قرص sildenafil citrate

خواص دارویی و گیاهی

1-{[3-(1-Methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-ethoxyphenyl]sulfonyl}-4-methylpiperazin (IUPAC)

G04BE03

PDE-5-Hemmer

Enzymhemmung der Phosphodiesterase-5

Achtung

قرص sildenafil citrate

Sildenafil ist ein Arzneistoff aus der Gruppe der PDE-5-Hemmer, einer Gruppe gefäßerweiternder (vasodilatierender) Substanzen. Große Bekanntheit erlangte er als Wirkstoff des 1998 von dem US-amerikanischen Unternehmen Pfizer unter dem Namen Viagra auf den Markt gebrachten Arzneimittels zur Behandlung der erektilen Dysfunktion (Erektionsstörung) beim Mann. Diese Wirkung wurde zufällig im Rahmen der Entwicklung von Sildenafil als Mittel zur Behandlung von Bluthochdruck und Angina pectoris entdeckt. Außer als Potenzmittel ist Sildenafil seit 2006 ferner zur Behandlung der idiopathischen pulmonal-arteriellen Hypertonie und der pulmonalen Hypertonie in Verbindung mit einer Bindegewebskrankheit zugelassen (Markenname Revatio).

Sildenafil war der erste Arzneistoff der Wirkstoffklasse der PDE-5-Hemmer. Umgangssprachlich wird der Name Viagra gelegentlich auch als Sammelbegriff für andere Medikamente dieser Wirkstoffgruppe, beispielsweise Tadalafil (Cialis), Vardenafil (Levitra) oder Avanafil (Spedra) verwendet.

In Deutschland, Österreich und der Schweiz sind sildenafilhaltige Arzneimittel verschreibungspflichtig.

Ein Teil des physischen Prozesses der Erektion beinhaltet die Freisetzung von Stickstoffmonoxid (NO) im Corpus cavernosum. Dadurch wird das Enzym Guanylatcyclase aktiviert, welches die Ausschüttung von cyclischem Guanosinmonophosphat (cGMP) erhöht. So wird eine leichte Muskelentspannung im Corpus cavernosum ausgelöst, welche das Einströmen von Blut und damit die Erektion ermöglicht.

Sildenafil ist ein potenter selektiver Hemmer der cGMP-spezifischen Phosphodiesterase vom Typ 5 (PDE-5), der damit die Abbaurate von cGMP vermindert.[4] Als Resultat wird beim Einsatz von Sildenafil eine normale sexuelle Stimulation zu erhöhten Blutspiegeln von cGMP im Corpus cavernosum und damit zu einer verstärkten Erektion führen. Ohne eine sexuelle Stimulation und Aktivierung des NO/cGMP-Systems löst Sildenafil keine Erektion aus.

Der gleiche Wirkmechanismus trifft auch für die Substanzen Tadalafil, Vardenafil und Avanafil zu. Somit können selektive PDE-5-Inhibitoren zur Therapie der erektilen Dysfunktion eingesetzt werden.

Sildenafil wird durch Leberenzyme abgebaut und sowohl über die Leber als auch über die Nieren ausgeschieden. Wenn es mit fettreicher Nahrung eingenommen wird, ist ein verzögerter Abbau und eine verringerte Wirkung zu erwarten.

Sildenafil ist in Dosen von 25 mg, 50 mg oder 100 mg peroral wirksam. In einer Dosis-Eskalations-Studie bewirkte Sildenafil in Dosen von bis zu 100 mg bei 69 % der männlichen Patienten eine Erektion, die für die Dauer eines Geschlechtsverkehrs aufrechterhalten wurde, gegenüber 22 % in der Placebo-Gruppe.[5]

Ausmaß und Dauer einer Erektion hängen vom Blutzufluss und Blutabfluss in den Schwellkörpern des Penis ab. Die Blutzufuhr wird durch ringförmige Muskeln in der Arterienwand des Corpus cavernosum gesteuert. Im nicht erigierten Zustand sind diese angespannt und verschließen die Gefäße. Wird der Mann jedoch sexuell erregt, führt dies in den betreffenden Muskelzellen zur Bildung von cGMP (cyclischem Guanosinmonophosphat). Die Muskeln entspannen sich und der Gefäßquerschnitt wird vergrößert, was dazu führt, dass arterielles Blut in die Schwellkörper fließt und eine Erektion auslöst. Molekularer Gegenspieler des cGMP ist das Enzym Phosphodiesterase-5 (PDE-5), welches das cGMP spaltet. Sildenafil wirkt, indem es PDE-5 blockiert und dafür sorgt, dass auch geringe Mengen von cGMP zu einer Erektion führen. Anders als Potenzmittel wie etwa Alprostadil, das intrakavernös (in den Penisschwellkörper) gespritzt oder in die Harnröhre eingebracht wird, wirkt Sildenafil nur dann, wenn der Patient auch sexuell erregt ist.

Untersuchungen haben gezeigt, dass Arginin die Wirkung verstärken kann.[6] Zudem konnte bei Sildenafil eine Art Dosiseinsparungseffekt festgestellt werden. Arginin setzt ebenfalls Stickstoffmonoxid frei, welches eine Erweiterung (Dilatation) der Blutgefäße bewirkt.[6]

Seit 2006 ist Sildenafil unter dem Markennamen Revatio zur peroralen Behandlung der idiopathischen pulmonal-arteriellen Hypertonie bei Patienten im NYHA-Stadium II und III im Handel. Kritiker bemängeln, dass die zugelassene Dosierung von 3×20 mg für eine optimale Therapie nicht ausreichend sei und die wichtigsten Studien mit bis zu 3×80 mg Sildenafil durchgeführt wurden. Diese Dosierung ist aber in Deutschland nicht für die Therapie zugelassen.[7]

Außer den oben genannten Bereichen ist eine Wirkung und ein Einsatz von Sildenafil bei verschiedenen speziellen Krankheitsbildern beschrieben:

In der Neonatologie wird Sildenafil in letzter Zeit außerhalb der Arzneimittelzulassung (Off-Label-Use) zunehmend bei extremen Frühgeborenen mit bronchopulmonaler Dysplasie (BPD) zur Senkung des pulmonalen arteriellen Gefäßwiderstands eingesetzt.[8]

Es gibt erste Untersuchungen, nach denen Sildenafil die Auswirkungen des bei der Krankheit Mukoviszidose durch einen Gendefekt gestörten CFTR-Proteins korrigieren kann. Ebenfalls diskutiert wird der Einsatz von Sildenafil zur Behandlung des Schlaganfalls.

Doxorubicin wird in der Therapie des Prostatakarzinoms verwendet und weist als Nebenwirkung eine hohe Kardiotoxizität auf und kann im schlimmsten Fall auch Herzversagen hervorrufen. Einige kleinere Studien geben Hinweise darauf, dass die Kombination von beiden Wirkstoffen die chemotherapeutische Effizienz von Doxorubicin erhöht und die schädlichen Wirkungen auf das Herz verringert.[9][10]

Ein weiteres Anwendungsgebiet von Sildenafil ergibt sich bei der Behandlung des Raynaud-Syndroms. Bei dieser häufigen Krankheit verengen sich die Gefäße an Fingern und Zehen wodurch sich die Durchblutung in diesen Gebieten vermindert. Es gibt Hinweise, dass die Einnahme von Sildenafil die Gefäße in den betroffenen Regionen wieder erweitert.[11][12]

Eine Studie an Schwangeren mit Plazenta-Unterfunktion wurde 2018 abgebrochen. Eine Unterfunktion hemmt das Wachstum eines Ungeborenen erheblich. Durch Sildenafil sollte die Durchblutung der Plazenta gesteigert und die Entwicklung des Fötus beschleunigt werden. Fast 20 Prozent der Frauen brachten jedoch Kinder mit Lungenproblemen zur Welt, die mehrheitlich starben.[13]

2004 entschied der Pharmakonzern Pfizer nach mehrjähriger Forschung, die Entwicklung von Sildenafil zur Behandlung sexueller Funktionsstörungen der Frau einzustellen. Tests an rund 3000 Frauen mit sexuellen Funktionsstörungen hätten keine ausreichende Wirksamkeit gezeigt. Nach dem großen Erfolg von Sildenafil im Einsatz bei Männern sollte eigentlich ein ähnlich gewinnbringender Markt für Frauen aufgebaut werden. Das Unternehmen war jedoch (vor allem durch die Fachzeitschrift British Medical Journal) in die Kritik geraten, unter dem Namen „weibliche sexuelle Funktionsstörung“ (FSD) gezielt ein Krankheitsbild zu schaffen.

Aufgrund der Popularität von Sildenafil, die mit dem Markennamen „Viagra“ in Verbindung gebracht wird, hat sich seit den 90er Jahren ein Schwarzmarkt für Sildenafil und Sildenafil-haltige Produkte etabliert, die weit abseits ihrer Zulassung agieren.

So werden dem Medikament eine Reihe von Wirkungen zugesprochen, die wissenschaftlich nicht begründet sind, wie Steigerung der Libido, erhöhte Erektionsqualität oder Vergrößerung der Penislänge.[14][15] Studien konnten jedoch zeigen, dass der Wirkstoff beim Gesunden kaum eine Wirkung zeigt, die über die physiologische hinausgeht, mit der Ausnahme, dass die Erholungszeit nach Ejakulation verkürzt wird.[16]

Sildenafil dient genauso wie andere PDE-5-Hemmer als Verschnittmittel für als Partydroge gehandeltes MDMA, um deren Nebenwirkung der erektilen Dysfunktion entgegenzuwirken. Die Beimengung zu Amylnitrit kann zu gefährlichen additiven Wirkungen führen, welche zum Tod führen können.[17][15]

Eine Forschungsgruppe konnte zeigen, dass Sildenafil in Wasser gelöst in der Lage ist, die Lebensdauer von Schnittblumen signifikant zu verlängern.[18]

Die gleichzeitige Einnahme von Sildenafil mit nitrathaltigen Medikamenten (z. B. das bei älteren Menschen weit verbreitete Nitrolingual-Spray) oder Stickstoffmonoxid-Donatoren (Amylnitrit, Szene-Drogen „Poppers“) ist kontraindiziert. Durch die kombinierte Wirkung auf den Blutdruck droht ein akuter lebensbedrohlicher Blutdruckabfall.

Abgesehen von dieser Kontraindikation stellt der Einsatz bei Patienten mit koronarer Herzkrankheit dann ein Risiko dar, wenn der erfolgreiche Geschlechtsverkehr für den Kreislauf eine zu hohe Beanspruchung bedeutet.

Die Verstoffwechselung von Sildenafil wird durch die Cytochrom-P450 (CYP)-Isoenzyme 3A4 und 2C9 vermittelt. Es kann zu Wechselwirkungen mit Arzneistoffen kommen, die ebenfalls unter Beteiligung dieser Enzyme metabolisiert werden (z. B. Ketoconazol, Itraconazol, Erythromycin, Cimetidin, Saquinavir). Weiterhin kann der starke Cytochrom P450 3A4-Inhibitor Ritonavir zu gefährlich hohen Sildenafil-Plasmaspiegeln führen, da der Abbau von Sildenafil gehemmt wird.

Bei der Einnahme auftretende Nebenwirkungen: Kopfschmerzen (10,8 %), Gesichtsrötung (10,9 %), Magenbeschwerden (3 %), Rhinitis (4 %), abnorme visuelle Wahrnehmungen (2,8 %; z. B. blaue Schleier im Gesichtsfeld, erhöhte Lichtempfindlichkeit), Herabsetzung des Reaktionsvermögens, Schwindelgefühle, Rücken- und Muskelschmerzen, Dauererektion (Priapismus). Es wurden bereits Fälle von nichtarteriitischer anteriorer ischämischer Optikusneuropathie beobachtet.[19] Dies führt in seltenen Fällen zu Einbußen der Sehfähigkeit oder zur Erblindung. Die aktuellen Erkenntnisse zu diesen Nebenwirkungen führten im Sommer 2006 zur entsprechenden Änderung der Fachinformation für Sildenafil. Neuerdings liegen auch Hinweise vor auf plötzlich auftretende Hörstörungen im Zusammenhang mit Sildenafileinnahme.

In der Vergangenheit wurde Sildenafil hin und wieder durch großaufgemachte Pressemitteilungen bekannt, in welchen von Todesfällen berichtet wurde. Diese traten aber in allen nachvollziehbaren Fällen durch Nichtbeachtung der Kontraindikationen auf.

Die Bezeichnung Viagra ist ein rechtlich geschütztes Kunstwort. Angeblich setzt sie sich aus den Begriffen vigor (lateinisch für „Stärke“) und Niagara zusammen. Nebenbei ist „Viagra“ homophon zu vyā́ghra व्याघ्र, dem Sanskrit-Wort für Tiger.

Große Bekanntheit hat das Produkt erhalten, weil es im Internet millionenfach mittels Spam-Mails beworben wird. Internetversandhändler, meist aus den USA, versenden die entsprechenden Tabletten auch ohne das notwendige Rezept in alle Welt. Abgesehen von den Nebenwirkungen des Wirkstoffs setzt man sich dabei dem Risiko aus, gefälschte oder verunreinigte Produkte zu erhalten.[20]

Mit der Markteinführung von Sildenafil war die erektile Dysfunktion erstmals bei vielen Patienten ohne große Unannehmlichkeiten behandelbar. Dies hatte weitreichende Folgen für das Sexualleben dieser Patienten. Auf der einen Seite war vielen Patienten, die aufgrund von Erkrankungen wie Diabetes, Koronarer Herzkrankheit usw. nicht mehr in der Lage waren, eine Erektion zu erlangen, wieder die Möglichkeit zu einem erfüllten Liebesleben gegeben.

Auf der anderen Seite klagten schon bald Partnerinnen, die an den sexarmen Zustand „gewöhnt“ waren, dass ihr Partner für sie plötzlich anstrengender geworden sei, als sie es sich wünschen würden. Es stellte sich heraus, dass für den Einsatz von Viagra eine intensive Beratung nicht nur mit dem Arzt, sondern auch mit der Partnerin sinnvoll ist.

Viagra gilt als dasjenige Medikament, das als erstes nachweislich zu einer Verbesserung des internationalen Artenschutzes beigetragen hat: Vor allem in asiatischen Ländern werden traditionell von seltenen Tieren gewonnene Stoffe als Aphrodisiaka verwendet. Durch die weltweite Verbreitung von Sildenafil ist die Jagd auf bedrohte Tierarten zum Zweck der Potenzmittel-Gewinnung mittlerweile zurückgegangen.[21]

Bis Mitte 2013 wurden weltweit rund 37 Millionen Männern 1,8 Milliarden Tabletten verschrieben. Pfizer setzte damit 24,8 Milliarden US-Dollar um.[22]

Die Herstellung von Sildenafil war patentrechtlich bis zum 22. Juni 2013 in Deutschland geschützt; es durfte daher nur von dem Unternehmen Pfizer oder in dessen Lizenz auf den Markt gebracht werden. Bis Ende Mai 2013 hatten 28 Unternehmen die Produktion von sildenafilhaltigen Medikamenten beantragt. In Österreich waren es 16 Anbieter.[22] Auch in anderen westlichen europäischen Ländern wie Großbritannien lief das Patent im Juni 2013 ab. Inzwischen wurden mehrere generische Sildenafil-Präparate EU-weit und national (beispielsweise in Österreich und Deutschland) zugelassen,[23] die nach Patentablauf auf den Markt kamen.[24] Darunter sind als Darreichungsform neben Tabletten auch Kautabletten und Schmelztabletten vertreten. Bereits zum 1. Juni 2013 bot Pfizer ein eigenes Generikum an. Ausgehend von Juni 2013 kletterte der Monatsabsatz innerhalb eines Jahres von 750.000 Packungen auf mehr als 1,7 Millionen Einheiten im Juni 2014 – eine Steigerung um 130 Prozent. Hexal und Ratiopharm haben mit ihren Generika das Original Viagra nach Absatz deutlich und – was entscheidender ist – auch nach Umsatz überholt. Zusammen mit dem eigenen Generikum verteidigt Pfizer allerdings immer noch Platz 1.[25]
قرص sildenafil citrate

Das Patent für Sildenafil-Citrat ist am 21. Juni 2013 in Österreich, Dänemark, Frankreich, Deutschland, Irland, Italien, den Niederlanden, Spanien, Schweden, Großbritannien und der Schweiz abgelaufen.[26][27] Ein Patent von Pfizer über PDE5-Hemmer wurde 2000 aufgrund von naheliegender Schöpfungshöhe für ungültig erklärt und das Urteil 2002 bestätigt.[28][29]

In den USA ist Sildenafil als Generikum erhältlich,[30] zu ungefähr einem fünfzigstel des Preises des Markenprodukts.[30] Das Markenprodukt kostete 2015 in den USA zwischen 25,17 und 37,88 US-Dollar.[31] In den USA hielt Pfizer zwei Patente für Sildenafil, zur Behandlung von pulmonaler arterieller Hypertonie (Revatio, niedrigere Dosis, Patentschutz 1993–2012) und der erektilen Dysfunktion (Viagra, Patentschutz 2002–2019).[30] Generisches Sildenafil zur Behandlung von pulmonaler arterieller Hypertonie wird in kleinerer Dosierung als Viagra in den USA von verschiedenen Herstellern angeboten.[32] Generisches Sildenafil darf in den USA off-label zur Behandlung der erektilen Dysfunktion verschrieben werden.[30] Teva klagte 2011 gegen den Patentschutz von Pfizer für die Anwendung bei erektiler Dysfunktion und verlor.[33] Aufgrund einer Einigung mit Pfizer wird Teva Sildenafil ab 2017 anbieten.[30]

In Kanada wurde das Patent für die Anwendung bei pulmonaler arterieller Hypertonie 2010 nach Klage durch Ratiopharm für ungültig erklärt.[34][35] Im Jahr 2012 befand der oberste Gerichtshof Kanadas (Teva Canada Ltd. v. Pfizer Canada Inc.), dass das Patent für Viagra von Beginn an ungültig sei, da nicht ausreichende Informationen bei der Anmeldung veröffentlicht worden seien, die nach Abschnitt 27(3)b des Patentgesetzes jeden Fachkundigen in die Lage zu versetzen haben, es herzustellen.[36][37] Am Tag der Veröffentlichung der Entscheidung brachte Teva generisches Sildenafil-Citrat auf den kanadischen Markt.[38][39][40] Daraufhin senkte Pfizer den Preis von Viagra in Kanada.[41] Eine Revision[42] wurde abschlägig entschieden[43][44]

In Indien gibt es keinen Patentschutz für Sildenafil-Citrat. Es wird unter den Handelsnamen Kamagra (Ajanta Pharma), Silagra (Cipla), Edegra (Sun Pharmaceutical), Penegra (Zydus Cadila) und Zenegra (Alkem Laboratories) verkauft. In China wird der Patentschutz für Sildenafil nicht umgesetzt. In Brasilien lief der Patentschutz für Sildenafil-Citrat 2010 aus.[45] In Ägypten wird generisches Sildenafil-Citrat legal verkauft.[46]

Die Kosten für den Wirkstoff machen nur einen geringen Anteil des Abgabepreises aus: Im Jahr 2004 kostete der Rohstoff für Viagra, Sildenafilcitrat, 650 Euro pro Kilogramm. Daraus lassen sich 20.000 Tabletten mit einem Verkaufswert des Markenprodukts von 240.000 Euro herstellen, was einen Kostenanteil von 0,26 Prozent für den Wirkstoff bzw. 0,0325 Euro pro Tablette bedeutet.[47]

Die Kostenübernahme für das Medikament in Deutschland war seit dessen Einführung Ende der 1990er Jahre umstritten; eine Liste der Gerichtsentscheidungen aus der Sozialgerichtsbarkeit (GKV), der Zivilgerichtsbarkeit (PKV) und der Verwaltungsgerichtsbarkeit (beamtenrechtliche Beihilferegelungen des Bundes und der jeweiligen Länder) findet sich in dem Urteil des Verwaltungsgerichts Frankfurt am Main vom 12. August 2003 (Geschäftsnummer 10 E 5407/01).[48] Die Bewilligung ist von den jeweiligen Gerichten aller drei Gerichtsbarkeiten in der Regel bei medizinischer Indikation für berechtigt gehalten worden.

Seit dem 1. Januar 2004 schließt das GKV-Modernisierungsgesetz vom 14. November 2003 (BGBl. I S. 2190) in § 34 Abs. 1 Satz 7 und 8 SGB V die Arzneimittel aus, bei deren Anwendung eine Erhöhung der Lebensqualität im Vordergrund steht. Dazu zählen u. a. Arzneimittel, die überwiegend zur Behandlung der erektilen Dysfunktion oder der Anreizung sowie Steigerung der sexuellen Potenz dienen, wie Viagra. Auf die Ursache der Störung kommt es nach dem Gesetzestext nicht an. Eine Ausnahmeregelung sehen weder Gesetz noch die Arzneimittel-Richtlinien (Anlage 8) vor.

Auch nach der Rechtsänderung und der Einbeziehung der Hilfeempfänger nach dem SGB II und SGB XII in die gesetzliche Krankenversicherung und die dadurch begründete Zuständigkeit der Sozialgerichte änderte sich die Rechtsprechung nicht. Die Kosten für die Behandlung der pulmoarteriellen Hypertonie mit Revatio werden von den gesetzlichen Krankenkassen getragen. Das vielfach von Versicherungen vorgebrachte Argument, Potenzprobleme bei älteren Männern seien „normale altersbedingte Fehlfunktionen“ wurde in einem Verfahren gegen eine private Krankenversicherung vor dem Landgericht Dortmund (Az: 2 S 25/04) im September 2004 zurückgewiesen. Ebenso entschied das OLG Karlsruhe – 12 U 32/03 – 3. Juli 2003; OLG München – 25 U 4628/99 – 8. August 2000 (NJW 2000, 3442). Anders hatte noch das LG Köln (23.O.57/02) am 20. August 2003 entschieden, als es eine erektile Dysfunktion für keine Krankheit und Viagra für kein symptomatisches Medikament erklärte.

Das Bundesverwaltungsgericht hat mit Urteilen vom 28. Mai 2008 entschieden, dass Sildenafil nicht über die nach den ab 2004 geltenden Beihilferegeln erstattungsfähig ist (Aktenzeichen 2 C 24.07.[49] und 2 C 108.07[50]) Das Oberverwaltungsgericht Rheinland-Pfalz hatte mit Urteil vom 17. Mai 2002 (Az. 2 A 11755/01.OVG) entschieden, dass Sildenafil ein Arzneimittel ist, dessen Kosten nicht grundsätzlich von der Beihilfegewährung ausgeschlossen werden dürfen, eine entsprechende medizinische Indikation (hier: erektile Dysfunktion nach Prostatakrebsoperation) vorausgesetzt. Auf ähnlicher Linie lag ein Urteil des Verwaltungsgericht Düsseldorf vom 2. September 2005 (26 K 371/05), das Tadalafil als ein über die Beihilfe erstattungsfähiges Medikament behandelt. Die Rechtsprechung ist vielfach kritisiert worden.[51]

Mit Urteil vom 12. August 2003 hat das Verwaltungsgericht Frankfurt am Main (Geschäftsnummer 10 E 5407/01) entschieden, dass Kranken Krankenhilfe nach dem Bundessozialhilfegesetz (§ 37 BSHG) zu gewähren ist, wenn sie sich selbst nicht helfen können. Die Sozialhilfe-Behörde durfte die Leistung eines Arzneimittels als Krankenhilfe nicht mit dem Verweis auf die Arzneimittelrichtlinien der gesetzlichen Krankenversicherung ablehnen, wonach unterschiedslos jegliche Behandlung einer [erektilen Dysfunktion] mit Arzneimitteln verweigert wird. Die Richtlinien seien nicht einschlägig, wenn es um die Behandlung einer Krankheit gehe. Deshalb hätten „Kassenpatienten“ wie Sozialhilfeempfänger bei einer Krankheit Anspruch auf Behandlung mit Viagra.[52]

Der Hessische Verwaltungsgerichtshof hat mit Urteil vom 11. Oktober 2004 (Geschäftsnummer: 10 UE 2731/03) entschieden, dass der durch das GKV-Modernisierungsgesetz vom 14. November 2003 (BGBl. I S. 2190) ab dem 1. Januar 2004 in § 34 Abs. 1 Satz 8 SGB V eingeführte Ausschluss von Medikamenten zur Behandlung der erektilen Dysfunktion von der Versorgung im Rahmen der gesetzlichen Krankenversicherung wegen der gleichzeitig eingeführten strengen Akzessorietät auch im Rahmen der Krankenhilfe nach dem Bundessozialhilfegesetz zu beachten sei. Nach dieser Neufassung komme jedenfalls ab dem 1. Januar 2004 ein Anspruch eines Hilfeempfängers auf Übernahme der Kosten für das Medikament Viagra im Rahmen der genannten Hilfeart nicht mehr in Betracht.[53]

Mit Beschluss vom 1. September 2005 hat das Hessische Landessozialgericht (Geschäftsnummer L 8 KR 80/05 ER) entschieden, dass das Medikament „Caverject“ (oder auch „Viagra“) als Leistung in der gesetzlichen Krankenversicherung nicht mehr vorgesehen sei, denn durch Artikel 1 Nr. 22 des Gesetzes zur Modernisierung der gesetzlichen Krankenversicherung (GMG) vom 14. November 2003 (BGBl. I S. 2190) seien mit Wirkung vom 1. Januar 2004 sämtliche Arzneimittel, die der Behandlung der erektilen Dysfunktion dienen, von der Verordnung zu Lasten der gesetzlichen Krankenversicherung ausgeschlossen.[54]

Anfang der 1990er Jahre suchte ein Forschungsteam eines Pfizer-Forschungsinstituts in Sandwich in England ein Mittel gegen Herzbeschwerden. Das dabei gefundene Mittel UK-92480 blockierte das Enzym PDE-5. Während erste Versuche an Patienten vielversprechend verlaufen waren, berichteten einige Männer von mehreren Erektionen einige Tage nach Einnahme des Medikaments. Der zuständige Versuchsleiter sah in dieser Wirkung kein Potential; Pfizer meldete daher 1991 den Wirkstoff als Sildenafil Citrate zum Patent an.[55]

Nachdem sich das Medikament für Herzbeschwerden letztlich als wirkungslos erwies, wurde die sexuelle Wirkung des Wirkstoffs genauer betrachtet. Bei einer Studie an 300 Männern in England, Frankreich und Schweden berichteten 90 Prozent über Erektionen; Nebenwirkungen wurden kaum beobachtet. 1998 erhielt Pfizer von der US-Gesundheitsbehörde die Genehmigung, Viagra zu verkaufen. Das Time Magazine berichtete in einer Titelgeschichte über die Potenzpille.[55]

Im Jahre 2003 wurden zwei weitere Medikamente mit gleichem Wirkmechanismus auf den Markt gebracht: Levitra (Bayer) und Cialis (Eli Lilly). 2012 folgte ein neuer Wirkstoff namens Avanafil (Mitsubishi Pharma), das schneller als Viagra wirken soll; der Handelsname ist Stendra.[55] Seit April 2014 ist Spedra (Berlin-Chemie mit dem Wirkstoff Avanafil) in Deutschland erhältlich.

Im Jahre 2007 hielt Pfizer auf dem Weltmarkt für Substanzen gegen erektile Dysfunktion einen Anteil von 47 Prozent, 2013 waren es 36 Prozent. Im Jahre 2012 erwirtschaftete Pfizer mit Viagra einen Umsatz von zwei Milliarden US-Dollar.[55]

اختلال نعوظ

عملكرد ايجاد نعوظ : سيلدنافيل هيچ اثر شُل‌كنندگي مستقيم بر كارپوس كاورنوزوم انسان ندارد، اما به واسطه مهار فسفودي‌استراز نوع 5 كه مسئول تخريب cGMP در كارپوس كاورنوزوم مي‌باشد، منجر به افزايش اثرات نيتريك اكسيد (NO) مي‌گردد.
زماني كه محرك جنسي منجر به افزايش رهاسازي NO مي‌گردد، مهار فسفودي‌استراز نوع 5 توسط سيلدنافيل باعث افزايش سطح cGMP در كارپوس كاورنوزوم شده، عضلات صاف شُل‌ گشته و خون به كارپوس كاورنوزوم جريان مي‌يابد.

در حساسيت مفرط به دارو يا هر يك از اجزاء فرمولاسيون و مصرف همزمان (منظم يا غير منظم) نيترات‌هاي ارگانيك به هر شکل دارويي منع مصرف دارد.
در بيماران دچار انسداد مسير خروجي بطن چپ (تنگي آئورت يا كارديوميوپاتي انسدادي هايپرتروفيك) بيماري عروق كرونري، ديابت، هايپرتانسيون كنترل نشده، هايپرليپيدمي، سيگاري‌ها، افراد بالاي 50 سال، بيماري‌هاي دژنراتيو رتين، بيماران دچار اختلالات آناتوميك آلت تناسلي، بيماري‌هاي خونريزي‌دهنده، هايپوتانسيون، آريتمي‌هاي تهديدكننده حيات، استروك يا انفاركتوس قلبي طي 6 ماه گذشته، نارسايي قلبي، شرايطي كه بيمار را مستعد پرياپيسم مي‌كند، نارسايي كبدي، زخم فعال گوارشي، هايپرتانسيون شريان ريوي و نارسايي كليوي بايد مصرف دارو با احتياط صورت گيرد.

اعصاب مرکزي: سردرد، بي‌خوابي، گيجي، تب، افسردگي، تشنج، ميگرن، نورآلژي، سرگيجه.
دستگاه گوارش: سوءهاضمه، اسهال، گاستريت، ديس‌فاژي، خونريزي از ركتوم، استفراغ، کوليت.
قلبي – عروقي: فلاشينگ، آنژين، بلوك AV، ايست قلبي، كارديوميوپاتي، ترومبوز مغزي، خونريزي داخل مغزي، ادم، نارسايي قلبي، هايپوتانسيون، هايپرتانسيون، ايسكمي ميوكارد، انفاركتوس قلبي، طپش قلب، افت فشار خون وضعيتي، شوك، تاكيكاردي، سنكوپ، آريتمي بطني.
متابوليك: هايپرگلاسيمي، هايپوگلاسيمي، هايپرناترمي، هايپراوريسمي.
عضلاني – اسكلتي: درد عضلاني، پارسترني، پارگي تاندون.
پوست: قرمزي، راش، درماتيت.
ادراري تناسلي: عفونت مجاري ادراري، سيستيت.
چشم: ديد غير طبيعي، خونريزي چشمي، افزايش فشار داخل چشمي، ميدرياز، بيماري عروق رتين يا خونريزي رتين، کاهش ميدان بينايي، حساسيت به نور.
گوش، حلق، بيني: خونريزي‌ بيني، كاهش شنوايي، كري، تشديد تنگي نفس، احتقان و آبريزش بيني، سينوزيت.
ساير عوارض: افزايش آنزيم‌هاي كبدي، واكنش‌هاي آلرژيك.

مهاركننده‌هاي فسفودي‌‌استراز نوع 5 منجر به افزايش اثرات كاهش فشار بلوك‌كننده‌هاي 1? مي‌شوند. استثناء در اين مورد داپي‌ پرازول مي‌باشد.
تركيبات ضد قارچ (مشتقات آزول، سيستميك) منجر به كاهش مهاركننده‌هاي فسفودي‌استراز نوع 5 مي‌شوند.
بوسنتان غلظت پلاسمايي مهاركننده‌هاي فسفودي‌استراز 5 را كاهش داده و اين داروها منجر به افزايش غلظت سرمي بوسنتان مي‌شوند.
متابوليسم سيلدنافيل توسط مهاركننده‌هاي CYP3A4 كاهش مي‌يابد.
دازاتينيب (Dasatinib) غلظت سرمي سيلدنافيل را افزايش مي‌دهد.
دفرازيروكس و اتراويرين غلظت سرمي سيلدنافيل را كاهش مي‌دهند.
سيلدنافيل منجر به كاهش متابوليسم استاتين‌ها به استثناء فلوواستانين، پراواستاتين و روزوواستاتين مي‌گردد.
آنتي‌بيوتيك‌هاي ماكروليدي و مهاركننده‌هاي پروتئاز منجر به كاهش متابوليسم سيلدنافيل مي‌شوند.
Peg: اينترفرون غلظت سرمي سيلدنافيل را كاهش مي‌دهد.قرص sildenafil citrate

FDA طبقه بندی: B. هيچ مطالعه كافي و كنترل شده‌اي در مورد سيلدنافيل در بارداري وجود ندارد.

ترشح سيلدنافيل در شير مشخص نيست و لازم است در خانم‌هاي باردار با احتياط مصرف شود.

برای اطلاع از مقدار و نحوه مصرف دارو با پزشک مشورت کنید.

قبل از استفاده از سيلدنافيل به عنوان درمان اختلال نعوظ، لازم است ساير علل ايجادكننده اين اختلال بررسي شود.
مصرف همزمان با آب‌ گريپ‌فروت منجر به افزايش خطر سميت مي‌شود و بايد از مصرف همزمان آنها پرهيز شود.

1- در صورت مصرف هر نوع تركيب نيترات، لازم است به پزشك معالج اطلاع داده شود.
2- در صورت بروز كاهش بينايي، مصرف دارو را قطع نموده و به پزشك اطلاع داده شود.
3- استفاده از سيلدنافيل هيچ‌گونه حفاظتي در مقابل بيماري‌هاي قابل انتقال توسط تماس جنسي ايجاد نمي‌كند.
مصرف در سالمندان: لازم است مصرف اين دارو در سالمندان با احتياط صورت گيرد و ممكن است لازم باشد دوز دارو تنظيم گردد.

Tablet: 25, 50, 100mg

اهران تجارت     تولید شده                                TABLET           ERECTO® 100MG TAB
بهستان دارو     تولید شده               TABLET           SILDENAFIL CITRATE 100MG TAB
بهستان دارو     تولید شده                                 TABLET           VIAGRA® 100MG TAB
پورسينا     تولید شده                TABLET          SILDENAFIL CITRATE 100MG TAB
خوارزمي     تولید شده                TABLET          SILDENAFIL CITRATE 100MG TAB
خوارزمي     تولید شده                               TABLET          SILERECT® 100MG TAB
رازك     تولید شده                                  TABLET          VIGRAZ® 100MG TAB
روز دارو     تولید شده                 TABLET          SILDENAFIL CITRATE 100MG TAB
شهر دارو     تولید شده                 TABLET          SILDENAFIL CITRATE 100MG TAB
فارماشيمي     تولید شده                 TABLET          SILDENAFIL CITRATE 100MG TAB
فارماشيمي     تولید شده             TABLET          SILDENAFIL-PHARMA® 100MG TAB
شهر دارو     تولید شده                   TABLET          SILDENAFIL CITRATE 25MG TAB
بهستان دارو     تولید شده                                    TABLET          VIAGRA® 50MG TAB
شهر دارو     تولید شده     TABLET          SILDENAFIL (SHAHREDAROU) 50MG TAB

روز دارو     تولید شده            F.C. Tablet     SILDENAFIL (RUZDAROU) 100MG TAB
شهر دارو     تولید شده                F.C. Tablet     SILDENAFIL (PURSINA) 100MG TAB
شهر دارو     تولید شده     F.C. Tablet     SILDENAFIL (SHAHREDAROU) 100MG TAB
شهر دارو     تولید شده       F.C. Tablet     SILDENAFIL (SHAHREDAROU) 25MG TAB
بهستان دارو     تولید شده                     F.C. Tablet     SILDENAFIL CITRATE 50MG TAB
پورسينا     تولید شده                     F.C. Tablet     SILDENAFIL CITRATE 50MG TAB
رازك     تولید شده                     F.C. Tablet     SILDENAFIL (RAZAK) 50MG TAB
رازك     تولید شده                     F.C. Tablet     SILDENAFIL CITRATE 50MG TAB
روز دارو     تولید شده              F.C. Tablet     SILDENAFIL (RUZDAROU) 50MG TAB
روز دارو     تولید شده                     F.C. Tablet     SILDENAFIL CITRATE 50MG TAB

مرهم دارو     تولید شده     Scored F.C.Tablet     SILDENAFIL (MARHAM DAROU) 100MG TAB
 

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بانک اطلاعات

ابزارهای بارداری و زایمان

ابزارهای رشد کودک

ابزارهای سنجش سلامت

پاسخ سوالات بر اساس تاریخ پرسش سوال

مطلب از سایر رسانه ها

Updated

December 20, 2018

If you are a consumer or patient please visit this version.

VIAGRA is a phosphodiesterase-5 (PDE5) inhibitor indicated for the treatment of erectile dysfunction (ED) (1)

Tablets: 25 mg, 50 mg, 100 mg (3)

Most common adverse reactions (≥ 2%) include headache, flushing, dyspepsia, abnormal vision, nasal congestion, back pain, myalgia, nausea, dizziness and rash (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Pfizer at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. قرص sildenafil citrate

See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.

Revised: 3/2014

VIAGRA is indicated for the treatment of erectile dysfunction.

For most patients, the recommended dose is 50 mg taken, as needed, approximately 1 hour before sexual activity. However, VIAGRA may be taken anywhere from 30 minutes to 4 hours before sexual activity.

The maximum recommended dosing frequency is once per day.

Based on effectiveness and toleration, the dose may be increased to a maximum recommended dose of 100 mg or decreased to 25 mg.

VIAGRA may be taken with or without food.

VIAGRA was shown to potentiate the hypotensive effects of nitrates and its administration in patients who use nitric oxide donors such as organic nitrates or organic nitrites in any form is therefore contraindicated [see Contraindications (4.1), Drug Interactions (7.1), and Clinical Pharmacology (12.2)].

When VIAGRA is co-administered with an alpha-blocker, patients should be stable on alpha-blocker therapy prior to initiating VIAGRA treatment and VIAGRA should be initiated at 25 mg [see Warnings and Precautions (5.5), Drug Interactions (7.2), and Clinical Pharmacology (12.2)].

Ritonavir

The recommended dose for ritonavir-treated patients is 25 mg prior to sexual activity and the recommended maximum dose is 25 mg within a 48 hour period because concomitant administration increased the blood levels of sildenafil by 11-fold [see Warnings and Precautions (5.6), Drug Interactions (7.4), and Clinical Pharmacology (12.3)].

CYP3A4 Inhibitors

Consider a starting dose of 25 mg in patients treated with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, or saquinavir) or erythromycin. Clinical data have shown that co-administration with saquinavir or erythromycin increased plasma levels of sildenafil by about 3 fold [see Drug Interactions (7.4) and Clinical Pharmacology (12.3)].

Consider a starting dose of 25 mg in patients > 65 years, patients with hepatic impairment (e.g., cirrhosis), and patients with severe renal impairment (creatinine clearance <30 mL/minute) because administration of VIAGRA in these patients resulted in higher plasma levels of sildenafil [see Use in Specific Populations (8.5, 8.6, 8.7) and Clinical Pharmacology (12.3)].

VIAGRA is supplied as blue, film-coated, rounded-diamond-shaped tablets containing sildenafil citrate equivalent to 25 mg, 50 mg, or 100 mg of sildenafil. Tablets are debossed with PFIZER on one side and VGR25, VGR50 or VGR100 on the other to indicate the dosage strengths.

Consistent with its known effects on the nitric oxide/cGMP pathway [see Clinical Pharmacology (12.1, 12.2)], VIAGRA was shown to potentiate the hypotensive effects of nitrates, and its administration to patients who are using nitric oxide donors such as organic nitrates or organic nitrites in any form either regularly and/or intermittently is therefore contraindicated.

After patients have taken VIAGRA, it is unknown when nitrates, if necessary, can be safely administered. Although plasma levels of sildenafil at 24 hours post dose are much lower than at peak concentration, it is unknown whether nitrates can be safely co-administered at this time point [see Dosage and Administration (2.3), Drug Interactions (7.1), and Clinical Pharmacology (12.2)].

VIAGRA is contraindicated in patients with a known hypersensitivity to sildenafil, as contained in VIAGRA and REVATIO, or any component of the tablet. Hypersensitivity reactions have been reported, including rash and urticaria [see Adverse Reactions (6.1)].

There is a potential for cardiac risk of sexual activity in patients with preexisting cardiovascular disease. Therefore, treatments for erectile dysfunction, including VIAGRA, should not be generally used in men for whom sexual activity is inadvisable because of their underlying cardiovascular status. The evaluation of erectile dysfunction should include a determination of potential underlying causes and the identification of appropriate treatment following a complete medical assessment.

VIAGRA has systemic vasodilatory properties that resulted in transient decreases in supine blood pressure in healthy volunteers (mean maximum decrease of 8.4/5.5 mmHg), [see Clinical Pharmacology (12.2)]. While this normally would be expected to be of little consequence in most patients, prior to prescribing VIAGRA, physicians should carefully consider whether their patients with underlying cardiovascular disease could be affected adversely by such vasodilatory effects, especially in combination with sexual activity.قرص sildenafil citrate

Use with caution in patients with the following underlying conditions which can be particularly sensitive to the actions of vasodilators including VIAGRA – those with left ventricular outflow obstruction (e.g., aortic stenosis, idiopathic hypertrophic subaortic stenosis) and those with severely impaired autonomic control of blood pressure.

There are no controlled clinical data on the safety or efficacy of VIAGRA in the following groups; if prescribed, this should be done with caution.

Prolonged erection greater than 4 hours and priapism (painful erections greater than 6 hours in duration) have been reported infrequently since market approval of VIAGRA. In the event of an erection that persists longer than 4 hours, the patient should seek immediate medical assistance. If priapism is not treated immediately, penile tissue damage and permanent loss of potency could result.

VIAGRA 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 anemia, multiple myeloma, or leukemia). However, there are no controlled clinical data on the safety or efficacy of VIAGRA in patients with sickle cell or related anemias.

Physicians should advise patients to stop use of all phosphodiesterase type 5 (PDE5) inhibitors, including VIAGRA, and seek medical attention in the event of a sudden loss of vision in one or both eyes. Such an event may be a sign of non-arteritic anterior ischemic optic neuropathy (NAION), a rare condition and a cause of decreased vision including permanent loss of vision, that has been reported rarely post-marketing in temporal association with the use of all PDE5 inhibitors. Based on published literature, the annual incidence of NAION is 2.5–11.8 cases per 100,000 in males aged ≥ 50. An observational study evaluated whether recent use of PDE5 inhibitors, as a class, was associated with acute onset of NAION. The results suggest an approximate 2 fold increase in the risk of NAION within 5 half-lives of PDE5 inhibitor use. From this information, it is not possible to determine whether these events are related directly to the use of PDE5 inhibitors or to other factors [see Adverse Reactions (6.2)].

Physicians should consider whether their patients with underlying NAION risk factors could be adversely affected by use of PDE5 inhibitors. Individuals who have already experienced NAION are at increased risk of NAION recurrence. Therefore, PDE5 inhibitors, including VIAGRA, should be used with caution in these patients and only when the anticipated benefits outweigh the risks. Individuals with “crowded” optic disc are also considered at greater risk for NAION compared to the general population, however, evidence is insufficient to support screening of prospective users of PDE5 inhibitors, including VIAGRA, for this uncommon condition.

There are no controlled clinical data on the safety or efficacy of VIAGRA in patients with retinitis pigmentosa (a minority of these patients have genetic disorders of retinal phosphodiesterases).

Physicians should advise patients to stop taking PDE5 inhibitors, including VIAGRA, and seek prompt medical attention in the event of sudden decrease or loss of hearing. These events, which may be accompanied by tinnitus and dizziness, have been reported in temporal association to the intake of PDE5 inhibitors, including VIAGRA. It is not possible to determine whether these events are related directly to the use of PDE5 inhibitors or to other factors [see Adverse Reactions (6.1, 6.2)].

Alpha-blockers

Caution is advised when PDE5 inhibitors are co-administered with alpha-blockers. PDE5 inhibitors, including VIAGRA, and alpha-adrenergic blocking agents are both vasodilators with blood pressure lowering effects. When vasodilators are used in combination, an additive effect on blood pressure may occur. In some patients, concomitant use of these two drug classes can lower blood pressure significantly [see Drug Interactions (7.2) and Clinical Pharmacology (12.2)] leading to symptomatic hypotension (e.g., dizziness, lightheadedness, fainting).

Consideration should be given to the following:

Anti-hypertensives

VIAGRA has systemic vasodilatory properties and may further lower blood pressure in patients taking anti-hypertensive medications.

In a separate drug interaction study, when amlodipine, 5 mg or 10 mg, and VIAGRA, 100 mg were orally administered concomitantly to hypertensive patients mean additional blood pressure reduction of 8 mmHg systolic and 7 mmHg diastolic were noted [see Drug Interactions (7.3) and Clinical Pharmacology (12.2)].

The concomitant administration of the protease inhibitor ritonavir substantially increases serum concentrations of sildenafil (11-fold increase in AUC). If VIAGRA is prescribed to patients taking ritonavir, caution should be used. Data from subjects exposed to high systemic levels of sildenafil are limited. Decreased blood pressure, syncope, and prolonged erection were reported in some healthy volunteers exposed to high doses of sildenafil (200–800 mg). To decrease the chance of adverse reactions in patients taking ritonavir, a decrease in sildenafil dosage is recommended [see Dosage and Administration (2.4), Drug Interactions (7.4), and Clinical Pharmacology (12.3)].

The safety and efficacy of combinations of VIAGRA with other PDE5 Inhibitors, including REVATIO or other pulmonary arterial hypertension (PAH) treatments containing sildenafil, or other treatments for erectile dysfunction have not been studied. Such combinations may further lower blood pressure. Therefore, the use of such combinations is not recommended.

There have been postmarketing reports of bleeding events in patients who have taken VIAGRA. A causal relationship between VIAGRA and these events has not been established. In humans, VIAGRA has no effect on bleeding time when taken alone or with aspirin. However, in vitro studies with human platelets indicate that sildenafil potentiates the antiaggregatory effect of sodium nitroprusside (a nitric oxide donor). In addition, the combination of heparin and VIAGRA had an additive effect on bleeding time in the anesthetized rabbit, but this interaction has not been studied in humans.

The safety of VIAGRA is unknown in patients with bleeding disorders and patients with active peptic ulceration.

The use of VIAGRA offers no protection against sexually transmitted diseases. Counseling of patients about the protective measures necessary to guard against sexually transmitted diseases, including the Human Immunodeficiency Virus (HIV), may be considered.

The following are discussed in more detail in other sections of the labeling:

The most common adverse reactions reported in clinical trials (≥ 2%) are headache, flushing, dyspepsia, abnormal vision, nasal congestion, back pain, myalgia, nausea, dizziness, and rash.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

VIAGRA was administered to over 3700 patients (aged 19–87 years) during pre-marketing clinical trials worldwide. Over 550 patients were treated for longer than one year.

In placebo-controlled clinical studies, the discontinuation rate due to adverse reactions for VIAGRA (2.5%) was not significantly different from placebo (2.3%).

In fixed-dose studies, the incidence of some adverse reactions increased with dose. The type of adverse reactions in flexible-dose studies, which reflect the recommended dosage regimen, was similar to that for fixed-dose studies. At doses above the recommended dose range, adverse reactions were similar to those detailed in Table 1 below but generally were reported more frequently.

When VIAGRA was taken as recommended (on an as-needed basis) in flexible-dose, placebo-controlled clinical trials of two to twenty-six weeks duration, patients took VIAGRA at least once weekly, and the following adverse reactions were reported:

The following events occurred in <2% of patients in controlled clinical trials; a causal relationship to VIAGRA is uncertain. Reported events include those with a plausible relation to drug use; omitted are minor events and reports too imprecise to be meaningful:

Body as a Whole: face edema, photosensitivity reaction, shock, asthenia, pain, chills, accidental fall, abdominal pain, allergic reaction, chest pain, accidental injury.

Cardiovascular: angina pectoris, AV block, migraine, syncope, tachycardia, palpitation, hypotension, postural hypotension, myocardial ischemia, cerebral thrombosis, cardiac arrest, heart failure, abnormal electrocardiogram, cardiomyopathy.

Digestive: vomiting, glossitis, colitis, dysphagia, gastritis, gastroenteritis, esophagitis, stomatitis, dry mouth, liver function tests abnormal, rectal hemorrhage, gingivitis.

Hemic and Lymphatic: anemia and leukopenia.

Metabolic and Nutritional: thirst, edema, gout, unstable diabetes, hyperglycemia, peripheral edema, hyperuricemia, hypoglycemic reaction, hypernatremia.

Musculoskeletal: arthritis, arthrosis, myalgia, tendon rupture, tenosynovitis, bone pain, myasthenia, synovitis.

Nervous: ataxia, hypertonia, neuralgia, neuropathy, paresthesia, tremor, vertigo, depression, insomnia, somnolence, abnormal dreams, reflexes decreased, hypesthesia.

Respiratory: asthma, dyspnea, laryngitis, pharyngitis, sinusitis, bronchitis, sputum increased, cough increased.

Skin and Appendages: urticaria, herpes simplex, pruritus, sweating, skin ulcer, contact dermatitis, exfoliative dermatitis.

Special Senses: sudden decrease or loss of hearing, mydriasis, conjunctivitis, photophobia, tinnitus, eye pain, ear pain, eye hemorrhage, cataract, dry eyes.

Urogenital: cystitis, nocturia, urinary frequency, breast enlargement, urinary incontinence, abnormal ejaculation, genital edema and anorgasmia.

Analysis of the safety database from controlled clinical trials showed no apparent difference in adverse reactions in patients taking VIAGRA with and without anti-hypertensive medication. This analysis was performed retrospectively, and was not powered to detect any pre-specified difference in adverse reactions.

The following adverse reactions have been identified during post approval use of VIAGRA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These events have been chosen for inclusion either due to their seriousness, reporting frequency, lack of clear alternative causation, or a combination of these factors.

Cardiovascular and cerebrovascular

Serious cardiovascular, cerebrovascular, and vascular events, including myocardial infarction, sudden cardiac death, ventricular arrhythmia, cerebrovascular hemorrhage, transient ischemic attack, hypertension, subarachnoid and intracerebral hemorrhages, and pulmonary hemorrhage have been reported post-marketing in temporal association with the use of VIAGRA. Most, but not all, of these patients had preexisting cardiovascular risk factors. Many of these events were reported to occur during or shortly after sexual activity, and a few were reported to occur shortly after the use of VIAGRA without sexual activity. Others were reported to have occurred hours to days after the use of VIAGRA and sexual activity. It is not possible to determine whether these events are related directly to VIAGRA, to sexual activity, to the patient’s underlying cardiovascular disease, to a combination of these factors, or to other factors [see Warnings and Precautions (5.1) and Patient Counseling Information (17.3)].

Hemic and Lymphatic: vaso-occlusive crisis: In a small, prematurely terminated study of REVATIO (sildenafil) in patients with pulmonary arterial hypertension (PAH) secondary to sickle cell disease, vaso-occlusive crises requiring hospitalization were more commonly reported in patients who received sildenafil than in those randomized to placebo. The clinical relevance of this finding to men treated with VIAGRA for ED is not known.

Nervous: seizure, seizure recurrence, anxiety, and transient global amnesia.

Respiratory: epistaxis

Special senses:

Hearing: Cases of sudden decrease or loss of hearing have been reported postmarketing in temporal association with the use of PDE5 inhibitors, including VIAGRA. In some of the cases, medical conditions and other factors were reported that may have also played a role in the otologic adverse events. In many cases, medical follow-up information was limited. It is not possible to determine whether these reported events are related directly to the use of VIAGRA, to the patient’s underlying risk factors for hearing loss, a combination of these factors, or to other factors [see Warnings and Precautions (5.4) and Patient Counseling Information (17.5)].

Ocular: diplopia, temporary vision loss/decreased vision, ocular redness or bloodshot appearance, ocular burning, ocular swelling/pressure, increased intraocular pressure, retinal edema, retinal vascular disease or bleeding, and vitreous traction/detachment.

Non-arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision including permanent loss of vision, has been reported rarely post-marketing in temporal association with the use of phosphodiesterase type 5 (PDE5) inhibitors, including VIAGRA. Most, but not all, of these patients had underlying anatomic or vascular risk factors for developing NAION, including but not necessarily limited to: low cup to disc ratio (“crowded disc”), age over 50, diabetes, hypertension, coronary artery disease, hyperlipidemia and smoking. It is not possible to determine whether these events are related directly to the use of PDE5 inhibitors, to the patient’s underlying vascular risk factors or anatomical defects, to a combination of these factors, or to other factors [see Warnings and Precautions (5.3) and Patient Counseling Information (17.4)].

Urogenital: prolonged erection, priapism [see Warnings and Precautions (5.2) and Patient Counseling Information (17.6)], and hematuria.

Administration of VIAGRA with nitric oxide donors such as organic nitrates or organic nitrites in any form is contraindicated. Consistent with its known effects on the nitric oxide/cGMP pathway, VIAGRA was shown to potentiate the hypotensive effects of nitrates [see Dosage and Administration (2.3), Contraindications (4.1), Clinical Pharmacology (12.2)].

Use caution when co-administering alpha-blockers with VIAGRA because of potential additive blood pressure-lowering effects. When VIAGRA is co-administered with an alpha-blocker, patients should be stable on alpha-blocker therapy prior to initiating VIAGRA treatment and VIAGRA should be initiated at the lowest dose [see Dosage and Administration (2.3),Warnings and Precautions (5.5), Clinical Pharmacology (12.2)].

When VIAGRA 100 mg was co-administered with amlodipine (5 mg or 10 mg) to hypertensive patients, the mean additional reduction on supine blood pressure was 8 mmHg systolic and 7 mmHg diastolic [see Warnings and Precautions (5.5), Clinical Pharmacology (12.2)].

Co-administration of ritonavir, a strong CYP3A4 inhibitor, greatly increased the systemic exposure of sildenafil (11-fold increase in AUC). It is therefore recommended not to exceed a maximum single dose of 25 mg of VIAGRA in a 48 hour period [see Dosage and Administration (2.4), Warnings and Precautions (5.6), Clinical Pharmacology (12.3)].

Co-administration of erythromycin, a moderate CYP3A4 inhibitor, resulted in a 160% and 182% increases in sildenafil Cmax and AUC, respectively. Co-administration of saquinavir, a strong CYP3A4 inhibitor, resulted in 140% and 210% increases in sildenafil Cmax and AUC, respectively. Stronger CYP3A4 inhibitors such as ketoconazole or itraconazole could be expected to have greater effects than seen with saquinavir. A starting dose of 25 mg of VIAGRA should be considered in patients taking erythromycin or strong CYP3A4 inhibitors (such as saquinavir, ketoconazole, itracanozole) [see Dosage and Administration (2.4), Clinical Pharmacology (12.3)].

In a drug-drug interaction study sildenafil 50 mg given with alcohol 0.5 g/kg in which mean maximum blood alcohol levels of 0.08% was achieved, sildenafil did not potentiate the hypotensive effect of alcohol in healthy volunteers [see Clinical Pharmacology (12.2)].

Pregnancy Category B.

VIAGRA is not indicated for use in women. There are no adequate and well-controlled studies of sildenafil in pregnant women.

Risk Summary

Based on animal data, VIAGRA is not predicted to increase the risk of adverse developmental outcomes in humans.

Animal Data

No evidence of teratogenicity, embryotoxicity or fetotoxicity was observed in rats and rabbits which received up to 200 mg/kg/day during organogenesis. These doses represent, respectively, about 20 and 40 times the Maximum Recommended Human Dose (MRHD) on a mg/m2 basis in a 50 kg subject. In the rat pre- and postnatal development study, the no observed adverse effect dose was 30 mg/kg/day given for 36 days. In the nonpregnant rat the AUC at this dose was about 20 times human AUC.

VIAGRA is not indicated for use in pediatric patients. Safety and effectiveness have not been established in pediatric patients.

Healthy elderly volunteers (65 years or over) had a reduced clearance of sildenafil resulting in approximately 84% and 107% higher plasma AUC values of sildenafil and its active N-desmethyl metabolite, respectively, compared to those seen in healthy young volunteers (18–45 years) [see Clinical Pharmacology (12.3)]. Due to age-differences in plasma protein binding, the corresponding increase in the AUC of free (unbound) sildenafil and its active N-desmethyl metabolite were 45% and 57%, respectively [see Clinical Pharmacology (12.3)].

Of the total number of subjects in clinical studies of Viagra, 18% were 65 years and older, while 2% were 75 years and older. No overall differences in safety or efficacy were observed between older (≥ 65 years of age) and younger (< 65 years of age) subjects.

However, since higher plasma levels may increase the incidence of adverse reactions, a starting dose of 25 mg should be considered in older subjects due to the higher systemic exposure [see Dosage and Administration (2.5)].

No dose adjustment is required for mild (CLcr=50–80 mL/min) and moderate (CLcr=30–49 mL/min) renal impairment. In volunteers with severe renal impairment (Clcr<30 mL/min), sildenafil clearance was reduced, resulting in higher plasma exposure of sildenafil (~2 fold), approximately doubling of Cmax and AUC. A starting dose of 25 mg should be considered in patients with severe renal impairment [see Dosage and Administration (2.5) and Clinical Pharmacology (12.3)].

In volunteers with hepatic impairment (Child-Pugh Class A and B), sildenafil clearance was reduced, resulting in higher plasma exposure of sildenafil (47% for Cmax and 85% for AUC). The pharmacokinetics of sildenafil in patients with severely impaired hepatic function (Child-Pugh Class C) have not been studied. A starting dose of 25 mg should be considered in patients with any degree of hepatic impairment [see Dosage and Administration (2.5) and Clinical Pharmacology (12.3)].

In studies with healthy volunteers of single doses up to 800 mg, adverse reactions were similar to those seen at lower doses but incidence rates and severities were increased.

In cases of overdose, standard supportive measures should be adopted as required. Renal dialysis is not expected to accelerate clearance as sildenafil is highly bound to plasma proteins and it is not eliminated in the urine.

VIAGRA (sildenafil citrate), an oral therapy for erectile dysfunction, is the citrate salt of sildenafil, a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5).

Sildenafil citrate is designated chemically as 1-[[3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-ethoxyphenyl]sulfonyl]-4-methylpiperazine citrate and has the following structural formula:

Sildenafil citrate is a white to off-white crystalline powder with a solubility of 3.5 mg/mL in water and a molecular weight of 666.7.

The physiologic mechanism of erection of the penis involves release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. NO then activates the enzyme guanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (cGMP), producing smooth muscle relaxation in the corpus cavernosum and allowing inflow of blood.

Sildenafil enhances the effect of NO by inhibiting phosphodiesterase type 5 (PDE5), which is responsible for degradation of cGMP in the corpus cavernosum. Sildenafil has no direct relaxant effect on isolated human corpus cavernosum. When sexual stimulation causes local release of NO, inhibition of PDE5 by sildenafil causes increased levels of cGMP in the corpus cavernosum, resulting in smooth muscle relaxation and inflow of blood to the corpus cavernosum. Sildenafil at recommended doses has no effect in the absence of sexual stimulation.

Binding Characteristics

Studies in vitro have shown that sildenafil is selective for PDE5. Its effect is more potent on PDE5 than on other known phosphodiesterases (10-fold for PDE6, >80-fold for PDE1, >700-fold for PDE2, PDE3, PDE4, PDE7, PDE8, PDE9, PDE10, and PDE11). Sildenafil is approximately 4,000-fold more selective for PDE5 compared to PDE3. PDE3 is involved in control of cardiac contractility. Sildenafil is only about 10-fold as potent for PDE5 compared to PDE6, an enzyme found in the retina which is involved in the phototransduction pathway of the retina. This lower selectivity is thought to be the basis for abnormalities related to color vision [see Clinical Pharmacology (12.2)].

In addition to human corpus cavernosum smooth muscle, PDE5 is also found in other tissues including platelets, vascular and visceral smooth muscle, and skeletal muscle, brain, heart, liver, kidney, lung, pancreas, prostate, bladder, testis, and seminal vesicle. The inhibition of PDE5 in some of these tissues by sildenafil may be the basis for the enhanced platelet antiaggregatory activity of NO observed in vitro, an inhibition of platelet thrombus formation in vivo and peripheral arterial-venous dilatation in vivo.

Effects of VIAGRA on Erectile Response: In eight double-blind, placebo-controlled crossover studies of patients with either organic or psychogenic erectile dysfunction, sexual stimulation resulted in improved erections, as assessed by an objective measurement of hardness and duration of erections (RigiScan®), after VIAGRA administration compared with placebo. Most studies assessed the efficacy of VIAGRA approximately 60 minutes post dose. The erectile response, as assessed by RigiScan®, generally increased with increasing sildenafil dose and plasma concentration. The time course of effect was examined in one study, showing an effect for up to 4 hours but the response was diminished compared to 2 hours.

Effects of VIAGRA on Blood Pressure: Single oral doses of sildenafil (100 mg) administered to healthy volunteers produced decreases in sitting blood pressure (mean maximum decrease in systolic/diastolic blood pressure of 8.3/5.3 mmHg). The decrease in sitting blood pressure was most notable approximately 1–2 hours after dosing, and was not different than placebo at 8 hours. Similar effects on blood pressure were noted with 25 mg, 50 mg and 100 mg of VIAGRA, therefore the effects are not related to dose or plasma levels within this dosage range. Larger effects were recorded among patients receiving concomitant nitrates [see Contraindications (4.1)].

Effects of VIAGRA on Blood Pressure When Nitroglycerin is Subsequently Administered: Based on the pharmacokinetic profile of a single 100 mg oral dose given to healthy normal volunteers, the plasma levels of sildenafil at 24 hours post dose are approximately 2 ng/mL (compared to peak plasma levels of approximately 440 ng/mL). In the following patients: age >65 years, hepatic impairment (e.g., cirrhosis), severe renal impairment (e.g., creatinine clearance <30 mL/min), and concomitant use of erythromycin or strong CYP3A4 inhibitors, plasma levels of sildenafil at 24 hours post dose have been found to be 3 to 8 times higher than those seen in healthy volunteers. Although plasma levels of sildenafil at 24 hours post dose are much lower than at peak concentration, it is unknown whether nitrates can be safely co-administered at this time point [see Contraindications (4.1)].

Effects of VIAGRA on Blood Pressure When Co-administered with Alpha-Blockers: Three double-blind, placebo-controlled, randomized, two-way crossover studies were conducted to assess the interaction of VIAGRA with doxazosin, an alpha-adrenergic blocking agent.

Study 1: VIAGRA with Doxazosin

In the first study, a single oral dose of VIAGRA 100 mg or matching placebo was administered in a 2-period crossover design to 4 generally healthy males with benign prostatic hyperplasia (BPH). Following at least 14 consecutive daily doses of doxazosin, VIAGRA 100 mg or matching placebo was administered simultaneously with doxazosin. Following a review of the data from these first 4 subjects (details provided below), the VIAGRA dose was reduced to 25 mg. Thereafter, 17 subjects were treated with VIAGRA 25 mg or matching placebo in combination with doxazosin 4 mg (15 subjects) or doxazosin 8 mg (2 subjects). The mean subject age was 66.5 years.

For the 17 subjects who received VIAGRA 25 mg and matching placebo, the placebo-subtracted mean maximum decreases from baseline (95% CI) in systolic blood pressure were as follows:

The mean profiles of the change from baseline in standing systolic blood pressure in subjects treated with doxazosin in combination with 25 mg VIAGRA or matching placebo are shown in Figure 2.

Figure 2: Mean Standing Systolic Blood Pressure Change from Baseline

Blood pressure was measured immediately pre-dose and at 15, 30, 45 minutes, and 1, 1.5, 2, 2.5, 3, 4, 6 and 8 hours after VIAGRA or matching placebo. Outliers were defined as subjects with a standing systolic blood pressure of 30 mmHg at one or more timepoints. There were no subjects treated with VIAGRA 25 mg who had a standing SBP 30mmHg following VIAGRA 25 mg, one subject with a decrease from baseline in standing systolic BP > 30 mmHg following placebo and two subjects with a decrease from baseline in standing systolic BP > 30 mmHg following both VIAGRA and placebo. No severe adverse events potentially related to blood pressure effects were reported in this group.

Of the four subjects who received VIAGRA 100 mg in the first part of this study, a severe adverse event related to blood pressure effect was reported in one patient (postural hypotension that began 35 minutes after dosing with VIAGRA with symptoms lasting for 8 hours), and mild adverse events potentially related to blood pressure effects were reported in two others (dizziness, headache and fatigue at 1 hour after dosing; and dizziness, lightheadedness and nausea at 4 hours after dosing). There were no reports of syncope among these patients. For these four subjects, the placebo-subtracted mean maximum decreases from baseline in supine and standing systolic blood pressures were 14.8 mmHg and 21.5 mmHg, respectively. Two of these subjects had a standing SBP < 85mmHg. Both of these subjects were protocol violators, one due to a low baseline standing SBP, and the other due to baseline orthostatic hypotension.

Study 2: VIAGRA with Doxazosin

In the second study, a single oral dose of VIAGRA 50 mg or matching placebo was administered in a 2-period crossover design to 20 generally healthy males with BPH. Following at least 14 consecutive days of doxazosin, VIAGRA 50 mg or matching placebo was administered simultaneously with doxazosin 4 mg (17 subjects) or with doxazosin 8 mg (3 subjects). The mean subject age in this study was 63.9 years.

Twenty subjects received VIAGRA 50 mg, but only 19 subjects received matching placebo. One patient discontinued the study prematurely due to an adverse event of hypotension following dosing with VIAGRA 50 mg. This patient had been taking minoxidil, a potent vasodilator, during the study.

For the 19 subjects who received both VIAGRA and matching placebo, the placebo-subtracted mean maximum decreases from baseline (95% CI) in systolic blood pressure were as follows:

The mean profiles of the change from baseline in standing systolic blood pressure in subjects treated with doxazosin in combination with 50 mg VIAGRA or matching placebo are shown in Figure 3.

Figure 3: Mean Standing Systolic Blood Pressure Change from Baseline

Blood pressure was measured after administration of VIAGRA at the same times as those specified for the first doxazosin study. There were two subjects who had a standing SBP of 30mmHg following VIAGRA 50 mg and one subject with a decrease from baseline in standing systolic BP > 30 mmHg following both VIAGRA 50 mg and placebo. There were no severe adverse events potentially related to blood pressure and no episodes of syncope reported in this study.

Study 3: VIAGRA with Doxazosin

In the third study, a single oral dose of VIAGRA 100 mg or matching placebo was administered in a 3-period crossover design to 20 generally healthy males with BPH. In dose period 1, subjects were administered open-label doxazosin and a single dose of VIAGRA 50 mg simultaneously, after at least 14 consecutive days of doxazosin. If a subject did not successfully complete this first dosing period, he was discontinued from the study. Subjects who had successfully completed the previous doxazosin interaction study (using VIAGRA 50 mg), including no significant hemodynamic adverse events, were allowed to skip dose period 1. Treatment with doxazosin continued for at least 7 days after dose period 1. Thereafter, VIAGRA 100 mg or matching placebo was administered simultaneously with doxazosin 4 mg (14 subjects) or doxazosin 8 mg (6 subjects) in standard crossover fashion. The mean subject age in this study was 66.4 years.

Twenty-five subjects were screened. Two were discontinued after study period 1: one failed to meet pre-dose screening qualifications and the other experienced symptomatic hypotension as a moderately severe adverse event 30 minutes after dosing with open-label VIAGRA 50 mg. Of the twenty subjects who were ultimately assigned to treatment, a total of 13 subjects successfully completed dose period 1, and seven had successfully completed the previous doxazosin study (using VIAGRA 50 mg).

For the 20 subjects who received VIAGRA 100 mg and matching placebo, the placebo-subtracted mean maximum decreases from baseline (95% CI) in systolic blood pressure were as follows:

The mean profiles of the change from baseline in standing systolic blood pressure in subjects treated with doxazosin in combination with 100 mg VIAGRA or matching placebo are shown in Figure 4.

Figure 4: Mean Standing Systolic Blood Pressure Change from Baseline

Blood pressure was measured after administration of VIAGRA at the same times as those specified for the previous doxazosin studies. There were three subjects who had a standing SBP of 30 mmHg following VIAGRA 100 mg, one subject with a decrease from baseline in standing systolic BP > 30 mmHg following placebo and one subject with a decrease from baseline in standing systolic BP > 30 mmHg following both VIAGRA and placebo. While there were no severe adverse events potentially related to blood pressure reported in this study, one subject reported moderate vasodilatation after both VIAGRA 50 mg and 100 mg. There were no episodes of syncope reported in this study.

Effect of VIAGRA on Blood Pressure When Co-administered with Anti-hypertensives: When VIAGRA 100 mg oral was co-administered with amlodipine, 5 mg or 10 mg oral, to hypertensive patients, the mean additional reduction on supine blood pressure was 8 mmHg systolic and 7 mmHg diastolic.

Effect of VIAGRA on Blood Pressure When Co-administered with Alcohol: VIAGRA (50 mg) did not potentiate the hypotensive effect of alcohol (0.5 g/kg) in healthy volunteers with mean maximum blood alcohol levels of 0.08%. The maximum observed decrease in systolic blood pressure was -18.5 mmHg when sildenafil was co-administered with alcohol versus -17.4 mmHg when alcohol was administered alone. The maximum observed decrease in diastolic blood pressure was -17.2 mmHg when sildenafil was co-administered with alcohol versus -11.1 mmHg when alcohol was administered alone. There were no reports of postural dizziness or orthostatic hypotension. The maximum recommended dose of 100 mg sildenafil was not evaluated in this study [see Drug Interactions (7.5)].

Effects of VIAGRA on Cardiac Parameters: Single oral doses of sildenafil up to 100 mg produced no clinically relevant changes in the ECGs of normal male volunteers.

Studies have produced relevant data on the effects of VIAGRA on cardiac output. In one small, open-label, uncontrolled, pilot study, eight patients with stable ischemic heart disease underwent Swan-Ganz catheterization. A total dose of 40 mg sildenafil was administered by four intravenous infusions.

The results from this pilot study are shown in Table 3; the mean resting systolic and diastolic blood pressures decreased by 7% and 10% compared to baseline in these patients. Mean resting values for right atrial pressure, pulmonary artery pressure, pulmonary artery occluded pressure and cardiac output decreased by 28%, 28%, 20% and 7% respectively. Even though this total dosage produced plasma sildenafil concentrations which were approximately 2 to 5 times higher than the mean maximum plasma concentrations following a single oral dose of 100 mg in healthy male volunteers, the hemodynamic response to exercise was preserved in these patients.

In a double-blind study, 144 patients with erectile dysfunction and chronic stable angina limited by exercise, not receiving chronic oral nitrates, were randomized to a single dose of placebo or VIAGRA 100 mg 1 hour prior to exercise testing. The primary endpoint was time to limiting angina in the evaluable cohort. The mean times (adjusted for baseline) to onset of limiting angina were 423.6 and 403.7 seconds for sildenafil (N=70) and placebo, respectively. These results demonstrated that the effect of VIAGRA on the primary endpoint was statistically non-inferior to placebo.

Effects of VIAGRA on Vision: At single oral doses of 100 mg and 200 mg, transient dose-related impairment of color discrimination was detected using the Farnsworth-Munsell 100-hue test, with peak effects near the time of peak plasma levels. This finding is consistent with the inhibition of PDE6, which is involved in phototransduction in the retina. Subjects in the study reported this finding as difficulties in discriminating blue/green. An evaluation of visual function at doses up to twice the maximum recommended dose revealed no effects of VIAGRA on visual acuity, intraocular pressure, or pupillometry.

Effects of VIAGRA on Sperm: There was no effect on sperm motility or morphology after single 100 mg oral doses of VIAGRA in healthy volunteers.

VIAGRA is rapidly absorbed after oral administration, with a mean absolute bioavailability of 41% (range 25–63%). The pharmacokinetics of sildenafil are dose-proportional over the recommended dose range. It is eliminated predominantly by hepatic metabolism (mainly CYP3A4) and is converted to an active metabolite with properties similar to the parent, sildenafil. Both sildenafil and the metabolite have terminal half lives of about 4 hours.

Mean sildenafil plasma concentrations measured after the administration of a single oral dose of 100 mg to healthy male volunteers is depicted below:

Absorption and Distribution: VIAGRA is rapidly absorbed. Maximum observed plasma concentrations are reached within 30 to 120 minutes (median 60 minutes) of oral dosing in the fasted state. When VIAGRA is taken with a high fat meal, the rate of absorption is reduced, with a mean delay in Tmax of 60 minutes and a mean reduction in Cmax of 29%. The mean steady state volume of distribution (Vss) for sildenafil is 105 L, indicating distribution into the tissues. Sildenafil and its major circulating N-desmethyl metabolite are both approximately 96% bound to plasma proteins. Protein binding is independent of total drug concentrations.

Based upon measurements of sildenafil in semen of healthy volunteers 90 minutes after dosing, less than 0.001% of the administered dose may appear in the semen of patients.

Metabolism and Excretion: Sildenafil is cleared predominantly by the CYP3A4 (major route) and CYP2C9 (minor route) hepatic microsomal isoenzymes. The major circulating metabolite results from N-desmethylation of sildenafil, and is itself further metabolized. This metabolite has a PDE selectivity profile similar to sildenafil and an in vitro potency for PDE5 approximately 50% of the parent drug. Plasma concentrations of this metabolite are approximately 40% of those seen for sildenafil, so that the metabolite accounts for about 20% of sildenafil’s pharmacologic effects.

After either oral or intravenous administration, sildenafil is excreted as metabolites predominantly in the feces (approximately 80% of administered oral dose) and to a lesser extent in the urine (approximately 13% of the administered oral dose). Similar values for pharmacokinetic parameters were seen in normal volunteers and in the patient population, using a population pharmacokinetic approach.

Pharmacokinetics in Special Populations

Geriatrics: Healthy elderly volunteers (65 years or over) had a reduced clearance of sildenafil, resulting in approximately 84% and 107% higher plasma AUC values of sildenafil and its active N-desmethyl metabolite, respectively, compared to those seen in healthy younger volunteers (18–45 years). Due to age-differences in plasma protein binding, the corresponding increase in the AUC of free (unbound) sildenafil and its active N-desmethyl metabolite were 45% and 57%, respectively [see Dosage and Administration (2.5), and Use in Specific Populations (8.5)]

Renal Impairment: In volunteers with mild (CLcr=50–80 mL/min) and moderate (CLcr=30–49 mL/min) renal impairment, the pharmacokinetics of a single oral dose of VIAGRA (50 mg) were not altered. In volunteers with severe (CLcr <30 mL/min) renal impairment, sildenafil clearance was reduced, resulting in approximately doubling of AUC and Cmax compared to age-matched volunteers with no renal impairment [see Dosage and Administration (2.5), and Use in Specific Populations (8.6)].

In addition, N-desmethyl metabolite AUC and Cmax values significantly increased by 200% and 79%, respectively in subjects with severe renal impairment compared to subjects with normal renal function.

Hepatic Impairment: In volunteers with hepatic impairment (Child-Pugh Class A and B), sildenafil clearance was reduced, resulting in increases in AUC (85%) and Cmax (47%) compared to age-matched volunteers with no hepatic impairment. The pharmacokinetics of sildenafil in patients with severely impaired hepatic function (Child-Pugh Class C) have not been studied [see Dosage and Administration (2.5), and Use in Specific Populations (8.7)].

Therefore, age >65, hepatic impairment and severe renal impairment are associated with increased plasma levels of sildenafil. A starting oral dose of 25 mg should be considered in those patients [see Dosage and Administration (2.5)].

Drug Interaction Studies

Effects of Other Drugs on VIAGRA

Sildenafil metabolism is principally mediated by CYP3A4 (major route) and CYP2C9 (minor route). Therefore, inhibitors of these isoenzymes may reduce sildenafil clearance and inducers of these isoenzymes may increase sildenafil clearance. The concomitant use of erythromycin or strong CYP3A4 inhibitors (e.g., saquinavir, ketoconazole, itraconazole) as well as the nonspecific CYP inhibitor, cimetidine, is associated with increased plasma levels of sildenafil [see Dosage and Administration (2.4)].

In vivo studies:

Cimetidine (800 mg), a nonspecific CYP inhibitor, caused a 56% increase in plasma sildenafil concentrations when co-administered with VIAGRA (50 mg) to healthy volunteers.

When a single 100 mg dose of VIAGRA was administered with erythromycin, a moderate CYP3A4 inhibitor, at steady state (500 mg bid for 5 days), there was a 160% increase in sildenafil Cmax and a 182% increase in sildenafil AUC. In addition, in a study performed in healthy male volunteers, co-administration of the HIV protease inhibitor saquinavir, also a CYP3A4 inhibitor, at steady state (1200 mg tid) with Viagra (100 mg single dose) resulted in a 140% increase in sildenafil Cmax and a 210% increase in sildenafil AUC. Viagra had no effect on saquinavir pharmacokinetics. A stronger CYP3A4 inhibitor such as ketoconazole or itraconazole could be expected to have greater effect than that seen with saquinavir. Population pharmacokinetic data from patients in clinical trials also indicated a reduction in sildenafil clearance when it was co-administered with CYP3A4 inhibitors (such as ketoconazole, erythromycin, or cimetidine) [see Dosage and Administration (2.4) and Drug Interactions (7.4)].

In another study in healthy male volunteers, co-administration with the HIV protease inhibitor ritonavir, which is a highly potent P450 inhibitor, at steady state (500 mg bid) with VIAGRA (100 mg single dose) resulted in a 300% (4-fold) increase in sildenafil Cmax and a 1000% (11-fold) increase in sildenafil plasma AUC. At 24 hours the plasma levels of sildenafil were still approximately 200 ng/mL, compared to approximately 5 ng/mL when sildenafil was dosed alone. This is consistent with ritonavir’s marked effects on a broad range of P450 substrates. VIAGRA had no effect on ritonavir pharmacokinetics [see Dosage and Administration (2.4) and Drug Interactions (7.4)].

Although the interaction between other protease inhibitors and sildenafil has not been studied, their concomitant use is expected to increase sildenafil levels.

In a study of healthy male volunteers, co-administration of sildenafil at steady state (80 mg t.i.d.) with endothelin receptor antagonist bosentan (a moderate inducer of CYP3A4, CYP2C9 and possibly of CYP2C19) at steady state (125 mg b.i.d.) resulted in a 63% decrease of sildenafil AUC and a 55% decrease in sildenafil Cmax. Concomitant administration of strong CYP3A4 inducers, such as rifampin, is expected to cause greater decreases in plasma levels of sildenafil.

Single doses of antacid (magnesium hydroxide/aluminum hydroxide) did not affect the bioavailability of VIAGRA.

In healthy male volunteers, there was no evidence of a clinically significant effect of azithromycin (500 mg daily for 3 days) on the systemic exposure of sildenafil or its major circulating metabolite.

Pharmacokinetic data from patients in clinical trials showed no effect on sildenafil pharmacokinetics of CYP2C9 inhibitors (such as tolbutamide, warfarin), CYP2D6 inhibitors (such as selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazide and related diuretics, ACE inhibitors, and calcium channel blockers. The AUC of the active metabolite, N-desmethyl sildenafil, was increased 62% by loop and potassium-sparing diuretics and 102% by nonspecific beta-blockers. These effects on the metabolite are not expected to be of clinical consequence.

Effects of VIAGRA on Other Drugs

In vitro studies:

Sildenafil is a weak inhibitor of the CYP isoforms 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (IC50 >150 µM). Given sildenafil peak plasma concentrations of approximately 1 µM after recommended doses, it is unlikely that VIAGRA will alter the clearance of substrates of these isoenzymes.

In vivo studies:

No significant interactions were shown with tolbutamide (250 mg) or warfarin (40 mg), both of which are metabolized by CYP2C9.

In a study of healthy male volunteers, sildenafil (100 mg) did not affect the steady state pharmacokinetics of the HIV protease inhibitors, saquinavir and ritonavir, both of which are CYP3A4 substrates.

VIAGRA (50 mg) did not potentiate the increase in bleeding time caused by aspirin (150 mg).

Sildenafil at steady state, at a dose not approved for the treatment of erectile dysfunction (80 mg t.i.d.) resulted in a 50% increase in AUC and a 42% increase in Cmax of bosentan (125 mg b.i.d.).

Carcinogenesis

Sildenafil was not carcinogenic when administered to rats for 24 months at a dose resulting in total systemic drug exposure (AUCs) for unbound sildenafil and its major metabolite of 29- and 42- times, for male and female rats, respectively, the exposures observed in human males given the Maximum Recommended Human Dose (MRHD) of 100 mg. Sildenafil was not carcinogenic when administered to mice for 18–21 months at dosages up to the Maximum Tolerated Dose (MTD) of 10 mg/kg/day, approximately 0.6 times the MRHD on a mg/m2 basis.

Mutagenesis

Sildenafil was negative in in vitro bacterial and Chinese hamster ovary cell assays to detect mutagenicity, and in vitro human lymphocytes and in vivo mouse micronucleus assays to detect clastogenicity.

Impairment of Fertility

There was no impairment of fertility in rats given sildenafil up to 60 mg/kg/day for 36 days to females and 102 days to males, a dose producing an AUC value of more than 25 times the human male AUC.

In clinical studies, VIAGRA was assessed for its effect on the ability of men with erectile dysfunction (ED) to engage in sexual activity and in many cases specifically on the ability to achieve and maintain an erection sufficient for satisfactory sexual activity. VIAGRA was evaluated primarily at doses of 25 mg, 50 mg and 100 mg in 21 randomized, double-blind, placebo-controlled trials of up to 6 months in duration, using a variety of study designs (fixed dose, titration, parallel, crossover). VIAGRA was administered to more than 3,000 patients aged 19 to 87 years, with ED of various etiologies (organic, psychogenic, mixed) with a mean duration of 5 years. VIAGRA demonstrated statistically significant improvement compared to placebo in all 21 studies. The studies that established benefit demonstrated improvements in success rates for sexual intercourse compared with placebo.

Efficacy Endpoints in Controlled Clinical Studies

The effectiveness of VIAGRA was evaluated in most studies using several assessment instruments. The primary measure in the principal studies was a sexual function questionnaire (the International Index of Erectile Function – IIEF) administered during a 4-week treatment-free run-in period, at baseline, at follow-up visits, and at the end of double-blind, placebo-controlled, at-home treatment. Two of the questions from the IIEF served as primary study endpoints; categorical responses were elicited to questions about (1) the ability to achieve erections sufficient for sexual intercourse and (2) the maintenance of erections after penetration. The patient addressed both questions at the final visit for the last 4 weeks of the study. The possible categorical responses to these questions were (0) no attempted intercourse, (1) never or almost never, (2) a few times, (3) sometimes, (4) most times, and (5) almost always or always. Also collected as part of the IIEF was information about other aspects of sexual function, including information on erectile function, orgasm, desire, satisfaction with intercourse, and overall sexual satisfaction. Sexual function data were also recorded by patients in a daily diary. In addition, patients were asked a global efficacy question and an optional partner questionnaire was administered.

Efficacy Results from Controlled Clinical Studies

The effect on one of the major end points, maintenance of erections after penetration, is shown in Figure 6, for the pooled results of 5 fixed-dose, dose-response studies of greater than one month duration, showing response according to baseline function. Results with all doses have been pooled, but scores showed greater improvement at the 50 and 100 mg doses than at 25 mg. The pattern of responses was similar for the other principal question, the ability to achieve an erection sufficient for intercourse. The titration studies, in which most patients received 100 mg, showed similar results. Figure 6 shows that regardless of the baseline levels of function, subsequent function in patients treated with VIAGRA was better than that seen in patients treated with placebo. At the same time, on-treatment function was better in treated patients who were less impaired at baseline.

The frequency of patients reporting improvement of erections in response to a global question in four of the randomized, double-blind, parallel, placebo-controlled fixed dose studies (1797 patients) of 12 to 24 weeks duration is shown in Figure 7. These patients had erectile dysfunction at baseline that was characterized by median categorical scores of 2 (a few times) on principal IIEF questions. Erectile dysfunction was attributed to organic (58%; generally not characterized, but including diabetes and excluding spinal cord injury), psychogenic (17%), or mixed (24%) etiologies. Sixty-three percent, 74%, and 82% of the patients on 25 mg, 50 mg and 100 mg of VIAGRA, respectively, reported an improvement in their erections, compared to 24% on placebo. In the titration studies (n=644) (with most patients eventually receiving 100 mg), results were similar.

The patients in studies had varying degrees of ED. One-third to one-half of the subjects in these studies reported successful intercourse at least once during a 4-week, treatment-free run-in period.

In many of the studies, of both fixed dose and titration designs, daily diaries were kept by patients. In these studies, involving about 1600 patients, analyses of patient diaries showed no effect of VIAGRA on rates of attempted intercourse (about 2 per week), but there was clear treatment-related improvement in sexual function: per patient weekly success rates averaged 1.3 on 50–100 mg of VIAGRA vs 0.4 on placebo; similarly, group mean success rates (total successes divided by total attempts) were about 66% on VIAGRA vs about 20% on placebo.

During 3 to 6 months of double-blind treatment or longer-term (1 year), open-label studies, few patients withdrew from active treatment for any reason, including lack of effectiveness. At the end of the long-term study, 88% of patients reported that VIAGRA improved their erections.

Men with untreated ED had relatively low baseline scores for all aspects of sexual function measured (again using a 5-point scale) in the IIEF. VIAGRA improved these aspects of sexual function: frequency, firmness and maintenance of erections; frequency of orgasm; frequency and level of desire; frequency, satisfaction and enjoyment of intercourse; and overall relationship satisfaction.

One randomized, double-blind, flexible-dose, placebo-controlled study included only patients with erectile dysfunction attributed to complications of diabetes mellitus (n=268). As in the other titration studies, patients were started on 50 mg and allowed to adjust the dose up to 100 mg or down to 25 mg of VIAGRA; all patients, however, were receiving 50 mg or 100 mg at the end of the study. There were highly statistically significant improvements on the two principal IIEF questions (frequency of successful penetration during sexual activity and maintenance of erections after penetration) on VIAGRA compared to placebo. On a global improvement question, 57% of VIAGRA patients reported improved erections versus 10% on placebo. Diary data indicated that on VIAGRA, 48% of intercourse attempts were successful versus 12% on placebo.

One randomized, double-blind, placebo-controlled, crossover, flexible-dose (up to 100 mg) study of patients with erectile dysfunction resulting from spinal cord injury (n=178) was conducted. The changes from baseline in scoring on the two end point questions (frequency of successful penetration during sexual activity and maintenance of erections after penetration) were highly statistically significantly in favor of VIAGRA. On a global improvement question, 83% of patients reported improved erections on VIAGRA versus 12% on placebo. Diary data indicated that on VIAGRA, 59% of attempts at sexual intercourse were successful compared to 13% on placebo.

Across all trials, VIAGRA improved the erections of 43% of radical prostatectomy patients compared to 15% on placebo.

Subgroup analyses of responses to a global improvement question in patients with psychogenic etiology in two fixed-dose studies (total n=179) and two titration studies (total n=149) showed 84% of VIAGRA patients reported improvement in erections compared with 26% of placebo. The changes from baseline in scoring on the two end point questions (frequency of successful penetration during sexual activity and maintenance of erections after penetration) were highly statistically significantly in favor of VIAGRA. Diary data in two of the studies (n=178) showed rates of successful intercourse per attempt of 70% for VIAGRA and 29% for placebo.

Efficacy Results in Subpopulations in Controlled Clinical Studies

A review of population subgroups demonstrated efficacy regardless of baseline severity, etiology, race and age. VIAGRA was effective in a broad range of ED patients, including those with a history of coronary artery disease, hypertension, other cardiac disease, peripheral vascular disease, diabetes mellitus, depression, coronary artery bypass graft (CABG), radical prostatectomy, transurethral resection of the prostate (TURP) and spinal cord injury, and in patients taking antidepressants/antipsychotics and anti-hypertensives/diuretics.

VIAGRA (sildenafil citrate) is supplied as blue, film-coated, rounded-diamond-shaped tablets containing sildenafil citrate equivalent to the nominally indicated amount of sildenafil and debossed on the obverse and reverse sides as follows:

Recommended Storage: Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F) [see USP Controlled Room Temperature].

See FDA-approved patient labeling (Patient Information)

Nitrates

Physicians should discuss with patients the contraindication of VIAGRA with regular and/or intermittent use of nitric oxide donors, such as organic nitrates or organic nitrites in any form [see Contraindications (4.1)].

Concomitant Use with Drugs Which Lower Blood Pressure

Physicians should advise patients of the potential for VIAGRA to augment the blood pressure lowering effect of alpha-blockers and anti-hypertensive medications. Concomitant administration of VIAGRA and an alpha-blocker may lead to symptomatic hypotension in some patients. Therefore, when VIAGRA is co-administered with alpha-blockers, patients should be stable on alpha-blocker therapy prior to initiating VIAGRA treatment and VIAGRA should be initiated at the lowest dose [see Warnings and Precautions (5.5)].

Cardiovascular Considerations

Physicians should discuss with patients the potential cardiac risk of sexual activity in patients with preexisting cardiovascular risk factors. Patients who experience symptoms (e.g., angina pectoris, dizziness, nausea) upon initiation of sexual activity should be advised to refrain from further activity and should discuss the episode with their physician [see Warnings and Precautions (5.1)].

Sudden Loss of Vision

Physicians should advise patients to stop use of all PDE5 inhibitors, including VIAGRA, and seek medical attention in the event of a sudden loss of vision in one or both eyes. Such an event may be a sign of non-arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision including possible permanent loss of vision, that has been reported rarely post-marketing in temporal association with the use of all PDE5 inhibitors. It is not possible to determine whether these events are related directly to the use of PDE5 inhibitors or to other factors. Physicians should discuss with patients the increased risk of NAION in individuals who have already experienced NAION in one eye. Physicians should also discuss with patients the increased risk of NAION among the general population in patients with a “crowded” optic disc, although evidence is insufficient to support screening of prospective users of PDE5 inhibitor, including VIAGRA, for this uncommon condition [see Warnings and Precautions (5.3) and Adverse Reactions (6.2)].

Sudden Hearing Loss

Physicians should advise patients to stop taking PDE5 inhibitors, including VIAGRA, and seek prompt medical attention in the event of sudden decrease or loss of hearing. These events, which may be accompanied by tinnitus and dizziness, have been reported in temporal association to the intake of PDE5 inhibitors, including VIAGRA. It is not possible to determine whether these events are related directly to the use of PDE5 inhibitors or to other factors [see Warnings and Precautions (5.4) and Adverse Reactions (6.2)].

Priapism

Physicians should warn patients that prolonged erections greater than 4 hours and priapism (painful erections greater than 6 hours in duration) have been reported infrequently since market approval of VIAGRA. In the event of an erection that persists longer than 4 hours, the patient should seek immediate medical assistance. If priapism is not treated immediately, penile tissue damage and permanent loss of potency may result [see Warnings and Precautions (5.2)].

Avoid Use with other PDE5 Inhibitors

Physicians should inform patients not to take VIAGRA with other PDE5 inhibitors including REVATIO or other pulmonary arterial hypertension (PAH) treatments containing sildenafil. Sildenafil is also marketed as REVATIO for the treatment of PAH. The safety and efficacy of VIAGRA with other PDE5 inhibitors, including REVATIO, have not been studied [see Warnings and Precautions (5.7)].

Sexually Transmitted Disease

The use of VIAGRA offers no protection against sexually transmitted diseases. Counseling of patients about the protective measures necessary to guard against sexually transmitted diseases, including the Human Immunodeficiency Virus (HIV), may be considered [see Warnings and Precautions (5.9)].

LAB-0221-13.0

What is the most important information I should know about VIAGRA?

VIAGRA can cause your blood pressure to drop suddenly to an unsafe level if it is taken with certain other medicines. Do not take VIAGRA if you take any other medicines called “nitrates.” Nitrates are used to treat chest pain (angina). A sudden drop in blood pressure can cause you to feel dizzy, faint, or have a heart attack or stroke.

Tell all your healthcare providers that you take VIAGRA. If you need emergency medical care for a heart problem, it will be important for your healthcare provider to know when you last took VIAGRA.

Stop sexual activity and get medical help right away if you get symptoms such as chest pain, dizziness, or nausea during sex.

Sexual activity can put an extra strain on your heart, especially if your heart is already weak from a heart attack or heart disease. Ask your doctor if your heart is healthy enough to handle the extra strain of having sex.

VIAGRA does not protect you or your partner from getting sexually transmitted diseases, including HIV—the virus that causes AIDS.

What is VIAGRA?

VIAGRA is a prescription medicine used to treat erectile dysfunction (ED). You will not get an erection just by taking this medicine. VIAGRA helps a man with erectile dysfunction get and keep an erection only when he is sexually excited (stimulated).

VIAGRA is not for use in women or children.

It is not known if VIAGRA is safe and effective in women or children under 18 years of age.

Who should not take VIAGRA?

Do not take VIAGRA if you:

What should I tell my healthcare provider before taking VIAGRA?

Before you take VIAGRA, tell your healthcare provider if you:

Tell your healthcare provider about all the medicines you take1, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

VIAGRA may affect the way other medicines work, and other medicines may affect the way VIAGRA works causing side effects. Especially tell your healthcare provider if you take any of the following:

Ask your healthcare provider or pharmacist for a list of these medicines, if you are not sure.

Know the medicines you take. Keep a list of them to show to your healthcare provider and pharmacist when you get a new medicine.

How should I take VIAGRA?

What are the possible side effects of VIAGRA?

VIAGRA can cause serious side effects. Rarely reported side effects include:

The most common side effects of VIAGRA are:

In addition, heart attack, stroke, irregular heartbeats and death have happened rarely in men taking VIAGRA. Most, but not all, of these men had heart problems before taking VIAGRA. It is not known if VIAGRA caused these problems.

Tell your healthcare provider if you have any side effect that bothers you or does not go away.

These are not all the possible side effects of VIAGRA. For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store VIAGRA?

Keep VIAGRA and all medicines out of the reach of children.

General information about the safe and effective use of VIAGRA.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use VIAGRA for a condition for which it was not prescribed. Do not give VIAGRA to other people, even if they have the same symptoms that you have. It may harm them.

This Patient Information leaflet summarizes the most important information about VIAGRA. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about VIAGRA that is written for health professionals.

For more information, go to www.viagra.com, or call 1-888-4VIAGRA

What are the ingredients in VIAGRA?

Active ingredient: sildenafil citrate

This Patient Information has been approved by the U.S. Food and Drug Administration.

LAB-0220-8.0

03/2014

This product’s label may have been updated. For current full prescribing information, please visit www.pfizer.com.

Viagra (sildenafil citrate), Revatio (sildenafil), Cardura (doxazosin mesylate), and Minipress (prazosin HCl) are registered trademarks of Pfizer Inc.

VIAGRA® (sildenafil citrate) tablets To learn more, visit www.viagra.com or call 1-800-446-3464.

VIAGRA® (sildenafil citrate) tablets

TRIAL PACK

TRIAL PACK: 4 TABLETS (4) 50 mg*

NDC 63539-421-97     Rx only Professional sample — not for sale.

Package not child resistant. Keep out of reach of children.

100 mg*VIAGRA® (sildenafil citrate) tablets To learn more, visit www.viagra.com or call 1-800-446-3464.

VIAGRA® (sildenafil citrate) tablets

TRIAL PACK: 2 TABLETS (2) 100 mg*

NDC 63539-422-03     Rx only PROFESSIONAL SAMPLE — NOT FOR SALE

PACKAGE NOT CHILD RESISTANT. KEEP OUT OF REACH OF CHILDREN.

100 mg* 6 cards x (2) 100 mg tablets

VIAGRA® (sildenafil citrate) tablets

PACKAGE NOT CHILD RESISTANT. KEEP OUT OF REACH OF CHILDREN.

NDC 63539-422-03PROFESSIONAL SAMPLE — NOT FOR SALERX ONLY

50 mg* 6 cards x (4) 50 mg tablets

VIAGRA® (sildenafil citrate) tablets

PACKAGE NOT CHILD RESISTANT. KEEP OUT OF REACH OF CHILDREN.

NDC 63539-421-97PROFESSIONAL SAMPLE — NOT FOR SALERX ONLY

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It works by relaxing the muscles in the walls of blood vessels in certain areas of the body. In most cases, Viagra works well and has changed people’s lives for the better.

The word Viagra is the brand name for sildenafil citrate and is used to treat erectile dysfunction and pulmonary arterial hypertension.Originally developed by scientists in the United Kingdom, it was brought onto the market by Pfizer Inc., a pharmaceutical company in the United States.Viagra is also sold under brand name Revatio. Sildenafil citrate’s chemical formula is C22H30N6O4S.

In this article, we look briefly at the effects of Viagra, why it is used, the side effects, and history.

Viagra is generally safe to use in moderation. However, taking it may cause a range of adverse effects.

According to clinical trial results, the most common side effects include:

Less commonly, some users have experienced cyanopsia, where everything appears to have a tinted blue tinge.

In very rare cases, Viagra use can lead to nonarteritic anterior ischemic optic neuropathy, or damage to the optic nerve.

Other potential side effects include:

Since 2007, Viagra’s labeling in the U.S. has included a warning of the potential risk of sudden hearing loss.

Viagra can decrease blood supply to the optic nerve, causing sudden vision loss. This very rare adverse event occurs mainly in people with heart disease, hypertension, diabetes, high cholesterol, or pre-existing eye problems. The link between vision loss and Viagra is as yet unknown.

People with HIV who take protease inhibitors should discuss using Viagra with their doctors. Protease inhibitors increase the risk and severity of side effects. These individuals should have no more than 25 milligrams (mg) of Viagra at a time, and not more often than every 48 hours.

Individuals taking alpha-blockers should make sure they take Viagra at least 4 hours before or after taking alpha-blockers. This can help prevent dangerously low blood pressure.

The following individuals should not take Viagra, or should check with their doctor first:

Some athletes take Revatio to increase their exercise capacity, but there is little evidence to support this use.

Effects

Viagra can help men who cannot achieve or sustain an erection due to erectile dysfunction. It improves the erectile response when a man is already sexually stimulated, but it does not provide sexual stimulation. If there is no sexual stimulation, viagra will not work.

When sexual stimulation occurs, nitric oxide is released by the nervous system in the erectile tissue of the penis. Nitric oxide stimulates an enzyme that produces messenger cyclic guanosine monophosphate (cGMP).

cGMP causes the arteries in the penis to dilate, so that the arteries and the erectile tissue fill with blood. An erection results.

Viagra prevents cGMP from becoming degraded, so the blood flow and the erection can continue.

The dosage will be different if the drug is taken for erectile dysfunction or for pulmonary arterial hypertension.

Viagra

For erectile dysfunction, Viagra comes in blue, diamond-shaped pills, in doses of 25, 50, or 100 mg.

The individual takes a maximum of one pill in a 24-hour period, 30 minutes to 1 hour before sexual intercourse.

Revatio

قرص sildenafil citrate

For pulmonary arterial hypertension, Viagra comes in white, round, film-coated tablets. People take one 20-mg Revatio tablet three times a day.

A Viagra overdose can be serious. If you believe you have had more than the standard dosage, call a doctor or local Poison Control Center.

symptoms of an overdose might include:

Deaths from viagra overdose are rare but possible.

Initially, Viagra was designed by Pfizer scientists working in the U.K. They were, in fact, working on a drug for hypertension, or high blood pressure, and angina pectoris, a symptom of ischemic heart disease.

During the phase 1 trials, it was noted that the drug did very little to prevent angina but did induce marked penile erections. Hitting the market in 1998, Viagra was the first oral treatment approved to treat erectile dysfunction in the U.S.

Viagra’s meteoric rise to fame has seen it enter usage as an illicit drug. But, Viagra use in individuals without erectile dysfunction does not seem to have any effect. Although, researchers have noted that there is a significant placebo effect. On a similar note, there is no proven benefit for women taking the drug.

In 2008, Viagra generated some $1.93 billion of revenue for Pfizer.

Article last updated by Yvette Brazier on Mon 19 November 2018.Visit our Erectile Dysfunction / Premature Ejaculation category page for the latest news on this subject, or sign up to our newsletter to receive the latest updates on Erectile Dysfunction / Premature Ejaculation.All references are available in the References tab.

Viagra (sildenafil) facts. (n.d.). Retrieved from https://www.bpas.org/more-services-information/erectile-dysfunction/viagra/

Worldwide revenue of Pfizer’s Viagra from 2003 to 2016 (in million U.S. dollars). (n.d.). Retrieved from https://www.statista.com/statistics/264827/pfizers-worldwide-viagra-revenue-since-2003/

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Sildenafil oral tablet doesn’t cause drowsiness, but it can cause other side effects.

The more common side effects of sildenafil can include:

If these effects are mild, they may go away within a few days or a couple of weeks. If they’re more severe or don’t go away, talk to your doctor or pharmacist.

Call your doctor right away if you have serious side effects. Call 911 if your symptoms feel life-threatening or if you think you’re having a medical emergency. Serious side effects and their symptoms can include the following:

Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs affect each person differently, we cannot guarantee that this information includes all possible side effects. This information is not a substitute for medical advice. Always discuss possible side effects with a healthcare provider who knows your medical history.قرص sildenafil citrate

Sildenafil is a prescription drug. It comes in the form of a tablet and suspension (liquid). Both are taken by mouth. It also comes in an intravenous (IV) form, which is only given by a doctor.

Sildenafil oral tablet is available as the brand-name drugs Viagra and Revatio. It’s also available as a generic drug. Generic drugs usually cost less than the brand-name version. In some cases, they may not be available in every strength or form as the brand-name drug.

Sildenafil oral tablet is used to treat ED and PAH. Generic oral tablets are available for both conditions, but the brand-name drugs each treat only one of the conditions.

Sildenafil belongs to a class of drugs called phosphodiesterase type 5 (PDE5) inhibitors. A class of drugs is a group of medications that work in a similar way. These drugs are often used to treat similar conditions.

Sildenafil works in different ways, depending on the condition it’s being used to treat.

Sildenafil oral tablet can interact with other medications, vitamins, or herbs you may be taking. An interaction is when a substance changes the way a drug works. This can be harmful or prevent the drug from working well.

To help avoid interactions, your doctor should manage all of your medications carefully. Be sure to tell your doctor about all medications, vitamins, or herbs you’re taking. To find out how this drug might interact with something else you’re taking, talk to your doctor or pharmacist.

Examples of drugs that can cause interactions with sildenafil are listed below.

Do not take these drugs with sildenafil. Doing so can cause dangerous effects in the body. Examples of these drugs include:

Side effects from sildenafil: Taking sildenafil with certain medications raises your risk of side effects from sildenafil. This is because the amount of sildenafil in your body is increased. Examples of these drugs include:

Side effects from other drugs: Taking sildenafil with certain medications raises your risk of side effects from these drugs. Examples of these drugs include:

Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs interact differently in each person, we cannot guarantee that this information includes all possible interactions. This information is not a substitute for medical advice. Always speak with your healthcare provider about possible interactions with all prescription drugs, vitamins, herbs and supplements, and over-the-counter drugs that you are taking.

This drug comes with several warnings.

Sildenafil can cause a severe allergic reaction. Symptoms can include:

If you develop these symptoms, call 911 or go to the nearest emergency room.

Don’t take this drug again if you’ve ever had an allergic reaction to it. Taking it again could be fatal (cause death).

The use of drinks that contain alcohol raises your risk of low blood pressure from sildenafil. If you drink alcohol, talk to your doctor. You may need to have your blood pressure monitored while you take this drug.

For people with heart problems: This drug can lower your blood pressure. If you’ve had certain heart problems in the last 6 months, ask your doctor whether this drug is safe for you. These problems include a heart attack, stroke, or life-threatening heart rhythm problem. Also talk with your doctor if you have a low or high resting blood pressure, or a history of heart failure or coronary artery disease.

For people with pulmonary veno-occlusive disease (PVOD): Taking this drug may worsen your heart function. You should not take this drug.

For people with eye problems: This drug may cause sudden loss of vision in one or both eyes. This may be a sign of non-arteritic anterior ischemic optic neuropathy (NAION). If you’ve already had NAION or have crowded optic disc, you may have a higher risk of NAION and vision changes with this drug.

For people with problems with the shape of their penis: If you have a problem with the shape of your penis, such as Peyronie’s disease, this drug raises your risk of having an erection that lasts more than 4 hours.

For people with a history of stomach ulcers or bleeding: This drug raises your risk of stomach bleeding, ulcers, or small holes in the lining of your digestive system. These events can be fatal (cause death). They can happen at any time, with or without symptoms.

For people with sickle cell anemia: This drug may cause a common painful complication of sickle cell anemia called vaso-occlusive crisis. If you have sickle cell anemia, ask your doctor whether this drug is safe for you.

For pregnant women: Research in animals has not shown a risk to the fetus when the mother takes the drug. However, there aren’t enough studies done in humans using the drug for PAH to show if the drug poses a risk to the fetus.

Talk to your doctor if you’re pregnant or planning to become pregnant. It appears unlikely that this drug will harm a pregnancy. However, this drug should only be used during pregnancy if clearly needed.

Viagra or generic sildenafil for ED should not be used in women.

For women who are breastfeeding: When used for PAH, sildenafil may pass into breast milk and may cause side effects in a child who is breastfed. Talk to your doctor if you breastfeed your child. You may need to decide whether to stop breastfeeding or stop taking this medication.

Viagra or generic sildenafil for ED should not be used in women.

For seniors: The kidneys, liver, or heart of older adults may not work as well as they used to. This can cause your body to process drugs more slowly. As a result, a higher amount of a drug stays in your body for a longer time. This raises your risk of side effects.

For children: This drug isn’t recommended in children younger than 18 years of age. In one study, children with PAH who took this drug had an increased chance of death.

All possible dosages and drug forms may not be included here. Your dosage, drug form, and how often you take the drug will depend on:

Generic: Sildenafil

Brand: Viagra

Adult dosage (ages 18–64 years)

Child dosage (ages 0–17 years)

قرص sildenafil citrate

This drug has not been confirmed to be safe or effective in children younger than 18 years.

Senior dosage (ages 65 years and older)

The kidneys, liver, or heart of older adults may not work as well as they used to. This can cause your body to process drugs more slowly. As a result, a higher amount of a drug stays in your body for a longer time. This raises your risk of side effects.

Your doctor may start you on a lowered dosage of sildenafil. This can help prevent levels of this drug from building up in your body.

Generic: Sildenafil

Brand: Revatio

Adult dosage (ages 18–64 years)

Child dosage (ages 0–17 years)

This drug shouldn’t be used in children younger than 18 years of age.

Senior dosage (ages 65 years and older)

The kidneys, liver, or heart of older adults may not work as well as they used to. This can cause your body to process drugs more slowly. As a result, a higher amount of a drug stays in your body for a longer time. This raises your risk of side effects.

Your doctor may start you on a lowered dosage of sildenafil. This can help prevent levels of this drug from building up in your body.

Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs affect each person differently, we cannot guarantee that this list includes all possible dosages. This information is not a substitute for medical advice. Always speak with your doctor or pharmacist about dosages that are right for you.

Sildenafil oral tablet is used for short-term treatment of ED, and long-term treatment of PAH. It comes with serious risks if you don’t take it as prescribed.

If you stop taking the drug suddenly or don’t take it at all:

If you miss doses or don’t take the drug on schedule:

If you take too much: You could have dangerous levels of the drug in your body. Symptoms of an overdose of this drug can include:

If you think you’ve taken too much of this drug, call your doctor or local poison control center. If your symptoms are severe, call 911 or go to the nearest emergency room right away.

What to do if you miss a dose:

How to tell if the drug is working:

Keep these considerations in mind if your doctor prescribes sildenafil for you.

A prescription for this medication is refillable. You should not need a new prescription for this medication to be refilled. Your doctor will write the number of refills authorized on your prescription.

When traveling with your medication:

If you’re taking this drug for PAH, your doctor may monitor your blood pressure and pulse regularly.

Not every pharmacy stocks this drug. When filling your prescription, be sure to call ahead to make sure your pharmacy carries it.

Many insurance companies require a prior authorization for this drug. This means your doctor may need to get approval from your insurance company before your insurance company will pay for the prescription.

There are other drugs available to treat your condition. Some may be better suited for you than others. Talk to your doctor about other drug options that may work for you.

Disclaimer: Healthline has made every effort to make certain that all information is factually correct, comprehensive, and up-to-date. However, this article should not be used as a substitute for the knowledge and expertise of a licensed healthcare professional. You should always consult your doctor or other healthcare professional before taking any medication. The drug information contained herein is subject to change and is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. The absence of warnings or other information for a given drug does not indicate that the drug or drug combination is safe, effective, or appropriate for all patients or all specific uses.

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