qanastek/EMEA-V3 huggingface dataset:
While the first study in occult disease showed some effectiveness, this was not confirmed by the second study, and the benefit of Visudyne in occult subfoveal choroidal neovascularisation has not been established.
Waqt li l- ewwel studju fuq il- marda okkulta wera xi effettività, dan ma kienx ikkonfermat mit- tieni studju, u l- benefiċċju ta ’ Visudyne f’ subfoveal choroidal neovascularisation okkulta ma ġiex stabbilit.
What is the risk associated with Visudyne?
X’ inhu r- riskju assoċjat ma ’ Visudyne?
The most common side effects with Visudyne (seen in between 1 and 10 patients in 100) are abnormal vision (blurry, hazy, fuzzy vision, flashes of light, decreased vision, grey or dark haloes, and black spots), reactions at the injection site (pain, swelling and inflammation), and infusion-related pain such as back pain, nausea (feeling sick), photosensitivity reactions (sunburn on skin areas exposed to light), asthenia (weakness) and hypercholesteraemia (high blood cholesterol).
L- iktar effetti sekondarji komuni b’ Visudyne (li dehru f’ bejn wieħed u għaxar pazjenti minn kull mija) huma vista anormali (vista mċajpra jew sfukata, leħħiet ta ’ dawl, vista mnaqqsa, ċrieki griżi jew skuri madwar l- oġġetti, u tikek suwed), reazzjonijiet fis- sit ta ’ l- injezzjoni (uġigħ, nefħa u infjammazzjoni), u uġigħ relatat ma ’ l- infużjoni bħal uġigħ fid- dar, dardir, reazzjonijiet ta ’ fotosensittività (ħruq fil - partijiet tal- ġilda esposti għad- dawl), astenja (dgħufija) u livell għoli ta ’ kolesterol fid- demm (hypercholesteraemia).
For the full list of side effects reported with Visudyne, see the Package Leaflet.
Għal- lista sħiħa ta ’ effetti mhux mixtieqa irrapportati ma ’ l- użu ta ’ Visudyne ara l- Fuljett ta ’ Tagħrif.
Visudyne should not be used in people who may be hypersensitive (allergic) to verteporfin or any of the other ingredients, in patients with porphyria (an inability to break down chemicals called porphyrins) or in patients with severe liver disease.
Visudyne m’ għandux jintuża minn persuni li jistgħu jkunu allerġiċi għal verteporfin jew għal xi sustanza oħra tiegħu, fil- pazjenti bil- porphyria (inabilità li jkissru kimiċi magħrufa bħala porphyrins) jew pazjenti b’ mard sever fil- fwied.
Why has Visudyne been approved?
Għaliex ġie approvat Visudyne?
The Committee for Medicinal products for Human Use (CHMP) decided that Visudyne’ s benefits are greater than its risks for the treatment of patients with subfoveal choroidal neovascularisation due to exudative age-related macular degeneration, when the lesions are predominantly classic, or due to pathological myopia.
Il- Kumitat għall- prodotti Mediċinali għal Użu mill- Bniedem (CHMP) iddeċieda li Visudyne għandu iktar benefiċċji milli riskji fit- trattament ta ’ pazjenti b’ subfoveal choroidal neovascularisation minħabba deġenerazzjoni makulari relatata ma ’ l- età tal- forma eżudativa (exudative), fejn il- leżjonijiet ikunu fil- biċċa l- kbira tagħhom klassiċi, jew minħabba mijopija patoloġika.
The Committee recommended that Visudyne be given marketing authorisation.
Il- Kumitat irrakkomanda li Visudyne jingħata awtorizzazzjoni għat- tqegħid fis- suq.
Other information about Visudyne:
Aktar tagħrif dwar Visudyne:
The European Commission granted a marketing authorisation valid throughout the European Union, for Visudyne to Novartis Europharm Limited on 27 July 2000.
Il- Kummissjoni Ewropea tat awtorizzazzjoni għat- tqegħid fis- suq valida madwar l- Unjoni Ewropea kollha għal Visudyne lil Novartis Europharm Limited fis- 27 ta ’ Lulju 2000.
The full EPAR for Visudyne is available here.
L- EPAR sħiħ dwar Visudyne huwa disponibbli minn hawnhekk.
This summary was last updated in 05-2007.
Dan is- sommarju ġie aġġornat l- aħħar f’ 05- 2007.
EU Number
Isem inventat Numru ta ’ l- EU
Powder for solution for infusion
Trab u solvent ghal soluzzjoni ghall - infużjoni
Intravenous use
Injezzjoni go vina
Glass vial
Kunjett tal - ħġieġ
1 x 10 ml vial
1 x 10 ml kunjett
Visudyne 15 mg powder for solution for infusion
Visudyne 15 mg trab għal soluzzjoni għall- infużjoni
Each vial contains 15 mg of verteporfin.
Kull kunjett fih 15 mg ta ’ verteporfin.
After reconstitution, 1 ml contains 2 mg of verteporfin.
Wara li jiġi mħallat, 1 ml ikun fih 2 mg ta ’ verteporfin.
7.5 ml of reconstituted solution contains 15 mg of verteporfin.
7. 5 ml tas- soluzzjoni mħallta jkun fiha 15 mg ta ’ verteporfin.
Dark green to black powder.
Trab aħdar skur għal iswed.
Visudyne is indicated for the treatment of
Visudyne jingħata għal kura ta ’
- patients with exudative (wet) age-related macular degeneration (AMD) with predominantly
- pazjenti b’ deġenerazzjoni makulari (AMD) relatata ma ’ l- età li tnixxi (imxarrba)
classic subfoveal choroidal neovascularisation (CNV) or
b’ neovaskularizzazzjoni korojdali subfoveali li hija prinċipalment klassika (CNV) jew,
- patients with subfoveal choroidal neovascularisation secondary to pathological myopia.
- pazjenti b’ neovaskularizzazzjoni korojdali subfoveali sekondarja għal mijopija patoloġika.
Visudyne should be used only by ophthalmologists experienced in the management of patients with age-related macular degeneration or with pathological myopia.
Visudyne għandu jinkiteb biss minn oftalmologi bl- esperjenza fil- maniġġar ta ’ pazjenti b’ deġenerazzjoni makulari marbuta ma ’ l- età jew ma ’ mijopija patoloġika.
Visudyne photodynamic therapy (PDT) is a two-step process:
It- terapija fotodinamika b’ Visudyne (PDT) hija proċess ta ’ żewġ stadji:
The first step is a 10-minute intravenous infusion of Visudyne at a dose of 6 mg/ m2 body surface area, diluted in 30 ml infusion solution (see section 6.6).
L- ewwel stadju huwa infużjoni minn ġol- vini għal 10 minuti ta ’ Visudyne b’ doża ta ’ 6 mg/ m2 erja tas - superfiċje tal- ġisem, miżjud bi 30 ml soluzzjoni għall- infużjoni (ara sezzjoni 6. 6).
The second step is the light activation of Visudyne at 15 minutes after the start of the infusion.
It- tieni stadju huwa l- attivazzjoni ta ’ Visudyne bid- dawl, 15 - il minuta wara l- bidu ta ’ l- infużjoni.
For this, a diode laser generating non-thermal red light (wavelength 689 nm ± 3 nm) is used via a slit lamp mounted fibre optic device and a suitable contact lens.
Għal dan, jintuża lejżer tad- dajowd li jiġġenera dawl aħmar mhux termali (wavelength 689 nm ± 3 nm) minn ġo strument tal- fibra ottika armat bi slit lamp, u lenti tal- kuntatt addattata.
At the recommended light intensity of 600 mW/ cm2, it takes 83 seconds to deliver the required light dose of 50 J/ cm2.
Bl- intensità irikmandata ta ’ 600 mW/ cm2, id- doża meħtieġa ta ’ dawl ta ’ 50 J/ cm2 tinlaħaq fi 83 sekonda.
The greatest linear dimension of the choroidal neovascular lesion is estimated using fluorescein angiography and fundus photography.
L- akbar dimensjoni lineari tal- leżjoni neovaskulari korojdali tiġi kkalkulata bl- użu ta ’ anġjografija permezz ta ’ sustanza fluworexxenti u fotografija tal- fundus.
Fundus cameras with a magnification within the range of 2.4 - 2.6X are recommended.
Kameras tal- fundus li jkabbru fil- medda ta ’ 2. 4– 2. 6 drabi huma rrikmandati.
The treatment spot should cover all neovasculature, blood and/ or blocked fluorescence.
Il- parti li se tiġi kkurata trid tkopri n- neovaskulatura kollha, id - demm, u/ jew il- fluworexxenza blukkata.
To ensure treatment of poorly demarcated lesion borders, an additional margin of 500 µm should be added around the visible lesion.
Biex tiġi żgurata l- kura ta ’ borduri ta ’ leżjonijiet mhux demarkati b’ mod ċar, wieħed għandu jżid marġni ta ’ 500 µm madwar il- leżjoni viżibbli.
The nasal edge of the treatment spot must be at least 200 μ m from the temporal edge of the optic disc.
Ix- xifer nażali tal- parti li se tiġi kkurata għandha tkun mill- anqas 200 μm mix- xifer temporali tad- diska optika.
The maximum spot size used for the first treatment in the clinical studies was 6,400 μ m.
Id - daqs massimu tal- parti kkurata wżata għall- ewwel trattament fl- istudji kliniċi kien 6, 400 μm.
For treatment of lesions that are larger than the maximum treatment spot size, apply the light to the greatest possible area of active lesion.
Għal kura ta ’ leżjonijiet akbar mid- daqs massimu, applika d- dawl għall- akbar erja possibbli ta ’ leżjoni attiva.
2 It is important to follow the above recommendations to achieve the optimal treatment effect.
2 Huwa importanti li ssegwi r- rikmandazzjonijiet ta ’ hawn fuq biex tikseb l- aqwa effett tal- kura.
Patients should be re-evaluated every 3 months.
Il- pazjenti għandhom jerġgħu jkunu eżaminati kull 3 xhur.
In the event of recurrent CNV leakage, Visudyne therapy may be given up to 4 times per year.
F’ każ ta ’ tnixxija rikorrenti tas- CNV, kura b’ Visudyne tista ’ tingħata sa 4 darbiet fis- sena.
Use in paediatric patients has not been investigated.
L- użu f’ pazjenti tfal ma ġiex investigat.
Visudyne is also contraindicated in patients with porphyria and in patients with severe hepatic impairment.
Visudyne huwa kontra- indikat ukoll f’ pazjenti b’ porfirja u f’ pazjenti b’ indeboliment epatiku qawwi.
Patients who receive Visudyne will become photosensitive for 48 hours after the infusion.
Pazjenti li qed jirċievu Visudyne isiru fotosensittivi għal 48 siegħa wara l- infużjoni.
During that period, patients should avoid exposure of unprotected skin, eyes or other body organs to direct sunlight or bright indoor light such as tanning salons, bright halogen lighting, or high power lighting in surgery operating rooms or dental surgeries.
Matul dak il - perijodu, il- pazjenti għandhom jevitaw espożizzjoni tal- ġilda, l- għajnejn jew organi oħra tal- ġisem li ma jkunux protetti mid- dawl tax- xemx dirett jew dawl qawwi ta ’ ġewwa bħal tanning salons, dawl aloġenu qawwi, jew dawl qawwi f’ kmamar ta ’ operazzjonijiet kirurġiċi jew f’ kmamar kliniċi tad - dentisti.
If patients have to go outdoors in daylight during the first 48 hours after treatment, they must protect their skin and eyes by wearing protective clothing and dark sunglasses.
Jekk il- pazjenti jkollhom joħorġu fid- dawl tax- xemx matul l- ewwel 48 siegħa ta ’ wara l- kura, jridu jipproteġu l- ġilda tagħhom u għajnejhom billi jilbsu ħwejjeġ protettiv u nuċċali tax- xemx skur.
UV sunscreens are not effective in protecting against photosensitivity reactions.
Is- sunscreens ma joffru l- ebda protezzjoni kontra reazzjonijiet ta ’ fotosensittività.
Ambient indoor light is safe.
Dawl ta ’ ġewwa normali mhux ta ’ periklu.
Patients should not stay in the dark and should be encouraged to expose their skin to ambient indoor light, as it will help eliminate the drug quickly through the skin by a process called photobleaching.
Il- pazjenti m’ għandhomx joqogħdu fid- dlam u għandhom ikunu nkoraġġiti li jesponu l- ġilda tagħhom għad- dawl normali ta ’ ġewwa, għax dan jgħin l - eliminazzjoni tal- mediċina minn ġol- ġilda malajr bi proċess imsejjaħ photobleaching.
Visudyne therapy should be considered carefully in patients with moderate hepatic impairment or biliary obstruction since no experience has been gained in these patients.
Kura b’ Visudyne għandha tiġi kkunsidrata b’ attenzjoni f’ pazjenti b’ indeboliment epatiku moderat jew imblukkar tal- marrara billi ma hemm l- ebda esperjenza f’ pazjenti bħal dawn.
Patients who experience a severe decrease of vision (equivalent to 4 lines or more) within one week after treatment should not be re-treated, at least until their vision has completely recovered to pre- treatment level and the potential benefits and risks of subsequent treatment have been carefully considered by the treating physician.
Pazjenti li jkollhom tnaqqis qawwi fil- vista (ekwivalenti għal 4 linji jew aktar) fi żmien ġimgħa mill - kura m’ għandhomx jerġgħu jiġu kkurati, għall- anqas sakemm il- vista tagħhom tkun irkuprat kompletament għall- livell ta ’ qabel il- kura u l- benefiċċji u r- riskji li jista ’ jkun hemm minn kura sussegwenti jkunu ġew meqjusa sew mit- tabib li qed jikkurahom.
Extravasation of Visudyne, especially if the affected area is exposed to light, can cause severe pain, inflammation, swelling, blistering or discoloration at the injection site.
Estravażjoni ta ’ Visudyne tista ’ toħloq uġigħ qawwi, infjammazzjoni, nefħa jew tibdil fil- lewn tal- parti fejn saret l- injezzjoni.
The relief of pain may require analgesic treatment.
Għas- serħan mill- uġigħ jista ’ jkun hemm bżonn kura bl- analġeżiċi.
If extravasation occurs, infusion should be stopped immediately.
Jekk ikun hemm estravażjoni, l- infużjoni għandha titwaqqaf minnufih.
Protect the affected area thoroughly from bright direct light until swelling and discoloration have disappeared, and put cold compresses on the injection site.
Ipproteġi sew il- parti affettwata minn dawl dirett qawwi sakemm jitilqu n- nefħa u t- tibdil fil- lewn, u poġġi pakkett kiesaħ (cold compressors) fuq is- sit ta ’ l- injezzjoni.
The largest possible arm vein, preferably the antecubital, should be used for the infusion and small veins in the back of the hand should be avoided.
Biex tiġi evitata l- estravażjoni, għandha tiġi stabbilita linja għal ġol- vina ta ’ fluss liberu IV qabel tibda l- infużjoni u l- linja għandha tkun immonitorjata. L- eħxen vina possibbli tad - driegħ, preferibbilment l- antekubitali, għandha tintuża għall- infużjoni u għandhom jiġu evitati vini rqaq fuq il- parti ta ’ wara ta ’ l- id.
Chest pain, vasovagal reactions and hypersensitivity reactions, which on rare occasions can be severe, have been reported.
Ġew irrappurtati episodji ta ’ uġigħ fis- sider, reazzjonijiet vażovagali nnifishom, u reazzjonijiet ta ’ sensittività eċċessiva, li f’ okkażjonijiet rari jistgħu jkunu qawwija.
Both vasovagal and hypersensitivity reactions are associated with general symptoms such as syncope, sweating, dizziness, rash, dyspnoea, flushing, and changes in blood pressure and heart rate.
Kemm reazzjonijiet vażovagali kif ukoll dawk ta ’ sensittività eċċessiva huma assoċjati ma ’ sintomi ġenerali bħal ħass ħażinijiet minn inżul tal- pressjoni, għaraq, sturdament, raxx, qtugħ ta ’ nifs, fwawar, u bidliet fil- pressjoni tad- demm u fit- taħbit tal- qalb.
Patients should be under close medical supervision during the Visudyne infusion.
Il- pazjenti għandhom ikunu taħt sorveljanza medika mill- qrib waqt l- infużjoni b’ Visudyne.
There are no clinical data on the use of Visudyne in anaesthetised patients.
Ma jeżisti l- ebda tagħrif kliniku dwar l- użu ta ’ Visudyne f’ pazjenti taħt il- loppju.
In sedated or anaesthetised pigs, a Visudyne dose significantly higher than the recommended dose in patients given as a bolus
Fi ħnieżer mogħtija l- kalmanti jew illuppjati, doża ta ’ Visudyne ogħla sew mid- doża rrikmandata għall- pazjenti, mogħtija bħala injezzjoni bolus ikkawżat effetti qawwija emodinamiċi fosthom il- mewt, x’ aktarx bħala riżultat ta ’ attivazzjoni komplementari.
3 injection caused severe haemodynamic effects including death, probably as a result of complement activation.
3 ma ġiex osservat fi ħnieżer f’ sensihom li ma kienux taħt kalmanti, jew fi speċi oħra inkluż il- bniedem.
Verteporfin at more than 5 times the expected maximum plasma concentration in treated patients, caused a low level of complement activation in human blood in vitro.
Meta Verteporfin qabeż b ’ 5 darbiet il- konċentrazzjoni massima fil- plażma mistennija f’ pazjenti kkurati, ikkawżat livell baxx ta ’ attivazzjoni komplimentari fid- demm tal- bniedem in vitro.
No clinically relevant complement activation was reported in clinical trials but anaphylactic reactions have been reported during post-marketing surveillance.
F’ studji kliniċi ma ġiex irrappurtat l- ebda attivazzjoni komplimentari klinikament relevanti imma kien hemm rapporti ta ’ reazzjonijiet anafilattiċi matul is- sorveljanza ta ’ wara li l- prodott tqiegħed fuq is- suq.
Patients should be under close medical supervision during the Visudyne infusion and caution should be exercised when Visudyne treatment under general anaesthesia is considered.
Il - pazjenti għandhom ikunu taħt superviżjoni medika stretta waqt l- infużjoni b’ Visudyne u għandha tittieħed kawtela meta tiġi kkunsidrata kura b’ Visudyne taħt loppju ġenerali.
There are no clinical data to support a concomitant treatment of the second eye.
Ma hemm l- ebda tagħrif kliniku li li jissostanzja kura konkomitanti tat- tieni għajn.
However, if treatment of the second eye is deemed necessary, light should be applied to the second eye immediately after light application in the first eye but no later than 20 minutes from the start of the infusion.
Madankollu, jekk kura fit- tieni għajn titqies meħtieġa, id- dawl għandu jiġi applikat fit- tieni għajn minnufih wara l - applikazzjoni tad- dawl fl- ewwel għajn imma mhux aktar tard minn 20 minuta mill- bidu ta ’ l- infużjoni.
No clinical experience is available in patients with unstable heart disease (class III or IV) or in patients with uncontrolled arterial hypertension.
Ma hemm l- ebda esperjenza klinika f’ pazjenti b’ mard tal- qalb instabbli (klassi III jew IV) jew f’ pazjenti bi pressjoni għolja arterjali mhux kkontrollata.
No specific drug-drug interaction studies have been conducted in humans.
Ma sarux studji ta ’ interazzjonijiet bejn mediċina u oħra fil- bniedem.
It is possible that concomitant use of other photosensitising agents (e. g. tetracyclines, sulphonamides, phenothiazines, sulfonylurea, hypoglycaemic agents, thiazide diuretics, and griseofulvin) could increase the potential for photosensitivity reactions.
Huwa possibbli li l- użu konkomitanti ta ’ aġenti oħra fotosensitizzanti (eż. tetracyclines, sulphonamides, phenothiazines, sulfonylurea, sustanzi ipogliċemiċi, dijuretiċi thiazide, u griseofulvin) jista ’ jżid il- potenzjal ta ’ reazzjonijiet ta ’ fotosensittività.
Pregnancy For verteporfin no clinical data on exposed pregnancies are available.
Tqala Għal verteporfin m’ hemmx tagħrif kliniku dwar l- użu waqt it- tqala.
Studies in animals have shown teratogenic effects in one species (rat) (see section 5.3).
Studji f’ annimali wrew effetti teratoġeniċi fi speċi wieħed (far) (ara sezzjoni 5. 3).
Visudyne should not be used during pregnancy unless clearly necessary (only if the benefit justifies the potential risk to the foetus).
Visudyne m’ għandux jintuża waqt it- tqala ħlief meta hemm bżonn ċar (f’ każ li l- benefiċċju jkun jagħmel tajjeb għar- riskju li jista ’ jkun hemm għall- fetu).
Lactation Verteporfin and its diacid metabolic are excreted in human milk in low amounts.
Treddigħ Verteporfin u l- metabolu biaċidu tiegħu jiġu eskretati fil- ħalib tal- mara f’ ammonti żgħar.
It should therefore not be administered to nursing mothers, or breast-feeding should be interrupted for 48 hours after administration.
Għalhekk m’ għandux jingħata lil nisa li jkunu qed ireddgħu, jew it- treddigħ għandu jieqaf għal 48 siegħa wara li jingħatalha.
Following Visudyne treatment, patients may develop transient visual disturbances such as abnormal vision, vision decrease, or visual field defects that may interfere with their ability to drive or use machines.
Wara kura b’ Visudyne, il- pazjenti jistgħu jiżviluppaw disturbi viżwali li jgħaddu, bħal vista mhux normali, tnaqqis fil- vista, jew difetti fil- kamp viżwali li jistgħu jinterferixxu mal- ħila tagħhom biex isuqu jew jużaw magni.
Patients should not drive or use machines as long as these symptoms persist.
Il- pazjenti m’ għandhomx isuqu jew jużaw magni sakemm jgħaddu dawn is - sintomi.
In clinical trials, the following adverse reactions were considered potentially related to Visudyne therapy.
Fi provi kliniċi, ir- reazzjonijiet avversi li ġejjin kienu kkunsidrati li jistgħu jkunu marbuta ma kura b’ Visudyne.
Ocular side effects:
Effetti oħra fuq l- għajnejn:
Common effects (1-10%):
Effetti komuni (1– 10%):
Abnormal vision such as blurry, hazy, fuzzy vision, or flashes of light, decreased vision, visual field defect such as grey or dark haloes, scotoma and black spots.
Vista mhux normali bħal sfukata, imċajpra, imżellġa, jew tberrieq ta ’ dawl, tnaqqis fil- vista, difett fil- kamp tal- viżjoni bħal ċrieki griżi jew skuri, skotoma u tikek suwed.
Severe vision decrease, equivalent to 4 lines or more, within seven days after treatment was reported in 2.1% of the verteporfin-treated patients in the placebo-controlled ocular Phase III clinical studies and in less than 1% of patients in uncontrolled clinical studies.
Kien irrappurtat tnaqqis qawwi fil- vista, ekwivalenti għal 4 linji jew aktar, fi żmien sebat ijiem fi 2. 1% tal- pazjenti kkurati b’ verteporfin fi studji kliniċi okulari ta ’ Fażi III ikkontrollati bi plaċebo u f’ anqas minn 1% tal- pazjenti fi studji kliniċi mhux ikkontrollati.
The event occurred mainly in patients 4 with occult only (4.9%) or minimally classic CNV lesions in patients with AMD and was not reported for placebo-treated patients.
4 irrappurtat f’ pazjenti li kienu fuq il- plaċebo.
Partial recovery of vision was observed in some patients.
Ġie osservat irkupru parzjali tal- vista f’ xi pazjenti.
Uncommon effects (0.1-1%):
Effetti mhux komuni (0. 1– 1%):
Retinal detachment (non-rhegmatogenous), subretinal/ retinal haemorrhage, vitreous haemorrhage.
Distakkament tar- retina (mhux regmatoġenu), emorraġija subretinali/ emorraġija fir- retina, emorraġija fil- vitreous humour.
Injection site side effects:
Effetti oħra fis- sit ta ’ l- injezzjoni:
Pain, oedema, inflammation, extravasation.
Uġigħ, edema, infjammazzjoni, estravażazzjoni.
Haemorrhage, discoloration, hypersensitivity.
Emorraġija, tibdil fil- lewn, sensittività eċċessiva.
Systemic side effects:
Effetti oħra sistemiċi:
Infusion-related pain primarily presenting as back pain, nausea, photosensitivity reaction, asthenia, hypercholesteraemia.
Uġigħ marbut ma ’ l- infużjoni li normalment jitfaċċa bħala uġigħ fid- dahar, dardir, reazzjoni ta ’ fotosensittività, astenja, iperkolesteremija.
Photosensitivity reactions (in 2.2% of patients and < 1% of Visudyne courses) occurred in the form of sunburn following exposure to sunlight, usually within 24 hours from Visudyne treatment.
Reazzjonijiet ta ’ fotosesittività (fi 2. 2% tal- pazjenti u < 1% ta ’ korsijiet ta ’ Visudyne) tfaċċaw taħt forma ta ’ ħruq bix- xemx wara espożizzjoni għad- dawl tax- xemx normalment fi żmien 24 siegħa mill - kura b’ Visudyne.
Such reactions should be avoided by compliance with the photosensitivity protection instructions given in section 4.4.
Reazzjonijiet bħal dawn għandhom jiġu evitati billi wieħed jimxi ma ’ l - istruzzjonijiet dwar protezzjoni minn fotosensittività mogħtija f’ sezzjoni 4. 4.
The higher incidence of back pain during infusion in the Visudyne group was not associated with any evidence of haemolysis or allergic reaction and usually resolved by the end of the infusion.
L- ogħla inċidenza ta ’ uġigħ fid- dahar waqt l- infużjoni fil- grupp ta ’ Visudyne ma kien marbut ma ’ l - ebda evidenza ta ’ emoliżi jew reazzjoni allerġika u normalment waqaf sat- tmiem ta ’ l- infużjoni.
Myocardial infarction has been reported, particularly in patients with previous cardiovascular history, sometimes within 48 hours after the infusion.
Infart mijokardijaku kien irrappurtat, l- aktar f’ pazjenti li kellhom problemi kardjovaskulari fil- passat, kultant fi żmien 48 siegħa wara l- infużjoni.
Pain, hypertension, hyperesthesia, fever.
Uġigħ, pressjoni għolja, iperesteżija, deni.
Rare undesirable effects in clinical trials (< 0.1%) or spontaneously reported during post-marketing surveillance included:
Effetti mhux mixtieqa li kienu rari fi provi kliniċi (< 0. 1%) jew rappurtati b’ mod spontanju matul is - sorveljanza ta ’ wara li l- prodott tpoġġa fuq is- suq:
Ocular side effects:
Effetti oħra okulari:
Retinal or choroidal vessel non-perfusion, retinal pigment epithelial tear.
Nuqqas ta ’ perfużjoni mill- vina retinali jew korojdali, tiċrit ta ’ l- epitilju tar- retina pigmentat.
Injection site side effects:
Effetti fuq is- sit mnejn tingħata l- injezzjoni:
Blistering.
Bżieżaq.
Vasovagal reactions and hypersensitivity reactions, which on rare occasions can be severe, have been reported.
Reazzjonijiet vażovagali u reazzjonijiet ta ’ sensittività eċċessiva, li f’ okkażjonijiet rari jistgħu jkunu qawwija.
General symptoms can include headache, malaise, syncope, sweating, dizziness, rash, urticaria, pruritus, dyspnoea, flushing, and changes in blood pressure and heart rate.
Sintomi ġenerali jistgħu jinkludu uġigħ ta ’ ras, ħass ħażin sinkope, għaraq, sturdament, raxx, urtikarja, ħakk, qtugħ ta ’ nifs, fwawar, u bidliet fil- pressjoni tad - demm u fir- rata tat- taħbit tal- qalb.
Infusion-related back and chest pain, which may radiate to other areas, including but not limited to, the pelvis, shoulder girdle or rib cage.
Uġigħ relatat mad- dahar u mas- sider, li jista ’ jinfirex għal postijiet oħra, inkluż iżda mhux limitat għall- pelvi, iċ- ċintura ta ’ l- ispallejn jew il- kustilji.
Most adverse reactions were mild to moderate and transient in nature.
Bosta reazzjonijiet avversi kienu minn ħfief sa moderati u ta ’ natura li jgħaddu.
Undesirable effects reported in patients with pathological myopia were similar to those reported in patients with AMD.
Effetti mhux mixtieqa rrappurtati f’ pazjenti b’ mijopija patoloġika kienu simili għal dawk rappurtati f’ pazjenti b’ AMD.
Overdose of drug and/ or light in the treated eye may result in non-selective non-perfusion of normal retinal vessels, with the possibility of severe vision decrease.
Doża eċċessiva ta ’ mediċina u/ jew dawl fl- għajn ikkurata jistgħu jwasslu għal nuqqas ta ’ selezzjoni u nuqqas ta ’ perfużjoni ta ’ vini normali tar- retina bil- possibiltà ta ’ tnaqqis qawwi fil- vista.
Overdose of the drug may result in the prolongation of the period during which the patient remains photosensitive.
Doża eċċessiva tal- mediċina tista ’ twassal għal titwil tal- perijodu li fih il- pazjent jibqa ’ fotosensittiv.
In such cases, the patient should prolong skin and eye protection from direct sunlight or bright indoor light for a period proportionate with the overdose given.
F’ każijiet bħal dawn, il- pazjent irid itawwal iż- żmien ta ’ protezzjoni tal- ġilda u ta ’ l- għajnejn mid - dawl tax- xemx dirett jew dawl ta ’ ġewwa qawwi għal perijodu fi proporzjon mad- doża eċċessiva mogħtija.
Verteporfin, also referred to as benzoporphyrin derivative monoacids (BPD-MA) consists of a 1:1 mixture of the equally active regioisomers BPD-MAC and BPD-MAD.
Verteporfin, magħruf ukoll bħala monoaċidi derivattivi ta ’ benzoporfirin (BPD- MA) jikkonsisti f ’ taħlita 1: 1 tar- reġjoiżomers attivi ndaqs BPD- MAC u BPD- MAD.
It is used as a light-activated drug (photosensitiser).
Jintuża bħala mediċina attivata b’ mod ħafif (fotosensibilizzatur).
By itself, the clinically recommended dose of verteporfin is not cytotoxic.
Waħidha, id- doża ta ’ verteporfin klinikament irrikmandata mhix ċitotossika.
It produces cytotoxic agents only when activated by light in the presence of oxygen.
Tipproduċi sustanzi ċitotossiċi biss meta tiġi attivata bid- dawl fil- preżenza ta ’ l- ossiġnu.
When energy absorbed by the porphyrin is transferred to oxygen, highly reactive short-lived singlet oxygen is generated.
Meta l- enerġija assorbita mill - porphyrin tgħaddi għall- ossiġnu, jiġi ġenerat ossiġnu singlet ta ’ ħajja qasira rejattiv ferm.
Singlet oxygen causes damage to biological structures within the diffusion range, leading to local vascular occlusion, cell damage and, under certain conditions, cell death.
L- Ossiġnu singlet jikkaġuna ħsara lil strutturi bijoloġiċi fejn jiġi diffuż, li twassal għal sadd vaskulari lokali, ħsara liċ- ċelluli u, f’ ċerti kundizzjonijiet, il- mewt taċ- celluli.
The selectivity of PDT using verteporfin is based, in addition to the localised light exposure, on selective and rapid uptake and retention of verteporfin by rapidly proliferating cells including the endothelium of choroidal neovasculature.
Is- selettività ta ’ PDT bl- użu ta ’ verteporfin hija bbażata, barra mill- espożizzjoni għad- dawl lokalizzat, fuq t- teħid u l- assorbiment selettiv u mgħaġġel u ritenzjoni ta ’ verteporfin minn ċelloli li jitkattru malajr inkluż l- endotelju ta ’ neovaskulatura korojdali.
Age-related Macular Degeneration with predominantly classic subfoveal lesions Visudyne has been studied in two randomised, placebo-controlled, double-masked, multicentre studies (BPD OCR 002 A and B or Treatment of Age-related Macular Degeneration with Photodynamic Therapy [TAP]).
Deġenerazzjoni Makulari marbuta ma ’ l- età b’ leżjonijiet subfoveali prinċipalment klassiċi Visudyne ġie studjat f’ żewġ studji randomised, ikkontrollati bi plaċebo, double- masked, u multiċentriċi (BPD OCR 002 A u B jew Kura ta ’ Deġenerazzjoni Makulari relatata ma ’ l- Età jew Terapija Fotodinamika [TAP]).
A total of 609 patients were enrolled (402 Visudyne, 207 placebo).
Ħadu sehem total ta ’ 609 pazjenti (402 Visudyne, 207 plaċebo).
The objective was to demonstrate the long-term efficacy and safety of photodynamic therapy with verteporfin in limiting the decrease in visual acuity in patients with subfoveal choroidal neovascularisation due to age-related macular degeneration.
L- għan kien li jintwerew l- effikaċja fit- tul u s- sigurta` ta ’ terapija fotodinamika b’ verteporfin biex jiġi llimitat it- tnaqqis ta ’ akutezza fil- vista f’ pazjenti b’ neovaskularizzazzjoni korojdali subfoveali ġejja minn deġenerazzjoni makulari marbuta ma ’ l- età.
The primary efficacy variable was responder rate, defined as the proportion of patients who lost less than 15 letters (equivalent to 3 lines) of visual acuity (measured with the ETDRS charts) at month 12 relative to baseline.
Il- varjant primarju ta ’ l- effikaċja kien ir- rata ta ’ rispons, definit bħala l- proporzjon ta ’ pazjenti li tilfu anqas minn 15– il ittra (ekwivalenti għal 3 linji) ta ’ l- akutezza viżwali (mkejla bit- tabelli ETDRS) fix - xahar numru 12 b’ relazzjoni mal- linja bażi.
The following inclusion criteria were considered for the treatment: patients older than 50 years of age, presence of CNV secondary to AMD, presence of classic lesion components in the CNV (defined as a well-demarcated area of the fluorescence on angiography), CNV located subfoveally (involved the geometric centre of the foveal avascular zone), area of classic plus occult CNV ≥ 50% of the total lesion surface, greatest linear dimension of the entire lesion ≤ 9 Macular Photocoagulation Study (MPS) disc area, and a best-corrected visual acuity between 34 and 73 letters (i. e. approximately 20/ 40 and 20/ 200) in the treated eye.
Ġew ikkunsidrati għall- kura l- kriterji ta ’ inklużjoni li ġejjin: pazjenti li għandhom aktar minn 50 sena, preżenza ta ’ CNV sekondarja għall- AMD, preżenza ta ’ komponenti klassiċi ta ’ leżjoni ta ’ CNV (definita bħala parti demarkata sew tal- fluworexxenza fuq l- anġjografija), CNV li tkun fuq il- foveja (li tinvolvi iċ- ċentru ġeometriku taż- żona avaskulari fovejali), erja ta ’ CNV klassika u okkulta ≥ 50% tas- superfiċje totali tal- leżjoni, l- akbar dimensjoni linjari tal- leżjoni kollha ≤ 9 erja tad- diska ta ’ l - Istudju ta ’ Fotokoagulazzjoni Makulari (MPS), u l- aqwa korrezzjoni fl- akutezza viżwali bejn 34 u 73 ittra (i. e. bejn wieħed u ieħor 20/ 40 u 20/ 200) fl- għajn ikkurata.
Presence of occult CNV lesions (fluorescence not well demarcated on the angiogram) was allowed.
Ġiet aċċettata preżenza ta ’ leżjonijiet okkulti tas- CNV (fluworexxenza mhux demarkata sew fuq l- anġjogramma).
Results indicate that, at 12 months, Visudyne was statistically superior to placebo in terms of the proportion of patients responding to the treatment.
Ir- riżultati jindikaw li, fit- 12– il xahar, Visudyne kien statistikament superjuri għall- plaċebo f’ termini tal- proporzjon ta ’ pazjenti li rrispondew għall- kura.
The studies showed a difference of 15% between treatment groups (61% for Visudyne-treated patients compared to 46% placebo-treated patients, p < 0.001, ITT analysis).
L- istudji wrew differenza ta ’ 15% bejn il- gruppi li ħadu t- trattament (61% għal pazjenti kkurati b’ Visudyne imqabbla ma ’ 46% tal- pazzjenti trattati bi plaċebo, p < 0. 001, analiżi ITT).
This 15% difference between treatment groups was confirmed at 24 months (53% Visudyne versus 38% placebo, p < 0.001).
Din id- differenza ta ’ 15%, bejn il- gruppi li ħadu t- trattament ġiet ikkonfermata wara l- 24 xahar (53% Visudyne kontra 38% plaċebo, p < 0. 001).
The subgroup of patients with predominantly classic CNV lesions (N=243; Visudyne 159, placebo 84) were more likely to exhibit a larger treatment benefit.
Is- sottogrupp ta ’ pazjenti b’ leżjonijiet CNV prinċipalment klassiċi (N=243; Visudyne 159, plaċebo 84) kellhom aktar tendenza li jieħdu benefiċċju akbar mill- kura.
After 12 months, these patients showed a difference of 28% between treatment groups (67% for Visudyne patients compared to 39% for placebo patients, p < 0.001); the benefit was maintained at 24 months (59% versus 31%, p < 0.001).
Wara 12- il xahar, dawn il- pazjenti wrew differenza ta ’ 28% bejn il- gruppi ttrattati (67% għal pazjenti kkurati b’ Visudyne imqabbla ma ’ 39% tal- pazjenti li ħadu l- plaċebo, p < 0. 001); Il- benefiċċju dam għall- 24 xahar (59% kontra 31%, p < 0. 001).
6 In relation to TAP extension:
B’ relazzjoni ma ’ l- estenzjoni TAP:
In patients followed from month 24 onwards and treated with uncontrolled, open-label Visudyne treatment as needed, long-term extension data suggest that month-24 vision outcomes may be sustained for up to 60 months.
6 meħtieġ, dejta mill- estenzjoni fit- tul tindika li r- riżultati fil- vista mar- 24 xahar jistgħu jinżammu sa 60 xahar.
In the TAP study in all lesion types, the average number of treatments per year were 3.5 in the first year after diagnosis and 2.4 in the second for the randomised placebo-controlled phase and 1.3 in the third year, 0.4 in the fourth and 0.1 in the fifth year for the open-label extension phase.
Fl- istudju TAP fit- tipi kollha ta ’ leżjonijiet, in- numru ta ’ kuri fis- sena kienu 3. 5 fl- ewwel sena wara d - dijanjosi u 2. 4 fit- tieni għal- fażi randomised kontrollata bi plaċebo u 1. 3 fit- tielet sena, 0. 4 fir- raba ’ u 0. 1 fil- ħames sena għall- fażi ta ’ l- estenzjoni open- label.
No additional safety concern was identified.
Ma ġiex identifikat xi tħassib ieħor dwar is- sigurtà.
Age-related Macular Degeneration with occult with no classic lesions The benefit of the product in the AMD patient population who have occult subfoveal CNV with evidence of recent or ongoing disease progression has not been demonstrated consistently.
Deġenerazzjoni Makulari relatata ma ’ l- età b’ okkult mingħajr leżjonijiet klassiċi Il- benefiċċju tal- prodott f’ popolazzjoni ta ’ pazjenti b’ AMD li għandhom CNV subfovejali okkult, b’ evidenza ta ’ progressjoni tal- marda reċenti jew kurrenti ma ntwerietx b’ mod konsistenti.
Two randomised, placebo-controlled, double-masked, multicentre, 24-month studies (BPD OCR 003 AMD, or Verteporfin in Photodynamic Therapy-AMD [VIP-AMD], and BPD OCR 013, or Visudyne in Occult Choroidal Neovascularisation [VIO]) were conducted in patients with AMD characterised by occult with no classic subfoveal CNV.
Fil- fatt, saru żewġ studji randomised, ikkontrollati bi plaċebo, double- masked, multiċentriċi li damu 24 xahar (BPD OCR 003 AMD jew Verteporfin f’ Terapija Fotodinamika - AMD [VIP- AMD] u BPD OCR 013 jew Visudyne Neovaskularizzazzjoni Korojdali Okkulta [VIO]) saru f’ pazjenti b’ AMD ikkaratterizzata minn CNV okkult bla ebda CNV subfoveali klassiku.
The VIO study included patients with occult with no classic subfoveal CNV with a visual acuity score of 73-34 letters (20/ 40-20/ 200), and patients with lesions > 4 MPS disc areas were to have baseline visual acuity < 65 letters (< 20/ 50).
L- istudju VIO, kien jinkludi pazjenti b’ okkult mingħajr CNV subfovejali klassiku b’ punteġġ fl - akutezza viżwali ta ’ 73- 34 ittra (20/ 40- 20/ 200) u pazjenti b’ leżjonijiet > 4 MPS erjas tad- disk kellu jkollhom akutezza viżwali ta ’ < 65 ittra (< 20/ 50).
364 patients (244 verteporfin, 120 placebo) were enrolled in this study.
364 pazjent (244 verteporfin, 120 plaċebo) ħadu sehem f’ dan l- istudju.
The primary efficacy parameter was the same as in TAP (see above), with an additional endpoint of month 24 defined.
Il- parametru ta ’ l- effikaċja ewlieni kien l- istess bħal f’ TAP (ara hawn fuq), b’ fini ieħor li kien definit f’ xahar 24.
Another efficacy parameter was also defined: the proportion of patients who lost less than 30 letters (equivalent to 6 lines) of visual acuity at months 12 and 24 relative to baseline.
Parametru ta ’ l- effikaċja ieħor kien definit ukoll: il- proporzjon ta ’ pazjenti li tilfu anqas minn 30 ittra (ekwivalenti għall- 6 linji) fl- akutezza viżwali f’ xahar 12 u 24 meta mqabbel mal- linja bażi.
The study did not show statistically significant results on the primary efficacy parameter at month 12 (15-letter responder rate 62.7% versus 55.0%, p=0.150; 30-letter responder rate 84.0% versus 83.3%, p=0.868) or at month 24 (15-letter responder rate 53.3% versus 47.5%, p=0.300; 30- letter responder rate 77.5% versus 75.0%, p=0.602).
Dan l- istudju ma weriex riżultati statistikament sinfikanti fuq il - parametru ta ’ l- effikaċja ewlieni f’ xahar 12 (15- il ittra b’ rata ta ’ rispons ta ’ 62. 7% kontra 55. 0%, p=0. 150; 30 ittra b’ rata ta rispons ta ’ 84. 0% kontra 83. 3%, p=0. 868) jew f’ xahar 24 (15- il ittra b’ rata ta ’ rispons ta ’ 53. 3% kontra 47. 5%, p=0. 300; 30 ittra b’ rata ta rispons ta ’ 77. 5% kontra 75. 0%, p=0. 602).
A higher percentage of patients who received Visudyne, compared with those who received placebo, experienced adverse events (88.1% versus 81.7%), associated adverse events (23.0% versus 7.5%), events leading to discontinuation (11.9% versus 3.3%) and events leading to death (n=10 [4.1%] versus n=1 [0.8%]).
Perċentwali ogħla ta ’ pazjenti li rċievew Visudyne meta mqabbel mal- plaċebo, kellhom każijiet avversi (88. 1% kontra 81. 7%), assoċjat ma ’ każijiet avversi (23. 0% kontra 7. 5%), każijiet li wasslu għat twaqqif (11. 9% kontra 3. 3%) u każijiet li wasslu għall- mewt (n=10 [4. 1%] kontra n=1 [0. 8%]).
No death was considered to be related to treatment.
L- ebda mewta ma kienet meqjusa bħala relata mal- kura.
The VIP-AMD included patients with occult with no classic subfoveal CNV with a visual acuity score of > 50 letters (20/ 100).
Il- VIP- AMD kien jinkludi pazjenti b’ okkult mingħajr CNV subfovejali klassiku b’ punteġġ ta ’ akutezza viżwali ta ’ > 50 ittra (20/ 100).
This study also included patients with classic containing CNV with a visual acuity score > 70 letters (20/ 40).
Dan l- istudju kien jinkludi wkoll pazjenti li kellhom punteġġ ta ’ akutezza viżwali ta ’ > 70 ittra (20/ 40).
339 patients (225 verteporfin, 114 placebo) were enrolled in this study.
339 pazjent (225 verteporfin, 114 plaċebo) ħadu sehem f’ dan l- istudju.
The efficacy parameter was the same as in TAP and VIO (see above).
Il- parametru ta ’ l- effikaċja kien l- istess bħal f’ TAP and VIO (ara hawn fuq).
At month 12, the study did not show statistically significant results on the primary efficacy parameter (responder rate 49.3% versus 45.6%, p=0.517).
Fit - 12- il xahar, l- istudju ma weriex riżultati statistikament sinifikanti fuq il- parametru primarju ta ’ l - effikaċja (rata ta ’ rispons 49. 3% kontra 45. 6%, p=0. 517).
At month 24, a statistically significant difference of 12.9% in favour of Visudyne compared to placebo was observed (46.2% versus 33.3%, p=0.023).
Fl- 24 xahar, ġiet osservata differenza statistikament sinifikanti ta ’ 12. 9% favur Visudyne imqabbel ma ’ plaċebo (46. 2% kontra 33. 3%, p=0. 023).
A group of patients who had occult with no classic lesions (n=258) showed a statistically significant difference of 13.7% in favour of Visudyne compared to placebo (45.2% versus 31.5%, p=0.032).
Grupp ta ’ pazjenti li kellhom leżjonijiet okkulti iżda mhux klassiċi (n=258), urew differenza statistikament sinifikanti ta ’ 13. 7% favur Visudyne imqabbel ma ’ plaċebo (45. 2% kontra 31. 5%, p=0. 032).
A higher percentage of patients who received Visudyne, compared with those who received placebo, experienced adverse events (89.3% versus 82.5%), associated adverse events (42.7% versus 18.4%) and events leading to discontinuation (6.2% versus 0.9%).
Perċentwali ogħla ta ’ pazjenti li rċevew Visudyne, meta mqabbel ma’ dawk li rċevew plaċebo, kellhom każijiet avversi (89. 3% kontra 82. 5%), każijiet avversi relatati (42. 7% kontra 18. 4%) u każijiet li wasslu għat- twaqqif (6. 2% kontra 0. 9%).
A lower percentage of Visudyne patients had events leading to death (n=4 [1.8%] versus n=3 [2.6%]); no death was considered to be related to treatment.
Perċentwali aktar baxx ta ’ pazjenti b’ Visudyne kellhom każijiet li wasslu għall- mewt (n=4 [1. 8%] kontra n=3 [2. 6%]); l- ebda mewta ma kienet meqjusa relatata mal- kura.
Pathological myopia One multicentre, double-masked, placebo-controlled, randomised study (BPD OCR 003 PM [VIP- PM]) was conducted in patients with subfoveal choroidal neovascularisation caused by pathological myopia.
7 Mijopja patoloġika Studju multiċentrat, double- masked, ikkontrollat bi plaċebo, randomised (BPD OCR 003 PM [VIP - PM]) sar fuq pazjenti b’ neovaskularizzazzjoni korojdali subfoveali kkawżata minn mijopija patoloġika.
A total of 120 patients (81 Visudyne, 39 placebo) were enrolled in the study.
Fl- istudju ħadu sehem total ta ’ 120 pazjent (81 Visudyne, 39 plaċebo).
The posology and retreatments were the same as in the AMD studies.
Il- pożoloġija u trattamenti mill- ġdid kienu l- istess bħal fl- istudji ta ’ l- AMD.
7 At month 12, there was a benefit of Visudyne for the primary efficacy endpoint (percentage of patients who lost less than 3 lines of visual acuity) – 86% for Visudyne versus 67% for placebo, p=0.011.
(perċentwal ta ’ pazjenti li tilfu anqas minn 3 linji ta ’ l- akutezza viżwali) – 86% għal Visudyne kontra 67% għal plaċebo, p=0. 011.
The percentage of patients who lost less than 1.5 lines was 72% for Visudyne and 44% for placebo (p=0.003).
Il- perċentwal ta ’ pazjenti li tilfu anqas minn 1. 5 linji kien 72% għal Visudyne u 44% għal plaċebo (p=0. 003).
At month 24, 79% Visudyne patients versus 72% placebo patients had lost less than 3 lines of visual acuity (p=0.38).
Fl- 24 xahar, 79% tal- pazjenti kkurati b’ Visudyne kontra 72% tal- pazjenti kkurati bi plaċebo kienu tilfu anqas minn 3 linji ta ’ akutezza viżwali (p=0. 38).
The percentage of patients who lost less than 1.5 lines was 64% for Visudyne and 49% for placebo (p=0.106).
Il- perċentwal ta ’ pazjenti li tilfu anqas minn 1. 5 linji kien 64% għal Visudyne u 49% għal plaċebo (p=0. 106).
This indicates that clinical benefit may diminish over time.
Dan jindika li l- benefiċċju kliniku jista ’ jonqos biż- żmien.
In relation to VIP-PM extension:
B’ relazzjoni ma ’ l- estenzjoni VIP- PM:
In patients followed from month 24 onwards and treated with uncontrolled, open-label Visudyne treatment as needed, long-term extension data suggest that month-24 vision outcomes may be sustained for up to 60 months.
Fil- pazjenti segwiti minn xahar 24 ’ l quddiem u kkurati b’ Visudyne open- label mingħajr il- kontroll kif meħtieġ, dejta ta ’ l- estenzjoni fit- tul tindika li r- riżultati tal- vista ma ’ xahar 24 jistgħu jinżammu sa 60 xahar.
In the VIP-PM study in pathological myopia, the average number of treatments per year were 3.5 in the first year after diagnosis and 1.8 in the second for the randomised placebo-controlled phase and 0.4 in the third year, 0.2 in the fourth and 0.1 in the fifth year for the open-label extension phase.
Fl- istudju VIP- PM f’ mijopja farmakoloġika, in- numru medju ta ’ kuri fis- sena kien 3. 5 fl- ewwel sena wara d- dijanjosi u 1. 8 fit- tieni għall- fażi randomised kontrollata bi plaċebo u 0. 4 fit- tielet sena, 0. 2 fir - raba ’ u 0. 1 fil- ħames għall- fażi ta ’ l- estenzjoni open- label.
Distribution Cmax after a 10-minute infusion of 6 and 12 mg/ m2 body surface area in the target population is approximately 1.5 and 3.5 µg/ ml, respectively.
Distribuzzjoni Cmax wara infużjoni ta ’ 10 minuti ta ’ 6 u 12 mg/ m2 erja tas- superfiċje tal- ġisem fil- popolazzjoni indirizzata hija bejn wieħed u ieħor 1. 5 u 3. 5 µg/ ml, rispettivament.
These values are somewhat higher (26% for the proposed dose of 6 mg/ m2) than those observed in young healthy volunteers and may result in a higher exposure.
Dawn il- valuri huma kemmxejn ogħla (26% għad- doża proposta ta ’ 6 mg/ m2) minn dawk osservati f’ voluntiera żgħar b’ saħħithom u jistgħu jirriżultaw f’ espożizzjoni ogħla.
The clinical relevance of this age-related difference is remote, as the risk/ benefit assessment determined in the target population is favourable.
Ir- relevanza klinika ta ’ din id- differenza marbuta ma ’ l- età hija remota, billi l- kejl tar- riskji/ benefiċċji determinat fil- popolazzjoni indirizzata huwa favorevoli.
A maximum 2-fold inter-individual variation in plasma concentrations at Cmax (immediately after end of the infusion) and at the time of light administration was found for each Visudyne dose administered.
Il- massimu ta ’ din il- varjazzjoni kien iddoppju.
For both regioisomers, Cmax and AUC values were proportional to dose.
Għaż- żewġ reġjoiżomers, il- valuri ta ’ Cmax u l- AUC kienu fi proporzjon mad- doża.
Cmax values obtained at the end of infusion were higher for BPD-MAD than for BPD-MAC.
Il- valuri ta ’ Cmax miksuba fl- aħħar ta ’ l- infużjoni kienu ogħla għal BPD- MAD milli għal BPD- MAC.
The volume of distribution was 0.5 l/ kg.
Il- volum ta ’ distribuzzjoni kien 0. 5 l/ kg.
Protein-binding In whole human blood, 90% of verteporfin is associated with plasma and 10% associated with blood cells, of which very little was membrane associated.
Twaħħil mal- proteini Fid- demm komplet uman, 90% ta ’ verteporfin jassoċja mal- plażma u 10% jassoċja maċ- ċelluli tad - demm, li minnu ammont żgħir ħafna assoċja mal- membrana.
In human plasma, 90% of verteporfin is associated with plasma lipoprotein fractions and approximately 6% are associated with albumin.
Fil- plażma tal- bniedem, 90% ta ’ verteporfin jassoċja ma ’ porzjonijiet ta ’ lipoproteina tal- plażma u bejn wieħed u ieħor 6% jassoċja ma ’ l- albumina.
Metabolism The ester group of verteporfin is hydrolysed via plasma and hepatic esterases, leading to the formation of benzoporphyrin derivative diacid (BPD-DA).
Metaboliżmu Il- grupp ta ’ l- ester ta ’ verteporfin huwa idrolizzat permezz ta ’ l- esterases tal- plażma u epatiċi, li jwassal għall- formazzjoni ta ’ diacid idderivat minn benzoporphyrin (BPD- DA).
BPD-DA is also a photosensitiser but its systemic exposure is low (5-10% of the verteporfin exposure, suggesting that most of the drug is eliminated unchanged).
BPD- DA huwa wkoll fotosensitizzatur imma l- espożizzjoni sistemika tiegħu hija baxxa (5– 10% ta ’ l- espożizzjoni ta ’ verteporfin, li jissuġġerixxi li ħafna mill- mediċina hija eliminata mhux midbula).
In vitro studies did not show any significant involvement of oxidative metabolism by cytochrome P450 enzymes.
Studji in vitro ma wrew l- ebda involviment sinifikanti ta ’ metaboliżmu ossidattiv minn enzimi tas- cytochrome P450.
Elimination Plasma elimination half-life mean values ranged from approximately 5– 6 hours for verteporfin.
8 Eliminazzjoni Valuri medji tal- half- life ta ’ l- eliminazzjoni tal- plażma varjaw minn bejn wieħed u ieħor 5– 6 sigħat għal verteporfin.
The mean area-under-the-curve (AUC) values for subjects with mild hepatic dysfunction were up to 1.4 times greater than those for subjects with normal hepatic function.
Il- valuri ta ’ l- erja medja taħt- il- kurva (AUC) għal individwi b’ funzjoni epatika mhux normali b’ mod ħafif kienu sa 1. 4 darbiet akbar minn dawk b’ funzjoni epatika normali.
This difference is not clinically relevant and does not require any dose adjustment in patients with mild hepatic impairment.
Din id- differenza mhix klinikament relevanti u ma titlob l- ebda tibdil fid- doża f’ pazjenti b’ indeboliment epatiku ħafif.
8 Combined excretion of verteporfin and BPD-DA in human urine was less than 1%, suggesting biliary excretion.
Tneħħija ta ’ verteporfin u BPD- DA flimkien fl- awrina tal- bniedem kienet anqas minn 1%, li jissuġġerixxi tneħħija mill- marrara.
In repeat-dose studies in rats and dogs (once per day without light for up to 4 weeks), mild extravascular haemolysis and haematopoietic responses were seen with exposure greater than approximately 70 times (rats) and 32 times (dogs) the exposure (based on AUC) of the recommended human dose.
Fi studji ta ’ dożi ripetuti f’ firien u klieb (darba kuljum bla dawl sa 4 ġimgħat), ġew osservati reazzjonijiet ta ’ emoliżi estravaskulari ħafifa u ematopoetiċi b’ espożizzjoni akbar minn madwar 70 darba (firien) u 32 darba (klieb) l- espożizzjoni (ibbażata fuq l- AUC) tad- doża rrikmandata għall - bnedmin.