FOSCAN Solution for injection Ref.[9097] Active ingredients: Temoporfin

All patients who receive Foscan will become temporarily photosensitive. Precautions must be taken to avoid exposure of skin and eyes to direct sunlight or bright indoor light during the first 15 days after injection. Skin photosensitivity reactions are caused by visible light; therefore ultraviolet sunscreens provide no protection. It is important that patients are re-introduced to normal light gradually (see the light protection guidelines for patients at the end of this section).

For 6 months following Foscan treatment prolonged direct sunlight exposure of the injection site arm shall be avoided. As a precautionary measure, if prolonged outdoor activity is planned, the injection arm should be protected by wearing a long sleeved, coloured shirt.

Clinicians should be aware that most of the toxicities associated with photodynamic therapy are local effects seen as consequence of photoactivation. Photoactivation induces local tissue damage resulting in acute inflammatory response. This response is commonly associated with oedema and pain, followed by necrosis. The photodynamic effect may also lead to damage of the surrounding tissue that may cause fistula, perforation, or vascular rupture as well as infection and subsequent sepsis. It is therefore important that during photoactivation by laser illumination care should be taken to protect normal tissue surrounding the tumour from photoactivation by proper illumination and shielding techniques. Proactively managing the local effects and diminishing photoactivation in non-tumour areas is important to manage the risks.

Special care must be taken to prevent extravasation at the injection site. If extravasation occurs, protect the area from light for at least 3 months. There is no known benefit from injecting the extravasation site with another substance.

Adverse reactions, including cholangitis, cholecystitis, liver abscess and oesophageal perforation have been reported after unapproved use in the treatment of malignant biliary strictures and mesothelioma. There is a risk of damage of the surrounding area following photoactivation.

Unplanned or emergency surgical procedures where Foscan has been administered within the previous 30 days must be undertaken only if absolutely necessary and the potential benefits outweigh the risk to the patient. All precautions must be taken to avoid direct illumination of the patient with surgical lamps during these procedures. The use of headlamps is recommended instead.

Some pulse oximeters may produce light of a wavelength close to that used for the photoactivation of Foscan. Oximeters must be repositioned at least every 10-15 minutes to avoid the risk of local skin burns.

Pain, other than injection site pain, listed in section 4.8 may require the use of NSAIDs or opiate analgesics for a short time following treatment. Pain occurs the day after illumination and usually lasts 2 to 4 weeks.

Illumination of airways may lead to local inflammation and oedema. The resulting complications (i.e. dyspnoea or even airway obstruction leading to, for instance, intubation or tracheotomy) should be anticipated. Prophylactic treatment with corticosteroids should be considered.

Clinicians must counsel patients to observe the following precautions that are provided in the Package Leaflet.

This medicinal product contains 48 vol % ethanol (alcohol), i.e up to 4.2 g per dose, equivalent to 84 ml of beer, 35 ml wine per dose. Harmful for those suffering from alcoholism. To be taken into account in pregnant or breast-feeding women, children and high-risk groups such as patients with liver disease or epilepsy.The amount of alcohol in this medicinal product may alter the effects of other medicines.The amount of alcohol in this medicinal product may impair the ability to drive or use machines.

There is potential for exacerbation of skin photosensitivity if temoporfin is used with other photosensitising active substances. Such a reaction has been reported with topical 5-fluorouracil.

No other interactions have been observed. An in vitro study with human liver tissue has shown no potential for drug interaction through inhibition of cytochrome P-450 enzymes by temoporfin.

Pregnancy

There are no data from the use of temoporfin in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). Foscan should not be used during pregnancy unless the clinical condition of the woman requires treatment with temoporfin.

Women of childbearing potential have to use effective contraception during and up 3 months after treatment.

Breast-feeding

It is unknown whether temoporfin/metabolites are excreted in human milk. A risk to the newborns/infants cannot be excluded. Breast-feeding should be discontinued for at least one month following injection of Foscan.

Fertility

The effects of Foscan on fertility in humans have not been studied.

The amount of alcohol in this medicinal product may impair the ability to drive or use machines.

On the basis of the pharmacodynamic profile, temoporfin is presumed to be safe or unlikely to produce an effect. To avoid photosensitivity problems, it is advised not to drive during the first 15 days after injection, and to use machines only if it is practical to do so under subdued lighting conditions according to the recommended lighting precautions (see section 4.4). Driving and use of machines may resume under normal lighting or daylight conditions once photosensitivity has been shown to have subsided.

Summary of the safety profile

All patients who receive Foscan will become temporarily photosensitive and must be instructed to observe precautions to avoid sunlight and bright indoor light. Regarding the tabulated adverse reactions gastrointestinal disorders, adverse skin reactions and general disorders and administration site conditions are the most frequently observed adverse reactions.

Most of the toxicities associated with photodynamic therapy are local effects seen in the region of illumination and occasionally in surrounding tissues. The local adverse reactions are characteristic of an acute tissue inflammatory response induced by photoactivation and commonly include oedema and pain followed by necrosis (see section 4.4).

Photosensitivity reactions may occur, however, complying with the light protection guidelines (see above section 4.4) and avoiding unnecessary indoor light during illumination reduces this risk.

The low number of treated patients did not allow identification of adverse reactions, which may be categorised as uncommon and rare. Injection site pain is transient and can be reduced by slowing the injection rate. For treatment of other types of pain listed in this section, please see section 4.4.

Tabulated summary of adverse reactions

Frequencies are defined as: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Infections and infestations

Common: Localised infection in the area of photoactivation, e.g. pharyngitis, stomatitis

Unknown: Sepsis¹

Blood and lymphatic system disorders

Common: Anaemia

Nervous system disorders

Common: Dizziness, burning sensation

Vascular disorders

Very common: Haemorrhage

Unknown: Vascular rupture: see section 4.3

Respiratory, thoracic and mediastinal disorders

Unknown: Airway obstruction³

Gastrointestinal disorders

Very common: Constipation, stomatitis necrotising, dysphagia

Common: Vomiting, nausea, mouth ulceration

Skin and subcutaneous tissue disorders

Common: Blister, erythema, skin hyperpigmentations, photosensitivity reaction, skin necrosis²

Musculoskeletal, connective tissue and bone disorders

Common: Trismus³

Unknown: Fistula

General disorders and administration site conditions

Very common: Pain in the photoactivated area, e.g. facial pain, headache, injection site pain, oedema in the photoactivated area, e.g. face oedema, tongue oedema

Common: Pyrexia, injection site reaction, oedema

Injury, poisoning and procedural complications

Very common: Scar²

Common: Thermal burn, sunburn²

¹ As a consequence of local infection
² In the photoactivated area
³ As a consequence of local oedema

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. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

Foscan must not be diluted with aqueous solutions.