Special Warning : אזהרת שימוש

4.4    Special warnings and precautions for use

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.
Because of the possibility of irreversible eye damage occurring as a side effect, the patient should be fully informed about the risks of this type of therapy.

Oxsoralen 20 mcg/ml should only be used ex vivo and is to be added directly to the separated leucocytes. If there is a possibility that the blood has been damaged during the procedure, it should only be reinfused into the patient if haemolysis has not occurred.

Hypotension
Transient hypotension may occur in some patients during therapy. In most patients it stays asymptomatic and disappears after reinfusion of the blood. Occasionally, normal saline solution must be infused during photopheresis to stabilise blood pressure. Patients regularly taking anti-hypertensives should wait with the intake until the end of the photopheresis procedure (see section 4.8).

Hypertriglyceridemia
In patients with increased blood triglyceride levels the efficacy of the procedure might be limited because the photopheresis instruments cannot separate white blood cells from fat- rich blood. Therefore patients about to get a photopheresis treatment should fast before the therapy – their triglyceride level should be lower than 300 mg/dl at the start of treatment.

Formation of cataracts
Exposure to large doses of UVA light causes cataracts in animals, an effect enhanced by the administration of oral methoxsalen. As the concentration of methoxsalen in the human lens is proportional to the serum level, the concentration will be substantially lower following ex vivo methoxsalen treatment (with Oxsoralen 20 mcg/ml) compared to the concentration seen after oral administration. Nevertheless, if the lens is exposed to UVA light during the time methoxsalen is present in the lens, photochemical action may lead to irreversible binding of methoxsalen to protein and DNA components of the lens. For this reason, the patients’ eyes should be protected from UVA light by wrap-around UVA-opaque sunglasses during the treatment cycle and during the following 24 hours (see section 4.8).

Adverse effects on the skin
Following oral administration of psoralen (where serum concentrations may exceed 200 ng/ml), exposure to sunlight or UV radiation (even through window glass) may result in serious burns and, over the long term, ‘premature aging’ of the skin.
Extracorporeal use of Oxsoralen 20 mcg/ml solution is associated with a much lower systemic exposure to methoxsalen (more than 80 % of the blood samples taken 30 minutes after reinfusion of the photoactivated buffy coat exhibited methoxsalen levels < 10 ng/ml and the average methoxsalen concentration in plasma was about 25 ng/ml). However, the amount of phototoxicity of these levels has not been investigated systematically. Therefore, as a precaution, patients should avoid exposure to sunlight during the 24 hours following photopheresis treatment.

Hepatic impairment
As hepatic biotransformation is necessary for urinary excretion, it is possible that hepatic impairment may result in an extended half-life of methoxsalen. This may result in prolonged photosensitivity. In patients with hepatic diseases precautions against exposure to sunlight should therefore be prolonged where required.
No specific information is available on the use of photopheresis with Oxsoralen 20 mcg/ml in patients with hepatic impairment.

Renal impairment
Although several renal transplant recipients with poor renal function have been treated with photopheresis, little additional information is available on the use of methoxsalen in renally- impaired patients. No extra precautions, such as dose reduction or prolongation of protection from UV light, were taken in the few renal transplant recipients who have undergone photopheresis treatment and the procedures were well tolerated and effective.

Information about certain excipients
This medicinal product contains small amounts of ethanol (alcohol): At an assumed treatment volume of 240 ml the patient is exposed to 4.1 ml of Oxsoralen 20 mcg/ml and therefore to 8.528 mg alcohol (2.08 mg alcohol/ml).
With extracorporeal administration systemic exposure is expected to be low, and clinical effects have not been observed yet. However, the prescribing physician should bear in mind possible interactions with other medicinal products. Special caution is advised in hepatic disease, alcoholism, epilepsy, brain injury or brain disease.

This medicinal product contains less than 1 mmol sodium (23 mg) per millilitre, that is to say essentially ‘sodium-free’.

Effects on Driving

4.7   Effects on ability to drive and use machines

As a result of the special mode of administration (extracorporeal use), transient cardiovascular instability may occur. In addition, patients should wear sunglasses following photopheresis treatment (see section 4.4). Therefore, patients should not drive or use machines immediately following photopheresis treatment.