HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights ------WARNINGS AND PRECAUTIONS------do not include all the information needed to use ESTRADIOL VALERATE TABLETS, AND ESTRADIOL VALERATE AND DIENOGEST TABLETS safely and effectively. See full prescribing x 9DVFXODU ULVNV 6WRS HVWUDGLRO YDOHUDWH WDEOHWV DQG HVWUDGLRO YDOHUDWH information for ESTRADIOL VALERATE TABLETS, AND DQG GLHQRJHVW WDEOHWV LI D WKURPERWLF HYHQW RFFXUV 6WRS HVWUDGLRO ESTRADIOL VALERATE AND DIENOGEST TABLETS. YDOHUDWH WDEOHWV DQG HVWUDGLRO YDOHUDWH DQG GLHQRJHVW WDEOHWV DW OHDVW ZHHNV EHIRUH DQG WKURXJK ZHHNV DIWHU PDMRU VXUJHU\ 6WDUW HVWUDGLRO ESTRADIOL VALERATE tablets, and ESTRADIOL VALERATE and YDOHUDWH WDEOHWV DQG HVWUDGLRO YDOHUDWH DQG GLHQRJHVW WDEOHWV QR HDUOLHU DIENOGEST tablets, for oral use WKDQ ZHHNV DIWHU GHOLYHU\ LQ ZRPHQ ZKR DUH QRW EUHDVWIHHGLQJ x /LYHU GLVHDVH 'LVFRQWLQXH HVWUDGLRO YDOHUDWH WDEOHWV DQG Initial U.S. Approval: 2010 HVWUDGLRO YDOHUDWH DQG GLHQRJHVW WDEOHWV LI MDXQGLFH RFFXUV x +LJK EORRG SUHVVXUH 'R QRW SUHVFULEH HVWUDGLRO YDOHUDWH WDEOHWV WARNING: CIGARETTE SMOKING AND SERIOUS DQG HVWUDGLRO YDOHUDWH DQG GLHQRJHVW WDEOHWV IRU ZRPHQ ZLWK CARDIOVASCULAR EVENTS XQFRQWUROOHG K\SHUWHQVLRQ RU K\SHUWHQVLRQ ZLWK YDVFXODU See full prescribing information for complete boxed warning. GLVHDVH x Women over 35 years old who smoke should not use estradiol x &DUERK\GUDWH DQG OLSLG PHWDEROLF HIIHFWV 0RQLWRU SUHGLDEHWLF valerate tablets, and estradiol valerate and dienogest tablets. DQG GLDEHWLF ZRPHQ WDNLQJ HVWUDGLRO YDOHUDWH WDEOHWV DQG (4) HVWUDGLRO YDOHUDWH DQG GLHQRJHVW WDEOHWV &RQVLGHU DQ DOWHUQDWH x Cigarette smoking increases the risk of serious cardiovascular FRQWUDFHSWLYH PHWKRG IRU ZRPHQ ZLWK XQFRQWUROOHG events from combination oral contraceptive (COC) use. (4) G\VOLSLGHPLD ------INDICATIONS AND USAGE------x +HDGDFKH (YDOXDWH VLJQLILFDQW FKDQJH LQ KHDGDFKHV DQG GLVFRQWLQXH HVWUDGLRO YDOHUDWH WDEOHWV DQG HVWUDGLRO YDOHUDWH DQG x (VWUDGLRO YDOHUDWH WDEOHWV DQG HVWUDGLRO YDOHUDWH DQG GLHQRJHVW WDEOHWV GLHQRJHVW WDEOHWV LI LQGLFDWHG DUH DQ HVWURJHQSURJHVWLQ &2& LQGLFDWHG IRU XVH E\ ZRPHQ WR x 8WHULQH EOHHGLQJ (YDOXDWH LUUHJXODU EOHHGLQJ RU DPHQRUUKHD SUHYHQW SUHJQDQF\ 7KH HIILFDF\ RI HVWUDGLRO YDOHUDWH WDEOHWV DQG HVWUDGLRO YDOHUDWH DQG GLHQRJHVW WDEOHWV LQ ZRPHQ ZLWK D ERG\ PDVV x &<3$ LQGXFWLRQ :RPHQ WDNLQJ VWURQJ &<3$ LQGXFHUV IRU LQGH[ %0, RI JUHDWHU WKDQ NJP KDV QRW EHHQ HYDOXDWHG H[DPSOH FDUEDPD]HSLQH SKHQ\WRLQ ULIDPSLFLQ DQG 6W -RKQ¶V ZRUW VKRXOG QRW FKRRVH HVWUDGLRO YDOHUDWH WDEOHWV DQG HVWUDGLRO YDOHUDWH DQG ------DOSAGE AND ADMINISTRATION------GLHQRJHVW WDEOHWV DV WKHLU RUDO FRQWUDFHSWLYH GXH WR WKH SRVVLELOLW\ RI GHFUHDVHG FRQWUDFHSWLYH HIILFDF\ x 7DNH RQH WDEOHW GDLO\ E\ PRXWK DW WKH VDPH WLPH HYHU\ GD\ x 7DEOHWV PXVW EH WDNHQ LQ WKH RUGHU GLUHFWHG RQ WKH EOLVWHU SDFN ------ADVERSE REACTIONS------x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Revised: 10/2015 FULL PRESCRIBING INFORMATION: CONTENTS* 7 DRUG INTERACTIONS WARNING: CIGARETTE SMOKING AND SERIOUS (IIHFWV RI 2WKHU 'UXJV RQ &RPELQHG 2UDO &RQWUDFHSWLYHV CARDIOVASCULAR EVENTS (IIHFWV RI &RPELQHG 2UDO &RQWUDFHSWLYHV RQ 2WKHU 'UXJV 1 INDICATIONS AND USAGE ,QWHUIHUHQFH ZLWK /DERUDWRU\ 7HVWV 2UDO &RQWUDFHSWLRQ 8 USE IN SPECIFIC POPULATIONS 2 DOSAGE AND ADMINISTRATION 3UHJQDQF\ +RZ WR 7DNH (VWUDGLRO 9DOHUDWH 7DEOHWV DQG (VWUDGLRO 9DOHUDWH DQG 1XUVLQJ 0RWKHUV 'LHQRJHVW 7DEOHWV 3HGLDWULF 8VH +RZ WR 6WDUW (VWUDGLRO 9DOHUDWH 7DEOHWV DQG (VWUDGLRO 9DOHUDWH DQG *HULDWULF 8VH 'LHQRJHVW 7DEOHWV 3DWLHQWV ZLWK 5HQDO ,PSDLUPHQW $GYLFH LQ &DVH RI *DVWURLQWHVWLQDO 'LVWXUEDQFHV 3DWLHQWV ZLWK +HSDWLF ,PSDLUPHQW 3 DOSAGE FORMS AND STRENGTHS %RG\ 0DVV ,QGH[ 4 CONTRAINDICATIONS 10 OVERDOSAGE 5 WARNINGS AND PRECAUTIONS 11 DESCRIPTION 7KURPERHPEROLF 'LVRUGHUV DQG 2WKHU 9DVFXODU 3UREOHPV 12 CLINICAL PHARMACOLOGY &DUFLQRPD RI WKH %UHDVWV DQG 5HSURGXFWLYH 2UJDQV 0HFKDQLVP RI $FWLRQ /LYHU 'LVHDVH 3KDUPDFRG\QDPLFV +LJK %ORRG 3UHVVXUH 3KDUPDFRNLQHWLFV *DOOEODGGHU 'LVHDVH 13 NONCLINICAL TOXICOLOGY &DUERK\GUDWH DQG /LSLG 0HWDEROLF (IIHFWV &DUFLQRJHQHVLV 0XWDJHQHVLV ,PSDLUPHQW RI )HUWLOLW\ +HDGDFKH $QLPDO 7R[LFRORJ\ DQGRU 3KDUPDFRORJ\ %OHHGLQJ ,UUHJXODULWLHV 14 CLINICAL STUDIES &2& 8VH %HIRUH RU 'XULQJ (DUO\ 3UHJQDQF\ 2UDO &RQWUDFHSWLYH &OLQLFDO 7ULDOV 'HSUHVVLRQ 16 HOW SUPPLIED/STORAGE AND HANDLING ,QWHUIHUHQFH ZLWK /DERUDWRU\ 7HVWV +RZ 6XSSOLHG 0RQLWRULQJ 6WRUDJH 'UXJ ,QWHUDFWLRQV 17 PATIENT COUNSELING INFORMATION 2WKHU &RQGLWLRQV 6 ADVERSE REACTIONS 6HFWLRQV RU VXEVHFWLRQV RPLWWHG IURP WKH IXOO SUHVFULELQJ LQIRUPDWLRQ DUH QRW &OLQLFDO 7ULDOV ([SHULHQFH OLVWHG 3RVWPDUNHWLQJ ([SHULHQFH
FULL PRESCRIBING INFORMATION
WARNING: CIGARETTE SMOKING AND SERIOUS CARDIOVASCULAR EVENTS Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptives (COC) use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked. For this reason, COCs should not be used by women who are over 35 years of age and smoke. [See Contraindications (4).]
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5.3 Liver Disease 'LVFRQWLQXH HVWUDGLRO YDOHUDWH WDEOHWV DQG HVWUDGLRO YDOHUDWH DQG GLHQRJHVW WDEOHWV LI MDXQGLFH GHYHORSV 6WHURLG KRUPRQHV PD\ EH SRRUO\ PHWDEROL]HG LQ SDWLHQWV ZLWK LPSDLUHG OLYHU IXQFWLRQ $FXWH RU FKURQLF GLVWXUEDQFHV RI OLYHU IXQFWLRQ PD\ QHFHVVLWDWH WKH GLVFRQWLQXDWLRQ RI &2& XVH XQWLO PDUNHUV RI OLYHU IXQFWLRQ UHWXUQ WR QRUPDO DQG &2& FDXVDWLRQ KDV EHHQ H[FOXGHG
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5.6 Carbohydrate and Lipid Metabolic Effects &DUHIXOO\ PRQLWRU SUHGLDEHWLF DQG GLDEHWLF ZRPHQ ZKR DUH WDNLQJ HVWUDGLRO YDOHUDWH WDEOHWV DQG HVWUDGLRO YDOHUDWH DQG GLHQRJHVW WDEOHWV &2&V PD\ GHFUHDVH JOXFRVH WROHUDQFH LQ D GRVHUHODWHG IDVKLRQ
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5.7 Headache ,I D ZRPDQ WDNLQJ HVWUDGLRO YDOHUDWH WDEOHWV DQG HVWUDGLRO YDOHUDWH DQG GLHQRJHVW WDEOHWV GHYHORSV QHZ KHDGDFKHV WKDW DUH UHFXUUHQW SHUVLVWHQW RU VHYHUH HYDOXDWH WKH FDXVH DQG GLVFRQWLQXH HVWUDGLRO YDOHUDWH WDEOHWV DQG HVWUDGLRO YDOHUDWH DQG GLHQRJHVW WDEOHWV LI LQGLFDWHG
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5.9 COC Use Before or During Early Pregnancy ([WHQVLYH HSLGHPLRORJLFDO VWXGLHV KDYH UHYHDOHG QR LQFUHDVHG ULVN RI ELUWK GHIHFWV LQ ZRPHQ ZKR KDYH XVHG RUDO FRQWUDFHSWLYHV SULRU WR SUHJQDQF\ 6WXGLHV DOVR GR QRW VXJJHVW D WHUDWRJHQLF HIIHFW SDUWLFXODUO\ LQ VR IDU DV FDUGLDF DQRPDOLHV DQG OLPEUHGXFWLRQ GHIHFWV DUH FRQFHUQHG ZKHQ WDNHQ LQDGYHUWHQWO\ GXULQJ HDUO\ SUHJQDQF\ 2UDO FRQWUDFHSWLYH XVH VKRXOG EH GLVFRQWLQXHG LI SUHJQDQF\ LV FRQILUPHG
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5.10 Depression :RPHQ ZLWK D KLVWRU\ RI GHSUHVVLRQ VKRXOG EH FDUHIXOO\ REVHUYHG DQG HVWUDGLRO YDOHUDWH WDEOHWV DQG HVWUDGLRO YDOHUDWH DQG GLHQRJHVW WDEOHWV GLVFRQWLQXHG LI GHSUHVVLRQ UHFXUV WR D VHULRXV GHJUHH
5.11 Interference with Laboratory Tests 7KH XVH RI &2&V PD\ FKDQJH WKH UHVXOWV RI VRPH ODERUDWRU\ WHVWV VXFK DV FRDJXODWLRQ IDFWRUV OLSLGV JOXFRVH WROHUDQFH DQG ELQGLQJ SURWHLQV :RPHQ RQ WK\URLG KRUPRQH UHSODFHPHQW WKHUDS\ PD\ QHHG LQFUHDVHG GRVHV RI WK\URLG KRUPRQH EHFDXVH VHUXP FRQFHQWUDWLRQV RI WK\URLGELQGLQJ JOREXOLQ LQFUHDVH ZLWK XVH RI &2&V [see Clinical Pharmacology (12.3)]
5.12 Monitoring $ ZRPDQ ZKR LV WDNLQJ &2&V VKRXOG KDYH D \HDUO\ YLVLW ZLWK KHU KHDOWKFDUH SURYLGHU IRU D EORRG SUHVVXUH FKHFN DQG IRU RWKHU LQGLFDWHG KHDOWKFDUH
5.13 Drug Interactions :RPHQ ZKR WDNH PHGLFDWLRQV WKDW DUH VWURQJ F\WRFKURPH 3 $ &<3$ LQGXFHUV IRU H[DPSOH FDUEDPD]HSLQH SKHQ\WRLQ ULIDPSLFLQ DQG 6W -RKQ¶V ZRUW VKRXOG QRW FKRRVH HVWUDGLRO YDOHUDWH WDEOHWV DQG HVWUDGLRO YDOHUDWH DQG GLHQRJHVW WDEOHWV DV WKHLU RUDO FRQWUDFHSWLYH ZKLOH XVLQJ WKHVH LQGXFHUV DQG IRU DW OHDVW GD\V DIWHU GLVFRQWLQXDWLRQ RI WKHVH LQGXFHUV GXH WR WKH SRVVLELOLW\ RI GHFUHDVHG FRQWUDFHSWLYH HIILFDF\ [See Drug Interactions (7.1) and Clinical Pharmacology (12.3).]
5.14 Other Conditions ,Q ZRPHQ ZLWK KHUHGLWDU\ DQJLRHGHPD H[RJHQRXV HVWURJHQV PD\ LQGXFH RU H[DFHUEDWH V\PSWRPV RI DQJLRHGHPD &KORDVPD PD\ RFFDVLRQDOO\ RFFXU HVSHFLDOO\ LQ ZRPHQ ZLWK D KLVWRU\ RI FKORDVPD JUDYLGDUXP :RPHQ ZLWK D WHQGHQF\ WR FKORDVPD VKRXOG DYRLG H[SRVXUH WR WKH VXQ RU XOWUDYLROHW UDGLDWLRQ ZKLOH WDNLQJ &2&V
6 ADVERSE REACTIONS 7KH IROORZLQJ VHULRXV DGYHUVH UHDFWLRQV ZLWK WKH XVH RI &2&V DUH GLVFXVVHG HOVHZKHUH LQ WKH ODEHOLQJ x 6HULRXV FDUGLRYDVFXODU HYHQWV DQG VWURNH [see Boxed Warning and Warnings and Precautions (5.1)] x 9DVFXODU HYHQWV [see Warnings and Precautions (5.1)] x /LYHU GLVHDVH [see Warnings and Precautions (5.3)]
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6.1 Clinical Trials Experience %HFDXVH FOLQLFDO WULDOV DUH FRQGXFWHG XQGHU ZLGHO\ YDU\LQJ FRQGLWLRQV DGYHUVH UHDFWLRQ UDWHV REVHUYHG LQ WKH FOLQLFDO WULDOV RI D GUXJ FDQQRW EH GLUHFWO\ FRPSDUHG WR UDWHV LQ WKH FOLQLFDO WULDOV RI DQRWKHU GUXJ DQG PD\ QRW UHIOHFW WKH UDWHV REVHUYHG LQ SUDFWLFH
Contraception Studies $ WRWDO RI ZRPHQ WR \HDUV RI DJH ZKR WRRN DW OHDVW RQH GRVH RI HVWUDGLRO YDOHUDWH WDEOHWV DQG HVWUDGLRO YDOHUDWH DQG GLHQRJHVW WDEOHWV ZHUH HQUROOHG LQ IRXU FOLQLFDO SKDVH WULDOV $ WRWDO RI VXEMHFWV ZHUH LQFOXGHG LQ WZR FOLQLFDO SKDVH VWXGLHV ZLWK D WUHDWPHQW GXUDWLRQ XS WR F\FOHV ZLWK HVWUDGLRO YDOHUDWH WDEOHWV DQG HVWUDGLRO YDOHUDWH DQG GLHQRJHVW WDEOHWV DV DQ RUDO FRQWUDFHSWLYH [See Clinical Studies (14.1)]
Adverse Reactions Leading to Study Discontinuation: RI WKH ZRPHQ GLVFRQWLQXHG IURP WKH FOLQLFDO WULDOV GXH WR DQ DGYHUVH UHDFWLRQ WKH PRVW IUHTXHQW DGYHUVH UHDFWLRQV OHDGLQJ WR GLVFRQWLQXDWLRQ ZHUH PHQVWUXDO GLVRUGHU PHWURUUKDJLD PHQRUUKDJLD PHQVWUXDWLRQ LUUHJXODU JHQLWDO KHPRUUKDJH YDJLQDO KHPRUUKDJH G\VIXQFWLRQDO XWHULQH EOHHGLQJ PRRG FKDQJHV GHSUHVVLRQ PRRG VZLQJV PRRG DOWHUHG GHSUHVVHG PRRG G\VWK\PLF GLVRUGHU FU\LQJ DFQH KHDGDFKH LQFOXGLQJ PLJUDLQHV DQG ZHLJKW LQFUHDVHG Common Adverse Reactions (greater than or equal to 2%): KHDGDFKH LQFOXGLQJ PLJUDLQHV EUHDVW SDLQ GLVFRPIRUW RU WHQGHUQHVV PHQVWUXDO GLVRUGHUV PHWURUUKDJLD PHQVWUXDWLRQ LUUHJXODU PHQRUUKDJLD YDJLQDO KHPRUUKDJH G\VIXQFWLRQDO XWHULQH EOHHGLQJ JHQLWDO KHPRUUKDJH DEQRUPDO ZLWKGUDZDO EOHHGLQJ XWHULQH KHPRUUKDJH QDXVHD RU YRPLWLQJ DFQH PRRG FKDQJHV GHSUHVVLRQ PRRG VZLQJV GHSUHVVHG PRRG PRRG DOWHUHG DIIHFW ODELOLW\ G\VWK\PLF GLVRUGHU FU\LQJ DQG LQFUHDVHG ZHLJKW
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7.1 Effects of Other Drugs on Combined Oral Contraceptives Substances diminishing the efficacy of COCs: 'LHQRJHVW LV D VXEVWUDWH RI &<3$ :RPHQ ZKR WDNH PHGLFDWLRQV WKDW DUH VWURQJ &<3$ LQGXFHUV VKRXOG QRW FKRRVH HVWUDGLRO YDOHUDWH WDEOHWV DQG HVWUDGLRO YDOHUDWH DQG GLHQRJHVW WDEOHWV DV WKHLU RUDO FRQWUDFHSWLYH ZKLOH XVLQJ WKHVH LQGXFHUV DQG IRU DW OHDVW GD\V DIWHU GLVFRQWLQXDWLRQ RI WKHVH LQGXFHUV GXH WR WKH SRVVLELOLW\ RI LQFUHDVHG EUHDNWKURXJK EOHHGLQJ DQGRU GHFUHDVHG FRQWUDFHSWLYH HIILFDF\
'UXJV RU KHUEDO SURGXFWV WKDW LQGXFH FHUWDLQ HQ]\PHV LQFOXGLQJ &<3$ PD\ GHFUHDVH WKH HIIHFWLYHQHVV RI &2&V RU LQFUHDVH EUHDNWKURXJK EOHHGLQJ 6RPH GUXJV RU KHUEDO SURGXFWV WKDW PD\ GHFUHDVH WKH HIIHFWLYHQHVV RI KRUPRQDO FRQWUDFHSWLYHV LQFOXGH SKHQ\WRLQ EDUELWXUDWHV FDUEDPD]HSLQH ERVHQWDQ IHOEDPDWH JULVHRIXOYLQ R[FDUED]HSLQH ULIDPSLQ WRSLUDPDWH DQG SURGXFWV FRQWDLQLQJ 6W -RKQ¶V ZRUW ,QWHUDFWLRQV EHWZHHQ RUDO FRQWUDFHSWLYHV DQG RWKHU GUXJV PD\ OHDG WR EUHDNWKURXJK EOHHGLQJ DQGRU FRQWUDFHSWLYH IDLOXUH &RXQVHO ZRPHQ WR XVH DQ DOWHUQDWLYH PHWKRG RI FRQWUDFHSWLRQ RU D EDFNXS PHWKRG ZKHQ HQ]\PH LQGXFHUV DUH XVHG ZLWK &2&V DQG WR FRQWLQXH EDFNXS FRQWUDFHSWLRQ IRU GD\V DIWHU GLVFRQWLQXLQJ WKH HQ]\PH LQGXFHU WR HQVXUH FRQWUDFHSWLYH UHOLDELOLW\
0XOWLSOH GRVH FRDGPLQLVWUDWLRQ RI VWURQJ &<3$ LQGXFHU ULIDPSLQ ZLWK HVWUDGLRO YDOHUDWHGLHQRJHVW WDEOHWV LQ KHDOWK\ SRVWPHQRSDXVDO ZRPHQ OHG WR D GHFUHDVH LQ GLHQRJHVW DQG HVWUDGLRO V\VWHPLF H[SRVXUH DW VWHDG\ VWDWH [See Clinical Pharmacology (12.3).]
Substances Increasing the Systemic Exposure of COCs (enzyme inhibitors): &RQFRPLWDQW DGPLQLVWUDWLRQ RI PRGHUDWH RU VWURQJ &<3$ LQKLELWRUV OLNH D]ROH DQWLIXQJDOV IRU H[DPSOH NHWRFRQD]ROH LWUDFRQD]ROH YRULFRQD]ROH IOXFRQD]ROH YHUDSDPLO PDFUROLGHV IRU H[DPSOH FODULWKURP\FLQ HU\WKURP\FLQ GLOWLD]HP DQG JUDSHIUXLW LQFUHDVHG WKH VHUXP FRQFHQWUDWLRQV RI ERWK HVWUDGLRO DQG GLHQRJHVW
,Q D PXOWLSOH GRVH VWXG\ LQYHVWLJDWLQJ WKH HIIHFW RI &<3$ LQKLELWRUV NHWRFRQD]ROH DQG HU\WKURP\FLQ RQ HVWUDGLRO YDOHUDWH WDEOHWV DQG HVWUDGLRO YDOHUDWH DQG GLHQRJHVW WDEOHWV VWHDG\ VWDWH HVWUDGLRO DQG GLHQRJHVW H[SRVXUHV ZHUH LQFUHDVHG ZKHQ FRDGPLQLVWHUHG ZLWK NHWRFRQD]ROH RU HU\WKURP\FLQ [see Clinical Pharmacology 12.3]
Human Immunodeficiency Virus (HIV)/Hepatitis C Virus (HCV) Protease Inhibitors and Non-Nucleoside Reverse Transcriptase Inhibitors: 6LJQLILFDQW FKDQJHV LQFUHDVH DQG GHFUHDVH LQ SODVPD FRQFHQWUDWLRQV RI HVWURJHQ DQG SURJHVWLQ KDYH EHHQ QRWHG LQ VRPH FDVHV RI FRDGPLQLVWUDWLRQ RI +,9+&9 SURWHDVH LQKLELWRUV RU ZLWK QRQQXFOHRVLGH UHYHUVH WUDQVFULSWDVH LQKLELWRUV
Antibiotics: 7KHUH KDYH EHHQ UHSRUWV RI SUHJQDQF\ ZKLOH WDNLQJ KRUPRQDO FRQWUDFHSWLYHV DQG DQWLELRWLFV EXW FOLQLFDO SKDUPDFRNLQHWLF VWXGLHV KDYH QRW VKRZQ FRQVLVWHQW HIIHFWV RI DQWLELRWLFV RQ SODVPD FRQFHQWUDWLRQV RI V\QWKHWLF VWHURLGV
7.2 Effects of Combined Oral Contraceptives on Other Drugs &2&V FRQWDLQLQJ HWKLQ\O HVWUDGLRO PD\ LQKLELW WKH PHWDEROLVP RI RWKHU FRPSRXQGV &2&V KDYH EHHQ VKRZQ WR VLJQLILFDQWO\ GHFUHDVH SODVPD FRQFHQWUDWLRQV RI ODPRWULJLQH OLNHO\ GXH WR LQGXFWLRQ RI ODPRWULJLQH JOXFXURQLGDWLRQ 7KLV PD\ UHGXFH VHL]XUH FRQWURO WKHUHIRUH GRVDJH DGMXVWPHQWV RI ODPRWULJLQH PD\ EH QHFHVVDU\ &RQVXOW WKH ODEHOLQJ RI WKH FRQFXUUHQWO\XVHG GUXJ WR REWDLQ IXUWKHU LQIRUPDWLRQ DERXW LQWHUDFWLRQV ZLWK &2&V RU WKH SRWHQWLDO IRU HQ]\PH DOWHUDWLRQV [See Clinical Pharmacology (12.3).]
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7.3 Interference with Laboratory Tests 7KH XVH RI FRQWUDFHSWLYH VWHURLGV PD\ LQIOXHQFH WKH UHVXOWV RI FHUWDLQ ODERUDWRU\ WHVWV VXFK DV FRDJXODWLRQ IDFWRUV OLSLGV JOXFRVH WROHUDQFH DQG ELQGLQJ SURWHLQV [see Warnings and Precautions (5.11) and Drug Interactions (7.2)]
8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy 7KHUH LV OLWWOH RU QR LQFUHDVHG ULVN RI ELUWK GHIHFWV LQ ZRPHQ ZKR LQDGYHUWHQWO\ XVH &2&V GXULQJ HDUO\ SUHJQDQF\ (SLGHPLRORJLF VWXGLHV DQG PHWDDQDO\VHV KDYH QRW IRXQG DQ LQFUHDVHG ULVN RI JHQLWDO RU QRQJHQLWDO ELUWK GHIHFWV LQFOXGLQJ FDUGLDF DQRPDOLHV DQG OLPEUHGXFWLRQ GHIHFWV IROORZLQJ H[SRVXUH WR ORZ GRVH &2&V SULRU WR FRQFHSWLRQ RU GXULQJ HDUO\ SUHJQDQF\
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:RPHQ ZKR GR QRW EUHDVWIHHG PD\ VWDUW &2&V QR HDUOLHU WKDQ IRXU ZHHNV SRVWSDUWXP 8.3 Nursing Mothers :KHQ SRVVLEOH DGYLVH WKH QXUVLQJ PRWKHU WR XVH RWKHU IRUPV RI FRQWUDFHSWLRQ XQWLO VKH KDV ZHDQHG KHU FKLOG (VWURJHQFRQWDLQLQJ &2&V FDQ UHGXFH PLON SURGXFWLRQ LQ EUHDVWIHHGLQJ PRWKHUV 7KLV LV OHVV OLNHO\ WR RFFXU RQFH EUHDVWIHHGLQJ LV ZHOOHVWDEOLVKHG KRZHYHU LW FDQ RFFXU DW DQ\ WLPH LQ VRPH ZRPHQ 6PDOO DPRXQWV RI RUDO FRQWUDFHSWLYH VWHURLGV DQGRU PHWDEROLWHV DUH SUHVHQW LQ EUHDVW PLON
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8.5 Geriatric Use (VWUDGLRO YDOHUDWH WDEOHWV DQG HVWUDGLRO YDOHUDWH DQG GLHQRJHVW WDEOHWV KDYH QRW EHHQ VWXGLHG LQ SRVWPHQRSDXVDO ZRPHQ DQG LV QRW LQGLFDWHG LQ WKLV SRSXODWLRQ
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8.7 Patients with Hepatic Impairment 7KH SKDUPDFRNLQHWLFV RI HVWUDGLRO YDOHUDWH WDEOHWV DQG HVWUDGLRO YDOHUDWH DQG GLHQRJHVW WDEOHWV KDYH QRW EHHQ VWXGLHG LQ VXEMHFWV ZLWK KHSDWLF LPSDLUPHQW 6WHURLG KRUPRQHV PD\ EH SRRUO\ PHWDEROL]HG LQ SDWLHQWV ZLWK LPSDLUHG OLYHU IXQFWLRQ $FXWH RU FKURQLF GLVWXUEDQFHV RI OLYHU IXQFWLRQ PD\ QHFHVVLWDWH WKH GLVFRQWLQXDWLRQ RI &2& XVH XQWLO PDUNHUV RI OLYHU IXQFWLRQ UHWXUQ WR QRUPDO [See Contraindications (4) and Warnings and Precautions (5.3).]
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The more pills missed and the closer they are to the end of the cycle, the higher the risk of a pregnancy. You should call your healthcare provider if you are unsure whether you are already pregnant. If you are still not sure of what to do about the pills you have missed: x &DOO \RXU KHDOWKFDUH SURYLGHU x 8VH EDFNXS FRQWUDFHSWLRQ VXFK DV FRQGRPV DQG VSHUPLFLGHV DQ\WLPH \RX KDYH VH[ DQG NHHS WDNLQJ SLOO HDFK GD\ Who Should Not Take Estradiol Valerate Tablets, and Estradiol Valerate and Dienogest Tablets? ,I DQ\ RI WKHVH FRQGLWLRQV KDSSHQ IRU WKH ILUVW WLPH ZKLOH XVLQJ HVWUDGLRO YDOHUDWH WDEOHWV DQG HVWUDGLRO YDOHUDWH DQG GLHQRJHVW WDEOHWV VWRS WDNLQJ HVWUDGLRO YDOHUDWH WDEOHWV DQG HVWUDGLRO YDOHUDWH DQG GLHQRJHVW WDEOHWV ULJKW DZD\ DQG WDON WR \RXU KHDOWKFDUH SURYLGHU $OVR GR QRW WDNH ELUWK FRQWURO SLOOV LI \RX x 6PRNH DQG DUH RYHU \HDUV ROG x $UH SUHJQDQW x +DYH DQ\ XQH[SODLQHG EOHHGLQJ IURP WKH YDJLQD %LUWK FRQWURO SLOOV PD\ QRW EH D JRRG FKRLFH IRU \RX LI \RX KDYH HYHU KDG MDXQGLFH \HOORZLQJ RI WKH VNLQ RU H\HV FDXVHG E\ SUHJQDQF\ DOVR FDOOHG FKROHVWDVLV RI SUHJQDQF\ What Else Should I Know about Taking Estradiol Valerate Tablets, and Estradiol Valerate and Dienogest Tablets? %LUWK FRQWURO SLOOV GR QRW SURWHFW \RX DJDLQVW DQ\ VH[XDOO\ WUDQVPLWWHG GLVHDVH LQFOXGLQJ +,9 WKH YLUXV WKDW FDXVHV $,'6 'R QRW VNLS DQ\ SLOOV HYHQ LI \RX GR QRW KDYH VH[ RIWHQ ,I \RX PLVV D SHULRG \RX FRXOG EH SUHJQDQW +RZHYHU VRPH ZRPHQ PLVV SHULRGV RU KDYH OLJKW SHULRGV RQ ELUWK FRQWURO SLOOV HYHQ ZKHQ WKH\ DUH QRW SUHJQDQW &RQWDFW \RXU KHDOWKFDUH SURYLGHU IRU DGYLFH LI \RX x 7KLQN \RX DUH SUHJQDQW x 0LVV RQH SHULRG DQG KDYH QRW WDNHQ \RXU ELUWK FRQWURO SLOOV DFFRUGLQJ WR GLUHFWLRQV x 0LVV WZR SHULRGV LQ D URZ %LUWK FRQWURO SLOOV VKRXOG QRW EH WDNHQ GXULQJ SUHJQDQF\ +RZHYHU ELUWK FRQWURO SLOOV WDNHQ E\ DFFLGHQW GXULQJ SUHJQDQF\ DUH QRW NQRZQ WR FDXVH ELUWK GHIHFWV ,I \RX DUH EUHDVWIHHGLQJ FRQVLGHU DQRWKHU ELUWK FRQWURO PHWKRG XQWLO \RX DUH UHDG\ WR VWRS EUHDVWIHHGLQJ %LUWK FRQWURO SLOOV WKDW FRQWDLQ HVWURJHQ OLNH HVWUDGLRO YDOHUDWH WDEOHWV DQG HVWUDGLRO YDOHUDWH DQG GLHQRJHVW WDEOHWV PD\ GHFUHDVH WKH DPRXQW RI PLON \RX PDNH $ VPDOO DPRXQW RI WKH SLOO¶V KRUPRQHV SDVV LQWR EUHDVW PLON ,I \RX KDYH YRPLWLQJ RU GLDUUKHD \RXU ELUWK FRQWURO SLOOV PD\ QRW ZRUN DV ZHOO 8VH DQRWKHU ELUWK FRQWURO PHWKRG OLNH FRQGRPV DQG D VSHUPLFLGH XQWLO \RX FKHFN ZLWK \RXU KHDOWKFDUH SURYLGHU ,I \RX DUH VFKHGXOHG IRU DQ\ ODERUDWRU\ WHVWV WHOO \RXU KHDOWKFDUH SURYLGHU \RX DUH WDNLQJ ELUWKFRQWURO SLOOV &HUWDLQ EORRG WHVWV PD\ EH DIIHFWHG E\ ELUWKFRQWURO SLOOV Tell your healthcare provider about all medicines and herbal products that you take LQFOXGLQJ SUHVFULSWLRQ DQG RYHUWKHFRXQWHU PHGLFLQHV YLWDPLQV DQG KHUEDO VXSSOHPHQWV. 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