Effexor XR ATTENZIONE: pensieri suicidari e comportamenti antidepressivi ha aumentato il rischio di pensieri suicidari e comportamenti nei bambini, adolescenti e giovani adulti in studi a breve termine. Questi studi non hanno mostrato un aumento del rischio di pensieri suicidari e comportamenti con l'uso di antidepressivi in pazienti con più di 24 anni c'è stata una riduzione del rischio con l'uso di antidepressivi in pazienti di età compresa tra 65 anni e più vedere Avvertenze e precauzioni (5.1). Nei pazienti di tutte le età che vengono avviati sulla terapia antidepressiva monitorare attentamente per il peggioramento clinico e comparsa di pensieri e comportamenti suicidari. Consigliano le famiglie e gli operatori sanitari della necessità di una stretta osservazione e la comunicazione con il medico prescrittore vedere Avvertenze e Precauzioni (5.1) e informazioni Counseling paziente (17). Indicazioni e impiego per il disturbo Effexor XR Depressivo Maggiore Effexor XR (cloridrato di venlafaxina) capsule a rilascio prolungato è indicato per il trattamento del disturbo depressivo maggiore (MDD). L'efficacia è stata stabilita in tre a breve termine (4, 8 e 12 settimane) e due a lungo termine, gli studi di manutenzione. Disturbo d'Ansia Generalizzato Effexor XR è indicato per il trattamento del Disturbo d'Ansia Generalizzato (GAD). L'efficacia è stata stabilita in due di 8 settimane e due studi controllati con placebo di 26 settimane. Disturbo d'ansia sociale Effexor XR è indicato per il trattamento del disturbo d'ansia sociale (SAD), noto anche come fobia sociale. L'efficacia è stata fondata nel quattro di 12 settimane e una 26 settimane, controllati con placebo. Disturbo di Panico Effexor XR è indicato per il trattamento del Disturbo di Panico (PD), con o senza agorafobia. L'efficacia è stata stabilita in due studi clinici controllati con placebo di 12 settimane. Effexor XR Dosaggio e Amministrazione Effexor XR deve essere somministrato in una singola dose con il cibo, o al mattino o alla sera circa alla stessa ora ogni giorno vedere Farmacologia Clinica (12.3). Ogni capsula deve essere deglutita intera con il liquido e non diviso, schiacciate, masticate o messo in acqua o può essere somministrato aprendo con attenzione la capsula e cospargere l'intero contenuto in un cucchiaio di salsa di mele. Questa miscela drugfood dovrebbe essere inghiottita immediatamente senza masticare e seguita con un bicchiere d'acqua per garantire la completa deglutizione del pellet (sferoidi). Disturbo Depressivo Maggiore Per la maggior parte dei pazienti, la dose iniziale raccomandata per Effexor XR è di 75 mg al giorno, somministrato in una singola dose. Per alcuni pazienti, può essere desiderabile per iniziare a 37,5 mg al giorno per 4 a 7 giorni per consentire nuovi pazienti per regolare al farmaco prima di aumentare a 75 mg al giorno. I pazienti che non rispondono alle iniziali di 75 mg per dose giorno possono beneficiare di un aumento della dose a un massimo di 225 mg al giorno. Gli incrementi di dose devono essere in incrementi fino a 75 mg al giorno, a seconda delle necessità, e devono essere fatti ad intervalli di non meno di 4 giorni, dal momento che i livelli plasmatici allo stato stazionario della venlafaxina e dei suoi principali metaboliti sono raggiunti nella maggior parte dei pazienti di giorno 4 vedi Farmacologia clinica (12.3). Negli studi clinici che stabiliscono l'efficacia, la titolazione verso l'alto è stato consentito ad intervalli di 2 settimane o più. Si deve notare che, mentre la dose massima raccomandata per pazienti esterni moderatamente depressi è 225 mg al giorno per Effexor (a rilascio immediato), ricoverati più gravemente depressi in uno studio del programma di sviluppo di tale prodotto risposto a una dose media di 350 mg al giorno (range da 150 a 375 mg al giorno). O meno dosi più elevate di Effexor XR sono necessari per i pazienti più gravemente depressi non è noto però, l'esperienza con Effexor XR dosi superiori a 225 mg al giorno è molto limitata. Disturbo d'Ansia Generalizzato Per la maggior parte dei pazienti, la dose iniziale raccomandata per Effexor XR è di 75 mg al giorno, somministrato in una singola dose. Per alcuni pazienti, può essere desiderabile per iniziare a 37,5 mg al giorno per 4 a 7 giorni per consentire nuovi pazienti per regolare al farmaco prima di aumentare a 75 mg al giorno. I pazienti che non rispondono alle iniziali di 75 mg per dose giorno possono beneficiare di un aumento della dose a un massimo di 225 mg al giorno. Gli incrementi di dose devono essere in incrementi fino a 75 mg al giorno, a seconda delle necessità, e devono essere fatti ad intervalli di non meno di 4 giorni, dal momento che i livelli plasmatici allo stato stazionario della venlafaxina e dei suoi principali metaboliti sono raggiunti nella maggior parte dei pazienti di giorno 4 vedi Farmacologia clinica (12.3). Disturbo d'ansia sociale (fobia sociale) La dose raccomandata è di 75 mg al giorno, somministrato in una singola dose. Non vi era alcuna prova che dosi più elevate conferiscono alcun beneficio aggiuntivo. Disturbo di Panico La dose iniziale raccomandata è di 37,5 mg al giorno di Effexor XR per 7 giorni. I pazienti che non rispondono a 75 mg al giorno possono beneficiare di incrementi della dose ad un massimo di circa 225 mg al giorno. Gli incrementi di dose devono essere in incrementi di fino a 75 mg al giorno, a seconda delle necessità, e deve essere fatto ad intervalli di non meno di 7 giorni. I pazienti da Effexor Compresse pazienti depressi che sono attualmente in trattamento con una dose terapeutica con Effexor (rilascio immediato) di commutazione può essere commutato Effexor XR alla dose equivalente più vicino (mg al giorno), per esempio 37,5 mg venlafaxina due volte al giorno a 75 mg Effexor XR una volta al giorno. Tuttavia, i singoli aggiustamenti del dosaggio possono essere necessari. Specifiche popolazioni di pazienti con insufficienza epatica La dose totale giornaliera deve essere ridotta da 50 in pazienti con lieve insufficienza epatica (Child-Pugh5ndash6) a moderata (Child-Pugh7ndash9). Nei pazienti con grave compromissione epatica (Child-Pugh10ndash15) o cirrosi epatica, può essere necessario ridurre la dose da 50 o più Vedere Uso in popolazioni specifiche (8.7). Pazienti con insufficienza renale La dose totale giornaliera deve essere ridotta da 25 a 50 nei pazienti con lieve (CLcr 60ndash89 mLmin) o (CLcr 30ndash59 mLmin) insufficienza renale moderata. Nei pazienti sottoposti ad emodialisi o con insufficienza renale grave (clearance della creatinina lt 30 mLmin), la dose totale giornaliera deve essere ridotta di 50 o più. Perché c'era molta variabilità individuale della clearance tra i pazienti con insufficienza renale, l'individualizzazione del dosaggio può essere desiderabile in alcuni pazienti vedono Uso in popolazioni specifiche (8.7). Il trattamento Manutenzione Non vi è alcun corpo di evidenze disponibili da studi controllati per indicare quanto tempo i pazienti con MDD, GAD, triste, o PD devono essere trattati con Effexor XR. E 'generalmente accettato che episodi acuti di MDD richiedono diversi mesi o più di terapia farmacologica sostenuta al di là risposta alla episodio acuto. Effexor XREffexor hanno dimostrato continuazione della risposta negli studi clinici fino a 52 settimane, alla stessa dose a cui i pazienti hanno risposto durante il trattamento iniziale vedere Studi clinici (14.1). Non è noto se la dose di Effexor XR necessarie per un intervento di manutenzione è identica alla dose necessaria per ottenere una risposta iniziale. I pazienti dovrebbero essere periodicamente riesaminati per determinare la necessità di un trattamento di mantenimento e la dose appropriata per tale trattamento. In pazienti con GAD e SAD, Effexor XR ha dimostrato di essere efficace negli studi clinici 6 mesi. La necessità di continuare il farmaco in pazienti con GAD e SAD che migliorare con il trattamento Effexor XR dovrebbe essere rivalutato periodicamente. In uno studio clinico per PD, pazienti che hanno continuato Effexor XR alla stessa dose a cui hanno risposto nel corso delle prime 12 settimane di trattamento sperimentato un tempo statisticamente significativamente più lungo di recidiva rispetto a pazienti randomizzati a placebo vedere Studi clinici (14.4). La necessità di continuare il farmaco nei pazienti con malattia di Parkinson che migliorano con il trattamento Effexor XR dovrebbe essere rivalutato periodicamente. L'interruzione Effexor XR una graduale riduzione della dose, piuttosto che una brusca interruzione, si raccomanda, quando possibile. Negli studi clinici con Effexor XR, si assottiglia è stato raggiunto riducendo la dose giornaliera di 75 mg ad intervalli di una settimana. Individuazione di rastremazione può essere Avvertenze Vedi necessarie e precauzioni (5.7). Il passaggio pazienti verso o da una monoamino ossidasi Inhibitor (MAO) destinato a trattare disturbi psichiatrici almeno 14 giorni tra l'interruzione di un IMAO (destinato a trattare i disordini psichiatrici) e l'inizio della terapia con Effexor XR. Inoltre, almeno 7 giorni dovrebbe essere dopo la sospensione di Effexor XR prima di iniziare il trattamento con un IMAO destinato a trattare i disordini psichiatrici vedi Controindicazioni (4.2). Avvertenze e precauzioni (5.2). e Interazioni con altri farmaci (7.2). L'uso di Effexor XR con altri MAO come Linezolid o endovenosa blu di metilene Non avviare Effexor XR in un paziente che viene trattato con linezolid o blu di metilene per via endovenosa, perché non vi è un aumentato rischio di sindrome serotoninergica. In un paziente che richiede un trattamento più urgente di una patologia psichiatrica, altri interventi, tra cui il ricovero in ospedale dovrebbe essere considerata vedere Controindicazioni 4.2). In alcuni casi, un paziente già in terapia Effexor XR può richiedere un trattamento urgente con linezolid o blu di metilene per via endovenosa. Se alternative accettabili per linezolid o blu di metilene endovenosa non sono disponibili e i potenziali benefici di linezolid o blu di metilene trattamento per via endovenosa sono ritenuti superiori ai rischi di sindrome serotoninergica in un determinato paziente, Effexor XR deve essere interrotto prontamente, e linezolid o blu di metilene per via endovenosa può essere somministrata. Monitorare il paziente per i sintomi della sindrome serotoninergica per 7 giorni o fino a 24 ore dopo l'ultima dose di linezolid o blu di metilene per via endovenosa, si verifica per primo. La terapia con Effexor XR può essere ripreso 24 ore dopo l'ultima dose di linezolid o blu di metilene endovenosa vedere avvertenze e precauzioni (5.2). Il rischio di somministrare blu di metilene per vie non per via endovenosa (come compresse per via orale o per iniezione locale) o in dosi per via endovenosa molto inferiore a 1 mgkg in concomitanza con Effexor XR è chiaro. Il medico deve, tuttavia, essere a conoscenza della possibilità di sintomi emergenti di sindrome serotoninergica con tale utilizzo vedere avvertenze e precauzioni (5.2). Forme di dosaggio e punti di forza Effexor XR reg (cloridrato venlafaxina) capsule a rilascio prolungato sono disponibili nei seguenti punti di forza: capsule 37,5 mg (corpo cappeach grigio con W e Effexor XR sul tappo e il 37,5 sul corpo) capsule 75 mg (cap pesca e corpo con W e Effexor XR sul cappuccio e 75 sul corpo) 150 mg capsule (cap arancione scuro e corpo con W e Effexor XR sul cappuccio e 150 sul corpo) Ipersensibilità Ipersensibilità alla venlafaxina cloridrato, desvenlafaxine succinato o ad uno qualsiasi eccipienti nella formulazione uso concomitante con monoamino ossidasi (IMAO) l'uso di MAO (destinati per trattare i disordini psichiatrici) in associazione con Effexor XR o entro 7 giorni dalla sospensione del trattamento con Effexor XR è controindicato a causa di un aumentato rischio di sindrome serotoninergica. L'uso di Effexor XR entro 14 giorni dalla sospensione del trattamento con un IMAO (destinato a trattare i disordini psichiatrici) è controindicato anche vedere Dosaggio e somministrazione (2.9). Avvertenze e precauzioni (5.2). e Interazioni con altri farmaci (7.2). A partire Effexor XR in un paziente che viene trattato con un IMAO, come linezolid o blu di metilene per via endovenosa è anche controindicato, a causa di un aumentato rischio di sindrome serotoninergica vedere Dosaggio e somministrazione (2.9). Avvertenze e precauzioni (5.2). e Interazioni con altri farmaci (7.3). Avvertenze e precauzioni pensieri suicidari e comportamenti nei bambini, adolescenti e giovani adulti pazienti con disturbo depressivo maggiore (MDD), sia per adulti e pediatrica, possono sperimentare peggioramento della loro depressione Andor la comparsa di ideazione e comportamento suicidario (suicida) o inusuali cambiamenti nel comportamento, anche se non stanno prendendo farmaci antidepressivi, e questo rischio può persistere fino a quando si verifica una remissione significativa. Il suicidio è un rischio noto di depressione e di alcuni altri disturbi psichiatrici, e questi disturbi stessi sono i più forti predittori di suicidio. C'è stata una preoccupazione di lunga data, tuttavia, che gli antidepressivi possono avere un ruolo nell'indurre peggioramento della depressione e l'emergere di suicidio in alcuni pazienti durante le prime fasi di trattamento. analisi combinate di studi controllati con placebo a breve termine di farmaci antidepressivi (SSRI e altri) hanno mostrato che questi farmaci aumentano il rischio di pensieri e comportamenti suicidari (suicidalità) in bambini, adolescenti e giovani adulti (età 18ndash24) con MDD e altre psichiatrica disturbi. studi a breve termine non hanno mostrato un aumento del rischio di suicidio con antidepressivi rispetto al placebo negli adulti oltre 24 anni c'è stata una riduzione con antidepressivi rispetto al placebo negli adulti di età compresa tra 65 e più anziani. Le analisi combinate di studi controllati con placebo nei bambini e negli adolescenti con MDD, disturbo ossessivo compulsivo (OCD), o di altri disturbi psichiatrici incluso un totale di 24 studi a breve termine di 9 farmaci antidepressivi in più di 4.400 pazienti. Le analisi combinate di studi controllati verso placebo in adulti con disturbo depressivo maggiore o altri disturbi psichiatrici incluso un totale di 295 studi a breve termine (durata media di 2 mesi) di 11 farmaci antidepressivi in più di 77.000 pazienti. C'era notevole variazione nel rischio di suicidio tra i farmaci, ma una tendenza verso un aumento nei pazienti più giovani per quasi tutti i farmaci studiati. Ci sono state differenze nel rischio assoluto di suicidio tra le diverse indicazioni, con la più alta incidenza di MDD. Le differenze di rischio (droga rispetto al placebo), tuttavia, sono stati relativamente stabili all'interno di strati di età e in tutte le indicazioni. Queste differenze di rischio (differenza farmaco-placebo nel numero di casi di suicidio per 1000 pazienti trattati) sono forniti nella tabella 1. Tabella 1: differenza nel numero di casi di suicidio per 1.000 pazienti trattati rispetto al placebo Aumenta, rispetto al placebo suicidi si è verificato in uno degli studi pediatrici. Ci sono stati suicidi negli studi sugli adulti, ma il numero non è stato sufficiente per raggiungere qualsiasi conclusione circa effetto del farmaco sul suicidio. Non è noto se il rischio suicida si estende per l'uso a lungo termine, vale a dire al di là di alcuni mesi. Tuttavia, non vi è sostanziale prove fornite da studi di manutenzione controllati con placebo in pazienti adulti con depressione che l'uso di antidepressivi può ritardare la ricorrenza della depressione. Tutti i pazienti in trattamento con antidepressivi per qualsiasi indicazione devono essere monitorati in modo appropriato e tenuti sotto stretta osservazione per un peggioramento clinico, suicida, e inusuali cambiamenti nel comportamento, soprattutto durante i primi mesi di un corso di terapia farmacologica, o in momenti di cambiamenti della dose, o aumenta o diminuisce. I seguenti sintomi, ansia, agitazione, attacchi di panico, insonnia, irritabilità, ostilità, aggressività, impulsività, acatisia (irrequietezza psicomotoria), ipomania e mania, sono stati riportati in pazienti adulti e pediatrici in trattamento con antidepressivi per MDD, così come per altre indicazioni, sia psichiatriche e non psichiatriche. Anche se non è stato stabilito un nesso di causalità tra la comparsa di tali sintomi e sia il peggioramento della depressione Andor l'emergere di impulsi suicidi, si teme che questi sintomi possono rappresentare precursori di suicidalità emergente. Occorre prendere in considerazione per la modifica del regime terapeutico, anche eventualmente la sospensione del farmaco, nei pazienti in cui la depressione è persistentemente peggio, o che stanno sperimentando suicidalità emergente o sintomi che potrebbero essere precursori di depressione peggioramento o suicida, soprattutto se questi sintomi sono gravi, brusca in insorgenza, o non facevano parte dei pazienti che presentano sintomi. Se è stata presa la decisione di interrompere il trattamento, il farmaco deve essere rastremato, quanto più rapido è fattibile, ma con il riconoscimento che la sospensione brusca può essere associato a certi sintomi vedere Avvertenze e Precauzioni (5.7) e Dosaggio e somministrazione (2.8). Le famiglie e gli operatori sanitari dei pazienti in trattamento con antidepressivi per MDD o di altre indicazioni, sia psichiatrici e non psichiatrici, dovrebbero essere avvertiti della necessità di monitorare i pazienti per la comparsa di agitazione, irritabilità, cambiamenti insoliti nel comportamento, e gli altri sintomi descritti sopra, come così come l'emergere di suicidio, e di riferire tali sintomi immediatamente agli operatori sanitari. Tale controllo dovrebbe includere l'osservazione quotidiana delle famiglie e gli operatori sanitari. Prescrizioni per Effexor XR devono essere scritti per la più piccola quantità di capsule compatibili con una buona gestione del paziente, al fine di ridurre il rischio di sovradosaggio. Lo screening dei pazienti per il disturbo bipolare un episodio depressivo maggiore può essere la presentazione iniziale del disturbo bipolare. Si ritiene generalmente (anche se non stabilito in studi controllati) che il trattamento di un tale episodio con solo un antidepressivo può aumentare la probabilità di precipitazione di un episodio di mixedmanic nei pazienti a rischio per il disturbo bipolare. Se uno qualsiasi dei sintomi sopra descritti rappresentano tale conversione è sconosciuta. Tuttavia, prima di iniziare il trattamento con un antidepressivo, i pazienti con sintomi depressivi devono essere adeguatamente screening per determinare se sono a rischio per il disturbo bipolare tale screening dovrebbe includere una storia psichiatrica dettagliate, tra cui una storia familiare di suicidio, disturbo bipolare e depressione. Va notato che Effexor XR non è approvato per l'uso nel trattamento della depressione bipolare. Sindrome serotoninergica 8203 Lo sviluppo di una sindrome serotoninergica potenzialmente pericolosa per la vita è stata riportata con SNRI e SSRI, compresi Effexor XR da solo, ma in particolare con l'uso concomitante di altri farmaci serotoninergici (inclusi triptani, gli antidepressivi triciclici, fentanil, litio, tramadolo, triptofano, buspirone, anfetamine, e St. Johns wort) e con farmaci che alterano il metabolismo della serotonina, in particolare, MAO, sia quelli destinati per il trattamento di disturbi e altri psichiatrici, come linezolid o blu di metilene per via endovenosa). I sintomi della sindrome serotoninergica possono includere modifiche dello stato mentale (per es agitazione, allucinazioni, delirio, coma) instabilità autonomica (ad esempio tachicardia, labile la pressione sanguigna, ipertermia, sudorazione, vampate di calore, e vertigini), sintomi neuromuscolari (ad esempio tremore, rigidità, mioclono, iperreflessia, incoordinazione) convulsioni e sintomi gastrointestinali (ad esempio nausea, vomito, diarrea). I pazienti devono essere monitorati per la comparsa di sindrome serotoninergica. L'uso concomitante di Effexor XR con MAO (destinato a trattare i disordini psichiatrici) è controindicato. Effexor XR non deve essere avviato anche in un paziente che è in trattamento con MAO quali linezolid o blu di metilene per via endovenosa. Tutti i rapporti con blu di metilene che ha fornito le informazioni sulla via di somministrazione coinvolti somministrazione endovenosa nel range di dosaggio di 1 mgkg a 8 mgkg. Nessun rapporto comportato la somministrazione di blu di metilene per altre vie (come compresse per via orale o iniezione del tessuto locale) oa dosi inferiori. Ci possono essere circostanze in cui è necessario iniziare il trattamento con un MAO come linezolid o blu di metilene per via endovenosa in un paziente di prendere Effexor XR. Effexor XR deve essere interrotto prima di iniziare il trattamento con l'IMAO vedi Controindicazioni (4.2). Dosaggio e somministrazione (2.6). e Interazioni con altri farmaci (7.3). Se l'uso concomitante di Effexor XR con altri farmaci serotoninergici (ad esempio triptani, gli antidepressivi triciclici, la mirtazapina, fentanil, litio, tramadolo, buspirone, anfetamine, triptofano, o erba di San Giovanni) è clinicamente giustificato, si consiglia un'attenta osservazione del paziente, in particolare durante il trattamento aumenta di iniziazione e la dose vedere Interazioni con altri farmaci (7.3). I pazienti devono essere consapevoli del potenziale rischio di sindrome serotoninergica. Il trattamento con Effexor XR e agenti serotoninergici concomitanti deve essere interrotto immediatamente se si verificano gli eventi di cui sopra, e deve essere iniziato un trattamento sintomatico di supporto. Aumenti della pressione arteriosa Negli studi controllati, si sono registrati aumenti correlati alla dose nella pressione sanguigna sistolica e diastolica, così come casi di ipertensione sostenuta vedere le reazioni avverse (6.2). Monitorare la pressione del sangue prima di iniziare il trattamento con Effexor XR e regolarmente durante il trattamento. Controllo dell'ipertensione preesistente prima di iniziare il trattamento con Effexor XR. Usare cautela nel trattamento di pazienti con ipertensione preesistente o malattie cardiovascolari o cerebrovascolari che potrebbero essere compromesse da un aumento della pressione sanguigna. Sostenuto aumento della pressione arteriosa può portare a esiti avversi. I casi di pressione sanguigna elevata che richiedono un trattamento immediato sono stati riportati con Effexor XR. Prendere in considerazione la riduzione del dosaggio o l'interruzione del trattamento per i pazienti che soffrono di un aumento sostenuto della pressione sanguigna. In tutti gli studi clinici con Effexor, 1,4 dei pazienti nel Effexor XR trattati gruppi hanno sperimentato un aumento mm Hg GE15 in posizione supina pressione arteriosa diastolica (SDBP) ge 105 millimetri Hg, rispetto ai 0,9 dei pazienti nel gruppo placebo. Allo stesso modo, 1 dei pazienti nel Effexor XR trattare gruppi sperimentato un ge 20 millimetri aumento Hg in posizione supina pressione arteriosa sistolica (SSBP) con la pressione del sangue ge 180 millimetri Hg, rispetto ai 0,3 dei pazienti nel gruppo placebo si veda la tabella 10 delle reazioni avverse ( 6.2). trattamento Effexor XR è stato associato ad ipertensione sostenuta (definita come emergente da trattamento SDBP ge 90 mm Hg e ge 10 mm Hg al di sopra della linea di base per tre consecutivi visite in terapia vedi tabella 11 Reazioni avverse (6.2). Un numero insufficiente di pazienti ha ricevuto media dosi di Effexor XR oltre 300 mg al giorno negli studi clinici per valutare pienamente l'incidenza di aumenti sostenuti della pressione arteriosa a queste dosi più elevate. sanguinamento anomalo SSRI e gli SNRI, compresi Effexor XR, può aumentare il rischio di sanguinamento eventi, che vanno da ecchimosi, ematomi, epistassi, petecchie, ed emorragia gastrointestinale per emorragia pericolosa per la vita. l'uso concomitante di aspirina, farmaci antinfiammatori non steroidei (FANS), warfarin, e altri anti-coagulanti o altri farmaci noti per influenzare la funzione piastrinica possono aggiungere a questo rischio. casi clinici e studi epidemiologici (caso-controllo e di coorte di progettazione) hanno dimostrato un'associazione tra uso di farmaci che interferiscono con la ricaptazione della serotonina e la comparsa di sanguinamento gastrointestinale. pazienti cautela circa il rischio di sanguinamento associato con l'uso concomitante di Effexor XR e FANS, l'aspirina o altri farmaci che influenzano la coagulazione. Glaucoma ad angolo chiuso La dilatazione della pupilla che si verifica l'uso successivo di molti farmaci antidepressivi tra Effexor XR possono scatenare un attacco chiusura d'angolo in un paziente con angoli stretti anatomicamente che non ha un iridectomia brevetto. L'attivazione di ManiaHypomania mania o ipomania è stata riportata in Effexor XR pazienti trattati negli studi pre-marketing di MDD, SAD, e PD (vedi tabella 2). Maniahypomania è stata riportata anche in una piccola percentuale di pazienti con disturbi dell'umore che sono stati trattati con altri farmaci in commercio per il trattamento di MDD. Effexor XR deve essere usato con cautela nei pazienti con una storia di mania o ipomania. Tabella 2: Incidenza () di mania o ipomania Riportato in Effexor XR pazienti trattati nei sintomi pre-marketing Studi interruzione sindrome da sospensione sono stati sistematicamente valutati in pazienti che assumono venlafaxina, tra cui analisi prospettiche di studi clinici in GAD e indagini retrospettive di studi in MDD e SAD . Brusca riduzione o sospensione della dose di venlafaxina a varie dosi è stato trovato per essere associato con la comparsa di nuovi sintomi, la cui frequenza aumentata all'aumentare del dosaggio e durata del trattamento. sintomi riferiti comprendono agitazione, anoressia, ansia, confusione, compromissione della coordinazione e l'equilibrio, diarrea, vertigini, secchezza delle fauci, disforico umore, fascicolazioni, stanchezza, sintomi simil-influenzali, mal di testa, ipomania, insonnia, nausea, nervosismo, incubi, disturbi sensoriali ( compresi sensazioni elettrici shock-simile), sonnolenza, sudorazione, tremore, vertigini e vomito. Durante la commercializzazione di Effexor XR, altro SNRI, e gli SSRI, ci sono state segnalazioni spontanee di eventi avversi che si verificano dopo la sospensione di questi farmaci, soprattutto se brusca, tra cui le seguenti: umore, irritabilità, agitazione, vertigini, disturbi sensoriali (ad esempio parestesie disforico, come ad esempio sensazione di scossa elettrica), ansia, confusione, mal di testa, letargia, labilità emotiva, insonnia, ipomania, tinnito, e convulsioni. Anche se questi eventi sono generalmente autolimitanti, ci sono state segnalazioni di gravi sintomi da sospensione. I pazienti devono essere monitorati per questi sintomi quando sospensione del trattamento con Effexor XR. Una riduzione graduale della dose, piuttosto che una brusca interruzione, si raccomanda quando possibile. Se i sintomi intollerabili verificarsi a seguito di una riduzione della dose o l'interruzione del trattamento, il ripristino della dose prescritta in precedenza può essere considerato. Successivamente, il medico può continuare a ridurre la dose, ma ad un ritmo più graduale vedere Dosaggio e somministrazione (2.8). Sequestri sono verificati la terapia con venlafaxina. Effexor XR, come molti antidepressivi, deve essere usato con cautela nei pazienti con una storia di convulsioni e deve essere interrotto nei pazienti che sviluppa convulsioni. Deve ridurre il rischio: fattori di rischio, meds concomitanti che abbassano la soglia convulsiva. L'iponatriemia L'iponatriemia può verificarsi a seguito del trattamento con SSRI e gli SNRI, compresi Effexor XR. In molti casi, l'iponatriemia sembra essere il risultato della Sindrome da inadeguata secrezione di ormone antidiuretico (SIADH). Sono stati riportati casi con siero di sodio inferiore a 110 mmolL. I pazienti anziani possono essere a maggior rischio di sviluppare iponatriemia con SSRI e SNRI vedere Uso in popolazioni specifiche (8.5). Inoltre, i pazienti che assumono diuretici, o coloro che sono altrimenti volume-impoverito, possono essere più a rischio. Prendere in considerazione la sospensione di Effexor XR nei pazienti con iponatriemia sintomatica, e istituire un intervento medico appropriato. Segni e sintomi di iponatremia includono mal di testa, difficoltà di concentrazione, disturbi della memoria, confusione, debolezza e instabilità, che possono portare a cadute. Segni e sintomi associati con più gravi casi acuti eo hanno incluso allucinazioni, sincope, convulsioni, coma, arresto respiratorio e morte. Peso e altezza Cambiamenti in pazienti pediatrici, l'andamento medio del peso corporeo e l'incidenza di perdita di peso (percentuale di pazienti che hanno perso 3,5 o più) negli studi pediatrici controllati con placebo in MDD, GAD, e SAD sono riportati nelle tabelle 3 e 4. Tabella 3: variazione media del peso corporeo (kg) da inizio del trattamento in pazienti pediatrici in doppio cieco, controllati con placebo della perdita di Effexor XR di peso non si è limitata a pazienti con anoressia emergente da trattamento vedere avvertenze e precauzioni (5.11). I rischi associati con l'uso a lungo termine Effexor XR sono stati valutati in uno studio in aperto MDD di bambini e adolescenti che hanno ricevuto XR Effexor per un massimo di sei mesi. I bambini e gli adolescenti nello studio avevano un aumento di peso che erano meno del previsto, sulla base di dati provenienti da coetanei per età e sesso. La differenza tra l'aumento di peso e aumento di peso osservato atteso era più grande per i bambini (lt 12 anni) che per gli adolescenti (GE 12 anni). La tabella 5 mostra l'aumento medio altezza in pazienti pediatrici nel breve termine, controllato con placebo MDD, GAD, e gli studi SAD. Le differenze di altezza aumenti di studi GAD e MDD erano più notevole nei pazienti di età inferiore ai dodici anni. Tabella 5: Aumenta altezza media (cm) in pazienti pediatrici in Studi di Effexor XR Placebo-controllato nei sei mesi, in aperto studio MDD, i bambini e gli adolescenti avevano altezza aumenta che erano meno del previsto, sulla base di dati provenienti da età - e coetanei sesso. La differenza tra i tassi di crescita osservati e attesi era più grande per i bambini (LT 12 anni) che per gli adolescenti (GE 12 anni). Alterazioni dell'appetito in pazienti pediatrici Diminuzione dell'appetito (segnalato come emergente da trattamento anoressia) è stato più comunemente osservata in Effexor XR pazienti trattati rispetto ai pazienti trattati con placebo nella valutazione pre-marketing di Effexor XR per MDD, GAD, e SAD (vedi Tabella 6). Tabella 6: Incidenza () di diminuzione dell'appetito e associati di interruzione Prezzi () in pazienti pediatrici in studi controllati con placebo su Effexor XR Effexor XR incidenza le percentuali di interruzione per la perdita di peso sono stati 0,7 per i pazienti trattati sia XR Effexor o placebo. MDD e GAD (pooled, 8 settimane) malattia polmonare malattia polmonare interstiziale e eosinofila polmonite interstiziale e polmonite eosinofila associato alla terapia con venlafaxina Raramente sono stati segnalati. La possibilità di questi eventi avversi dovrebbe essere considerata in pazienti trattati con venlafaxina che si presentano con dispnea progressiva, tosse o fastidio al torace. Tali pazienti devono essere sottoposti ad una valutazione medica tempestiva, e l'interruzione della terapia con venlafaxina devono essere considerati. Reazioni avverse Le seguenti reazioni avverse sono discussi in maggior dettaglio in altre sezioni del marchio: Studi clinici esperienza perché gli studi clinici vengono condotti in condizioni molto diverse, velocità di reazione avversi osservati negli studi clinici di un farmaco non può essere direttamente confrontati con tariffe nel studi clinici di un altro farmaco e potrebbero non riflettere i tassi osservati nella pratica. Reazioni avverse più comuni Le reazioni avverse più comunemente osservati nel database studio clinico in Effexor XR pazienti trattati in MDD, GAD, SAD, e PD (incidenza ge 5 e almeno il doppio del tasso di placebo) sono stati: nausea (30,0), sonnolenza (15.3), secchezza delle fauci (14,8), sudorazione (11.4), eiaculazione anomala (9.9), anoressia (9,8), costipazione (9.3), l'impotenza (5.3) e diminuzione della libido (5.1). Le reazioni avverse riportate come ragioni per la sospensione del trattamento combinato di tutto a breve termine, gli studi pre-marketing controllati con placebo per tutte le indicazioni, 12 dei 3.558 pazienti che hanno ricevuto Effexor XR (37.5ndash225 mg) hanno interrotto il trattamento a causa di un evento avverso, contro il 4 di i 2.197 pazienti trattati con placebo in questi studi. Le reazioni avverse più comuni che portano alla sospensione in ge 1 della Effexor XR pazienti trattati negli studi a breve termine (fino a 12 settimane) in tutte le indicazioni sono riportati nella tabella 7. Tabella 7: Incidenza () di pazienti che hanno riportato reazioni avverse che portano alla la sospensione in placebo-controllato Studi clinici (fino a 12 settimane Durata) sistema corpo Reazione avversa Effexor XR n 3.558 Placebo n 2.197 reazioni avverse comuni in studi controllati con placebo il numero di pazienti che hanno ricevuto dosi multiple di Effexor XR durante la valutazione pre-marketing per ogni approvato indication is shown in Table 8. The conditions and duration of exposure to venlafaxine in all development programs varied greatly, and included (in overlapping categories) open and double-blind studies, uncontrolled and controlled studies, inpatient (Effexor only) and outpatient studies, fixed-dose, and titration studies. Table 8: Patients Receiving Effexor XR in Premarketing Clinical Studies In addition, in the premarketing assessment of Effexor, multiple doses were administered to 2,897 patients in studies for MDD. The incidences of common adverse reactions (those that occurred in ge 2 of Effexor XR treated patients 357 MDD patients, 1,381 GAD patients, 819 SAD patients, and 1,001 PD patients and more frequently than placebo) in Effexor XR treated patients in short-term, placebo-controlled, fixed - and flexible-dose clinical studies (doses 37.5 to 225 mg per day) are shown in Table 9. The adverse reaction profile did not differ substantially between the different patient populations. Table 9: Common Adverse Reactions: Percentage of Patients Reporting Adverse Reactions (ge 2 and gt placebo) in Placebo-controlled Studies (up to 12 Weeks Duration) across All Indications Body System Adverse Reaction Effexor XR n 3,558 Placebo n 2,197 Percentages based on the number of men (Effexor XR, n 1,440 placebo, n 923) dagger Percentages based on the number of women (Effexor XR, n 2,118 placebo, n 1,274) Other Adverse Reactions Observed in Clinical Studies Body as a whole ndash Photosensitivity reaction, chills Cardiovascular system ndash Postural hypotension, syncope, hypotension, tachycardia Digestive system ndash Gastrointestinal hemorrhage see Warnings and Precautions (5.4) , bruxism Nervous system ndash Seizures see Warnings and Precautions (5.8) , manic reaction see Warnings and Precautions (5.6) , agitation, confusion, akathisia, hallucinations, hypertonia, myoclonus, depersonalization, apathy Skin and appendages ndash Urticaria, pruritus, rash, alopecia Special senses ndash Mydriasis, abnormality of accommodation, tinnitus, taste perversion Urogenital system ndash Urinary retention, urination impaired, urinary incontinence, urinary frequency increased, menstrual disorders associated with increased bleeding or increased irregular bleeding (e. g. menorrhagia, metrorrhagia) Vital Sign Changes In placebo-controlled premarketing studies, there were increases in mean blood pressure (see Table 10 ). Across most indications, a dose-related increase in mean supine systolic and diastolic blood pressure was evident in patients treated with Effexor XRs. Across all clinical studies in MDD, GAD, SAD and PD, 1.4 of patients in the Effexor XR groups experienced an increase in SDBP of ge15 mm Hg along with a blood pressure ge 105 mm Hg, compared to 0.9 of patients in the placebo groups. Similarly, 1 of patients in the Effexor XR groups experienced an increase in SSBP of ge 20 mm Hg with a blood pressure ge 180 mm Hg, compared to 0.3 of patients in the placebo groups. Table 10: Final On-therapy Mean Changes From Baseline in Supine Systolic (SSBP) and Diastolic (SDBP) Blood Pressure (mm Hg) in Placebo-controlled Studies Effexor XR treatment was associated with sustained hypertension (defined as treatment-emergent Supine Diastolic Blood Pressure SDBP ge 90 mm Hg and ge 10 mm Hg above baseline for three consecutive on-therapy visits (see Table 11 ). An insufficient number of patients received mean doses of Effexor XR over 300 mg per day in clinical studies to fully evaluate the incidence of sustained increases in blood pressure at these higher doses. Table 11: Sustained Elevations in SDBP in Effexor XR Premarketing Studies Dose Range (mg per day) Effexor XR was associated with mean increases in pulse rate compared with placebo in premarketing placebo-controlled studies (see Table 12 ) see Warnings and Precautions (5.3. 5.4) . Table 12: Approximate Mean Final On-therapy Increase in Pulse Rate (beatsmin) in Effexor XR Premarketing Placebo-controlled Studies (up to 12 Weeks Duration) Laboratory Changes Effexor XR was associated with mean final increases in serum cholesterol concentrations compared with mean final decreases for placebo in premarketing MDD, GAD, SAD and PD clinical studies (Table 13). Table 13: Mean Final On-therapy Changes in Cholesterol Concentrations (mgdL) in Effexor XR Premarketing Studies Effexor XR (venlafaxine hydrochloride) extended-release capsules treatment for up to 12 weeks in premarketing placebo-controlled trials for major depressive disorder was associated with a mean final on-therapy increase in serum cholesterol concentration of approximately 1.5 mgdL compared with a mean final decrease of 7.4 mgdL for placebo. Effexor XR treatment for up to 8 weeks and up to 6 months in premarketing placebo-controlled GAD trials was associated with mean final on-therapy increases in serum cholesterol concentration of approximately 1.0 mgdL and 2.3 mgdL, respectively while placebo subjects experienced mean final decreases of 4.9 mgdL and 7.7 mgdL, respectively. Effexor XR treatment for up to 12 weeks and up to 6 months in premarketing placebo-controlled Social Anxiety Disorder trials was associated with mean final on-therapy increases in serum cholesterol concentration of approximately 7.9 mgdL and 5.6 mgdL, respectively, compared with mean final decreases of 2.9 and 4.2 mgdL, respectively, for placebo. Effexor XR treatment for up to 12 weeks in premarketing placebo-controlled panic disorder trials was associated with mean final on-therapy increases in serum cholesterol concentration of approximately 5.8 mgdL compared with a mean final decrease of 3.7 mgdL for placebo. Patients treated with Effexor (immediate release) for at least 3 months in placebo-controlled 12-month extension trials had a mean final on-therapy increase in total cholesterol of 9.1 mgdL compared with a decrease of 7.1 mgdL among placebo-treated patients. This increase was duration dependent over the study period and tended to be greater with higher doses. Clinically relevant increases in serum cholesterol, defined as 1) a final on-therapy increase in serum cholesterol ge50 mgdL from baseline and to a value ge261 mgdL, or 2) an average on-therapy increase in serum cholesterol ge50 mgdL from baseline and to a value ge261 mgdL, were recorded in 5.3 of venlafaxine-treated patients and 0.0 of placebo-treated patients. Effexor XR was associated with mean final on-therapy increases in fasting serum triglycerides compared with placebo in premarketing clinical studies of SAD and PD up to 12 weeks (pooled data) and 6 months duration (Table 14). Table 14: Mean Final On-therapy Increases in Triglyceride Concentrations (mgdL) in Effexor XR Premarketing Studies Pediatric Patients In general, the adverse reaction profile of venlafaxine (in placebo-controlled clinical studies) in children and adolescents (ages 6 to 17) was similar to that seen for adults. As with adults, decreased appetite, weight loss, increased blood pressure, and increased serum cholesterol were observed see Warnings and Precautions (5.3. 5.10. 5.11 ) and Use in Specific Populations (8.4) . In pediatric clinical studies, the adverse reaction, suicidal ideation, was observed. Particularly, the following adverse reactions were observed in pediatric patients: abdominal pain, agitation, dyspepsia, ecchymosis, epistaxis, and myalgia. Adverse Reactions Identified During Postapproval Use The following adverse reactions have been identified during postapproval use of Effexor XR. 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: Body as a whole ndash Anaphylaxis, angioedema Cardiovascular system ndash QT prolongation, ventricular fibrillation, ventricular tachycardia (including torsade de pointes) Digestive system ndash Pancreatitis HemicLymphatic system ndash Mucous membrane bleeding see Warnings and Precautions (5.4 ) , blood dyscrasias (including agranulocytosis, aplastic anemia, neutropenia and pancytopenia), prolonged bleeding time, thrombocytopenia MetabolicNutritional ndash Hyponatremia see Warnings and Precautions (5.9) , Syndrome of Inappropriate Antidiuretic Hormone (SIADH) secretion see Warnings and Precautions (5.9) , abnormal liver function tests, hepatitis, prolactin increased Musculoskeletal ndash Rhabdomyolysis Nervous system ndash Neuroleptic Malignant Syndrome (NMS) see Warnings and Precautions (5.2) , serotonergic syndrome see Warnings and Precautions (5.2) , delirium, extrapyramidal reactions (including dystonia and dyskinesia), impaired coordination and balance, tardive dyskinesia Respiratory system ndash Dyspnea, interstitial lung disease, pulmonary eosinophilia see Warnings and Precautions (5.12) Skin and appendages ndash Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme Special senses ndash Angle-closure glaucoma see Warnings and Precautions (5.5) Drug Interactions Central Nervous System (CNS)-Active Drugs The risk of using venlafaxine in combination with other CNS-active drugs has not been systematically evaluated. Consequently, caution is advised when Effexor XR is taken in combination with other CNS-active drugs. Monoamine Oxidase Inhibitors Adverse reactions, some of which were serious, have been reported in patients who have recently been discontinued from an MAOI and started on antidepressants with pharmacological properties similar to Effexor XR (SNRIs or SSRIs), or who have recently had SNRI or SSRI therapy discontinued prior to initiation of an MAOI see Dosage and Administration (2.9). Contraindications (4.2) and Warnings and Precautions (5.2) . Serotonergic Drugs Based on the mechanism of action of Effexor XR and the potential for serotonin syndrome, caution is advised when Effexor XR is coadministered with other drugs that may affect the serotonergic neurotransmitter systems, such as triptans, SSRIs, other SNRIs, linezolid (an antibiotic which is a reversible non-selective MAOI), lithium, tramadol, or St. Johns wort. If concomitant treatment with Effexor XR and these drugs is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases. The concomitant use of Effexor XR with tryptophan supplements is not recommended see Dosage and Administration (2.9). Contraindications (4.2). and Warnings and Precautions (5.2) . Drugs that Interfere with Hemostasis (e. g. NSAIDs, Aspirin, and Warfarin) Serotonin release by platelets plays an important role in hemostasis. The use of psychotropic drugs that interfere with serotonin reuptake is associated with the occurrence of upper gastrointestinal bleeding and concurrent use of an NSAID or aspirin may potentiate this risk of bleeding see Warnings and Precautions (5.4) . Altered anticoagulant effects, including increased bleeding, have been reported when SSRIs and SNRIs are coadministered with warfarin. Patients receiving warfarin therapy should be carefully monitored when Effexor XR is initiated or discontinued. Weight Loss Agents The safety and efficacy of venlafaxine therapy in combination with weight loss agents, including phentermine, have not been established. Coadministration of Effexor XR and weight loss agents is not recommended. Effexor XR is not indicated for weight loss alone or in combination with other products. Effects of Other Drugs on Effexor XR Figure 1: Effect of interacting drugs on the pharmacokinetics of venlafaxine and active metabolite O-desmethylvenlafaxine (ODV). Abbreviations: AUC, area under the curve Cmax, peak plasma concentrations OH, hydroxyl Data for 2-OH desipramine were not plotted to enhance clarity the fold change and 90 CI for Cmax and AUC of 2-OH desipramine were 6.6 (5.5, 7.9) and 4.4 (3.8, 5.0), respectively. Note: : Administration of venlafaxine in a stable regimen did not exaggerate the psychomotor and psychometric effects induced by ethanol in these same subjects when they were not receiving venlafaxine. Drug-Laboratory Test Interactions False-positive urine immunoassay screening tests for phencyclidine (PCP) and amphetamine have been reported in patients taking venlafaxine. This is due to lack of specificity of the screening tests. False positive test results may be expected for several days following discontinuation of venlafaxine therapy. Confirmatory tests, such as gas chromatographymass spectrometry, will distinguish venlafaxine from PCP and amphetamine. USE IN SPECIFIC POPULATIONS Teratogenic Effects ndash Pregnancy Category C Venlafaxine did not cause malformations in offspring of rats or rabbits given doses up to 2.5 times (rat) or 4 times (rabbit) the maximum recommended human daily dose on a mgm 2 basis. However, in rats, there was a decrease in pup weight, an increase in stillborn pups, and an increase in pup deaths during the first 5 days of lactation, when dosing began during pregnancy and continued until weaning. The cause of these deaths is not known. These effects occurred at 2.5 times (mgm 2 ) the maximum human daily dose. The no effect dose for rat pup mortality was 0.25 times the human dose on a mgm 2 basis. In reproductive developmental studies in rats and rabbits with O-desmethylvenlafaxine (ODV), the major human metabolite of venlafaxine, evidence of teratogenicity was not observed at exposure margins of 13 in rats and 0.3 in rabbits. There are no adequate and well-controlled studies in pregnant women. Effexor XR should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Neonates exposed to Effexor XR, other SNRIs, or SSRIs, late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. These features are consistent with either a direct toxic effect of SSRIs and SNRIs, or possibly a drug discontinuation syndrome. It should be noted, that in some cases the clinical picture is consistent with serotonin syndrome see Warnings and Precautions (5.2) and Drug Interactions (7.3) . When treating a pregnant woman with Effexor XR during the third trimester, the physician should carefully consider the potential risks and benefits of treatment. Labor and Delivery The effect of venlafaxine on labor and delivery in humans is unknown. Nursing Mothers Venlafaxine and ODV have been reported to be excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from Effexor XR, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Use Two placebo-controlled trials in 766 pediatric patients with MDD and two placebo-controlled trials in 793 pediatric patients with GAD have been conducted with Effexor XR, and the data were not sufficient to support a claim for use in pediatric patients. Anyone considering the use of Effexor XR in a child or adolescent must balance the potential risks with the clinical need see Boxed Warning. Warnings and Precautions (5.1. 5.10. 5.11 ) and Adverse Reactions (6.4 ) . Although no studies have been designed to primarily assess Effexor XRs impact on the growth, development, and maturation of children and adolescents, the studies that have been done suggest that Effexor XR may adversely affect weight and height (see Warnings and Precautions (5.10) ). Should the decision be made to treat a pediatric patient with Effexor XR, regular monitoring of weight and height is recommended during treatment, particularly if treatment is to be continued long-term see Warnings and Precautions (5.10. 5.11) . The safety of Effexor XR treatment for pediatric patients has not been systematically assessed for chronic treatment longer than six months in duration. In the studies conducted in pediatric patients (ages 6ndash17), the occurrence of blood pressure and cholesterol increases considered to be clinically relevant in pediatric patients was similar to that observed in adult patients. Consequently, the precautions for adults apply to pediatric patients see Warnings and Precautions (5.3 ,6.3) . Geriatric Use The percentage of patients in clinical studies for Effexor XR for MDD, GAD, SAD, and PD who were 65 years of age or older are shown in Table 15. Table 15: Percentage (and Number of Patients Studied) of Patients 65 Years of Age and Older by Indication No overall differences in effectiveness or safety were observed between geriatric patients and younger patients, and other reported clinical experience generally has not identified differences in response between the elderly and younger patients. However, greater sensitivity of some older individuals cannot be ruled out. SSRIs and SNRIs, including Effexor XR, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse event see Warnings and Precautions (5.9) . The pharmacokinetics of venlafaxine and ODV are not substantially altered in the elderly see Clinical Pharmacology (12.3) and (see Figure 3) . No dose adjustment is recommended for the elderly on the basis of age alone, although other clinical circumstances, some of which may be more common in the elderly, such as renal or hepatic impairment, may warrant a dose reduction see Dosage and Administration (2.6) . Age and Gender A population pharmacokinetic analysis of 404 Effexor-treated patients from two studies involving both twice daily and three times daily regimens showed that dose-normalized trough plasma levels of either venlafaxine or ODV were unaltered by age or gender differences. Dosage adjustment based on the age or gender of a patient is generally not necessary see Dosage and Administration (2.6) (see Table 15 ). Use in Patient Subgroups Figure 3: Pharmacokinetics of venlafaxine and its metabolite O-desmethylvenlafaxine (ODV) in special populations. Abbreviations: ODV, O-desmethylvenlafaxine AUC, area under the curve Cmax, peak plasma concentrations Similar effect is expected with strong CYP2D6 inhibitors Drug Abuse and Dependence Controlled Substance Effexor XR is not a controlled substance. While venlafaxine has not been systematically studied in clinical studies for its potential for abuse, there was no indication of drug-seeking behavior in the clinical studies. However, it is not possible to predict on the basis of premarketing experience the extent to which a CNS-active drug will be misused, diverted, andor abused once marketed. Consequently, physicians should carefully evaluate patients for history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse of venlafaxine (e. g. development of tolerance, incrementation of dose, drug-seeking behavior). Dependence In vitro studies revealed that venlafaxine has virtually no affinity for opiate, benzodiazepine, phencyclidine (PCP), or N-methyl-D-aspartic acid (NMDA) receptors. Venlafaxine was not found to have any significant CNS stimulant activity in rodents. In primate drug discrimination studies, venlafaxine showed no significant stimulant or depressant abuse liability. Discontinuation effects have been reported in patients receiving venlafaxine see Dosage and Administration (2.8) . Overdosage Human Experience During the premarketing evaluations of Effexor XR (for MDD, GAD, SAD, and PD) and Effexor (for MDD), there were twenty reports of acute overdosage with Effexor (6 and 14 reports in Effexor XR and Effexor patients, respectively), either alone or in combination with other drugs andor alcohol. Somnolence was the most commonly reported symptom. Among the other reported symptoms were paresthesia of all four limbs, moderate dizziness, nausea, numb hands and feet, and hot-cold spells 5 days after the overdose. In most cases, no signs or symptoms were associated with overdose. The majority of the reports involved ingestion in which the total dose of venlafaxine taken was estimated to be no more than several-fold higher than the usual therapeutic dose. One patient who ingested 2.75 g of venlafaxine was observed to have two generalized convulsions and a prolongation of QTc to 500 msec, compared with 405 msec at baseline. Mild sinus tachycardia was reported in two of the other patients. Actions taken to treat the overdose included no treatment, hospitalization and symptomatic treatment, and hospitalization plus treatment with activated charcoal. All patients recovered. In postmarketing experience, overdose with venlafaxine has occurred predominantly in combination with alcohol andor other drugs. The most commonly reported events in overdosage include tachycardia, changes in level of consciousness (ranging from somnolence to coma), mydriasis, seizures, and vomiting. Electrocardiogram changes (e. g. prolongation of QT interval, bundle branch block, QRS prolongation), ventricular tachycardia, bradycardia, hypotension, rhabdomyolysis, vertigo, liver necrosis, serotonin syndrome, and death have been reported. Published retrospective studies report that venlafaxine overdosage may be associated with an increased risk of fatal outcomes compared to that observed with SSRI antidepressant products, but lower than that for tricyclic antidepressants. Epidemiological studies have shown that venlafaxine-treated patients have a higher preexisting burden of suicide risk factors than SSRI-treated patients. The extent to which the finding of an increased risk of fatal outcomes can be attributed to the toxicity of venlafaxine in overdosage, as opposed to some characteristic(s) of venlafaxine-treated patients, is not clear. Prescriptions for Effexor XR should be written for the smallest quantity of capsules consistent with good patient management, in order to reduce the risk of overdose. Management of Overdosage Consult a Certified Poison Control Center for up-to-date guidance and advice (1-800-222-1222 or poison. org). In case of an overdose, provide supportive care, including close medical supervision and monitoring. Treatment should consist of those general measures employed in the management of overdosage with any drug. Consider the possibility of multiple drug overdose. Ensure an adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs. Provide supportive and symptomatic measures. Effexor XR Description Effexor XR is an extended-release capsule for once-a-day oral administration that contains venlafaxine hydrochloride, a serotonin and norepinephrine reuptake inhibitor (SNRI). Venlafaxine is designated (RS)-1-2-(dimethylamino)-1-(4-methoxyphenyl)ethyl cyclohexanol hydrochloride or (plusmn)-1-alpha - (dimethylamino)methyl-p-methoxybenzyl cyclohexanol hydrochloride and has the empirical formula of C 17 H 27 NO 2 HCl. Its molecular weight is 313.86. The structural formula is shown as follows: Venlafaxine hydrochloride is a white to off-white crystalline solid, with a solubility of 572 mgmL in water (adjusted to ionic strength of 0.2 M with sodium chloride). Its octanol:water (0.2 M sodium chloride) partition coefficient is 0.43. Drug release is controlled by diffusion through the coating membrane on the spheroids and is not pH-dependent. Capsules contain venlafaxine hydrochloride equivalent to 37.5 mg, 75 mg, or 150 mg venlafaxine. Inactive ingredients consist of cellulose, ethylcellulose, gelatin, hypromellose, iron oxide, and titanium dioxide. Effexor XR - Clinical Pharmacology Mechanism of Action The exact mechanism of the antidepressant action of venlafaxine in humans is unknown, but is thought to be related to the potentiation of serotonin and norepinephrine in the central nervous system, through inhibition of their reuptake. Non - clinical studies have demonstrated that venlafaxine and its active metabolite, ODV, are potent and selective inhibitors of neuronal serotonin and norepinephrine reuptake and weak inhibitors of dopamine reuptake. Pharmacodynamics Venlafaxine and ODV have no significant affinity for muscarinic-cholinergic, H 1 - histaminergic, or alpha 1 - adrenergic receptors in vitro. Pharmacologic activity at these receptors is hypothesized to be associated with the various anticholinergic, sedative, and cardiovascular effects seen with other psychotropic drugs. Venlafaxine and ODV do not possess monoamine oxidase (MAO) inhibitory activity. Pharmacokinetics Steady-state concentrations of venlafaxine and ODV in plasma are attained within 3 days of oral multiple-dose therapy. Venlafaxine and ODV exhibited linear kinetics over the dose range of 75 to 450 mg per day. MeanplusmnSD steady-state plasma clearance of venlafaxine and ODV is 1.3plusmn0.6 and 0.4plusmn0.2 Lhkg, respectively apparent elimination half-life is 5plusmn2 and 11plusmn2 hours, respectively and apparent (steady-state) volume of distribution is 7.5plusmn3.7 and 5.7plusmn1.8 Lkg, respectively. Venlafaxine and ODV are minimally bound at therapeutic concentrations to plasma proteins (27 and 30, respectively). Absorption and Distribution Venlafaxine is well absorbed and extensively metabolized in the liver. ODV is the major active metabolite. On the basis of mass balance studies, at least 92 of a single oral dose of venlafaxine is absorbed. The absolute bioavailability of venlafaxine is approximately 45. Administration of Effexor XR (150 mg once daily) generally resulted in lower C max and later T max values than for Effexor (immediate release) administered twice daily (Table 16). When equal daily doses of venlafaxine were administered as either an immediate-release tablet or the extended-release capsule, the exposure to both venlafaxine and ODV was similar for the two treatments, and the fluctuation in plasma concentrations was slightly lower with the Effexor XR capsule. Therefore, Effexor XR provides a slower rate of absorption, but the same extent of absorption compared with the immediate-release tablet. Table 16: Comparison of C max and T max Values for Venlafaxine and ODV Following Oral Administration of Effexor XR and Effexor (Immediate Release) Venlafaxine C max (ngmL) Food did not affect the bioavailability of venlafaxine or its active metabolite, ODV. Time of administration (AM versus PM) did not affect the pharmacokinetics of venlafaxine and ODV from the 75 mg Effexor XR capsule. Venlafaxine is not highly bound to plasma proteins therefore, administration of Effexor XR to a patient taking another drug that is highly protein-bound should not cause increased free concentrations of the other drug. Metabolism and Elimination Following absorption, venlafaxine undergoes extensive presystemic metabolism in the liver, primarily to ODV, but also to N-desmethylvenlafaxine, N, O-didesmethylvenlafaxine, and other minor metabolites. In vitro studies indicate that the formation of ODV is catalyzed by CYP2D6 this has been confirmed in a clinical study showing that patients with low CYP2D6 levels (poor metabolizers) had increased levels of venlafaxine and reduced levels of ODV compared to people with normal CYP2D6 levels (extensive metabolizers) see Use in Specific Populations 8.7 . Approximately 87 of a venlafaxine dose is recovered in the urine within 48 hours as unchanged venlafaxine (5), unconjugated ODV (29), conjugated ODV (26), or other minor inactive metabolites (27). Renal elimination of venlafaxine and its metabolites is thus the primary route of excretion. Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment of Fertility Tumors were not increased by venlafaxine treatment in mice or rats. Venlafaxine was given by oral gavage to mice for 18 months at doses up to 120 mgkg per day, which was 1.7 times the maximum recommended human dose on a mgm 2 basis. Venlafaxine was also given to rats by oral gavage for 24 months at doses up to 120 mgkg per day. In rats receiving the 120 mgkg dose, plasma concentrations of venlafaxine at necropsy were 1 times (male rats) and 6 times (female rats) the plasma concentrations of patients receiving the maximum recommended human dose. Plasma levels of the O-desmethyl metabolite (ODV) were lower in rats than in patients receiving the maximum recommended dose. O-desmethylvenlafaxine (ODV), the major human metabolite of venlafaxine, administered by oral gavage to mice and rats for 2 years did not increase the incidence of tumors in either study. Mice received ODV at dosages up to 500300 mgkgday (dosage lowered after 45 weeks of dosing). The exposure at the 300 mgkgday dose is 9 times that of a human dose of 225 mgday. Rats received ODV at dosages up to 300 mgkgday (males) or 500 mgkgday (females). The exposure at the highest dose is approximately 8 (males) or 11 (females) times that of a human dose of 225 mgday. Venlafaxine and the major human metabolite, ODV, were not mutagenic in the Ames reverse mutation assay in Salmonella bacteria or the Chinese hamster ovaryHGPRT mammalian cell forward gene mutation assay. Venlafaxine was also not mutagenic or clastogenic in the in vitro BALBc-3T3 mouse cell transformation assay, the sister chromatid exchange assay in cultured Chinese hamster ovary cells, or in the in vivo chromosomal aberration assay in rat bone marrow. ODV was not clastogenic in the in vitro Chinese hamster ovary cell chromosomal aberration assay or in the in vivo chromosomal aberration assay in rats. Impairment of Fertility Reproduction and fertility studies of venlafaxine in rats showed no adverse effects of venlafaxine on male or female fertility at oral doses of up to 2 times the maximum recommended human dose of 225 mgday on a mgm 2 basis. However, reduced fertility was observed in a study in which male and female rats were treated with O-desmethylvenlafaxine (ODV), the major human metabolite of venlafaxine, prior to and during mating and gestation. This occurred at an ODV exposure (AUC) approximately 2 to 3 times that associated with a human venlafaxine dose of 225 mgday. Clinical Studies Major Depressive Disorder The efficacy of Effexor XR (venlafaxine hydrochloride) extended-release capsules as a treatment for Major Depressive Disorder (MDD) was established in two placebo-controlled, short-term (8 weeks for study 1 12 weeks for study 2), flexible-dose studies, with doses starting at 75 mg per day and ranging to 225 mg per day in adult outpatients meeting DSM-III-R or DSM-IV criteria for MDD. In moderately depressed outpatients, the initial dose of venlafaxine was 75 mg per day. In both studies, Effexor XR demonstrated superiority over placebo on the primary efficacy measure defined as change from baseline in the HAM-D-21 total score to the endpoint visit, Effexor XR also demonstrated superiority over placebo on the key secondary efficacy endpoint, the Clinical Global Impressions (CGI) Severity of Illness scale. Examination of gender subsets of the population studied did not reveal any differential responsiveness on the basis of gender. A 4-week study of inpatients meeting DSM-III-R criteria for MDD with melancholia utilizing Effexor in a range of 150 to 375 mg per day (divided in a three-times-a-day schedule) demonstrated superiority of Effexor over placebo based on the HAM-D-21 total score. The mean dose in completers was 350 mg per day (study 3). In a longer-term study, adult outpatients with MDD who had responded during an 8-week open-label study on Effexor XR (75, 150, or 225 mg, once daily every morning) were randomized to continuation of their same Effexor XR dose or to placebo, for up to 26 weeks of observation for relapse. Response during the open-label phase was defined as a CGI Severity of Illness item score of le3 and a HAM-D-21 total score of le10 at the day 56 evaluation. Relapse during the double-blind phase was defined as follows: (1) a reappearance of major depressive disorder as defined by DSM-IV criteria and a CGI Severity of Illness item score of ge4 (moderately ill), (2) 2 consecutive CGI Severity of Illness item scores of ge4, or (3) a final CGI Severity of Illness item score of ge4 for any patient who withdrew from the study for any reason. Patients receiving continued Effexor XR treatment experienced statistically significantly lower relapse rates over the subsequent 26 weeks compared with those receiving placebo (study 4). In a second longer term trial, adult outpatients with MDD, recurrent type, who had responded (HAM-D-21 total score le 12 at the day 56 evaluation) and continued to be improved defined as the following criteria being met for days 56 through 180: (1) no HAM-D-21 total score ge 20 (2) no more than 2 HAM-D-21 total scores gt 10, and (3) no single CGI Severity of Illness item score ge 4 (moderately ill) during an initial 26 weeks of treatment on Effexor 100 to 200 mg per day, on a twice daily schedule were randomized to continuation of their same Effexor dose or to placebo. The follow-up period to observe patients for relapse, defined as a CGI Severity of Illness item score ge 4, was for up to 52 weeks. Patients receiving continued Effexor treatment experienced statistically significantly lower relapse rates over the subsequent 52 weeks compared with those receiving placebo (study 5). Table 17: Major Depressive Disorder Studies: Generalized Anxiety Disorder The efficacy of Effexor XR as a treatment for Generalized Anxiety Disorder (GAD) was established in two 8-week, placebo-controlled, fixed-dose studies (75 to 225 mg per day), one 6-month, placebo-controlled, flexible-dose study (75 to 225 mg per day), and one 6-month, placebo-controlled, fixed-dose study (37.5, 75, and 150 mg per day) in adult outpatients meeting DSM-IV criteria for GAD. In one 8-week study, Effexor XR demonstrated superiority over placebo for the 75, 150, and 225 mg per day doses as measured by the Hamilton Rating Scale for Anxiety (HAM-A) total score, both the HAM-A anxiety and tension items, and the Clinical Global Impressions (CGI) scale. However, the 75 and 150 mg per day doses were not as consistently effective as the highest dose (study 1). A second 8-week study evaluating doses of 75 and 150 mg per day and placebo showed that both doses were more effective than placebo on some of these same outcomes however, the 75 mg per day dose was more consistently effective than the 150 mg per day dose (study 2). A dose-response relationship for effectiveness in GAD was not clearly established in the 75 to 225 mg per day dose range studied. Two 6-month studies, one evaluating Effexor XR doses of 37.5, 75, and 150 mg per day (study 3) and the other evaluating Effexor XR doses of 75 to 225 mg per day (study 4), showed that daily doses of 75 mg or higher were more effective than placebo on the HAM-A total, both the HAM-A anxiety and tension items, and the CGI scale during 6 months of treatment. While there was also evidence for superiority over placebo for the 37.5 mg per day dose, this dose was not as consistently effective as the higher doses. Examination of gender subsets of the population studied did not reveal any differential responsiveness on the basis of gender. Table 18: Generalized Anxiety Disorder Studies: Primary Efficacy Measure: HAM-A Score Mean Baseline Score (SD) LS Mean Change from Baseline (SE) Placebo Subtracted Difference (95 CI) SD: standard deviation SE: standard error LS Mean: least-squares mean CI: confidence interval. Doses statistically significantly superior to placebo. Difference (drug minus placebo) in least-squares mean change from baseline Social Anxiety Disorder (also known as Social Phobia) The efficacy of Effexor XR as a treatment for Social Anxiety Disorder (SAD) was established in four double-blind, parallel-group, 12-week, multicenter, placebo-controlled, flexible-dose studies (studies 1ndash4) and one double-blind, parallel-group, 6-month, placebo-controlled, fixedflexible-dose study, which included doses in a range of 75 to 225 mg per day in adult outpatients meeting DSM-IV criteria for SAD (study 5). In these five studies, Effexor XR was statistically significantly more effective than placebo on change from baseline to endpoint on the Liebowitz Social Anxiety Scale (LSAS) total score. There was no evidence for any greater effectiveness of the 150 to 225 mg per day group compared to the 75 mg per day group in the 6-month study. Examination of subsets of the population studied did not reveal any differential responsiveness on the basis of gender. There was insufficient information to determine the effect of age or race on outcome in these studies. Table 19: Social Anxiety Disorder Studies Primary Efficacy Measure: LSAS Score Mean Baseline Score (SD) LS Mean Change from Baseline (SE) Placebo Subtracted Difference (95 CI) SD: standard deviation SE: standard error LS Mean: least-squares mean CI: confidence interval. Doses statistically significantly superior to placebo. Difference (drug minus placebo) in least-squares mean change from baseline Panic Disorder The efficacy of Effexor XR as a treatment for Panic Disorder (PD) was established in two double-blind, 12-week, multicenter, placebo-controlled studies in adult outpatients meeting DSM-IV criteria for PD, with or without agoraphobia. Patients received fixed doses of 75 or 150 mg per day in one study (study 1) and 75 or 225 mg per day in the other study (study 2). Efficacy was assessed on the basis of outcomes in three variables: (1) percentage of patients free of full-symptom panic attacks on the Panic and Anticipatory Anxiety Scale (PAAS) (2) mean change from baseline to endpoint on the Panic Disorder Severity Scale (PDSS) total score and (3) percentage of patients rated as responders (much improved or very much improved) on the Clinical Global Impressions (CGI) Improvement scale. In these two studies, Effexor XR was statistically significantly more effective than placebo (for each fixed dose) on all three endpoints, but a dose-response relationship was not clearly established. Examination of subsets of the population studied did not reveal any differential responsiveness on the basis of gender. There was insufficient information to determine the effect of age or race on outcome in these studies. In a longer term study (study 3), adult outpatients meeting DSM-IV criteria for PD who had responded during a 12-week open phase with Effexor XR (75 to 225 mg per day) were randomly assigned to continue the same Effexor XR dose (75, 150, or 225 mg) or switch to placebo for observation for relapse under double-blind conditions. Response during the open phase was defined as le 1 full-symptom panic attack per week during the last 2 weeks of the open phase and a CGI Improvement score of 1 (very much improved) or 2 (much improved). Relapse during the double-blind phase was defined as having 2 or more full-symptom panic attacks per week for 2 consecutive weeks or having discontinued due to loss of effectiveness as determined by the investigators during the study. Randomized patients were in response status for a mean time of 34 days prior to being randomized. In the randomized phase following the 12-week open-label period, patients receiving continued Effexor XR experienced a statistically significantly longer time to relapse. Table 20: Panic Disorder Studies: Primary Efficacy Measure: Whether Free of Full-symptom Panic Attacks Percent of patients Free of Full symptom panic attack Adjusted Odds Ratio to placebo Adjusted Odds Ratio 95 Confidence Interval 95CI: 95 confidence interval without adjusting for multiple dose arms. Odds ratio (drug to placebo) in terms of probability of free of full-symptom panic attacks based on logistic regression model. dagger Doses statistically significantly superior to placebo. Pediatric Patients Two placebo-controlled studies in 766 pediatric patients with MDD and two placebo-controlled studies in 793 pediatric patients with GAD have been conducted with Effexor XR, and the data were not sufficient to support a claim for use in pediatric patients. How SuppliedStorage and Handling Effexor XR reg (venlafaxine hydrochloride) extended-release capsules are available as follows: 37.5 mg, grey cappeach body with W and Effexor XR on the cap and 37.5 on the body. NDC 0008-0837-20, bottle of 15 capsules in unit-of-use package. NDC 0008-0837-21, bottle of 30 capsules in unit-of-use package. NDC 0008-0837-22, bottle of 90 capsules in unit-of-use package. NDC 0008-0837-03, carton of 10 Redipak reg blister strips of 10 capsules each. 75 mg, peach cap and body with W and Effexor XR on the cap and 75 on the body. NDC 0008-0833-20, bottle of 15 capsules in unit-of-use package. NDC 0008-0833-21, bottle of 30 capsules in unit-of-use package. NDC 0008-0833-22, bottle of 90 capsules in unit-of-use package. NDC 0008-0833-03, carton of 10 Redipak reg blister strips of 10 capsules each. 150 mg, dark orange cap and body with W and Effexor XR on the cap and 150 on the body. NDC 0008-0836-20, bottle of 15 capsules in unit-of-use package. NDC 0008-0836-21, bottle of 30 capsules in unit-of-use package. NDC 0008-0836-22, bottle of 90 capsules in unit-of-use package. NDC 0008-0836-03, carton of 10 Redipak reg blister strips of 10 capsules each. Store at controlled room temperature, 20deg to 25degC (68deg to 77degF). The unit-of-use package is intended to be dispensed as a unit. The appearance of these capsules is a trademark of Wyeth Pharmaceuticals. Patient Counseling Information See FDA-approved patient labeling (Medication Guide ). Prescribers or other healthcare professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with Effexor XR and should counsel them in its appropriate use. A patient Medication Guide about Antidepressant Medicines, Depression and Other Serious Mental Illnesses, and Suicidal Thoughts or Actions is available for Effexor XR. The prescriber or healthcare professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have. The complete text of the Medication Guide is reprinted at the end of this document. Patients should be advised of the following issues and should be asked to alert their prescriber if these occur while taking Effexor XR. Suicidal Thoughts and Behaviors Advise patients, their families and caregivers to look for the emergence of suicidality, worsening of depression, and other psychiatric symptoms (anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, psychomotor restlessness, hypomania, mania, other unusual changes in behavior), especially early during treatment and when the dose is adjusted up or down. Such symptoms should be reported to the patients prescriber or health professional, especially if they are severe, abrupt in onset, or were not part of the patients presenting symptoms. Symptoms such as these may be associated with an increased risk for suicidal thinking and behavior and indicate a need for very close monitoring see Boxed Warning and Warnings and Precautions (5.1) . Advise patients taking Effexor XR not to use concomitantly other products containing venlafaxine or desvenlafaxine. Healthcare professionals should instruct patients not to take Effexor XR with an MAOI or within 14 days of stopping an MAOI and to allow 7 days after stopping Effexor XR before starting an MAOI see Contraindications (4.2) . Patients should be cautioned about the risk of serotonin syndrome, with the concomitant use of Effexor XR and triptans, tramadol, amphetamines, tryptophan supplements, with antipsychotics or other dopamine antagonists, or other serotonergic agents s ee Warnings and Precautions (5.2) and Drug Interactions (7.3) . Elevated Blood Pressure Advise patients that they should have regular monitoring of blood pressure when taking Effexor XR see Warnings and Precautions (5.3) . Patients should be cautioned about the concomitant use of Effexor XR and NSAIDs, aspirin, warfarin, or other drugs that affect coagulation since combined use of psychotropic drugs that interfere with serotonin reuptake and these agents has been associated with an increased risk of bleeding see Warnings and Precautions (5.4) . Angle Closure Glaucoma Patients should be advised that taking Effexor XR can cause mild pupillary dilation, which in susceptible individuals, can lead to an episode of angle closure glaucoma. Pre-existing glaucoma is almost always open-angle glaucoma because angle closure glaucoma, when diagnosed, can be treated definitively with iridectomy. Open-angle glaucoma is not a risk factor for angle closure glaucoma. Patients may wish to be examined to determine whether they are susceptible to angle closure, and have a prophylactic procedure (e. g. iridectomy), if they are susceptible see Warnings and Precautions (5.5) . Activation of ManiaHypomania Advise patients, their families and caregivers to observe for signs of activation of maniahypomania see Warnings and Precautions (5.6) . Caution is advised in administering Effexor XR to patients with cardiovascular, cerebrovascular, or lipid metabolism disorders see Adverse Reactions (6.1) . Serum Cholesterol and Triglyceride Elevation Advise patients that elevations in total cholesterol, LDL and triglycerides may occur and that measurement of serum lipids may be considered see Warnings and Precautions (6.3) . Advise patients not to stop taking Effexor XR without talking first with their healthcare professional. Patients should be aware that discontinuation effects may occur when stopping Effexor XR see Warnings and Precautions (5.7) and Adverse Reactions (6.1) . Interference with Cognitive and Motor Performance Caution patients about operating hazardous machinery, including automobiles, until they are reasonably certain that Effexor XR therapy does not adversely affect their ability to engage in such activities. Advise patients to avoid alcohol while taking Effexor XR see Drug Interactions (7.6) . Advise patients to notify their physician if they develop allergic phenomena such as rash, hives, swelling, or difficulty breathing. Advise patients to notify their physician if they become pregnant or intend to become pregnant during therapy see Use in Specific Populations (8.1) . Advise patients to notify their physician if they are breast-feeding an infant see Use in Specific Populations (8.3) . Effexor XR contains spheroids, which release the drug slowly into the digestive tract. The insoluble portion of these spheroids is eliminated, and patients may notice spheroids passing in the stool or via colostomy. Patients should be informed that the active medication has already been absorbed by the time the patient sees the spheroids. Medication Guide Effexor XR (e-fex-or) (venlafaxine hydrochloride) (Extended-Release Capsules) Read the Medication Guide that comes with Effexor XR before you start taking it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your healthcare provider about your medical condition or treatment. Talk with your healthcare provider if there is something you do not understand or want to learn more about. What is the most important information I should know about Effexor XR Effexor XR and other antidepressant medicines may cause serious side effects, including: 1. Suicidal thoughts or actions: Effexor XR and other antidepressant medicines may increase suicidal thoughts or actions in some children, teenagers, or young adults within the first few months of treatment or when the dose is changed. Depression or other serious mental illnesses are the most important causes of suicidal thoughts or actions. Watch for these changes and call your healthcare provider right away if you notice: New or sudden changes in mood, behavior, actions, thoughts, or feelings, especially if severe. Pay particular attention to such changes when Effexor XR is started or when the dose is changed. Keep all follow-up visits with your healthcare provider and call between visits if you are worried about symptoms. Call your healthcare provider right away if you have any of the following symptoms, or call 911 if an emergency, especially if they are new, worse, or worry you: attempts to commit suicide acting on dangerous impulses acting aggressive or violent thoughts about suicide or dying new or worse depression new or worse anxiety or panic attacks feeling agitated, restless, angry or irritable trouble sleeping an increase in activity or talking more than what is normal for you other unusual changes in behavior or mood Visual problems eye pain changes in vision swelling or redness in or around the eye Only some people are at risk for these problems. You may want to undergo an eye examination to see if you are at risk and receive preventative treatment if you are. Call your healthcare provider right away if you have any of the following symptoms, or call 911 if an emergency. Effexor XR may be associated with these serious side effects : 2. Serotonin Syndrome This condition can be life-threatening and may include : agitation, hallucinations, coma or other changes in mental status coordination problems or muscle twitching (overactive reflexes) racing heartbeat, high or low blood pressure sweating or fever nausea, vomiting, or diarrhea muscle rigidity 3. Changes in blood pressure. Effexor XR may: increase your blood pressure. Control high blood pressure before starting treatment and monitor blood pressure regularly 4. Enlarged pupils (mydriasis). 5. Anxiety and insomnia. 6. Changes in appetite or weight. 7. Manichypomanic episodes: greatly increased energy severe trouble sleeping racing thoughts reckless behavior unusually grand ideas excessive happiness or irritability talking more or faster than usual 8. Low salt (sodium) levels in the blood. Elderly people may be at greater risk for this. Symptoms may include: headache weakness or feeling unsteady confusion, problems concentrating or thinking or memory problems 9. Seizures or convulsions. 10. Abnormal bleeding. Effexor XR and other antidepressant medicines may increase your risk of bleeding or bruising, especially if you take the blood thinner warfarin (Coumadin reg. Jantoven reg ), a non-steroidal anti-inflammatory drug (NSAIDs, like ibuprofen or naproxen), or aspirin. 11. Elevated cholesterol. 12. Lung disease and pneumonia. Effexor XR may cause rare lung problems. Symptoms include: worsening shortness of breath cough chest discomfort 13. Severe allergic reactions: trouble breathing swelling of the face, tongue, eyes or mouth rash, itchy welts (hives) or blisters, alone or with fever or joint pain. Do not stop Effexor XR without first talking to your healthcare provider. Stopping Effexor XR too quickly or changing from another antidepressant too quickly may cause serious symptoms including: anxiety, irritability feeling tired, restless or problems sleeping headache, sweating, dizziness electric shock-like sensations, shaking, confusion, nightmares vomiting, nausea, diarrhea What is Effexor XR Effexor XR is a prescription medicine used to treat depression. It is important to talk with your healthcare provider about the risks of treating depression and also the risks of not treating it. You should discuss all treatment choices with your healthcare provider. Effexor XR is also used to treat: Generalized Anxiety Disorder (GAD) Social Anxiety Disorder (SAD) Panic Disorder (PD) Talk to your healthcare provider if you do not think that your condition is getting better with Effexor XR treatment. Who should not take Effexor XR Do not take Effexor XR if you: are allergic to Effexor XR or any of the ingredients in Effexor XR. See the end of this Medication Guide for a complete list of ingredients in Effexor XR . have uncontrolled angle-closure glaucoma take a Monoamine Oxidase Inhibitor (MAOI). Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI, including the antibiotic linezolid. Do not take an MAOI within 7 days of stopping Effexor XR unless directed to do so by your physician. Do not start Effexor XR if you stopped taking an MAOI in the last 2 weeks unless directed to do so by your physician. People who take Effexor XR close in time to an MAOI may have serious or even life-threatening side effects. Get medical help right away if you have any of these symptoms: high fever uncontrolled muscle spasms stiff muscles rapid changes in heart rate or blood pressure confusion loss of consciousness (pass out) What should I tell my healthcare provider before taking Effexor XR Ask if you are not sure. Before starting Effexor XR. tell your healthcare provider if you: Are taking certain drugs such as: Amphetamines Medicines used to treat migraine headaches such as: triptans Medicines used to treat mood, anxiety, psychotic or thought disorders, such as: tricyclic antidepressants lithium SSRIs SNRIs antipsychotic drugs Medicines used to treat pain such as: tramadol Medicines used to thin your blood such as: warfarin Medicines used to treat heartburn such as: Cimetidine Over-the-counter medicines or supplements such as: Aspirin or other NSAIDs Tryptophan St. Johns Wort have heart problems have diabetes have liver problems have kidney problems have thyroid problems have or had seizures or convulsions have bipolar disorder or mania have low sodium levels in your blood have high blood pressure have high cholesterol have or had bleeding problems are pregnant or plan to become pregnant. It is not known if Effexor XR will harm your unborn baby. Talk to your healthcare provider about the benefits and risks of treating depression during pregnancy are breast-feeding or plan to breast-feed. Some Effexor XR may pass into your breast milk. Talk to your healthcare provider about the best way to feed your baby while taking Effexor XR . Tell your healthcare provider about all the medicines that you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Effexor XR and some medicines may interact with each other, may not work as well, or may cause serious side effects. Your healthcare provider or pharmacist can tell you if it is safe to take Effexor XR with your other medicines. Do not start or stop any medicine while taking Effexor XR without talking to your healthcare provider first. If you take Effexor XR. you should not take any other medicines that contain (venlafaxine) including: venlafaxine HCl. How should I take Effexor XR Take Effexor XR exactly as prescribed. Your healthcare provider may need to change the dose of Effexor XR until it is the right dose for you. Effexor XR is to be taken with food. If you miss a dose of Effexor XR. take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take two doses of Effexor XR at the same time. If you take too much Effexor XR. call your healthcare provider or poison control center right away, or get emergency treatment. When switching from another antidepressant to Effexor XR your doctor may want to lower the dose of the initial antidepressant first to avoid side effects What should I avoid while taking Effexor XR Effexor XR can cause sleepiness or may affect your ability to make decisions, think clearly, or react quickly. You should not drive, operate heavy machinery, or do other dangerous activities until you know how Effexor XR affects you. Do not drink alcohol while using Effexor XR . What are the possible side effects of Effexor XR Effexor XR may cause serious side effects, including: See What is the most important information I should know about Effexor XR Increased cholesterol - have your cholesterol checked regularly Newborns whose mothers take Effexor XR in the third trimester may have problems right after birth including: problems feeding and breathing seizures shaking, jitteriness or constant crying Angle-closure glaucoma Common possible side effects in people who take Effexor XR include. unusual dreams sexual problems loss of appetite, constipation, diarrhea, nausea or vomiting, or dry mouth feeling tired, fatigued or overly sleepy change in sleep habits, problems sleeping yawning tremor or shaking dizziness, blurred vision sweating feeling anxious, nervous or jittery headache increase in heart rate Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of Effexor XR. For more information, ask your healthcare provider or pharmacist. CALL YOUR DOCTOR FOR MEDICAL ADVICE ABOUT SIDE EFFECTS. YOU MAY REPORT SIDE EFFECTS TO THE FDA AT 1-800-FDA-1088. How should I store Effexor XR Store Effexor XR at room temperature between 68degF and 77degF (20degC to 25degC). Keep Effexor XR in a dry place. Keep Effexor XR and all medicines out of the reach of children. General information about EFFEXOR Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Effexor XR for a condition for which it was not prescribed. Do not give Effexor XR to other people, even if they have the same condition. It may harm them. This Medication Guide summarizes the most important information about Effexor XR. If you would like more information, talk with your healthcare provider. You may ask your healthcare provider or pharmacist for information about Effexor XR that is written for healthcare professionals. For more information about Effexor XR call 1-800-438-1985 or go to Effexor XR . What are the ingredients in Effexor XR Active ingredient: (venlafaxine) Extended-Release Capsules. cellulose, ethylcellulose, gelatin, hypromellose, iron oxides, and titanium dioxide. This Medication Guide has been approved by the U. S. Food and Drug Administration for all antidepressants. This products label may have been updated. For current full prescribing information, please visit pfizer PRINCIPAL DISPLAY PANEL - 37.5 mg Capsule Bottle Label ALWAYS DISPENSE WITH MEDICATION GUIDE Pfizer NDC 0008-0837-20 Effexor XR reg (venlafaxine HCl) Extended-Release Capsules 15 Capsules Rx only PRINCIPAL DISPLAY PANEL - 37.5 mg Capsule Blister Pack Effexor XR reg (venlafaxine HCl) Extended-Release Capsules 37.5 mg Wyeth reg Phila. PA 19101 PRINCIPAL DISPLAY PANEL - 37.5 mg Capsule Blister Pack Carton ALWAYS DISPENSE WITH MEDICATION GUIDE NDC 0008-0837-03 Effexor XR reg (venlafaxine HCl) Extended-Release Capsules 10 Redipak reg Blister Strips of 10 Capsules 100 Capsules PRINCIPAL DISPLAY PANEL - 75 mg Capsule Bottle Label ALWAYS DISPENSE WITH MEDICATION GUIDE Effexor XR reg (venlafaxine HCl) Extended-Release Capsules PRINCIPAL DISPLAY PANEL - 75 mg Capsule Blister Pack Effexor XR reg (venlafaxine HCl) Extended-Release Capsules 75 mg Wyeth reg Phila. PA 19101 PRINCIPAL DISPLAY PANEL - 75 mg Capsule Blister Pack Carton ALWAYS DISPENSE WITH MEDICATION GUIDE NDC 0008-0833-03 Effexor XR reg (venlafaxine HCl) Extended-Release Capsules 10 Redipak reg Blister Strips of 10 Capsules 100 Capsules PRINCIPAL DISPLAY PANEL - 150 mg Capsule Bottle Label ALWAYS DISPENSE WITH MEDICATION GUIDE Effexor XR reg (venlafaxine HCl) Extended-Release Capsules PRINCIPAL DISPLAY PANEL - 150 mg Capsule Blister Pack Effexor XR reg (venlafaxine HCl) Extended-Release Capsules 150 mg Wyeth reg Phila. PA 19101 PRINCIPAL DISPLAY PANEL - 150 mg Capsule Blister Pack Carton ALWAYS DISPENSE WITH MEDICATION GUIDE NDC 0008-0836-03 Effexor XR reg (venlafaxine HCl) Extended-Release Capsules 10 Redipak reg Blister Strips of 10 Capsules 100 Capsules
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