natgillin/translations-raw huggingface dataset:
Sikkerhed og effekt af sildenafil ved samtidig anvendelse af andre PDE5-hæmmere er ikke undersøgt hos patienter med pulmonal arteriel hypertension (se pkt.
The safety and efficacy of sildenafil when co-administered with other PDE5 inhibitors has not been studied in pulmonary arterial hypertension patients (see section 4.4).
Forsøgspersoner, der vejede ≤ 20 kg, blev inkluderet i middel- eller højdosisgruppen (1:1), mens forsøgspersoner, der vejede > 20 kg, blev inkluderet i lav-, middel- eller højdosisgruppen (1:1:1).
Subjects who had been in the placebo group in the short-term study were randomly reassigned to sildenafil treatment; subjects weighing ≤20 kg entered the medium or high dose groups (1:1), while subjects weighing >20 kg entered the low, medium or high dose groups (1:1:1).
Anvendelse til andre former for pulmonal arteriel hypertension anbefales ikke.
The use of sildenafil in other forms of PAH is not recommended.
Det anbefales at udvise forsigtighed, når sildenafil anvendes hos patienter, der samtidigt anvender en alfa-blokker, idet dette hos følsomme patienter kan føre til symptomatisk hypotension (se pkt.
Caution is advised when sildenafil is administered to patients taking an alpha-blocker as the co-administration may lead to symptomatic hypotension in susceptible individuals (see section 4.5).
Sildenafils virkningsevne hos patienter, der allerede er i behandling med bosentan, er ikke påvist endegyldigt (se pkt.
The efficacy of sildenafil in patients already on bosentan therapy has not been conclusively demonstrated (see sections 4.5 and 5.1).
Studier med sildenafil er udført med typer af pulmonal arteriel hypertension, der er relateret til primær (idiopatisk) sygdom eller forbundet med bindevævssygdom eller kongenit hjertesygdom.
Studies with sildenafil have been performed in forms of pulmonary arterial hypertension related to primary (idiopathic), connective tissue disease associated or congenital heart disease associated forms of PAH (see section 5.1).
Spørg lægen eller sundhedspersonalet, hvis der er noget, De er i tvivl om.
Check with your doctor or pharmacist if you are not sure.
Samtidig indgift med HIV-proteasehæmmeren, ritonavir, som er en meget potent P450 hæmmer, ved steady-state (500 mg 2 gange dagligt) og enkeltdosis af sildenafil (100 mg) gav en stigning i sildenafils Cmax på 300% (4 gange) og en stigning i sildenafils plasma AUC på 1.000% (11 gange).
Co-administration of the HIV protease inhibitor ritonavir, which is a highly potent P450 inhibitor, at steady state (500 mg twice daily) with sildenafil (100 mg single dose) resulted in a 300% (4-fold) increase in sildenafil Cmax and a 1,000% (11-fold) increase in sildenafil plasma AUC.
Hos raske frivillige forsøgspersoner gav cimetidin (800 mg), en CYP450-hæmmer og ikke specifik CYP3A4-hæmmer, en 56% stigning i plasmakoncentrationer af sildenafil ved indgift sammen med sildenafil (50 mg).
Cimetidine (800 mg), a cytochrome P450 inhibitor and a non-specific CYP3A4 inhibitor, caused a 56% increase in plasma sildenafil concentrations when co-administered with sildenafil (50 mg) to healthy volunteers.
Patienter, der deltog i studiet, hvor sildenafil blev anvendt i tillæg til epoprostol, kunne inkluderes i et åbent, langvarigt forlængelsesstudie.
Long-term Survival Data in the background epoprostenol study Patients enrolled into the epoprostenol add-on therapy study were eligible to enter a long term open label extension study.
LÆGEMIDLETS NAVN Granpidam 20 mg filmovertrukne tabletter
NAME OF THE MEDICINAL PRODUCT Granpidam 20 mg film-coated tablets
medicin, der indeholder perikon (naturmedicin), rifampicin (mod tuberkulose), carbamazepin, phenytoin og phenobarbital (bruges bl.a. til behandling af epilepsi).
- Therapies for pulmonary hypertension (e.g. bosentan, iloprost) - Medicines containing St. John's Wort (herbal medicinal product), rifampicin (used to treat bacterial infections), carbamazepine, phenytoin and phenobarbital (used, among others, to treat epilepsy) - Blood thinning medicines (for example warfarin) although these did not result in any side effect.
Kaplan-Meier-estimat af overlevelse efter 3 år for patienter >20 kg ved baseline var hhv. 94%, 93% og 85% for lav-, middel- og højdosis-grupperne.
Kaplan-Meier estimates of survival at 3 years in patients >20 kg in weight at baseline were 94%, 93% and 85% in the low, medium and high dose groups, respectively; for patients ≤20 kg in weight at baseline, the survival estimates were 94% and 93% for subjects in the medium and high dose groups respectively (see sections 4.4 and 4.8).
Det primære endepunkt for effekt var ændring fra baseline til uge 16 for en 6 minutters gangdistance.
The primary efficacy endpoint was the change from baseline at week 16 in 6-minute walk distance.
Placebo-korrigeret stigning i 6MWD var 45 meter (p<0,0001), 46 meter (p<0,0001) og 50 meter (p<0,0001) for hhv. sildenafil 20 mg, 40 mg og 80 mg. Der var ingen signifikant forskel i effekten mellem sildenafildoserne.
Placebo corrected increases in 6MWD 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 TID respectively.
Totalt seponerede hhv. 2,9%, 3,0% og 8,5% af patienterne behandlingen med 20 mg, 40 mg og 80 mg sildenafil 3 gange dagligt sammenlignet med 2,9% i placebogruppen.
The overall frequency of discontinuation in sildenafil treated patients at doses of 20 mg, 40 mg and 80 mg TID was 2.9%, 3.0% and 8.5% respectively, compared to 2.9% with placebo.
Hos patienter med primær PAH (67 personer) var den gennemsnitlige ændring fra baseline hhv. 26,39 m (95% CI: 10,70 til 42,08) i sildenafilgruppen og 11,84 m (95% CI: -8,83 til 32,52) i placebogruppen.
For subjects with primary PAH (67 subjects), mean changes from baseline were 26.39 m (95% CI: 10.70 to 42.08) and 11.84 m (95% CI: -8.83 to 32.52) for the sildenafil and placebo groups, respectively.
Følgende alvorlige bivirkninger er almindelige (det sker hos mellem 1 og 10 patienter): lungebetændelse, hjertesvigt, højresidigt hjertesvigt, shock pga. hjerteproblemer, højt blodtryk i lungerne, smerter i brystet, besvimelse, infektion i luftvejene, bronkitis, virusinfektion i maven og tarmen, urinvejsinfektion og huller i tænderne.
The following serious adverse events have been reported commonly (may affect up to 1 in 10 people); pneumonia, heart failure, right heart failure, heart related shock, high blood pressure in the lungs, chest pain, fainting, respiratory infection, bronchitis, viral infection in the stomach and intestines, urinary tract infections and tooth cavities.
Det primære endepunkt for effekt var ændring fra baseline til uge 12 for en 6 minutters gangdistance (6MWD).
The primary efficacy endpoint was the change from baseline at week 12 in 6-minute walk distance (6MWD).
Der bør ikke anvendes højere doser end de anbefalede til pædiatriske patienter med PAH (se også pkt.
Therefore, doses higher than the recommended doses should not be used in paediatric patients with PAH (see also sections 4.2 and 5.1).
Hvis De oplever en af følgende bivirkninger, skal De stoppe med at tage Granpidam og straks søge læge (se også afsnit 2): pludseligt nedsat syn eller synstab (hyppighed er ukendt) erektion, som varer uafbrudt i mere end 4 timer.
- if you experience sudden decrease or loss of vision (frequency not known) - if you have an erection, which lasts continuously for more than 4 hours.
Samtidig indgift med HIV-proteasehæmmeren saquinavir, en CYP3A4-hæmmer, ved steady-state (1200 mg 3 gange dagligt) og enkeltdosis sildenafil (100 mg) gav en stigning i sildenafils Cmax på 140% og en stigning i sildenafils plasma AUC på 210%.
Co-administration of the HIV protease inhibitor saquinavir, a CYP3A4 inhibitor, at steady state (1200 mg three times a day) with sildenafil (100 mg single dose) resulted in a 140% increase in sildenafil Cmax and a 210% increase in sildenafil AUC.
Ved indgift af en enkeltdosis sildenafil 100 mg sammen med erythromycin, en moderat CYP3A4hæmmer, i steady-state (500 mg 2 gange daglig i 5 dage) ses en 182% stigning i optagelsen af sildenafil
When a single 100 mg dose of sildenafil was administered with erythromycin, a moderate CYP3A4 inhibitor, at steady state (500 mg twice daily for 5 days), there was a 182% increase in sildenafil systemic exposure (AUC).
Kontakt straks lægen, hvis De tager mere medicin, end lægen har foreskrevet.
If you take more medicine than you have been told to take contact your doctor immediately.
Risk/benefit-ratio for sildenafil er ikke fastslået hos patienter med pulmonal arteriel hypertension funktionsklasse I efter WHO-klassifikation.
The benefit-risk balance of sildenafil has not been established in patients assessed to be at WHO functional class I pulmonary arterial hypertension.
I alt 106 ud af 234 (45%) forsøgspersoner kunne evalueres ved CPET, hvilket omfattede børn ≥7 år, som udviklingsmæssigt var i stand til at udføre testen.
A total of 106 out of 234 (45%) subjects were evaluable for CPET, which comprised those children ≥7 years old and developmentally able to perform the test. Children <7 years (sildenafil combined dose = 47; placebo = 16) were evaluable only for the secondary endpoints.
Meget almindelige bivirkninger (det sker hos flere end 1 ud af 10 patienter): hovedpine, opkastning, halsbetændelse, feber, diarré, influenza og næseblod.
Side effects reported very commonly (may affect more than 1 in 10 people) were headache, vomiting, infection of the throat, fever, diarrhoea, flu and nosebleed.
Sildenafil må ikke anvendes til patienter med pulmonal hypertension sekundært til seglcelleanæmi.
Vaso-occlusive crises in patients with sickle cell anaemia Sildenafil should not be used in patients with pulmonary hypertension secondary to sickle cell anaemia.
Virkninger af andre præparater på sildenafil In vitro studier
Effects of other medicinal products on sildenafil
Sildenafils sikkerhed og effekt ved samtidig anvendelse af andre PDE5-hæmmere, herunder kombinationsbehandling med sildenafil mod erektil dysfunktion, er ikke undersøgt hos patienter med pulmonal arteriel hypertension og samtidig anvendelse kan ikke anbefales (se pkt.
The safety and efficacy of sildenafil when co-administered with other PDE5 inhibitor products, including the combined use of sildenafil for erectile dysfunction, has not been studied in PAH patients and such concomitant use is not recommended (see section 4.5).
Efter enten oral eller intravenøs indgift udskilles sildenafil som metabolitter hovedsageligt i fæces (ca. 80% af indgivet oral dosis) og i mindre grad i urinen (ca. 13% af indgivet oral dosis).
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).
Patienter med PAH forbundet med bindevævssygdom (36 personer) havde imidlertid en gennemsnitlig ændring fra baseline på -18,32 m (95% CI: -65,66 til 29,02) i sildenafilgruppen og 17,50 m (95% CI: -9,41 til 44,41) i placebogruppen.
However, for subjects with PAH associated with connective tissue disease (36 subjects) mean changes from baseline were -18.32 m (95% CI: -65.66 to 29.02) and 17.50 m (95% CI: -9.41 to 44.41) for the sildenafil and placebo groups, respectively.
Patienterne var behandlings-naive for specifik PAH-behandling, og brug af prostacyclin, prostacyclinanaloger og endothelinreceptor-antagonister var ikke tilladt under studiet.
Patients were naïve for specific PAH therapy and the use of prostacyclin, prostacyclin analogues and endothelin receptor antagonists was not permitted in the study, and neither was arginine supplementation, nitrates, alpha-blockers and potent CYP450 3A4 inhibitors.
Nyrer og urinveje Ikke almindelig hæmaturi
Renal and urinary disorders Uncommon haematuria
Ved baseline var overlevelse for patienter i WHOfunktionsklasse II efter 1, 2 og 3 år hhv. 99 %, 91 % og 84 %, og for patienter i WHO-funktionsklasse III hhv. 94 %, 90 % og 81 %.
3 years was 99%, 91%, and 84% respectively, and for patients of WHO functional class III at baseline was 94%, 90%, and 81%, respectively.
Hos patienter med en baseline gangdistance på 325 m var behandlingseffekten 38,4 m til sildenafils fordel.
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.
Sådan skal De tage Granpidam
How to take Granpidam
har for højt blodtryk i blodkarrene i lungerne.
- have a problem with the pumping chambers of your heart - have high blood pressure in the blood vessels in the lungs.
Almindelig myalgi, rygsmerter
Common myalgia, back pain
Bivirkninger, der forekommer hos >1% af sildenafil-behandlede patienter, og som er hyppigere (>1% forskel) for sildenafil i pivotal-studiet eller i det sildenafilkombinerede datasæt for begge placebokontrollerede studier med pulmonal arteriel hypertension i doser på 20 mg, 40 mg eller 80 mg 3 gange dagligt, er anført i skemaet nedenfor.
Adverse reactions which occurred in >1% of sildenafil-treated patients and were more frequent (>1% difference) on sildenafil in the pivotal study or in the sildenafil combined data set of both the placebo-controlled studies in pulmonary arterial hypertension, at doses of 20, 40 or 80 mg TID are listed in the table below by class and frequency grouping (very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to ≤1/100) and not known (cannot be estimated from the available data).
Patienter, som pga. non-arteritis anterior iskæmisk opticusneuropati (NAION), har nedsættelse af synet på det ene øje.
Patients who have loss of vision in one eye because of non-arteritic anterior ischaemic optic neuropathy (NAION), regardless of whether this episode was in connection or not with previous PDE5 inhibitor exposure (see section 4.4).
Der bør ikke anvendes højere doser end den anbefalede til pædiatriske patienter med PAH (se pkt.
Higher than recommended doses should not be used in paediatric patients with PAH (see sections 4.2 and 4.4).
Det primære virkningsendepunkt var ændring i 6MWD i forhold til baseline i uge 12.
The primary efficacy endpoint was the change from baseline at Week 12 in 6MWD.
Placebokorrigeret stigning i gangdistance var 49 meter (p=0,0007) for klasse II og 45 meter (p=0,0031) for klasse III.
For class II and class III, placebo corrected increases of 49 metres (p = 0.0007) and 45 metres (p = 0.0031) were observed respectively.
Patienten skal informeres om straks at søge læge, hvis en erektion varer længere end 4 timer.
In the event of an erection that persists longer than 4 hours, the patient should seek immediate medical assistance.
Følgende alvorlige bivirkninger betragtes som forbundet med behandlingen og er ikke almindelige (det sker hos mellem 1 og 10 ud af 100 patienter): allergisk reaktion (såsom hududslæt, hævelser i ansigt, læber og tunge, hvæsende vejrtrækning, åndedrætsbesvær og synkebesvær), kramper,
The following serious adverse events were considered to be treatment related and were reported uncommonly (may affect up to 1 in 100 people), allergic reaction (such as skin rash, swelling of the face, lips and tongue, wheezing, difficulty breathing or swallowing), convulsion, irregular heart-beat, hearing impairment, shortness of breath, inflammation of the digestive tract, wheezing due to disrupted airflow.
Vaskulære sygdomme Meget almindelig ansigtsrødme
Vascular disorders Very common flushing
I de prækliniske forsøg blev der kun set virkninger efter doser, der i væsentlig grad overstiger den maksimale eksponering.
Effects in non-clinical studies were observed at exposures considered sufficiently in excess of the maximum human exposure indicating little relevance to clinical use.
Meget almindelige bivirkninger (det sker hos flere end 1 ud af 10 patienter) er hovedpine, rødmen i ansigtet, mavebesvær, diarré og smerter i arme og ben.
Side effects reported very commonly (may affect more than 1 in 10 people) were headache, facial flushing, indigestion, diarrhoea and pain in the arms or legs.
Hvis De har taget for meget Granpidam
If you take more Granpidam than you should
Som en konsekvens bør muligheden for en veneokklusiv sygdom overvejes, hvis der er tegn på lungeødem, når sildenafil anvendes hos patienter med pulmonal hypertension.
Consequently, should signs of pulmonary oedema occur when sildenafil is administered in patients with pulmonary hypertension, the possibility of associated veno-occlusive disease should be considered.
Patienterne blev randomiseret til 1 af 4 behandlingsgrupper: Placebo, sildenafil 20 mg, sildenafil 40 mg eller sildenafil 80 mg 3 gange dagligt.
sildenafil 20 mg, sildenafil 40 mg or sildenafil 80 mg, three times a day.
Efter enkeltdosis på 10 mg oral sildenafil blev Cmax estimeret til hhv. 24, 53 og 85 ng/ml for patienter, der vejede 70, 20 og 10 kg. Tmax blev estimeret til ca. 1 time og var stort set uafhængig af legemsvægt.
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.
De fleste forsøgspersoner var WHOfunktionsklasse I (75/234, 32%) eller II (120/234, 51%) ved baseline.
Most subjects were WHO Functional Class I (75/234, 32%) or II (120/234, 51%) at baseline; fewer patients were Class III (35/234, 15%) or IV (1/234, 0.4%); for a few patients (3/234, 1.3%), the WHO Functional Class was unknown.
Mikrokrystallinsk cellulose
Musculoskeletal and connective tissue disorders
Efter oral indgift af 3 daglige doser af sildenafil øges AUC og Cmax proportionalt med dosis over det anbefalede dosisområde (20-40 mg).
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.
Samtidig anvendelse af sildenafil og intravenøs epoprostenol er undersøgt (se pkt.
Co-administration of oral sildenafil and intravenous epoprostenol has been evaluated (see sections 4.8 and 5.1).
Få patienter var klasse I (3/267, 1%) eller IV (16/267, 6%) ved baseline.
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.
Navn og adresse på den fremstiller (de fremstillere), der er ansvarlig(e) for batchfrigivelse
Name and address of the manufacturers responsible for batch release Accord Healthcare Ltd
Granpidam kan øge disse præparaters virkning i uønsket, alvorlig grad. Fortæl Deres læge, hvis De tager nogle af disse præparater.
Granpidam can cause a serious increase in the effects of these medicines.
Dosisrekommandation, se pkt.
For dose recommendations, see section 4.2.
Tablettens filmovertræk indeholder lactosemonohydrat.
Lactose monohydrate is present in the tablet film coat.
Riociguat
Breast-feeding
ANVENDT LÆGEMIDDEL SAMT AFFALD HERAF
SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE
Titandioxid (E171)
Hypromellose (15 cp) (E464) Titanium dioxide (E171) Lactose monohydrate Triacetin
Almindelige bivirkninger (det sker hos mellem 1 og 10 patienter): kvalme, hyppigere, forlænget eller kraftigere erektion, herunder spontan erektion, lungebetændelse og løbenæse.
Side effects reported commonly (may affect up to 1 in 10 people) were nausea, increased erections, pneumonia and runny nose.
Det reproduktive system og mammae Ikke almindelig blødning fra penis, hæmospermi, gynækomasti
Reproductive system and breast disorders Uncommon penile haemorrhage, haematospermia, gynaecomastia
I overensstemmelse med sildenafils kendte effekt på nitrogenoxid/cGMP-vejen (se pkt.
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).
AUC og Cmax-værdierne for
Excipient(s) with known effect
Vasodilaterende effekt
Vasodilatory action
Indhold Pakningsstørrelse EU/1/00/135/001 DaTSCAN 74 MBq/ml Injektionsvæske, opløsning.
Invented name Strength Pharmaceutical Form Route of administration Packaging
Lægemiddelform Indgivelsesvej
Package size
Relevansen af de kliniske endepunkter er tvivlsom.
The relevance of clinical endpoints is questionable.
Man kan have formodning om underindberetning på baggrund af, at:
Under-notification can be suspected given that:
De foreliggende data tyder faktisk på en sådan årsagssammenhæng.
Available data is in fact indicative of such causal relationship.
Samlet resumé af den videnskabelige vurdering af lægemidler, der indeholder dihydroergotamin (se bilag I)
Overall summary of the scientific evaluation of dihydroergotamine containing medicinal products (see Annex I)
Skønt nogle af de foreslåede foranstaltninger kan tænkes at være medvirkende til tidlig identifikation af patienter med fibrose, kan det være for sent, da disse reaktioner undertiden er irreversible.
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.
Klinisk sikkerhed
Clinical safety
Patienternes sygdom er ikke veldefineret, hvilket ligeledes gælder endepunkterne.
The patients disease is not well defined, nor the efficacy endpoints.
Vedrørende de indberettede tilfælde hæftede CHMP sig ved problemet med underindberetning for dette produkt i betragtning af den periode, det har været på markedet.
With regard to the reported cases, the CHMP noted the problem of under-reporting for this product considering the period that it is on the market.
• bivirkninger med et stof, der har været markedsført i lang tid, sædvanligvis indberettes mindre
• Adverse drug reactions with a substance marketed for a long time are generally less reported
Virkningen blev vurderet ved sammenholdelse af målinger af det absolutte blodtryk efter behandling frem for ved sammenligning af forskelle mellem liggende og stående blodtryk, hvilket ikke blev anset for acceptabelt.
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.
Den 18. januar 2012 indbragte Frankrig en sag i henhold til artikel 31 i direktiv 2001/83/EF vedrørende følgende lægemidler indeholdende ergotderivater: dihydroergocryptin/caffein, dihydroergocristin, dihydroergotamin, dihydroergotoxin og nicergolin.
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.
Desuden var det den intravenøse formulering af produktet, der blev anvendt, ikke den orale formulering, som denne indbringelsesprocedure vedrører.
In addition, it was the IV formulation of the product that was used and not the oral formulation that is in the scope of this referral procedure.
• fibrose nævnes i flere gældende europæiske produktresuméer, og forventede reaktioner bliver ofte underindberettet
• Fibrosis is mentioned in several current European Summaries of Product Characteristics (SmPCs) and expected reactions are often under-reported
Udvalget fastslog derfor, at de foreslåede foranstaltninger er utilstrækkelige til at undgå, at nogle patienter udvikler fibrose og ergotisme under behandlingen.
The Committee therefore pointed out that the proposed measures are insufficient to avoid that some patients develop fibrosis and ergotism during treatment.