EXHIBIT 1010
`
`EXHIBIT 1010
`
`

`

`EDITI.ON
`
`2002
`
`PHVSCANS'
`DESK
`REFERENCE®
`
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`.
`. ·
`.
`.
`
`ISBN: 1·563~11·2
`
`Petitioner Exhibit 1010
`Petition for Inter Partes Review of U.S. Patent No. 7,704,984
`Page 1
`
`

`

`PRODUCT INFORMATION
`
`ORTHO-MCNEIL/2543
`
`acquired pneumonia due to penicillin-resistantS. pMumo·
`niae (MIC value for penicillin ~2 pglmL) were iilentiJied. Of
`the 18 levofto:tacin-treated patients, 15 were evaluabl e fol(cid:173)
`lowing the completion• or therapy. Fifteen out of the 15
`evaluable Jevofioxacin-treated patients with commUnity(cid:173)
`acquired pneumonia due- to penicillin-resistant S. pneumo·
`niae achieved clinica1 success (cure or improVement). Of
`these 15 patients, 6 were bacteremic and 5 were classified
`as having severe disease. Of the 4 comparstor-treoted pa(cid:173)
`tients with community-acqujred pneumonia due to penicil(cid:173)
`lin-resistantS. pneumon.i"eJ 3 were evaluable for clinieal ef(cid:173)
`ficacy. Tbme out of the 3 evaluable comparator-treated pa(cid:173)
`tients achieved clinicalsue<:esS. All three of the comparator:
`treated patie'\ts were bacteremic and bad disease classified
`as sever.e.
`Complicated Skin And Skin Structure Infections
`Three bund.red ninety-nine patients wet& en.ro11ed in an
`open-label, randomized, comparitive study for complicated
`skin and skin structure inf'eetio.ns. Ths patients wert~ ran·
`domized to receive either levofloxacin 750mg QD (N fol(cid:173)
`lowed by oral), or an approved comparator for a median of
`10 ;t 4.7 days. As is expected in compliceted skin and skin
`structure infections. surgical procedures wefe performed in
`the levoftoxacin and comparator groups. Surgery (inc;:ision
`and drainage or debridement) was performed on 45% of the
`levoftoxacin treated patients and 44% of the comparator
`treatAld patiet(ts, either shortly before or d'!ring antibiotic
`treatment nnd formed an iniAlgral part of therapy for this
`indie.ation~
`Among those who could be evaluated clinically 2-5 days af(cid:173)
`ter completion of study drug, overall success rates (im·
`proved or cured) were 116/138 (84.1%) for patients treatAld
`with levofloxacin nnd 1061132 (80.3%) for patients treawd
`.,;tb the comparator.
`Succcss rates varied with the type of diagnQsis ranging from
`68% in patients with infected ulcen to 90% in patients with
`infootcd wounds and abscesses. These rates were equivalent.
`to those seen with oomparator druga.
`ANIMAL PHARMACOLOGY
`Levoftoxacin and other quinolones have been shown to
`cause arthropathy in hnn1ature an.imals of most species
`IAlsted. (See WARNINGS.) In immature dogs (4-5 months
`old), oral doses of 10 mglkglday for 7 days and' intravenous
`doses of 4 mg/kg/day for 14 days of-levoftoxacin resulted in
`arthropathic lesions. Administration at oral doses of 300
`intravenous doses of
`for 7 days and
`mg/kg/day
`::.g/kg/day for 4 'l'••¥ P-';')duced arthropat~~ _in juvc_nile
`When .~~d ~n a mouse ear swelling bioassay, levoftOxacirl
`e~bjt.Od )>hototoxicity siniilar in ,JDagnitud~ to ·oftoxac~
`but les.' phototoiicity than other quinolones.
`·
`While crYstalluria has been observed in some intravenous
`rat studio$, urioary ~iys!als. '!'re not forin~d-U\ the bladder;
`beingP,rose~t'only allcr'mictuption anq ilr~ .. not ass,ociated
`~vith Oephrotoxieily.
`·
`1n· niicc, ihe CNS stimUlatory effect of qumoloiies is ~~~­
`ha.ncOO by concomitant adm.inistnitlon of Uon:SterOidafariti·~·
`inflammatory drugs.
`In dogs, l~vooo .. cin adminiatered a.t 6 mg/kg or bighe; ~Y
`rapid' intravenous injection produced hypotensive effects:
`Tb..re effects were considered to be related to histamine re(cid:173)
`lease.
`In vitro a.nd in vivo . s~udies in animals indicate that
`lcvoftoxacin is Iicither an enzyme inducer or-inhibitor in the
`human therapeutic plasma concentration r"-!lge; th~refore,
`no 4rui: metabolizing- tinzyuic-relatcd inte'l'):ti!iri¥ "witb
`other' drugs or agents are anticipat<:<~-
`.. ,
`REFERENCES
`':
`1: National Committee for Clinical Laboratory Standards.
`·
`·
`·
`·
`· Susce tibilit
`ts
`Fourth. Edition. p-
`MU~; Voti?.;~o;
`2, NCS, Wayne, PA, January, 1997.
`2. National Committee for Clinical Laborotory Standards.
`Performance Standards for Antimicrobial Disk Suscepti:
`bility Tests Sixth' Edition. Approved StandaT<l· N'CClS
`Docum~t M2;=As; Vol. 17,_-Iilo. 1, Ncgr.s, Wayne; PA,
`January, 1997.
`··
`..
`
`Patient Information About:
`LEVAQUIN®
`(hiitofloxacin tablats]
`250 mg Tablets, 500 mg Tablel5, and 750 mg -Tablets
`iOfOrination· about
`'l'his
`leaflet contains
`important
`LEVAQUI.N® Oevoftoxacin), and should be read completely
`before you begin treatment. This leoftet does not take the
`place of discussions with your doctor or health caze profes(cid:173)
`sional alwut your medical condition or your treatment. '!'his
`leaflet doos not liSt.' all ben'efir,.: nrid risks of LEVAQUIN~.
`The medicine·described here cin be presmbed only by a li:
`cEinsed health eare professional. If you have any 'quostiorul
`about LEVAQUIN® talk to yo"' -~~al_th care professio~l.
`
`Only you.r health O!'re. profe~sional can ~etermine if
`L);!VAQUIN~ is rigbt{or .j'OU. .
`,_, . •
`•• .
`,
`,
`•
`"'!ha) \s I,EVJI:OUIN? . .
`•
`.. ...
`• •
`.•
`•. •
`LEVAQUIN® is a quiQolone antihioJ;jc 'l-'ed. to ~t. lung,
`sinus, skin, and urinary tract infections. ca~l?ed by~ certain
`germs called bae!eria. LEVAQUIN® kills many of the types
`of bacteria that can infect the Junga,'sinus.S, skin, a.nd uri(cid:173)
`nary tract ond has beon abown in a large number.of clinical
`trials to be safe and effective for the treatment o[ bacterial
`inf~ctions.
`
`Sometimes viruses rather than bacteria may 1J1fect tbe
`lungs and sinuseS {for example the common cold).
`LIWAQUIN®, like other antibiotics, does not kill viruses.
`You should contact' your healt h care professional if you
`think that your condition is not improving while taking
`LEVAQUIN®. LEVAQUIN®Tablets are terra eolia pink for
`the 250 mg tablet, peach colored for the 500 mg tablet, or
`white for the 750 mg tablel
`How and when should.! take LEVAQUIN?
`LEVAQUIN® should be taken once a day for 8, 7, 10, or 14
`days depending on your prescription. It sho.uld be swal(cid:173)
`lowed and may be taken with or without food. 'fry to take
`the tablet at the same time each day and drink fluids liber-
`ally.
`.
`You may begin to feel better quickly; however, in order to
`make SUTe· that all bacteria are killed, you shoo lei completa
`the full course of medication. Do not take more than the pre(cid:173)
`scribed dose of LEVAQUIN® even if yon missed a dose by
`mistake. You should not take a double dose.
`·
`.
`Who should not t•ke l EVAOUIN®?
`You should not take LEVAQUIN® if you have ever had a
`severe allergic reaction to any of tho gtoup of antibiotics
`known as "quinolon~ such as ciprofloxacin. Serious and oc(cid:173)
`casionally fatal allergic reactions have been re'ported in pa(cid:173)
`t-ients receiving therapy with quinolones, inelodh~g
`LEVAQUIN®.
`.
`.
`.
`lf you are pregnant or ate planning to become pregnant
`while taking LEVAQUIN®, talk to your health care profes·
`sionol before taking this medication. LEVAQUIN® is not
`recommended for use during pregnancy or n'ursing, iis the
`effects on''tbe unborn child or nursing infant are unknown.
`LEVAQUIN® is not recommended for children.
`What are possibl~ side effects of LEVAQUIN®7
`LEVAQUIN® is generally well tolerawd. Tbe most common
`side effects caw;ad by LEVAQUIN®, which are usually mild,
`inc.ludc .. n'ausea, diarrhea, itchingJ abdominal Pain, dizZi(cid:173)
`ness, '113.tulence, rash and vaginitis in women.
`You aboUld be cereful about driv\ng or operating machinery
`until you are sure LEVAQUIN® is not causing'dizziness.
`Allergic ·reactions have been reported in patients receiving
`quinolones including LEVAQUIN®, even a.J\erjust one do5e.
`If you develop hives, skin rash or other sjmptoms of an al(cid:173)
`lergic reaction, yl)u should stop taking this medication arid
`· call your health caie professional.
`..
`.
`•
`· Ruptures of shoulder, band, or Achilles tcndonB havo been
`reported in pat.ients receiving quinolones, including
`LEVAQUIN®. If yon develop pain, swclling, or rupture of a
`tc~don yon should .stop ta!rin& LEVAQUIN® a~d contact
`.
`..
`.
`;rour bealtll care professional.
`Some quinolone ant,ibiotics have be~n associal<ld with the
`develop'!'ent of pbototoxi~ity _<•sunb~" and "blistering
`sunburns") following exposure to sunUgM or other sources
`oj ultraviolet light such as aryifi.cial ultraviolet light used in
`tanning salons. ~VAQu;Il\'0 has been infrequently .. soci(cid:173)
`ate~ ~vith pbototox:i~ty. You should avoid excessive eXposure
`to sunlight or _artificial ultraviolet light while you OTe taking
`, l.)>VAQUIN®.
`'·
`:- -
`.
`•
`If you bave'diabetes and you develop a hypoglycemic reac(cid:173)
`.tion while. on LEVAQUIN, . you -~bould s(9p talting
`.LEVAQUIN_®.-and call your health ~re P'l'fessiooal.
`Convulsions have beon reported in pati~n~ receiving qui(cid:173)
`nolonc antibiotics including LEVAQUIN(!). IJ'you have expe(cid:173)
`rienced c.:onvulsions in the pru..-t, be sure to let your physician
`·know that you have· a· history of convulsions. ·
`•
`Quinolones, including LEVAQUIN®, may also cailse central
`nervous system stimulatiou which may l~ad to tre:ruors,
`restlessness, anxiety, lightheadedness, confusion. ballocina(cid:173)
`tions, paranoia, depression •. nightmares, insomnia, and
`rarely, suicidal thougbts·ot acts. ,
`• .-. .
`If yo~ no~ce any side. effe~ not mentic;med in *:his )~aflet or
`you h;ave concerns about the side effects yo.,u arc expori~nc.
`ing, pleaso inform your health care professiop.al. .
`.
`.
`For more corople~ informatioo regarding .}evofiox.aein.
`ple¥& refer to the full prescribing information. which may
`be obtained from your heli.lth ca.;e professional, pharmacist,
`or t.he Physicians Desk Refereni:e (PI:iR). ·
`Wha1:'8bout other medicineS 1 am taking?
`,
`Taking 'warfarin (Cownadin®) and LEvAQQIN®' togetber
`can further predispose you tj> the de•elopment of blee'ding
`prob1ems. rr you take 'warfarin, be sure to tell yoUr health
`care professional.
`.
`·
`. .
`· ·
`.
`Many antacids 'and ·multivitamins may'interfere with the
`absoi-J)tiiin ofLEVAQUIN® and maY prev~nt it from work(cid:173)
`
`4
`
`U;gproperly: You should take LEVAQUJN® either'2 hours
`before or 2 hours after filking'these products.
`It 'is important to let yoi.u- health care professional kfiow all
`Of the mediCines you ax:e using.
`·
`Other inform3tion
`·
`Take your dose of LEVAQlJJN® once a day.·
`C<lmple\e ·the course of medicetion even if you· are 'feeling
`better.
`•
`.
`.
`Keep trus medieation out of the reach ofcbiidren. ·
`This wo,.;,ation does ';;ot take th~ place or cliselissions with
`ybl!r ~O<:tor or health care prof.Ssiona1.about your medical
`OonCiition or jour .treatment .. .
`QRTHO-MoNEIL
`.
`OMPDMSION
`ORTHO-McNEIL PHARMAC~UTICAL, INC.
`·'
`Raritan, New Jersey, U.SA 08869 ·
`U.S. Patent No. 4,382,892 and U.S. Paient No.·5,053,407
`.. 7518201
`•
`C OMP 2000
`Re,;scd ·Novembcr 2000
`633-10-816-2
`Shown in Product ldentificotion Guide, page 329 .
`
`MlCRONOR® Tablets
`(norethindrone] 0.35 m9
`[mrc-ro·n6r)
`
`Patients should be counseled that this product does not
`protect against HIV infection (AIDS) and other sexually
`transmitted diseases.
`'
`· · ·
`
`DESCRri>:nON
`MICRONOR<!/28 Day Regimen
`Each tablet contains 0.35 mg norethindrone: Inactive ingre(cid:173)
`dients include D&C Green No.5, D&CYeUow·No. 10, lac(cid:173)
`tose, magnes~um s~~ate, J?~vidonp· and si~.
`
`•
`
`0
`
`OH _
`
`- loo'..
`·•c=CH
`
`''indrotl~ '
`
`CLINICAL PHARMACOLOGY
`i. 'MODE OF ACTION
`MICRONOR progestin-only oral contraceptives preven.t
`COO)ception by supp.rossing ,ovul~tion in-approximately half
`of users, thickening the e<:rvical mucus to inhibit sperm
`penetration, lowering the midcY.clc LH and FSH peaks,
`slowing the movement of the oyum through the fallopian
`tubes, and altering the cndometri\Jlll . .
`2. PHARMACOI{lNETJCS
`Serum progestin levels peak about two bouTs after oral ad·
`ministration, followed by rapid distribution and elimina(cid:173)
`tion. By 24- hours after drug ingestion~ serum levels are near
`baseliJ>e, making e_fficacy dependent upon rigid adherence to
`the .dosing 6Ched:ule. There are large variations in serum
`levels among individual users. l!r<>gestin-only administra(cid:173)
`tion res·ults in lower steady-state serum progestin levels
`and a sl>orter elimination half-lifo than concomitant admin(cid:173)
`istration with estrogens.
`INDICATlONSWD USAGE
`. , .
`..
`.
`1. Indication.s
`.
`Progestin-only oral contraceptives ¥• indicalkd for the pre(cid:173)
`vention of pregnancy.
`2. Efficacy
`If used perfectly, the first.-year failuro rate for .progestin(cid:173)
`only oral contraceptives is 0.5%. However, the typical fail(cid:173)
`ure rate is esthnated to be closer t.O 5%, due to late or omit(cid:173)
`ted pills. Table llists the pregnancy rates for u5en nf all
`· ·• ·
`major methods of <:Aintraeeption.
`(See .. table .at _top of next ,P.age)
`· ··
`
`'
`
`OONTRAINDICATlONS
`~~ogestin-onl_y oral ~ntrac~~ti~es ,<Po'Ps> should not be
`used by women wbo'turrently bovel.be following conditions:
`• Known or suspected pregnancy
`. • ~own or•suspeded c~r_~in~nit~ of the brea$
`• Undiagnosed abnormal gc!>ital bleeding
`. • Hypersensitivity to any component of this pf9ducl
`· . • Beniiln or' malignant liver tumol1 .
`• .
`• AcutC'livcr.,dis?asc '
`:.
`t •
`
`WARNINGS
`Cigaretfc sm'ok:ing increases the risk ofSerious cardiovascu4
`lar .disease .. Women who u.se oral contraceptives sho.uid be
`-
`sttoiigly <idviired ilot to; smoke. ·
`MICRON OR does nol ootitain estrogen and, therefore, this
`insert does not discuss the serious health risks that have
`bek a~atlld 'with th~ estrogen con)ponent of combined
`oral contraceptives (COGS). Tbe health care provider is re(cid:173)
`ferred to .the pre5ci:;bing inforina_tion of combined oral con(cid:173)
`traceptives for a discussion of those risks. Tbe relationship
`between progestin-only oral contraceptives and these risks
`is not fully defined. The ph_ysician shoUld remain alert to
`the earliest mairifestation or' symptoms of any serious
`disease and discontinue oral contraceptiVe the.rapy when
`appropriate. ·
`·
`·
`·
`1. Ectopic )'regnancy
`1'be incidence of ectopic·pregna/>.c:ies for progestin-only oral
`contraceptive users is 5 pei 1000 woman-yean. Up to 10%
`of pregnancies reported in clinical stydies of prog .. tin-only
`oral <.-ontraceptive users are extrauterine. Although symp4
`toms of ~opic preg!!ancy should be. watched for, a histOry of
`ectopic pr91!"ancy neeil not be co~sidcred a contraindication
`to u~e of this contraceptive method. Health providers should
`~ rilert to the possibility of al:i ectopic pregnancy in women
`who become preilnant or rom plain oflower abdominal pain
`while on progestin-only oral contniceptiyeS.
`2. Delayed Follicular Atresia/Ovarian Cysts
`If follicular davclopment occurs, atresia of the follicle is
`sometimes delayed and the follicle may continue to grow be(cid:173)
`yond. the size if;: would attain in a normal cycle. Generally
`these enlarged follicles disappear spontaneously. Often they
`are asymptomatic; in some ca<;es they aTe associated \vith
`mild abdominal pain. Rarely they may twiat or rupture, re(cid:173)
`quiring surgical intervention.
`
`Continued on neKt page
`
`Cons-ult 2 002 POR• supplements and rutuJe editions ror revisions
`
`Petitioner Exhibit 1010
`Petition for Inter Partes Review of U.S. Patent No. 7,704,984
`Page 2
`
`

`

`2544/0RTHO-MCNEIL
`
`Micronor-Cont.
`
`3 . lrregul.,. Genitalllleeding
`Irregular menstrual patterns are common among women
`usmg progestin-only oral contraceptives. If genital bleeding
`is suggestive of infection, malignancy or 0ther abnormal
`conditions, such nonpharmacologic causes should be ·ruled
`out. If prolonged amenorrhea occurs, the possibility of preg·
`nancy should be evaluated.
`.
`4. Carcinoma of the Breas~ and Reproductive Organs
`Some epidemiologioal. srudics of oral contraceptive usen
`have reported an mcreased relative risk of developing
`breast cancer, p.,.Ucularly at a younger age aod apP"'ently
`related to duration of use. Thoso studies have predomi·
`Molly involved combined oral contraceptives and there is
`insufficient data to determine whether the use of POPs sim·
`ilarly increases the risk.
`A meta-analysis of 54 studies found a small increase in tb.e
`frequency of having breast cancer diagnosed for women who
`were Clln"Cntly usi~g combined oral contraceptives or had
`used them within the past ten years. This increase in the
`frequency of breast caocer diagnos;is, within ten years of
`stopping use, was generally acCounted for by cancers local(cid:173)
`ized to the breasl There was no increase tn the frequency of
`having breast cancer diagoosed Un or more years after ces· .
`sation of use.
`•
`Women with breast cancer should not use oral contracep-(cid:173)
`tives beeause the role of feuiale hormones in breast 'cancer
`has not been fully determined. ·
`Some studies suggest that oral contraceptive Usc has been
`AssoCiated ~tb an ine:rease in the riak of cervical intraepi(cid:173)
`theati.W tteoplasia in some populations ofwometL However,
`there continUes to be controversy about the extent tc which
`such findings may be due tO differences in soxual behavior
`ond other factors: There is insufficient data to determine
`whether the use of POPs ·increases the risk of developing
`cervical i.ritra.epithelial neoplasia.
`5. Hepatic Neoplasia ·' ·
`Benign hepatic adenomas are associated with comb.ined ore!
`contraceptive 'use, although the incidence of bcnigxi tumors
`is rare in ·the United States. Rupture of benign, hepatic
`adenomas may cause death through intraabdominal hemor-
`rhage.
`·
`Stcdies have shown an increased risk of developing hepato(cid:173)
`cellular carcinoma in combined ora] cont{ac.eptive u2Se~.
`However, these cancers are n.re in the U.S. There is insuf(cid:173)
`ficient data to determine whether POPs increase tho risk of
`developing hepatic neoplasia.
`'
`PRECAUTIONS
`. .
`.
`.
`~- General
`Patients sl>ould be.couusele.d that this prpdact does n9~ pro·
`teet against IDV infection (AIDS) and othet sexually trans-
`mitted diseaSes.
`•
`·
`·
`2. Physical Examination and Follow up
`It is ~Msidared gOod medical pt_acticc for scxua]Jy active
`women using oral contraceptives tO have annual bi$tOry And
`physical elCarninations. The phy$jca) examination may be
`deferred until afulr initiation of oral contraceptives if
`re!juested by the woman ;.,.d judge(! appropriate by the eli·
`nician.
`·
`·
`·
`3. Carbohydrate and Lipitl MetaboUsm ·
`Somo users" triay experience slight deterioration in glucose
`toleronoo. with increases in plasma insulin but women with
`diabetes mellitus who uso progestin-only oral coutracep(cid:173)
`tives do not generally experience changes in their fusulin
`requirements. Nonetheless, prediabetic and dia\>etic women
`in particular should be carefully monitored while takinJ!
`POPs.
`Lipid D?•tabolism is occasionally a.ffected in that .. HDL,
`HDL2, and ap01ipoprotein A-I and A-D m!Q' be decrea.:red;
`hepatic lipase niay be increased. There is usually no l'ffcct
`on total cholesterol, HDL,, LDL, or VLDL..
`·
`4. Drag Interactions
`•
`. · ·
`Tbe effectiveness of progestin-only pills is reduceg .bY 'Jie(cid:173)
`patic en.zym~>oinducing drugs such as the antici>nvulsailts
`phenytoin, carbaroaz.epine, 9.o.d. barbirurates, and the anti·
`ruberculosi.s drug riJ"anjpin . . Nosigni6.eaot interaction has ·
`been found with broad·speclruin antibiotics.
`. •
`~
`5. Interactioo.s with.Laboratory Tests
`.
`·
`Tbe following endOcrine tests may be affeCted bY. progestin·
`only oral contraceptive ~:
`..
`• Sex hormone-binding globulin (SHBG) conoontrations
`may be deereased.
`• Thyroxine concentrations may be decreased, due to a
`•
`decrease in thyroid binding .. globulin (TBG).
`6. Carcinogen~is
`"'
`See WARNINGS section.
`7. Pregnancy
`Many studies have found no effects on f~tal development as(cid:173)
`·sOciated with long:term usc of contraceptive doses of oral
`progestins. 'l'h8 few srudies of infant" growth nod develop·
`ment that have been con!lucted have not demonstrated sig(cid:173)
`nificant adverse CJrects. It is nonetheless prudent ui rule out
`s"uspected pregnancy oofore initiating any hormonal eontra·
`ceptive use.
`·
`·
`8. -Nursing Mothers ..
`No adverse elfects have been 'found on breastfeeding perfor(cid:173)
`mance or on the health, growth or development of the in·
`fant. Small amounts of progestin pass into the breast milk,
`resulting in steroid levels in infant plasma of 1-6% of tho
`levels of maternal .plasma:
`9. Pediatric Usc
`Safety and ot!icacy of ~OCBONOR Tablets have been estab·
`lished in women of reproductive age. Safety and efficacy arc
`
`PHYSICIANS' DESK REFERENCE®
`
`'!'ABLE I: PERCENTAGE OF WOMEN EXPERIENCING
`AN UNINTENDED PREGNANCY DURING THE FlRSTYEAR OF TYPICAL USE
`AND 'tHE FIRST YEAR OF PERFECT USE OF CONTRACEPI'ION
`AND THE PERCENTAGE CONTINUING USE AT TilE ·END OF THE FIRST YEAR.
`UNITED STA:rBS.
`
`Method
`(1)
`
`Chance•
`Spermitides'
`Periodic abstinence
`·calendar
`Ovulation method
`Sympto-Thermal'
`Post-Ovulation
`Withdrawal
`Cap7
`Parous Women
`Nulliparous Women
`Sponge
`Parous Women
`Nulliparous Women
`Diaphrr'
`Condom
`femal.e (Real_ity)
`Male
`Pill
`Progestin Ouly
`Combined
`IUD
`Ptogeste..;,n.;· T
`Copper T380A
`LNg20
`Depo-J>roveia
`Norplant and No.q,lant-2
`Female Sterilization
`~1ale Sterilization
`
`% of Women Experiencing an
`Unintended Pteg;aaocy
`within the First Year of Use
`Perfeci use•
`(3)
`
`Typical Uso1
`(2)
`
`85
`29 .
`25
`
`J.9
`
`40
`zo
`
`40
`2Q
`·zo
`21 .
`14 s·
`
`2:o
`0.8
`0.1
`0.3
`0.05
`0.5
`0.15
`
`..
`
`·'
`
`85
`6
`
`9
`3
`2
`1
`4
`
`26
`9
`zo
`9 .
`6
`
`0.5
`0.1
`
`! .5
`0.6
`0.1
`0.3
`0.05
`0.5
`0.10
`
`%of Women
`Continuing Use
`atOne Year*
`
`(4)
`
`40
`63
`
`42
`56
`
`.42
`56
`56
`
`56
`61
`71
`
`81
`78
`81
`7o
`88
`100
`100
`
`Adapted from 'l'tussel J. Contraceptive ot!icacy. Jn Hatcher RA, '!'russel J, Stewart F, Cates.W, Stewart GK, KDwal D,
`Guest F, Contraceptive Technology: Sev.enteenth Revised Edition. New York NY: Irvington Publiabers, 1~98,, ip. press.
`
`1. Among typical couples who initiate use of a method (not necess.,.ily for the first time), tbe percentage who experience an
`accidental pregnancy during the first year if they do not stop use for any other reason.
`•
`2. Among couples who initiate usa of a method (not necessa'rily for the first time) a11d who use it perfectly (both consistently
`and correctly), the percentage who experience an accidental pregnancy during the first year if they do not stop '!"" for any
`other reason. · ·
`;;
`3. Among couples attempting to avoid pr~a.ncy, the pcrecntage ·who continue to usc a method for one year.
`4. The percents bei:oming pregnan_t in columns (2} o.nd (S)"ro:e based op. data from populations ')'here controception ~·not
`used and froiD women who cease usi.!ig contra"'lption in order to be'come pragnaot. Among such populations, about 89\1>
`become p~t Within one yell This estimate WitSJow~red slightly (!I> ~5%) to r<present the percent who would become
`pregnant within one year among women nOw relying ori revet3ible, methods of contra~ptio~ if they abandoned contra·
`ception altogether.
`.
`·
`5. Foams, o:eOJ!lS, gels, vaginal suppositories, and vaginal film.
`6. Cervic"al mucus (ovulation) n1ethod supplemented by calendar in the pre-ovulatory and basal body temperature in the
`post.-o,'ulatory phases.
`·
`7. With spermicidal cream or jelly.
`8. Without spermicides.
`
`expected to be the same for postpubertal adolescents under
`the age of 16 and for u.ser8 16 years and older. Use of this
`product before menarche is not indicated.
`•
`· ·•
`10. Fertility Following Dis.;ontinuation
`The limited available data indicate a r~pid retu.ro• of normal
`ov'u.lation and fertility following discontinuation of proges·
`tin-only oral contrilceptives.
`'11. Headache
`Th'e oriset or exacerbation of migxa.i:oe or development of se(cid:173)
`vere headache with .foca1 neurological ayrnptoms which is
`recurrent or persistent requires discontinuation of proges(cid:173)
`tin-only contr!lc:eptivc$ ~deValuation of the cause.
`INFORMATION FOR THE PATIENT . .
`•
`1. SOe Detailed Patient Labeling for detailed information.
`2. CounsellDg ~sues
`·
`·
`The foUo'ving points should be discussed with prospective
`users before prescrihilig prog.,-t;n-only oral oontraceptives:
`• The necessity ~f taJtiog pills lit the same time every
`day, "including throughout all bleeding epi~odes.
`•
`• The need to use a backup method such' ss condoms and
`siicrmicides for the next 48 hours whenever a prog.,..
`tin-only oral contraceptive is taken 3 or more hours
`late.
`• The poten.tial side effects of progestin-only oral contra·
`captives; particularly menstrual irregularities.
`• The o~ to inform the clinician of prolonged episodes
`of bleeding, amenorrhea or severe abdominal pain.
`•· The imPortance of ~sing a barrief method in addition to
`progestin-only" ore! contraceptives if a woman is at risk
`of contrac:1.ing or transmitting STDsiHN.
`
`ADVERSE REACTIONS
`Advo""' reactions reperted with the use ofPOPa includ"'
`• Menstrual irregularity is the most frequently reported
`side effect.
`·
`• FrequenL and irregular bleeding are common, while
`long duration of bleeding episodes aud amenorchea are
`less likely.
`
`• Headache. breast tenderness; nausea. and dizz:ip.ess arc
`in«eased among progestin-only -oral contraceptive us·
`en• in some studies.
`·
`~ ·
`.~ Androgenic side effects such as acne, hirsutism, and
`weight gsm occur rarely.
`
`OVERDOSAGE
`There have b~en no repo-Q.s ·of serious ill effects from over(cid:173)
`dosage, including ingestion by. cQi!dreq.
`~OSAGE AND ADMINISTRA110N
`To al!hieve maximum
`e1lectiveo~ss,
`contraceptiv·e
`MICRON OR must be ta.\en exactly as directed. One tablet
`is taken cvecy day, at the same time. Administration is CoD·
`tinuous, with no interruption between pill packs. See De·
`tailed Patient Labeling fOr detailed instruction.
`
`HOWSUPPLmn
`MICRONOR Tablets are available in a DIALPAK® Tablet
`Dispenser (NDC 0062·14U-01) conteining 28 green tablets
`(0.35 mg norethindrone).
`_
`STORAGE: Store at controlled room temperature (15·30'C;
`59·86'F) . .
`
`REFERENCE
`McCaim M, and Potter L. Ptogestin:o'n1y Oral Contracep·
`tives: A. Comprehensi~e' Review. Contraception, 50:60
`(Suppl. 1), Decemb~ 1994.
`
`DETAILED PATIENT LABELING
`MICRONOR& (norethindrone! Tablets
`Th1s produc;t (like all oral contraceptives) is used to 'prevent
`pregnancy. It does not protect against HIV infe-ction (AIDS)
`or other sexUally transmitt~d dis·eases.
`DESPRIP'l"lON
`MICRONOR® 28 Day. Regimen ·
`Each tablet contains 0.85 mg norethindrone. Inactive ingre(cid:173)
`dients include D&C Green No . .5, D&C Yellow No. 10, lac(cid:173)
`tose, magnesium stcaxate, povidone ~d sta:rch.
`
`Information Will be superseded by supph!ments and subuquent editions
`
`Petitioner Exhibit 1010
`Petition for Inter Partes Review of U.S. Patent No. 7,704,984
`Page 3
`
`

`

`PRODUCT INFORMATION
`
`ORTHO-MCNEIL/2545
`
`TABLE D! PERCEN'!'AGE OF WOMEN EXPERIENCING
`AN lfNlNTENDED P!iEGNANCY DURJNG THE FIRST YEAR OF TYPICAL USE
`AND THE FIRST YEAR OF PERFECT USE OF CONTRACEPTION
`AND THE PERCENTAGE CONTIJ'.'UING USE AT TRE ENn.OF TRE FIRST YEAR.
`IJNITED;STATES:
`.
`
`INTRODUCTION
`This leaflet is abOut birth control pills that contain one hor·
`mone, a progestin. Please road this leiulet before you begin
`to take your pillo. It is meant to be used along with talking
`with your iloctor or clinic.
`·
`Progestin-only pills .,-e often called "POPs" or·"tho "'ini(cid:173)
`pill". POPsliave less progeotin than the combined birth con(cid:173)
`trol pill (ot "the pill') which tonlain~ both an estrogen and a
`progestin.
`·
`HOW EFFECTIVE ARE POPs?
`About 1 ii:\200 POP uoers will get pNgllant in tqc first year
`if they all take POPs perfectly (that is, on lime, every day).
`About 1 in 20 "typical" POP users (including women who are
`lati> taking'j).Us or miss pills) gets pregnant in the first year
`of use. Table 2 will help you compare the efficacy of different
`methods.
`[See table above]
`HOW DO POPs WORK?
`POPs can prevent Pre{.'llancy in diffJent ways including:
`• They ~ake the eervicaJ mucus ~t the entrance to the
`womb '.(~be uterus) too tb.ick for the sperm to get
`through io the egg.
`• They prevent ovulation (release of the egg from the
`ovary) in about half of the cycles:
`• They also affect othe.r hormone$, the fallopian tubos
`Md the lining of the uterus.
`YOU SHOI)LD NOT TAKE POPs
`• If ther~ is any chance you may ~ pregnant.
`• If you have breast cancer.
`• 1f you ha,•e bleeding between your periods that has not
`been diagnosed.
`.
`• If you are I<! king certain drugs for epilepsy (seizures) or
`for TB. (Sec "Using POPs with Other Medici.nes"
`below.)_;
`• If you are hypersensitive. or anergic., to any compOnent
`of tb.is product.
`• If you have liver tumors, cithor ~nign or canoerous.
`• It you have ac\•te liver clisease. ·
`RISKS OF !AKING POPs
`Cigarette si:nokJng greatly increases the possibility of suffer- '
`ing heart attacks and strokes. Women wl)o use oriil contra-_
`cept_iv.e~ "':~ s;trongly ad