# Presentation: 768537

## One Year Post Exclusivity Adverse Event Review:Ofloxacin Ophthalmic Pediatric Advisory Committee Meeting September 15, 2004

**Hari Cheryl Sachs, MD, FAAP****Medical Officer**
**Division of Pediatric Drug Development****Center for Drug Evaluation and Research **
**Food and Drug Administration**

## Background Drug Information 

**Moiety: **Ocuflox® (ofloxacin)
**Therapeutic Category: **ophthalmic anti-infective
**Sponsor:  **Allergan
**Adult and Pediatric Indications: **treatment of conjunctivitis and corneal ulcers for susceptible bacteria in patients > 1 year
**Dosage:  **1-2 drops at frequent intervals depending on condition
**Original Market Approval: **July 30, 1993
**Pediatric Exclusivity Granted: **March 12, 2003

## Drug Use Trends in Outpatient Settings: Ofloxacin

- Comprises 12 % of total 11.6 million prescriptions for medium and broad spectrum ophthalmics during exclusivity period (decreased from 20 % prior two years)1
- While total dispensed prescriptions have decreased from 2.2 million to 1.4 million during April 2003- March 20041, pediatric usage has remained steady.2
- Pediatric patients (ages 1-16) accounted for approximately one third of total U.S. prescriptions of Ocuflox® between April 2003 – March 2004  (460,752)*.*1,2*
**1**IMS Health, National Prescription Audit *Plus*, On-Line, Apr 2001 – Mar 2004, Data Extracted May 2004
**2**AdvancePCS Dimension Rx, On-Line, Apr 2002 – Mar 2004, Data Extracted May 2004
- *Calculation based on application of proportions of pediatric ofloxacin prescriptions in AdvancePCS  to IMS
-  Health, National Prescription Audit *Plus* to  estimate number of ofloxacin  prescriptions dispensed nationwide to
-  pediatric population

## Drug Use Trends in Outpatient Settings: Ofloxacin

- Prescribers:  Ophthalmologists (39 %) and Pediatricians (26 %)1
- Pediatric Diagnosis:  Conjunctivitis (77 % drug mentions)2
**1**IMS Health, National Prescription Audit *Plus*, On-Line , Apr 2001- Mar 2004,  Data Extracted May 2004
- 2IMS Health, National Disease and Therapeutic Index, CD-Rom, Apr 2001 - Mar 2004,***  ***Data Extracted May 2004
***	***

## http://www.fda.gov/cder/pediatric/Summaryreview.htm

## Pediatric Exclusivity Studies: Ofloxacin

- One week, multicenter, randomized, double blind, parallel group trial comparing ofloxacin 0.3 % to trimethoprim sulfate/polymyxin b in neonates.
- Cure rate= 60 % (vehicle 70 %)
- Safety comparable to prior studies
- Unable to determine from data submitted why clinical cure rate was low
- No label change resulted

- Pregnancy Category C
- Pediatric Use:  Arthropathy in immature  animals from oral (not topical) quinolones
- Warning:  Hypersensitivity/anaphylaxis
- Adverse Reactions:
- Transient ocular burning or discomfort
- Other local symptoms (stinging, redness itching, chemical conjunctivitis/keratitis, edema, tearing, dryness and eye pain)
- Visual changes- photophobia, blurred vision
- Rare dizziness and nausea

**Relevant Safety Labeling**

## Adverse Event Reports Since Market Approval: Ofloxacin July 1993 – April 2004

- Total number of reports, all ages:
- 66 reports (50 US)
- 18 serious (7 US)
- 4 deaths (0 US)
- Pediatric reports:
- 3 reports (2 US)
- 1 serious (0 US)
- 0 deaths
**	****	**
**Raw counts (US reports are in parenthesis)- includes duplicates**

## Adverse Events during the One-Year Post-Exclusivity Period: Ofloxacin March 2003 – April 2004

- Adult (2)
- Deafness neurosensory (1)
- Hearing loss (1)
- Pediatric (1)
- 	Corneal deposits (1)
- All events are unlabeled**	****	****	****	**

## Pediatric Adverse Event (n=1)

- 6 year old male
- Treatment for vernal conjunctivitis with topical ofloxacin ointment and drops TID for 3 weeks, along with prednisolone
- Developed dense, white, sharply demarcated corneal deposits treated with corneal scraping

## Summary

- With one event, no meaningful conclusion can be drawn.
- This completes the one-year post-exclusivity adverse event monitoring as mandated by BPCA.
- FDA will continue its routine monitoring of adverse events for this drug.