clinical picture and the patient’s response.