natgillin/translations-raw huggingface dataset:
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).
Sukladno njegovim poznatim učincima na signalni put dušikova oksida/cGMP-a (vidjeti dio 5.1), pokazalo se da sildenafil pojačava hipotenzivne učinke nitrata.
Name and address of the manufacturers responsible for batch release Accord Healthcare Ltd
Nazivi i adrese proizvođača odgovornih za puštanje serije lijeka u promet
The total body clearance of sildenafil is 41 l/h with a resultant terminal phase half-life of 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).
Nakon peroralne ili intravenske primjene sildenafil se izlučuje u obliku metabolita pretežito fecesom (oko 80% primijenjene peroralne doze) te u manjoj mjeri mokraćom (oko 13% primijenjene peroralne doze).
The benefit-risk balance of sildenafil has not been established in patients assessed to be at WHO functional class I pulmonary arterial hypertension.
Nije utvrđena ravnoteža koristi i rizika primjene sildenafila u bolesnika s plućnom arterijskom hipertenzijom funkcionalnog stupnja I prema SZO klasifikaciji.
Therefore, doses higher than the recommended doses should not be used in paediatric patients with PAH (see also sections 4.2 and 5.1).
Stoga se u pedijatrijskih bolesnika s PAH-om ne smiju primjenjivati više doze od preporučenih (vidjeti i dijelove 4.2 i 5.1).
Cmax after a single 20 mg sildenafil dose administered PO was estimated at 49, 104 and 165 ng/ml for 70, 20 and 10 kg patients, respectively.
Procjenjuje se da nakon jedne peroralne doze od 20 mg sildenafila Cmax iznosi 49 ng/ml u bolesnika tjelesne težine 70 kg, 104 ng/ml u bolesnika tjelesne težine 20 kg, odnosno 165 ng/ml u bolesnika tjelesne težine 10 kg.
A total of 234 subjects aged 1 to 17 years were treated in a randomized, double-blind, multi-centre, placebo controlled parallel group, dose ranging study.
U randomiziranom, dvostruko slijepom, multicentričnom, placebom kontroliranom ispitivanju raspona doza s paralelnim skupinama liječena su ukupno 234 ispitanika u dobi od 1 do 17 godina.
Data from one lactating woman indicate that sildenafil and its active metabolite N-desmethylsildenafil are excreted into breast milk at very low levels.
Podaci dobiveni od jedne dojilje ukazuju na to da se sildenafil i njegov aktivni metabolit
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.
Većina je bolesnika imala bolest funkcionalnog stupnja II (107/277, 39%) ili III (160/277, 58%) prema klasifikaciji SZO.
Cmax after a single 10 mg sildenafil dose administered PO was estimated at 24, 53 and 85 ng/ml for 70, 20 and 10 kg patients, respectively.
Procjenjuje se da nakon jedne peroralne doze od 10 mg sildenafila Cmax iznosi 24 ng/ml u bolesnika tjelesne težine 70 kg, 53 ng/ml u bolesnika tjelesne težine 20 kg, odnosno 85 ng/ml u bolesnika tjelesne težine 10 kg.
Higher than recommended doses should not be used in paediatric patients with PAH (see also sections 4.4 and 5.1).
U pedijatrijskih bolesnika s PAH-om ne smiju se primjenjivati više doze od preporučenih (vidjeti i dijelove 4.4 i 5.1).
6.6 Special precautions for disposal and other handling No special requirements for disposal.
6.6 Posebne mjere za zbrinjavanje i druga rukovanja lijekom
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. After oral doses of 80 mg three times a day a more than dose proportional increase in sildenafil plasma levels has been observed.
Nakon peroralne primjene sildenafila tri puta na dan, AUC i Cmax povećavaju se razmjerno dozi u rasponu doza od 20-40 mg.
Common migraine, tremor, paraesthesia, burning sensation, hypoaesthesia
Poremećaji živčanog sustava vrlo često glavobolja često migrena, tremor, parestezija, osjećaj
The primary efficacy endpoint was the change from baseline at week 12 in 6-minute walk distance (6MWD).
Primarni ishod djelotvornosti bila je promjena od početne 6-minutne postignute udaljenosti hodom (engl.
Skin rash and sudden decrease or loss of hearing and decreased blood pressure have also been reported at an unknown frequency (frequency cannot be estimated from the available data).
Prijavljeni su i kožni osip, naglo smanjenje ili gubitak sluha te sniženje krvnog tlaka.
What Granpidam contains - The active substance is sildenafil.
Djelatna tvar je sildenafil.
Reproductive system and breast disorders Uncommon penile haemorrhage, haematospermia, gynaecomastia
Poremećaji reproduktivnog sustava i dojki manje često penilno krvarenje, hematospermija, ginekomastija nepoznato prijapizam, pojačana erekcija
Granpidam 20 mg
16. PODACI NA BRAILLEOVOM PISMU Granpidam 20 mg
Tablet core:
Rok valjanosti:
sildenafil 20 mg, sildenafil 40 mg or sildenafil 80 mg, three times a day.
Bolesnici su randomizirani u jednu od četiri terapijske skupine da primaju placebo, sildenafil u dozi od 20 mg, sildenafil u dozi od 40 mg ili sildenafil u dozi od 80 mg tri puta na dan.
NAME OF THE MEDICINAL PRODUCT Granpidam 20 mg tablets sildenafil
Granpidam 20 mg tablete sildenafil
Patients on all sildenafil doses achieved a statistically significant reduction in mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR) compared to those on placebo.
U usporedbi s bolesnicima koji su primali placebo, u bolesnika na svim dozama sildenafila postignuto je statistički značajno sniženje srednje vrijednosti plućnog arterijskog tlaka i plućnog krvožilnog otpora.
Non-arteritic anterior ischaemic optic neuropathy (NAION)*, Retinal vascular occlusion*, Visual field defect*
nepoznato neuobičajeni osjeti u oku nearterijska prednja ishemijska optička neuropatija*, okluzija krvnih žila
- have low blood pressure at rest. - lose a large amount of body fluids (dehydration) which can occur when you sweat a lot or do not drink enough liquids.
Obratite se svom liječniku prije nego uzmete Granpidam ako: - imate bolest koja je posljedica začepljenja ili suženja vene u plućima, a ne začepljenja ili suženja arterije - imate teških srčanih tegoba - imate tegoba sa srčanim komorama koje pumpaju krv - imate visok krvni tlak u krvnim žilama u plućima - imate nizak krvni tlak u mirovanju - izgubite veliku količinu tjelesne tekućine (dehidracija), što se može dogoditi kad se jako znojite ili ne pijete dovoljno tekućine.
Ear and labyrinth disorders Common vertigo
Poremećaji uha i labirinta mrežnice, poremećaj vidnog polja*
Nervous system disorders Very common headache
Poremećaji bubrega i mokraćnog sustava manje često hematurija
Estimated difference
Prijavljivanjesumnjinanuspojavu
CARTON
OBLIK
(PAOD Stage II)
(PAOD stadij II)
The relevance of clinical endpoints is questionable.
Relevantnost kliničkih završnih točaka je upitna.
Néphrologie Vol. 24 n° 4 2003, pp. 173-180).
Néphrologie Vol. 24 n° 4 2003, str. 173-180)).
Clinical safety
Klinička sigurnost
Available data is in fact indicative of such causal relationship.
Dostupni su podaci u stvari indikativni za takav kauzalni odnos.
Therefore, in accordance with Article 116 of Directive 2001/83/EC the CHMP recommends:
Direktive 2001/83/EZ, CHMP preporučuje:
Under-notification can be suspected given that:
U premalo prijava o nuspojavama može se posumnjati s obzirom da:
Some of them assessed the injection route or doses higher than recommended (up to 42mg daily, instead of 10mg daily).
Pojedina ispitivanja ocjenjivala su put injekcije ili doze veće od preporučenih (do 42 mg dnevno, umjesto 10 mg dnevno).
The patients disease is not well defined, nor the efficacy endpoints.
Bolest bolesnika nije dobro definirana kao ni završne točke djelotvornosti.
Although some of the proposed measures could help the early identification of patients with fibrosis, it may be too late as these reactions are sometimes irreversible.
Iako pojedine predložene mjere mogu pomoći pri ranoj identifikaciji bolesnika s fibrozom, može biti prekasno s obzirom da su ove reakcije ireverzibilne.
Almost all cases were serious (93% of the cases where seriousness was reported) and treatment with dihydroergotamine was discontinued in 91% of the cases (for which information is available) and in 57% of these cases, the outcome has been reported as improved or recovered.
Gotovo svi slučajevi su bili ozbiljni (u 93% slučajeva prijavljena je ozbiljnost) te je prekinuto liječenje dihidroergotaminom u 91% slučajeva (za koje su dostupne informacije), a u 57% ovih slučajeva kao ishodi su prijavljeni poboljšanje ili oporavak.
• The Committee considered that a potential causal association between fibrotic reactions or ergotism and oral dihydroergotamine cannot be excluded.
• Povjerenstvo smatra da se ne mogu isključiti potencijalne kauzalne poveznice između fibrotičkih reakcija ili ergotizma i oralnog dihidroergotamina.
A post-hoc analysis was performed in the sub-group of patients (n=288) with functional handicap and quality of life (QOL) decrease (defined by Migraine Specific Quality of Life, MSQ<80).
Izvršena je post-hoc analiza u podgrupi bolesnika (n=288) s funkcionalnim hendikepom i smanjenom kvalitetom života (QOL) (definirano kvalitetom života specifičnom za migrenu, MSQ<80).
• The Committee considered the procedure under Article 31 of Directive 2001/83/EC for ergot derivatives containing medicinal products in the concerned indications.
• Povjerenstvo je razmotrilo postupak sukladno članku 31. Direktive 2001/83/EC za lijekove koji sadrže derivate ergota u predmetnim indikacijama.
In order to lift the suspension, MAHs must identify a specific patient population for which the benefits of the product outweigh the risk.
Da bi se ukinula suspenzija, nositelji odobrenja moraju identificirati određenu populaciju bolesnika, za koju koristi nadmašuju rizik.
It has long been used in the treatment of migraine on the grounds of its vasoconstrictor activity, which is milder than that of ergotamine.
Dugo se već koristi u liječenju migrene zbog svog vazokonstrikcijskog djelovanja, koje je blaže od djelovanja ergotamina.
• Fibrosis is mentioned in several current European Summaries of Product Characteristics (SmPCs) and expected reactions are often under-reported
• je fibroza spomenuta u nekoliko aktualnih europskih sažetaka opisa svojstava lijeka (SmPC) i očekivane reakcije su uvijek premalo prijavljivane
However, more than half of the cases of ergotism reported have been described out of a context of overdose or without the use of a contraindicated drug.
No, više od polovice slučajeva prijavljenog ergotizma opisano je izvan konteksta predoziranja ili bez uporabe kontraindiciranog lijeka.
Efficacy was assessed by comparing absolute blood pressure measurements after treatment rather than comparing the differences between supine and standing position which was not considered acceptable.
Djelotvornost je ocijenjena usporedbom mjerenja apsolutnog krvnog tlaka nakon liječenja, a ne usporedbom razlika između krvnog tlaka u ležećem i stajaćem položaju, što se ne smatra prihvatljivim.
The CHMP has considered the totality of the available data on the safety and efficacy of dihydroergotamine.
CHMP je razmotrio ukupnost dostupnih podataka o sigurnosti i djelotvornosti dihidroergotamina.
The Committee therefore pointed out that the proposed measures are insufficient to avoid that some patients develop fibrosis and ergotism during treatment.
Stoga je Povjerenstvo naglasilo da predložene mjere nisu dostatne kako bi se izbjeglo da pojedini bolesnici razviju fibrozu i ergotizam tijekom liječenja.
Therefore, the group was of the opinion that based on the available evidence there is no need for this substance as there is no clear subset of patients that would benefit from it.
Stoga, grupa je bila mišljenja da na temelju dostupnih dokaza ne postoji potreba za ovom tvari s obzirom da nema jasnog podskupa bolesnika koji bi imali koristi od nje.
Ergotism is a serious reaction, which leads in rare cases reported to important sequelae following amputation or colon resection for example.
Ergotizam je ozbiljna reakcija, koja u rijetkim prijavljenim slučajevima rezultira važnim sekvelama nakon kojih slijedi primjerice amputacija ili resekcija kolona.
Patient population was heterogeneous, or patients with hypotension induced by treatment with psychotropic drugs.
Populacija bolesnika bila je heterogena ili bolesnici s hipotenzijom koja je inducirana liječenjem psihotropnim lijekovima.
On 18 January 2012, France triggered a referral under Article 31 of Directive 2001/83/EC for the following ergot derivatives containing medicinal products: dihydroergocryptine/caffeine, dihydroergocristine, dihydroergotamine, dihydroergotoxine and nicergoline.
Dana 18. siječnja 2012. godine, Francuska je pokrenula postupak upućivanja sukladno članku 31. Direktive 2001/83/EZ za sljedeće lijekove koji sadrže derivate ergota: dihidroergokriptin/kafein, dihidroergokristin, dihidroergotamin, dihidroergotoksin i nicergolin.
• The Committee considered the overall submitted data provided by the MAHs and the outcome of the scientific advisory group.
• Povjerenstvo je razmotrilo sve podnijete podatke koje su dostavili nositelji odobrenja i zaključak znanstvene savjetodavne grupe.
As expected, fibrosis occurred mostly in female patients (68%) after long time of treatment with dihydroergotamine (9.1 years on average) and the most frequent type of fibrosis reaction reported was retroperitoneal (36%), followed by cardiac (30%) and pleural (18%).
Kako je očekivano, fibroza je nastupila većinom u ženskih bolesnika (68%) nakon dugotrajnog liječenja dihidroergotaminom (prosječno 9,1 godinu), a najčešće prijavljivani tip fibrotičke reakcije bio je retrorerotonealan (36 %), nakon čega slijedi srčani (30%) i pleuralni (18%).
• Fibrosis is also an insidious reaction that occurs after a long period of treatment and thus with often a delayed diagnosis.
• je fibroza također spor i neprimjetan odgovor koji nastupa nakon dugog razdoblja liječenja i stoga često s kasnom dijagnozom.
The studies presented are old and of poor methodological quality: uncontrolled, open designed, with a low number of patients (n=12 in Wenzel, 1989, the most recent study).
Dostavljena ispitivanja su stara i slabe metodičke kvalitete: nekontrolirana, otvorenog dizajna, s malim brojem bolesnika (n=12 u Wenzel, 189., najnovije ispitivanje).
The MAHs also submitted their own overviews and critical summaries of all spontaneous reports of fibrotic reactions (cardiac with or without pulmonary arterial hypertension, pulmonary, pleural, peritoneal, retroperitoneal, etc) and ergotism with their ergot derivatives-containing medicinal products.
Nositelji odobrenja dostavili su, također, i svoje vlastite preglede i kritičke sažetke svih spontanih prijava fibrotičkih reakcija (srčanih s ili bez pulmonalne arterijske hipertenzije, pulmonalnih, pleuralnih, peritonealnih, retroperitonealnih, itd.) i ergotizma povezanih s njihovim lijekovima koji sadrže derivate ergota.
The number of patients included was small and the duration of treatment was too short.
Uključen je mali broj bolesnika, a trajanje liječenja je prekratko.
This reaction occurred in young patients (mean age among cases reported: 41 years-old), with a short time to onset after dihydroergotamine initiation (less than 2 months, mean: 2 days).
Ova reakcija nastupa u mladih bolesnika (prosječna dob prijavljenih slučajeva: 41 godina), s kratkim vremenom pojave nakon početka uzimanja dihidroergotamina (manje od 2 mjeseca, srednje: 2 dana).
Symptoms of ergotism are listed in the sections 4.8, 4.9 of all the SmPCs and ergotism is identified in section 4.4 as a consequence of a prolonged use of dihydroergotamine or high dosage.
Simptomi ergotizma navedeni su u dijelovima 4.8, 4.9 svih sažetaka opisa svojstava lijeka, a ergotizam je definiran u dijelu 4.4 kao posljedica produžene uporabe dihidroergotamina ili velike doze.
Dihydroergotamine mesilate (dihydroergotamine - DHE) is a semi-synthetic derivative of ergotamine.
Dihidroergotamin mesilat (dihidroergotamin - DHE) je polusintetički derivat ergotamina.
In addition, patients were included if they displayed a reduction of systolic blood pressure of more than 10 mmHg, which does not comply with the established definition of orthostatic hypotension (at least 20 mm Hg below baseline).
Nadalje, bolesnici su uključeni ako su pokazali smanjenje sistoličkog krvnog tlaka veće od 10 mmHg, što ne udovoljava utvrđenoj definiciji ortostatske hipotenzije (najmanje 20 mm Hg ispod osnovne vrijednosti).
The seriousness of such adverse effects and their possible fatal outcome is underlined.
Naglašena je ozbiljnost ovakvih nuspojava i njihov mogući smrtonosni ishod.
• The Committee is of the opinion that the evidence for clinically significant efficacy of oral dihydroergotamine in the currently assessed indications is very limited, and therefore the potential benefit for patients in these indications is outweighed by the above identified risk.
• Povjerenstvo je mišljenja da su dokazi klinički značajne djelotvornosti oralnog dihidroergotamina za trenutno ocjenjene indikacije vrlo ograničeni, te stoga identificirani rizici nadmašuju potencijalne koristi za bolesnike u ovim indikacijama.
In the reported cases, dihydroergotamine is mostly indicated for migraine or headache (30 patients) and used with the recommended daily dosage.
U prijavljenim slučajevima, dihidroergotamin je većinom indiciran za migrenu ili glavobolju (30 bolesnika), te se koristi s preporučenim dnevnim dozama.
Therefore, the group was of the opinion that there is not a clearly defined population, which unsatisfactorily responds to standard migraine prophylaxis treatment, where there is a therapeutic need for this substance as alternative/last line treatment.
Stoga je mišljenje grupe da ne postoji jasno definirana populacija, koja nezadovoljavajuće odgovara na standardnu profilaksu migrene, kada postoji terapijska potreba za ovom tvari kao alternativno liječenje/posljednja opcija.
A total of 363 subjects were treated with dihydroergotamine or placebo during 4 months after 1 month of placebo “run-in”.
Ukupno su liječene 363 osobe dihidroergotaminom ili placebom tijekom 4 mjeseca nakon 1 mjeseca „run-in“ razdoblja s placebom.
The design of this study was considered acceptable by the CHMP (i.e. controlled, randomised, double-blind) but the size of the study was considered small (n=58).
CHMP smatra dizajn ovog ispitivanja prihvatljivim (odnosno kontrolirano, randomizirano, dvostruko slijepo), no smatra veličinu ispitivanja malom (n=58).
However, the CHMP noted that for most of these patients an improvement or recovering had been observed after corticosteroid treatment or surgery (valve replacement), and in most cases the improvement is stated based on clinical symptoms (no scan).
No, CHMP je napomenuo da je u većini ovih bolesnika uočeno poboljšanje ili oporavak nakon liječenja kortikosteroidima ili kirurškog zahvata (zamjena zaliska), te je u većini slučajeva poboljšanje navedeno na temelju kliničkih simptoma (bez skeniranja).
In the acute treatment of migraine, it is administered parenterally or in the form of a nasal spray because of the low bioavailability of the unchanged drug by the oral route.
U slučaju akutnog liječenja migrene, lijek se primjenjuje parenteralno ili u obliku spreja za nos zbog slabe bioraspoloživosti nepromijenjenog lijeka oralnoga puta.
The CHMP was therefore requested to give its opinion on whether the marketing authorisations for ergot derivatives containing medicinal products should be maintained, varied, suspended or withdrawn in relation to the below mentioned indications:
Stoga je zatraženo od CHMP-a da iznese mišljenje trebaju li se odobrenja za stavljanje u promet lijekova koji sadrže derivate ergota zadržati, izmijeniti, suspendirati ili ukinuti s obzirom na niže navedene indikacije:
From the approved indications of the dihydroergotamine containing medicinal products the ones that are in the scope of this referral procedure and are approved in at least one Member State are the following (specific wording of the indication may vary from product to product):
Od odobrenih indikacija za lijekove koji sadrže dihidroergotamin, sljedeće su indikacije predmetom ovog postupka upućivanja i odobrene su od barem jedne države članice (točna formulacija indikacije može varirati od proizvoda do proizvoda):
Moreover, the 8 new spontaneous notifications reported during the French survey conducted in 2011 show that the risk minimisation measures that are currently in place are not sufficient to prevent the risk of fibrotic reactions.
Nadalje, 8 novih spontanih prijava zabilježeno je tijekom francuskog istraživanja provedenog 2011. godine, koji pokazuju da mjere za smanjivanje rizika, koje su trenutno na snazi nisu dostatne kako bi se spriječio razvoj fibrotičkih reakcija.
Only one study, Thulesius (1986), demonstrated a significant decrease of immediate drop in blood pressure after standing up with 10mg per day dihydroergotamine compared to placebo, in patients with hypotension induced by treatment with psychotropic drugs and it became available after the initial marketing authorisation was granted.
Samo jedno ispitivanje, Thulesius (1986.), prikazalo je značajno smanjenje neposrednog pada u krvnom tlaku nakon ustajanja s 10 mg dihidroegotamina po danu u usporedbi s placebom u bolesnika s hipotenzijom koja je inducirana liječenjem psihotropnim lijekovima, te je postalo dostupno nakon prvotnog odobrenja za stavljanje lijeka u promet.
Twelve patients suffering from peripheral venous insufficiency were treated first with intravenous dihydroergotamine followed by oral dihydroergotamine administration for one week.
Dvanaest bolesnika, koji su bolovali od periferne venske insuficijencije, liječeni su prvo intravenoznim dihidroergotaminom nakon čega je slijedila oralna primjena dihidroergotamina jednom tjedno.
One case was confounded by medical history and in 25 cases co-suspected drugs were reported: benfluorex (4 cases), dexflenfuramine (4 cases), pergolide (1 case), beta blockers (9 cases), fenofibrate (2 cases) and ergot derivative drug (8 cases).
Jedan slučaj je zamijenjen anamnezom, a u 25 slučajeva prijavljeni su lijekovi koji mogu izazvati iste nuspojave: benfluoreks (4 slučaja), deksflenfuramin (4 slučaja), pergolid (1 slučaj), beta blokeri (9 slučajeva), fenofibrat (2 slučaja) i lijek koji sadrži derivat ergota (8 slučajeva).
For the indication “orthostatic hypotension” the submitted studies were considered by the CHMP of poor methodological quality: they were mainly uncontrolled trials with only 1 double-blind study but with low number of patients.
Za indikaciju „ortostatska hipotenzija“, CHMP smatra da su dostavljena ispitivanja slabe metodičke kvalitete: to su bila uglavnom nekontrolirana istraživanja sa samo 1 dvostruko slijepim ispitivanjem, no mali brojem bolesnika.
• Acute retinopathies of vascular origin
• akutne retinopatije vaskularnog porijekla
Following a national pharmacovigilance review held in 2011 new spontaneous notifications reported with some of those products identified serious cases of fibrosis and ergotism and France considered that this safety concern is not outweighed by the limited evidence of efficacy.
Nakon nacionalnog farmakovigilancijskog pregleda provedenog 2011. godine, nove spontane prijave zabilježene za pojedine prethodno navedene lijekove identificirale su teške slučajeve fibroze i ergotizma, te je Francuska smatrala da ovo sigurnosno pitanje nije nadmašeno ograničenim dokazom djelotvornosti.
• Ancillary treatment of intermittent claudication in symptomatic peripheral arterial occlusive disease
• pomoćno liječenje intermitentne klaudikacije u slučaju simptomatske bolesti perifernih arterija