Eyeworld

N O H 2 N HN OH O OH N N --------------------------------------------INDIC Initial U AN (ganciclo G ZIR See full pr hese highlights do not include all of the information needed t T HIGHLIGHT AND TIONS AT --------------------------------------------INDIC 9 98 al: 1 v o .S. appr Initial U % 15 . vir ophthalmic gel) 0 AN (ganciclo AN. G escribing information for ZIR See full pr hese highlights do not include all of the information needed t TION ORMATION CRIBING INF S OF PRES HIGHLIGHT • • --------------------------------------- None. ---------------------------------------------C GE------------------------------------------- A US AND . ely tiv nd eec afely a s ® AN G o use ZIR hese highlights do not include all of the information needed t .2) AN. (5 G y with ZIR se of ther e signs or s v act lenses if they ha ear cont atients should not w P AN is indicated for topical ophthalmic use only G ZIR S AND PRE ARNING W --------------------------------------- None. AINDIC ONTR ---------------------------------------------C atitis or during the er ymptoms of herpetic k e signs or s 1) . . (5 AN is indicated for topical ophthalmic use only UTIONS---------------------------------------- A C S AND PRE TIONS---------------------------------------------- ATIONS---------------------------------------------- AINDIC AN cont G ZIR --------------------------------------DO y 3 hour er v e ecommended dosing r The r ---------------------------------------DO s). (1) ulcer AN is a topical ophthalmic antivir G ZIR --------------------------------------------INDIC 5 5 W 5 C 4 DO 3 DO 2 INDIC 1 FULL PRES ed topical ophthalmic gel. (3) v eser vir in a sterile pr % of ganciclo 15 . ains 0 AN cont ORMS AND S GE F A S --------------------------------------DO e) until the corneal ulcer heals, and then 1 dr ak w s while a y 3 hour op in the a†ected ey AN is 1 dr G egimen for ZIR ecommended dosing r ADMINIS AND GE A S ---------------------------------------DO s). (1) al that is indicated for the tr AN is a topical ophthalmic antivir AND TIONS AT --------------------------------------------INDIC enses act L ont oidance of C v Av .2 5 opical Ophthalmic Use Only Topical Ophthalmic Use Only 1 . 5 UTIONS A C S AND PRE ARNING W TIONS ATIONS AINDIC ONTR C THS TRENG ORMS AND S GE F A S DO TION AT TR GE AND ADMINIS A S DO GE A TIONS AND US ATIONS AND US INDIC * S ONTENT TION: C ORMAT CRIBING INF FULL PRES See 17 for P at 1-800-FD o r T er k Most common adv ---------------------------------------------- AD ed topical ophthalmic gel. (3) THS-------------------------------------- TRENG ORMS AND S s. (2) op 3 times per day for 7 day e) until the corneal ulcer heals, and then 1 dr ximately o e 5 times per day (appr op in the a†ected ey --------------------------------------- TION ATION TR ADMINIS atitis (dendritic er te herpetic k eatment of acu al that is indicated for the tr GE------------------------------------------- A US AND 14 13 12 11 TION ORMATION. OUNSELING INF TIENT C ATIENT C e 17 for P PA ch. at medw /m v/ go fda. . w w 1088 or w A- at 1-800-FD TIONS, cont C A VERSE RE TED AD C t SUSPE epor o r %). (6) emia (5 al hyper %), and conjunctiv atitis (5 er e blurr er ted in patients w epor eactions r se r er Most common adv VERSE RE ---------------------------------------------- AD .2) AN. (5 G y with ZIR ap se of ther cour TUDIES AL S CLINIC agenesis, and Impairment of F t cinogenesis, Mu Car 1 13. Y OG OL XIC O AL T NONCLINIC harmacokinetics P 12.3 ction Mechanism of A 1 12. Y OG OLO C AL PHARMA CLINIC TION CRIP DES Geriatric Use 8.5 10 vised: June 20 e R TION. A -0000 or FD 323 omb at 1-800- ausch & L t B ac TIONS, cont ate ation (20%), punct e irrit ed vision (60%), ey e blurr TIONS --------------------------------------------- C A y tilit er agenesis, and Impairment of F 8. 8.3 8. USE IN SPE 8 AD 6 AN cont G ZIR 3 y 3 hour er v e ecommended dosing r The r 2 s). ulcer AN (ganciclo G ZIR 1 FULL PRES ediatric Use P 4 8. s sing Mother Nur 8.3 egnancy r P 1 8. TIONS ATIONS OPUL CIFIC P USE IN SPE TIONS C A VERSE RE AD ed topical ophthalmic gel. v eser vir in a sterile pr % of ganciclo 15 . ains 0 AN cont THS TRENG ORMS AND S GE F A S DO e) until the corneal ulcer heals, and then 1 dr ak w s while a y 3 hour op in the a†ected ey AN is 1 dr G egimen for ZIR ecommended dosing r TION AT TR GE AND ADMINIS A S DO s). % is indicated for the tr 15 . vir ophthalmic gel) 0 AN (ganciclo GE A TIONS AND US ATIONS AND US INDIC TION ORMAT CRIBING INF FULL PRES *Sections or subsections omitted fr 17 16 C The estimated maximum daily dose of ganciclo 12.3 eplication. r and dir antivir is tr deriv ZIR 12. 12 ed topical ophthalmic gel. s. op 3 times per day for 7 day e) until the corneal ulcer heals, and then 1 dr ximately o e 5 times per day (appr op in the a†ected ey atitis (dendritic er te herpetic k eatment of acu % is indicated for the tr escribing information ar om the full pr *Sections or subsections omitted fr TION ORMATION OUNSELING INF TIENT C ATIENT C PA GE AND HANDLING A OR T /S W SUPPLIED HO vir administer The estimated maximum daily dose of ganciclo Pharmacokinetics 12.3 eplication. esulting in DNA chain termination and pr and DNA, r al primer str ation into vir ect incorpor and dir al DNA in 2 w ynthesis of vir y inhibiting the s al agent b antivir al and cellular thymidine kinases (TK) to ganciclo y vir ansformed b is tr eplication b ylation, inhibits DNA r e that, upon phosphor ativ deriv ains the activ % cont 15 . vir ophthalmic gel) 0 AN (ganciclo G ZIR tion c nism of A Mecha 1 12. Y OGY OL C AL PHARMA CLINIC e not listed. escribing information ar GE AND HANDLING vir) and 5 vir of 900 mg (or 5 mg. 7 .3 , 5 times per day is 0 op ed as 1 dr vir administer ention of v e esulting in DNA chain termination and pr ase al DNA-polymer e inhibition of vir s: competitiv ay al DNA in 2 w orks as an vir triphosphate, which w al and cellular thymidine kinases (TK) to ganciclo vir ). Ganciclo V x viruses (HS y herpes simple eplication b , which is a guanosine vir, which is a guanosine edient, ganciclo e ingr ains the activ 1 8 1 8 atitis (5 er k Most common adv 6 ap of ther atients should not w P .2 5 AN is indicated for topical ophthalmic use only G ZIR 1 . 5 5 None. 4 ts ogenic Eec at ncy: T P TIONS ATIONS OPUL CIFIC P USE IN SPE %). emia (5 al hyper %), and conjunctiv atitis (5 e blurr er ted in patients w epor eactions r se r er Most common adv TIONS C A VERSE RE AD AN. G y with ZIR ap ymptoms of herpetic k e signs or s v act lenses if they ha ear cont atients should not w t Lenses ac nce of Cont oida v Av . AN is indicated for topical ophthalmic use only opical Ophthalmic Use Only Topical Ophthalmic Use Only UTIONS A C S AND PRE ARNING W TIONS ATIONS AINDIC ONTR C 50 to 500 and 250 to 2, mu human counterpar ascular origin. Although the pr v dose). Ex No car as noted in the pr w gland, and v (nonglandular mucosa) in males and females, and r mg/k and Ganciclo 13. 13 dose and IV doses, r mg/k ompar C ate ation (20%), punct e irrit ed vision (60%), ey e blurr se atitis or during the cour er ymptoms of herpetic k . ely. espectiv mL, r 000 mcg/ /mL, r 50 to 500 and 250 to 2, t mu ed a potential car vir should be consider ts, ganciclo human counterpar al glands, for tial and clitor epu ascular origin. Although the pr vir , ganciclo er, ganciclo coma of the liv tic sar cept for histocy dose). Ex ed ganciclo ed in mice administer v as obser cinogenic e†ect w No car derian glands in males, for tial and har epu as noted in the pr 20 mg/k t the dose of er in females. A agina) and liv gland, and v oductiv epr (nonglandular mucosa) in males and females, and r ease in the incidence of t as a significant incr e w day ther g/day ther mg/k day g/day 000x the human ocular dose of 6.25 mcg/k , 160 and al doses of 20 and 1, cinogenic in the mouse at or as car vir w Ganciclo airment of F nd Imp agenesis, a t cinogenesis, Mu Car 1 .1 Y OG OL XIC O AL T NONCLINIC xposur stemic e y , thus minimal s ely, thus minimal s espectiv dose and IV doses, r ed daily dose is appr vir), the ophthalmically administer g (IV ganciclo mg/k stemically administer y ed to maintenance doses of s ompar ) (2 g (IV een ations betw o at concentr tes in vitr eased vir incr cinogen in humans. Ganciclo ed a potential car e v derian glands of mice do not ha estomach and har al glands, for ally of epithelial or e gener er s w umor -induced t vir day (160x the human ocular g/day (160x the human ocular vir at 1 mg/k ed ganciclo er in females. estomach in males and females, and liv derian glands in males, for s umor eased incidence of t , a slightly incr day, a slightly incr g/day 20 mg/k al y gland, clitor terus, mammar aries, u v sues (o e tis oductiv estomach tial gland in males, for epu s of the pr umor ease in the incidence of t 000 1, t the dose of suming complete absorption). A , as y, as 000x ximately 3, o day (appr g/day (appr 000 mg/k al doses of 20 and 1, y tilt er airment of F xpected. e is e xposur al 1% of the or . % and 0 04 . ximately 0 o ed daily dose is appr vir) and 5 alganciclo al v vir of 900 mg (or ed ganciclo stemically administer sing mother nur oduce detect to pr It is not kno 8.3 egnancy only if the potential benefit justifies the potential risk to the fet pr e ar Ther Impairment of F as pathologic changes in the nonglandular r during lact day g/day (14, k In mice, e†ects obser palate, anophthalmia/ th r w o gr of 6.25 mcg/k administer administr egnancy Categor r P 1 8.1 s. sing mother tion should be e east milk. Cau able quantities in br oduce detect vir administr wn whether topical ophthalmic ganciclo It is not kno s sing Mother Nur egnancy only if the potential benefit justifies the potential risk to the fet egnant w udies in pr olled st ell-contr e no adequate and w e ar y). tilit er Impairment of F egion of the stomach (see Car as pathologic changes in the nonglandular r esicles in the month-old male o†spring, as w ation caused hypoplasia of the testes and seminal v during lact ed to female mice prior to mating, during gest 000x the human ocular dose) administer day (14, y and embr xicit al to fet e maternal/ /fet er ed w v In mice, e†ects obser gans (kidney and pancr ophthalmia, aplastic or micr anophthalmia/ /micr or mate , and/ /or maternal to y, and/ atogenicit , ter y, ter olethalit y dation, embr ar et th r suming complete absorption. E†ects obser , as ely, as espectiv day), r g/day), r of 6.25 mcg/k ximately 1 o day (appr g/day (appr 08 mg/k day and 1 g/day and 1 ed 60 mg/k administer er esorptions w al r et abbits. F atogenic in r ation and ter administr wn to be embr vir has been sho y C: Ganciclo egnancy Categor ts ogenic Eec at er ncy: T Ter egna r P 16 for acy with dendritic ulcer trials which enr 3% esolu r er k In one open-label, r 14 human ocular dose). dogs follo 6.25 mcg/k in female mice follo Ganciclo the Ames Salmonella as 80 In the mouse micr ed to AN is administer G cised when ZIR er x tion should be e stemic absorption y esult in sufficient s ation could r vir administr us. egnancy only if the potential benefit justifies the potential risk to the fet AN should be used during G omen. ZIR egnant w agenesis, and t cinogenesis, Mu egion of the stomach (see Car ell esicles in the month-old male o†spring, as w ation, and ed to female mice prior to mating, during gest enous doses of 90 mg/ v a aily intr . D y olethalit y y and embr gnathia. achy , and br ocephaly, and br dr eas), hy gans (kidney and pancr t atogenic changes included clef er . T Ter y. T xicit or maternal to al abbits included: fet ed in r v suming complete absorption. E†ects obser 000x the human ocular dose , 000x and 17 7, , 0 ximately 1 abbits and mice % of r esent in at least 85 e pr enous v a wing intr abbits and mice follo xic in r oto y wn to be embr GE AND HANDLING A OR T /S W SUPPLIED D/S HO 9%). . 20 %- 6 . % CI - 15 5 %, 9 ence 2.5 vir (di†er clo for acy as achie ay 7 w tion at D esolu s. Clinical r with dendritic ulcer as non-inferior to acy AN w G al patients, ZIR olled 213 tot trials which enr andomiz r ee thr In 18.3%). %- 6 . 9 - CI % 5 9 .8%, 5 ence (di†er 3% ed in 77% (5 v as achie ay 7 w s) at D tion (healed ulcer esolu ophthalmic vir clo acy to non-inferior as w AN G ZIR atitis, er olled, multicenter clinical trial which enr ed, contr andomiz In one open-label, r TUDIES AL S CLINIC human ocular dose). ation of doses r enous administr v a al or intr wing daily or dogs follo y in male mice and hypospermatogenesis in mice and tilit eased fer vir caused decr day). Ganciclo g/day). Ganciclo 6.25 mcg/k da g/day (appr enous doses of 90 mg/k v a wing intr in female mice follo eased fer , decr vior, decr eased mating beha vir caused decr Ganciclo 000 mcg/ , ations of 500 to 5 say at concentr the Ames Salmonella as 000x human ocular dose). Ganciclo g (8, t not 50 mg/k 000x human ocular dose) bu , 80 as clastogenic at doses of 150 and 500 mg/k vir w , ganciclo say, ganciclo onucleus as In the mouse micr GE AND HANDLING 9) 4 4/4 9% (3 sus 6 er AN v G ) for ZIR 7 5 1/ 2% (4 ed in 7 v vir ophthalmic ointment 3% in patients clo as non-inferior to acy clinical multicenter olled, contr ed, single-mask ed, andomiz vir clo ) for acy 7 6 / 2% (48 sus 7 er AN v G 71) for ZIR / 5 s. Clinical ulcer dendritic with patients in 3% ointment, ophthalmic olled 164 patients with herpetic olled, multicenter clinical trial which enr 600x the g (30x to 1, 0 mg/k .2 to 1 om 0 anging fr ation of doses r y in male mice and hypospermatogenesis in mice and 000x the human ocular dose of ximately 14, o day (appr y olethalit y eased incidence of embr , and an incr y, and an incr tilit eased fer mL. 000 mcg/ /mL. agenic in t as not mu vir w 000x human ocular dose). Ganciclo 000x to 4, ) (2 g (IV as clastogenic at doses of 150 and 500 mg/k PRESER carbopol, w Each gr N 13 H 9 C Ganciclo esented b epr r name is AN (ganciclo G ZIR 11 er v No o 8.5 y and efficacy in pediatric patients belo Safet 4 8. 5 mg. 7 0 . onium chloride 0 TIVE: benzalk AT V PRESER xide (to adjust the pH to 7 o dr ater for injection, sodium hy carbopol, w %). INA 15 . vir 1.5 mg (0 TIVE: ganciclo C ains: A am of gel cont Each gr . 4 O 5 N .23, and the empirical formula is 5 eight of 25 vir has a molecular w Ganciclo al formula: ur wing struct y the follo esented b xy]methyl]guanine xymethyl)etho o dr 1-(hy - xy o dr 9-[[2-hy name is ains a sterile, topical antivir % cont 15 . vir ophthalmic gel) 0 AN (ganciclo TION CRIP DES e been obser v s ha enes y or e†ectiv ences in safet all di†er er Geriatric Use ear w the age of 2 y y and efficacy in pediatric patients belo ediatric Use P N © B ausch & L B ZIR e R lenses when using ZIR aggr sur This pr 17 Stor or St 4 2 of ganciclo ZIR 4), mannitol. . H to 7 7. TIVES: C %). INA .23, and the empirical formula is vir is 32-0). Ganciclo 0- 1 4 2 S number 8 A (C xy]methyl]guanine al for ophthalmic use. The chemical ains a sterile, topical antivir ounger patients. een elderly and y ed betw v e been obser ablished. e not been est v s ha ear O H 2 N HN OH O OH N N ated omb Incorpor ausch & L © B 7 363 ampa, FL 3 ated, T Tampa, FL 3 omb Incorpor ausch & L ation licensed b orpor es Théa C atoir ademark of Labor AN is a tr G ZIR 10 vised: June 20 AN. G lenses when using ZIR sician. P ated, the patient should be advised to consult a phy v a aggr elops, or if r v aminate the gel. If pain de face, as this may cont sur atients should be advised not to allo aged. P oduct is sterile when pack This pr TION ORMATION OUNSELING INF TIENT C ATIENT C PA e. eez o not fr 77°F). D - 9°F °C (5 25 °C- e at 15 Stor age or 5). 3 5- 3 208-5 ube with a white poly coated aluminum t vir in a poly of ganciclo ed, clear v eser ams of a sterile, pr AN is supplied as 5 gr G ZIR 1 0 1 9 18 9 ated. omb Incorpor ausch & L y B ation licensed b act ear cont atients should be advised not to w sician. P s, itching, or inflammation becomes ednes elops, or if r opper tip to touch any w the dr atients should be advised not to allo e band (NDC otectiv ethylene tip and cap and pr ube with a white poly % 15 . aining O s, topical ophthalmic gel cont , colorles ar r, colorles

• Cover