CIPRODEX (ciprofloxacin and dexamethasone), otic suspension Initial U.S. Approval: 2003

Transcription

1 HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights d nt include all the infrmatin needed t use CIPRODEX safely and effectively. See full prescribing infrmatin fr CIPRODEX CIPRODEX (ciprflxacin and dexamethasne), tic suspensin Initial U.S. Apprval: INDICATIONS AND USAGE CIPRODEX is a cmbinatin f ciprflxacin, a flurquinlne antibacterial and dexamethasne, a crticsterid, indicated fr the treatment f infectins caused by susceptible islates f the designated micrrganisms in the specific cnditins listed belw: Acute Otitis Media in pediatric patients (age 6 mnths and lder) with tympanstmy tubes due t Staphylcccus aureus, Streptcccus pneumniae, Haemphilus influenzae, Mraxella catarrhalis, and Pseudmnas aeruginsa. (1) Acute Otitis Externa in pediatric (age 6 mnths and lder), adult and elderly patients due t Staphylcccus aureus and Pseudmnas aeruginsa. (1) DOSAGE AND ADMINISTRATION CIPRODEX is fr tpical use nly, and nt fr phthalmic use, r fr injectin. (2.1) Shake well immediately befre use. (2.1) Instill fur drps int the affected ear twice daily, fr seven days. (2) CONTRAINDICATIONS CIPRODEX is cntraindicated in patients with a histry f hypersensitivity t ciprflxacin, t ther quinlnes, r t any f the cmpnents in this medicatin. (4) Use f this prduct is cntraindicated in viral infectins f the external canal including herpes simplex infectins and fungal tic infectins. (4) WARNINGS AND PRECAUTIONS Hypersensitivity and anaphylaxis have been reprted with systemic use f quinlnes. Discntinue use if this ccurs with use f CIPRODEX. (5.1) Prlnged use may result in vergrwth f nn-susceptible bacteria and fungi. (5.2) ADVERSE REACTIONS Mst cmmn adverse reactins were ear discmfrt (3%), ear pain (2.3%), and ear pruritus (1.5%). (6) T reprt SUSPECTED ADVERSE REACTIONS, cntact Alcn at r FDA at FDA-1088 r See 17 fr PATIENT COUNSELING INFORMATION and FDAapprved patient labeling. Revised: 12/ DOSAGE FORMS AND STRENGTHS Otic Suspensin: Each ml f CIPRODEX cntains ciprflxacin hydrchlride 0.3 % (equivalent t 3 mg ciprflxacin base) and dexamethasne 0.1 % (equivalent t 1 mg dexamethasne). (3) FULL PRESCRIBING INFORMATION: CONTENTS* 1 INDICATIONS AND USAGE 2 DOSAGE AND ADMINISTRATION 2.1 Imprtant Administratin Instructins 2.2 Dsage 3 DOSAGE FORMS AND STRENGTHS 4 CONTRAINDICATIONS 5 WARNINGS AND PRECAUTIONS 5.1 Hypersensitivity Reactins 5.2 Ptential fr Micrbial Overgrwth with Prlnged Use 5.3 Cntinued r Recurrent Otrrhea 6 ADVERSE REACTIONS 6.1 Clinical Trials Experience 6.2 Pstmarketing Experience 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy 8.3 Nursing Mthers 8.4 Pediatric Use 10 OVERDOSAGE 11 DESCRIPTION 12 CLINICAL PHARMACOLOGY 12.1 Mechanism f Actin 12.3 Pharmackinetics 12.4 Micrbilgy 13 NONCLINICAL TOXICOLOGY 13.1 Carcingenesis, Mutagenesis, Impairment f Fertility 13.2 Animal Txiclgy and/r Pharmaclgy 14 CLINICAL STUDIES 16 HOW SUPPLIED/STORAGE AND HANDLING 17 PATIENT COUNSELING INFORMATION * Sectins r subsectins mitted frm the full prescribing infrmatin are nt listed.

2 FULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE CIPRODEX is indicated fr the treatment f infectins caused by susceptible islates f the designated micrrganisms in the specific cnditins listed belw: Acute Otitis Media in pediatric patients (age 6 mnths and lder) with tympanstmy tubes due t Staphylcccus aureus, Streptcccus pneumniae, Haemphilus influenzae, Mraxella catarrhalis, and Pseudmnas aeruginsa. Acute Otitis Externa in pediatric (age 6 mnths and lder), adult and elderly patients due t Staphylcccus aureus and Pseudmnas aeruginsa. 2 DOSAGE AND ADMINISTRATION 2.1 Imprtant Administratin Instructins CIPRODEX is fr tic use nly, and nt fr phthalmic use, r fr injectin. Shake well immediately befre use. 2.2 Dsage Fr the treatment f Acute Otitis Media in pediatric patients (age 6 mnths and lder) with tympanstmy tubes The recmmended dsage regimen thrugh tympanstmy tubes is as fllws: Fur drps (equivalent t 0.14 ml f CIPRODEX, (cnsisting f 0.42 mg f ciprflxacin and 0.14 mg f dexamethasne)) instilled int the affected ear twice daily fr seven days. The suspensin shuld be warmed by hlding the bttle in the hand fr ne r tw minutes t avid dizziness, which may result frm the instillatin f a cld suspensin. The patient shuld lie with the affected ear upward, and then the drps shuld be instilled. The tragus shuld then be pumped 5 times by pushing inward t facilitate penetratin f the drps int the middle ear. This psitin shuld be maintained fr 60 secnds. Repeat, if necessary, fr the ppsite ear. Discard unused prtin after therapy is cmpleted. Fr the treatment f Acute Otitis Externa (age 6 mnths and lder) The recmmended dsage regimen is as fllws: Fur drps (equivalent t 0.14 ml f CIPRODEX, (cnsisting f 0.42 mg ciprflxacin and 0.14 mg dexamethasne)) instilled int the affected ear twice daily fr seven days. The suspensin shuld be warmed by hlding the bttle in the hand fr ne r tw minutes t avid dizziness, which may result frm the instillatin f a cld suspensin. The patient shuld lie with the affected ear upward, and then the drps shuld be instilled. This psitin shuld be maintained fr 60 secnds t facilitate penetratin f the drps int the ear canal. Repeat, if necessary, fr the ppsite ear. Discard unused prtin after therapy is cmpleted. 3 DOSAGE FORMS AND STRENGTHS Otic Suspensin: Each ml f CIPRODEX cntains ciprflxacin hydrchlride 0.3 % (equivalent t 3 mg ciprflxacin base) and dexamethasne 0.1 % equivalent t 1 mg dexamethasne. 4 CONTRAINDICATIONS CIPRODEX is cntraindicated in patients with a histry f hypersensitivity t ciprflxacin, t ther quinlnes, r t any f the cmpnents in this medicatin. Use f this prduct is cntraindicated in viral infectins f the external canal including herpes simplex infectins and fungal tic infectins. 5 WARNINGS AND PRECAUTIONS 5.1 Hypersensitivity Reactins CIPRODEX shuld be discntinued at the first appearance f a skin rash r any ther sign f hypersensitivity. Serius and ccasinally fatal hypersensitivity (anaphylactic) reactins, sme fllwing the first dse, have been reprted in patients receiving systemic quinlnes. Sme reactins were accmpanied by cardivascular cllapse, lss f cnsciusness, angiedema (including laryngeal, pharyngeal r facial edema), airway bstructin, dyspnea, urticaria and itching. 5.2 Ptential fr Micrbial Overgrwth with Prlnged Use Prlnged use f CIPRODEX may result in vergrwth f nn-susceptible, bacteria and fungi. If the infectin is nt imprved after ne week f treatment, cultures shuld be btained t guide further treatment. If such infectins ccur, discntinue use and institute alternative therapy. 5.3 Cntinued r Recurrent Otrrhea If trrhea persists after a full curse f therapy, r if tw r mre episdes f trrhea ccur within six mnths, further evaluatin is recmmended t exclude an underlying cnditin such as chlesteatma, freign bdy, r a tumr. 6 ADVERSE REACTIONS The fllwing serius adverse reactins are described elsewhere in the labeling:

3 Hypersensitivity Reactins [see Warnings and Precautins (5.1)] Ptential fr Micrbial Overgrwth with Prlnged Use [see Warnings and Precautins (5.2)] 6.1 Clinical Trials Experience Because clinical trials are cnducted under widely varying cnditins, adverse reactin rates bserved in the clinical trials f a drug cannt be directly cmpared t the rates in the clinical trials f anther drug and may nt reflect the rates bserved in practice. In Phases II and III clinical trials, a ttal f 937 patients were treated with CIPRODEX. This included 400 patients with acu te titis media with tympanstmy tubes and 537 patients with acute titis externa. The reprted adverse reactins are listed belw: Acute Otitis Media in Pediatric Patients with Tympanstmy Tubes The fllwing adverse reactins ccurred in 0.5% r mre f the patients with nn-intact tympanic membranes. Adverse Reactins Ear discmfrt 3.0% Ear pain 2.3% Ear precipitate (residue) 0.5% Irritability 0.5% Taste Perversin 0.5% Incidence (N=400) The fllwing adverse reactins were each reprted in a single patient: tympanstmy tube blckage; ear pruritus; tinnitus; ral mniliasis; crying; dizziness; and erythema. Acute Otitis Externa The fllwing adverse reactins ccurred in 0.4% r mre f the patients with intact tympanic membranes. Adverse Reactins Ear pruritus 1.5% Ear debris 0.6% Superimpsed ear infectin 0.6% Ear cngestin 0.4% Ear pain 0.4% Erythema 0.4% Incidence (N=537) The fllwing adverse reactins were each reprted in a single patient: ear discmfrt; decreased hearing; and ear disrder (tingling). 6.2 Pstmarketing Experience The fllwing adverse reactins have been identified during pst apprval use f CIPRODEX. Because these reactins are reprted vluntarily frm a ppulatin f unknwn size it is nt always pssible t reliably estimate their frequency r establish a causal relatinship t drug expsure. These reactins include: auricular swelling, headache, hypersensitivity, trrhea, skin exfliatin, rash erythematus, and vmiting. 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Teratgenic Effects. Pregnancy Categry C: N adequate and well cntrlled studies with CIPRODEX have been perfrmed in pregnant wmen. Cautin shuld be exercised when CIPRODEX is used by a pregnant wman. Animal reprductin studies have nt been cnducted with CIPRODEX. Reprductin studies with ciprflxacin have been perfrmed in rats and mice using ral dses f up t 100 mg/kg and IV dses up t 30 mg/kg and have revealed n evidence f harm t the fetus. In rabbits, ciprflxacin (30 and 100 mg/kg rally) prduced gastrintestinal disturbances resulting in maternal weight lss and an increased incidence f abrtin, but n teratgenicity was bserved at either dse. After intravenus administratin f dses up t 20 mg/kg, n maternal txicity was prduced in the rabbit, and n embrytxicity r teratgenicity was bserved. Crticsterids are generally teratgenic in labratry animals when administered systemically at relatively lw dsage levels. The mre ptent crticsterids have been shwn t be teratgenic after dermal applicatin in labratry animals. 8.3 Nursing Mthers Ciprflxacin and crticsterids, as a class, appear in milk fllwing ral administratin. Dexamethasne in breast milk culd suppress grwth, interfere with endgenus crticsterid prductin, r cause ther untward effects. It is nt knwn whether tpical tic administratin f ciprflxacin r dexamethasne culd result in sufficient systemic absrptin t prduce detectable quantities in human milk. Because f the ptential fr unwanted effects in nursing infants, a decisin shuld be made whether t discntinue nursing r t discntinue the drug, taking int accunt the imprtance f the drug t the mther. 8.4 Pediatric Use The safety and efficacy f CIPRODEX have been established in pediatric patients 6 mnths and lder (937 patients) in adequate and well-cntrlled clinical trials.

4 N clinically relevant changes in hearing functin were bserved in 69 pediatric patients (age 4 t 12 years) treated with CIPRODEX and tested fr audimetric parameters. 10 OVERDOSAGE Due t the characteristics f this preparatin, n txic effects are t be expected with an tic verdse f this prduct. 11 DESCRIPTION CIPRODEX (ciprflxacin 0.3% and dexamethasne 0.1%) Sterile Otic Suspensin cntains the quinlne antimicrbial, ciprflxacin hydrchlride, cmbined with the crticsterid, dexamethasne, in a sterile, preserved suspensin fr tic use. Each ml f CIPRODEX cntains ciprflxacin hydrchlride (equivalent t 3 mg ciprflxacin base), 1 mg dexamethasne, and 0.1 mg benzalknium chlride as a preservative. The inactive ingredients are bric acid, sdium chlride, hydrxyethyl cellulse, tylxapl, acetic acid, sdium acetate, edetate disdium, and purified water. Sdium hydrxide r hydrchlric acid may be added fr adjustment f ph. Ciprflxacin, a quinlne antimicrbial is available as the mnhydrchlride mnhydrate salt f 1-cyclprpyl-6-flur-1,4-dihydr-4-x-7-(1- piperazinyl)-3-quinline carbxylic acid. The empirical frmula is C 17H 18FN 3O 3 HCl H 2O. The mlecular weight is and the structural frmula is: Figure 1: Structure f Ciprflxacin Dexamethasne, 9-flur-11(beta),17,21-trihydrxy-16(alpha)-methylpregna-1,4-diene-3,20-dine, is a crticsterid. The empirical frmula is C 22H 29FO 5. The mlecular weight is and the structural frmula is: Figure 2: Structure f Dexamethasne 12 CLINICAL PHARMACOLOGY 12.1 Mechanism f Actin Ciprflxacin is a flurquinlne antibacterial [see Micrbilgy (12.4)]. Dexamethasne, a crticsterid, has been shwn t suppress inflammatin by inhibiting multiple inflammatry cytkines resulting in decreased edema, fibrin depsitin, capillary leakage and migratin f inflammatry cells Pharmackinetics Fllwing a single bilateral 4-drp (ttal dse = 0.28 ml, 0.84 mg ciprflxacin, 0.28 mg dexamethasne) tpical tic dse f CIPRODEX t pediatric patients after tympanstmy tube insertin, measurable plasma cncentratins f ciprflxacin and dexamethasne were bserved at 6 hurs fllwing administratin in 2 f 9 patients and 5 f 9 patients, respectively. Mean ± SD peak plasma cncentratins f ciprflxacin were 1.39 ± ng/ml (n=9). Peak plasma cncentratins ranged frm ng/ml t 3.45 ng/ml and were n average apprximately 0.1% f peak plasma cncentratins achieved with an ral dse f 250-mg. Peak plasma cncentratins f ciprflxacin were bserved within 15 minutes t 2 hurs pst dse applicatin. Mean ± SD peak plasma cncentratins f dexamethasne were 1.14 ± 1.54 ng/ml (n=9). Peak plasma cncentratins ranged frm ng/ml t 5.10 ng/ml and were n average apprximately 14% f peak cncentratins reprted in the literature fllwing an ral 0.5-mg tablet dse. Peak plasma cncentratins f dexamethasne were bserved within 15 minutes t 2 hurs pst dse applicatin. Dexamethasne has been added t aid in the reslutin f the inflammatry respnse accmpanying bacterial infectin (such as trrhea in pediatric patients with acute titis media with tympanstmy tubes) Micrbilgy Mechanism f Actin The bactericidal actin f ciprflxacin results frm interference with the enzyme, DNA gyrase, which is needed fr the synthesis f bacterial DNA. Resistance Crss-resistance has been bserved between ciprflxacin and ther flurquinlnes. There is generally n crss-resistance between ciprflxacin and ther classes f antibacterial agents such as beta-lactams r aminglycsides. Antimicrbial Activity

5 Ciprflxacin has been shwn t be active against mst islates f the fllwing micrrganisms, bth in vitr and clinically in tic infectins [see Indicatins and Usage (1)]. Aerbic Bacteria Gram-psitive Bacteria Staphylcccus aureus Streptcccus pneumniae Gram-negative Bacteria Haemphilus influenzae Mraxella catarrhalis Pseudmnas aeruginsa 13 NONCLINICAL TOXICOLOGY 13.1 Carcingenesis, Mutagenesis, Impairment f Fertility Lng-term carcingenicity studies in mice and rats have been cmpleted fr ciprflxacin. After daily ral dses f 750 mg/kg (mice) and 250 mg/kg (rats) were administered fr up t 2 years, there was n evidence that ciprflxacin had any carcingenic r tumrigenic effects in these species. N lng term studies f CIPRODEX have been perfrmed t evaluate carcingenic ptential. Eight in vitr mutagenicity tests have been cnducted with ciprflxacin, and the test results are listed belw: Salmnella/Micrsme Test (Negative) E. cli DNA Repair Assay (Negative) Muse Lymphma Cell Frward Mutatin Assay (Psitive) Chinese Hamster V79 Cell HGPRT Test (Negative) Syrian Hamster Embry Cell Transfrmatin Assay (Negative) Saccharmyces cerevisiae Pint Mutatin Assay (Negative) Saccharmyces cerevisiae Mittic Crssver and Gene Cnversin Assay (Negative) Rat Hepatcyte DNA Repair Assay (Psitive) Thus, 2 f the 8 tests were psitive, but results f the fllwing 3 in viv test systems gave negative results: Rat Hepatcyte DNA Repair Assay Micrnucleus Test (Mice) Dminant Lethal Test (Mice) Fertility studies perfrmed in rats at ral dses f ciprflxacin up t 100 mg/kg/day revealed n evidence f impairment. This wuld be ver 100 times the maximum recmmended clinical dse f ttpical ciprflxacin based upn bdy surface area, assuming ttal absrptin f ciprflxacin frm the ear f a patient treated with CIPRODEX twice per day accrding t label directins. Lng term studies have nt been perfrmed t evaluate the carcingenic ptential f tpical tic dexamethasne. Dexamethasne has been tested fr in vitr and in viv gentxic ptential and shwn t be psitive in the fllwing assays: chrmsmal aberratins, sister-chrmatid exchange in human lymphcytes, and micrnuclei and sister-chrmatid exchanges in muse bne marrw. Hwever, the Ames/Salmnella assay, bth with and withut S9 mix, did nt shw any increase in His+ revertants. The effect f dexamethasne n fertility has nt been investigated fllwing tpical tic applicatin. Hwever, the lwest txic dse f dexamethasne identified fllwing tpical dermal applicatin was mg/kg in a 26-week study in male rats and resulted in changes t the testes, epididymis, sperm duct, prstate, seminal vessicle, Cwper's gland and accessry glands. The relevance f this study fr shrt-term tpical tic use is unknwn Animal Txiclgy and/r Pharmaclgy Guinea pigs dsed in the middle ear with CIPRODEX fr ne mnth exhibited n drug-related structural r functinal changes f the cchlear hair cells and n lesins in the ssicles. 14 CLINICAL STUDIES In a randmized, multicenter, cntrlled clinical trial, CIPRODEX dsed 2 times per day fr 7 days demnstrated clinical cures in the per prtcl analysis in 86% f Acute Otitis Media with Tympanstmy Tubes (AOMT) patients cmpared t 79% fr flxacin slutin, 0.3%, dsed 2 times per day fr 10 days. Amng culture psitive patients, clinical cures were 90% fr CIPRODEX cmpared t 79% fr flxacin slutin, 0.3%. Micrbilgical eradicatin rates fr these patients in the same clinical trial were 91% fr CIPRODEX cmpared t 82% fr flxacin slutin, 0.3%. In 2 randmized multicenter, cntrlled clinical trials, CIPRODEX dsed 2 times per day fr 7 days demnstrated clinical cures in 87% and 94% f per prtcl evaluable Acute Otitis Externa (AOE) patients, respectively, cmpared t 84% and 89%, respectively, fr tic suspensin cntaining nemycin 0.35%, plymyxin B 10,000 IU/mL, and hydrcrtisne 1.0% (ne/ply/hc). Amng culture psitive patients clinical cures were 86% and 92% fr CIPRODEX cmpared t 84% and 89%, respectively, fr ne/ply/hc. Micrbilgical eradicatin rates fr these patients in the same clinical trials were 86% and 92% fr CIPRODEX cmpared t 85% and 85%, respectively, fr ne/ply/hc. 16 HOW SUPPLIED/STORAGE AND HANDLING Hw Supplied: CIPRODEX (ciprflxacin 0.3% and dexamethasne 0.1%) Sterile Otic Suspensin is a white-t ff-white suspensin supplied as fllws: 7.5 ml fill in a DROP-TAINER system. The DROP-TAINER system cnsists f a natural plyethylene bttle and natural plug, with a white plyprpylene clsure. Tamper evidence is prvided with a shrink band arund the clsure and neck area f the package.

6 NDC , 7.5 ml fill Strage: Stre at C (68-77 F); excursins permitted t C (59-86 F). [See USP Cntrlled Rm Temperature]. Avid freezing. Prtect frm light. 17 PATIENT COUNSELING INFORMATION Advise the patient t read the FDA-apprved patient labeling (Patient Infrmatin and Instructins fr Use) Fr Otic Use Only Advise patients that CIPRODEX is fr tic use nly. This prduct is nt apprved fr use in the eye. Administratin Instructins Patients shuld be instructed t warm the bttle in their hand fr ne t tw minutes prir t use and shake well immediately befre using. Allergic Reactins Advise patients t discntinue use immediately and cntact their physician, if rash r allergic reactin ccurs. Avid Cntaminatin f the Prduct Advise patients t avid cntaminating the tip with material frm the ear, fingers, r ther surces. Duratin f Use Advise patients that it is very imprtant t use the ear drps fr as lng as their dctr has instructed, even if the symptms imprve. Prtect frm Light Advise patients t prtect the prduct frm light. Unused Prduct Advise patients t discard unused prtin after therapy is cmpleted. What is CIPRODEX? PATIENT INFORMATION CIPRODEX (CI-PRO-DEX) (ciprflxacin and dexamethasne) tic suspensin CIPRODEX is a prescriptin medicine used in the ear nly (tic use) that cntains 2 medicines, a quinlne antibitic medicine called ciprflxacin and a crticsterid medicine called dexamethasne. CIPRODEX is used in adults and children 6 mnths f age r lder t treat certain types f infectins caused by certain germs called bacteria. These bacterial infectins include: middle ear infectin (knwn as acute titis media) in peple wh have a tube in their eardrum knwn as a tympanstmy t prevent having t much fluid in the middle ear uter ear canal infectin (knwn as acute titis externa) It is nt knwn if CIPRODEX is safe and effective in children under 6 mnths f age. Wh shuld nt use CIPRODEX? D nt use CIPRODEX if yu: are allergic t ciprflxin, quinlnes, r any f the ingredients in CIPRODEX. See the end f this Patient Infrmatin leaflet fr a cmplete list f ingredients in CIPRODEX. have an uter ear canal infectin caused by certain viruses including the herpes simplex virus have an ear infectin caused by a fungus What shuld I tell my dctr befre using CIPRODEX? Befre using CIPRODEX, tell yur dctr abut all f yur medical cnditins, including if yu: are pregnant r plan t becme pregnant. It is nt knwn if CIPRODEX will harm yur unbrn baby. are breastfeeding r plan t breastfeed. CIPRODEX can pass int yur breast milk and may harm yur baby. Yu and yur dctr shuld decide if yu will use CIPRODEX r breastfeed. Yu shuld nt d bth. Tell yur dctr abut all the medicines yu take, including prescriptin and ver-the-cunter medicines, vitamins, and herbal supplements.

7 Hw shuld I use CIPRODEX? Read the detailed Instructins fr Use that cme with CIPRODEX. Use CIPRODEX exactly as yur dctr tells yu t. CIPRODEX is fr use in the ear nly (tic use). D nt inject CIPRODEX r use CIPRODEX in the eye. Apply 4 drps f CIPRODEX int the affected ear 2 times a day fr 7 days. D nt stp using CIPRODEX unless yur dctr tells yu t, even if yur symptms imprve. If yur symptms d nt imprve after 7 days f treatment with CIPRODEX, call yur dctr. Call yur dctr right away if: yu have fluid that cntinues t drain frm yur ear (trrhea) after yu have finished yur treatment with CIPRODEX yu have fluid that drains frm yur ear 2 r mre times within 6 mnths after yu stp treatment with CIPRODEX What are the pssible side effects f CIPRODEX? CIPRODEX may cause serius side effects, including: allergic reactins. Stp using CIPRODEX and call yur dctr if yu have any f the fllwing signs r symptms f an allergic reactin: hives (urticaria) swelling f yur face, lips, muth, r tngue rash itching The mst cmmn side effects f CIPRODEX include: ear discmfrt ear pain truble breathing dizziness, fast heartbeat, r punding in yur chest ear itching (pruritus) These are nt all the pssible side effects f CIPRODEX. Call yur dctr fr medical advice abut side effects. Yu may reprt side effects t FDA at FDA Hw shuld I stre CIPRODEX? Stre CIPRODEX at rm temperature between 68 F t 77 F (20 C t 25 C). D nt freeze CIPRODEX. Keep CIPRODEX ut f light. Keep CIPRODEX and all medicines ut f the reach f children. General infrmatin abut the safe and effective use f CIPRODEX. Medicines are smetimes prescribed fr purpses ther than thse listed in a Patient Infrmatin leaflet. D nt use CIPRODEX fr a cnditin fr which it was nt prescribed. D nt give CIPRODEX t ther peple, even if they have the same symptms that yu have. It may harm them. Yu can ask yur pharmacist r dctr fr infrmatin abut CIPRODEX that is written fr health prfessinals. What are the ingredients in CIPRODEX? Active ingredients: ciprflxacin hydrchlride, dexamethasne, and benzalknium chlride as a preservative Inactive ingredients: bric acid, sdium chlride, hydrxyethyl cellulse, tylxapl, acetic acid, sdium acetate, edetate disdium, and purified water. Sdium hydrxide r hydrchlric acid may be added fr adjustment f ph Distributed by: Alcn Labratries, Inc. Frt Wrth, TX USA CIPRODEX is a registered trademark f Bayer Intellectual Prperty GmbH, licensed t Alcn by Bayer Intellectual Prperty GmbH 2003, 2004, 2008, 2009, 2012, 2015 Nvartis U.S. Pat.:

8 Fr mre infrmatin, call This Patient Infrmatin has been apprved by the U.S. Fd and Drug Administratin Revised: December 2015 Instructins fr Use CIPRODEX (CI-PRO-DEX) (ciprflxacin and dexamethasne) tic suspensin Read this Instructins fr Use that cmes with CIPRODEX befre yu start using it and each time yu get a refill. There may be new infrmatin. This infrmatin des nt take the place f talking with yur dctr abut yur medical cnditin r treatment. Imprtant infrmatin abut CIPRODEX: Use CIPRODEX exactly as yur dctr tells yu t use it. CIPRODEX is fr use in the ear nly (tic use). D nt inject CIPRODEX r use CIPRODEX in the eye. Shake CIPRODEX well befre each use. D nt tuch yur ear, fingers r ther surfaces with the tip f the CIPRODEX bttle. Yu may get bacteria n the tip f the bttle that can cause yu t get anther infectin. Hw shuld I use CIPRODEX? Step 1. Wash yur hands with sap and water. Step 2. Warm the bttle f CIPRODEX by rlling the bttle between yur hands fr 1 t 2 minutes (See Figure A). Shake the bttle f CIPRODEX well. Figure A Step 3. Remve the CIPRODEX cap. Put the cap in a clean and dry area. D nt let the tip f the bttle tuch yur ear, fingers r ther surfaces. Step 4. Lie dwn n yur side s that the affected ear faces upward (See Figure B).

9 Figure B Step 5. Hld the bttle f CIPRODEX between yur thumb and index finger (See Figure C). Place the tip f the bttle clse t yur ear. Be careful nt t tuch yur fingers r ear with the tip f the bttle. Figure C Step 6. Gently squeeze the bttle and let 4 drps f CIPRODEX fall int the affected ear. If a drp misses yur ear, fllw the instructins in Step 5 again. Step 7. Stay n yur side with the affected ear facing upward (See Figure B) It is imprtant that yu fllw the instructins belw fr yur specific ear infectin, t allw CIPRODEX t enter the affected part f yur ear. Step 8. If yu use CIPRODEX t treat a middle ear infectin and yu have a tube in yur eardrum knwn as a tympanstmy: Gently press the part f the ear knwn as the tragus (See Figure D) 5 times using a pumping mtin (See Figure D). This will allw the drps f CIPRODEX t enter yur middle ear. Remain n yur side with the affected ear facing upward (See Figure B) fr 1 minute. Figure D If yu use CIPRODEX t treat an uter ear canal infectin: Gently pull the uter ear lbe upward and backward (See Figure E). This will allw the drps f CIPRODEX t enter yur ear canal. Remain n yur side with the affected ear facing upward (See Figure B) fr 1 minute.

10 Figure E Step 9. If yur dctr has tld yu t use CIPRODEX in bth ears, repeat steps 5-8 fr yur ther ear. Step 10. Put the cap back n the bttle and clse it tightly. Step 11. After yu have used all f yur CIPRODEX dses, there may be sme CIPRODEX left in the bttle. Thrw the bttle away. Hw shuld I stre CIPRODEX? Stre CIPRODEX at rm temperature between 68F t 77F (20C t 25C). D nt freeze CIPRODEX. Keep CIPRODEX ut f light. Keep CIPRODEX and all medicines ut f the reach f children. If yu wuld like mre infrmatin, talk with yur dctr. Yu can ask yur pharmacist r dctr fr mre infrmatin abut CIPRODEX that is written fr health prfessinals. This Instructins fr Use has been apprved by the U.S. Fd and Drug Administratin. Distributed by: Alcn Labratries, Inc. Frt Wrth, TX USA U.S. Pat.: CIPRODEX is a registered trademark f Bayer Intellectual Prperty GmbH, licensed t Alcn by Bayer Intellectual Prperty GmbH. 2003, 2004, 2008, 2009, 2015 Nvartis Revised: December 2015