Foscan, INN-temoporfin
Contents
1. Figure 4 Remove the intravenous cannula immediately following the injection Do NOT flush with aqueous solutions such as sodium chloride 9 mg ml 0 9 solution for injection or water for injections Special care should 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 45 Foscan is photosensitive Once removed from its packaging it should be administered immediately Where delay is unavoidable the solution must be protected from light 4 LASER ILLUMINATION OF TREATMENT SITE Please refer to the laser user manual and to the microlens fibre optic user leaflet 96 hours after the administration of Foscan the treatment site is to be illuminated with light at 652 nm from an approved laser source Light must be delivered to the entire surface of the tumour using an approved microlens fibre optic Wherever possible the illuminated area must extend beyond the tumour margin by a distance of 0 5cm Light must be administered not less than 90 hours and not more than 110 hours after Foscan injection The incident light dose is 20J cm delivered by the microlens fibre optic in a circular field to the tumour surface at an irradiance of 100mW cm implying an illumination time of 200 seconds Each field is to be illuminated once only at each treatment Multiple non overlappi2. Medicinal product subject to medical prescription 15 INSTRUCTIONS ON USE 16 INFORMATION IN BRAILLE Justification for not including Braille accepted 25 MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS VIAL LABEL OF 1 MG ML 1 NAME OF THE MEDICINAL PRODUCT AND ROUTE S OF ADMINISTRATION Foscan 1 mg ml solution for injection Temoporfin Intravenous use 2 METHOD OF ADMINISTRATION 3 EXPIRY DATE EXP 4 BATCH NUMBER Lot 5 CONTENTS BY WEIGHT BY VOLUME OR BY UNIT 1 mg 1 ml 3 mg 3 ml 6 mg 6 ml 6 OTHER 26 MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS VIAL LABEL OF 4 MG ML 1 NAME OF THE MEDICINAL PRODUCT AND ROUTE S OF ADMINISTRATION Foscan 4 mg ml solution for injection Temoporfin Intravenous use 2 METHOD OF ADMINISTRATION 3 EXPIRY DATE EXP 4 BATCH NUMBER Lot 5 CONTENTS BY WEIGHT BY VOLUME OR BY UNIT 14 mg 3 5 ml 20 mg 5 ml 6 OTHER 27 B PACKAGE LEAFLET 28 PACKAGE LEAFLET INFORMATION FOR THE USER Foscan 1 mg ml solution for injection Temoporfin Read all of this leaflet carefully before you start using this medicine Keep this leaflet You may need to read it again If you have further questions please ask your doctor or your pharmacist This
3. 1 NAME OF THE MEDICINAL PRODUCT Foscan 4 mg ml solution for injection Temoporfin 2 STATEMENT OF ACTIVE SUBSTANCE S Each ml contains 4 mg of temoporfin 3 LIST OF EXCIPIENTS Ethanol anhydrous and propylene glycol see package leaflet for further information 4 PHARMACEUTICAL FORM AND CONTENTS Solution for injection 14 mg 3 5 ml Solution for injection 20 mg 5 ml Sterile filter 5 METHOD AND ROUTE S OF ADMINISTRATION For intravenous use Read the package leaflet before use 6 SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF THE REACH AND SIGHT OF CHILDREN Keep out of the reach and sight of children 7 OTHER SPECIAL WARNING S IF NECESSARY Single dose Discard the remainder after use 8 EXPIRY DATE EXP 24 9 SPECIAL STORAGE CONDITIONS Do not store above 25 C Store in the original package in order to protect from light 10 SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS IF APPROPRIATE 11 NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER biolitec pharma Itd United Drug House Magna Drive Dublin 24 Ireland 12 MARKETING AUTHORISATION NUMBER S EU 1 01 197 001 3 5 ml EU 1 01 197 002 5 ml 13 BATCH NUMBER Lot 14 GENERAL CLASSIFICATION FOR SUPPLY
4. 4 7 Effects on ability to drive and use machines 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 4 8 Undesirable effects 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 toxicities associated with this 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 The low number of treated patients did not allow identification of adverse reactions which may be categorised as uncommon and rare
5. Antineoplastic agents other antineoplastic agents ATC code LO1XDO5 Temoporfin is a photosensitising agent used in the photodynamic therapy of tumours The pharmacological activity is initiated by photoactivation of temoporfin with non thermal light at 652nm following intravenous administration The therapeutic effect is mediated through the generation of highly reactive oxygen species a process dependent on the intracellular interaction of temoporfin with light and oxygen In a clinical trial of 147 patients with advanced head and neck squamous cell carcinoma tumour response defined as a reduction of a minimum of 5046 of the tumour mass for a minimum of four weeks was observed in 2546 after a single treatment A WHO local complete response was observed in 1446 of patients Tumour responses are enhanced in patients with fully illuminated lesions of 10mm or less in depth The median observed duration of tumour response for all patients was 57 days for overall response and 84 days for complete response Thirty seven patients received at least 2 treatments with Foscan Ten patients achieved a tumour response due to re treatment Of these 6 had a complete local response according to WHO criteria 5 0 Pharmacokinetic properties Temoporfin is a low clearance substance with a terminal plasma half life of 65 hours in patients Peak plasma levels occur at 2 4 hours post injection thereafter plasma levels decline in a bi exponential manner An ex
6. injections Special care should 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 36 Foscan is photosensitive Once removed from its packaging it should be administered immediately Where delay is unavoidable the solution must be protected from light 4 LASER ILLUMINATION OF TREATMENT SITE Please refer to the laser user manual and to the microlens fibre optic user leaflet 96 hours after the administration of Foscan the treatment site is to be illuminated with light at 652 nm from an approved laser source Light must be delivered to the entire surface of the tumour using an approved microlens fibre optic Wherever possible the illuminated area must extend beyond the tumour margin by a distance of 0 5cm Light must be administered not less than 90 hours and not more than 110 hours after Foscan injection The incident light dose is 20J cm delivered by the microlens fibre optic in a circular field to the tumour surface at an irradiance of 100mW cm implying an illumination time of 200 seconds Each field is to be illuminated once only at each treatment Multiple non overlapping fields may be illuminated Care must be taken to ensure that no area of tissue receives more than the specified light dose Tissue outside the target area must be shielded completely to avoid
7. and hands and wear dark glasses The type of clothes you must wear are e Wide brimmed hat for head neck nose and ears e Scarf for head and neck e Sunglasses with side panels for eyes and skin around eyes e Long sleeved top for upper body arms e Long trousers for lower body legs e Gloves for hands wrist and fingers e Socks for feet and ankles e Closed shoes for feet e Do not wear very thin clothing because it will not protect you from strong light Wear dark closely woven clothing e If you expose yourself to light by mistake you may get a prickly or burning feeling on the skin You must get out of the light immediately Your eyes may be very sensitive to bright lights during this week You may get eye pain or headache when lights are switched on If you have this problem wear dark glasses Days 8 14 You can now begin to go outside during daylight hours Stay in shaded areas or go out when it is cloudy Continue to wear dark closely woven clothing Start on Day 8 with 10 15 minutes outdoors If you do not see any skin redness in the next 24 hours you can gradually increase your time outdoors during the week Avoid direct sunlight or strong indoor lighting Stay in the shade Day 15 onward Your sensitivity to light is gradually getting back to normal You must test this carefully by exposing the back of your hand to the sun for 5 minutes Wait 24 hours to see if there is any redness If there i
8. for about 15 days after your injection This means that normal daylight or bright indoor lighting could give you skin burns To stop this you must follow carefully the instructions for gradual exposure to increasing light levels indoors over the first week and outdoor shaded light during the second week after treatment please see the table at the end of this leaflet Please speak to your doctor about this before you go home after being injected with Foscan Sunscreen creams will not prevent this sensitivity You will gradually become less sensitive to light Normally people are able to begin to return to normal outdoor lighting after 15 days Do not let an optician or ophthalmologist examine your eyes with bright lights for 30 days after Foscan injection Do not use UV sunbeds or sunbathe for 3 months after Foscan injection 29 e For 6 months following Foscan treatment avoid prolonged direct sunlight exposure of the injection site arm As a precautionary measure if prolonged outdoor activity is planned protect your injection arm by wearing long sleeved coloured clothing The table of instructions tells you what to do to prevent skin burns You must follow these instructions carefully Please ask your doctor nurse or pharmacist if you are not sure about anything Time after What should I do to prevent burns Foscan Injection Day 1 0 24 Stay indoors in a darkened room Keep the curtains drawn and use light bulbs of hours 60W o
9. medicine has been prescribed for you Do not pass it on to others It may harm them even if their symptoms are the same as yours If any of the side effects gets serious or if you notice any side effects not listed in this leaflet please tell your doctor or your pharmacist In this leaflet 1 What Foscan is and what it is used for 2 Before you use Foscan 3 How to use Foscan 4 Possible side effects 5 How to store Foscan 6 Further information 1 WHAT FOSCAN IS AND WHAT IT IS USED FOR Foscan is a porphyrin photosensitising medicine which increases your sensitivity to ultraviolet UV light and is activated by light from a laser in a treatment called photodynamic therapy Foscan is used for the treatment of head and neck cancer in patients who cannot be treated with other therapies 2 BEFORE YOU USE FOSCAN Do not use Foscan if you are allergic hypersensitive to temoporfin or any of the ingredients of Foscan see section 6 Further Information if you are hypersensitive allergic to porphyrins if you have porphyria or any other disease that is made worse by light if the tumour being treated goes through a large blood vessel if you are going to have an operation in the next 30 days if you have an eye disease which needs examination with bright light in the next 30 days if you are already being treated with a photosensitising agent Take special care with Foscan Foscan will make you sensitive to light
10. out of the light immediately Your eyes may be very sensitive to bright lights during this week You may get eye pain or headache when lights are switched on If you have this problem wear dark glasses Days 8 14 You can now begin to go outside during daylight hours Stay in shaded areas or go out when it is cloudy Continue to wear dark closely woven clothing Start on Day 8 with 10 15 minutes outdoors If you do not see any skin redness in the next 24 hours you can gradually increase your time outdoors during the week Avoid direct sunlight or strong indoor lighting Stay in the shade Day 15 onward Your sensitivity to light is gradually getting back to normal You must test this carefully by exposing the back of your hand to the sun for 5 minutes Wait 24 hours to see if there is any redness If there is redness you should avoid direct sunlight for another 24 hours You can then repeat the test If there is no redness you can gradually increase your exposure to sunlight day by day Do not stay in the sunlight for more than 15 minutes the first time Most 39 people will be able to go back to their normal routine by Day 22 On the first day after the skin test you can stay in direct sunlight for 15 minutes You can increase your exposure by another 15 minutes each day i e second day 30 minutes third day 45 minutes fourth day 60 minutes and so on If at any time you notice a prickly or burning feeling or se
11. therapy with a photosensitizing agent 4 4 Special warnings and precautions for use 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 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 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 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 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
12. 45 minutes fourth day 60 minutes and so on If at any time you notice a prickly or burning feeling or see skin reddening after exposure to sun wait until this disappears before exposing your skin to light for this length of time again For 30 days following Foscan treatment avoid eye tests that use bright lights 12 For 3 months following Foscan treatment avoid UV tanning beds Do not sunbathe For 6 months following Foscan treatment care should be taken to avoid direct prolonged sunlight exposure of the arm used for Foscan injection As a precautionary measure if prolonged outdoor activity is planned the injection arm should be protected by wearing long sleeved coloured clothing This medicinal product contains 48 vol ethanol alcohol i e up to 1 0 g per dose equivalent to 21 ml of beer 9 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 4 5 Interaction with other medicinal products and other forms of interaction 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 cytochr
13. ANNEXI SUMMARY OF PRODUCT CHARACTERISTICS 1 NAME OF THE MEDICINAL PRODUCT Foscan 1 me ml solution for injection 2 QUALITATIVE AND QUANTITATIVE COMPOSITION Each ml contains 1 mg of temoporfin Excipients Each ml contains 376 mg of ethanol anhydrous and 560 mg of propylene glycol For a full list of excipients see section 6 1 3 PHARMACEUTICAL FORM Solution for injection Dark purple solution 4 CLINICAL PARTICULARS 4 1 Therapeutic indications Foscan is indicated for the palliative treatment of patients with advanced head and neck squamous cell carcinoma failing prior therapies and unsuitable for radiotherapy surgery or systemic chemotherapy 4 2 Posology and method of administration Foscan photodynamic therapy must only be administered in specialist oncology centres in which a multidisciplinary team assesses patient treatment and under the supervision of physicians experienced in photodynamic therapy Posology The dose is 0 15mg kg body weight Paediatric population There is no relevant use of Foscan in the paediatric population Method of administration Foscan is administered via an in dwelling intravenous cannula in a large proximal limb vein preferably in the antecubital fossa as a single slow intravenous injection over not less than 6 minutes The patency of the in dwelling cannula should be tested before injection and every precaution taken against extravasation see section 4 4 The dark purple col
14. ENTS Solution for injection 1 mg 1 ml Solution for injection 3 mg 3 ml Solution for injection 6 mg 6 ml Sterile filter 5 METHOD AND ROUTE S OF ADMINISTRATION For intravenous use Read the package leaflet before use 6 SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF THE REACH AND SIGHT OF CHILDREN Keep out of the reach and sight of children 7 OTHER SPECIAL WARNING S IF NECESSARY Single dose Discard the remainder after use 8 EXPIRY DATE EXP 22 9 SPECIAL STORAGE CONDITIONS Do not store above 25 C Store in the original package in order to protect from light 10 SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS IF APPROPRIATE 11 NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER biolitec pharma Itd United Drug House Magna Drive Dublin 24 Ireland 12 MARKETING AUTHORISATION NUMBER S EU 1 01 197 003 1 ml EU 1 01 197 004 3 ml EU 1 01 197 005 6 ml 13 BATCH NUMBER Lot 14 GENERAL CLASSIFICATION FOR SUPPLY Medicinal product subject to medical prescription 15 INSTRUCTIONS ON USE 16 INFORMATION IN BRAILLE Justification for not including Braille accepted 23 PARTICULARS TO APPEAR ON THE OUTER PACKAGING OUTER CARTON OF 4 MG ML
15. 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 21 10 common 21 100 to lt 1 10 uncommon 21 1 000 to 1 100 rare 21 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 System Organ Class Undesirable effects Infections and infestations Common localised infection Blood and lymphatic system disorders Common anaemia Nervous system disorders Common dizziness burning sensation Vascular disorders Very common haemorrhage 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 necrosis Musculoskeletal connective tissue and bone Common disorders trismus General disorders and administration site Very common conditions pain injection site pain facial pain face oedema Common pyrexia injection site reaction oedema Injury poisoning and procedural complications Very common Scar Common thermal burn sunburn 4 9 Overdose In the event o
16. It is important that patients are re introduced to normal light gradually 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 Clinicians must counsel patients to observe the following precautions that are provided in the Package Leaflet 11 Time after Foscan Injection What should I do to prevent burns Day 1 0 24 Stay indoors in a darkened room Keep the curtains drawn and use light bulbs of hours 60W or less Avoid exposure to direct sunlight Days 2 7 You can gradually return to normal indoor lighting Remember to avoid direct sunlight coming through the window or direct light from household appliances such as reading lamps You may watch television You can go outdoors after dusk If it is absolutely necessary to go outdoors during the hours of daylight you must be careful to cover up all your skin including your face and hands and wear dark glasses The type of clothes you must wear are e Wide brimmed hat for head neck nose and ears e Scarf for head and neck e Sunglasses with side panels for eyes and skin around eyes e Long sleeved top for upper body arms e Long trousers for lower body legs e Gloves for hands wrist and fingers e Socks for feet and ankles e Closed shoes for feet e Do not wear very thin clothing because it will not protect you from strong light Wear dark closely woven cl
17. Itd Tel 353 1 463 7415 Ireland biolitec pharma Itd Tel 353 1 463 7415 sland biolitec pharma Itd Tel 353 1 463 7415 Italia Bracco SpA Tel 39 02 21 771 Ko7npoc biolitec pharma Itd Tel 353 1 463 7415 Latvija Gedeon Richter Plc Tel 371 6784 5338 Lietuva Gedeon Richter Plc Tel 370 5 261 0154 This leaflet was last approved in Romania Gedeon Richter Romania SA Tel 40 265 264 067 Slovenija biolitec pharma Itd Tel 353 1 463 7415 Slovensk republika Gedeon Richter Plc Tel 421 2 5020 5801 Suomi Finland biolitec pharma Itd Tel 353 1 463 7415 Sverige biolitec pharma Itd Tel 353 1 463 7415 United Kingdom biolitec pharma Itd Tel 353 1 463 7415 Detailed information on this medicine is available on the European Medicines Agency web site http www ema europa eu 34 The following information is intended for medical or healthcare professionals only Foscan 1 mg ml solution for injection Temoporfin 1 PACK CONTENTS The active substance is temoporfin Each ml of solution contains 1 mg of temoporfin The excipients are ethanol anhydrous and propylene glycol A filter with Luer lock connections for syringe and cannula is provided Each pack provides 1 vial containing 1 ml 3ml or 6ml solution for injection Each vial represents a single dose and any unused solution must be discarded 2 CALCULATION OF DOSE Calculate the required dose of Foscan a
18. arma Itd Tel 353 1 463 7415 sterreich biolitec pharma Itd Tel 353 1 463 7415 Polska Gedeon Richter Marketing Polska Sp z o o Tel 48 22 593 93 00 Portugal biolitec pharma Itd Tel 353 1 463 7415 Romania Gedeon Richter Romania SA Tel 40 265 264 067 Ireland biolitec pharma Itd Tel 353 1 463 7415 sland biolitec pharma Itd Tel 353 1 463 7415 Italia Bracco SpA Tel 39 02 21 771 Kobmpoc biolitec pharma Itd Tel 353 1 463 7415 Latvija Gedeon Richter Plc Tel 371 6784 5338 Lietuva Gedeon Richter Plc Tel 370 5 261 0154 This leaflet was last approved in Slovenija biolitec pharma Itd Tel 353 1 463 7415 Slovensk republika Gedeon Richter Plc Tel 421 2 5020 5801 Suomi Finland biolitec pharma Itd Tel 353 1 463 7415 Sverige biolitec pharma Itd Tel 353 1 463 7415 United Kingdom biolitec pharma Itd Tel 353 1 463 7415 Detailed information on this medicine is available on the European Medicines Agency web site http www ema europa eu 43 The following information is intended for medical or healthcare professionals only Foscan 4 mg ml solution for injection Temoporfin 1 PACK CONTENTS The active substance is temoporfin Each ml of solution contains 4 mg of temoporfin The excipients are ethanol anhydrous and propylene glycol A filter with Luer lock connections for syringe and cannula is provided Each pack provides 1 vial c
19. ccording to the bodyweight of the patient The dose is 0 15 mg kg bodyweight 3 ADMINISTRATION OF FOSCAN 96 hours prior to laser illumination of treatment site Foscan must be administered intravenously via an in dwelling cannula in a large proximal limb vein preferably in the antecubital fossa The patency of the in dwelling cannula should be tested before injection The dark purple colour of the solution together with the amber vial makes a visual check for particulates impossible Thus an in line filter must be used as a precautionary measure and is provided in the package Draw up the entire contents of the vial containing Foscan into a syringe and expel air Figure 1 m u Figure 1 35 Attach the filter to the syringe Figure 2 Figure 2 Press the syringe plunger to fill all dead space within the filter Continue pressing the plunger to expel excess Foscan until the required volume is left in the syringe allowing sufficient to cover the dead space in the intravenous cannula Figure 3 Figure 3 Attach the syringe and filter to the cannula Administer the required dose of Foscan by slow intravenous injection over not less than 6 minutes Figure 4 Figure 4 Remove the intravenous cannula immediately following the injection Do NOT flush with aqueous solutions such as sodium chloride 9 mg ml 0 9 solution for injection or water for
20. cur in more than 1 in 100 patients e There may be some irritation a burning sensation or skin damage where Foscan is injected but this will not last long You may also get ulcers blisters skin redness or skin darkening vomiting fever nausea anaemia light sensitivity sunburn burns difficulty with swallowing giddiness There may be swelling or you may have a stiff jaw Some people may get an infection in the treated area If any of the side effects gets serious or if you notice any side effects not mentioned in this leaflet please tell your doctor or pharmacist 5 HOW TO STORE FOSCAN Keep out of the reach and sight of children Do not use after the expiry date which is stated on the label and the carton The expiry date refers to the last day of that month Foscan will be stored at the hospital pharmacy Do not store above 25 C Store in the original package in order to protect from light Once removed from its package this medicine must be used immediately Each vial is a single dose and any unused medicine must be discarded Medicines should not be disposed of via waste water or household waste These measures will help to protect the environment 32 6 FURTHER INFORMATION What Foscan contains The active substance is temoporfin Each ml contains 1 mg of temoporfin The other ingredients are ethanol anhydrous E1510 and propylene glycol E1520 What Foscan looks like and contents of the pac
21. d 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 toxicities associated with this 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 The low number of treated patients did not allow 13 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 21 10 common 21 100 to lt 1 10 uncommon 21 1 000 to 1 100 rare 21 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 System Organ Class Undesirable effects Infections and infestations Common localised infection Blood and lymphatic system disorders Common anaemia Nervous system disorders Common dizziness burning sensation Vascular disord
22. e skin reddening after exposure to sun wait until this disappears before exposing your skin to light for this length of time again For 30 days following Foscan treatment avoid eye tests that use bright lights For 3 months following Foscan treatment avoid UV tanning beds Do not sunbathe For 6 months following Foscan treatment care should be taken to avoid direct prolonged sunlight exposure of the arm used for Foscan injection As a precautionary measure if prolonged outdoor activity is planned the injection arm should be protected by wearing long sleeved coloured clothing Using other medicines Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines including medicines obtained without a prescription Using Foscan with food and drink Your normal food and drink will not affect your treatment with Foscan Pregnancy e You must avoid becoming pregnant for 3 months after Foscan treatment e Ask your doctor or pharmacist for advice before taking any medicine if you are pregnant Breast feeding Do not breastfeed for at least 1 month after Foscan injection Driving and using machines e tis not recommended to drive or operate machines for the first 15 days after Foscan injection because of the recommended light exposure restrictions Important information about some of the ingredients of Foscan Warning This product contains 48 vol ethanol alcohol i e up to 1 g per dose e
23. ed appropriate with a recommended minimum interval of 4 weeks between treatments 4 3 Contraindications Hypersensitivity to the active substance or to any of the excipients Porphyria or other diseases exacerbated by light Hypersensitivity to porphyrins Tumours known to be eroding into a major blood vessel in or adjacent to the illumination site A planned surgical procedure within the next 30 days Co existing ophthalmic disease likely to require slit lamp examination within the next 30 days Existing therapy with a photosensitizing agent 4 4 Special warnings and precautions for use 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 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 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 Unplanned or emergency surgical procedures where Foscan has been administered within the previous 30 days must be undertaken only if absolutely nece
24. ed for Foscan injection As a precautionary measure if prolonged outdoor activity is planned the injection arm should be protected by wearing long sleeved coloured clothing Using other medicines Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines including medicines obtained without a prescription Using Foscan with food and drink Your normal food and drink will not affect your treatment with Foscan Pregnancy e You must avoid becoming pregnant for 3 months after Foscan treatment e Ask your doctor or pharmacist for advice before taking any medicine if you are pregnant Breast feeding Do not breastfeed for at least 1 month after Foscan injection Driving and using machines e The amount of alcohol in this medicine may impair your ability to drive or use machines for a few hours after injection e tis not recommended to drive or operate machines for the first 15 days after Foscan injection because of the recommended light exposure restrictions Important information about some of the ingredients of Foscan Warning e This 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 This product is also harmful for those suffering from alcoholism Pregnant or breast feeding women children and high risk groups such as patients with liver disease or epilepsy are also at risk The amount of alcohol in this product may alter
25. er source Light must be delivered to the entire surface of the tumour using an approved microlens fibre optic Wherever possible the illuminated area must extend beyond the tumour margin by a distance of 0 5cm Light must be administered not less than 90 hours and not more than 110 hours after Foscan injection The incident light dose is 20J cm2 delivered at an irradiance of 100mW cm to the tumour surface implying an illumination time of approximately 200 seconds Each field is to be illuminated once only at each treatment Multiple non overlapping fields may be illuminated Care must be taken to ensure that no area of tissue receives more than the specified light dose Tissue outside the target area must be shielded completely to avoid photoactivation by scattered or reflected light A second course of treatment may be given at the discretion of the treating physician in patients where additional tumour necrosis and removal is deemed appropriate with a recommended minimum interval of 4 weeks between treatments 4 3 Contraindications Hypersensitivity to the active substance or to any of the excipients Porphyria or other diseases exacerbated by light Hypersensitivity to porphyrins Tumours known to be eroding into a major blood vessel in or adjacent to the illumination site A planned surgical procedure within the next 30 days Co existing ophthalmic disease likely to require slit lamp examination within the next 30 days Existing
26. ers Very common haemorrhage Gastrointestinal disorders Very common constipation stomatitis necrotising dysphagia Common vomiting nausea mouth ulceration Skin and subcutaneous tissue disorders Musculoskeletal connective tissue and bone disorders Common blister erythema skin hyperpigmentations photosensitivity reaction skin necrosis Common trismus General disorders and administration site conditions Very common pain injection site pain facial pain face oedema Common pyrexia injection site reaction oedema Injury poisoning and procedural complications Very common Scar Common thermal burn sunburn 4 9 Overdose In the event of an overdose laser treatment would result in deeper tumour necrosis than would be expected with the recommended dose Illumination of the tumour should only be carried out if the potential benefit justifies the potential risk of excessive necrosis If the tumour is not illuminated a period of at least 4 weeks between overdose and re administration of Foscan must be allowed The adverse reactions associated with overdose would be expected to be limited to photosensitivity reactions Exposure to ambient light after overdose carries an increased risk of photosensitivity reactions Published clinical research has shown that the duration and intensity of photosensitivity at the recommended dose of 0 15 mg kg were reduced by one third relative to a do
27. ete response was observed in 1446 of patients Tumour responses are enhanced in patients with fully illuminated lesions of 10mm or less in depth The median observed duration of tumour response for all patients was 57 days for overall response and 84 days for complete response Thirty seven patients received at least 2 treatments with Foscan Ten patients achieved a tumour response due to re treatment Of these 6 had a complete local response according to WHO criteria 5 0 Pharmacokinetic properties Temoporfin is a low clearance substance with a terminal plasma half life of 65 hours in patients Peak plasma levels occur at 2 4 hours post injection thereafter plasma levels decline in a bi exponential manner An extensive volume of distribution is observed that is intermediate between total and extracellular body water Temoporfin does not concentrate in the tissues Plasma protein binding is at 85 8796 Temoporfin is bound to plasma lipoproteins and high density proteins such as albumin in the blood By 15 days post infusion temoporfin plasma concentration has declined to background such that patients are generally able to begin a gradual return to normal outdoor lighting conditions Limited data are available on the elimination of temoporfin in humans Animal data show temoporfin is exclusively eliminated by the liver into the bile and excreted in the faeces Two major metabolites of temoporfin are eliminated into the bile There is no enterohepat
28. f an overdose laser treatment would result in deeper tumour necrosis than would be expected with the recommended dose Illumination of the tumour should only be carried out if the potential benefit justifies the potential risk of excessive necrosis If the tumour is not illuminated a period of at least 4 weeks between overdose and re administration of Foscan must be allowed The adverse reactions associated with overdose would be expected to be limited to photosensitivity reactions Exposure to ambient light after overdose carries an increased risk of photosensitivity reactions Published clinical research has shown that the duration and intensity of photosensitivity at the recommended dose of 0 15 mg kg were reduced by one third relative to a dose of 0 3 mg kg Animal studies have shown some haematological and blood chemistry changes decreased platelets erythrocytes and haemoglobin increased neutrophils fibrinogen bilirubin triglyceride and cholesterol Strict observance of the reduced light regime is required A skin photosensitivity test must be carried out before the patient returns to normal light conditions No specific systemic symptoms are known to be associated with overdose Treatment should be supportive Limited information is available on the effects of overexposure to laser light during treatment Increased damage to tissue was noted 5 PHARMACOLOGICAL PROPERTIES 5 1 Pharmacodynamic properties Pharmacotherapeutic group
29. he active substance is temoporfin Each ml contains 4 mg of temoporfin The other ingredients are ethanol anhydrous E1510 and propylene glycol E1520 What Foscan looks like and contents of the pack Foscan solution for injection is a dark purple solution in an amber glass vial containing 3 5ml or 5ml of solution Each pack contains 1 glass vial and a filter Not all pack sizes may be marketed Marketing Authorisation Holder and Manufacturer biolitec pharma Itd United Drug House Magna Drive Dublin 24 Ireland For any information about this medicine please contact the local representative of the Marketing Authorisation Holder Belgi Belgique Belgien biolitec pharma Itd Tel 353 1 463 7415 br arapus I eneon Puxtep AJI ten 359 2 812 9062 Cesk republika l Gedeon Richter Marketing CR s r o Tel 420 26 114 1200 Danmark biolitec pharma Itd Tel 353 1 463 7415 Deutschland biolitec pharma Itd Tel 353 1 463 7415 Eesti Gedeon Richter Plc Tel 372 7 42 7056 E6600 biolitec pharma Itd Tel 353 1 463 7415 Espa a Industrial Farmac utica Cantabria S A Tel 34 91 382 40 26 France biolitec pharma Itd Tel 353 1 463 7415 Luxembourg Luxemburg biolitec pharma Itd Tel 353 1 463 7415 Magyarorsz g Gedeon Richter Plc Tel 36 1 431 4040 Malta biolitec pharma Itd Tel 353 1 463 7415 Nederland biolitec pharma Itd Tel 353 1 463 7415 Norge biolitec ph
30. hildren 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 4 5 Interaction with other medicinal products and other forms of interaction 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 4 6 Fertility pregnancy and lactation There are no data from the use of temoporfin in pregnant women Animal studies are insufficient with respect to effects on embryonal foetal development see section 5 3 The potential risk for humans is unknown Temoporfin should not be used during pregnancy unless clearly necessary Animal studies suggest a toxic effect in early pregnancy see section 5 3 The potential risk for humans is unknown Therefore pregnancy must be avoided for 3 months after treatment with temoporfin It is not known if temoporfin is excreted in human milk Women receiving Foscan must not breast feed for at least one month following injection The effects of Foscan on fertility in humans have not been studied
31. ic recirculation of these metabolites Both these metabolites show conjugated character No metabolites are seen in the systemic circulation 5 3 Preclinical safety data In repeated dose toxicity studies in rats and dogs the main undesirable effects of temoporfin were phototoxicity and adverse injection site reactions Local irritancy of Foscan solution for injection after intravenous administration occurred with all doses High rates of administration caused death in dogs and rabbits No other signs of toxicity were found however in dogs treated with the recommended therapeutic dose systemic exposure exceeded that of humans 15 The genotoxicity of temoporfin has been investigated to a limited extent Due to the generation of reactive oxygen species temoporfin poses a minor risk of mutagenicity This risk can be controlled in the clinical situation by minimising direct exposure to light see section 4 4 In developmental toxicity studies in rabbits temoporfin at systemic exposures equal to those obtained in humans with the recommended therapeutic dose caused an increase in early post implantation loss Although no other developmental effects were observed the applied doses were not sufficiently in excess of the human therapeutic dose to provide an adequate margin of safety 6 PHARMACEUTICAL PARTICULARS 6 1 List of excipients Ethanol anhydrous E1510 Propylene glycol E1520 6 2 Incompatibilities In the absence of compatibil
32. ity studies this medicinal product must not be mixed with other medicinal products except those mentioned in section 6 6 6 3 Shelf life 5 years Once opened the solution must be used immediately 6 4 Special precautions for storage Do not store above 25 C Store in the original package in order to protect from light 6 5 Nature and contents of container Type I amber glass vials with a bromobutyl elastomer stopper and aluminium seal containing either 3 5 ml or 5 ml of solution for injection Each pack contains 1 vial and a filter with Luer lock connections for syringe and cannula Not all pack sizes may be marketed 6 6 Special precautions for disposal and other handling Appropriate precaution must be taken when handling this medicinal product Studies have shown that Foscan is non irritant Each vial represents a single dose and any unused solution must be discarded Foscan is photosensitive Once removed from its packaging it must be administered immediately Where delay is unavoidable the solution must be protected from light Foscan shall not be diluted with aqueous solutions Any unused product or waste material should be disposed of in accordance with local requirements 7 MARKETING AUTHORISATION HOLDER biolitec pharma Itd United Drug House Magna Drive Dublin 24 Ireland 8 MARKETING AUTHORISATION NUMBER S EU 1 01 197 001 EU 1 01 197 002 9 DATE OF FIRST AUTHORISATION RENEWAL OF THE AUTHORISATION Date
33. k Foscan solution for injection is a dark purple solution in an amber glass vial containing 1ml 3ml or 6ml of solution Each pack contains 1 glass vial and a filter Not all pack sizes may be marketed Marketing Authorisation Holder and Manufacturer biolitec pharma Itd United Drug House Magna Drive Dublin 24 Ireland For any information about this medicine please contact the local representative of the Marketing Authorisation Holder Belgi Belgique Belgien biolitec pharma Itd Tel 353 1 463 7415 br arapus I eneon Puxrep AM tem 359 2 812 9062 Cesk republika Gedeon Richter Marketing CR s r o Tel 420 26 114 1200 Danmark biolitec pharma Itd Tel 353 1 463 7415 Deutschland biolitec pharma Itd Tel 353 1 463 7415 Eesti Gedeon Richter Plc Tel 372 7 42 7056 E4600 biolitec pharma Itd Tel 353 1 463 7415 Espa a Industrial Farmac utica Cantabria S A Tel 34 91 382 40 26 33 Luxembourg Luxemburg biolitec pharma Itd Tel 353 1 463 7415 Magyarorsz g Gedeon Richter Plc Tel 36 1 431 4040 Malta biolitec pharma Itd Tel 353 1 463 7415 Nederland biolitec pharma Itd Tel 353 1 463 7415 Norge biolitec pharma Itd Tel 353 1 463 7415 sterreich biolitec pharma Itd Tel 353 1 463 7415 Polska Gedeon Richter Marketing Polska Sp z o o Tel 48 22 593 93 00 Portugal biolitec pharma Itd Tel 353 1 463 7415 France biolitec pharma
34. ng fields may be illuminated Care must be taken to ensure that no area of tissue receives more than the specified light dose Tissue outside the target area must be shielded completely to avoid photoactivation by scattered or reflected light 5 SAFETY INFORMATION Foscan is non irritant 46
35. of first authorisation 24 October 2001 Date of last renewal 10 DATE OF REVISION OF THE TEXT Detailed information on this medicinal product is available on the website of the European Medicines Agency http www ema europa eu ANNEX II A MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH RELEASE B CONDITIONS OF THE MARKETING AUTHORISATION A MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH RELEASE Name and address of the manufacturer responsible for batch release biolitec pharma Itd United Drug House Magna Drive Dublin 24 Ireland B CONDITIONS OF THE MARKETING AUTHORISATION CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE IMPOSED ON THE MARKETING AUTHORISATION HOLDER Medicinal product subject to restricted medical prescription See Annex I Summary of Product Characteristics section 4 2 CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT Not applicable ANNEX III LABELLING AND PACKAGE LEAFLET 20 A LABELLING 21 PARTICULARS TO APPEAR ON THE OUTER PACKAGING OUTER CARTON OF 1 MG ML 1 NAME OF THE MEDICINAL PRODUCT Foscan 1 mg ml solution for injection Temoporfin 2 STATEMENT OF ACTIVE SUBSTANCE S Each ml contains 1 mg of temoporfin 3 LIST OF EXCIPIENTS Ethanol anhydrous and propylene glycol see package leaflet for further information 4 PHARMACEUTICAL FORM AND CONT
36. ome P 450 enzymes by temoporfin 4 6 Fertility pregnancy and lactation There are no data from the use of temoporfin in pregnant women Animal studies are insufficient with respect to effects on embryonal foetal development see section 5 3 The potential risk for humans is unknown Temoporfin should not be used during pregnancy unless clearly necessary Animal studies suggest a toxic effect in early pregnancy see section 5 3 The potential risk for humans is unknown Therefore pregnancy must be avoided for 3 months after treatment with temoporfin It is not known if temoporfin is excreted in human milk Women receiving Foscan must not breast feed for at least one month following injection The effects of Foscan on fertility in humans have not been studied 4 7 Effects on ability to drive and 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 4 8 Undesirable effects Summary of the safety profile All patients who receive Foscan will become temporarily photosensitive an
37. ontaining 3 5 ml or 5 ml solution for injection Each vial represents a single dose and any unused solution must be discarded 2 CALCULATION OF DOSE Calculate the required dose of Foscan according to the bodyweight of the patient The dose is 0 15 mg kg bodyweight 3 ADMINISTRATION OF FOSCAN 96 hours prior to laser illumination of treatment site Foscan must be administered intravenously via an in dwelling cannula in a large proximal limb vein preferably in the antecubital fossa The patency of the in dwelling cannula should be tested before injection The dark purple colour of the solution together with the amber vial makes a visual check for particulates impossible Thus an in line filter must be used as a precautionary measure and is provided in the package Draw up the entire contents of the vial containing Foscan into a syringe and expel air Figure 1 y u Figure 1 44 Attach the filter to the syringe Figure 2 Figure 2 Press the syringe plunger to fill all dead space within the filter Continue pressing the plunger to expel excess Foscan until the required volume is left in the syringe allowing sufficient to cover the dead space in the intravenous cannula Figure 3 Figure 3 Attach the syringe and filter to the cannula Administer the required dose of Foscan by slow intravenous injection over not less than 6 minutes Figure 4
38. othing e If you expose yourself to light by mistake you may get a prickly or burning feeling on the skin You must get out of the light immediately Your eyes may be very sensitive to bright lights during this week You may get eye pain or headache when lights are switched on If you have this problem wear dark glasses Days 8 14 You can now begin to go outside during daylight hours Stay in shaded areas or go out when it is cloudy Continue to wear dark closely woven clothing Start on Day 8 with 10 15 minutes outdoors If you do not see any skin redness in the next 24 hours you can gradually increase your time outdoors during the week Avoid direct sunlight or strong indoor lighting Stay in the shade Day 15 onward Your sensitivity to light is gradually getting back to normal You must test this carefully by exposing the back of your hand to the sun for 5 minutes Wait 24 hours to see if there is any redness If there is redness you should avoid direct sunlight for another 24 hours You can then repeat the test If there is no redness you can gradually increase your exposure to sunlight day by day Do not stay in the sunlight for more than 15 minutes the first time Most people will be able to go back to their normal routine by Day 22 On the first day after the skin test you can stay in direct sunlight for 15 minutes You can increase your exposure by another 15 minutes each day i e second day 30 minutes third day
39. our of the solution together with the amber vials makes a visual check for particulates impossible Thus an in line filter must be used as a precautionary measure and is provided in the package Foscan shall not be diluted nor flushed with sodium chloride or any other aqueous solution The required dose of Foscan is administered by slow intravenous injection over not less than 6 minutes 96 hours after the administration of Foscan the treatment site is to be illuminated with light at 652 nm from an approved laser source Light must be delivered to the entire surface of the tumour using an approved microlens fibre optic Wherever possible the illuminated area must extend beyond the tumour margin by a distance of 0 5cm Light must be administered not less than 90 hours and not more than 110 hours after Foscan injection The incident light dose is 20J cm2 delivered at an irradiance of 100mW cm to the tumour surface implying an illumination time of approximately 200 seconds Each field is to be illuminated once only at each treatment Multiple non overlapping fields may be illuminated Care must be taken to ensure that no area of tissue receives more than the specified light dose Tissue outside the target area must be shielded completely to avoid photoactivation by scattered or reflected light A second course of treatment may be given at the discretion of the treating physician in patients where additional tumour necrosis and removal is deem
40. photoactivation by scattered or reflected light 5 SAFETY INFORMATION Foscan is non irritant 37 PACKAGE LEAFLET INFORMATION FOR THE USER Foscan 4 mg ml solution for injection Temoporfin Read all of this leaflet carefully before you start using this medicine Keep this leaflet You may need to read it again If you have further questions please ask your doctor or your pharmacist This medicine has been prescribed for you Do not pass it on to others It may harm them even if their symptoms are the same as yours If any of the side effects gets serious or if you notice any side effects not listed in this leaflet please tell your doctor or your pharmacist In this leaflet 1 What Foscan is and what it is used for 2 Before you use Foscan 3 How to use Foscan 4 Possible side effects 5 How to store Foscan 6 Further information 1 WHAT FOSCAN IS AND WHAT IT IS USED FOR Foscan is a porphyrin photosensitising medicine which increases your sensitivity to ultraviolet UV light and is activated by light from a laser in a treatment called photodynamic therapy Foscan is used for the treatment of head and neck cancer in patients who cannot be treated with other therapies 2 BEFORE YOU USE FOSCAN Do not use Foscan if you are allergic hypersensitive to temoporfin or any of the ingredients of Foscan see section 6 Further Information if you are hypersensitive allergic to porphyrins if you have por
41. phyria or any other disease that is made worse by light if the tumour being treated goes through a large blood vessel if you are going to have an operation in the next 30 days if you have an eye disease which needs examination with bright light in the next 30 days if you are already being treated with a photosensitising agent Take special care with Foscan Foscan will make you sensitive to light for about 15 days after your injection This means that normal daylight or bright indoor lighting could give you skin burns To stop this you must follow carefully the instructions for gradual exposure to increasing light levels indoors over the first week and outdoor shaded light during the second week after treatment please see the table at the end of this leaflet Please speak to your doctor about this before you go home after being injected with Foscan Sunscreen creams will not prevent this sensitivity You will gradually become less sensitive to light Normally people are able to begin to return to normal outdoor lighting after 15 days Do not let an optician or ophthalmologist examine your eyes with bright lights for 30 days after Foscan injection Do not use UV sunbeds or sunbathe for 3 months after Foscan injection 38 e For 6 months following Foscan treatment avoid prolonged direct sunlight exposure of the injection site arm As a precautionary measure if prolonged outdoor activity is planned protect your injection arm by wea
42. quivalent to 21 ml of beer 9 ml wine per dose This product is harmful for those suffering from alcoholism Pregnant or breast feeding women children and high risk groups such as patients with liver disease or epilepsy are also at risk 3 HOW TO USE FOSCAN e Your doctor or nurse will give you Foscan by a slow injection into a vein which will take approximately 6 minutes e If necessary your doctor or nurse may give you another injection at least 4 weeks later e Four days after your injection your doctor will treat your cancer with laser light If you are given more Foscan than you should e You may not be given the laser treatment e You may be sensitive to light for more than 15 days You must follow carefully the instructions on preventing skin burns 40 4 POSSIBLE SIDE EFFECTS Like all medicines Foscan can cause side effects although not everybody gets them e Everyone who takes Foscan will become sensitive to light for about 15 days after injection e You must follow the instructions given to you to avoid sunlight and bright indoor light e These instructions are written in this leaflet Your doctor will also tell you what to do If you do not follow these instructions you may get severe sunburn that leads to permanent scarring Very common side effects likely to occur in more than 1 in 10 patients e You may feel some pain when Foscan is injected e After the laser treatment you may feel pain in your face and pain a
43. r less Avoid exposure to direct sunlight Days 2 7 You can gradually return to normal indoor lighting Remember to avoid direct sunlight coming through the window or direct light from household appliances such as reading lamps You may watch television You can go outdoors after dusk If it is absolutely necessary to go outdoors during the hours of daylight you must be careful to cover up all your skin including your face and hands and wear dark glasses The type of clothes you must wear are Wide brimmed hat for head neck nose and ears Scarf for head and neck Sunglasses with side panels for eyes and skin around eyes Long sleeved top for upper body arms Long trousers for lower body legs Gloves for hands wrist and fingers Socks for feet and ankles Closed shoes for feet Do not wear very thin clothing because it will not protect you from strong light Wear dark closely woven clothing If you expose yourself to light by mistake you may get a prickly or burning feeling on the skin You must get out of the light immediately Your eyes may be very sensitive to bright lights during this week You may get eye pain or headache when lights are switched on If you have this problem wear dark glasses Days 8 14 You can now begin to go outside during daylight hours Stay in shaded areas or go out when it is cloudy Continue to wear dark closely woven clothing Start on Day 8 with 10 15 minutes outdoors If
44. ration of reactive oxygen species temoporfin poses a minor risk of mutagenicity This risk can be controlled in the clinical situation by minimising direct exposure to light see section 4 4 In developmental toxicity studies in rabbits temoporfin at systemic exposures equal to those obtained in humans with the recommended therapeutic dose caused an increase in early post implantation loss Although no other developmental effects were observed the applied doses were not sufficiently in excess of the human therapeutic dose to provide an adequate margin of safety 6 PHARMACEUTICAL PARTICULARS 6 1 List of excipients Ethanol anhydrous E1510 Propylene glycol E1520 6 2 Incompatibilities In the absence of compatibility studies this medicinal product must not be mixed with other medicinal products except those mentioned in section 6 6 6 3 Shelf life 5 years Once opened the solution must be used immediately 6 4 Special precautions for storage Do not store above 25 C Store in the original package in order to protect from light 6 5 Nature and contents of container Type I amber glass vials with a bromobutyl elastomer stopper and aluminium seal containing either 1 ml or 3 ml or 6 ml of solution for injection Each pack contains 1 vial and a filter with Luer lock connections for syringe and cannula Not all pack sizes may be marketed 6 6 Special precautions for disposal and other handling Appropriate precaution mus
45. ring long sleeved coloured clothing The table of instructions tells you what to do to prevent skin burns You must follow these instructions carefully Please ask your doctor nurse or pharmacist if you are not sure about anything Time after What should I do to prevent burns Foscan Injection Day 1 0 24 hours Stay indoors in a darkened room Keep the curtains drawn and use light bulbs of 60W or less Avoid exposure to direct sunlight Days 2 7 You can gradually return to normal indoor lighting Remember to avoid direct sunlight coming through the window or direct light from household appliances such as reading lamps You may watch television You can go outdoors after dusk If it is absolutely necessary to go outdoors during the hours of daylight you must be careful to cover up all your skin including your face and hands and wear dark glasses The type of clothes you must wear are e Wide brimmed hat for head neck nose and ears e Scarf for head and neck e Sunglasses with side panels for eyes and skin around eyes e Long sleeved top for upper body arms e Long trousers for lower body legs e Gloves for hands wrist and fingers e Socks for feet and ankles e Closed shoes for feet e Do not wear very thin clothing because it will not protect you from strong light e Wear dark closely woven clothing e If you expose yourself to light by mistake you may get a prickly or burning feeling on the skin You must get
46. round the treatment area e There may also be bleeding ulcers swelling and scarring e You may get constipation These effects may make it difficult to eat and drink Common side effects likely to occur in more than 1 in 100 patients e There may be some irritation a burning sensation or skin damage where Foscan is injected but this will not last long You may also get ulcers blisters skin redness or skin darkening vomiting fever nausea anaemia light sensitivity sunburn burns difficulty with swallowing giddiness There may be swelling or you may have a stiff jaw Some people may get an infection in the treated area If any of the side effects gets serious or if you notice any side effects not mentioned in this leaflet please tell your doctor or pharmacist 5 HOW TO STORE FOSCAN Keep out of the reach and sight of children Do not use after the expiry date which is stated on the label and the carton The expiry date refers to the last day of that month Foscan will be stored at the hospital pharmacy Do not store above 25 C Store in the original package in order to protect from light Once removed from its package this medicine must be used immediately Each vial is a single dose and any unused medicine must be discarded Medicines should not be disposed of via waste water or household waste These measures will help to protect the environment 41 6 FURTHER INFORMATION What Foscan contains T
47. s redness you should avoid direct sunlight for another 24 hours You can then repeat the test If there is no redness you can gradually increase your exposure to sunlight day by day Do not stay in the sunlight for more than 15 minutes the first time Most people will be able to go back to their normal routine by Day 22 On the first day after the skin test you can stay in direct sunlight for 15 minutes You can increase your exposure by another 15 minutes each day i e second day 30 minutes third day 45 minutes fourth day 60 minutes and so on If at any time you notice a prickly or burning feeling or see skin reddening after exposure to sun wait until this disappears before exposing your skin to light for this length of time again For 30 days following Foscan treatment avoid eye tests that use bright lights For 3 months following Foscan treatment avoid UV tanning beds Do not sunbathe For 6 months following Foscan treatment care should be taken to avoid direct prolonged sunlight exposure of the arm used for Foscan injection As a precautionary measure if prolonged outdoor activity is planned the injection arm should be protected by wearing long sleeved coloured clothing 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 c
48. se of 0 3 mg kg Animal studies have shown some haematological and blood chemistry changes decreased platelets erythrocytes and haemoglobin increased neutrophils fibrinogen bilirubin triglyceride and cholesterol Strict observance of the reduced light regime is required A skin photosensitivity test must be carried out before the patient returns to normal light conditions 14 No specific systemic symptoms are known to be associated with overdose Treatment should be supportive Limited information is available on the effects of overexposure to laser light during treatment Increased damage to tissue was noted 5 PHARMACOLOGICAL PROPERTIES 5 1 Pharmacodynamic properties Pharmacotherapeutic group Antineoplastic agents other antineoplastic agents ATC code LO1XDO5 Temoporfin is a photosensitising agent used in the photodynamic therapy of tumours The pharmacological activity is initiated by photoactivation of temoporfin with non thermal light at 652nm following intravenous administration The therapeutic effect is mediated through the generation of highly reactive oxygen species a process dependent on the intracellular interaction of temoporfin with light and oxygen In a clinical trial of 147 patients with advanced head and neck squamous cell carcinoma tumour response defined as a reduction of a minimum of 5046 of the tumour mass for a minimum of four weeks was observed in 2546 after a single treatment A WHO local compl
49. ssary 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 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 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 Clinicians must counsel patients to observe the following precautions that are provided in the Package Leaflet Time after Foscan Injection What should I do to prevent burns Day 1 0 24 Stay indoors in a darkened room Keep the curtains drawn and use light bulbs of hours 60W or less Avoid exposure to direct sunlight Days 2 7 You can gradually return to normal indoor lighting Remember to avoid direct sunlight coming through the window or direct light from household appliances such as reading lamps You may watch television You can go outdoors after dusk If it is absolutely necessary to go outdoors during the hours of daylight you must be careful to cover up all your skin including your face
50. t be taken when handling this medicinal product Studies have shown that Foscan is non irritant Each vial represents a single dose and any unused solution must be discarded Foscan is photosensitive Once removed from its packaging it must be administered immediately Where delay is unavoidable the solution must be protected from light Foscan shall not be diluted with aqueous solutions Any unused product or waste material should be disposed of in accordance with local requirements 7 MARKETING AUTHORISATION HOLDER biolitec pharma Itd United Drug House Magna Drive Dublin 24 Ireland 8 MARKETING AUTHORISATION NUMBER S EU 1 01 197 003 EU 1 01 197 004 EU 1 01 197 005 9 DATE OF FIRST AUTHORISATION RENEWAL OF THE AUTHORISATION Date of first authorisation 24 October 2001 Date of latest renewal 10 DATE OF REVISION OF THE TEXT Detailed information on this medicinal product is available on the website of the European Medicines Agency http www ema europa eu 1 NAME OF THE MEDICINAL PRODUCT Foscan 4 mg ml solution for injection 2 QUALITATIVE AND QUANTITATIVE COMPOSITION Each ml contains 4 mg of temoporfin Excipients Each ml contains 376 mg of ethanol anhydrous and 560 mg of propylene glycol For a full list of excipients see section 6 1 3 PHARMACEUTICAL FORM Solution for injection Dark purple solution 4 CLINICAL PARTICULARS 4 1 Therapeutic indications Foscan is indicated for the palliative trea
51. tensive volume of distribution is observed that is intermediate between total and extracellular body water Temoporfin does not concentrate in the tissues Plasma protein binding is at 85 8796 Temoporfin is bound to plasma lipoproteins and high density proteins such as albumin in the blood By 15 days post infusion temoporfin plasma concentration has declined to background such that patients are generally able to begin a gradual return to normal outdoor lighting conditions Limited data are available on the elimination of temoporfin in humans Animal data show temoporfin is exclusively eliminated by the liver into the bile and excreted in the faeces Two major metabolites of temoporfin are eliminated into the bile There is no enterohepatic recirculation of these metabolites Both these metabolites show conjugated character No metabolites are seen in the systemic circulation 5 3 Preclinical safety data In repeated dose toxicity studies in rats and dogs the main undesirable effects of temoporfin were phototoxicity and adverse injection site reactions Local irritancy of Foscan solution for injection after intravenous administration occurred with all doses High rates of administration caused death in dogs and rabbits No other signs of toxicity were found however in dogs treated with the recommended therapeutic dose systemic exposure exceeded that of humans The genotoxicity of temoporfin has been investigated to a limited extent Due to the gene
52. the effects of other medicines 3 HOW TO USE FOSCAN e Your doctor or nurse will give you Foscan by a slow injection into a vein which will take approximately 6 minutes e If necessary your doctor or nurse may give you another injection at least 4 weeks later e Four days after your injection your doctor will treat your cancer with laser light 31 If you are given more Foscan than you should e You may not be given the laser treatment e You may be sensitive to light for more than 15 days You must follow carefully the instructions on preventing skin burns 4 POSSIBLE SIDE EFFECTS Like all medicines Foscan can cause side effects although not everybody gets them e Everyone who takes Foscan will become sensitive to light for about 15 days after injection e You must follow the instructions given to you to avoid sunlight and bright indoor light e These instructions are written in this leaflet Your doctor will also tell you what to do If you do not follow these instructions you may get severe sunburn that leads to permanent scarring Very common side effects likely to occur in more than 1 in 10 patients e You may feel some pain when Foscan is injected e After the laser treatment you may feel pain in your face and pain around the treatment area e There may also be bleeding ulcers swelling and scarring e You may get constipation These effects may make it difficult to eat and drink Common side effects likely to oc
53. tment of patients with advanced head and neck squamous cell carcinoma failing prior therapies and unsuitable for radiotherapy surgery or systemic chemotherapy 4 2 Posology and method of administration Foscan photodynamic therapy must only be administered in specialist oncology centres in which a multidisciplinary team assesses patient treatment and under the supervision of physicians experienced in photodynamic therapy Posology The dose is 0 15mg kg body weight Paediatric population There is no relevant use of Foscan in the paediatric population Method of administration Foscan is administered via an in dwelling intravenous cannula in a large proximal limb vein preferably in the antecubital fossa as a single slow intravenous injection over not less than 6 minutes The patency of the in dwelling cannula should be tested before injection and every precaution taken against extravasation see section 4 4 The dark purple colour of the solution together with the amber vials makes a visual check for particulates impossible Thus an in line filter must be used as a precautionary measure and is provided in the package Foscan shall not be diluted nor flushed with sodium chloride or any other aqueous solution The required dose of Foscan is administered by slow intravenous injection over not less than 6 minutes 96 hours after the administration of Foscan the treatment site is to be illuminated with light at 652 nm from an approved las
54. you do not see any skin redness in the next 24 hours you can gradually increase your time outdoors during the week Avoid direct sunlight or strong indoor lighting Stay in the shade Day 15 onward Your sensitivity to light is gradually getting back to normal You must test this carefully by exposing the back of your hand to the sun for 5 minutes Wait 24 hours to see if there is any redness If there is redness you should avoid direct sunlight for another 24 hours You can then repeat the test If there is no redness you can gradually increase your exposure to sunlight day by day Do not stay in the sunlight for more than 15 minutes the first time Most 30 people will be able to go back to their normal routine by Day 22 On the first day after the skin test you can stay in direct sunlight for 15 minutes You can increase your exposure by another 15 minutes each day i e second day 30 minutes third day 45 minutes fourth day 60 minutes and so on If at any time you notice a prickly or burning feeling or see skin reddening after exposure to sun wait until this disappears before exposing your skin to light for this length of time again For 30 days following Foscan treatment avoid eye tests that use bright lights For 3 months following Foscan treatment avoid UV tanning beds Do not sunbathe For 6 months following Foscan treatment care should be taken to avoid direct prolonged sunlight exposure of the arm us
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