qanastek/EMEA-V3 huggingface dataset:
In these study populations, mean additional reductions of supine systolic and diastolic blood pressure of 7/ 7 mmHg, 9/ 5 mmHg, and 8/ 4 mmHg, respectively, and mean additional reductions of standing blood pressure of 6/ 6 mmHg, 11/ 4 mmHg, and 4/ 5 mmHg, respectively were observed.
F’ dawn il- popolazzjonijiet ta ’ l- istudju, ġie osservat tnaqqis addizzjonali medju fil- pressjoni supine systolic u l- pressjoni diastolic ta ’ 7/ 7 mmHg, 9/ 5 mmHg u 8/ 4 mmHg, rispettivament, u tnaqqis addizzjonali medju fil- pressjoni tad- demm bil - wieqfa ta ’ 6/ 6 mmHg, 11/ 4 mmHg u 4/ 5 mmHg rispettivament.
When sildenafil and doxazosin were administered simultaneously to patients stabilized on doxazosin therapy, there were infrequent reports of patients who experienced symptomatic postural hypotension.
Meta sildenafil u doxazosin ġew amministrati flimkien lil pazjenti stabilizzati fuq doxazosin, kien hemm rapporti mhux frekwenti ta ’ pazjenti li esperjenzaw sintomi ta ’ pressjoni baxxa minħabba l- pożizzjoni.
These reports included dizziness and lightheadedness, but not syncope.
Dawn ir- rapporti jinkludu sensazzjoni ta ’ sturdament qawwi u ta ’ sturdament ħafif, imma mhux sinkope.
Concomitant administration of sildenafil to patients taking alpha- blocker therapy may lead to symptomatic hypotension in susceptible individuals (see section 4.4).
Għoti fl- istess ħin ta ’ sildenafil lil pazjenti li qed jieħdu terapija ta ’ alpha- blockers jista ’ jwassal għal tnaqqis fil pressjoni f’ persuni suxxettibbli (ara sezzjoni 4. 4).
Sildenafil (100 mg single dose) did not affect the steady state pharmacokinetics of the HIV protease inhibitor saquinavir, which is a CYP3A4 substrate/ inhibitor.
Sildenafil (100 mg) ma affettwax il- farmakokinetiċi fi stat fiss ta ’ l- inibitur ta ’ HIV protease, saquinavir, li huwa sustrat/ inibitur ta ’ CYP3A4.
Consistent with its known effects on the nitric oxide/ cGMP pathway (see section 5.1), sildenafil was shown to potentiate the hypotensive effects of nitrates, and its co-administration with nitric oxide donors or nitrates in any form is therefore contraindicated (see section 4.3).
Konsistenti ma ’ l- effetti magħrufa tiegħu fuq il- pathway nitric oxide / cGMP (ara sezzjoni 5. 1), sildenafil intwera li jsaħħaħ l- effetti ipotensivi tan- nitrati, u għalhekk il- ko- amministrazzjoni tiegħu ma ’ donaturi ta ’ nitric oxide jew nitrati f’ xi forma oħra hija kontra- indikata (ara sezzjoni 4. 3).
Sildenafil had no clinically significant impact on the plasma levels of oral contraceptives (ethinyloestradiol 30 μ g and levonorgestrel 150 μ g).
Sildenafil ma kellu l- ebda effett klinikament sinifikanti fuq il- livelli tal- plażma ta ’ kontraċettivi orali (ethinyloestradiol 30 μg u levonorgestrel 150 μg).
There are no data from the use of sildenafil in pregnant women.
M’ hemm l- ebda tagħrif fuq l- użu ta ’ sildenafil f’ nisa tqal.
Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy and embryonal/ foetal development.
Studji fuq l- annimali ma jurux effetti ħżiena diretti jew indiretti fuq it- tqala, fuq l- iżvilupp ta 'l- embriju/ fetu.
Studies in animals have shown toxicity with respect to postnatal development (see section 5.3).
Studji fl- annimali wrew tossiċità fir - rigward ta ’ l- iżvilupp wara t- twelid (ara sezzjoni 5. 3).
Due to lack of data, Revatio should not be used in pregnant women unless strictly necessary.
Minħabba in- nuqqas ta ’ tagħrif, Revatio m’ għandux jintuża f’ nisa tqal sakemm dan ma jkunx assolutament neċessarju.
It is not known whether sildenafil enters the breast milk.
M’ huwiex magħruf jekk sildenafil jgħaddix fil- ħalib tas- sider.
Revatio should not be administered to breast- feeding mothers.
Revatio m’ għandux jingħata lil nisa li qed ireddgħu.
As dizziness and altered vision were reported in clinical trials with sildenafil, patients should be aware of how they might be affected by Revatio, before driving or operating machinery.
Minħabba li ġew rappurtati sturdament u viżjoni mibdula fi provi kliniċi b’ sildenafil, il- pazjenti għandhom ikunu konxji ta ’ kif jirreaġġixxu għal Revatio, qabel ma jsuqu jew iħaddmu xi magni.
In the pivotal placebo-controlled study of Revatio in pulmonary arterial hypertension, a total of 207 patients were treated with Revatio at daily doses ranging from 20 mg to 80 mg three times a day and 70 patients were treated with placebo.
Fl- istudju ewlieni ikkontrollat bi plaċebo ta ’ kif jaħdem Revatio fuq pressjoni għolja arterjali tal - pulmun, total ta ’ 207 pazjent ġew trattati b’ Revatio f’ doża ta ’ ġurnata li tvarja minn 20 mg għal 80 mg tlett darbiet kuljum u 70 pazjent li ġew trattati bi plaċebo.
The duration of treatment was 12 weeks.
It- tul tat- trattament kien ta ’ 12- il ġimgħa.
259 subjects who completed the pivotal study entered a long-term extension study.
259 suġġett li temmew l- istudju pivitali daħlu f’ estensjoni ta ’ l- istudju għal perijodu ta ’ żmien twil.
Doses up to 80 mg three times a day (4 times the recommended dose of 20 mg three times a day) were studied (N=149 patients treated for at least 1 year, 101 on 80 mg three times a day).
Dożi sa 80 mg tlett darbiet kuljum (4 darbiet id- doża rakkomandata ta ’ 20 mg tlett darbiet kuljum) ġew studjati (N=149 pazjent trattati ta ’ l- inqas għal sena, 101 fuq 80 mg tlett darbiet kuljum).
The overall frequency of discontinuation in sildenafil treated patients at the recommended daily dose of 20 mg three times a day (2.9%) was low and the same as placebo (2.9%).
Il- frekwenza totali ta ’ pazjenti li waqqfu t- trattament b’ sildenafil fid- dożi rakkomandati ta ’ 20 mg tlett darbiet kuljum (2. 9%) kienet waħda baxxa u l- istess jista ’ jingħad għall- plaċebo (2. 9%).
7 In a placebo-controlled study of Revatio as an adjunct to intravenous epoprostenol in pulmonary arterial hypertension, a total of 134 patients were treated with Revatio (in a fixed titration starting from 20 mg, to 40 mg and then 80 mg, three times a day) and epoprostenol, and 131 patients were treated with placebo and epoprostenol.
Fi studju pivitali kkontrollat bi plaċebo fuq Revatio bħala appendiċi għal epoprostenol mogħti ġol- vini għal pressjoni għolja arterjali tal- pulmun, total ta ’ 134 pazjent ġew trattati b’ Revatio (f’ titrazzjoni fissa minn 20 mg għal 40 mg u mbagħad 80 mg, tlett darbiet kuljum) u epoprostenol, u 131 pazjent ġew trattati bi plaċebo u epoprostenol.
The duration of treatment was 16 weeks.
It- tul tat- trattament kien ta ’ 16- il ġimgħa.
The overall frequency of discontinuations in sildenafil/ epoprostenol treated patients due to adverse events was 5.2% compared to 10.7% in the placebo/ epoprostenol treated patients.
Il- frekwenza totali ta ’ waqfien f’ pazjenti trattati b’ sildenafil/ epoprostenol minħabba effetti avversi kienet ta ’ 5. 2% meta mqabbla ma ’ 10. 7% f’ pazjenti ttrattati bi plaċebo/ epoprostenol.
Newly reported adverse drug reactions, which occurred more frequently in the sildenafil/ epoprostenol group, were bloodshot eyes/ red eyes, blurred vision, nasal congestion, night sweats, back pain and dry mouth.
Rapporti ġodda ta ’ reazzjonijiet avversi tal- mediċina, li ġraw fi frekwenza ikbar fil- grupp ta ’ sildenafil/ epoprostenol, kienu għajnejn ħomor, vista mċajpra, konġestjoni fl- imnieħer, għaraq bil- lejl, uġigħ fid- dahar u nixfa fil- ħalq.
The known adverse events headache, flushing, pain in extremity and oedema were noted in a higher frequency in sildenafil/ epoprostenol treated patients compared to placebo/ epoprostenol treated patients.
L - effetti avversi magħrufa, uġigħ ta ’ ras, fwawar, uġigħ fl- estremitajiet u edema ġew innutati fi frekwenza ogħla f’ pazjenti ttrattati b’ sildenafil/ epoprostenol meta mqabbla ma ’ pazjenti ttrattati bi plaċebo/ epoprostenol.
In the two-placebo controlled studies adverse events were generally mild to moderate in severity.
Fiż- żewġ studji ikkontrollati bi plaċebo effetti negattivi kienu ġeneralment ta ’ serjetà ħafifa għal moderata.
The most commonly reported adverse reactions that occurred (greater or equal to 10%) on Revatio compared to placebo were headache, flushing, dyspepsia, diarrhoea and limb pain.
L- iktar reazzjonijiet avversi komuni li ġew irrappurtati (iktar jew daqs 10%) b’ Revatio meta mqabbel mal- plaċebo kienu uġigħ ta ’ ras, fwawar, dispepsja, dijarea u uġigħ fl- idejn u saqajn.
Adverse reactions which occurred in > 1% of Revatio-treated patients and were more frequent (> 1% difference) on Revatio in the pivotal study or in the Revatio combined data set of both the placebo- controlled studies in pulmonary arterial hypertension, at doses of 20, 40 or 80 mg three times a day are listed in the table below by class and frequency grouping (very common (≥ 1/ 10), common (≥ 1/ 100, < 1/ 10), uncommon (≥ 1/ 1000, < 1/ 100) and not known (cannot be estimated from the available data).
Reazzjonijiet avversi li ġraw f ’ > 1% tal- pazjenti ttrattati b’ Revatio u li kienu iktar frekwenti (> 1% differenza) b’ Revatio fl- istudju pivitali jew fis- sett ta ’ tagħrif ikkombinat ta ’ Revatio, fiż- żewġ studji kkontrollati bi plaċebo fuq pressjoni għolja arterjali tal- pulmun, f’ dożi ta ’ 20, 40 jew 80 mg tlett darbiet kuljum huma mniżżla fit- tabella hawn taħt f’ sezzjonijiet ta ’ frekwenza (komuni ħafna (≥1/ 10), komuni (≥1/ 100, < 1/ 10), mhux komuni (≥1/ 1000, < 1/ 100) u mhux magħrufa (ma tistax tiġi stmata mit- tagħrif disponibbli).
Reports from post-marketing experience are included in italics.
Rapporti minn esperjenzi wara t- tqegħid fuq is- suq huma mniżżlin f’ ittri korsivi.
MedDRA System Organ Class Infections and infestations
Sistema tal- klassifika tal- organi fid- database MedDRA Infezzjonijiet u infestazzjonijiet
Adverse Drug Reaction
Reazzjonijiet avversi tal- mediċina
Cellulitus, influenza, sinusitis not otherwise specified (NOS)
Ċellulite, influwenza, sinusite mhux speċifikata (NOS)
Anaemia NOS
Anemija NOS
Metabolism and nutrition disorders Common
Disturbi fil- metaboliżmu u n- nutrizzjoni Komuni
Fluid retention
Ritenzjoni tal- likwidi
Insomnia, anxiety
Insomnja, ansjeta
Nervous system disorders Very Common Common
8 Disturbi fis- sistema nervuża Komuni ħafna Komuni
Headache Migraine NOS, tremor, paresthesia, burning sensation NOS, hypoaesthesia
Uġigħ ta ’ ras Emikranja, NOS, rogħda, paresteżja, NOS b’ sensazzjoni ta ’ ħruq, ipoesteżja
Retinal haemorrhage, visual disturbance NOS, blurred vision, photophobia, chromatopsia, cyanopsia, eye irritation, blood shot eyes/ red eyes
Emorroġija retinali, NOS b’ taħwid fil - vista, vista mċajpra, fotofobija, kromatopsja, sijanopsja, irritazzjoni fl - għajnejn, għajnejn ħomor
Visual acuity reduced, diplopia, abnormal sensation in eye
Tnaqqis fl- akutezza tal- vista, diplopja, sensazzjoni anormali fl- għajn
Ear and labyrinth disorders Common
Disturbi fil- widnejn u fis- sistema labirintika Komuni Mhux magħrufa Disturbi vaskulari
Vertigo
Vertigo Nuqqas ta ’ smigħ f’ daqqa *
Not known Vascular disorders
Komuni ħafna
Sudden deafness*
Fwawar
Flushing
Bronkite NOS, epistassi, rinite NOS, sogħla, konġestjoni fl- imnieħer
8 Respiratory, thoracic and mediastinal disorders Common
Disturbi gastro- intestinali Komuni ħafna Komuni
Bronchitis NOS, epistaxis, rhinitis NOS, cough, nasal congestion
Dijarea, dispepsja Gastrite NOS, gastroenterite NOS, marda tal- gastrooesophageal reflux, murliti, nefħa fl- istonku, ħalq xott
Very Common Common
Komuni Mhux magħruf
Diarrhoea, dyspepsia Gastritis NOS, gastroenteritis NOS, gastrooesophageal reflux disease, haemorrhoids, abdominal distension, dry mouth
Alopeċja, eritema, għaraq bil- lejl Raxx fil- ġilda
Skin and subcutaneous tissue disorders Common Not known
Disturbi muskolu- skeltrali u tal- connective tissue Komuni ħafna Komuni
Musculoskeletal, connective tissue and bone disorders
Uġigħ fl- idejn u s- saqajn Mijalġja, uġigħ fid- dahar
Limb pain Myalgia, back pain
Disturbi fis- sistema riproduttiva u fis- sider
Reproductive system and breast disorders Uncommon Not known
Mhux komuni Mhux magħrufa
Gynaecomastia Priapism, prolonged erection
Gynaecomastia Prijapiżmu, erezzjoni prolungata
General disorders and administration site conditions
Disturbi ġenerali u kondizzjonijiet ta 'mnejn jingħata Komuni
Common
Deni
* Sudden decrease or loss of hearing has been reported in a small number of post-marketing and clinical trial cases with the use of all PDE5 inhibitors, including sildenafil.
* Tnaqqis f’ daqqa jew telf ta ’ smigħ ġie rrappurtat f’ numru żgħir ta ’ każijiet ta ’ provi kliniċi u ta ’ wara tqegħid fis- suq bl- użu ta ’ l- inibituri PDE5 kollha, inkluż sildenafil.
Eye disorders:
F’ sorveljanza wara t- tqegħid fis- suq, reazzjonijiet avversi li ġew irrappurtati minn kwantita mhux magħrufa f’ pazjenti li kienu qed jieħdu sildenafil għat- trattament ta ’ disturbi fl- erezzjoni fl- irġiel (MED) jinkludu:
Non-arteritic anterior ischaemic optic neuropathy (NAION), retinal vascular occlusion, visual field defect.
Disturbi fil- viżta: newropatija anterjuri iskimika, mhux arterika tal- għajn (NAION), sadd fis- sistema vaskulari ġewwa r- retina, difett fil- kamp visiv.
In single dose volunteer studies of doses up to 800 mg, adverse reactions were similar to those seen at lower doses, but the incidence rates and severities were increased.
9 Fi studji ta ’ voluntiera b’ doża waħda, ta ’ dożi sa 800 mg, reazzjonijiet avversi kienu simili għal dawk li ġraw b’ dożi iżgħar, iżda r- rati ta ’ inċidenza u s- severità żdiedu.
At single doses of 200 mg the incidence of adverse reactions (headache, flushing, dizziness, dyspepsia, nasal congestion, altered vision) was increased.
Dożi singli ta ’ 200 mg iriżultaw f’ żieda fl- inċidenza ta ’ reazzjonijiet avversi (uġigħ ta ’ ras, ħmura, sturdament, dispepsja, konġestjoni nażali, vista mibdula).
In cases of overdose, standard supportive measures should be adopted as required.
F’ każi ta ’ doża eċċessiva, miżuri normali ta ’ support għandhom jingħataw kif meħtieġ.
Renal dialysis is not expected to accelerate clearance as sildenafil is highly bound to plasma proteins and not eliminated in the urine.
Dijaliżi tal - kliewi mhux mistennija li tħaffef il- tneħħija għax sildenafil huwa marbut b’ mod qawwi ma ’ proteini tal- plażma u mhux eliminat fl- awrina.
Drugs used in erectile dysfunction, ATC code:
Kodiċi ATC:
Sildenafil is a potent and selective inhibitor of cyclic guanosine monophosphate (cGMP) specific phosphodiesterase type 5 (PDE5), the enzyme that is responsible for degradation of cGMP.
Sildenafil huwa inibitur potenti u selettiv ta ’ cyclic guanosine monophosphate (cGMP) specific phosphodiesterase type 5 (PDE5), l- enzima li hija responsabli għad- degradazzjoni ta ’ cGMP.
Apart from the presence of this enzyme in the corpus cavernosum of the penis, PDE5 is also present in the pulmonary vasculature.
Apparti l- preżenza ta ’ din l- enzima fil- corpus cavernosum tal- pene, PDE5 huwa preżenti wkoll fil- vaskolatura tal- pulmun.
Sildenafil, therefore, increases cGMP within pulmonary vascular smooth muscle cells resulting in relaxation.
Sildenafil, għalhekk, iżid cGMP fiċ- ċelloli lixxi tal- muskoli vaskulari pulmonari li jsaħħaħ l- effett rilassanti.
In patients with pulmonary arterial hypertension this can lead to vasodilation of the pulmonary vascular bed and, to a lesser degree, vasodilatation in the systemic circulation.
F’ pazjenti bi pressjoni għolja arterjali tal- pulmun dan jista ’ jwassal għal vażodilatazzjoni tas- sodda vaskulari u, fuq skala iżgħar, vażodilatazzjoni fiċ- ċirkolazzjoni sistemika.
Studies in vitro have shown that sildenafil is selective for PDE5.
Studji in vitro wrew li sildenafil huwa selettiv għal PDE5.
Its effect is more potent on PDE5 than on other known phosphodiesterases.
L- effett tiegħu huwa iżjed potenti fuq PDE5 minn phosphodiesterases magħrufa oħra.
There is a 10-fold selectivity over PDE6 which is involved in the phototransduction pathway in the retina.
Hemm selettività ta ’ 10- darbiet fuq PDE6 li huwa nvolut fil - phototransduction pathway fir- retina.
There is an 80-fold selectivity over PDE1, and over 700-fold over PDE 2, 3, 4, 7, 8, 9, 10 and 11.
Hemm selettività ta ’ 80- darba fuq PDE1, u aktar minn 700- darba fuq PDE2, 3, 4, 7, 8, 9, 10 u 11.
In particular, sildenafil has greater than 4,000-fold selectivity for PDE5 over PDE3, the cAMP-specific phosphodiesterase isoform involved in the control of cardiac contractility.
B’ mod partikulari, sildenafil għandu selettività ta ’ aktar minn 4, 000- darba għal PDE5 fuq PDE3, is- cAMP – specific phosphodiesterase isoform involut fil - kontroll tal- kontrattilità tal- qalb.
Sildenafil causes mild and transient decreases in systemic blood pressure which, in the majority of cases, do not translate into clinical effects.
Sildenafil jikkaġuna tnaqqis ħafif u temporanju fil- pressjoni tad- demm sistematika li, fil- maġġoranza tal- każi ma jissarfux f’ effetti kliniċi.
After chronic dosing of 80 mg three times a day to patients with systemic hypertension the mean change from baseline in systolic and diastolic blood pressure was a decrease of 9.4 mmHg and 9.1 mm Hg respectively.
Wara dożi kroniċi ta ’ 80 mg tlett darbiet kuljum lil pazjenti bi pressjoni għolja sistemika il- bidla medja mil- linja bażi fil- pressjoni sistolika u dijastolika naqset b’ 9. 4 mmHg u 9. 1 mmHg rispettivament.
After chronic dosing of 80 mg three times a day to patients with pulmonary arterial hypertension lesser effects in blood pressure reduction were observed (a reduction in both systolic and diastolic pressure of 2 mmHg).
Wara dożi kroniċi ta ’ 80 mg tlett darbiet kuljum lil pazjenti bi pressjoni għolja arterjali tal- pulmun, dehru inqas effetti fit- tnaqqis tal- pressjoni tad- demm (tnaqqis fil- pressjoni kemm dik sistolika kif ukoll dik dijastolika ta ’ 2 mmHg).
At the recommended dose of 20 mg three times a day no reductions in systolic or diastolic pressure were seen.
Fid- doża rakkomandata ta ’ 20 mg tlett darbiet kuljum ma deher l- ebda tnaqqis fil- pressjoni sistolika jew dijastolika.
Single oral doses of sildenafil up to 100 mg in healthy volunteers produced no clinically relevant effects on ECG.
Dożi orali singoli ta ’ sildenafil sa 100 mg f’ voluntiera b’ saħħithom ma pproduċew l- ebda effett klinikament relevanti fuq l- ECG.
After chronic dosing of 80 mg three times a day to patients with pulmonary arterial hypertension no clinically relevant effects on the ECG were reported.
Wara dożi kroniċi ta ’ 80 mg, tlett darbiet kuljum f’ pazjenti bi pressjoni għolja arterjali tal- pulmun l- ebda effett klinikament relevanti fuq l- ECG ma ġie rrapportat.
In a study of the hemodynamic effects of a single oral 100 mg dose of sildenafil in 14 patients with severe coronary artery disease (CAD) (> 70% stenosis of at least one coronary artery), the mean resting systolic and diastolic blood pressures decreased by 7% and 6% respectively compared to baseline.
10 Fi studju ta ’ l- effetti imodinamiċi ta ’ doża waħda orali ta ’ 100 mg sildenafil f’ 14- il pazjent b’ mard sever ta ’ l- arterji tal- qalb (CAD) (> 70% stenożi f’ ta mill- anqas arterja waħda tal- qalb), il- pressjoni medja tad- demm sistolika u dijastolika waqt is- serħan naqsu b’ 7% u 6% rispettivament mqabbla mal - linja bażi.
Mean pulmonary systolic blood pressure decreased by 9%.
Il- pressjoni medja tad- demm sistolika tal- pulmun naqset b’ 9%.
Sildenafil showed no effect on cardiac output, and did not impair blood flow through the stenosed coronary arteries.
Sildenafil ma wera ebda effett fuq il- produzzjoni tal- qalb, u ma fixkilx iċ- ċirkolazzjoni tad- demm fl- arterji stenożati tal- qalb.
Mild and transient differences in colour discrimination (blue/ green) were detected in some subjects using the Farnsworth-Munsell 100 hue test at 1 hour following a 100 mg dose, with no effects evident after 2 hours post-dose.
Instabu differenzi ħfief u temporanji ta ’ diskriminazzjoni tal- kulur (blu / aħdar) f’ xi pazjenti li wżaw il- Farnsworth- Munsell 100 Hue Test, siegħa wara li ħadu doża ta ’ 100 mg, u ebda effett ma deher sagħtejn wara d- doża.
The postulated mechanism for this change in colour discrimination is related to inhibition of PDE6, which is involved in the phototransduction cascade of the retina.
Il- mekkaniżmu maħsub għal din il- bidla fid- diskriminazzjoni tal- kulur jinvolvi l- inibizzjoni ta ’ PDE6, li huwa nvolut fil- phototransduction cascade tar- retina.
Sildenafil has no effect on visual acuity or contrast sensitivity.
Sildenafil m’ għandux effett fuq kemm tkun akuta l- vista jew fuq is- sensittività tal- kuntrast.
In a small size placebo-controlled study of patients with documented early age-related macular degeneration (n=9), sildenafil (single dose, 100 mg) demonstrated no significant changes in visual tests conducted (visual acuity, Amsler grid, colour discrimination simulated traffic light, Humphrey perimeter and photostress).
Fi studju żgħir kontrollat bil - plaċebo ta ’ pazjenti b’ deġenerazzjoni makulari bikrija dokumentata relatata ma ’ l- età (n=9), sildenafil (doża waħda, 100 mg) ma wera ebda tibdil sinifikanti f’ testijiet tal- vista li saru (kemm tkun akuta l - vista, Amsler grid, diskriminazzjoni ta ’ kulur ta ’ dwal tat- traffiku simulati, Humphrey perimeter u photostress).
Efficacy in adult patients with pulmonary arterial hypertension (PAH) A randomised, double-blind, placebo-controlled study was conducted in 278 patients with primary pulmonary hypertension, PAH associated with connective tissue disease (CTD), and PAH following surgical repair of congenital heart lesions.
Studju b’ mod każwali, double- blind, ikkontrollat bi plaċebo twettaq fuq 278 pazjent bi pressjoni għolja tal- pulmun primarja, PAH assoċjata ma ’ mard tat- tessut konnettiv (CTD), u PAH wara kirurġija ta ’ feriti konġenitali tal- qalb.
Patients were randomised to one of four treatment groups: placebo, sildenafil 20 mg, sildenafil 40 mg or sildenafil 80 mg, three times a day.
Il- pazjenti tpoġġew b’ mod każwali f’ wieħed minn 4 gruppi ta ’ trattament; plaċebo, sildenafil 20 mg, sildenafil 40 mg jew sildenafil 80 mg, tlett darbiet kuljum.
Of the 278 patients randomised, 277 patients received at least 1 dose of study drug.
Minn 278 pazjent fuq bażi każwali, 277 pazjent irċievew ta ’ l- inqas doża waħda tal- mediċina li qed tiġi studjata.
The study population consisted of 68 (25%) men and 209 (75%) women with a mean age of 49 years (range:
Il- popolazzjoni ta ’ l- istudju kienet magħmula minn 68 (25%) raġel u 209 (75%) mara b’ età medja ta ’ 49 sena (medda:
18-81 years) and baseline 6-minute walk test distance between 100 and 450 metres inclusive (mean:
18- 81sena) b’ mixja ta ’ 6 minuti bħala l- linja bażi ttestjata fuq 100 u 450 metru inklużi (medja ta ’:
344 metres).
344 metru).
175 patients (63%) included were diagnosed with primary pulmonary hypertension, 84 (30%) were diagnosed with 10 PAH associated with connective tissue disease (CTD) and 18 (7%) of the patients were diagnosed with PAH following surgical repair of congenital heart lesions.
175 pazjent (63%) inklużi ġew dijanjostikati bi pressjoni għolja tal- pulmun primarja,, 84 (30%) ġew dijanjostikati b’ PAH assoċjata ma ’ mard tat- tessut konnettiv (CTD) u 18 (7%) il- pazjent ġew dijanjostikati b’ PAH wara kirurġija ta ’ feriti konġenitali fil- qalb.
Most patients were WHO Functional Class II (107/ 277, 39%) or III (160/ 277, 58%) with a mean baseline 6 minute walking distance of 378 meters and 326 meters respectively; fewer patients were Class I (1/ 277, 0.4%) or IV (9/ 277, 3%) at baseline.
Ħafna mill- pazjenti kienu ta ’ Klassi Funzjonali II ta ’ WHO (107/ 277, 39%) jew III (160/ 277, 58%) b’ mixja ta ’ 6 minuti ta ’ 378 metri u 326 metri rispettivament bħala l- linja bażi; inqas pazjenti kienu ta ’ Klassi I (1/ 277, 0. 4%) jew IV (9/ 277, 3%) fil- linja bażi.
Patients with left ventricular ejection fraction < 45% or left ventricular shortening fraction < 0.2 were not studied.
Pazjenti bi frazzjoni ta ’ ejection tal - ventrikola tax- xellug < 45% jew bi frazzjoni ta ’ tnaqqis fil- ventrikola tax- xellug < 0. 2 ma ġewx studjati.
Sildenafil (or placebo) was added to patients’ background therapy which could have included a combination of anticoagulation, digoxin, calcium channel blockers, diuretics or oxygen.
Sildenafil (jew plaċebo) ġie miżjud mat- terapija mhux ewlenija tal- pazjenti li setgħat tinkludi kumbinazzjoni ta ’ anti- koagulant, digoxin, calcium channel blockers, diuretics jew ossiġenu.
The use of prostacyclin, prostacyclin analogues and endothelin receptor antagonists was not permitted as add-on therapy, and neither was arginine supplementation.
L- użu ta ’ prostacyclin, prostacyclin analogues u endothelin receptor antagonists ma kienx permess bħala terapija miżjuda, u lanqas suppliment ta ’ arginine.
Patients who previously failed bosentan therapy were excluded from the study.
Pazjenti li t- terapija b’ bosentan ma ħadmitx fuqhom qabel, ġew esklużi minn dan l- istudju.
The primary efficacy endpoint was the change from baseline at week 12 in 6-minute walk distance.
Il- punt ta ’ tmiem primarju ta ’ l- effikaċja kien il- bidla mil- linja bażi fil- ġimgħa 12, fil- mixja ta ’ 6 minuti.
A statistically significant increase in 6-minute walk distance was observed in all 3 sildenafil dose groups compared to those on placebo.
Żieda fid- distanza koperta f’ 6 minuti b’ sinifikat statistiku ġiet osservata fit- 3 gruppi ta ’ dożi ta ’ sildenafil meta mqabbla ma ’ dawk fuq plaċebo.
Placebo corrected increases in walk distance were 45 metres (p < 0.0001), 46 metres (p < 0.0001) and 50 metres (p < 0.0001) for sildenafil 20 mg, 40 mg and 80 mg respectively.
Iż- żidiet fid- distanza koperti minħabba l- plaċebo kienu ta ’ 45 metru (p < 0. 0001), 46 metri (p < 0. 0001) u 50 metru (p < 0. 0001) għal sildenafil 20 mg, 40 mg u 80 mg rispettivament.
There was no significant difference in effect between sildenafil doses.
Ma kienx hemm differenza sinifikanti fl- effett bejn dożi differenti ta ’ sildenafil.
The improvement in walk distance was apparent after 4 weeks of treatment and this effect was maintained at weeks 8 and 12.
It- titjib fid- distanza koperta beda jidher wara 4 ġimgħat ta ’ trattament u dan l- effett baqa ’ jidher fit- 8 u fit- 12- il ġimgħa.
Results were generally consistent in subgroups according to baseline walking distance, aetiology (primary and CTD-associated PAH), WHO functional class, gender, race, location, mean PAP and PVRI.
Ir- riżultati kienu ġeneralment konsistenti f’ sottogruppi skond it- tul tal- mixi fil- linja bażi, etjoloġijja (primarja u PAH assoċjat ma ’ CTD), klassi funzjonali tal- WHO, sess, razza, post, medja ta ’ PAP u PVRI.
Patients on all sildenafil doses achieved a statistically significant reduction in mean pulmonary arterial pressure (mPAP) compared to those on placebo.
11 Il- pazjenti li kienu qegħdin jieħdu kwalunkwe doża ta ’ sildenafil laħqu tnaqqis ta ’ sinifikat statistiku fil- pressjoni arterjali tal- pulmun medja (mPAP) meta mqabbla ma ’ dawk fuq plaċebo.
The placebo-corrected treatment was – 2.7 mmHg (p=0.04) for sildenafil 20 mg three times a day.
It- trattament ikkoreġut bi plaċebo kien ta ’ – 2. 7 mmHg (p=0. 04) għal sildenafil 20 mg tlett darbiet kuljum.
There was no evidence of a difference in effect between sildenafil 20 mg and the higher doses tested.
Ma kien hemm ebda evidenza ta ’ xi differenza fl- effett bejn sildenafil 20 mg u d- dożi iktar għoljin li ġew ittestjati.
The mean change from baseline in pulmonary vascular resistance (PVR) was – 122 dyne. sec/ cm5 for sildenafil 20 mg three times a day.
Il- bidla medja mil- linja bażi f’ reżistenza vaskolari pulmonari (PVR) kienet ta ’ – 122 dyne. sec/ ċm5 għal sildenafil 20 mg tlett darbiet kuljum.
The percent reduction at 12 weeks for sildenafil 20 mg in PVR (11.2%) was proportionally greater than the reduction in systemic vascular resistance (SVR) (7.2%).
Il- perċentwali ta ’ tnaqqis fit- 12- il ġimgħa għal sildenafil 20 mg f’ PVR (11. 2%) kien proporzjonalment ikbar mit- tnaqqis fir- reżistenza sistemika vaskolari (SVR) (7. 2%).
The effect of sildenafil on mortality is unknown.
L- effett ta ’ sildenafil fuq il- mortalità m’ huwiex magħruf.
Efficacy in adult patients with PAH (when used in combination with epoprostenol) A randomised, double-blind, placebo controlled study was conducted in 267 patients with PAH who were stabilised on intravenous epoprostenol.
Effikaċja f’ pazjenti adulti b ’ PAH (meta jintużaw f’ kumbinazzjoni ma ’ epoprostenol) Sar studju b’ mod każwali, double- blind, ikkontrollat bi plaċebo fuq 267 pazjent b’ PAH li kienu stabbilizzati fuq epoprostenol mogħti ġol- vini.
The PAH patients included those with Primary Pulmonary Arterial Hypertension (212/ 267, 79%) and PAH associated with CTD (55/ 267, 21%).
Il- pazjenti b’ PAH inkludew dawk bi pressjoni għolja primarja pulmonari u arterjali (212/ 267, 79%) u PAH assoċjata ma ’ CTD (55/ 267, 21%).
Most patients were WHO Functional Class II (68/ 267, 26%) or III (175/ 267, 66%); fewer patients were Class I (3/ 267, 1%) or IV (16/ 267, 6%) at baseline; for a few patients (5/ 267, 2%), the WHO Functional Class was unknown.
Ħafna mill - pazjenti kienu ta ’ Klassi Funzjonali II (68/ 267, 26%) jew III (175/ 267, 66%) ta ’ WHO; inqas pazjenti kienu ta ’ Klassi I (3/ 267, 1%) jew IV (16/ 267, 6%) fil- linja bażi; għal xi ftit pazjenti (5/ 267, 2%), il - Klassi Funzjonali tal- WHO ma kienitx magħrufa.
Patients were randomised to placebo or sildenafil (in a fixed titration starting from 20 mg, to 40 mg and then 80 mg, three times a day) when used in combination with intravenous epoprostenol.
Pazjenti ngħataw plaċebo jew sildenafil (b’ titrazzjoni fissa li tibda minn 20 mg, 40 mg jew 80 mg tlett darbiet kuljum) b’ mod każwali f’ kumbinazzjoni ma ’ epoprostenol mogħti ġol- vini.
The primary efficacy endpoint was the change from baseline at week 16 in 6-minute walk distance.
Il- punt ta ’ tmiem primarju ta ’ l- effikaċja kien il- bidla mil- linja bażi fil- ġimgħa 16 fid- distanza koperta f ’ 6 minuti bil- mixi.
There was a statistically significant benefit of sildenafil compared to placebo in 6-minute walk distance.
Kien hemm benefiċċju ta ’ sinjifikat statistiku f’ sildenafil meta mqabbel mal - plaċebo.
A mean placebo corrected increase in walk distance of 26 metres was observed in favour of sildenafil (95% CI:
Ġiet osservata żieda medja fid- distanza koperta bil- mixi minħabba l- plaċebo ta ’ 26 metri favur sildenafil (95% CI:
10.8, 41.2) (p=0.0009).
10. 8, 41. 2) (p=0. 0009).
For patients with a baseline walking distance ≥ 325 metres, the treatment effect was 38.4 metres in favour of sildenafil; for patients with a baseline walking distance < 325 metres, the treatment effect was 2.3 metres in favour of placebo.
Għall- pazjenti b’ linja bażi fid- distanza koperta bil - mixi ta ’ ≥325 metri, it- trattament effettiv kien ta ’ 2. 3 metri favur il- plaċebo.
For patients with primary PAH, the treatment effect was 31.1 metres compared to 7.7 metres for patients with PAH associated with CTD.
Għal pazjenti bi PAH primarja, l- effett tat- trattament kien ta ’ 31. 1 metri meta mqabbel ma ’ 7. 7 metri għal pazjenti b’ PAH assoċjat ma ’ CTD.
The difference in results between these randomisation subgroups may have arisen by chance in view of their limited sample size.
Id- differenza fir- riżultati bejn dawn is- subgruppi fuq bażi każwali setgħet ġiet b’ kumbinazzjoni minħabba d- daqs limitat tal- kampjun.
Patients on sildenafil achieved a statistically significant reduction in mean Pulmonary Arterial Pressure (mPAP) compared to those on placebo.
Pazjenti fuq sildenafil laħqu tnaqqis fil- medja ta ’ pressjoni arterjali pulmonari (mPAP) ta ’ sinjifikat statistiku meta mqabbla ma ’ plaċebo.
A mean placebo-corrected treatment effect of -3.9 mmHg was observed in favour of sildenafil (95% CI: -5.7, -2.1) (p=0.00003).
Trattament medju kkoreġut bl- effett ta ’ plaċebo ta ’ 3. 9 mmHg ġie osservat favur sildenafil (95% CI: - 5. 7, - 2. 1) (p=0. 00003).
Sildenafil is rapidly absorbed.
Sildenafil jiġi assorbit malajr.
Maximum observed plasma concentrations are reached within 30 to 120 minutes (median 60 minutes) of oral dosing in the fasted state.
L- ogħla konċentrazzjonijiet ta ’ plażma osservati jintlaħqu fi żmien 30 għal 120 minuta (medjan 60 minuta) ta ’ doża orali fi stat sajjem.
The mean absolute oral bioavailability is 41% (range 25-63%).
Il- medja assoluta ta ’ bijodisponibilità orali hija 41% (medda 25- 63%).
After oral three times a day dosing of sildenafil, AUC and Cmax increase in proportion with dose over the dose range of 20-40 mg.
Wara dożi orali ta ’ tlett darbiet kuljum ta ’ sildenafil, AUC u Cmax żiedu fil- proporzjon ma ’ dożi ikbar mill- medda ta ’ 20- 40 mg.
After oral doses of 80 mg three times a day a more than dose proportional increase in sildenafil plasma levels has been observed.
Wara dożi orali ta ’ 80 mg tlett darbiet kuljum, ġiet osservata żieda ikbar min dik proporzjonali mad- doża fil- livelli fil- plażma.
In pulmonary arterial hypertension patients, the oral bioavailability of sildenafil after 80 mg three times a day was on average 43% (90% CI:
F’ pazjenti bi pressjoni arterjali pulmonari għolja, il- bijodisponibbiltà orali ta ’ sildenafil wara 80 mg tlett darbiet kuljum kienet bejn wieħed u ieħor ta ’ 43% (90% CI:
27% - 60%) higher compared to the lower doses.
27% - 60%) ogħla meta mqabbla ma ’ dik fuq dożi baxxi.
When sildenafil is taken with food, the rate of absorption is reduced with a mean delay in Tmax of 60 minutes and a mean reduction in Cmax of 29% however, the extent of absorption was not significantly affected (AUC decreased by 11%).
Meta sildenafil jittieħed ma ’ l- ikel, ir- rata ta ’ assorbiment titnaqqas b’ dewmien medju fit- tmax ta ’ 60 minuta u tnaqqis medju fis- Cmax ta ’ 29%, madankollu l- ammont ta ’ assorbiment ma ġiex affetwat b’ mod sinifikanti (AUC mnaqqas bi 11%).
The mean steady state volume of distribution (Vss) for sildenafil is 105 l, indicating distribution into the tissues.
Il- medja tal- volum ta ’ distribuzzjoni fiss (Vss) għal sildenafil huwa 105 l, li jindika distribuzzjoni fit - tessuti.
After oral doses of 20 mg three times a day, the mean maximum total plasma concentration of sildenafil at steady state is approximately 113 ng/ ml.
Wara dożi orali ta ’ 20 mg tlett darbiet kuljum, il- medja fil- konċentrazzjonijiet massimi totali fil- plażma ta ’ sildenafil fi stat fiss hija bejn wieħed u ieħor 113 ng/ ml.
Sildenafil and its major circulating N- desmethyl metabolite are approximately 96% bound to plasma proteins.
Sildenafil u l- metabolit maġġur tiegħu fiċ- ċirkolazzjoni, N- desmethyl, huma bejn wieħed u ieħor 96% marbutin mal- proteini tal - plażma.
Protein binding is independent of total drug concentrations.
L- irbit mal- proteini huwa indipendenti mill- konċentrazzjoni totali tal- mediċina.
Sildenafil is cleared predominantly by the CYP3A4 (major route) and CYP2C9 (minor route) hepatic microsomal isoenzymes.
Sildenafil huwa mneħħi primarjament mill- iżo- enzimi mikrożomali CYP3A4 (rotta ewlenija) u CYP2C9 (rotta minuri) tal- fwied.
The major circulating metabolite results from N-demethylation of sildenafil.
Il- metabolu ċirkulatorju ewlieni jirriżulta minn N- demethylation ta ’ sildenafil.
This metabolite has a phosphodiesterase selectivity profile similar to sildenafil and an in vitro potency for PDE5 approximately 50% that of the parent drug.
Dan il- metabolu għandu profil selettiv ta ’ phosphodiesterase simili għal sildenafil u potenza in vitro għal PDE5 bejn wieħed u ieħor 50% ta ’ dik tal- mediċina mhux mibdula.
The N-desmethyl metabolite is further metabolised, with a terminal half-life of approximately 4 h.
Il- metabolu N - desmethyl jiġi metabolizzat iżjed, b’ half life terminali ta ’ bejn wieħed u ieħor 4 sigħat.
In patients with pulmonary arterial hypertension, plasma concentrations of N-desmethyl metabolite are approximately 72% those of sildenafil after 20 mg three times a day dosing (translating into a 36% contribution to sildenafil’ s pharmacological effects).
F’ pazjenti bi pressjoni arterjali pulmonari għolja, il- konċenetrazzjonijiet fil- plażma tal- metabolu N- desmethyl huma bejn wieħed u ieħor 72% ta ’ dawk ta ’ sildenafil wara 20 mg tlett darbiet kuljum (li ssarraf f’ kontribuzzjoni ta ’ 36% għall- effetti farmakoloġiċi ta ’ sildenafil).
The subsequent effect on efficacy is unknown.
L- effett sussegwenti fuq l- effikaċja m’ huwiex magħruf.
The total body clearance of sildenafil is 41 l/ h with a resultant terminal phase half-life of 3-5 h.
Il- tneħħija totali tal- ġisem ta ’ sildenafil huwa 41 l/ h li jirriżulta f’ half life fil- fażi terminali ta ’ 3- 5 h.
After either oral or intravenous administration, sildenafil is excreted as metabolites predominantly in the faeces (approximately 80% of administered oral dose) and to a lesser extent in the urine (approximately 13% of administered oral dose).
Wara amministrazzjoni orali jew fil- vina, sildenafil jitneħħa bħala metaboli b’ mod predominanti fl - ippurgar (bejn wieħed u ieħor 80% tad- doża orali amministrata) u f’ proporzjon anqas fl- awrina (bejn wieħed u ieħor 13% tad- doża orali amministrata).
Pharmacokinetics in special patient groups Elderly:
Farmakokinetiċi fi gruppi speċjali ta ’ pazjenti Anzjani:
Healthy elderly volunteers (65 years or over) had a reduced clearance of sildenafil, resulting in approximately 90% higher plasma concentrations of sildenafil and the active N-desmethyl metabolite compared to those seen in healthy younger volunteers (18-45 years).
Voluntiera anzjani b’ saħħithom (65 sena jew iżjed) kellhom tneħħija mnaqqsa ta ’ sildenafil, li jirriżulta f’ bejn wieħed u ieħor 90% tal- konċentrazzjonijiet ogħla fil- plażma ta ’ sildenafil u l - metabolu attiv N- desmethly mqabbel ma ’ dawk li nstabu f’ voluntiera żagħżagħ b’ saħħithom (18- 45 sena).
Due to age-differences in plasma protein binding, the corresponding increase in free sildenafil plasma concentration was approximately 40%.
Minħabba differenzi relatati ma ’ l- età fl- irbit tal- proteini tal- plażma, ż- żieda korrispondenti fil - konċentrazzjoni fil- plażma ta ’ sildenafil ħieles kienet ta ’ bejn wieħed u ieħor 40%.
In volunteers with mild to moderate renal impairment (creatinine clearance = 30-80 ml/ min), the pharmacokinetics of sildenafil were not altered after receiving a 50 mg single oral dose.
F’ voluntiera b’ indeboliment ħafif għal moderat tal- kliewi (tneħħija tal- kreatinina = 30- 80 ml/ min), il - farmakokinetiċi ta ’ sildenafil ma tbiddlux wara li rċievew doża orali waħda ta ’ 50 mg.
In volunteers with severe renal impairment (creatinine clearance < 30 ml/ min), sildenafil clearance was reduced, resulting in mean increases in AUC and Cmax of 100% and 88% respectively compared to age- matched volunteers with no renal impairment.
F’ voluntiera b’ indeboliment gravi tal- kliewi (tneħħija tal- kreatinina < 30 ml/ min), il- tneħħija ta ’ sildenafil naqas, b’ riżultat ta ’ żidiet medji fil- valuri ta ’ AUC u Cmax ta ’ 100% u 88% rispettivament meta mqabbla ma ’ voluntiera ta ’ l- istess età mingħajr indeboliment renali.
In addition, N-desmethyl metabolite AUC and Cmax values were significantly increased 200% and 79% respectively in subjects with severe renal impairment compared to subjects with normal renal function.
Barra minn hekk il- valuri ta ’ AUC u Cmax għall- metabolu N- desmethyl, żdiedu b’ mod sinifikanti b ’ 200% u 79% rispettivament f’ pazjenti b’ indeboliment gravi meta mqabbla ma ’ suġġetti b’ funzjoni renali normali.
12 In volunteers with mild to moderate hepatic cirrhosis (Child-Pugh class A and B) sildenafil clearance was reduced, resulting in increases in AUC (85%) and Cmax (47%) compared to age-matched volunteers with no hepatic impairment.
F’ voluntiera b’ ċirożi ħafifa għal moderata tal- fwied (Child- Pugh A u B) il- tneħħija ta sildenafil tnaqqas, u rriżulta f’ żidiet fl- AUC (84%) u Cmax (47%) mqabbel ma ’ voluntiera ta ’ l- istess età li ma kellhomx ħsara fil- fwied.
In addition, N-desmethyl metabolite AUC and Cmax values were significantly increased by 154% and 87%, respectively in cirrhotic subjects compared to subjects with normal hepatic function.
Barra minn hekk, il- valuri ta ’ AUC u Cmax għall- metabolu N- desmethyl, żdiedu b’ mod sinifikanti b’ 154% u 87% rispettivament f’ suġġetti b’ ċirrożi meta mqabbla ma ’ pazjenti b’ funzjoni renali normali.
The pharmacokinetics of sildenafil in patients with severely impaired hepatic function have not been studied.
Il- farmakokinetiċi ta ’ sildenafil f’ pazjenti bi ħsara severa tal- fwied ma ġewx studjati.
Population pharmacokinetics:
Farmakokinetiċi tal- popolazzjoni:
In patients with pulmonary arterial hypertension, the average steady state concentrations were 20 – 50% higher over the investigated dose range of 20– 80 mg three times a day compared to healthy volunteers.
F’ pazjenti bi pressjoni għolja arterjali tal- pulmun, il- konċentrazzjoni medja fissa kienet ta ’ 20- 50% ogħla, fuq il- medda ta ’ dożi li kienu qegħdin jiġu investigati ta ’ 20- 80 mg tlett darbiet kuljum meta mqabbla ma ’ voluntiera b’ saħħithom.
There was a doubling of the Cmin compared to healthy volunteers.
Kien hemm irduppjar ta ’ Cmin meta mqabbla ma ’ voluntiera b’ saħħithom.
Both findings suggest a lower clearance and/ or a higher oral bioavailability of sildenafil in patients with pulmonary arterial hypertension compared to healthy volunteers.
Iż- żewġ skoperti jissuġerixxu tneħħija iktar baxxa u/ jew bijodisponibbiltà orali ogħla ta ’ sildenafil f’ pazjenti bi pressjoni arterjali pulmonari għolja meta mqabbla ma ’ voluntiera b’ saħħithom.
Non-clinical data revealed no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity and carcinogenic potential, fertility and embryonal/ foetal development.
5. 3 Tagħrif ta 'qabel l- użu kliniku dwar is- sigurtà tal- mediċina 13 Informazzjoni li mhiex klinika, magħmula fuq studji konvenzjonali ta ’ sigurtà farmakoloġika, effett tossiku minn dożi ripetuti, effett tossiku fuq il- ġeni, riskju ta ’ kanċer, effett tossiku fuq is- sistema riproduttiva, ma turi l- ebda periklu speċjali għall- bniedem.
In pups of rats which were pre- and postnatally treated with 60 mg/ kg sildenafil, a decreased litter size, a lower pup weight on day 1 and a decreased 4-day survival were seen at exposures which were approximately fifty times the expected human exposure at 20 mg three times a day.
Fi frieħ ta ’ firien li kienu trattati kemm qabel kif ukoll wara t- twelid b’ 60 mg/ kg sildenafil, kien hemm tnaqqis fin- numru ta ’ frieħ, piż iżgħar tal- frieħ fl- ewwel ġurnata u tnaqqis fis- sopravivenza wara 4 ijiem, f’ espożizzjonijiet ta ’ bejn wieħed u ieħor ħamsin darba l- espożizzjoni mistennija fil- bnedmin ta ’ 20 mg tlett darbiet kuljum.
These effects were observed at exposures considered sufficiently in excess of the maximum human exposure indicating little relevance to clinical use.
Dawn l- effetti dehru wara esponimenti meqjusa ferm aktar għolja mill - massimu ta ’ l- esponimenti lill- bniedem, li juru ftit li xejn relevanza għall- użu kliniku.
Tablet core: microcrystalline cellulose calcium hydrogen phosphate (anhydrous) croscarmellose sodium magnesium stearate
Qalba tal- pillola: microcrystalline cellulose calcium hydrogen phosphate (anhydrous) croscarmellose sodium magnesium stearate
Film coat: hypromellose titanium dioxide (E171) lactose monohydrate glycerol triacetate
Kisja b’ rita: hypromellose titanium dioxide (E171) lactose monohydrate glycerol triacetate
5 years.
5 snin.
Do not store above 30 °C.
Taħżinx f’ temperatura ‘ l fuq minn 30 °C.
PVC/ Aluminium blisters of 90 tablets (15 tablets per blister strip) in a carton.
Folji tal- PVC/ Aluminju ta ’ 90 pillola (15- il pillola kull strixxa) f’ kartuna.
Pfizer Limited, Sandwich, Kent CT13 9NJ, United Kingdom.
Pfizer Limited, Sandwich, Kent CT13 9NJ, Ir- Renju Unit.
28 October 2005
28 ta ’ Ottubru 2005
14 ANNEX II
08/ 2008
MANUFACTURING AUTHORISATION HOLDER(S) RESPONSIBLE FOR BATCH RELEASE
Informazzjoni dettaljata dwar dan il- prodott tinsab fuq il- website ta ’ l- Aġenzija Ewropea dwar il - Mediċini (EMEA) http: // www. emea. europa. eu
Pfizer PGM Zone Industrielle 29 route des Industries 37530 Poce sur Cisse FRANCE
Pfizer PGM Zone Industrielle 29 route des Industries 37530 Poce sur Cisse FRANZA
• CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE IMPOSED ON THE MARKETING AUTHORISATION HOLDER
• KONDIZZJONIJIET JEW RESTRIZZJONIJIET FUQ IL- FORNIMENT U L- UŻU IMPOSTI FUQ ID- DETENTUR TA ’ L- AWTORIZZAZZJONI GĦAT- TQEGĦID FIS - SUQ
Medicinal product subject to restricted medical prescription (See Annex I:
Prodott mediċinali jingħata bir- riċetta tat- tabib (Ara Anness I:
• CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
• KONDIZZJONIJIET JEW RESTRIZZJONIJIET FIR- RIGWARD TA ’ L- UŻU MINGĦAJR PERIKLU U EFFTTIV TAL- PRODOTT MEDIĊINALI
Pharmacovigilance system The MAH must ensure that the system of pharmacovigilance, as described in version 1.1 presented in Module 1.8.1. of the Marketing Authorisation Application, is in place and functioning before and whilst the product is on the market.
Sistema tal- Farmakoviġilanza L- MAH għandu jiżgura li s- sistema ta ’ farmakoviġilanza kif deskritta f’ verżjoni 1. 1 u ppreżentata f’ Modulu 1. 8. 1 tal- Applikazzjoni għal Awtorizazzjoni għat- Tqegħid fuq is- Suq, hija f’ posta u tiffunzjona qabel u waqt li l- prodott qiegħed fuq is- suq.
Risk Management Plan The MAH commits to performing the studies and additional pharmacovigilance activities detailed in the Pharmacovigilance Plan, as agreed in version 2.1 of the Risk Management Plan (RMP) presented in Module 1.8.2. of the Marketing Authorisation Application and any subsequent updates of the RMP agreed by the CHMP.
Pjan ta ’ Mmaniġġjar ta ’ Riskju Id- Detentur ta ’ l- Awtorizzazzjoni għat- tqegħid fis- Suq jobbliga ruħu li jwettaq studji u attivitajiet oħra ta ’ Farmakoviġilanza kif dettaljat fil pjan ta ’ Farmakoviġilanza, kif miftiehem f’ versjoni 2. 1 tal - Pjan ta ’ mmaniġġjar tar- riskju (RMP) kif preżentat f’ Modulu 1. 8. 2 ta ’ l- applikazzjoni għat- tqegħid fis- suq u kull tiġdid tal RMP miftiehem mas- CHMP.
In addition, an updated RMP should be submitted • When new information is received that may impact on the current Safety Specification, Pharmacovigilance Plan or risk minimisation activities • Within 60 days of an important (pharmacovigilance or risk minimisation) milestone being reached • At the request of the EMEA
Ukoll, RMP imġedded irid jiġi sottomess • Meta jkun hemm informazzjoni ġdida li teffetwa l- speċifikazzjonijijiet ta ’ sigurta ’, pjan ta ’ Farmakoviġilanza, jew attivitajiet li jnaqqsu r- riskju. • Fi żmien 60 ġurnata ta ’ avveniment importanti (Farmakoviġilanza jew tnaqqis tar- riskju). • Fuq talba ta l- EMEA
18 PARTICULARS TO APPEAR ON THE OUTER PACKAGING
TIKKETTA
OUTER PACKAGING/ CARTON
PAKKETT TA ’ BARRA / KARTUNA
REVATIO 20 mg film-coated tablets Sildenafil
REVATIO 20 mg pilloli miksijin b’ rita Sildenafil
Each tablet contains 20 mg of sildenafil (as citrate).
Kull pillola fiha 20 mg ta ’ sildenafil (bħala citrate).
Contains lactose monohydrate See leaflet for further information
Fih lactose monohydrate Ara l- fuljett għal aktar tagħrif
90 film-coated tablets
90 pillola miksijin b’ rita
Read the package leaflet before use.
Għal użu orali Aqra l- fuljett ta ’ tagħrif qabel l- użu.
Do not store above 30oC.
Taħżinx f’ temperatura ’ l fuq minn 30oC.
Store in the original package in order to protect from moisture.
Aħżen fil- pakkett oriġinali sabiex tilqa ’ mill- umidità.
20 MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS IMMEDIATE PACKAGING/ BLISTER
21 TAGĦRIF MINIMU LI GĦANDU JIDHER FUQ IL- FOLJI JEW FUQ L- ISTRIXXI PAKKETT EWLIENI/ FOLJA
22 PACKAGE LEAFLET:
FULJETT TA ’ TAGĦRIF
INFORMATION FOR THE USER REVATIO 20mg film-coated tablets Sildenafil citrate
INFORMAZZJONI GĦAL MIN QED JAGĦMEL UŻU MINNU REVATIO 20 mg pilloli miksijin b’ rita Sildenafil citrate
- If you have any further questions, please ask your doctor or pharmacist.
- Jekk ikollok aktar mistoqsijiet, jekk jogħġbok staqsi lit- tabib jew lill- ispiżjar tiegħek.
if their symptoms are the same as yours.
anki jekk ikollom l- istess sintomi bħal tiegħek.
What Revatio is and what it is used for 2.
X’ inhu Revatio u għalxiex jintuża 2.
Before you take Revatio 3.
Qabel ma tieħu Revatio 3.
How to take Revatio 4.
Kif għandek tieħu Revatio 4.
Possible side effects 5 How to store Revatio 6.
X’ effetti oħra jista ’ jkollu 5.
Further information
Kif taħżen Revatio 6.
WHAT REVATIO IS AND WHAT IT IS USED FOR
X’ INHU REVATIO U GĦALXIEX JINTUŻA
Revatio belongs to a group of medicines called phosphodiesterase type 5 inhibitors.
Revatio jifforma parti minn grupp ta ’ mediċinali msejħa inibituri ta ’ phosphodiesterase type 5.