1208/CHIRON
`
`TOBI-Cont.
`
`t'lchniques. In addition, approximately 77% of patients were
`concurrently treated with dornase alfa (PULMOZYME®,
`Genenrech).
`In each study, TOBI-treat'ld pat.ients experienced signifi·
`cant improvement in pulmonary function. Improvement
`was demonstrat'ld in the TOBI group in Study 1 by an av(cid:173)
`erage increase in FEV1% predicted of about 11% relative to
`baseline (Week 0) during 24 weeks compared fu no average
`change in placebo patients. ln Study 2, TOBJ treat'ld pa·
`tients bad an average increase of about 7% compared fu an
`average decrease of about 1% in placebo patients. Figure 1
`shows the average relative change in FEV1% predicted over
`24 weekB for both studies.
`
`CibaGeneva Pharmaceuticals
`
`Ciba-Geigy Corporation
`
`Geneva Pharmaceuticals, Inc.
`
`PLEASE NOTE:
`Due to tbe merger of CibaGeneva Pharmaceutical$ and
`Sandoz Pharmaceuticals Corporation, please refer fu
`Novartis Pharmaceuticals Corporation for branded product
`information and Geneva Pharmaceuticals, Inc. for branded
`generic product information.
`
`Colgate Oral Pharmaceuticals,
`Inc.
`a subsidiary of Colgate-Palmolive C9mpany
`ONE COLGATE WAY
`CANTON, MA 02021 U.S .A.
`
`=..::l ' - - Stuctyt:I'I«MIOill• l .. 1
`,. ·~·" ......
`20
`
`Figure 1: Relative Change From Baseline in FEV,o/o
`Predicted
`
`Direct Inquiries to:
`Professional Services Department
`(800) 226-&428
`For Medieallnformation Contact:
`In EmergencieS:
`Pittsburgh Poison Control
`(412) 692-5596
`
`In each study, TOBI therapy result'ld in a significant reduc(cid:173)
`tion in the number of P. aeruginosa colony forming units
`(CFUs) in sputum during the on-drug period.s. Sputum hac·
`terial density returned fu baseline during the off-drug peri(cid:173)
`ods. Reductions in sputum bact'lrial density were smaller in
`each successive cycle (see Figure 2).
`
`LURIDE<!!I DROPS
`brand of sodium fluoride
`oral solution
`1.69 fl oz (50 mL) bottles, calibrat'ld dropper
`
`~~-....------=~=
`r.;,;,;.;;;;t:47"--c<·
`
`.,...,,_ -·-
`
`LURIDE<!!ILOZI-TABS<!!I
`brand of sodium fluoride
`
`120 tablet bottles 0.25 mg F vanilla
`120 tablet bottles 0.5 mg F grape
`120 tablet bottles 1 mg F cherry
`
`Figure 2: Absol ute Change From Baseline in
`Log,0 CFUs
`
`PERIOGARD®
`(chlorhexidine gluconate
`oral rinse, 0.12%1
`
`16 fl oz bottles
`
`Patients treat'ld with TOBI were hospitalized for an aver(cid:173)
`age of 5.1 days compared t.o 8.1 days for placebo pati.ents.
`Patients treat'ld With TOBI required an average of9.6 days
`of parenteral anti-pseudomonal antibiotic treatment com(cid:173)
`pared fu 14.1 days for placebo patients. During the six
`months of trMtment, 40% ofTOBI patients and 53% of pla(cid:173)
`cebo patients were
`treated with parenteral anti·
`pseudomonal antibiotics.
`The relationship between in vitro s usceptibility rest results
`and clinical outcome with T081 therapy is not clear. How(cid:173)
`ever • .four TOBI patients who began the clinical trial with P.
`aerugirwsa isolaws having MIC values <!:128 J.I&ImL did not
`experience an imp.rove:ment in FEV 1 or a decreas.e in spu·
`· tum bacwrial density.
`Treatn1ent with TOBI did not affect the susceptibility of the
`majority of P. aeruginosa isolates during the siK month stud(cid:173)
`ies. However, some P. aerugi,.osa isolates did exhibit in(cid:173)
`creased tobramycin ~1!Cs. The pereentage of patients with
`P. aeruginosa isolates wilh fubramycin MICs "' 16 Jig/mL
`was 13% at the beginning, and 23% at the end of six months
`of the TOBI regimen.
`REFERENCES
`1. Neu RC. Tobramycin: an overview. [Re,•iew]. J Infect
`Dis 1976; Suppl 134:S3·19.
`2. Weber A, Smith A, Williams-Warren Jet al. NebuliZ<lr
`delivery of robramycin fu the lower nespirafury tract.. Pe(cid:173)
`diatr Pulmonol1994; 17 (5):331-9.
`3. Bryan LE. Aminoglycoside resistance. Bryan LE, Ed.
`Antimicrobial drug resistance. Orlando, FL: Academic
`Press, 1984: 241-77.
`Rx Only
`Manufactured for
`CHIRON Corporation
`Emeryville, CA 94608
`by Automatic Liquid Packaging, lnc.,
`Woodstock, fL 60098
`Packaged by Packaging Coordinafurs lnc.,
`Philadelphia, PA 19114-1123
`DATE OF ISSUANCE 412001
`OOH!RON Corporation, 2001
`Shown in Producl ldenti~alion Guide, page 3 IQ
`
`\nformation wm be supOf'Seded by supplements and subsequent edition&
`
`2
`of
`formula
`empirical
`an
`with
`(C22H 24N20 8·HCil2·C2H00·H20 and a molecular weigh~ of
`
`PREVIDENT® 5000 PLUS®
`brand of 1.1% Sodium Fluoride
`prescription toothpaste
`1.8 oz. (51g) net wt. tubes Spearmint or Fruitastic"''
`'1\vin Pack (two 1.8 oz (&1g) net wt. tubes) Spearmint
`
`CollaGenex Pharmaceuticals,
`Inc.
`41 UNIVERSITY DRIVE, STE. 200
`NEWTOWN, PA 18940
`
`Direct inquiries to:
`888-339-5678
`
`PERIOST AT®
`[puro-sta.tl
`(doxycycline hyclate tablets! 20 mg
`Formerly available es 20 o;ng capsules
`
`- ~
`
`1841-00
`Rev. 04/01
`DESCRIPTION
`Periostat® is available as a 20 mg tablet formulation of
`doxycycline for oral administration.
`l'he structural formula of doxycycline hyclate is:
`
`, ]
`
`<?J3 9fi N(CH,),
`~~:1
`~CONH,
`[
`
`OH
`
`0
`
`OH
`
`0
`
`PHYSICIANS' DESK REFERENCE®
`
`1025.89. Tbe chemical designation for doxycycline is 4-(dim·
`ethylamino)-1,4,4a,5,&a,6,ll,l2a-octahydro-3,5,10,12,12a(cid:173)
`pen~ahydroxy·6·methyl-1,11-dioxo-2·naphthace.necarboxa­
`mide mooobydrochloride, compound with ethyl alcohol (2:1),
`monohydrate.
`Doxycycline byclate is a yellow fu light-yellow crystalline
`powder which is soluble in watar.
`Inert ingredients in tbe formulation a,re: hydroxypropyl
`metbylcellulose, lactose, magnesium st'larata, microcrystal(cid:173)
`line cellulose. titsnium dioxide, and triacetin. Each tablet
`contains 23 mg of doxyeycline byclate equivalent fu ZO mg of
`doxycycline.
`
`CLINICAL PHARMACOLOGY
`After oral administration, doxycycline hyclate is rapidly and
`nearly complewly absorbed from the gastrointestinal tract.
`Doxycycline is eliminat'ld with a half-life of approximawly
`18 hours by renal and fecal excretion of unchanged drug.
`Mechanism of Action: Doxycycline has been shown fu in(cid:173)
`hibit collagenase activity in vitro.1 Additional studies have
`shown that doxycycline reduces the elevat'ld collagenase ac(cid:173)
`tivity in the !fngival crevicular Ouid of patients with adult
`periodontitis. •3 The clinical significance of those findings is
`not known.
`Microbiology: Doxycycline is a member of the tetracycline
`class of antibiotics. The dosage of doxycycline achieved with
`this product during administration is well below the concen(cid:173)
`tration required to inhibit microorganisms commonly asso(cid:173)
`ciated with adult periodontitis. Clinical studies with this
`product demonstrat'ld no effect on total anaerobic and fac(cid:173)
`ultative bact'lria in plaque samples from patients adminis·
`tered this dose regimen for 9 fu 18 months. This product
`should not be used for reducing the numbers of or eliminat(cid:173)
`ing those microorganisms associaW with periodontitis.
`Pharmacokinetics
`The pbacmacokinetics of doxyeycline following oral admin·
`istration of Periostat® were investigated in 4 volunwer
`studies involving 107 adults. Additionally, doxycycline phar(cid:173)
`macokinetics have been characterized in numerous scion·
`tific publications.• Pharmacokinetic paramewrs for
`Periostat® following single oral doses and at steady-state in
`healthy subjects are prcse.nt'ld as follows:
`{See first table at fup of next page I
`Absorption: Doxycycline is well absorbed after oral ad(cid:173)
`ministration. In a single-dose .;tudy, concomitant adminis(cid:173)
`tration of Periostat® with a 1000 calorie, high-fat, high·
`prowin meal which included dairy products, in bealtby vol·
`unt'lers. resulted in a decrease in the raw and extent or
`absorption and delay in the time t.o maximum concentra·
`tion.
`·
`Distribution: Doxycycline is greater than 90% bound to
`plasma prowins. Its apparent volume of distribution is var(cid:173)
`iously report'ld aa between 52.6 and 134 L.•.•
`Metabolism: M~or metabolites of doxycycline have nol
`been identified. However, enzyme inducers such as barbitu·
`rates, carbamazepine, and phenyfuin decrease the half-life
`of doxycycline.
`Excretion: Doxycycline is excreted in the urine and feces
`as unchanged drug. It is variously report'ld that between
`29% and 55.4% of an adminiswred dose can be accounwd for
`in the urine by 72 hours•·• Half-life averaged 18 hours in
`subjects receiving a single 20 mg doxycycline dose.
`Special Populations
`Geriatric: Doxycycline pharmacokinetics have not been
`evaluated in geriatric patients.
`Pediatric: Doxycycline pharmacokinetics have not been
`evaluated in pediatric patients. (See WARNINGS section).
`Gender: Doxycycline pharmacokinetics were compared in
`9 men and ll women under fed and fast'ld conditions. While
`female subjects bad a higher rate (Cmaxl and extent of aJ>.
`sorption (AUC), these differences are thought to be due to
`differences in body weight/lean body mass. Differences in
`other pbannacokinetic parameters were not signiJlcant.
`Racs: Differences in doxycycline pharmacokinetics among
`racial groups have not been evaluat'ld.
`Rena/Insufficiency: Studies have sho\vn no significant dif(cid:173)
`ference in serum half-life of doxycycline in patients with
`normal and severely impaired renal function. Hemodialysis
`does not alter the half-life of doxycycline.
`Hepatic Insufficiency: Doxycycline pharmacokinetics have
`not been evaluated in patients with hepatic insu.fficiency.
`Orug Interactions: (See PRECAUTIONS section)
`
`Clinical Study
`1n a randomized, multi-cenoored, double-blind, 9-month
`Phase 3 study involving 190 adult pati.onts with' periodontal
`disease fat least two probing sites per quadrant of between
`5 and 9 mm pocket depth (PO) and attachment level (A1v)J,
`the effects of oral administration of 20 mg twice a day or
`doxycycline hyclate (using a bioequivalent capsule formula·
`tion) plus scaling and root planing (SRP) were compared to
`placebo control plus SRP. Both treatment groups were ad·
`ministered a course of scaling and root planing· in 2 quad(cid:173)
`rants at Baseline. Measurements of ALv, PD and bleeding·
`on-probing (BOP) were obtained at Baseline, 3, 6, and 9
`months from each sit'l about each tooth in the two quad·
`rants that received SRP using the UNC-15 manual probe_
`Each tooth site was categorized into one of three strata
`based on Baseline PO: 0-3 mm (no disease), 4-6 mm (mild/
`moderate disease), ;;,: 7 mm (severe disease). For each sb-a·
`tum and treatment group, tho following were calculated at
`month 3, 6, and 9: mean change in ALv from basellne, mean
`change in PO from baseline, mean pcreentage of tooth sites
`
`1
`
`

`

`PRODUCT INFORMATION
`
`COLLAGENEX/1209
`
`Pharmacokinetic Parameter. for Perlostate
`
`n
`
`20
`
`30
`
`Cmax•
`(ng/mU
`362 = 101
`
`790 = 285
`
`Tm1x .. •
`!hrl
`
`1.4
`(l.o-2.5)
`
`2
`(0.98-12.0)
`
`CI/F'
`!Lihrl
`
`t,n .
`
`(hrl
`
`3.85: 1.3
`
`18.1;!; -4.85
`
`3.76 :!: 1.06
`
`Not
`Dctormlned
`
`Single dose 20 mg
`(tablet)
`
`Steady-State
`20mgBID• ..
`
`• Mean : SO
`•• Mean BJJd range
`•••Stoady-State datn were obtained from normal volunteers administered a biocquivalent formulation.
`
`Parameter
`
`Number of Patients
`(Periastat® 20mg BID)
`Number of Patients
`(Placebo)
`Mean Gain (SD"J In ALv"
`Periostnl® 20 mg SID
`Placebo
`
`Mean Decrease (SJYI)
`in PD""'
`Periosta~ 20 mg BTD
`Placebo
`'J> of Sites (SI)'i) with toea
`of ALv" ;,2 mm
`Periastnl® 20 mg BID
`Placebo
`
`'J> of Sites (SD'I with BOP'
`Periostat® 20 mg BID
`Placebo
`
`Clinic.ol Results at Nine Months of Doxycycline HyeJote Capsules,
`20 mg, as an Adjunct to SRP
`(Bioequivalent to Doxycycline Hyclata Ttblots, 20 mgl
`BasoUno Pocket o.t>th
`4-6mm
`
`~3mm
`
`90
`
`93
`
`90
`
`93
`
`:.::7mm
`
`79
`
`78
`
`0.26 (0.29) mm
`0.20 (0.29) mm
`
`1.03 (0.47) mm•
`0.86 (0.48) mm
`
`1.65 ( 1.16) mm•
`1.17 (1.15) mm
`
`.
`
`0.16 (0.19) mm••
`0.05 (0.19) mm
`
`0.96 (0.47) mm••
`0.69 (0.48) mm
`
`1.68 (1.07) mm••
`1.20 (1.06) mm
`
`1.9(4.2~
`2.2(4-t~
`
`39 (19.)%••
`48(19~
`
`U{4.5~
`2.4 (4.4,.
`
`&I (IS~·
`70 (18~
`
`0.3(9.4~·
`3.6(9.4~
`
`75 (29~
`80(29,.
`
`• p<O.OSQ vs. the placebo control group.
`•• p<O.OIO vs. the placebo control group.
`"' Alv : Clinical Attachment Level
`"1>D : Pocket Depth
`1 BOP : BleC!ding on Probing
`11 SD : Standa:rd Deviation
`
`Common Cold
`
`Flu Symptoma
`
`Periodontal A~
`
`Tooth Diaonlor
`
`Nausea
`
`47 (22%)
`
`24 (11~)
`
`14 (7'J>)
`
`8(4'J>)
`
`13 (6'J>)
`
`17 (8'J>)
`
`7(3~)
`
`46 (211J>)
`
`40(1~)
`
`28(13~)
`
`21 (10%)
`
`19 (!I'J>)
`
`l2 (6'J>)
`
`ptt paden~ exhibiting attachment loss of;t: 2 mm from base(cid:173)
`bt, 1111d pem!ntage of tooth sites with bleedilll on probing.
`lilt multi are summarized in t.be toUowilll table.
`ISle .-n.d Ulble at rigbtl
`L\'DICATIONS AND USAGE
`I'W1tata~ is indical.ed for use as an adjunct to scaling and
`fool plllning to promote attachment levtl gain and to reduce
`pocel dtpth in patients with adult periodontitis.
`CON'TRAINDICA:riONS
`'!hil drug ia contraindicated in per110ns who hove sbown hy·
`perscnsltivity to doxycycline or any of the other tot.racy(cid:173)
`dlne$.
`WAllNlNGS
`'!liE USE OF DRUGS OF THE TETRACYCLINE CLASS
`DURING TOOTH DEVELOPMENT (LAST HALF OF
`PREGNANCY, INFANCY AND CHILDFIOOD TO THE
`AGE OF 8 YEAR$) MAY CAUSE PERMANENT DISCOL(cid:173)
`ORATION OF THE TEETH (YELLOW-GRAY-BROWN).
`'l1llt advenre reaction is more common during long·Ur!n uae
`.Cthe cJrucs but has been observed foUowing repeatC!d ahort(cid:173)
`lmll eounea. Enamel hypoplasia baa also been reported..
`Tll'I'RACYCLINE DRUGS, THEREFORE, SHOULD NOT
`BE USED IN THIS AGE GROUP AND IN PREGNANT OR
`NURSING MOTHERS UNLESS THE POTENTIAL BEN·
`EPITS MAY BE ACCEPTABLE DESPITE THE POTEN·
`TW. RISKS.
`Alllctraoyulines fonn a stable calcium complex in any bone
`f~tmlng tissue. A decrease in fibula growth roto hns been
`•rved in premature infant.! given oral tatracycUnas in
`mof26 mgikgevery 6 hours. This reaction wos shown to
`be reversible when the drug waa discont.inucd.
`llox~line can cause fetal harm when admlniatcred to a
`p~3nl woman. Results of animal studies indicate that
`~attaeytlines cross the placenta, are found in felal timsues,
`wl can have toxie eJfects on the developing fetu. (ol\en re(cid:173)
`liwd to retllrdation of skeletal development), Evidence of
`~lY he5 also been noted in animat. treated early
`11: prepADey. If any tetracyclines are caed durinc preg(cid:173)
`IIA!Iq, or if the patient becomes pregnant whil~ taking this
`druc. the patient should be apprised of the potential htuMd
`._the fetu..
`'1M cotsbolie action of the tetracyclines may cauac an in(cid:173)
`crnase in BUN. Previous studies have not observed an in·
`ttWC in BUN with the use of doxycycline !n patients with
`Impaired renal function.
`Pho~Qsruleitivity manifested by an exaggerated sunburn re(cid:173)
`arlion hu been ob&!rved in some individuals taking tetro(cid:173)
`cydinet. Patients apt to be exposed to direct sunlight or ul(cid:173)
`tmiolet light should be ad-.ised that thiB reaction can occur
`With tetracycline drugs, and treatment should be di&CQntin·
`lleCi at. the 6rst evidence of skin erythema.
`PRECAtrriONS
`Whllot no overgrowth by opportunistic mieroorpniams such
`u JIUI were noted during-cliniatJ awdiea, u with other
`&ntimieJObiab, Periostal® therapy may reault in ov«·
`powth or oonsusceptible microorganisms including fungi.
`Tbe use of unncyclines may increase the incidence of vag·
`•311 candldjaais.
`Ptriostst.® should be used with caution in patients with a
`history or pred!spo.Ution to oral candidiasis. The safety and
`tll'ectivenesa of Periostat® has not been establisbed for the
`trtabnant of periodontitis in patients with ooexistan~ oral
`w.dldiosis.
`If superinfection is sllSpected, appropriate measures should
`betaken.
`In long tenn therapy, periodic laboro(cid:173)
`laboratory Tests:
`txyevaluations of organ systems, includin~ hematopoietic,
`rw~ and hepatic studies should be performC!d.
`liNg lntt,.ctions: Because tetracyclines have been abown
`It depress plasma prothrombin activity, palienta who are on
`J~~~~to~~gulant therapy may require downward acijUJtment
`.C lhcit anticoagulant dosage.
`SUa b..cterial anb"bioties, such as the tettncyclin" clasa of
`&ntlh!otics, may interfere with the bactericidal action of
`1111mbers of the -I adam (e.g. penicillin) clasa of antibiotics,
`a II not advisable to administer these antibiotics concomi(cid:173)
`tanUy.
`Ablorption of tetracyclines is impaired by antacids contain(cid:173)
`in& alurolnum, cakium, or magnesium, and iron·containing
`preparations, and by bismuth subsalicylnto.
`Batbiturates, carbamazepine, and phenytoin decrease the
`balf.life or doxycycline.
`1111 concllmlnt use of tetracycline and methOJcyfturane bas
`been reported to result in fatal renal toxicity.
`C.Unent ase of tetracyclines may render oral contraeep(cid:173)
`b<'el leu elfec:tive.
`Dova/labonltory Test Interactions' False elevations of uri·
`111f1 ea!«holamine levels may occur due to interference
`wilh lbe fluorescence test.
`c.rctnogonesls, Mutagenesis. lmpoirment of F..-tllity:
`~ine hyc4te he5 not been evalu.atod for can:lnogenic
`pclmtiol in long-term animal studies. Evidence of oncogenic
`ldivity was obtained in studies with related compounds,
`''·• oxytatrncycUne (adrenal and pituitary tumors), nnd mJ.
`llCC)'tline (thyroid tumors).
`Doxy~cline nyelate demonstrated no potential to cause ge(cid:173)
`netic toxicity in an in uitro point mutation atudy with mam(cid:173)
`ulian cells (CHOIHGPRT forward mutation aseay) or in
`111 U. uivo micronucleus assay conducted in CD-I mice.
`
`However, data from nn i11 vitro assay with CHO cella for per
`tnntial to cause chromosomal aberTations suggest that doxy(cid:173)
`cycline hyclate is a wenk daatogen.
`Oral administration of do>cyeycline hyclate to male and fe(cid:173)
`male Sprague-Oawley rata ad\'enely alfected fertility and
`reproductive performance, as cwidenced by increased time
`for mating to ooc:ur, reduced aperm motility, velocity, and
`concentration, abnonnal apenn morphology, and increased
`pre-and post-implanta~ion loues. Doxycycline byclat.e in·
`duced reproductive toxicity at aU dosages that were exam·
`ined in this study, 8.f even the lowest dosage tested
`(SQ mglkg/dayl induced a atatistically significant reductJon
`in sporm velocity. Not<! that 60 mglkg/day is approximately
`10 times the amount of doxycycline hyelate contained in the
`re<:ommendC!d daily dose of Periostat.® ror a 60 kg bwnan
`when compared on the basis of body surface area estimates
`(mg/m2). Although do~ycline impairs the fertility of rat.!
`when administered at sufficient dosage, the effect of
`Periostat® on human fertility is unknown.
`Pregnancy: Ter•togenlc EffKtlJ: Pregnancy Category D.
`(See WARNINGS Section). Results from animal studies in·
`dicate that dox;)-q.-dino Ct'OI&eSlhe placenta and is found in
`fetal tis-~.
`Nonter~~togenlc ttffiH!IJ~: (See WARNINGS Section).
`Labor and Delivery: The etrect of t.etneyclines on labor
`and deUvery is unknown.
`Nursing Mothers: Tet:rocycline8 are excreted in human
`milk. Because of the potenUal for serious adverse reaetioClll
`in nursing infanta from doxycycline, the uae ofPeriosta!® in
`nursing mothers is oontraindicatod. (See WARNINGS Sec(cid:173)
`tion).
`Pediatric Use: The \I.Se of Porlostat.® in infancy and child·
`hood is contraindicated. (See WAllNINGS section.)
`ADVERSE REACTIONS
`Adveru ReBctions In Clinical Trials of a bloequivBient form
`of doxycyclin• hyclate capsules: In clinical trials of adult
`patients with periodontal disease 213 patients received 20
`mg BID over a 9-12 month period. The most frequent ad(cid:173)
`verse reactions occurring in 1tudi01 involving treatment
`with a bioequivalent form of d~ine byclAt.e capsules or
`pl~bo are listed below:
`
`Incidence ('1'.1 of Adverse Rnctlons In CUnic.ol Trials
`of Doxycycline HyeJato CapsuiM, 20mg
`(Bioequivslent to Doxycycline Hyclate Tabl&t$, 20mg)
`vs. Pltcebo
`
`Adverse Reaction
`
`Doxycycllna Hyclate Placebo
`Capsules 20 mg BID
`(n:2151
`(n=2131
`
`Headache
`
`55 (26%)
`
`66 (26'J>)
`
`Sinusltis
`
`Injury
`
`Dyspopaio
`
`Soro Thront
`
`Joint Pain
`
`Diarrhea
`
`Sinus Coneeat.ion
`
`Sinua Headache
`
`Rash
`
`Back Pain
`
`Back Acha
`
`Menstrual Crnmp
`
`Acid !ndiaeatlon
`
`Pain
`
`!nfoc:tion
`
`Gum Pain
`
`Bronchitis
`
`Mu&<:lc·Pnin
`
`11 (5~)
`
`13(6%)
`
`11 (5%)
`
`12 (6'J>)
`
`12 (6'J>)
`
`11 (5'J>)
`
`9 (4'J>)
`
`8(4'J>)
`
`8(4%)
`
`7(3%)
`
`4 (2'J>)
`
`9 (4%)
`
`8 (4'J>)
`
`8 (4%)
`
`4 (2'\111)
`
`1 (< l'J>)
`
`7 (3'J>)
`
`2(1%)
`
`18 (8%)
`
`18 (8%)
`
`5(2%)
`
`13(6%)
`
`8(4'J>)
`
`8(4\1)
`
`11 (5\1)
`
`11 (6%)
`
`8(4'J>)
`
`8(8%)
`
`8 (4'*>)
`
`9(4%)
`
`6 (2%)
`
`7(3'J>)
`
`6(2'1)
`
`6(3'-')
`
`6(3'J>)
`
`6(2'\111)
`
`6(3%)
`
`Note: Pertlentages nre based on total number of study pnr(cid:173)
`ticipantll in each treatment group.
`
`Continued on n•xt page
`
`Cot>SUit 2002 PORI' oupplements and future aditiono foe rwlolons
`
`2
`
`

`

`1210/COLLAGENEX
`
`Periostat- Cont.
`
`Adverse React ions for Tetracyclines: The following nd·
`verse reactions have been observed in patients receiving tet(cid:173)
`racyclines:
`Gastrointestinal: anorexia, nausea, vomiting, diarrhea,
`glossitis, dysphagia, enterocolitis, and inflammatory lesions
`(with vaginal candidi~U~is) in the anogenital region. Hepato(cid:173)
`toxicity biU! been reported rarely. Rare instances of esopha(cid:173)
`gitis and esophageal ulcerations have been reported in pa(cid:173)
`tients receiving the capsuJe forms of the drugs in the tetra(cid:173)
`cycline class. Most of these patients took medications
`immed;ately before going to bed. (See DOSAGE AND AD·
`MINISTRATION Section).
`Skin: maculopapular and erythematous rashes. Exfolia(cid:173)
`tive dermatitis has been reported but is uncommon. Photo(cid:173)
`sensitivity is discussed above. (See WARNINGS Section).
`Renal toxicity: Rise in BUN has been reported and is ap·
`parently dose related. (See WARNINGS Section).
`Hypersensitivity
`reactions: urticaria,
`angioneurotic
`edema, anaphylaxis, anaphylactoid purpura, serum sick(cid:173)
`ness, pericard;tis, and exacerbation of systemic lupus ery·
`thematosus.
`Blood: Hemolytic anemia, thrombocytopenia, neutropenia,
`and eosinophilia have been reported.
`
`OVERDOSAGE
`ln case of overdosage, discontinue medication, treat symp(cid:173)
`tomatically and institute supportive measures. Dialysis
`does not alter serum half-Ufe and thus would not be of ben.
`efit in treating cases of overdose.
`DOSAGE AND ADI'<IINISTRATION
`THE DOSAGE OF PERIOSTAT® DIFFERS FROM THAT
`OF DOXYCYCLINE USED TO TREAT INFECTIONS. EX(cid:173)
`CEEDING THE RECOMMENDED DOSAGE MAY RE(cid:173)
`SULT IN AN INCREASED INCIDENCE OF SIDE EF·
`FECTS INCLUDING THE DEVEWPMENT OF RESIS(cid:173)
`TANT MICROORGANISMS.
`Periostat® 20 mg twice daily as an adj unct following scaling
`and root planing may be administered for up to 9 months.
`Periostat® should be taken twice daily at 12 hour intervals,
`usually in the morning and evening. It is recommended that
`if Periost.at® is taken close to meal times, allow at least one
`hour prior to or two hours afl:er meals. Safety beyond 12
`months and efficacy beyond 9 months have not been estab(cid:173)
`lished.
`Administration or adequate amounts of lluid along with the
`tablets is recommended to wash down tbe drug and reduce
`the risk of esophageal irritation and ulceration. (See AD·
`VERSE REACTIONS Section).
`
`HOW SUPPLIED
`Periostat® (white tablet imprinted with a PS20) containing
`doxycycline byclate equivalent to 20 mg doxycycline. Bottle
`of 60 (NDC 64682-{)08-01), Bottle of 100 (NDC 64682-008·
`02) and Bottle of 1000 (NDC 64682-008..03).
`Storage: All products are to be stored at controlled room
`temperatures of 15'0-aO'C (59'F-86'F) and d;spensed in
`tight, light-resistant containers CUSP).
`Rx Only
`PERJOSTAT® is a trademark of CollaGenex Pharmaceuti(cid:173)
`cals, Inc., Newtown, PA, 18940
`Manufactured by:
`Pharmaceutical Manufacturing Researeh Services, Inc.
`Horsham, PA 19044
`Marketed by:
`CollaGenex Pharmaceuticals, Inc.
`Newtown, PA, 18940
`
`REFERENCES
`1. Golub L.M., Sorsa T., Lee H·M, Ciancio S., Sorbi D., Ra(cid:173)
`mamurthy N.S., Gruber B., Salo T., Konttinen Y.T.: Doxy(cid:173)
`cycline Inhibits Neutrophil (PMN)-type Matrix Metallo·
`proteinases in Human Adult Periodontitis Gingiva. J.
`Clin. Periodontol 1995; 22: 100-109.
`2. Golub L.M., Ciancio S., Ramamurt.by N.S., Leung M., Me•
`Namara T.F.: Low-dose Doxycycline Therapy: Effect on
`Gingival and Crevicular F luid Collagenase Activity in
`Humans. J. Periodont Res 1990; 25: 321-330.
`3. Golub L.M., Lee H.M., Greenwald R.A., Ryan M.E., Siuo
`T., Giannobile W.V.: A Matrix Metalloproteinase Inhibitor
`Reduces Bone-type Collagen Degradation Fragxneo.ts and
`Specific Collegenases in Gingival Crevicular Fluid Dur(cid:173)
`ing Adult Pericxlontitis. Inflammation Research 1997; 46:
`310-319.
`4 . Saivain S., Houin G.: Clinical Pharmacolcinetics of Doxy(cid:173)
`cycline and Minocycline. Olin. Pharmacolcinetics 1988;
`15; 355-366.
`5. Schach von Wittenau M., '!Womey T.: The Disposition of
`Doxycycline by Mao and Dog. Chemoth.erapy \9-71; 16:
`217- 228.
`6. Campistron G.; Coulaia Y., Caillard C., Mosser J., Pontag(cid:173)
`nier H., Rouin G.: Pharmacokinetics aod Bioavailability
`of Doxycycline in Humans. A:rzneimittel Forschung 1986;
`36: 1705-1707.
`
`Connetics Corporation
`3294 W ES T BAYSHORE ROAD
`PALO ALTO. CA 94303
`
`Direct lnquirill$ to:
`(650) 843-2800
`FAX: (650) 843-2899
`www.connetics.com
`For Medical Information Contact:
`Med;cal Information Department
`(877) 821·5337
`FAX: (510) 595-8183
`E-mail: medicalaffairs@eonnetics.com
`
`L UXiQTM
`fbetamethasone valerate) Foa m, 0.12%
`Rx Only
`For Dermatologic Use Only
`Not for Ophthalmic Use
`
`DESCRJPTION
`Luxiq contains betamethasone valerate, USP, a synthetic
`corticosteroid, for topical dermatologic use. The corticostar(cid:173)
`oids constit11te a class of primarily synthetic steroids used
`topically as anti-inflammatory agents.
`Chemi~lly, betamethasone valerate is 9-lluoro-1113,17,21·
`t•·ihydroxy-16J3-methylpregna-1.4·diene·3,20-dione 17-val(cid:173)
`erate, with the empirical formula C27H37F06, a molecular
`weight of 476.58 (CAS Registry Number 2152-44--5) and the
`following structural formula :
`
`BelameUtasone 17-waferate
`Bctamethasone valerate is a white to practically white,
`odorless crystalline powder, and is practically insoluble in
`water, freely soluble in acetone and in chloroform, soluble in
`alcohol and slightly soluble in benzene and in ether.
`Eacb gram of Luxlq contains 1.2 mg betamethasone
`valerate, !JSP, in a hydroalcobolic, ther molabile foam. The
`foam also contains cetyl alcohol, citric acid, ethanol (60.4%),
`polysorbate 60, potassium citrate, propylene glycol, purified
`water, and stearyl alcohol, and is dispensed from ao alumi(cid:173)
`num can pressurized with a hydrocarbon propellant (p.ro(cid:173)
`panelbutane).
`CLINICAL P HARMACOLOGY
`Like other topical corticosteroids, betamethasooe valerate
`foam has anti-inflammatory, anti-pr uritic, and vasoconstric·
`tive properties. The mechanism of the anti-inflammatory
`activity of the topical steroids, in general, is unclear. How(cid:173)
`ever, corncosteroids are thought to act by the induction of
`phosphotipase A., inhibitory proteins, collectively called lipo(cid:173)
`cortins. It is postulated that these proteins control the bio(cid:173)
`syothesb of potent med;ators of inflammation such as pros(cid:173)
`taglandins and leukotrienes by inhibiting the release of
`their common precursor arachidonic acid. Arachidonic acid
`is released from membrane phospholipids by phospholipase
`A.,.
`Pharmacokinetics:
`1bpical corticosteroids can be absorbed from intact healthy
`skin. The extent of percutaneous absorption of topical corti(cid:173)
`costeroids is determined by many factors, including the ve(cid:173)
`hicle and th.e integrity of the epidermal barrier. Occlusion,
`inflammation and/or other clisease processes in the skin
`may also increase percutaneous absorption.
`The use of pharmacodynam.ic endpoints for assessing the
`systemic exposure of topical cort.icosteroi'ds is necessary due
`to the fact that circulating levels are well below the level of
`detection. Once absorbed through the sldn, topical corticos(cid:173)
`teroids are handled through pharmacokinetic pathways
`similar to systemically administered corticosteroids. They
`are metabolized, primarily in the liver, and are then ex·
`creted by the kidneys. In addition, some corticosteroids and
`their metabolites are a.lso excreted in the bile.
`CLINICAL STUDIES
`The safety and efficacy ofLuxiq has been demonstrated in a
`four-wee:< trial. An adequato and well-controlled clinical
`
`PHYSICIANS' DESK REFERENCE®
`
`trial was conducted in 190 patients with moderate to severe
`scalp psoriasis. Patients were treated twice daily for four
`weeks with Luxlq Foam, Placebo foam. a commercially
`available betamethasone valerate lotion 0.12% (formerly ex·
`pressed as 0.1% betamethasone), or Placebo lotion. At four
`weeks of treatment, study results of 159 patients demon(cid:173)
`strated that the efficacy ofLuxiq Foam in treating scalp pso(cid:173)
`riasis is superior to that of P lacebo foam, and is comparable
`to that of a eurrently marketed BMV lotion (see Table be(cid:173)
`low).
`(See table below)
`INDICATIONS AND USAGE
`Luxlq is a med;um potency topical corticosteroid inclicated
`for relief of the inflammatory and pruritic manifestations of
`corticosteroid-responsive dermatoses of the scalp.
`CONTRAINDI CATIONS
`Luxlq is contrainclicated in patients wbo are hypersensitive
`to betamethasone va.lerate, to other corticosteroids, or to
`any ingredient in this preparation.
`PRECAUTIONS
`General: Systemic absorption of topical corticosteroids bas
`caused reversible hypothalamic·pituitary-adrenal (HPA)
`axis suppression with the potential for glucocorticosteroid
`insufficiency after withdrawal of treatment. Manifestations
`of Cushing's syndrome, hyperglycemia, and glucosuria ean
`also be produced in some patients by systemic absorption of
`topical corticosteroids while on treatment.
`Conclitions which augment systemic absorption include the
`application of the more potent staroids, use over large sur(cid:173)
`face areas, prolonged use, and the addition of occlusive
`dressings.
`Therefore, patients applying a topical steroid to a large sur·
`face area or to areas under occlusion should be evaluated
`periodically for evidence of HPA axis s uppression. l f HPA
`axis s uppression is noted, an attempt should be made to
`withdraw the drug, to reduce the frequency of application,
`or to substitute a less potent steroid.
`Recovery ofHPA axis function is generally prompt upon dis(cid:173)
`continuation of topical corticostoroids. Infrequently, signs
`and symptoms of glucocorticosteroid insufficiency may occur
`requiring supplemental systemic corticosteroids. For infor(cid:173)
`mation on systemic supplementation, see prescribing infor(cid:173)
`mation for those products.
`Pediatric patients may be more susceptible to systemic tox(cid:173)
`icity from equivaJeot doses due to their larger skin surface
`to body mass ratios. (See PRECAUTIONS-Pediatric Use.)
`If irritation develops, Lux1q should be cliscontinued and ap(cid:173)
`propriate therapy instituted. Allergic contact dermatitis
`with corticosteroids is usually cliagnosed by observing a fail(cid:173)
`ure to heal rather than noting a clinical exacerbation, as
`with mosL topicaJ products not containing corticosteroids.
`Such an observation should be corroborated with appropri·
`ato diagnostic patch testing.
`In the presence of dermatological infections, the use of an
`appropriate antifungal or antibacterial agent should be in(cid:173)
`stituted. If a favorable response does not occur promptly,
`use of Luxiq should be d;scontinued untiJ the infection bas
`been adequately controlled.
`Information for Patients: Patients using topical corticos·
`teroids should receive the following information and in(cid:173)
`structions:
`L This roed;cation is to be used as clirected by the physi·
`clan. lt is for external use onJy. Avoid contact with the
`eyes.
`2. This medication should not be used for any disorder other
`than that for which it was prescribed.
`3. The treated scalp area should not be bandaged or other(cid:173)
`wise covered or wrapped so a~ to be occlusive unless di(cid:173)
`rected by the physician.
`4. Patients should report to their physician any s igns of lo(cid:173)
`cal adverse reactions.
`5. As with other corticosteroids, therapy should be discon(cid:173)
`tinued when control is achieved. If no improvement is
`seen Within 2 weeks, contact the physician.
`Laboratory Tests: The following tests may be helpful in
`evaluating patients for HPA axis suppression:
`ACTH stimulation test
`A.M. plasma cortisol tost
`Urinary free cortisol test
`Carcinoganesis. Mutagenesis, and Impairment of Fertility:
`Long-term animal studi