natgillin/translations-raw huggingface dataset:
Data fra et begrænset antal antyder, at en pludselig afbrydelse af Revatio- behandlingen ikke er forbundet med et forværret tilbagefald af pulmonal arteriel hypertension.
Limited data suggests that the abrupt discontinuation of Revatio is not associated with rebound worsening of pulmonary arterial hypertension.
Anvendelse hos patienter, som får anden medicin:
Use in patients using other medicines:
4. 8 og 5. 1).
Co-administration of sildenafil and intravenous epoprostenol has been evaluated (see section 4.8 and 5.1).
Sikkerhed og effekt af sildenafil ved samtidig anvendelse af andre lægemidler for pulmonal arteriel hypertension (f. eks bosentan, iloprost) er ikke undersøgt i kontrollerede kliniske studier.
The efficacy and safety of sildenafil co-administered with other treatments for pulmonary arterial hypertension (eg. bosentan, iloprost) has not been studied in controlled clinical trials.
Sikkerhed og effekt af Revatio ved samtidig anvendelse af andre PDE5- hæmmere er ikke undersøgt hos patienter med pulmonal arteriel hypertension.
The safety and efficacy of Revatio when co-administered with other PDE5 inhibitors has not been studied in pulmonary arterial hypertension patients.
5. 1) har sildenafil vist sig at potensere nitraters hypotensive effekt, hvorfor indgift sammen med nitrogenoxiddonorer (som amylnitrit) eller enhver form for nitrater derfor er kontraindiceret.
Consistent with its known effects on the nitric oxide/ cyclic guanosine monophosphate (cGMP) pathway (see section 5.1), sildenafil was shown to potentiate the hypotensive effects of nitrates, and its co-administration with nitric oxide donors (such as amyl nitrite) or nitrates in any form is therefore contraindicated.
4. 5).
Combination with potent CYP3A4 inhibitors (eg. ketoconazole, itraconazole, ritonavir) (see section 4.5).
Kontraindikationen gælder uanset om synsnedsættelsen opstod i forbindelse med brug af PDE5- hæmmere eller ej (se pkt.
Revatio is contraindicated in 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).
Sikkerheden af sildenafil er ikke undersøgt hos følgende patientundergrupper, og dets anvendelse er derfor kontraindiceret: svært nedsat leverfunktion, nyligt overstået slagtilfælde eller myokardieinfarkt, svær hypotension (blodtryk < 90/ 50 mmHg) ved initiering.
The safety of sildenafil has not been studied in the following sub-groups of patients and its use is therefore contraindicated: severe hepatic impairment, recent history of stroke or myocardial infarction, severe hypotension (blood pressure < 90/ 50 mmHg) at initiation.
Effekten af Revatio er ikke fastslået hos patienter med alvorlig pulmonal arteriel hypertension (funktionel- klasse IV).
The efficacy of Revatio has not been established in patients with severe pulmonary arterial hypertension (functional class IV).
4. 2).
If the clinical situation deteriorates, therapies that are recommended at the severe stage of the disease (e. g. epoprostenol) should be considered (see section 4.2).
Risk/ benefit- ratio af sildenafil er ikke fastslået hos patienter med klasse I i den funktionelle klassificering af pulmonal arteriel hypertension.
The benefit-risk balance of sildenafil has not been established in patients with class I functional classification of pulmonary arterial hypertension.
Der er udelukkende udført studier på pulmonær arteriel hypertension relateret til bindevævssygdom og kirurgisk intervention.
No studies have been performed in related forms of pulmonary arterial hypertension other than related to connective tissue disease and surgical repair.
Sikkerheden af sildenafil er ikke undersøgt hos patienter med kendte arvelige degenerative sygdomme i retina, som Retinitis pigmentosa (et mindretal af disse patienter har arvelige sygdomme i retinas fosfodiesteraser), og dets anvendelse kan derfor ikke anbefales.
The safety of sildenafil has not been studied in patients with known hereditary degenerative retinal disorders such as Retinitis pigmentosa (a minority of these patients have genetic disorders of retinal phosphodiesterases) and therefore its use is not recommended.
Generelt bør enhver dosisjustering kun foretages efter en omhyggelig risk/ benefit- vurdering.
3 In general, any dose adjustment should be administered only after a careful benefit-risk assessment.
3 Dosisjustering af sildenafil til 20 mg 2 gange daglig bør overvejes til patienter, der allerede anvender middelpotente 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 medium potency CYP3A4 inhibitors like erythromycin or saquinavir.
Dosisjustering til 20 mg 1 gang daglig anbefales i tilfælde ved samtidigt anvendelse af sildenafil og mellempotente CYP3A4 - hæmmere som clarithromycin, telithromycin og nefazodone.
A downward dose adjustment to 20 mg once daily is recommended in case of co- administration with CYP3A4 inhibitors of intermediate potency like clarithromycin, telithromycin and nefazodone.
4. 3).
Co-administration of potent CYP3A4 inhibitors (e. g. ketoconazole, itraconazole, ritonavir) with sildenafil for pulmonary arterial hypertension is contraindicated (see section 4.3).
4. 5).
Dose adjustments of sildenafil may be required when co-administered with CYP3A4 inducers (see section 4.5).
4. 4).
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).
4. 3).
Sildenafil potentiates the hypotensive effect of nitrates therefore concomitant use of Revatio with nitrates is contraindicated (see section 4.3).
De fleste, men ikke alle, af disse patienter havde allerede eksisterende kardiovaskulære risikofaktorer.
Most, but not all, of these patients had pre- existing cardiovascular risk factors.
Sildenafil, bør anvendes med forsigtighed hos patienter med anatomisk deformitet af penis (som f. eks. vinkling, kavernøs fibrose eller Peyronies sygdom), eller hos patienter med lidelser, som kan prædisponere til priapisme (som f. eks. seglcelleanæmi, multipelt myelom eller leukæmi).
Sildenafil should be used with caution in patients with anatomical deformation of the penis (such as angulation, cavernosal fibrosis or Peyronie’ s disease), or in patients who have conditions which may predispose them to priapism (such as sickle cell anaemia, multiple myeloma or leukaemia).
Der er rapporteret synsdefekter og tilfælde af non- arteritis anterior iskæmisk opticusneuropati (NAION) i forbindelse med indtagelse af sildenafil og andre PDE5- hæmmere.
Visual defects and cases of non-arteritic anterior ischaemic optic neuropathy have been reported in connection with the intake of sildenafil and other PDE5 inhibitors.
4. 3).
The patient should be advised that in case of sudden visual defect, he should stop taking Revatio and consult a physician immediately (see section 4.3).
4. 5).
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).
For at mindske risikoen for udvikling af ortostatisk hypotension, bør patienterne være hæmodynamisk stabile på alfa- blokker- behandling, førend sildenafilbehandling initieres.
In order to minimize the potential for developing postural hypotension, patients should be hemodynamically stable on alpha-blocker therapy prior to initiating sildenafil treatment.
Lægen bør informere patienten om, hvad han/ hun skal gøre i tilfælde af ortostatiske hypotensive symptomer.
Physicians should advise patients what to do in the event of postural hypotensive symptoms.
Der er ingen sikkerhedsinformation vedrørende anvendelsen af sildenafil til patienter med blødningslidelser eller aktive sår i mave- tarmkanalen.
There is no safety information on the administration of sildenafil to patients with bleeding disorders or active peptic ulceration.
Sildenafil bør derfor kun anvendes til disse patienter efter omhyggelig risk/ benefit- vurdering.
Therefore sildenafil should be administered to these patients only after careful benefit-risk assessment.
Hos patienter med pulmonal arteriel hypertension kan der være en potential øget risiko for blødning, når sildenafil initieres hos patienter, der allerede anvender en vitamin- K- antagonist, især hos patienter med pulmonal arteriel hypertension sekundært til bindevævssygdom.
In pulmonary arterial hypertension patients, there may be a potential for increased risk of bleeding when sildenafil is initiated in patients already using a Vitamin K antagonist, particularly in patients with pulmonary arterial hypertension secondary to connective tissue disease.
4 Tablettens filmovertræk indeholder lactosemonohydrat.
4 Lactose monohydrate is present in the tablet film coat.
Lægemidlet bør derfor ikke anvendes til patienter med arvelig galactoseintolerans, en særlig form af hereditær lactasemangel (Lapp Lactase deficiency) eller glucose/ galactosemalabsorption.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Virkninger af andre præparater på sildenafil In vitro undersøgelser:
Effects of other medicinal products on sildenafil In vitro studies:
In vivo undersøgelser:
In vivo studies:
Populationsfarmakokinetiske analyser af kliniske undersøgelsesdata af pulmonal arteriel hypertension tyder på en reduktion af sildenafils clearance og/ eller en stigning i oral biotilgængelighed, ved administration sammen med CYP3A4- substrater og kombinationen af CYP3A4- substrater og beta - blokkere.
Population pharmacokinetic analysis of pulmonary arterial hypertension clinical trial data indicated a reduction in sildenafil clearance and/ or an increase of oral bioavailability when co-administered with CYP3A4 substrates and the combination of CYP3A4 substrates and beta-blockers.
Hos patienter på CYP3A4- substrater og CYP3A4- substrater plus beta- blokker, var eksponeringen til sildenafil henholdsvis 43% og 66% højere sammenlignet med patienter, der ikke fik disse lægemidler.
The exposure to sildenafil in patients on CYP3A4 substrates and CYP3A4 substrates plus beta-blockers was 43% and 66% higher, respectively, compared to patients not receiving these classes of medicines.
Sildenafils eksponering var 5 gange højere ved doser 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.
Dette koncentrationsinterval dækker stigningen i sildenafils eksponering set i specielt designede lægemiddelinteraktionsstudier med CYP3A4- hæmmere (undtagen mere potente CYP3A4 - hæmmere som f. eks. ketoconazol, itraconazol, ritonavir).
This concentration range covers the increase in sildenafil exposure observed in specifically designed drug interaction studies with CYP3A4 inhibitors (except more potent CYP3A4 inhibitors e. g. ketoconazole, itraconazole, ritonavir).
CYP3A4- induktorer ser ud til at have en betydelig indvirkning på farmakokinetikken af sildenafil hos patienter med pulmonal arteriel hypertension, hvilket er bekræftet i et in- vivo interaktionsstudie med CYP3A4- induktoren bosentan.
CYP3A4 inducers seemed to have a substantial impact on the pharmacokinetics of sildenafil in pulmonary arterial hypertension patients, which was confirmed in the in-vivo interaction study with CYP3A4 inducer bosentan.
Samtidig anvendelse af bosentan (en moderat induktor af CYP3A4, CYP2C9 og muligvis af CYP2C19) 125 mg 2 gange dagligt og sildenafil 80 mg 3 gange dagligt (ved steady state) i 6 dage gav et fald i sildenafils AUC på 63% hos raske frivillige forsøgspersoner.
Co-administration of bosentan (a moderate inducer of CYP3A4, CYP2C9 and possibly of CYP2C19) 125mg twice daily with sildenafil 80 mg three times a day (at steady state) concomitantly administered during 6 days in healthy volunteers resulted in a 63% decrease of sildenafil AUC.
Forsigtighed tilrådes ved samtidig anvendelse.
Caution is recommended in case of co-administration.
Effekten af sildenafil bør overvåges nøje hos patienter, der samtidigt anvender potente CYP3A4 - induktorer som carbamazepin, phenytoin, phenobarbital, prikbladet perikon og rifamipicin.
Efficacy of sildenafil should be closely monitored in patients using concomitant potent CYP3A4 inducers, such as carbamazepine, phenytoin, phenobarbital, St John’ s wort and rifamipicine.
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.
5 ng/ ml, når sildenafil bliver anvendt alene.
At 24 hours, the plasma levels of sildenafil were still approximately 200 ng/ ml, compared to approximately 5 ng/ ml when sildenafil was administered alone.
Dette er i overensstemmelse med ritonavirs udtalte virkning på et bredt udvalg af P450 - substrater.
This is consistent with ritonavir’ s marked effects on a broad range of P450 substrates.
4. 3).
Based on these pharmacokinetic results co-administration of sildenafil with ritonavir is contraindicated in pulmonary arterial hypertension patients (see section 4.3).
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.
5 Ved indgift af en enkeltdosis sildenafil 100 mg sammen med erythromycin, en specifik CYP3A4 - hæmmer, i steady state (500 mg 2 gange daglig i 5 dage) ses en 182% stigning i optagelsen af sildenafil (AUC).
When a single 100 mg dose of sildenafil was administered with erythromycin, a specific CYP3A4 inhibitor, at steady state (500 mg twice daily for 5 days), there was a 182% increase in sildenafil systemic exposure (AUC).
Hos normale raske mandlige frivillige forsøgspersoner ses for azithromycin (500 mg daglig i 3 dage) ingen tegn på ændringer af AUC, Cmax, Tmax, eliminationshastigheds- konstanten eller efterfølgende halveringstid for sildenafil eller dets væsentligste cirkulerende metabolit.
In normal healthy male volunteers, there was no evidence of an effect of azithromycin (500 mg daily for 3 days) on the AUC, Cmax, Tmax, elimination rate constant, or subsequent half-life of sildenafil or its principal circulating metabolite.
Hos raske frivillige forsøgspersoner gav cimetidin (800 mg), en cytokrom P450- 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.
Potente CYP3A4- hæmmere såsom ketoconazol og itraconazol må forventes at have en effekt tilsvarende ritonavir (se pkt 4. 3).
5 Potent CYP3A4 inhibitors such as ketoconazole and itraconazole would be expected to have effects similar to ritonavir (see section 4.3).
Mellempotente CYP3A4- hæmmere (f. eks. clarithromycin, telithromycin og nefazodon) forventes at have en effekt, der ligger imellem ritonavir og middelpotente CYP4A4- hæmmere (f. eks. saquinavir/ erythromycin), formodet en 7- gange øgning i eksponering.
CYP3A4 inhibitors of intermediate potency (e. g. clarithromycin, telithromycin and nefazodone) are expected to have an effect in between that of ritonavir and CYP3A4 inhibitors of medium potency (e. g. saquinavir/ erythromycin), a seven-fold increase in exposure is assumed.
4. 4).
Therefore dose adjustments are recommended when using CYP3A4 inhibitors of intermediate potency (see section 4.4).
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.
Grapefrugtjuice er en svag CYP3A4- hæmmer af tarmvæggens metabolisme, og kan give en mindre stigning i plasmakoncentrationen af sildenafil.
Grapefruit juice is a weak inhibitor of CYP3A4 gut wall metabolism and may give rise to modest increases in plasma levels of sildenafil.
Enkeltdoser af antacida (magnesiumhydroxid/ aluminiumhydroxid) påvirker ikke biotilgængeligheden af sildenafil.
Single doses of antacid (magnesium hydroxide/ aluminium hydroxide) did not affect the bioavailability of sildenafil.
Samtidig administration af orale antikonceptiva (30 μg ethinylestradiol og 150 μg levonorgestrel) påvirker ikke sildenafils farmakokinetik.
Co-administration of oral contraceptives (ethinyloestradiol 30 μ g and levonorgestrel 150 μ g) did not affect the pharmacokinetics of sildenafil.
På grund af nitratkomponenten kan det muligvis give alvorlig interaktion med sildenafil.
Due to the nitrate component it has the potential to have serious interaction with sildenafil.
Virkninger af sildenafil på andre lægemidler In vitro undersøgelser:
Effects of sildenafil on other medicinal products In vitro studies:
Sildenafil er en svag hæmmer af cytokrom P450- isoformer 1A2, 2C9, 2C19, 2D6, 2E1 og 3A4 (IC50 > 150 µM).
Sildenafil is a weak inhibitor of the cytochrome P450 isoforms 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (IC50 > 150 μ M).
Der er ingen data vedrørende interaktion af sildenafil og ikke- specifikke fosfodiesterasehæmmere, såsom teofyllin eller dipyridamol.
There are no data on the interaction of sildenafil and non-specific phosphodiesterase inhibitors such as theophylline or dipyridamole.
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.
Sildenafil (50 mg) did not potentiate the hypotensive effects of alcohol in healthy volunteers with mean maximum blood alcohol levels of 80 mg/ dl.
I et studie med raske frivillige forsøgspersoner gav sildenafil ved steady state (80 mg 3 gange dagligt) en stigning i bosentans AUC på 50% (125 mg 2 gange dagligt).
In a study of healthy volunteers sildenafil at steady state (80 mg three times a day) resulted in a 50% increase in bosentan AUC (125 mg twice daily).
6 I en særlig interaktionsundersøgelse, hvor sildenafil (100 mg) blev givet sammen med amlodipin til hypertensive patienter, sås et yderligere fald i det systoliske blodtryk i liggende stilling på 8 mmHg.
6 In a specific interaction study, where sildenafil (100 mg) was co-administered with amlodipine in hypertensive patients, there was an additional reduction on supine systolic blood pressure of 8 mmHg.
I 3 specifikke lægemiddel- lægemiddel interaktionsundersøgelser blev alfa- blokkeren doxazosin (4 mg og 8 mg) og sildenafil (25 mg, 50 mg eller 100 mg) anvendt samtidigt hos patienter med benign prostatahyperplasi (BPH) stabiliseret på doxazosinbehandling.
In three specific drug-drug interaction studies, the alpha-blocker doxazosin (4 mg and 8 mg) and sildenafil (25 mg, 50 mg, or 100 mg) were administered simultaneously to patients with benign prostatic hyperplasia (BPH) stabilized on doxazosin therapy.
Hos disse studiepopulationer ses gennemsnitlig yderligere fald i det systoliske og diastoliske blodtryk i liggende stilling på henholdsvis 7/ 7 mmHg, 9/ 5 mmHg og 8/ 4 mmHg, og gennemsnitlig yderligere fald i blodtrykket i stående stilling på henholdsvis 6/ 6 mmHg, 11/ 4 mmHg og 4/ 5 mmHg.
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.
4. 4).
Concomitant administration of sildenafil to patients taking alpha- blocker therapy may lead to symptomatic hypotension in susceptible individuals (see section 4.4).
Sildenafil (100 mg enkeltdosis) påvirker ikke steady state farmakokinetikken af HIV - proteasehæmmeren saquinavir, som er et CYP3A4- substrat/ hæmmer.
Sildenafil (100 mg single dose) did not affect the steady state pharmacokinetics of the HIV protease inhibitor saquinavir, which is a CYP3A4 substrate/ inhibitor.
4. 3).
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).
Sildenafil har ingen klinisk betydende indvirkning på plasmaniveauerne af orale antikonceptiva (30 μg ethinylestradiol og 150 μg levonorgestrel).
Sildenafil had no clinically significant impact on the plasma levels of oral contraceptives (ethinyloestradiol 30 μ g and levonorgestrel 150 μ g).
Dyreforsøg viser ikke direkte eller indirekte skadelige virkninger ved graviditet, embryonets/ fosterets udvikling.
Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy and embryonal/ foetal development.
5. 3).
Studies in animals have shown toxicity with respect to postnatal development (see section 5.3).
Revatio bør på grund af manglende data ikke anvendes til gravide, medmindre det er strengt nødvendigt.
Due to lack of data, Revatio should not be used in pregnant women unless strictly necessary.
Revatio bør ikke anvendes i ammeperioden.
Revatio should not be administered to breast- feeding mothers.
Da der er rapporteret svimmelhed og ændret syn i kliniske studier med sildenafil, bør patienter være opmærksomme på, hvordan de reagerer på Revatio, inden de kører bil eller betjener maskiner.
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.
I det pivotale placebo- kontrollerede studie af Revatio ved pulmonal arteriel hypertension blev i alt 207 patienter behandlet med Revatio i daglige doser fra 20- 80 mg 3 gange dagligt, og 70 patienter blev behandlet med placebo.
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.
259 forsøgspersoner, som fuldførte pivotal- studiet, blev inkluderet i langtids forlængelsesstudiet.
259 subjects who completed the pivotal study entered a long-term extension study.
Doser på op til 80 mg 3 gange dagligt (4 gange den anbefalede dosis på 20 mg 3 gange dagligt) blev undersøgt (N=149 patienter behandlet i mindst 1 år, 101 på 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 studied (N=149 patients treated for at least 1 year, 101 on 80 mg three times a day).