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 'R QRW VNLS RU GHOD\ LQWDNH E\ PRUH WKDQ KRXUV 7KH PRVW FRPPRQ DGYHUVH UHDFWLRQV JUHDWHU WKDQ RU HTXDO WR LQ FOLQLFDO ---------------------DOSAGE FORMS AND STRENGTHS---------------------- WULDOV IRU HVWUDGLRO YDOHUDWH WDEOHWV DQG HVWUDGLRO YDOHUDWH DQG GLHQRJHVW WDEOHWV DUH KHDGDFKH LQFOXGLQJ PLJUDLQHV EUHDVW SDLQ PHQVWUXDO GLVRUGHUV (VWUDGLRO YDOHUDWH WDEOHWV DQG HVWUDGLRO YDOHUDWH DQG GLHQRJHVW WDEOHWV FRQVLVW QDXVHD RU YRPLWLQJ DFQH PRRG FKDQJHV DQG LQFUHDVHG RI ILOPFRDWHG XQVFRUHG WDEOHWV DQG XQFRDWHG XQVFRUHG WDEOHWV LQ WKH ZHLJKW IROORZLQJ RUGHU To report SUSPECTED ADVERSE REACTIONS, contact Actavis x RUDQJH WDEOHWV HDFK FRQWDLQLQJ PJ HVWUDGLRO YDOHUDWH at 1-800-272-5525 or FDA at 1-800-FDA-1088 or x SLQN WDEOHWV HDFK FRQWDLQLQJ PJ HVWUDGLRO YDOHUDWH DQG PJ www.fda.gov/medwatch GLHQRJHVW ------------------------------DRUG INTERACTIONS------------------------------- x \HOORZ WDEOHWV HDFK FRQWDLQLQJ PJ HVWUDGLRO YDOHUDWH DQG PJ GLHQRJHVW 'UXJV RU KHUEDO SURGXFWV WKDW LQGXFH FHUWDLQ HQ]\PHV IRU H[DPSOH &<3$ x EURZQ WDEOHWV HDFK FRQWDLQLQJ PJ HVWUDGLRO YDOHUDWH PD\ GHFUHDVH WKH HIIHFWLYHQHVV RI &2&V RU LQFUHDVH EUHDNWKURXJK EOHHGLQJ &RXQVHO SDWLHQWV WR XVH D EDFNXS RU DOWHUQDWLYH PHWKRG RI FRQWUDFHSWLRQ ZKHQ x JUHHQ WDEOHWV LQHUW HQ]\PH LQGXFHUV DUH XVHG ZLWK &2&V -------------------------------CONTRAINDICATIONS------------------------------ -----------------------USE IN SPECIFIC POPULATIONS------------------------ x $ KLJK ULVN RI DUWHULDO RU YHQRXV WKURPERWLF GLVHDVHV x 1XUVLQJ PRWKHUV 1RW UHFRPPHQGHG FDQ GHFUHDVH PLON SURGXFWLRQ x 8QGLDJQRVHG DEQRUPDO XWHULQH EOHHGLQJ x %UHDVW FDQFHU RU RWKHU HVWURJHQ RU SURJHVWLQVHQVLWLYH FDQFHU x %RG\ 0DVV ,QGH[ 7KH VDIHW\ DQG HIILFDF\ RI HVWUDGLRO YDOHUDWH WDEOHWV DQG HVWUDGLRO YDOHUDWH DQG GLHQRJHVW WDEOHWV LQ ZRPHQ ZLWK D ERG\ x /LYHU WXPRUV RU OLYHU GLVHDVH PDVV LQGH[ %0, RI JUHDWHU WKDQ NJP KDV QRW EHHQ HYDOXDWHG x 3UHJQDQF\ See for PATIENT COUNSELING INFORMATION and FDA- approved patient labeling. 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).] 1 INDICATIONS AND USAGE 1.1 Oral Contraception (VWUDGLRO YDOHUDWH WDEOHWV DQG HVWUDGLRO YDOHUDWH DQG GLHQRJHVW WDEOHWV DUH LQGLFDWHG IRU XVH E\ ZRPHQ WR SUHYHQW SUHJQDQF\ 7KH HIILFDF\ RI HVWUDGLRO YDOHUDWH WDEOHWV DQG HVWUDGLRO YDOHUDWH DQG GLHQRJHVW WDEOHWV LQ ZRPHQ ZLWK D ERG\ PDVV LQGH[ %0, RI JUHDWHU WKDQ NJP KDV QRW EHHQ HYDOXDWHG 2 DOSAGE AND ADMINISTRATION 2.1 How to Take Estradiol Valerate Tablets, and Estradiol Valerate and Dienogest Tablets 7R DFKLHYH PD[LPXP FRQWUDFHSWLYH HIIHFWLYHQHVV HVWUDGLRO YDOHUDWH WDEOHWV DQG HVWUDGLRO YDOHUDWH DQG GLHQRJHVW WDEOHWV PXVW EH WDNHQ H[DFWO\ DV GLUHFWHG 7DNH RQH WDEOHW E\ PRXWK DW WKH VDPH WLPH HYHU\ GD\ 7DEOHWV PXVW EH WDNHQ LQ WKH RUGHU GLUHFWHG RQ WKH EOLVWHU SDFN 7DEOHWV VKRXOG QRW EH VNLSSHG RU LQWDNH GHOD\HG E\ PRUH WKDQ KRXUV )RU SDWLHQW LQVWUXFWLRQV IRU PLVVHG SLOOV VHH )'$$SSURYHG 3DWLHQW /DEHOLQJ 2.2 How to Start Estradiol Valerate Tablets, and Estradiol Valerate and Dienogest Tablets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o $QRWKHU SLOO o 9DJLQDO ULQJ o 3DWFK x ,QVWUXFW KHU WR WDNH WKH ILUVW RUDQJH SLOO RQ WKH ILUVW GD\ RI KHU ZLWKGUDZDO EOHHG 6KH VKRXOG QRW FRQWLQXH WDNLQJ WKH SLOOV IURP KHU SUHYLRXV ELUWK FRQWURO SDFN ,I VKH GRHV QRW KDYH D ZLWKGUDZDO EOHHG UXOH RXW SUHJQDQF\ EHIRUH VWDUWLQJ HVWUDGLRO YDOHUDWH WDEOHWV DQG HVWUDGLRO YDOHUDWH DQG GLHQRJHVW WDEOHWV x ,I VKH