TOXNET
`
`http://toxnet.nlm.nih.gov/cgi-bin/sis/search2/r?dbs+hsdb:@term+@rn+g...
`
`-)- HSIDS
`
`> Full Record
`
`HSDB: MIN C)CYC LIN E CASRN: 10118-90-8 This record appears in multiple databases.
`
`View record in another database: ! HSDB
`
`ti:;
`
`Pnr::
`
`r".(iy
`
`MINOCYCLINE
`CASRN: 10118-90-8
`
`FULL RECORD DISPLAY
`
`Displays all fields in the record.
`
`For other data. click on the Table of Contents
`
`flumari Heziltil Effects:
`
`Human Toxicity E"''
`
`r.
`
`r-
`
`r
`
`LONG-TERM THERAPY WITH TETRACYCLINES MAY PRODUCE CHANGES IN PERIPHERAL BLOOD.
`
`LEUKOCYTOSIS, ATYPICAL LYMPHOCYTES, TOXIC GRANULATION OF GRANULOCYTES & THROMBOPENIC
`
`PURPURA HAVE BEEN OBSERVED. /TETRACYCLINES/
`
`tr-:irmn..J G.. I..
`
`l Lin-bird REt. Molinoff
`
`Goodrnon (c;;.ì. Co:>:::nan
`
`t:)tiin».-)n't;
`
`No,
`
`NY 1).1c):..)).rt-r,
`
`p.
`
`-PEER ;REVIEWED
`
`CHILDREN RECEIVING LONG OR SHORT TERM THERAPY WITH A TETRACYCLINE MAY DEVELOP BROWN
`
`DISCOLORATIONS OF TEETH. LARGER THE DOSE...RELATIVE TO BODY WI, MORE INTENSE
`
`DISCOLORATION OF ENAMEL. DURATION OF THERAPY APPEARS TO SE LESS IMPORTANT THAN
`
`TOTAL.../AMT/ ANTIBIOTIC ADMIN. /TETRACYCLINES!
`
`ftiardmar, G..
`
`P.E) Molintsff, R.
`
`Rudtjo»,
`
`t.itoodrnon (c)-.1".).)
`
`orti t.):),:tnon'o Tho
`
`Et» or Thei-apt.?).)tio::- 9th ot1 Nrw. Vo:k.
`
`;),'C. .));-:.)v.,
`
`p.
`
`I I 3t).)] -PEER REVIEWED-
`
`Benign imracranial hypertension. with 5th nerve palsy and papilledema, has been reported in a girl taking
`
`minocycline...
`
`[Gran.f. V .1r
`REVIEWED' '
`
`ir)xmology
`
`Illf?
`
`:Itni rri 8pPri0:!Of.i.
`
`l'hurw*:
`
`pr.
`
`Drug Warrting5:
`
`UNTOWARD EFFECTS CAUSED BY MINOCYCLINE ARE ESSENTIALLY THOSE OF TETRACYCLINES IN
`
`GENERAL. HOWEVER, PHOTOTOXICITY SEEMS TO BE MUCH LESS THAN \MTH OTHER TETRACYCLINES.
`
`MORE CLINICAL OBSERVATIONS ARE NEEDED TO ESTABLISH EXACT TOXIC POTENTIAL...
`
`A. and
`
`A-100,,,P,,
`
`PA.
`
`Reomigtoo-
`
`oi:)11s:snr,i Co .
`
`I) 1141I
`
`Sr'.r r
`
`ìh oti Easton PE)nr.,.,yivon)a
`
`Exhibit
`1073
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`2 01'27
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`Apotex Exhibit 1073
` Page 1 of 26
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`

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`TOXNET
`
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`
`CROSS -SENSITIZATION AMONG VARIOUS TETRACYCLINES IS COMMON. /TETRACYCLINES/
`
`U.S. Matinal Library of Medicine 8600 Rockville Pike, Bethesda, MID 20894
`National Institutes of Health, Health & Human Services
`
`[Hardman, J.G.. LE.. L.imbfrd. P.B. feir..Einof
`: R!r'a: Redden: A.G. Goodman (ads.). Goodman and Gilman's ?'he
`Pharmacological Basis or '''herapoutits. The ed. New York, NY: McGraw -Hill, 1993.. p. t íi0] -° 0 -T2EtilíU":b.
`
`VESTIBULAR DISTURBANCE MAY POSE HAZARD FOR PT ENGAGED IN ACTIVITIES REQUIRING UNIMPAIRED
`MOTOR COORDINATION.
`
`[Goodman: L.S., and , >,. Gilman. (eds. 1 The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan
`Publìs::::y Co., loc., 1575., e. 1190]' PEER. REVIEWED "
`
`...TETRACYCLINES ADMIN ORALLY OR PARENTERALLY MAY LEAD TO DEVELOPMENT OF
`
`SUPRAINFECTIONS THAT ARE USUALLY DUE TO STRAINS OF BACTERIA OR YEASTS RESISTANT TO THESE
`
`AGENTS.... INCIDENCE OF SUPRAINFECTIONS IS MUCH HIGHER WITH TETRACYCLINES THAN WITH
`PENICILLIN OR STREPTOMYCIN. /TETRACYCLINES/
`
`Gouronso, L.S., and A. Gilman. (eds.) The Pharmacological Basis ef'I Therapeutics, 5th ed. New York: Macmillan
`
`Publishing Co.. Inc., 1075., o, 11901 " -PEER REVIEWED "
`
`ORAL, PHARYNGEAL, & EVEN SYSTEMIC INFECTIONS WITH YEASTS & FUNGI, PARTICULARLY CANDIDA,
`
`ARE NOT UNCOMMON; THEY TEND TO OCCUR MOST OFTEN IN INDIVIDUALS WITH DISORDERS SUCH AS
`
`DIABETES, LEUKEMIA, SYSTEMIC LUPUS ERYTHEMATOSUS, DIFFUSE VASCULITIS, & LYMPHOMA, ESP IF
`STEROIDS ARE ALSO BEING ADMIN. /TETRACYCLINES/
`
`[Goodman; L.S.; and A. Gilman. reds.) The Pharmacological Basis of ll',erape ;tics. 5th ed. New York' Macreiif-
`Pubiishing Co., Inc... 1973., p. !i901 "PEER REVIEWED"ED"
`
`IT IS IMPERATIVE THAT... /DIARRHEA RESULTING FROM IRRITATION OF TETRACYCLINES GIVEN ORALLY/ BE
`
`PROMPTLY DISTINGUISHED FROM THAT WHICH RESULTS FROM PSEUDOMEMBRANOUS COLITIS CAUSED
`
`BY OVERGROWTH OF CLOSTRIDIUM DIFFICILE, A POTENTIALLY LIFE - THREATENING COMPLICATION.
`
`/TETRACYCLINES/
`
`[Hardman, J. G.. . L.E. !_imbird. P.B. M;olinof', P,.V.. Rs.eTece. A.G. ,Gond^,rm (e:l. <...i. Goodman and Gil en'e':Iw
`t,t e.. n. 111 97 P, .El Rüi V üU: ;`.
`Pharmacological 13asis of . ier.peeti_r . ec t ed. New York, NY: McGraw-Hill,!,
`
`MICROORGANISMS THAT HAVE BECOME INSENSITIVE TO ONE TETRACYCLINE FREQUENTLY EXHIBIT
`RESISTANCE TO OTHERS. /TETRACYCLINES/
`,.
`[Hardman. i J. -.. t..
`Hcai °ürrir . ,
`
`n, A. s. Goodman (eds.). Goodman -"..-` i,ii:::ari s The
`Pharmacological Basis of Therapeutics. 0t: ed. New York. N`.!: McGraw-Hill, 1905.. p..l.i "L' C'i "PEER EEV1E;`:rt;,.,
`
`. Lirnbird, P.B. Tslolinc.lf, R.ThJ. Red
`
`ALTHOUGH IT IS GENERALLY ACCEPTED THAT TETRACYCLINES OR OTHER ANTIBIOTICS HAVE BENEFICIAL
`
`EFFECT IN ACNE, SOME PLACEBO CROSSOVER STUDIES RAISE DOUBT CONCERNING VALUE OF THIS
`KIND OF THERAPY. /TETRACYCLINES/
`
`Hardman,
`rr.:a.::n:,.! Basis
`' :ia::::,.,,,,,,,,:ca, x.",.,::: u;
`
`:
`
`-,ir d, P.:3. Mn . nbf , R.
`a:,:.:c",
`iero{,z:,.;,:,.,. T :o ed, fvëLb : t;l.r,, N :. Ifc:ïta,v..Hi s, iéGS p. 1129 "PEER RI= V1-4'rr..('e.
`York,
`
`Redden, A.G. Goodman reds.). Goodman and :.,!irr,an`, ^, The
`
`THEY SHOULD NOT BE GIVEN TO PREGNANT PT; THEY SHOULD NOT BE EMPLOYED FOR TREATMENT OF
`
`COMMON INFECTIONS IN CHILDREN UNDER AGE OF 8 YR; UNUSED SUPPLIES...DISCARDED.
`
`/TETRACYCLINES/
`
`if' ; P.B.
`.:., .
`:...
`[Hardman: , . V.;
`tro
`'. ;:,. s':ü friü i.
`RAN, ca3an. %.".C, Goodman (eds.). Goodman and CSiii'i an's The
`R.
`Pharmacological Basis ,. . ztaa ï'i;ir.'r 9th t. , New v ore. .,
`
`'1900., P. !i3G; "PEE' ? RFV3"`¡ia1'
`
`4
`
`Tetracyclines cross the placenta; use is not recommended during the last half of pregnancy since tetracyclines may
`
`cause permanent discoloration of teeth, enamel hypoplasia, and inhibition of skeletal growth in the fetus. In addition,
`
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`TOXNET
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`http: / /toxnet.nlm.nih.gov /cgi- bin /sis /search2 /r ?dbs +hsdb: @term + @rn + @...
`
`fatty infiltration of the liver may occur in pregnant women, especially with high intravenous doses. !Tetracyclines/
`
`(LISP Convention. tiSPDI .. Drug Information for the Heal d/ Care Professional. 17th ad. Volume i. Rockville. MD:
`Convention, Inc., 199:. (Plus Updates)., [ Es 1tj "PEER1FV E Er.
`
`Tetracyclines are distributed into breast milk; although tetracyclines may form nonabsorbable complexes with
`breast -milk calcium, use in not recommended because of the possibility of their causing permanent discoloration of
`
`teeth, enamel hypoplasia, inhibition of linear skeletal growth, photosensitivity reactions, and oral and vaginal thrush in
`infants. In addition, vestibular disturbances may occur with minocycline.
`
`[1.1SP Convention. ,i::í'01 - Drug Infom.. ion for the Health Care Professional. 17th ed. Volume's. Rockville, MD:
`
`Convention: Inc 1997. (Plus Updates)., p, 29101 " -PEER REVIrEWED "
`
`In infants and children up to 8 years of age, tetracyclines may cause permanent discoloration of teeth, enamel
`hypoplasia, and a decrease in linear skeletal growth rate. Therefore, use is not recommended in patients in these age
`
`groups unless other antibacterials are unlikely to be effective or are contraindicated. /Tetracyclines/
`
`[1.I.9!' Convention. t.USPDI .. Drug Ir *lorrr:a!ion !1)r the He:lth Coe Professional. 17th ed. Volume!. I2£ ckvil e. Mt:)
`
`Convention. h:c.. 1997. (Plus U.pdate's)., p. 2810] `°"'EE.R REV SEWED"
`
`Bulging fontanels have been reported in young infants who received full therapeutic doses of tetracyclines. This side
`
`effect disappeared rapidly upon discontinuation of the drug. /Tetracyclines/
`
`(LISP Convention. USi')DI - Drug Information for the'.+erri!.h :,... e Professional. 17th E;d. Volume I. Rockville; MD:
`1997 l''tus i.ipdatea \., p. 2'310:Í "PEER R RE VIEü;^:1üD ".
`Convention,
`
`Tetracycline- induced hepatotoxicity is usually seen as a fatty degeneration of the liver. It is more likely to occur in
`
`pregnant women, in patients receiving high -dose intravenous therapy, and in patients with renal function impairment.
`
`However, hepatotoxicity has also occurred in patients without these predisposing conditions. Tetracycline- induced
`
`pancreatitis has also been described in associated with hepatotoxicity, and without associated liver disease.
`
`/Tetracyclines/
`
`[LISP í onventif:n. usPl:)I - Drug Information for the Elea. lll :,e)re í:trc)fessianal.
`Convention's: Inc., 1997, (Plus Updates)., p. 29141 "PEER REVIEWED ""
`
`ume i. Rockville- MD:
`
`PATIENTS RECEIVING MINOCYCLINE MAY EXPERIENCE VESTIBULAR TOXICITY, MANIFESTED BY
`
`DIZZINESS, ATAXIA, NAUSEA & VOMITING. SYMPTOMS OCCUR SOON AFTER INITIAL DOSE & GENERALLY
`DISAPPEAR WITHIN 24-48 HR AFTER DRUG ADMIN IS STOPPED.
`,.R, .
`i_l°:his!í. P.B. tr`:r< tnrff, E'.c r<,.5;idon, A G. s_ ?E;r<E ^,a °a (eds.). Goodman ird Gi- :an ' >'ï "f).z
`
`.. =., t.:
`
`arEsm:.5t3,
`
`Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McEirrwwidiii, 1996.: p. 1139] ..'PE.Ef1 REL'IE`IJED°
`
`GASTROINTESTINAL IRRITATIVE EFFECTS ARE MORE COMMON AFTER ORAL ADMINISTRATION... THEY ALL
`PRODUCE GI IRRITATION TO VARYING DEGREE IN SOME BUT NOT ALL INDIVIDUALS. EPIGASTRIC BURNING
`
`& DISTRESS, ABDOMINAL DISCOMFORT, NAUSEA & VOMITING MAY OCCUR. DIARRHEA MAY ALSO RESULT
`FROM IRRITATIVE EFFECTS... /TETRACYCLINES/
`
`,' art:mF.in, , .
`
`...
`
`.. ",
`.:::: )!7a,
`
`"'. !:5. v:n irti. !,
`i
`
`!. ' -. sC:i; , ^í)9t, A ;. Goodman t£.:í5.1.
`(eds.
`
`t-.;o.,.;>~,an and ïxi!r^twYs 577,a
`
`Pharmacological Basis E.: Therapeutics. u::) ?E'. Nev.; York,
`
`.. MCGfäy, ^.H3ü 1999.; p. 1129 "PEER
`
`OTHER EFFECTS THAT HAVE BEEN ATTRIBUTED TO HYPERSENSITIVITY ARE BURNING OF EYES,
`
`CHEILOSIS, ATROPHIC OR HYPERTHROPHIC GLOSSITIS, PRURITUS ANI OR VULVAE & VAGINITIS; THESE
`EFFECTS OFTEN PERSIST FOR WEEKS OR MONTHS AFTER CESSATION OF TETRACYCLINE THERAPY.
`/TETRACYCLINES/
`
`>yd..x..3u ,: ,at Basis OF
`
`:,:
`
`'`for:^^f §'1
`0 ;!) <_.., hl. -kV 'fork,K, f`I .. 11.......<,, l-I . , 1999.; t 1130;
`
`f .`...: R RE'
`
`. >..
`
`VARIOUS SKIN REACTIONS, INCL MORBILLIFORM RASHES, URTICARIA, FIXED DRUG ERUPTIONS &
`
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`

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`TOXNET
`
`http: / /toxnet.nlm.nih.gov /cgi- bin /sis /search2 /r ?dbs +hsdb: @term + @rn +@...
`
`GENERALIZED EXFOLIATIVE DERMATITIS, MAY FOLLOW USE OF ANY OF THE TETRACYCLINES. AMONG
`MORE SEVERE ALLERGIC RESPONSES ARE ANGIOEDEMA& ANAPHYLAXIS; ANAPHYLACTOID REACTIONS
`CAN OCCUR EVEN AFTER ORAL USE OF THESE AGENTS. /TETRACYCLINES/
`
`'Hardman, J.G ,
`I _i? ,u . RB. Molinari, RAN. <ui on, A.G. Goodman reds.). Goodman and Gi iman;, The
`, ,
`n<)rmsta o:ra; .:,acs c,; 'Therapeutics
`tic
`P. c:. New York, NY: h r {.rau-H l, trvr .. p. 113 0) -.PE E: Rt VIE::Vv:::Cì °"
`9i
`
`IV ADMIN OF TETRACYCLINES IS FREQUENTLY FOLLOWED BY THROMBOPHLEBITIS, ESP WHEN SINGLE
`VEIN IS USED FOR REPEATED INFUSION. /TETRACYCLINES/
`
`[Hardman. J.G.. L.E. Limbird. P.B. Molínoft, R.W. Reddon, A.G. Goodman (eds.). Goodman and GI::::.grts The
`: : Y'.
`..)a!rn., o, :.,a:
`: .':'.aa.rFi "i ¡,
`'uses o°
`i
`°sea. ,
`j7Et.... ,, r..... g:r
`:.....
`"'PEER REVIEWED"
`<.
`<:{.'.::.:s.
`L
`c,rx.
`i
`s.
`
`125'
`
`û,.
`
`¡,
`
`t1C
`
`i
`
`>.
`
`:
`
`as
`
`TETRACYCLINES HAVE BEEN FOUND TO DELAY BLOOD COAGULATION....IT HAS BEEN SUGGESTED THAT
`
`IT IS RELATED TO ABILITY OF THESE DRUGS TO ALTER PLASMA LIPOPROTEINS. PT RECEIVING
`
`TETRACYCLINE IV HAVE SLIGHT -TO- MARKED DECR IN PROTHROMBIN ACTIVITY & AN IMPAIRMENT IN RATE
`
`OF THROMBOPLASTIN REGENERATION. /TETRACYCLINES/
`end ° Gilman.
`.
`(Goodman, rr.S.; c >.:,: :... ,,,c rna ?;. ;a "5.ì The Phannacolo:cai Basis of Tt ?araa::_:'' .
`,r..s, 5th ed
`<.::
`.
`
`r,! ;t <
`
`YorK: f;acrncllan
`
`.
`
`Publishing Co., Inc.. '1975.. p. 1 891 ** PER RE::V(E_`J ED"
`
`TETRACYCLINES MAY CAUSE INCR INTRACRANIAL PRESSURE & TENSE BULGING OF FONTANELS
`
`(PSEUDOTUMOR CEREBRI) IN YOUNG INFANTS, EVEN WHEN GIVEN IN USUAL THERAPEUTIC DOSES.
`
`EXCEPT FOR ELEVATED PRESSURE, SPINAL FLUID IS NORMAL. DISCONTINUATION OF THERAPY RESULTS
`
`IN PROMPT RETURN OF PRESSURE TO NORMAL. /TETRACYCLINES/
`
`(Hardrn_ +n. J.:.. LE. Lirribird. I).3. Melheeff, R.YL !fir) ddoc, A.G. Goodman (eds.). Goodman and Giimeri s The
`r T 11 r1
`'?azarm,:coi ^;ca. Basis c° Therapeutics. rt °i ed. New :erk, N.. McGraw-Hill, 1:..... ,
`..: T ed. New York, NY:
`
`' ^P ?::F::F3 RE::`:iE::Vv;::i:ì °.
`
`?
`
`Pregnant women appear to be particularly susceptible to severe tetracycline- induced hepatic damage. Jaundice
`appears first, and azotema, acidosis, and irreversible shock may follow. /Tetracyclines/
`
`[Hardman. J.{::.. LE. L:r ^bird, E.B. Mcdieclf, R.W. iïud,lan, A.G. Goodman (eds.). Goodman : re G lc an s The
`,Cci- ;f _
`Pi ..,,
`..
`)a.... ;;;>ioy: -a! ..<.... *:
`Irerap "::;,cs. fi"`) ed. New York. Fri McGrew-Hill, Ifs 16.. p. E 221 ' "PEER IEV1FWEE):°
`
`TREATMENT OF PREGNANT PT WITH TETRACYCLINES MAY PRODUCE DISCOLORATION OF TEETH
`
`IN...OFFSPRING. PERIOD OF GREATEST DANGER...IS FROM MIDPREGNANCY TO ABOUT 4 -6 MO OF
`POSTNATAL PERIOD... /TETRACYCLINES/
`
`[Hardman,
`
`_ LE. Limbed. P.B. MnEir ±rfi. R!v'.í Redden, .3.. Goodman (eds.). Goodman a!,^ r.ìi¡.,,an,s ,tin
`harmer:oink :a: Besis of Therapeutics. TEh ed. New York, NY: McGr. w Hili, 192ä., p. 11301 "PE.ER REVIEWED
`
`,
`
`40% DEPRESSION OF BONE GROWTH, AS DETERMINED BY MEASUREMENT OF FIBULAS, HAS BEEN
`
`DEMONSTRATED IN PREMATURE INFANTS TREATED WITH THESE AGENTS. THIS IS READILY REVERSIBLE
`IF PERIOD OF EXPOSURE TO DRUG IS SHORT. /TETRACYCLINES/
`
`[Hardman, J. G., LE, Limbird, Pcé(inef*, RAN. fT1d:;71, A.G. Goodman Ea '.Ì:î.7. Goodman and C3:'!î:iT3) $ ! IRe
`,:r.
`...
`,.,:Trs!,T, <,-.o:),..:..,.: Basis of iht:)aI+n:,,,< 9th ed '`::.r York, NY: McGraw-Hill.
`
`s; >:F)..t:? {:
`
`ACHROMYCIN & MINOCIN GIVEN TO HUMANS IN VARIOUS AMT WITHIN THERAPEUTIC DOSE OF UP TO 85
`
`DAYS. THYROID SPECIMENS FROM THOSE GROUPS SHOWED DARK DISCOLORATION, RESEMBLING
`NATURALLY OCCURRING PIGMENTS.
`
`1lÁ1 ROk ULOS Evi,i ET AL, TOXICOLOGY R ;.-ARCH, ME.L) RESEARCH DIV, AME. CYANAMID CO. PEA
`RIVER, íÿ'J1 ''PEER REV1EV,ED"
`
`Reported Fahl Dose:
`
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`

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`TOXNET
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`http: / /toxnet.nlm.nih.gov /cgi- bin /sis /search2 /r ?dbs +hsdb: @term + @rn +@...
`
`2 OR 3. 2= SLIGHTLY TOXIC: PROBABLE ORAL LETHAL DOSE (HUMAN) 5 -15 G /KG; BETWEEN 1 PINT & QT
`
`FOR 70 KG PERSON (150 LB). 3= MODERATELY TOXIC: PROBABLE ORAL LETHAL DOSE (HUMAN) 0.5 -5 G /KG;
`BETWEEN 1 OZ & 1 PINT (OR 1 LB) FOR 70 KG PERSON (150 LB). !TETRACYCLINES/
`
`(tlosselin. R..., N.C. Hodw. R.P. Srmilt. and M.N. Gleason. í:;ür.ic :I Tòxic :olo y oi' í::omnnerc =aa1 l'raGucls. 41h ed.
`Baifisme: Williams and Wilkins, 197ti., p. 11.1721 'T EER ? REV1EW'EC°
`
`Emergency Medical Treatment:
`
`Emergency Medicai Treatment:
`
`EMT Copyright Disclaimer.
`
`The information contained in the Truven Health Analytics inc. products is intended as an educational aid only. All
`
`treatments or procedures are intended to serve as an information resource for physicians or other competent
`
`healthcare professionals performing the consultation or evaluation of patients and must be interpreted in view of all
`
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`your sole risk. These products are provided as is and "as available" for use, without warranties of any kind, either
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`timeliness, usefulness or completeness of any of the information contained in the productsAdditionally, Truven Health
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`
`The following Overview, *" TETRACYCLINES * * *, is relevant for this HSDB record chemical.
`
`Life Support:
`
`This overview assume: that basic life support measures
`have been instituted.
`
`Clinical Effects:
`
`0.2.1 3r,Mt7ART OF EXPOSURE
`
`A)
`
`I FS: Tet.ra vci inee are is=d in th= treatment. cf A wise
`
`E)
`
`C)
`
`P)
`
`11
`
`varioty of gran, nc:Jstiws and gram-positivo _nfcct.ion
`PHARMACOLOGY: Tetracyclines are bacteriostatic and exert
`their antinéc:robial effects by inhibition of protein
`synthesis.
`
`.
`
`EPIDEMIOLOGY: Exposure is relatively common. however,
`revere toxicity is not obsessed.
`WITH THERAPEUTIC USE
`ACUTE EFFECTS: COMMON: Nausea and vomiting with
`therapee.tic use. Epigastrio burning and ulceration may
`also oc:_ur. Skin hyperpigmenLaLiuu may deveiot_.
`vpersersitivity reactions can develop with therapy in
`the form of carious skin rashes along with more severe
`reactions including :ngi. edema and. anaphylaxis. Renal
`
`dysfunction, including elevated RITI, may ,:.cur due to
`the antianabo__I activity of tetracyclines.
`
`a)
`
`2)
`
`E)
`
`1)
`
`2)
`
`3)
`
`DEMECLOC CLIRE: 7. diabetes inapt d..ts syndrome has been
`reported following demeoloc.yc__re.
`
`CHRONIC EFFECTS: Chronic _r.ge: ti,::n of therapeutic doses
`can cause discoloration anS enamel detects in the teed
`of the fetus if used after the 12th week of pregnancy
`or in infants during the first f to 8 months cf life.
`WITH POIEiNING /EXPOSURE
`
`OVER.D0SE: Severe toxicity folla::: ;',q acute overdomacre as
`unlikely.
`MILD TO MODERATE TOXICITY: Nausea and vomiting are
`
`corvaon fc.11cwin. overdose.
`Sushi _iCXIOJTY: Hypersensitivity reactions can develop
`
`6 of 27
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`
`Apotex Exhibit 1073
` Page 5 of 26
`
`

`
`http://toxnet.nlm.nih .gov/cgi-bin/sis/search2/r?dbs+hsdb:@term+@m+@. ..
`
` O 2.7
`
`L .
`.‘-.) Headatrhe , pap
`
`h gaze rte. ca=.1s1nr._1 eezolz-hageai
`
`13¢ L1nr:c:mn'.r.:n .
`
`ixicex .t1<::‘z, but this
`
`
`
`
` TH _= = . ESE
`
`TetrAcy
`1)
`e and 1 A0¢ycl :9 have been impiicated in
`ca.=
`1':ep;=.tc:tex:?.ci1:'_v'.
`‘ie-induced au
`' :nu'nu:'ze hep-at
`
` . has been
`
`
`
`
`icdliy BUN, may
`£uucL;cu LesLs, spac
`F
`Towing ch‘:->n‘.«r =~.r mrerrh.-'2 ..=: of t.=r.rac\~“‘:iru=..*.,
`;~_»3:1: p'n pcrsons with prc-cxi5_ing r
`ma;
`dvsfunction.
`1: dezrr-ease
`arv ::o:'ncent1~at.iu.r.1 A
`fiollw
`of tetracy
`
`
`2)
`
`
`
`
`
`
`
`syndrome has bean repnr:ed in eéc?esnenr3
`.€ke
` minmcy:
`a therapy to treat acne.
` ' C pr-eumcvn La
`t.her:.1t~eL‘.t‘
`.adn'xir.i.~:tr.3t*'
`O . 2 . 2-3 REP?.ODUC"‘
`2‘-\)
`Tet
` <'10:»:y~:.'y' se ,
`
`2'1
`
`are cziexetszfiertl as FD?-.
`..-m=.*1
`trig
`'
`:etra:.“_~,-'
`pzegnan y categmry D. Maternai
`.-es ulurzng 1;-I
`may -‘Jamie t..::otr.
`axwl othe‘-
`Jenital
`exmLeLed in humtL bLbd5L
`ea :£€
`'e:. TeL1auy
`"hm-,'eveJ.',
`the extem: of ahacnrpticvn of t-=.=tra:.~yclin-es
`
`ed infant
`4
`by the b1:
`0.2.21 CA.
`1%“
`A) Mik-IOCYCL
`1)
`
`
`
`
`
`n at" Tf1'1‘_JI'LJi-'f{ and lsoxzes and
`‘ti-an in a:;‘\1its have
`reported.
`
` nee '
`Ob1:..=.in :1
`
`
`
`3)
`
`Treatment Overview:
`
`0.12.2 ORAL/'PAP.EN'E'E?.f-.L E.XE’O:"5-UL"-(E
`A)
`I-‘;P~_NAGEl~lEIG'I OE‘ WELD "")
`1)
`
`lv1O[‘IEP."I?:'.
`
`’?C':)(I'3I’E"{
`
` 4 orcier «sf
`
`t-:xi<:ir..y.
`
`Apotex Exhibit 1073
` Page 6 of 26
`
`

`
`_/.n
`http://toxn et.n1m .nih .g0v/cgi-bin/sis/search2/r‘?dbs+hsdb:@term+@rn+@
`
`
`
`
` CF
`‘SEE TOXICITY
`
`/mptm
`Txefltmeut is
`1 5 ppoItiV6. ANAPHYLAXIS:
`
`reactions m
`be treate& with
`
` antih
`
`th or without inhaled beta adrenergic
`stamines
`agcnists, cor?
`ostercids or epinephr
`
`50 mg 0
`mg era!
`-72 hours. Q
`‘LU: 1.25 mg/kg
`then 5 mg/kg/day oral-V in
`
`
`
`
`hours
`,
`C.-If
`
` JOE:
`
`1)
`
`
`
`G)
`1)
`
`N
`
`3}
`
`4)
`
`
`
`airway
`ECG monztoring, and IV E:
`
`'ke1y,
`generaily NOT
`ae and dcxycycline have
`
`jlu_.
`(120 to 240 mL)
`to 5 ounces
`to ezweed 4 ounces or 126 vL in 3
`
`(not
`
`low crder of
`
`
`
` Cu‘
`
`
`
`
`
`
`
` i hemoperfusion are un
`
`h these agents)
` is not
`prote'fi bi
` Tetracy
`PATEENT DESPO
`HOME
`
`
`
`to be at
`
`
`
`0U5m D]W
`-harm incest-
`
`I and monitored unr
`‘-e CBC and r9
`
`ute with 4 ts
`(not re
`
`u;l0wing 3
`arqed tc
`
`SEON CRITEREA: Patients experien
`“rent anaphvlactic synmtoms
`
`
`
`
`
`ate
` iuated by a mental
`ALLS
`
`
`
`' absorbed, boL"
`.se agents are
`e and are e
` wentrateu by the
` uonuenttdtions.
`in the U1
`6:‘ and 5
`
`Half—‘ for tetra’
`to 10 haura in adults
`
`normal ren
`
`functicn. OTHER AGENTS: DGXYCYCLINE:
`
`in 60 to 90%; renal
`
`
`gastrc1nt.'
`
`ation will not he I uired. Antacids may be
`zul Ln managing gastrac irritat‘
`
`
`RY HAHAG
`SET
`D)
`
`1} Airway support is w
` to be necessary fo
`IIJ‘ erate 6)..
`"\.lIE'y'
`r’.-Iilflz-I
`.--axy in pat_e.
`FDOTE
`
`Apotex Exhibit 1073
` Page 7 of 26
`
`

`
`TOXNET
`
`http://toxnet.nlm.nih.gov/cgi-bin/sis/search2/r?dbs+hsdb:@term+@rn+@...
`
`hair-lire is 10 to 20 hours in adults with normal renal
`function. MINOCYCLINE: protein binding 55 to 75; 5 tO
`10'* i a due is recovered unchanged in Lhe
`Half-life is 10 to 20 hours in adults with normal renal
`functior in patients takina demeclocycline/minoeylcine.
`DIFFERENTIAL DIAGNOSIS
`
`Other agents that may produce anapnylaxis.
`Gastrointestinal irritation or esdohagitis due to other
`agents such as NA1.1)(7 or a combination of antibiotics
`and other drugs or alcohol.
`
`.7)
`
`1)
`
`K)
`
`DILUTION: If no respiratory compromise is pre(ient,
`administer milk or water as soon as possible ingestion.
`
`Dilution muy only be helpful if performed in the first
`seconds tc minutes after ingestion. The ideal amount is
`unknown; s: more than & ounces (240 mL) in adults and 4
`ounces (12) mL) in children ia recommended to minimize
`the risk cf vomiting.
`Tetracyclines are generally of a low order of toxicity.
`In most cases gastrointestinal decdntamination will not
`be required.
`
`L)
`
`Range of Toxicity:
`
`A)
`
`TOXICITY: The minimal toxic or lethal dose is not well
`eetablished in the literature. Severe toxicity following
`acute tetracycline overdose is unlikely:
`THERAPEUTIC [OBE: ADULT: ORAL: Tetracycline: 1 to 2
`g/dav; Doxycycline: 10
`to 200 mg/day (up to 400 mg/day
`for come indications); Minecycline: 200 mg/day;
`
`B)
`
`Demeclocycline: 600 mg/day. PEDIATRIC: ORAL: Tetracycline
`(older than i years): 25 to 50 mg/kg/day, up to 3 g/day;
`Demeclocycline: 6.6 to 13.2 mg/kg/day; max 600 mg/day;
`Doxycycline (older than t years): 4 to
`
`mg/kg/day,
`usually up to 200 mg/day (up tc, 400 mg/Jay for some
`indications); Minocycline (older than n years): 4 mg/kg
`initial dose, then 2 mg/kg every 12 hours.
`
`[Rumack BH POISINDEXt:R) information System tylicromedex, Inc Englewood.
`2014; CCiS Voiume 162,
`edition expires Nov, 2014. Hall AH & Rumonk PH tfilds): TOMES(R) information System Micromedex. Inc.,
`
`Englewood. CO. 2014: (MS Volume 162, eclition expires Nov, 2014.1 "PEER REMEWED"
`
`Animal Toxic
`
`Non-Human Toxicity Excerpts:
`
`RATS GIVEN.../400 MG/KG/ IP...DEVELOPED POTENTIALLY LETHAL METABOLIC ACIDOSIS. ACCOMPANYING
`
`HYPERKALEMIA RESULTED IN DANGEROUS CARDIAC ARRHYTHMIAS. /TETRACYCLINES/
`
`posselin.
`
`H.C. Hodge RS', Smith. and M.N. Glesoen, Clinical To:Ace:oily of Cominemal Prditucts. 4tti ed.
`Baltimore: lAtillianis arid Wilkins, 1976 p. Ili:172] "PEER REVIEWED**
`
`Metabolism/ Pharrnacokinetics:
`
`Metaboiisin: Metabolites:
`
`MINOCYCLINE IS PARTIALLY METABOLIZED...
`
`tThe Chem:sal Seitiely. Foreign Compound Metabolism in fiilammais Warne 3. 1..0116)31: The Chemical Sordety,
`
`9 of 27
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`
`Apotex Exhibit 1073
` Page 8 of 26
`
`

`
`TOXNET
`
`http: / /toxnet.nlm.nih.gov /cgi- bin /sis /search2 /r ?dbs +hsdb:@a term + @rn +n...
`
`19:15 , p ". 4;
`
`Absorption, Distribution & Excretion:
`
`ALL TETRACYCLINES ARE ADEQUATELY BUT INCOMPLETELY ABSORBED FROM GI TRACT. MOST
`
`ABSORPTION TAKES PLACE FROM STOMACH & UPPER SMALL INTESTINE & IS GREATEST IN FASTING
`
`STATE. /TETRACYCLINES/
`
`. ,N. K.1. díJn, AG. Goodrna í) ií?í $. ì. (a:'JJí:': 'iéìn äf7ä (:s3i:::Eln S The
`[Hardman,
`P1)f. § *)?)i`cologica? Base of Thel'apeu13CS. 9th È d. Nev York. NY: )311ci.1r w -Hiii. 1999.. p. 11261 " ".PEER P EVE .ti i::D*"
`
`-.'+_, Lirebird. P.B.
`
`i(: Eno t.
`
`The percentage of an oral dose that is absorbed is 100 %.
`
`Nordrnan, J.(:ì.. LE. i..ìrnbird, P.B. Molinolf, R.: ^?.:Rod :on. A.O. Goodman (eds.). Goodenan anti (:iii:r:,zri s The
`Ph .r)aco og:cal Basis of .: het<,íe,,:i.<s.:
`
`ed. Now York. NY: McGraw- tií! . í95;r >.,1a. D25] "`t:'í-E: Et
`
`ALL TETRACYCLINES ARE REMOVED FROM BLOOD BY LIVER, WHERE THEY ARE CONCENTRATED & THEN
`
`EXCRETED, BY...BILE, INTO INTESTINE, FROM WHICH THEY ARE PARTIALLY REABSORBED. BILIARY CONCN
`
`OF THESE AGENTS AVG AT LEAST 5-10 TIMES HIGHER THAN SIMULTANEOUS VALUES IN PLASMA.
`
`/TETRACYCLINES/
`
`r
`[Goodman. (...,.., car:,, a.:.,i rnan. (eds.) The í' hr. §tanrìri) ogi;x§ i:SaS:S n¢
`
`s
`
`Publish'.
`
`Inc., 19:7 5., p. 11851 ',PEER REVIEWEDw
`
`ri;f:l'Fií)£:i31.1::S. , i1§ ed. New York: Mí3:drlÌll2ln
`
`\
`
`FOOD DOES NOT INTERFERE WITH ABSORPTION OF...MINOCYCLINE.
`
`1Herdrnan. J.G.. LE.. Li nhird. P. i. Molín(if, R.W R adceon, AG. Goodman (eds.), Goodman and Gisr.an's The
`
`Basis of ".
`Pharmacological BG
`c::
`! 7E'.rK.pët:;s:.s.
`
`i °Yt ed. New York, NY: McGraw-Hill, 1896.. p, 112f1 -"PEER REVIEWED":
`
`CONCN OF TETRACYCLINE IN UMBILICAL CORD PLASMA REACH 60% & IN AMNIOTIC FLUID 20% OF THOSE
`
`IN CIRCULATION OF MOTHER. RELATIVELY HIGH CONCN OF THESE DRUGS ARE ALSO FOUND IN MILK.
`
`/TETRACYCLINES/
`
`Hardol an. ,i.+3., i...E . i.lr:)()ii7í. RB. Molina'. f ?!:v: Ruddon, A.G. Goodman (eds,.), GOO:. man and Gilrnan's' fie
`sera, r
`i, 1s9ä.} 1126' "'PEER REVI l
`fr)ftarrnecologkni Basis c: Therapeutics.:>..::) et, New York, NY:
`
`D ,
`
`INFLAMMATION OF MENINGES IS NOT PREREQUISITE FOR PASSAGE OF TETRACYCLINES INTO
`
`CEREBROSPINAL FLUID. /TETRACYCLINES/
`
`(Hardman. J.G.. LE, í_imhird. RB. Mciinoff: R.W. Ru ddc)n, A.G. Goodman (eds,). Goodman and Giilman's The
`
`Plaarn.,:cnio;,cai
`
`.;si:, or Therapeutics.
`_P
`
`9th ed. New York, NY: McGraw-FR, 19f3,.. p. 1125) -"PEER RE 'Lní::t'v;::(:;"
`
`PENETRATION OF THESE DRUGS INTO MOST OTHER FLUIDS & TISSUES IS EXCELLENT. TETRACYCLINES
`
`ACCUMULATE IN RETICULOENDOTHELIAL CELLS OF LIVER, SPLEEN, & BONE MARROW, & IN BONE &
`
`DENTINE & ENAMEL OF UNERUPTED TEETH. TETRACYCLINES CROSS PLACENTA AND ENTER FETAL
`
`CIRCULATION AND AMNIOTIC FLUID. /TETRACYCLINES/
`;...ill ^ 1). AG. Goodman (eds.). Goodman 8:.d Gilman' The
`-
`New
`NY:
`tit -*PEER
`l2Eci'3 íE :'rí:í :; "
`
`.
`
`_i.
`
`lí. P.B. Molinari
`
`[Hardman,
`l'
`
`Basis
`
`Therapeutics.
`
`DECR HEPATIC FUNCTION OR OBSTRUCTION OF COMMON BILE DUCT RESULTS IN REDUCTION IN BILIARY
`
`EXCRETION OF THESE AGENTS, RESULTING IN LONGER HALF -LIVES AND HIGHER PLASMA
`
`CONCENTRATIONS. BECAUSE OF THEIR ENTEROHEPATIC CIRCULATION, THE TETRACYCLINES MAY BE
`
`PRESENT IN BLOOD FOR LONG TIME AFTER CESSATION OF THERAPY. /TETRACYCLINES/
`
`(E'lareiman, J.G., LE. (_;
`
`:b1rd. E %, 3. E':eEtnr,ft; N'r':: rCit;ldot). A.G. lzordT^:'a r { §9<,i. Goz "^^r§n and c,l man:'ì'f7e
`Gi
`':'harrrierologica Ba... 43 of Therapeutics. Sue ed. New York, NY: MCGi ew.H1), 15iß. , p..125) ".'Pi1.ER REVIEWED':"
`
`10 of 27
`
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`
`Apotex Exhibit 1073
` Page 9 of 26
`
`

`
`TOXNET
`
`http: / /toxnet.nlm.nih.gov /cgi- bin /sis /search2 /r ?dbs +hsdb: @term + @rn +@...
`
`DEPOSITION OF DRUG IN TEETH & BONES IS PROBABLY DUE TO ITS CHELATING PROPERTY & FORMATION
`
`OF A TETRACYCLINE- CALCIUM ORTHOPHOSPHATE COMPLEX.... TETRACYCLINES ARE DEPOSITED IN
`
`SKELETON OF HUMAN FETUS & YOUNG CHILDREN. /TETRACYCLINES/
`
`[Harriman, .1.0., 1...E.. Ifrobírd, P.B. Molincff. R.W Ruddon. A.G. Goo:in:ion (eds.). Goodman and Giirnan's'The
`! n.
`., lir . t.,.s.: P. 1130; "PEER REVIEi ".'EL;"
`"
`..
`,
`- York: NY: is :. :r-
`cG a .
`Basis u: Therapeutics. 9113 ed. Nov,'
`N
`
`Pharmacological
`
`HALF -LIVES & URINARY EXCRETION RATES OF MINOCYCLINE & DOXYCYCLINE WERE COMPARED IN 8
`
`NORMAL & 8 PT WITH CHRONIC RENAL FAILURE. MINOCYCLINE WAS VIRTUALLY INDEPENDENT OF RENAL
`
`FUNCTION, WHEREAS DOXYCYCLINE APPEARED TO ACCUM TO SOME DEGREE IN RENAL FAILURE PT.
`
`[HE :EANEY D. EKNOYAN G. CLiN PHA:' <Mr:,6101.. THER 24: 233 (197.'.91 "PEER REViEriJED
`
`PubMed Abstract
`
`MINOCYCLINE IS RECOVERABLE...FROM URINE & FECES IN SIGNIFICANTLY LOWER AMT THAN ARE OTHER
`
`TETRACYCLINES... RENAL CLEARANCE...IS LOW..../IT/ PERSISTS IN BODY AFTER ADMIN IS STOPPED; THIS
`
`MAY BE DUE TO RETENTION IN FATTY TISSUES. HALF -LIFE OF MINOCYCLINE IS APPARENTLY NOT
`
`PROLONGED IN PT 11TH HEPATIC FAILURE.
`r ini
`
`arEtncn, ...:;..
`
`...:....
`
`,u3 .
`
`.....
`
`G Goodman
`rC.iE aorr. G.
`
`,t:E s.,, Goodman
`3n <iil. Ci ?irníitl';i
`..>
`
`.
`
`;
`
`to
`
`iharrr:e oloí;Ica': Basis of Therapeutics. 91h e.d. New York, NY: McGraw-Hill, 1995.; p..1281 "PEER REV'lrVVCO"
`
`THE PRIMARY ROUTE OF ELIMINATION FOR MOST TETRACYCLINES IS THE KIDNEY, ALTHOUGH THEY ARE
`
`ALSO CONCENTRATED IN THE LIVER AND EXCRETED BY ... BILE, INTO INTESTINE, FROM WHICH THEY ARE
`
`PARTIALLY REABSORBED. /TETRACYCLINES/
`
`iarrr3r<:n....è.. LE, Lirnbird, RE. >:c eras :, Z.W. ;- ,udc;o;a. A.C. Goodman (eds.). Goodman "m' Gilman'.
`"PEER
`;rx, P!Y McGraw-Hill. 1 JÖ., p. t 26;
`99
`°'F ..1::I E;f :lili :l- EE :`
`York,
`
`i
`
`1
`
`Pharmacological Basis .,f 'Fl,ara 3e oh(s. 918 cd
`t
`
`Nay,'
`
`ELIMINATION FROM INTESTINAL TRACT OCCURS EVEN WHEN DRUGS ARE GIVEN PARENTERALLY, AS
`
`RESULT OF EXCRETION IN BILE. /TETRACYCLINES/
`
`. Limbic+: P.B. %i, linoff. R.W. Ruddon. A.G. Goodin an [clot). Good r:at
`rs :d Giirr!an's The
`[HE3rc' :n.bn, ,I.G., t..
`>>r3 a or; :r.. ,l ?a; :< itif Therapeutics, 9th cr. :v :vv York. N R :rf9r<w-1.81i. gsíì., 6:.1: 231 "Pí
`
`>
`
`SINCE RENAL CLEARANCE OF THESE DRUGS IS BY GLOMERULAR FILTRATION, THEIR EXCRETION IS
`
`SIGNIFICANTLY AFFECTED BY STATE OF RENAL FUNCTION. /TETRACYCLINES/
`
`[Harriman. J.:'
`Priarrnecologleal Basis of Therapeutics. 9ih ed. N -vr York, NY: McGra r-Hiii. 1995.: p. 1128] "PEER REVIEWED'
`
`I... : :.. I..:,;birtl. P.E. Molinoft. R',',t Ruddon, AG.Goodman (eds.). Goodman a'-d nil man's' "'he
`
`Biologi
`
`Half -Life:
`
`.../MINOCYCLINE HALF-LIFE IS/ LONG (16-18 HR)...
`
`[Hardman. d.G.. i..: . E.:rnhìrci. RE. hlolín«4f, RAN". R:EdE;on, AG. Goodman (eds.). Goodman and c,,iimari> TI
`Pharmacological Basis of i17Yn.fJEU;iCs. 9th ed. New York. NY: McGraw-Hill, 1996.. p. 11261 "PEER REvI:
`
`IN MAN MINOCYCLINE, A NEW TETRACYCLINE, HAS BIOLOGICAL HALF -LIFE APPROX THAT OF
`
`DOXYCYCLINE BUT APPRECIABLY LONGER THAN THAT OF OTHER TETRACYCLINES.
`
`(MACDONAI. D F! .... Ai..'. C:I..IN PHARMACOLOGY T 1-1ER 14: 852 E1973)1 PEER REVIEWED'
`
`Mochanis1r; of Action:
`
`11 of 27
`
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`
`Apotex Exhibit 1073
` Page 10 of 26
`
`

`
`TETRACYCLINES ARE THOUGHT TO INHIBIT PROTEIN SYNTHESIS BY BINDING TO 30xRIBOSOMES. THEY
`
`APPEAR TO PREVENT ACCESS OF AMINOACYL TRNA TO MRNA-RIBOSOME COMPLEX. ONLY SMALL
`
`PORTION OF DRUG IS IRREVERSIBLY BOUND, & INHIBITORY EFFECTS OF TETRACYCLINES CAN BE
`REVERSED BY WASHING. /TETRACYCLINES/
`
`/xo,m"p..1s.1...s.u."m.d. RS. wmmmr.
`nx000n. AG. Goodman (*xs.). Goodman and snme.,sThe
`Us o Thsrsp
`9th ed, Nw \'cwk. NY: McGre.HHi, 995.. p 1125j iER REVIEWD
`Pharmacological Basis of Therapami,s, gth ed. New York: NY: McGraw- Hill, 1995.. p. 1125; i'"PEER REVIEWED"
`
`IT IS POSSIBLE THAT REVERSIBLY BOUND ANTIBIOTIC IS RESPONSIBLE FOR ANTIBACTERIAL ACTION.
`
`/TETRACYCLINES/
`
`«Gon"=1.c, and a Gilman. ,mw The Pharmacological oæu,"r Therapeutics. om ed. New mm.Macmillan
`
`PHOTOALLERGIC REACTIONS ARE BELIEVED TO RESULT FROM LIGHT ENERGY ACTING ON OR ALTERING
`
`DRUG & SKIN PROTEINS IN SUCH MANNER AS TO FORM AN ANTIGEN. THESE ERUPTIONS REQUIRE
`
`PREViOUS CONTACT \MTH OFFENDING SUBSTANCE, ARE NOT DOSE-RELATED, & EXHIBIT CROSS-
`sewamvnvvwr*o*sMneuns000upo. /Tsrn^o,ouwsm
`oOso/,a. end 1e. Hoover, et al. ((tits ).nomo.uto"'o Pharmaceutical Sciences. mo. od. saux`. Pennsylvania: madt
`Publishing Go_ ma,x.,275]~pss*nsveeæn~
`
`Interactions:
`
`BECAUSE METHOTREXATE BINDS TO PLASMA PROTEINS, IT CAN BE DISPLACED FROM ITS BONDING
`SITES & MADE AVAILABLE ro REACT VVIr*mmmnopoLmEnsouoTAus.'zmmpo
`
`THAT...DISPLACE...INCL...TETRACYCLINES. /TETRACYCLINES/
`
`ls,el"ammx oil Drug interactions. 2nd ed. and svn^^".^../^wmw`/"uxm.DC: American Pharmaceutical ^m,``
`
`STRIKING ANTAGONISM BETWEEN PENICILLIN & TETRACYCLINES HAS BEEN OBSERVED CLINICALLY IN
`
`/TETRACYCLINES/
`
`(Gnod:nn.L . o. and A.amn:.vawne. Pharmacological Basic of Therapeutics, 5th ed. New York: Macmillan
`Publishing Go.. Inc., 1975.. p.-t1:35j 'PEER RliiVIEWED"
`
`NEOMYCIN & RELATED ANTIBIOTICS PRODUCE PROFOUND NEUROMUSCULAR BLOCKADE IN HUMANS.
`
`USE OF THESE ANTIBIOTICS WITH NEUROMUSCULAR BLOCKING AGENTS COULD LEAD TO...RESP
`FAILURE. /NEOMYCIN/
`
`|E. \.111vuon,rr Drug interactions, 2nd ed. end ru,momæ/y, Washington, DC: American Pharmaceutical Assn,
`
`'.Posumurvop'mEVEnsnswALpmLunsIN PT WHO RECEIVE TETRACYCLINE AFTER BEING
`ANESTHETIZED \Mr*wETHnxvr URANE; IN THOSE WHO DIED, KIDNEYS CONTAINED NUMEROUS
`CALCIUM OXALATE CRYSTALS. /TETRACYCLINES/
`
`moo^m":./'o. and aomme:.m^s/ The Pharmacological Basis *Therapeutics, 13th ad. New York: MeerrülIan
`Publishing Co., Inc 1975., e. 1189] "'PEER RE.V1EWED"
`
`TETRACYCLINES ALSO INTERACT WITH DIURETICS TO CAUSE AZOTEMIA. /TETRACYCLINES/
`
`mmx A. and J.E.. Hoover