METHOXSALEN MACOPHARMA

1 ml of Methoxsalen Paediatric population The safety and efficacy of Methoxsalen in children and adolescents (under 18 years of age) have not been established for this indication. Hepatic or renal impairment Methoxsalen has not been clinically tested in patients with renal or hepatic impairment.

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. . 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, Methoxsalen 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 Methoxsalen 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. 6

The most commonly reported side effects with extracorporeal use of methoxsalen were phototoxic reactions, nausea, vomiting, congestive heart failure and hypotension. During the course of therapy, the severity and frequency of undesirable effects may decline and generally do not require discontinuation of the therapy.

g. g. 4) General disorders and administration site conditions Fever (2 to 12 hours after therapy low-grade fever may occur) Injury, poisoning and procedural complications Venous access complication after repeated venipuncture Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App store.

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. Methoxsalen 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. 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 Methoxsalen) 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. 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 ageing’ of the skin.

Extracorporeal use of METHOXSALEN MACOPHARMA 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 Methoxsalen 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 renal 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.

08 mg ethanol 96%/ml). 984 mg of alcohol (ethanol 96%) in each ampoule. The amount in one ampoule (5 ml) of this medicine is equivalent to less than 0,25 ml beer or 0,1 ml wine 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’.

This medicinal product contains 35,4 mg sodium per two ampoules (10 ml), equivalent to 1,77 % of the WHO recommended maximum daily intake of 2 g sodium for an adult.

1. g. g. 6) - Aphakia - Pregnancy and lactation. g. ) - Previous splenectomy - Coagulation disorder - Leucocyte count above 25,000/mm³.