PHOTOBARR Powder for solution for injection Ref.[9109] Active ingredients: Porfimer

Photodynamic therapy with PhotoBarr should be performed only by, or under the supervision of, a physician with experience in endoscopic laser procedures. The medicinal product should only be administered when material and personnel experienced in evaluating and treating anaphylaxis are immediately available.

Posology

The recommended dose of PhotoBarr is 2 mg/kg body weight.

Reconstituted PhotoBarr solution (ml) = Patient’s weight (kg) x 2 mg/kg / 2.5 mg/ml = 0.8 x patient’s weight

After reconstitution, PhotoBarr is a dark red to reddish brown, opaque solution.

Only a solution without particles should be used and without visible signs of deterioration.

Photodynamic therapy with PhotoBarr is a two-stage process requiring administration of both medicinal product and light. One course of PDT consists of one injection plus one or two light applications.

In case of persistence of HGD, further treatment courses (up to a maximum of three courses) may be given (separated by a minimum of 90 days) to increase the response rate. This has to be balanced against the increased rate of stricture formation (see section 4.8 and section 5.1).

Progression to cancer was related to the number of PDT courses administered. Patients who received one course of PDT had a greater risk of progression to cancer than patients who received two or three courses of PDT (50% vs. 39% and 11% respectively).

Method of administration

For instructions on reconstitution prior to administration, see section 6.6.

Physicians should be trained in the use of PDT. The first stage of PDT is the slow intravenous injection of PhotoBarr. The second stage of therapy is illumination with laser light 40-50 hours following injection with PhotoBarr. Patients may receive a second laser light application 96-120 hours after administration.

PhotoBarr should be administered as a single slow intravenous injection over 3 to 5 minutes. If accidentally injected paravenously there may be damage to paravenous tissue. Therefore, care should be taken to prevent extravasation at the injection site. If extravasation does occur, the area should be protected from light for a minimum of 90 days. There is no known benefit from injecting the extravasation site with another substance.

Approximately 40-50 hours after PhotoBarr administration, light should be delivered by a fibre optic diffuser passed through the central channel of a centring balloon. The choice of fibre optic/balloon diffuser combination will depend on the length of oesophagus to be treated (Table 1).

Table 1. Fibre optic diffuser/balloon combination^a:

^a Whenever possible, the BO segment selected for treatment should include normal tissue margins of a few millimetres at the proximal and distal ends.

Light doses

Photoactivation is controlled by the total light dose delivered. The objective is to expose and treat all areas of HGD and the entire length of BO. The light dose administered will be 130 Joules/cm (J/cm) of diffuser length using a centring balloon. Based on preclinical studies, acceptable light intensity for the balloon/diffuser combination ranges from 175-270 mW/cm of diffuser.

To calculate the light dose, the following specific light dosimetry equation applies for all fibre optic diffusers:

The light dose (J/cm) = power output from diffuser (W) x treatment time (sec) / Diffuser length (cm)

Table 2 provides the settings that would be used to deliver the dose within the shortest time (light intensity of 270 mW/cm). A second option (light intensity of 200 mW/cm) has also been included where necessary to accommodate lasers with a total capacity that does not exceed 2.5 W.

Table 2. Fibre optic power outputs and treatment times required to deliver 130 J/cm of diffuser length using the centring balloon:

^a As measured by immersing the diffuser into the cuvette in the power meter and slowly increasing the laser power. Note: No more than 1.5 times the required diffuser power output should be needed from the laser. If more than this is required, the system should be checked.

Short fibre optic diffusers (<2.5 cm) are to be used to pretreat nodules with 50 J/cm diffuser length prior to regular balloon treatment in the first laser light session or for the retreatment of “skip” areas after the first light session. For this treatment, the fibre optic diffuser is used without a balloon, and a light intensity of 400 mW/cm should be used. Table 3 lists appropriate fibre optic power outputs and treatment times using a light intensity of 400 mW/cm.

Table 3. Short fibre optic diffusers to be used without a centering balloon to deliver 50 J/cm of diffuser length at a light intensity of 400 mW/cm:

^a As measured by immersing the diffuser into the cuvette in the power meter and slowly increasing the laser power. Note: No more than 1.5 times the required diffuser power output should be needed from the laser. If more than this is required, the system should be checked.

First light application

A maximum of 7 cm of Barrett’s mucosa is treated at the first light session using an appropriate size of centering balloon and fibre optic diffuser (Table 1). Whenever possible, the segment selected for the first light application should include all the areas of HGD. Also, whenever possible, the BO segment selected for the first light applications should include normal tissue margin of a few millimetre at the proximal and distal ends. Nodules are to be pre-treated at a light doses of 50 J/cm of diffuser length with a short (<2.5 cm) fibre optic diffuser placed directly against the nodules followed by standard balloon application as described above.

Repeat light application

A second laser light application may be given to a previously treated segment that shows a ‘skip’ area, (i.e., an area that does not show sufficient mucosal response) using a short <2.5 cm fibre optic diffuser at the light dose of 50 J/cm of diffuser length (see Table 3). The treatment regimen is summarized in Table 4. Patients with BO >7 cm, should have the remaining untreated length of Barrett’s epithelium treated with a second PDT course at least 90 days later.

Table 4. High-grade dysplasia in Barrett’s oesophagus of ≤7 cm:

^a Discrete nodules will receive an initial light application of 50 J/cm (using short diffuser) before the balloon light application.

Patients may receive a second course of PDT a minimum of 90 days after the initial therapy; up to three courses of PDT (each injection separated by a minimum of 90 days) should be given to a previously treated segment which still shows HGD or to a new segment if the initial Barrett’s segment was >7 cm in length. Both residual and additional segments may be treated in the same light session(s) if the total length of the segments treated with the balloon/diffuser combination is not greater than 7 cm. In the case of a previously treated oesophageal segment, if it has not sufficiently healed and/or histological assessment of biopsies is not clear, the subsequent course of PDT may be delayed for an additional 1-2 months.

Special care to ensure accurate PhotoBarr dosing and/or light dose is crucial, since miscalculation of either medicinal product or light dose may lead to a less effective treatment or cause detrimental effect to the patient. Photodynamic therapy with PhotoBarr should be applied by physicians trained in endoscopic use of PDT and only in those facilities properly equipped for the procedure.

Special populations

Paediatric patients

PhotoBarr is not recommended for use in children below age 18 years due to a lack of data on safety and efficacy.

Elderly patients (≥65 years old)

Dose modification based upon age is not required.

Renal impairment

The influence of renal impairment on exposure to porfimer sodium has not been evaluated (see section 4.3).

Hepatic impairment

The influence of hepatic impairment on exposure to porfimer sodium has not been evaluated (see section 4.3 and 4.4).

PhotoBarr

There is no information on overdose of PhotoBarr. The recommended 2 mg/kg dose, instead of the recommended single administration, was given twice two days apart (10 patients) and three times within two weeks (1 patient), without any notable adverse reactions being reported. The effects of an overdose on the duration of photosensitivity are unknown. Laser treatment should not be given if an overdose of PhotoBarr is administered. In the event of an overdose, patients should protect their eyes and skin from direct sunlight or bright indoor lights for 90 days. At this time, patients should test for residual photosensitivity (see section 4.4). Porfimer sodium is not dialyzable.

Laser light

Light doses of two to three times the recommended dose have been administered to a few patients with superficial endobronchial tumours. One patient experienced life-threatening dyspnoea and the others had no notable complications. Increased symptoms and damage to normal tissue might be expected following an overdose of light.

Shelf life

Powder: 3 years.

After reconstitution: use immediately (within 3 hours).

After it has been reconstituted, PhotoBarrshould be used immediately (within 3 hours) and protected from light. Chemical and physical in-use stability has been demonstrated for 3 hours at 23°C. From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage time and conditions prior to use are the responsibility of the user.

Keep out of the reach and sight of children.

Do not use after the expiry date stated on the carton and vial after EXP.

Do not store above 25°C.

Keep the vial in the outer carton in order to protect from light.

For storage conditions of the reconstituted medicinal product, see section 6.3.

15 mg powder in a vial (glass type I, 7 ml capacity) with a grey butyl stopper.

Pack size: 1 vial.

Instructions for reconstitution

PhotoBarr 15 mg vial should be reconstituted with 6.6 ml of 5% glucose solution for injection resulting in a final porfimer sodium concentration of 2.5 mg/ml in the solution for injection.

Do not use other diluents. Do not mix PhotoBarr with other medicinal products in the same solution.

Sufficient vials of PhotoBarr should be reconstituted to provide the patient with a dose of 2 mg/kg. For most patients (up to 75 kg) two vials of PhotoBarr 75 mg will suffice. A PhotoBarr 15 mg vial will be needed for every additional 7.5 kg body weight.

Spills and disposal

Spills of PhotoBarr should be wiped up with a damp cloth. Skin and eye contact should be avoided due to the potential for photosensitivity reactions upon exposure to light; use of rubber gloves and eye protection is recommended. PhotoBarr is for single use only and any unused solution should be discarded. Any unused product or waste material should be disposed of in accordance with local requirements.

Accidental exposure

PhotoBarr is neither a primary ocular irritant nor a primary dermal irritant. However, because of its potential to induce photosensitivity, PhotoBarr might be an eye and/or skin irritant in the presence of bright light. It is important to avoid contact with the eyes and skin during preparation and/or administration. As with therapeutic overdose, any accidentally overexposed person must be protected from bright light.'