natgillin/translations-raw huggingface dataset:
Forsøgspersonerne (38% drenge og 62% piger) havde en legemsvægt ≥8 kg, primær pulmonal hypertension (PPH) (33%) eller PAH sekundært til kongenit hjertesygdom (systemisk-pulmonal shunt 37%, kirurgisk intervention 30%).
Subjects (38% male and 62% female) had a body weight ≥8 kg, and had primary pulmonary hypertension (PPH) [33%], or PAH secondary to congenital heart disease [systemic-to-pulmonary shunt 37%, surgical repair 30%].
Ud af de 94 forsøgspersoner, som rapporterede en alvorlig bivirkning, var 14/55 (25,5%) forsøgspersoner i lavdosis-gruppen, 35/74 (47%) i middeldosis-gruppen og 45/100 (45%) i højdosisgruppen.
Of the 94 subjects reporting a serious adverse event, 14/55 (25.5%) subjects were in the low dose group, 35/74 (47.3%) in the medium dose group, and 45/100 (45%) in the high dose group.
Den procentvise reduktion i PVR (11,2%, 12,9%, 23,3%) efter 12 uger for sildenafil 20 mg, 40 mg og 80 mg 3 gange dagligt var proportionelt større end reduktionen i systemisk vaskulær modstand (SVR) (7,2%, 5,9%, 14,4%).
The percent reduction at 12 weeks for sildenafil 20 mg, 40 mg and 80 mg TID in PVR (11.2%, 12.9%, 23.3%) was proportionally greater than the reduction in systemic vascular resistance (SVR) (7.2%, 5.9%, 14.4%).
Patienter på alle doser af sildenafil opnåede en statistisk signifikant reduktion i middel pulmonalt arterielt tryk (mPAP) og pulmonal vaskulær modstand (PVR) sammenlignet med dem, der fik placebo.
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.
Farmakokinetikken af sildenafil er ikke undersøgt hos patienter med alvorlig nedsat leverfunktion.
The pharmacokinetics of sildenafil in patients with severely impaired hepatic function have not been studied.
Hos patienter med pulmonal arteriel hypertension er de gennemsnitlige steady-state koncentrationer 2050% højere end de undersøgte doser på 20-80 mg 3 gange dagligt sammenlignet med raske frivillige forsøgspersoner.
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.
Forsigtighed tilrådes derfor ved samtidig anvendelse.
Therefore, caution is recommended in case of co-administration.
Samtidig administration af PDE5-hæmmere, inklusive sildenafil, med guanylatcyklase-stimulatorer, som f.eks. riociguat, er kontraindikeret, da det kan føre til symptomatisk hypotension (se pkt.
The co-administration of PDE5 inhibitors, including sildenafil, with guanylate cyclase stimulators, such as riociguat, is contraindicated as it may potentially lead to symptomatic hypotension (see section
Almene symptomer og reaktioner på administrationsstedet Almindelig pyreksi *Disse bivirkninger/hændelser er rapporteret hos patienter, der tager sildenafil til behandling af erektil dysfunktion (MED).
Common pyrexia *These adverse events/reactions have been reported in patients taking sildenafil for the treatment of male erectile dysfunction (MED).
I denne population var Kaplan-Meier-estimater for 1, 2 og 3 års overlevelse hhv. 96 %, 91 % og 82 %.
In this population, Kaplan-Meier estimates of 1, 2 and 3 year survival were 96%, 91% and 82%, respectively.
Filmovertræk:
Film coat:
Metabolisme og ernæring Almindelig væskeophobning
Metabolism and nutrition disorders Common fluid retention
Den estimerede forskel mellem den gennemsnitlige sildenafildosis og placebo var 11,33% (95% CI: 1,72-20,94) (se tabel 2).
The estimated difference between the medium sildenafil dose and placebo was 11.33% (95% CI: 1.72 to 20.94) (see Table 2).
Tabel 2: Procentvis ændring i maksimal VO2 fra baseline i sildenafilgrupperne korrigeret for placebo
Table 2: Placebo Corrected % Change from Baseline in Peak VO2 by Active Treatment Group
Sildenafils eksponering var 5 gange højere ved dosis på 80 mg 3 gange dagligt sammenlignet med en eksponering med en dosis på 20 mg 3 gange dagligt.
Sildenafil exposure was 5-fold higher at a dose of 80 mg three times a day compared to the exposure at a dose of 20 mg three times a day.
Filmovertræk: Hypromellose (15cp) (E464), titandioxid (E171), lactosemonohydrat, triacetin.
Film coat: hypromellose (15cp) (E464), titanium dioxide (E171), lactose monohydrate, triacetin.
Enkelte orale doser af sildenafil på op til 100 mg gav ingen klinisk relevant effekt på EKG hos raske frivillige forsøgspersoner.
Single oral doses of sildenafil up to 100 mg in healthy volunteers produced no clinically relevant effects on ECG.
Svær hypotension (blodtryk <90/50 mmHg) ved initiering.
Recent history of stroke or myocardial infarction, Severe hypotension (blood pressure <90/50 mmHg) at initiation.
Indeholder lactosemonohydrat.
Contains lactose monohydrate.
Hvis De oplever pludseligt nedsat syn eller synstab, skal De stoppe med at tage Granpidam og straks kontakte Deres læge (se også afsnit 4).
If you experience sudden decrease or loss of vision, stop taking Granpidam and contact your doctor immediately (see also section 4).
Hos raske ældre frivillige forsøgspersoner (65 år og derover) ses en reduceret clearance af sildenafil, som medfører ca. 90% højere plasmakoncentration af sildenafil og den aktive N-desmethylmetabolit, sammenlignet med yngre frivillige forsøgspersoner (18-45 år).
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).
Granpidam bør pga. manglende data ikke anvendes til gravide, medmindre det er strengt nødvendigt.
Due to lack of data, Granpidam should not be used in pregnant women unless strictly necessary.
I pivotalstudiet blev i alt 207 patienter behandlet med sildenafil, og status for patienternes langtidsoverlevelse blev vurderet i mindst 3 år.
A total of 207 patients were treated with sildenafil in the pivotal study, and their long term survival status was assessed for a minimum of 3 years.
Patienter på sildenafil opnåede en statistisk signifikant reduktion i middel pulmonalt arterielt tryk (mPAP) sammenlignet med dem, der fik placebo.
Patients on sildenafil achieved a statistically significant reduction in mean Pulmonary Arterial Pressure (mPAP) compared to those on placebo.
Brugen af prostacyclin, prostacyclin analoger og endothelinreceptorantagonister som tillægsbehandling samt arginin-tilskud var ikke tilladt.
The use of prostacyclin, prostacyclin analogues and endothelin receptor antagonists was not permitted as add-on therapy, and neither was arginine supplementation.
Bivirkninger rapporteret efter markedsføring er anført i kursiv.
Reports from post-marketing experience are included in italics.
Efter kronisk dosering på 80 mg 3 gange dagligt til patienter med pulmonal arteriel hypertension ses en mindre effekt i blodtryksreduktionen (en reduktion i både systolisk og diastolisk tryk på 2 mmHg).
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).
Ved ordination af sildenafil skal lægen omhyggeligt overveje, om patienter med visse underliggende tilstande vil kunne blive påvirket af sildenafils lette til moderate vasodilaterende effekt, f.eks. hypotensive eller dehydrerede patienter eller patienter med svær venstre ventrikel udløbsobstruktion eller autonom dysfunktion (se pkt.
When prescribing sildenafil, physicians should carefully consider whether patients with certain underlying conditions could be adversely affected by sildenafil's mild to moderate vasodilatory effects, for example patients with hypotension, patients with fluid depletion, severe left ventricular outflow obstruction or autonomic dysfunction (see section 4.4).
Sikkerhed og effekt af sildenafil ved samtidig anvendelse af andre lægemidler til pulmonal arteriel hypertension (f.eks. ambrisentan, iloprost) er ikke undersøgt i kontrollerede kliniske studier.
The efficacy and safety of sildenafil co-administered with other treatments for pulmonary arterial hypertension (e.g. ambrisentan, iloprost) has not been studied in controlled clinical trials.
Det primære endepunkt var procentvis ændring i maksimalt iltforbrug (VO2) fra baseline til uge 16 bestemt ved CPET-test af forsøgspersonerne i de kombinerede doseringsgrupper (se tabel 2).
The primary endpoint was the placebo-corrected percentage change in peak VO2 from baseline to week 16 assessed by CPET testing in the combined dose groups (Table 2).
I denne population var Kaplan-Meier-estimater for 1-, 2- og 3-års overlevelse hhv. 92%, 81% og 74%.
In this population, Kaplan-Meier estimates of 1, 2 and 3 year survival were 92%, 81% and 74%, respectively.
Den anbefalede dosis er 20 mg 3 gange dagligt.
The recommended dose is 20 mg three times a day (TID).
alfa-blokker (f.eks. doxazosin) til behandling af for højt blodtryk eller vandladningsbesvær ved forstørret blærehalskirtel (prostata), da kombination af disse to lægemidler kan give symptomer på grund af blodtryksnedsættelse (f.eks. svimmelhed).
- Alpha-blocker therapy (e.g. doxazosin) for the treatment of high blood pressure or prostate problems, as the combination of the two medicines may cause symptoms resulting in the lowering of your blood pressure (e.g. dizziness, light headedness).
PDE5-hæmmere, såsom sildenafil, har vist sig at øge den blodtrykssænkende virkning af denne medicin.
PDE5 inhibitors, such as sildenafil have been shown to increase the hypotensive effects of this medicine.
Når PDE5-hæmmere, herunder sildenafil, anvendes til behandling af rejsningsproblemer hos mænd, er der med ukendt hyppighed set bivirkninger, der påvirker synet: delvist, pludseligt, midlertidigt eller permanent nedsat syn eller synstab på det ene eller begge øjne.
When used to treat male erectile dysfunction (ED), the following visual side effects have been reported with PDE5 inhibitors, including sildenafil at an unknown frequency; partial, sudden, temporary, or permanent decrease or loss of vision in one or both eyes.
Sildenafil (50 mg) øger ikke den af acetylsalicylsyre (150 mg) forlængede blødningstid.
Sildenafil (50 mg) did not potentiate the increase in bleeding time caused by acetyl salicylic acid (150 mg).
Tabletkerne: Mikrokrystallinsk cellulose, vandfrit calciumhydrogenfosfat, croscarmellosenatrium, hypromellose (5cp) (E464), magnesiumstearat.
Tablet core: microcrystalline cellulose, anhydrous calcium hydrogen phosphate, croscarmellose sodium, hypromellose (5cp) (E464), magnesium stearate
En større procentdel af patienterne på alle 3 sildenafil-doser (28%, 36% og 42% af patienterne, der fik hhv. 20 mg, 40 mg og 80 mg 3 gange dagligt) viste forbedring på mindst en WHO-funktionsklasse efter 12 uger sammenlignet med placebo (7%).
A greater percentage of patients on each of the sildenafil doses (i.e. 28%, 36% and 42% of subjects who received sildenafil 20 mg, 40 mg and 80 mg TID doses, respectively) showed an improvement by at least one WHO functional class at week 12 compared to placebo (7%).
Bivirkninger, der blev rapporteret hos >10% af 229 forsøgspersoner, der blev behandlet med sildenafil (alle dosisgrupper, inklusive 9 patienter, som ikke fortsatte i det langvarige studie), var infektion i øvre luftveje (31%), hovedpine (26%), opkastning (22%), bronkitis (20%), pharyngitis (18%), pyreksi (17%), diarré (15%) samt influenza og epistaxis (12% hver).
Adverse reactions reported in >10% of 229 subjects treated with sildenafil (combined dose group, including 9 patients that did not continue into the long-term study) were upper respiratory infection (31%), headache (26%), vomiting (22%), bronchitis (20%), pharyngitis (18%), pyrexia (17%), diarrhoea (15%), and influenza, epistaxis (12% each).
Psykiske forstyrrelser Almindelig søvnløshed, angst
Psychiatric disorders Common insomnia, anxiety
PVC/alu-blister med 90 tabletter.
PVC/Alu blisters of 90 tablets.
Almindelig cellulitis, influenza, bronkitis, sinuitis, rinitis, gastroenteritis
Infections and infestations Common cellulitis, influenza, bronchitis, sinusitis, rhinitis, gastroenteritis
Sildenafil havde ingen effekt på slagvolumen og nedsatte ikke blodcirkulationen i de forsnævrede koronararterier.
Sildenafil showed no effect on cardiac output, and did not impair blood flow through the stenosed coronary arteries.
De mest almindeligt rapporterede bivirkninger (større eller lig med 10%) for sildenafil sammenlignet med placebo er hovedpine, ansigtsrødme, dyspepsi, diarré og smerter i ekstremiteterne.
The most commonly reported adverse reactions that occurred (greater or equal to 10%) on sildenafil compared to placebo were headache, flushing, dyspepsia, diarrhoea and pain in extremity.
I et placebo-kontrolleret studie med sildenafil til patienter i alderen 1-17 år med pulmonal arteriel hypertension blev i alt 174 patienter behandlet med enten lavdosis (10 mg til patienter >20 kg, ingen patienter ≤20 kg fik lavdosis), middeldosis (10 mg til patienter ≥8-20 kg, 20 mg til patienter ≥2045 kg, 40 mg til patienter >45 kg) eller højdosis (20 mg til patienter ≥8-20 kg, 40 mg til patienter ≥2045 kg, 80 mg til patienter >45 kg) sildenafil og 60 blev behandlet med placebo.
In the placebo-controlled study of sildenafil in patients 1 to 17 years of age with pulmonary arterial hypertension, a total of 174 patients were treated three times a day with either low (10 mg in patients >20 kg; no patients ≤20 kg received the low dose), medium (10 mg in patients ≥8-20 kg; 20 mg in patients ≥20-45 kg; 40 mg in patients >45 kg) or high dose (20 mg in patients ≥8-20 kg; 40 mg in patients ≥20-45 kg; 80 mg in patients >45 kg) regimens of sildenafil and 60 were treated with placebo.
NAVN PÅ INDEHAVEREN AF MARKEDSFØRINGSTILLADELSEN Accord
NAME OF THE MARKETING AUTHORISATION HOLDER Accord
Sildenafil (50 mg) forstærker ikke den hypotensive effekt af alkohol hos raske frivillige forsøgspersoner med gennemsnitlige maksimale koncentrationer af alkohol i blodet på 80 mg/dl (0,8 ‰).
Sildenafil (50 mg) did not potentiate the hypotensive effects of alcohol in healthy volunteers with mean maximum blood alcohol levels of 80 mg/dl.
FREMSTILLER(E) ANSVARLIG(E) FOR BATCHFRIGIVELSE
A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE
For patienter med 6MWD < 325 meter ved baseline blev der set bedre effekt ved højere doser (placebo-korrigeret stigning på 58 meter, 65 meter og 87 meter for hhv. 20 mg, 40 mg og 80 mg 3 gange dagligt).
For patients with a baseline 6MWD <325 m improved efficacy was observed with higher doses (placebo-corrected improvements of 58 metres, 65 metres and 87 metres for 20 mg, 40 mg and 80 mg doses TID, respectively).
Mave-tarmkanalen Meget almindelig diarré, dyspepsi
Gastrointestinal disorders Very common diarrhoea, dyspepsia
Prækliniske studier viste en additiv systemisk blodtrykssænkende virkning, når PDE5-hæmmere blev kombineret med riociguat.
Riociguat: Preclinical studies showed additive systemic blood pressure lowering effect when PDE5 inhibitors were combined with riociguat.
Kontakt lægen, før De tager Granpidam, hvis De har sygdom forårsaget af blokeret eller forsnævret vene i lungerne og ikke en blokeret eller forsnævret arterie.
- have a disease due to a blocked or narrow vein in the lungs rather than a blocked or narrow artery.
Er De usikker, så spørg lægen eller på apoteket.
If you are not certain, ask your doctor or pharmacist.
I dette studie var 63 af 234 (27%) af patienterne <7 år (sildenafil lavdosis=2, middeldosis=17, højdosis=28, placebo=16), og 171 af 234 (73%) af patienterne var >7 år (sildenafil lavdosis=40, middeldosis=37, højdosis=49, placebo=44 se nedenfor).
In this trial, 63 of 234 (27%) patients were <7 years old (sildenafil low dose = 2; medium dose = 17; high dose = 28; placebo = 16) and 171 of 234 (73%) patients were 7 years or older (sildenafil low dose = 40; medium dose = 38; and high dose = 49; placebo = 44).
Almindelig migræne, tremor, paræstesi, brændende følelse, hypæstesi
Common migraine, tremor, paraesthesia, burning sensation, hypoaesthesia
Samtidig administration af orale antikonceptiva (30 µg ethinylestradiol og 150 µg levonorgestrel) påvirker ikke sildenafils farmakokinetik.
Co-administration of oral contraceptives (ethinyloestradiol 30 µg and levonorgestrel 150 µg) did not affect the pharmacokinetics of sildenafil.
I tilfælde af overdosering bør der gives symptomatisk behandling efter behov.
In cases of overdose, standard supportive measures should be adopted as required.
Der blev givet doser på op til 80 mg 3 gange dagligt (4 gange den anbefalede dosis på 20 mg 3 gange dagligt) og efter 3 år blev 87% af 183 patienter behandlet med sildenafil 80 mg 3 gange dagligt.
Doses up to 80 mg three times a day (4 times the recommended dose of 20 mg three times a day) were administered and after 3 years 87% of 183 patients on study treatment were receiving sildenafil 80 mg TID.
Øjne Almindelig retinablødning, nedsat syn, sløret syn, fotofobi, chromatopsia, cyanopsia, øjenirritation, okulær hyperæmi
Eye disorders Common retinal haemorrhage, visual impairment, vision blurred, photophobia, chromatopsia, cyanopsia, eye irritation, ocular hyperaemia
Lægemidler til erektil dysfunktion, ATC-kode: G04B E03.
Pharmacotherapeutic group: Urologicals, Drugs used in erectile dysfunction, ATC code: G04BE03
hvis De tager medicin, som indeholder nitrater eller nitrogenoxiddonorer som amylnitrit (“poppers”).
- if you are taking medicines containing nitrates, or nitric oxide donors such as amyl nitrate (“poppers”).
Et randomiseret dobbelt-blindt, placebo-kontrolleret studie blev udført på 278 patienter med primær pulmonal hypertension, PAH forbundet med bindevævssygdom og PAH efterfulgt af kirurgisk intervention af medfødte hjertelidelser.
A randomised, double-blind, placebo-controlled study was conducted in 278 patients with primary pulmonary hypertension, PAH associated with connective tissue disease, and PAH following surgical repair of congenital heart lesions.
Placebogruppen: n=29.
n=29 for placebo group
for tiden har mavesår eller har blødningsforstyrrelse (som f.eks. hæmofili) eller hyppigt får næseblod.
- currently have a stomach ulcer, a bleeding disorder (such as haemophilia) or problems with nose bleeds.
De patienter, der blev inkluderet i det pivotale studie, var egnede til at indgå i et langvarigt, åbent, studie, der blev forlænget.
Patients enrolled into the pivotal study were eligible to enter a long term open label extension study.
Populationsfarmakokinetiske analyser hos patienter med pulmonal arteriel hypertension tyder på, at samtidig anvendelse af beta-blokkere i kombination med CYP3A4-substrater kan resultere i en øget sildenafil-eksponering sammenlignet med anvendelse af CYP3A4-substrater alene.
The population pharmacokinetic analysis in pulmonary arterial hypertension patients suggested that co-administration of beta-blockers in combination with CYP3A4 substrates might result in an additional increase in sildenafil exposure compared with administration of CYP3A4 substrates alone.
Sildenafils metabolisme finder overvejende sted via CYP (cytokrom P450) isoformer 3A4 (primær vej) og 2C9 (sekundær vej).
Sildenafil metabolism is principally mediated by the cytochrome P450 (CYP) isoforms 3A4 (major route) and 2C9 (minor route).
Det Europæiske Lægemiddelagentur har udsat kravet om fremlæggelse af resultaterne af studier med sildenafil til nyfødte med pulmonal arteriel hypertension (se pkt.
The European Medicines Agency has deferred the obligation to submit the results of studies with sildenafil in newborns with pulmonary arterial hypertension (see section 4.2 for information on paediatric use).
Efter markedsføringen er der i forbindelse med brugen af sildenafil til mandlig erektil dysfunktion rapporteret alvorlige kardiovaskulære hændelser, inklusive myokardieinfarkt, ustabil angina pectoris, pludselig hjertedød, ventrikulær arytmi, cerebrovaskulær blødning, transitorisk iskæmisk attak, hypertension og hypotension.
In post-marketing experience with sildenafil for male erectile dysfunction, serious cardiovascular events, including myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmia, cerebrovascular haemorrhage, transient ischaemic attack, hypertension and hypotension have been reported in temporal association with the use of sildenafil.
Medicin, der indeholder nitrater eller såkaldte nitrogenoxiddonorer som f.eks. amylnitrit (“poppers”).
- Medicines containing nitrates, or nitric oxide donors such as amyl nitrate (“poppers”).
For samtidig behandling med sildenafil og de mest potente CYP3A4hæmmere, se pkt.
For the use of sildenafil with the most potent CYP3A4 inhibitors, see section 4.3.
De mest potente af CYP3A4-hæmmerne såsom ketoconazol og itraconazol må forventes at have en effekt tilsvarende ritonavir (se pkt.
The most potent of the CYP3A4 inhibitors such as ketoconazole and itraconazole would be expected to have effects similar to ritonavir (see section 4.3).
Derfor anbefales dosisjustering ved anvendelse af CYP3A4-hæmmere (se pkt.
Therefore dose adjustments are recommended when using CYP3A4 inhibitors (see section 4.2).
Dosisjustering til 20 mg 1 gang dagligt anbefales ved samtidig behandling med mere potente CYP3A4-hæmmere som clarithromycin, telithromycin og nefazodon.
A downward dose adjustment to 20 mg once daily is recommended in case of co-administration with more potent CYP3A4 inhibitors clarithromycin, telithromycin and nefazodone.
Patienterne blev randomiserede til placebo eller sildenafil (i en fast dosistitrering, som starter fra 20 mg 3 gange dagligt til 40 mg og herefter 80 mg 3 gange dagligt alt efter hvor godt det blev tolereret) anvendt i kombination med intravenøs epoprostenol.
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 as tolerated) when used in combination with intravenous epoprostenol.
Dosisjustering af sildenafil til 20 mg 2 gange dagligt bør overvejes til patienter i behandling med CYP3A4-hæmmere som erythromycin eller saquinavir.
A downward dose adjustment to 20 mg twice daily should be considered when sildenafil is co-administered to patients already receiving CYP3A4 inhibitors like erythromycin or saquinavir.
De hyppigste bivirkninger (med en frekvens ≥1%) hos sildenafil-patienter (kombinerede doser) og med en frekvens på > 1% i forhold til placebo-patienter var pyreksi, øvre luftvejsinfektioner (hver 11,5%), opkastning (10,9%), kraftigere erektion (herunder spontane erektioner hos drenge) (9,0%), kvalme, bronkitis (hver 4,6%), pharyngitis (4,0%), næseflåd (3,4%) samt pneumoni og rhinitis (hver 2,9%).
The most common adverse reactions that occurred (with a frequency ≥1%) in sildenafil patients (combined doses) and with a frequency >1% over placebo patients were pyrexia, upper respiratory tract infection (each 11.5%), vomiting (10.9%), erection increased (including spontaneous penile erections in male subjects) (9.0%), nausea, bronchitis (each 4.6%), pharyngitis (4.0%), rhinorrhoea (3.4%), and pneumonia, rhinitis (each 2.9%).