1111111111 GIJ<oi'J"DI ... Injodlon, USII

Rx:anly NOT FOR USE IN NEONATES CONTAINS BENZVL ALCOHOL

DESCRIPTION Glycopyrrolate Injection is a synthetic anticholinergic agent.

Each 1 ml contains: Glycopyrrolate, USP 0.2 mg Water for Injection, USP q.s. Benzyl Alcohol, NF 0.9% (preservative) pH adjusted, when necessary, with hydrochloric acid and/or sodium hydroxide.

For Intramuscular (IM) or Intravenous (IV) administration.

Glycopyrrolate is a quaternary ammonium salt with the follmMng chemical name: 3[(cyclopentylhydroxyphenytacetyl}oxy}-1,1-dimethyl pyrrolidinium bromide. The molecular formula is C

1,H

218lNO, and the molecular

weight is 39833.

Its structural formula is as follows:

MW398.33

Glycopyrrolate occurs as a white, odorless crystalline powder.lt is soluble in water and alcohol, and practically insoluble in chloroform and ether.

Unlike atropine, glycopyrrolate is completely ionized at physiological pH values. Glycopyrrolate Injection is a clei!IT, colorless, sterile liquid; pH 2.0 - 3.0. The partition coefficient of glycopyrrolate in a n-octanol /water system is 0.304 (log,0 P= -1.52) at ambient room temperature (2411C).

CUNICAL PHARMACOLOGY

Glycopyrrolate, like other anticholinergic (antimuscarinic) agents. inhibits the action of acetylcholine on structures innervated by postganglionic cholinergic nerves and on smooth muscles that respond to acetylcholine but lack cholinergic innervation. These peripheral cholinergic receptors are present in the autonomic effector cells of smooth muscle, cardiac muscle, the sinoatrial node, the atrioventricular node, exocrine glands and, to a limited degree. in the autonomic ganglia. Thus, it diminishes the volume and free acidity of gastrk secretions and controls excessive pharyngeal, tracheal, and bronchial secretions.

Glycopyrrolate antagonizes muscarinic symptoms (e.g .. bronchorrhea, bronchospasm, bradycardia, and intestinal hypennotility) induced by cholinergic drugs such as the anticholinesterases.

The highly polar quaternary ammonium group of glycopyrrolate limits its passage aaoss lipid membranes, such as the blood-brain barrier, in contrast to atropine sulfate and scopolamine hydrobromide, which are highly non-polar tertiary amines which penetrate lipid barriers easily.

With intravenous injection, the onset of action is generally evident within one minute. Following intramuscular administration, the onset of action is noted in 15 to 30 minutes, with peak effects occurring within approximately 30 to45 minutes. The vagal blocking effects persist for 2 to 3 hours and the antisialagogue effects persist up to 7 hours, periods longer than for atropine.

Ph•rm•cokinettcs

The following phannacokinetic information and conclusions were obtained from published studies that used nonspecific assay methods.

Distribution: The mean volume of distribution of gtycopyrrolate was estimated to be 0.42 ± 0.22 Llkg.

Metabolism:The in viW> metabolism of glycopyrrolate in humans has nat been studied.

Excretion: The mean dearance and mean T11l values were reported to be 0.54±0.14 Ukglhr and 0.83±0.13 hr, respectively post IV administration. After IV administration of a 0.2 mg radiolabeled glycopyrrolate, 85% of dose recovered was recovered in urine .S hours postdose and some of radioactivity wa.s also recovered in bile. After IM administn~tion of glycopyrrolate to adults, the mean T,n Vlllue is reported to be between 0.55 to 1.25 hrs. Over 80% of IM dose administef'MI was recovered in urine and the bi le as unchanged drug and half the IM dose: Is excreted wtthln 3 hrs. The folowlng table summarizes the mean and standard deviation of pharmacokln~lc parameters from a study.

V11 CL Tma: Cmax AUC (Liko) ~l (mm) (_,..) (.......,.)

(6~IV) O.Ut0.27 0_4l,I,0,22 O.S4:l0.14 1.64:0:1.49"'

(lmcglkciM) 27.41h6.12 3.47:.1.48 6.64=.2.33'

SPECIAL POPULATIONS

Gender: Gender dlfference.s In pharmacokinetics of glycopyrrolate have not been Investigated

Rena/Impairment: In one study glycopyrrolate was administered IV In uremic patients undergcMng renal transplantation. The mean eUmlnatlon half-life was significantly longer (46.8 minutes) than In healthy patients (18.6 minutes). The mean area-under-the<oncentratlon-tlme cui"Ve (1 0.15 hr-mcg/L), mean plasma clearance (0.43 Uhrlkg), and mean 3-hour urine excretion (0.7%) for glycopyrrolate were also significantly different than those of controls (3.73 hr-mcg/L, 1.14 Uhr/kg, and SO%, respectively). These results suggest that the elimination of gtycopyrrolate Is severely Impaired In patients with renal failure.

Hepatic Impairment Pharmacoklnettc Information In patients wtth hepatic lmpatnnent Is unavailable.

Pediatrics: Following IV administration {S meg/kg glycopyrrolate) to Infants and children, the meanT~ values were reported to be between 21.6 and 130.0 minutes and between 19.2 and 99.2 minutes, respectively.

INDICATIONS AND USAGE

In Anesthesi•: Glycopyrrolate Injection Is Indicated for use as a preoperative antlmuscarlnlc to reduce salivary, tracheobronchial, and pharyngeal secretions; to reduce the volume and free addfty of gastric secretions; and to block cardiac vagal inhibitory reflexes during induction of anesthe.sla and Intubation. When indicated, GlycopyrTOiate Injection may be used Intraoperatively to counteract surgically or drug­induced or vagal reflexe.s associated arrhythmias. Glycopyrrolate protects against the peripheral muscarinic effects (e.g .. bradycardia and excessive secretions) of cholinergic agents such as neostigmine and pyrtdostlgrnlne given to reverse the neuromuscular blockade due to non-depolarizing muscle relaxants.

In '-Ptlc Ulcer: For use In adults a.s adjunctive therapy for the treatment of peptk ulcer when rapid anticholinergic effect Is desired or when oral medication is not tolerated.

CONTRAINOICAnONS

Known hypetsensltlvfty to glycopyrrolate or any of Its Inactive ingredients.

In addltton, In the management of plfllk ulcel patients, because of the kmger duration of therapy, Glycopyrrolate Injection may be contraindicated In patients with the following concurrent condltion.s: glaucoma; obstructive uropathy (ftw example, bladder neck obstruction due to prostatic hypertrophy); obstructive disease of the gastrointestinal tract (as In achalasia. pyloroduodenal stenosis. etc.); paralytic Ileus, Intestinal atony of the elderly or debilitated patient unstable cardiovascular status In acute hemorrhage; severe ulcerative coltti.s; toxic megacolon complicating ulcerative colitis; myasthenia gravis.

WARNINGS

This drug should be used with great caution, if at all, In patients with glaucoma.

Exposure to excessive amounts of benzyl alcohol has been associated wtth toxldty (hypotension, metabolic acidosis), partiC\llarty In neonates, and an increased Incidence of kernicterus, particularly In small preterm Infants. There have been rare reports of deaths, primarily in preterm Infants, associated with exposure to excessive amounts of benzyt alcohol. The amount of benzyl alcohol from medications Is usually considered negligible compared to that received In flush solutions containing benzyl alcohol. Administration of high dosages of medications containing thl.s preservative must take Into account the total amount of benzyl alcohol administered. The amount of benzyl alcohol at which toxicity may occur Is not known. If the patlent requires more than the recommended dosages or other medications containing thl.s preservative, the practitioner must con.sider the dally metabolic load of benzyl alcohol from these combined sources. (See PRECAUTIONS, PodlotncUM).

Glycopyrrolate Injection may produce drowsiness or blurred vision. The patient should be cautioned regarding activities requiring mental alertness such as operating a motor vehicle or ather machinery or performing hazardou.s work while taking thl.s drug.

In addition, In the presence of fever, high environmental ternperat\Jre and/or during physical exercise, heat prostration can occur with use of anticholinergic agents Including glycopyrrolate (due to decreased sweating), particularly in children and the elderly.

Oiarrtlea may be an ear1y .symptom of Incomplete Intestinal obstruction, especially In patients with Ileostomy or colostomy.ln this Instance treatment with Glycopyrrolate Injection would be Inappropriate and possibly harmful.

PRECAUTIONS

Investigate any tachycardia before giving GlyoopytTOlate Injection slna an Increase In the heart rate may occur.

Use wtth caution in patients with: coronary art:ery disease; congestive heart failure; cardiac arrhythmias; hypertension; hyperthyroidism.

Use with caution In patients with renal dlsease slnathe renal elimination of glycopyrrolate may be severely Impaired in patients with renal failure. Dosage ad]\Jstments may be necessary (see PMnn~~coldnetla - Renal Impairment).

Use Glycopyrrolate with caution in the elderty and In all patients with autonomic neuropathy, hepatic disease, ulcerative colitis, prostlc hypertropny, or hiatal hemla, .since anticholinergic drugs may aggravate these conditions.

The use of antlchollnergettc drugs In the treatment of gastric ulcer may produce a delay In gastric emptying due to antral statls.

lnformM:Ion for the htlent Because Gtycopyrrolate Injection may produce drowsiness or blurred vision, the patient should be cautioned not to engage In activities requiring mental alertness and/or visual acutty such as operating a motor vehicle or other machinery, or performing haz.ardou.s work while taking this drug (see WARNINGS}.

The pattent also should be cautioned about t he use of this drug durtng exen:::lse or hot weather since overheating may result In heat stroke.

The pattent may experience a possible sensttlvity of the eyes to light

Drug Interactions

The concurrent use of Glycopyrrolate Injection wtth other antlchollnerglcs or medications with anticholinergic activity, such as phenothlaz:lnes. anti parkinson drugs, or tricyclic antidepressants, may Intensify the antlmuscartnk effects and may result In an Increase In anttchollnerglc side effects.

Concomitant administration of Glycopyrrolate Injection and potassium chlorkle In a wax matrtx may Increase the severtty of potassium chlorlde·lnduced gastrointestinal lesions as a result of a slower ga.strolntestlnal t ransit time.

Long-term studies In animals have not been performed to evaluate carcinogenic potential. Studies to evaluate the mL.Jtagenlc potential of glycopyrrolate have not been conducted. In reproduction studies In rats, dietary administration of glycopyrrolate resulted In dlmlnl.shed rates of conception In a dose-related manner. Other studies In dogs suggest that this may be due to diminished seminal secretion which Is evident at high doses of glycopyrro late.

Teratogonlc Efftcts- PregnoncyCatogory B. Reproduction studies with glycopyrrolate were performed In rats at a dietary dose of approxlmatefy 65 mg/kg/day (exposLMe was approximately 320 times the maximum recommended dally human dose of 2 mg on a mgtml basis) and rabbits at Intramuscular doses of up to 0.5 mg/kglday (exposure was approximately 5 times the maximum recommended daily human dose on a mgtm~ basis). The.se studie.s produced no teratogenic eft'ects to the fetus. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

SlngltHiose studies In humans found that very small amounts of glycopyrrolate passed the placental barrier.

Nonterotogenkeffects Published literature sugge.stthefollowtng regarding the useofglycopyrrolate during pregnancy. Unlike atropine, glycopyrrolate In normal doses {0.004 mg/kg) does not appear to affect fetal heart rate or fetal heart rate variability to a .significant degree. Concentrations of glycopyrrolate In umbilical venous and aterlal blood and In the amniotic fluid are low after Intramuscular administration to parturlents. Therefore, gtycopyrrolate does not appear to penetrate through the placental barrler In significant amounts. In reproduction studies In rats, dietary administration of glycopyrrolate resulted In diminished rats of pup survlvalln a dose-related manner.

It Is not known whi!'lhertllls drug l!i e~~:~:reted In human milk. 81!mum many drugs are !!'liO'l!ted In hul'l'llln mAk,omtion sllol..lld be I!!'MI'd!ied when Giympymlliite ~~~m is Oldmrnl~ to 01 nun;lng .....aman.k. with otlw!r antlchollnergia, glyoopyrroliite mil)' 01use su~lon <;Of ~h;on (Jee ADVEME IIEACT101\1$l.

l)ylrhythmlas amxlated with the use of giympym~liite lntfiM!nal.l$1y ;ns a pmmedicant Of during anerth~~Sla hiM! been ob5er.'ed in pWf.lotrl~~ntJ,

Infants, prtlentJ; with Down's ~rome,. and pedfitrk patients with !pii!!ol:k par.lljrsl! 01' brain d;!m;r,ge may mperi!!I"'CC! ~n lrn:!l!aSI!!l rwponsor to ~n!;lr;hg!lraergk:!;, thus ir>l;l'9s1ng !he poWrrtl=l fw *~!: ~

A p.;u11dtlldcai !l!ild:lon ~zed by hypl!rmdtabU!ty mil)' ocwr In pedlalrlc p;rtlentJ; tll::lngl~rge dOSI!!I of antidlollner;alc Including G~l!ll lnjm;tion, l.m.nti ;nd )'I:'Ung <;hlldren ;re espe;l;ll~ :~~.~ll;eptlble to the toxl~ effem; <;Of ~ntil;hdinesgk:s.

B<!flzyl alcohol, a Ol.'ll!'fiponmt of till§ drug produd;, ha~ bei!fl ~ wilt! serious illdlrme ~and dealt!, po~rtlwlatiy In pedl;Wk: poltients. The•g!llPing 'lt'ndmme."(chio~ by(lllntr~l nermuJ $Jt'$tl!m deprenlon, metisbolkOJCidollls, gllltplng fll5!l'll'llkions,~nd high I11!'W!Iscfben:ey4 mloohal and Its mll!tlibol!1.\15found In 1he blood and urine) hills been amx:hrted with ben:ey4 ah:ohol dM&ges :>99 mg/i'l,j!fdllljl In neol'iille§ and law-bfrt!).welght ~ Addltlonall)lmptom5 may lndude gr.rdual neurolaglr.iil dl!teriorntion, M1fatf!!!;, irrtr.IOWllal h!imorrk!oge, h~l~ ~bnorm~lltl~ ~kin bre!!>kdow"' h!ip;~tl~ ~nd ~ fioll~"" hypotel"'flon. bf~~~ ~nd aordiQ\Ill~l!or mllmp3e. Atthough oormmllhempem:k d!lWI cf thl1 product dei!Ver amool"lt!! cf benzyl alooh!M that are !ubltantislly lnwer than those f!!PCI't!!d In ;urod/Jtloo with tlle"g;uplnQ S)'l'ld!OO'II!,"tile minimum ani'IO!.mt of benzyl alootlol it whk:h b!ldty may OWJr !{ nat koowrl. Prm111t\lre =nd low-b!l"!trtwlghllruf.m~ iU well a~ P!ltlmt'l r!it::ellllng high di;~Mges, rmy be rrtr;~R llkitl)' to~ toJik:lty. I'Mctttlwim. admlnlltellng th!J and Olt!er medlatloo1 COI'Iti!lnlng hemyl mh::ohol1hou!d oonlldertherombllled dirty m!!tilbcllc load of hemyllllcohol fmm;allsauro!S.

ClfniGIII Studies cf Glycopyrrokrte lrlfectkln did not lndude suffident numbel'5 of subjern 1ged 65 lind tl'fflr to determine whetller they re5pond differently from )'OOnger !iUb}a:t5. Other reported dlnk:DI experiern:e hlls not idll!flttfled dl«erentes In response betwll!en the elderly and j!Otlnglt!!r patfl!l!1b. In gener.d, dare r.electlon fur ~n ekietiy patient should be caullo!J§, usmlly !rtilrting a the law end of the i:~Pilng r.~ng11:. reileo;ting the gre;rter freq""'ncy of detrellred h~ reml, or o::llrdi!l.~ function. ~m:l of r;ol"!tQQlll\lllnt dl-soe lill' other therapy.

Antldlolloorglc, lndudlng G~lli! lnjectloo, c;~n prodi.Kl! Oi!rlliln efl'eru, I'II'IOSt cf whldl aN! externlons of lhl!lr ph;rm~mltl!llk: iictkms. Mvem. reilctlorn; mil)' ln~ll.!de Mrmtomlil (dry ITIOl.!th); urll'lllry heilblncy 11nd retentlm; biYrred vlslon md photaphoblii di.Nl to fl'fjdrta!lll; (dllatton of !he pupil); ~egla; lncrea>ed ocular tension; !liehyoln:iia; palpltD!Ion; deaeil!led sweating; Hm of wte; heiidad'w!; nefVOUifle!i!l; dl'llW!iln-> Wl!ilkne!;s; dtzllfle!is; lf\i!lmnr~; nil~ wmltlng; lmpeb!fl~ SUPfl'tiikln of lacti11on; OOI'Istfp:itkm; bloared fueling; -relllllerglt l'elldlwii induding m~phyiilldldl!Mr*rJtjilctold reactkm5.: 11ypet1rensltlv!ty; urtlt~~rla. pruritus. dry ildn,lllnd other dermal manifestltlcml; some degree of mentlll canfu5ian andtorf!l!dtement, espetially in elderly pol!f50!'IL

In i!ddl&n. the fullowlng illl'flln;~ ~ h<~W been reported from poot-mllrketlng e!Q)eriooce with Glya:>pyrrolm m~~llqn~nt l'lyperthermll; ardiill!c !rrhythmiill!! (induding bradymn:il!!, wnt!i!:<IIar tlldtymrdia, Y!!ntrirulmr fibrill!!tioo); an:ii!C 1r151< hjlperten!loo; ~on; 51!fZIJ~ and l"!!§j..lratory iim&. l'o!t-miirla!tlng repom h;we rndud!!d c:il!e!i of 0011 bkxk and QTc lnt.i!!'wl prolongation IIHOdi!.Wd with tile tumb1ned Yse of glyropyrrolillte ~nd &n ~ntk:holin~e. lnjectiafl !ilte mi!ctloo~ lndudlng pruritu:r, !!demi!, <!!i'jrtlw!m!!, and pa111 have aim beer! reported.

G~li! il doemiGII!Iy a qW~li!mmry amm011ium CM'Ipo!Jn.d; hena!, b paiSigl! DCro!IS lipid memb!'DM:I, sudl iii the blood-bmin hilrrler k lrmlled In~ to atropine 5utfm. and soopelamlflol! hydrobromlde. F<Nthli fl!amn tile oo::ul'l'l!!I"'CC!ofCJIIS.Il!lated side effect\ Is lower, in romp;:n'iiKH'I to their lm:idmcefullowlng ildmlnlitr.ltlon of ilnikhol!nergk:i whk:h m: dlemiGII!Iy tertliuy ilmlneo; thilt am CI'Oi5

thlsblll!'lll!rmadily . ......... , To oombllt periphl!ml enti!:h!Mineugk, "' qu!!temlry Jllmmonlum Jllntidlollm!xl!!mte ru.:h 1111 n!!!OS!igmine mmhylsulfllte (which dM!II net O'Oti tile blotld-bniln bmlel') may bl! gl\lli!n lntr.rwno!..Wy In lncrementJ; of 0.25 mg In adult!. This do5age may bl! repeated e'\1'1!1}' filii! to ten mln!Jtei until ~ntk:halinevgk ~I~ rewrood ill!' up to 1 mulmum of 2.5 rrtg. Proportlonlltfll)' :im!ilklr dtlil!li shook! bl! used fn pafOII!'I~ patlenl3. lnditBtion fur repetition! dale~ of nemtigmin.e should be bl!!lled on dose manitaring- of the decreare in lliiNirt !'!!lte lind the relllm of bowel round£.

If OilS i)ll'l'ipt!lmi (e.;j., I!!IOCIW'rlent. ~nli!'i'%WI'IVUWort;;, p!>)'COOI!:Ic betlilvlol') orour, ph)riml:lgmlne (whldl does mmthe blood-btall'l bmlerl miiY be used. ~lgmfne ll5 to 2 mg should be slowly iidmlnl:m!red lntri~YJ~!r!ous;ty 1nd mPMI'Iild 111 naol!mlry up to a1oiiil cf 5 mg in adultll. Pmportinnl!teiy smaller dosa 1hmlld be <ili!d In pedilltric patients.

Following mrertla!lilg~>, :o cumre-lilo!! 111ct1oo may <XWr, i~ nl!!.!romuM:uiM bla.::kao:le leM!ing to mUU>.~IBI111RM!knl!!l!l and pa11ib!e paraly.l;;s. In the I!Wfrt of a uuare-llb! effKt on i't!!iplratory ml.l!d~ artll'idal l'll!!!!plratlon $hould be lrulllutl!d and maintained unlll effectrw mplrii'kwy iictlon rehimi!.

l'itrentJimd dl'll9 produW liloukl bll! lmpected Yi:IYJ!IIyfur partlt~Jii!'ffi mitt!!f illn:l dlocoloolllon prior to lldm!nirtmlm wftl!l'l!!'IIW rolutlo:m "'nd C<:Jntalner permit

----The F'ECQmmendo.d dose of Glycopym;lillili! Injection is CUl04 mglkg by int!'DmuM:ul;ir injection, giwm 30 to 60 mii'i\Jtf!S prior to the .~ontldp;;rted time oflndur.:tr~m of 111'1115thi!!'ila IN attheti!TN! tile p11!!111'1115thet1c ne=tkand/or iedlitlw!! Qfe admlnlm!red. ---G~te lnJectloo rtlilo/ be liSII!d dul'lng $1.1lgt!!ryto IOOUI'Itemct drug-Induced or VII!Jill retii!!!IIIM and their llliwd!rted whythmliils (e.g,. brndymrd!al.ltshould be iidmlnllrti!red lntmlll!ooui!ly u i!lnglii!d!:nmof!l. I mg ilnd ~ u neet:kd. ill: lntli!!'w!!s of2to 3 minute. Thii! !.l:lU!Illrttempb; 1h<:lllld be rmde to de!i!rmlne the lrtfology cfth.e ~fl'hythmll!, ~nd the xu~gbl or ~~t <mnlj:l\!ii!tk:m~ n~ry to m!\00 p.;~~pi!tl'H!tk lmbal!lna! should be p.ll'furmed.

~cl~~ The rewmmendeddos!! ofGiywpyrmlate lnJm;t/01"1 b 02 m; fur each 1 m; ofi'II!!IJ«ttgmll'll! or Sll'tl!!il of~gmln!!.ln on:lerto mlllfmlze tha ilppi!<ll!ilnoe of U~n:lliK: side i!l'l'!!cb:.lhl! druQII mil)!' be i1dm1ntstei1N:I slmulbl!'iE!OUily by lntnmmot~i lnjl!dlon and mil)' be mixed In tllii! l<!me$jflirlg=.

Peptk:Uk:er The UW~~I !llQJml'i'l!il~ 00.., of G~te lnjec;tion i!l 0.1 mg 'dminlm.....:l :ot 4-haur intefY!IIIs, 3 or 4 tim~ d~lly i~noudy Of

lntnhmU!!Cularly. Where mo~e p!'Ofo!JnrJI effect 11 required, !1.2 mg ITIIII)'begl\len • .!ioo'w! patient!: may need only a ~1ngk! dO!IIlrand frequency of idmlniWitlon sh<:l\lld be dldilted by pirtj'i!!l'lt resp:liUI! up toil mro:fmum of fum llmeJ dilly.

Pedlii!trl' Pllticnti !see PmECAIJ'I10N5- Padlatl'lc U.l

Pmim!Mthl!tk: Mediation The recommet'ldad dDii!! of' Gly<:opym~lll!te lnjec.tian in pedilltric patl!!ntl; is CUl04 mgl1ig lrltmrlu3a.illrly, ghn!n 30 ttl 60 minlltt!l prior to the antrclp.;iiOOd time of Induction of aneslill!!;la or ill: the tima the p!'l!ilnesthll!!tic nai'Wtlc and/or sedatl\lli! are admlnl!rtel'ed.

lnt.lnts. [1 month to 2 yeJI'5 of lOge) mq fflqi.il!ll up to 0.009 mgl1ig --kai!J!ll!! ofthe long dumtlon of action of GlywP'Jifi""Jiillte lnjet.:tli:m lf\JSII!d llll preMe!thetkmedl.:at~on,addltlonal G~te Injection fur ~ntlcholinergk: li!ffl!ct lntr.roper.!tlwly I$ rilrely needed; fn the event !!: Is required the I"'CCO!mended p!!dli1rlc dooe 11 <UXM mgfkg ~~~ly, ng!Jf:o~ ll.1 mgln~ 5lngle~whlch ITIIII)'~ ~lllf; nel!ded,lithrtentlll~of2to3 minute~!. The Wi<dlltw'npb 4lould be made to dete!mln!! the !!tkllogy d the mnflythmla, and the ~urglcai or anm:lw!tk: manlpulatioru ~ry to mired pili15}'ITipilthll!'l:lc lmbiilance should be performed .

.Relomalof~Bh:'k<lde The rnmmiTii!nded pedlit!i!: dose ofG~iiE: Injection Oi tl2 mg fur eadll mg of I'IE!OStlgmlne or 5 mg of pyrldwilgm!ne.ln oo:ier to minlmlze the IP]lCIIW'I'-"' rJl an:iiK i!lde ~the drugJ mill)' ~ :odmlni:rten!d l!imultllneoWily by intmvenoo~ injedion 1m:IITIIII)' be m!Ked In the !li!ITN! tyrlnge. --GI)'!~te Injection i! not ~Kt~mmended rorthe tre<ltment of' pept.ir.: ukl!r in pedil!bic pati!!nta {iee Pl'teCAITnDIIS- Plldliltl'k ll'!!a).

DILUENT COMMTIIIIIUTIIES

Oettrose 5'1011lnd 10% In Wilter, or saline, d&trns~ S'Ji!lln sodium chloride 0.4S%,-sodlum chklrlde 0.9%, md Ringer's lnji!Ctlon.

DILUENT INO:IIIIIPA111111UE5

Lattllted Rlngm; sollll:lon

IIDMRTU!l;i; COMM1111111Lmi!!S

~lad O.:.mplltlbllrty: Th!i IM doe~ mrt oonstrtute an mdorsemmt of the dlnk:iiil lltlllty or iarety of m-iidmlnlstl'ilt!an of G~ with lt!e!ie drugs, G~re lnjectiafl I~ wmpatibk: fur mbllng lllnd injection wM the fullawln; lnlcd.>lblc ~e furm~ ;rtroplne wi111te. USP; Antilrrium" {phyl:ostigmine salicylate}; l!etliidl')le (dfphenh)'dramine HCIJ; .:odeiM phm:phete, USF'; Em~n" (ben..-quinarroidi! Hd); h)idrommplmne HCI, USP; lnipslne" (drope!Mo!); Li!'tl'o-Drornol'iln~ 011!V0Yphinol ton1riite); lrdol:iRine, USP; mepertdlnil!' HO, USf>; Mi151:1non" !Rcgonoi• {pyrkk>itigmloo bromide}; I'I'!Off,lhlne wlfate. USP; Nubiiln• (nllbuphlne Hat: Nf.lmwphan" {J»lYY''''Ili'Phllne Hat prot:;lliine HQ, USI'; p!'fH'fl>l!!thltzirt.e HC~ USP; Prm1.igmin" {~mim. meltrjtiwlf11te, USI"); $Wpt!lf;lmir'll!! Hllr, USP; stadale {butorphar'ICI 11.1rt!'!!lte); Subflmue• (funtnnyl citrate); 11gin° (trimetlmbenZimlde HCI); and V!!itirlle (llydrmt)'Zine HCl}. G~te lnjectioo may be ildmlnl:rtemd vl~ the1u.bing of"' running lnfu~lon tl'fnom111i nlln~.

l'hyl:iallnt:M'Ipatibility: Sino;, the lti!blllty of g~te Is questlorn!b!e l!lbwe a pH of M do not oomblne G~pyrralate Injection In the SOITN! syringe wilt! Bircvlbll~ (mcthahiiiiXItiil Nil); Olloromy«:tine {dllorllmphoolml Nlll rua:il'lllltc); Drllmlllmlnc'" {dfmcnh)'dr!nlltfl); Ncmbutilll" (~rblt!l Na); Pl!ntothal" (tlliepellt!ll Ne); Sl!ctlnale (!latdlarbital N.l); :mdium biar~ (Abbott); Valium• {d~m}; O!!admne (dhi!N!tlla­sone Na pholiphllili!); INTiilwln" {pei'ltizodna lilctate). T11115e mbi1JJre; will ~~SUit In a pH highEr then !ill md may re;ult In fi15 prod!Jctkln cr preclpltlrtlon.

0.2 mg/1 mL Singl!!-tkl:!i! Yiel~ padager.l in lli {NIX 70llM-011-25) 0.4 mg/'2. mL (0.2 rngtmL} Single-dose \/!ill packiged In 255 (NOC 7(l009.(11:1-25) 1 mg/5 mL (0.2 lllllfmlJ Multiple-dam VIal" ~ed In 25m !NOC 70059-01!11-25) 4 mgl2!l mL (0.2 m.Vml.} Mi.ih:ipl!!~ VIall; pet:kagecl in lOll (NOC 71X169-614-10)

Stand 3G"CII!i :IJ<'C (II&'F tG 7J"f) [S;HI USP CGritmlkid ~ Tilll'llplli'&tln(l.

To !'!jX!rt SIJ:!>PECTED ADVERSE REI\CT10NS. o:ant.tet St.trw\t!!'!<!!l; Thoimlpeutia, l.iC Ill: 1-4!00-417-9175 or FDA 1111: 1-aoo-FOA-100:6 ar liiiWWidagOY/meltwatd1,

Manufactured 8y: WintM: Umlted Si;l'lgoll~S62123 India Gode No.: IIM:lRIJGS/KTKfJ.Ill'l89JS7

Manufactured fur. Soo!ersetThmlpeuth::s, l.iC SOmli!ll'$ol!l:. N.l 00673

1111111111