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`www, PDR.Net
`ED
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`AMN1037
`Amneal v. Almirall, LLC
`IPR2018-00608
`
`1
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`€
`

`

`The Property of
`Steme, Kessler, Goldstein & Fax, P.L.L.C.
`
`PDR’
`60
`
`2006
`
`EDITION
`
`
`
`PHYSICIANS
`EOK
`REFERENCE
`
`Senior Vice President, PDR Sales and Marketing: Dikran N. Barsamian
`Vice President, Product Management:William T. Hicks
`Vice President, Regulatory Affairs: Mukesh Mehta, RPh
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`Senior Director, Publishing Sales and Marketing: Michael Bennett
`Director, Trade Sales: Bill Gaffney
`Associate Director, Marketing: Jennifer M. Fronzaglia
`Senior Marketing Manager: Kim Marich
`t
`Direct Mail Manager: Lorraine M. Loening
`Manager, Marketing Analysis: Dina A. Maeder
`Promotion Manager: Linda Levine
`
`Director, Client Services: Stephanie Struble
`Director, Clinical Content: Thomas Fleming, PharmD
`Director, Editorial Services: Bette LaGow
`
`Drug information Specialists: Michael DeLuca, PharmD, MBA;
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`Copyright © 2006 and published by Thomson PDRat Montvale, NJ 07645-1742. All rights reserved. None of the contentof this publication
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`ISBN: 1-56363-526:
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`2
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`
`
`
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`a
`- Solagé
`=
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`0.3 mg/vial
`
`olage
`Solagé®
`Betaseron®
`(mequinol 2%,tretinoin
`(Interferon beta-1b)
`0.01% topical solution, 30 mL)
`**The name BEACHappears onthe reverseside of these tablets.
`
`3
`
`

`

`PHYSICIANS’ DESK REFERENoy8
`FREQUENCY*
`AGE? «:,
`The-mechanismof.actionof;mequinol-is.unknown,
`th,
`‘
`al
`Balamine DM Oral Drops
`mequinol'is.a substrate forthe enzyme tyrosinase ay,sth
`‘
`,
`For Oral Use Only
`as a competitive inhibitor of theformation, of melan
`cursors, the clinical significance of thesefindings"me
`he
`qid.
`1/4 dropperful (1/4 mL)
`1-3 months
`é
`quid.
`wee
`1/2:dropperful(1/2, mL)
`3-6 months
`known. The;mechanism -of action. of tretinoin ag aos
`as
`q.id.
`3/4 dropperful (3/4 mL).
`6-9 months
`menting agent also is unknown.
`PHARMACOKINETICS
`
`
`9-18 months ‘I dropperful(1mL)., qid.-
`Balamine DM Syrup
`an
`dei
`- The percutaneous absorption of tretinoin and the<S¥5
`18 months-6 years
`1/2 teaspoonful
`q.id.
`exposure to tretinoin and tmequinol were Asseay“tig
`:
`i
`5
`(2.5 mL)
`healthy subjects (n=8)°following two weeks of twiceee
`adults and children
`1 teaspoonful
`qid.
`topical treatment ofSolagé Solution.. Approximatelyv0, ally
`6 years and over
`(6 mL)
`of Solagé Solution was applied to 2400 cm? areg But
`back, corresponding to a dose of 37.3 g/cm? for oethe
`: and 0.23 pg/om? for tretinoin. The percutaneous abso
`2
`oftretinoin was‘approximately 44%, andsystemic »teme
`Cyaxfor mequinolwas9.92 ng/mL (range 4.22 to’o3°2
`trations did not increase over endogenous levels, The
`miL)'and the Tox:was 2how ‘(range 1 to2hours),
`~ Ogy
`INDICATIONS AND:USAGE
`(To understand fully the indication for this product; ple
`read the entire INDICATIONSAND amasectionoe
`labeling).
`Solagé (mequinol 2%, tretinoin-0.01%) Topieal Solution®
`indicated for the treatmentofsolar lentigines.
`Solagé Solution should only be used under medica] Supe
`vision as an adjunct to a comprehensive skin care ed
`avoidance program where the patient shouldPrimarily .:
`ther avoid the sun.or use ‘protectiveclothing.
`Neither the safety nor effectiveness of Solagé. Sohution for
`the preventionor treatment;ofjmelasma or ppostinflamm,.
`tory hyperpigmentation has been established.
`a
`Theefficacy of using Solagé Solution.daily for
`24 weeks has not been established.
`Sreaterthay
`Thelocal cutaneoussafety of using Solagé Solutionin nigh:
`Caucasians has not been adequately established (sée Chan.
`ical Studies section).
`vat
`CONTRAINDICATIONS
`The combination of mequinol and tretinoin may|Cause feta]
`harm,when administered to a pregnant, woman. Due éo the
`known effects of.thesé*‘active ingredients,Solage Topical
`Solution should “not be used in women of childbearing
`potential.
`In a dermal teratology study in New Zealand White rabbits,
`there were no statistically, significant differences among
`treatment groups in fetal malformation data; however
`marked hydrocephaly with visible doming of the head was
`observed in one mid-doselitterh2 and 0:06<mg/kg-or 133
`| and 0.66 mg/m?ofmequinol and tretinoin, respectively) and
`two fetuses in one high doselitter (40.and 0.2 me/kg or,dai
`and 2.2.mg/m? of mequinol and tretinoin, respectively) of
`Solagé Solution, and two. high-dosetretinoin (0.2 mg/kg,
`2.2-meg/m*) treated litters. These malformations ‘were con:
`sidered‘to be tréatment related and dueto the knowneffecis
`of tretinoin. This was further: supported*by ‘coincident ap-
`peararice ofother malformation§ associated with tPetinoin;
`such as, cleft -palate and appendiculariskeletal defects. No
`effects attributed to treatinent were ‘ébserved in ‘rabbits in
`that study treatedtopically with. mequinol alone: (dose
`40 mg/kg, 440mg/m?») Ano-observed-effect level (NOEL) fo:
`teratogenicity;“in . crabbit3" was established at 4 and
`| 0.02 mg/kg (44 arid 0.22 mg/m? mequitiol and tretinoin, Te
`spectively) for Solagé Solution whichis approximately the
`maximum possiblehuman-daily:doséybased on clinical-ap-
`plication to 5% oftotal,body surface area. Plasma sretinoul
`concentrations, were not raised above endogenous levels,
`even at teratogenic doses. Plasma mequinol concentrations
`in rabbits at the NOEL. at.one hour after application W&"
`iD
`124 ng/mL, or approximately twelve.times.the mean pe
`plasma concentrations. of that.substance seen in huma
`subjects in a clinical pharmacokinetic. study. Ina repeated
`‘ study. in pregnant rabbits administered-the same:dose?!
`els.as the study described above,;additional precautionalis
`measureswere taken to prevent ingestion, although ese|
`no evidenceto confirm that ingestion occurred in;the !
`study. Precautionary measures additionally .limited tat
`dermal absorption-to a.six-hour exposure period, or Pole
`imately. one-fourth.of the human. clinical daily continulyte
`exposure time. This: study.‘did not show any. significan the
`atogenic effects at doses up to approximately,-13 times
`human. dose on'a-mg/m” basis. However, a concurrent
`tinoin. dose group (0.2 mg/kg/day).did include two li
`with limb malformations.
`.
`‘qpaetlt
`In a published study in albino rats (J.‘Arms Coll;
`12
`4(5):31-63, 1985), topical application of 5% of mequiN?
`cream vehicle during gestation was embryotoxic 4%ated
`bryolethal. Embryenic loss prior to implantation,Was
`ost
`in that study where animals were treated through onl
`tation. Coincidentally, mean preimplantation em?”
`dl
`loss was increasedin the’first rabbit study in‘all- m¢
`treated groups, relative to control;and in the high @ose
`quinol/tretinoin and tretinoin onlytreated grove +i08
`second study. In those studies, dosing -began at geoaste
`day 6, when implantation is purported. to oecur.
`1n¢ “pint
`preimplantation loss was also noted’ at the high cor
`ewe
`tion dose in astudy of early embryonic effects in rat,"re cor
`decreased bodyweightin male pups: these finding? 4”
`sistent with.the published study.
`Daoe
`er.
`Solagé Solution was not teratogenicin'gprage
`Mm
`rats when given in topical doses of 80 ‘And 0.4 mi
`quinol and tretinoin, respectively (480 and 2.4 mé!mni
`times the maximum human daily-dose). The maximtiedrail
`- mandoseis defined asithe amountof-solution apP!”
`to 5% of the total body surface. area.
`tt
`
`* In mild cases or in particularlysensitivepatients, less frequent. or reduced doses may be adequate. .
`gi Aes
`anticonvulsantsto CoxonCNS Exciter’‘and aati
`Balamine DM—Cont.
`h) Physostigmine may.,reverse; anticholinergicsymptoms,
`i) Ammonium chloride may acidify the urineto increase
`urinary excretion. of pseudoephedrine. j) qurcharsecare is’
`symptomatic and supportive.
`DOSAGE AND ADMINISTRATION
`[See table above]
`N 1
`HOW SUPPLIED.
`: Balamine DM Oral Drops, grape flavored, in 30‘miL bottles,
`with’calibrated droppets, NDC 63162-509-30.
`Balamine DM Syrup, grape flavored, in 16-f1. 62: (15pint)
`bottles, NDC 63162-508-16.
`Dispense. in USPtight, light-resistant container.eee
`posure*to excessive. heat.
`ue
`a
`+
`Rx ONLY
`:
`
`Revised 12/01 :
`BALLAY.
`uae
`Manufactured for:
`
`Ballay-Pharmaceuticals, Ine.
`Wimberley, Tx.'78676
`
`-
`ue
`
`Direct Inquiries to:
`Phone:-866-440-5508"
`
`sivas
`
`SOLAGE@
`[s0=laj-@']
`(mequinol 2%, tretinoin 0.01%).
`‘Topical Solution a
`‘For Dermatologicuse only. Not for ophthalmic, oralcor,
`intrayaginaluse.
`Rx. only
`
`1S
`
`Sey
`ofr pt
`Solagé® Topical Solution contains mequinol2% and tre-
`tinoin 0.01%, byweight, :in.a solution base of ethyl alechol
`(77.8% viv), polyethylene glycol,4400; butylated hydroxytolu-
`ene, ascorbic acid,citric acid,sasorby!palmitate, edetate di-
`sodium -andpurified,water.
`at
`
`
`Mequinoliis 4--hydroxyanisole, the TONG ethyl ether:of hy;
`droquinone; or 1;hydroxy-4-methox!
`
`chemical formula, CaHg0., a moleg
`and the structural formula:
`H3COCO)os
`The. chemical name for iretinoin, a retinoid,iis (all-E)-3,q-
`dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-non-
`atetraenoic.acid, also.referredto as all-trans-retinoic acid.It
`has the chemical. formula, CopH,0., a molecular weightof
`300.44, and the structural formula:
`
`
`
`a
`CLINICAL PHARMACOLOGY
`Solar lentigines are loc#lized, pigmented, macularlesiéns of
`the skin on thé areasof the ‘body which have been chroni-
`cally exposed to sunlight.
`Biopsy specimensofsolar lentigines werecollected ina clin-
`icalstudy with Solagé Solution at ‘baséline, at the end of a
`24 week treatmentperiod and at the erid of a subsequent 24
`week, no treatment, follow-up period. The end oftreatment
`specimens showed a decreasé in melanin pigmentation in
`both-melanocytes and keratinocytes, and an increased-lym-
`phocytic infiltration, which may have beentie result of ir-
`ritation or an immunologic reaction. The end ‘of follow-“up
`period specimens showed repigmentation of the melano-
`cytes and keratinocytes to a state similar to -the baseline
`specimens. These results indicate that there isno assurande
`that any improvement obtained would: persist upon discon-
`tinuation of drug therapy.
`
`
`
`.
`
`
`
`
`
`DOSE*, .
`
`=;
`
`Kee
`
`excreted iin-human milk. Becausemany | DESCRIPTION
`
`coughand take caution that modification of mint doesnot
`inerédse the risk of clinical or physiologic complications.
`Dextromethorphan should be used with, caution in sedated
`or debilitated patients and in patients confined to supine
`positions.
`Use with caution ‘in patients’ with |hypertension, heart
`disease, asthma, hyperthyroidism,increased’ intraocular
`pressure, diabetes mellitus and prostatic’‘hypertrophy.
`s
`Information for Patients: Avoid alcohol and other CNS de-
`pressants while taking these products. Patients sensitive|to
`antihistamines may experience moderate to severe drowsi-
`ness. Patients:“sensitive to sympathomimetic amines may
`note mild CNS stimulation. While takitig. thesé products,
`exercise care indriving or dperating.appliances, machinery,
`ete.
`DrugInteractions: Antihistamines. may enhance the ef-
`fects of tricycli¢, antidepregsants, barbiturates, alcohol, and
`other CNS deptessants. MAO inhibitors prolong and inten-
`sify the:anticholinergi¢ effects of antihistamines.
`~
`Sympathomimétic amines may reduce the antihypertensive
`effects’ of reserpine, vératrum alkaloids, méthyldopa and
`mecamylamine. Effects of sympathomimetits are increased
`with MAO inhibitors and: beta-adrenergic blockers:
`.The
`cough-suppressantaction of:dextromethorphan: and narcotic
`antitussivesare additive. -Dextromethorphan:iis contraindi;
`cated with monoamine oxidaseinhibitors (MAQD).See. Con;
`traindications section.
`Pregnancy:Category c: _Animal reproduction studies have
`not been.conducted with Balamine DM.It is alsonot known
`whether these products cancause fetal harm when admin-
`istered to apregnant woman or. affectreproduction capacity.
`Giveto, pregnant, women only ifclearly rneeded.
`Nursing; Mothers:
`It is not,known whether the drugsiin
`Balamine DM. are
`drugs-are excreted in human milk and becauseofthepoten-
`‘tial for-serious adverse reactionsin nursing:infants, a deci-
`sion should be made whether to discontinue nursingior,dis-
`continue theproduct, taking into account,the. importanceof
`the-drug. to:the mother.
`ai
`ADVERSE REACTIONS
`Antihistamines: Sedation,dizziness, diplopia, vorniting,
`diarrhea, dry mouth, ‘headache; -neryousness, nausea,
`Anorexia, heartburn,weakness, polydria and dysusia and,
`rarely, excitabilityiin children: Urinary retentiontinay‘occur
`in-patients with prostatic ‘hypertrophy.’
`Sympathomimetic Amines: Convulsions, CNS stimulation,
`.eardiac arrhythmias, respiratory difficulty, increased heart
`rate or. blood.pressure, hallucinations, .tremors, nervous:.
`ness, insomnia, weakness, pallor and ‘dysuria,
`‘and GI
`Dextromethorphan: Drowsiness, dizziness,.
`disturbance.
`eet,
`OVERDOSAGE
`No.information is available as to specific results of an,over-
`dose of these products. The signs, symptoms and treatment
`described. belowsare those of H, antihistamine, ephedrine
`and.,dextromethorphan overdose.
`.
`Symptoms: Should antihistamine effects predominate,
`central action-constitutes the greatest, danger, In the small
`child, predominant symptomsareexcitation, hallucination,
`ataxia, incoordination,tremors, flushed.face andfever.
`Convulsions, fixed anddilated pupils, coma anddeath may
`occur in severe.cases. In the aduilt, fever and flushing are
`_ uncommon;excitement leading to convulsions and postictal
`depression is dfteri preceded by drowsiiess and toma. Res-
`pirationis-usually not Sreeperense ipspressureds
`usually stable. *:
`ype
`Should aynipathiiiimatic Syaiptoing pipdodiinates central
`effects include restlessness, dizziness, tiemor, hyperactive
`reflexes, talkativeness, irritability and insomnia. Cardio-
`vascular ahd. renal effects include difficulty in ‘micturition,
`héadache;flishing, palpitation, cardiac arrhythmias; ‘hy-
`pertefision with subséquent hypotension and circulatory
`collapse. Gastroiiitestinal effects ‘include’ diy mouth, metal-
`lictaste, anoréxid; nausea, vomiting, diarrhea, and‘abdom:
`inal cramps.
`Dextromethorphan may-catse respiratory‘depressionwitht a
`large overdose.
`Treatment:
`a) Evacuate stomach as condition warrants.
`Activated charcoal may be useful. b) Maintain a non-
`stimulating envirenment. c) Monitor cardiovascular status,
`d) Do notgive stimulants. e) Reduce fever with cool. spong-
`ing. f) Treat respiratory depression with naloxoneif dextro-
`methorphan toxicity..is suspected. g) Use sedatives or
`
`|
`
`Information will,be superseded by supplementsand subsequenteditions
`
`4
`
`4
`
`

`

`
`
`ORMATION
`
`
`
`BARRIER/741
`
`
`
`
`
`
`
`
`
`
`Avely, representing approximately 5 times
`
`
`
`
`
`
`
`
`
`
`_ Face
`i Foréatiris/Back of Hands
`
`“
`Solagé Solutién |
`Vehicle
`Sree Solution
`fu
`2Vehiele a
`
`
`Moderate Improvement
`51%
`15%" ote |
`. “54%
`Ss 14%
`:
`or greater’
`iri
`Be
`:
`eRe
`
`Slight Improvement
`28% ee
`36%
`26%.
`38%Te
`
`No Change? ~,..
`ue
`49%
`"20%.
`53%
`LIncludes the following grades: Moderate Improvement, Marked Improvement, Almost Clear, Completely Clear.“Moderate
`, fmprovement or greater was consideredclinicallymiéaningful.
`a
`? Includes the followinggrades,NoChange,.Worse(less than 1%.ofpatie treated“with Sélagé Solutionwere yated as
`worse).
`the maximurh'‘possib le systemi¢ human exposure,was riot
`carcinogenic,'‘in a _photocarcinogenicity study.
`tilizing
`Cri:SRh-I(br/hr’ BR) ‘hairless albino mice, medidii
`time to
`anéet!of”tumors, decreased. ‘Also, the number of tumors iin:
`creaséd-i‘in all dose groupsadministered 1.4°4'3 of14 ulof"
`Sblagé Solition/em? of skin (24 ‘nd‘‘0. 12, 72 and 0.36, or
`340 and 1,2 mg/m? ‘of méquinol and tretinoin; respectively:
`0.6, 1.9,or6.5times the daily human doseon.a mg/m” basis)
`following chronic topical dosing with intercurrent exposure
`to ultraviolet radiation for upto.40 weeks, Similar animal
`Studies have shown an increased tumorigenic risk!with the
`useofretinoids when ‘followed by ultraviolet radiation. Al-
`though theSignificance ofthese studies to human useis not
`cleaf, patients”‘using this product should be.advised to avoid
`or minimizeexposuré to either sunlight or artificial ultravi-
`olet irradiation sources.
`i
`Mequinol wasnon-mutagénie in the Ames/Salmonella a:assay
`using strains TA98, TA100, TA1535, and TA1537, all of
`which are ins éhsitive to mutagéhic effects: of’structurally-
`
`related’quindhes.*Solagé Solution was non-genotoxiciin an
`in vivo dérmal micronucleus assay in rats;but exposure of
`bone marrowto drug was not demonstrated.
`A dermal ¥eproduction stud}: with ‘Solagé Solution in
`Sprague-Dawley rats at a daily dose'of 80 and 0.4! mg/kg
`(480 and 2.4mg/rii”) ofmequinol andtretitibin, respectively,
`approximately 11 times the corresponding1maximum possi-
`ble human exposure; Assuming 100%bioavailability follow-
`ing topical application to 5% ‘6f the total body ‘surface
`area, showed'no impairmentoffertility.
`rs
`Pregnancy: Teratogenic effects: Pregnancy Category’xer
`Although the magnitude’‘of the potential for teratogenicity
`may notbe well-defined; Solagé' Solution is labeled as an
`“X”because the potential risk of the useof this drug-to treat
`this particular indication (solar lentigines) in a pregnant
`woman clearly outweighs any- possiblebenefit-(see CON-
`TRAINDICATIONSsection): »
`Nursing Mothers:
`It ig not known to whatextent mequinol
`and/or tretinoin is excreted in:human Inilk. Because many
`drugs are excretediin human milk, caution should be exer-
`cised when Solagé Soliition is administered to"a” nursing
`woman.
`Pediatric Use: The safety ¢and effectiveness ofthis product
`have not been establishediin pediatric patients. Solagé,So-
`lution should not be ‘used on’‘children:
`Gefiatric Use:' Of the.total, number'‘of patients in clinical
`studies of!Solagé Solution,
`aapproximately,43%were 65'and
`older, while approximately 8% were 15.and over. No overall
`differencesiin effectivenéss or saféty were observed between
`these patients and¥youhger patients.
`ADVERSE REACTIONS., ‘
`WA
`In clinical trials; adverse reactions were primarily'mild to
`moderate in intensity, occurring.in 66% and 30% ofpatients,
`
`respectively. The majority of these. events ‘were limited ’to -
`the skin and -64%'had ‘an onset ofa skin related adverse
`reaction early in treatment (by weék 8); The mést-frequenit
`adverse reactions in patientstreated with Solagé Solution
`were erythema (49%: of patients), burning, stinging, or'tin-
`gling (26%), desquamhation (14%), poatees); and skin
`irritation (5%).
`Some patients experienced. EerieOeer hypopiéshontation of
`treatedlesions(5%) or of the,skin surrounding treated le-
`sions (7%). Ninety-four of 106 patients (89%),hadresolution
`of hypopigmentation wupon discontinuation. of treatment to
`the lesion,and/or:ré-instruction on proper application to the
`lesion only. ‘Another 8% (9/106) of patients with hypopig-
`mentation events had resolution within 120.), days after.the
`end of treatment,Three ofthe 106 patients Q.8%) had per:
`sistenceof. hypopigmentation beyond, 120. days. ‘Approxi-
`mately 6% ofpatients discontinued study participation with
`Solagé Solution due to.adversereactions. These discontinu-
`ations were due primarily to‘skin redness (erythema) or re-
`lated cutaneous advérse reactions. Solagé Solution was
`Zenerally ‘wellfolerated.
`oe
`Sakcl
`a
`As
`{See first table,above] nee
`Sap
`es
`a
`OVERDOSAGE
`on
`ite
`If SolagéSolution is applied’Exdessivly, ¥ho more-rapid or
`better results will be obtainéd ahid'itiarked rednéss, peeling,
`discomfort, or:hypopigmentation may occur. Oral ‘ingestion
`of the drug may lead to the same adverse effects as °those
`associated with excedsive oral'intdke ‘ofvitamin A(hypervi-
`taminosis A). Iforal ingestionoccurs, the patient should be
`monitored, anid:appropriaté supportive®measures shouldbe
`
`adminis
`a necessary. ‘The. inaximalné-effectevel
`for oral
`adi nistration89F° Solagé Solution in rats
`was5.0 mL/kg (30 “mg/m? ). Clinical‘sigtis- observed were
`attributed 8 the aaTey alcohol content 17) of the drug
`formulation.”
`DOSAGE AND ADMINISTRATION
`Patients require detailed instruction to obtain maximal
`benefits and to understandall the precautions necessary to
`use this product with greatest safety. The physician should
`reviewithe Patient Medication Guide
`Apply Solagé Solution to the solar lentigines using the ap-
`plicator ‘tip:while avoiding application to the surrounding
`skin.cUse twice daily, morning and.evening at least 8;hours
`apart; or as directed’ by a-physician. Patients. should nét
`shower or bathe the:treatment areas for at:least_6) hours
`after application: of Solagé.Solution. Special eaution should
`be taken ‘when. applying Solagé Solution: to avoid the eyes,
`mouth;.paranasal creases, and mucous membranes.
`Application of Solagé Solution may cause transitory sting:
`ing, burningorirritation.
`
`|
`
`
`
`5
`
`Consult 2006:PDR® ‘supplements and future editions for revisions
`
`Continued on next page
`
`
`Adverse Events.Occui¥ing-in>1% of the Population —All Studies
`¢ any drug, a small numbérof birth
`
`
`
`: ead" Be 4 temporally!withthé administra:|[ooqee—— = ay Oe
`
`
`wiaeasso"steexpected by chatice’alone. Thirty|Body System, Solagé Solution,,
`vatrtvo gsociated’ congenital malformations
`(mequinol:2%,
`'}
`«©
`Tretinoin,
`Mequinol,;
`Vehicle
`
`gelthe porene two decadesofclifiical use of:an-
`uattetinoin 0.01%)
`eet OOTY:
`2%
`ve}
`
`SE ‘ae -
`ae
`:
`085 te
`orted du pical tretinoin. Although’‘no definite
`Skin-and
`aNeasy
`%
`% N
`%
`N
`85 post OP on of tOP
`i
`tion has been
`d
`'
`"
`ye Bee
`lati
`and nocasuaLassociatior
`has
`bée
`%
`Diet ee genic cases, 6 ofthe repolts’ describe the,Appendages 7 an] “8 | ‘
`
`
`
`
`
`a M4 4 fro!
`thes ory holoprosencephaly (defetts aiss0-
`
`Fei defect onoa midline developmentof the fore:|Erythema 549 44.6 261 55.3 13 5.1: 8 | 4a
`
`
`
`
`
`
`
`
`
`a
`a:
`ae
`:
`T
`bi
`com]
`spontaneous reports in
`:
`TOG
`Tar
`:
`road
`f
`irs
`r
`re
`PP
`in
`of these spon
`p'
`
`
`eared WithgpificanceOT own’Noadequateor well.|Burning/Stinging/ 270,|21.9 173 86.7 26 10:2 20 14
`
`
`
`
`
`Tingl
`<i8
`phe’s
`e fetus is
`.
`brof8%seve beot'‘conducted with SolaghiSolution
`ngs
`
`irowot|js contraindicated in individual
`Desquamation
`158,
`|
`98
`19.7
`7
`2.8
`2
`it
`{
`rs
`Tee
`ae
`3
`zs
`Pa
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`als
`
`in preg Topi
`itivityreactionsto anyofits ingredi- 7
`‘
`Sa
`;
`(
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`solectoFoe“Geeontinuedifhypersensitivityto:art
`Pruritus
`185
`66
`14,0
`12
`4.7
`3
`L7
`L
`
`
`wig1$204 ted. Irritation Skin 90 25 5.3: 1 0.4 1 “0.6
`
`
`
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`
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`ents- entsno’
`rl
`Y
`AL
`0.
`2
`=
`
`Po
`~
`i
`its}
`ings
`fy Lotiibeen,
`
`
`
`
`
`L adermal ribatityand the Teculialofcon-|Halo r . 76 16 3.4 2 0.8 2 | 1a
`
`
`
`
`
`
`gé olution iethe,skin. for greater. than 52,weéks in|Hypopigmentation se
`
`solei tation ° use arejnot known, Tretinoinhas been
`75
`—e
`1
`=o
`3 =
`
`nic10ng severe invitation on.eczematous.skin and|Hypopigmentation 50 LT | nines 4 0.8 é 0.0 |
`
`
`
`
`
`
`
`
`oor 0 Ciodeel veitht utmost caution in patients with
`Skin Dry
`38
`— i
`$8
`2
`ae
`7
`fs =phties
`orgbeuse
`Fa
`=
`ibe
`AG
`.
`
`i
`show
`:
`fl
`iS
`3
`dition.
`fSolagé, Solution:in individuals
`Rash
`31
`2.5
`21
`44
`0
`0.0
`1
`0.6™:
`this com
`ctiveness 0
`i
`:
`sa)aon,heavily pigmented.skinhave:Rotbeen
`sai
`=
`;
`
`establisheedPerTT not:be administered ifthe Pecanis
`og ae
`patente
`oe
`a
`eae
`o eet
`ie ri
`a”
`oe
`
`
`
`
`solagé 57”drugs known torbe photosensitizers.(e.g., thia:|Rash Vesicular 18 21. 4 ogke 7 0 0.0 0 | 00
`
`
`
`
`also
`Boeyelines,
`flusroquinolones, phenothiazines,
`Bullae
`C
`‘
`rides,
`tedes) because of:the:possibility, of augmen a
`|
`
`sulfoneet
`are
`Dermatitis
`;
`phototoxicttof heightened burning susceptibility, exposure to
`Because °
`sunlamps).to.,treated areas should be
`
`sunlight ede during,the use;of,Solagé Solution. Pa-
`
`avoider abe advised to use,protective clothingand voriply
`
`tients pi srehensive sun:avoidance.“programwhen using
`
`with a Beiution. Data:
`not available to establish how or
`a Solagé Solutionsisdegraded (either by sunlight or
`hynormal- interior lighting) following application to the
`skin, Patients with sunburn should He advised not.to use
`Solagé Solutionuntil fully. recovered.Patients who may
`have considerable sunexposuredue;toe their o¢cupation.and
`those patients with inherent sensitivity to sunlight should
`exercise particular caution when using Solagé Solution and
`ensure that the precautions outlined.in the Patient, Medica;
`tion Guide are observed.
`L
`Solagé Solution should bekeptout, ofthe eyes, facilepara-
`nagal creases,.and mucous membranes. Solagé,Solution
`may cause skin.irritation, erythema,-burning, stinging.or
`tingling, peeling,.and pruritis. If the degree,of such local ir-
`Titation warrants; patients, should be directed to-use less
`medication,decrease the.frequency of application, discon-
`tinue use temporarily, or
`discontinue use altogether. The
`oeee frequencies of abpheation has not been
`establishes
`feat
`Solagé Solution should,.beused with:annie by: patients
`with a history, orfamily history, of vitiligo. One-patient;in
`the trials, whose brother had vitiligo; experienced hypopig-
`Mentation in areas that had not.been treated with study
`pasion. Some’of these areas, continued to worsen for at
`ee Ppst, treatment swith, Solagé Solution. Six
`aaethe severity of the:‘hypopigmentation had de-
`the patiePerrctorate to mild and.106 days post treatment,
`Wlatic i resolution of somebut not all lesions.
`eet ee larger amounts of; medication’ than recom-
`marked aelead to,more-rapid or better results, and
`ofthe skin ene discomfort, or hypopigmentation
`PRECAUTIONS
`;
`.
`General
`c
`or fie
`>
`SolaggSohatiotey
`rehensivee
`ould only beused as-an adjunct to‘a com-
`in care‘atid sun avo