Released by FDA: 2/20/03.  Posted by FDA:  3/3/03

Ms. Nancy Yee
Regulatory Affairs Specialist 11 Santen, Inc.
555 Gateway Drive Napa, CA 94558

RE:    NDA 21-199
         Quixin (levofloxacin ophthalmic solution), 0.5%
         MACMIS # 11193

Dear Ms. Yee:

This letter objects to Santen, Inc.'s (Santen) dissemination of false or misleading promotional materials for Quixin (levofloxacin ophthalmic solution), 0.5%.  As part of its routine monitoring and surveillance program, the Division of Drug Marketing, Advertising, and Communications (DDMAC) has reviewed a promotional flashcard for Quixin (levofloxacin ophthalmic solution), 0.5% identified as QXN-207-00 and entitled, "Antibiotic Susceptibility Pattern of Coagulase-Negative Staphylococci in Patients Undergoing Intraocular Surgery."   We have concluded that it is false or misleading in violation of the Federal Food, Drug, and Cosmetic Act (Act) and applicable regulations. Our specific objections follow:

Background

Quixin is a sterile ophthalmic solution of levofloxacin, which is a fluoroyuinolone antibacterial agent, that is indicated for the treatment of bacterial conjunctivitis, an external or extraocular bacterial infection, caused by susceptible strains of selected organisms.¹
 

Unapproved New Use

Promotional materials are false or misleading if they contain representations or suggestions that a drug is useful in a broader range of conditions than has been demonstrated by substantial evidence or substantial clinical experience.

Your promotional flashcard features the prominent header on both sides of the card, "Antibiotic Susceptibility Pattern of Coagulase-Negative Staphylococci in Patients Undergoing Intraocular Surgery" (emphasis added)  followed by a bar graph entitled, "SUSCEPTIBILITIES & RESISTANCES OF FLUOROQUINOLONES TESTED." The graph depicts Quixin (levofloxacin) with the highest rate of in vitro susceptibility (91%) and the lowest rate of resistance (5%) against coagulase-negative staphylococci compared to norfloxacin, ofloxacin, and ciprofloxacin.   In addition, the back of the flashcard states that, "This study suggests that fluoroquinolones and aminoglycosides are effective prophylactic antibiotics against most coagulase-negative staphylococci."   The header and the statement on the back, touting Quixin's use in intraocular surgery patients, in conjunction with the graph depicting in vitro susceptibility and resistance, suggests that Quixin (levofloxacin) is safe and effective to prevent infection caused by coagulase-negative staphylococci in patients undergoing intraocular surgery.   This suggestion is false or misleading.   Therefore, the flashcard is violative because it suggests that the drug is safe and effective for an unapproved new use, i.e., for prophylactic, preoperative use in intraocular surgery to prevent infections inside the eye.
This claim is particularly troublesome because Quixin has been proven only to be safe and effective in adequate and well-controlled trials for the treatment of bacterial conjunctivitis, an external infection of the delicate membrane that lines the eyelids and covers the exposed surface of the sclera (white) of the eye.   FDA is not aware of any substantial evidence or substantial clinical experience that would support Santen's claim that Quixin is safe and effective to prevent internal infections of the eye due to invasive ocular surgery.   If, at some future time, you develop such evidence that would support this additional indication, please submit that data in a supplemental NDA to FDA for review.

You should immediately cease dissemination of the promotional flashcard and other similar promotional materials for Quixin that make the same or similar claims or representations.   Please respond in writing to us regarding this issue by March 6, 2003. Your response should include Santen's intent to comply with the above request, the date that you ceased disseminating this promotional flashcard and any other violative promotional materials with the same or similar presentations, and a list of the discontinued materials.

If you have any questions, please contact me by facsimile at (301) 594-6771, or by written communication at the Division of Drug Marketing, Advertising, and Communications, HFD-42; Room 813-45; 5600 Fishers Lane; Rockville, MD 20857.
We remind you that only written communications are considered official. In all future correspondence regarding this matter, please refer to MACMIS 4 11193 and NDA 21-199.

Sincerely,

Rebecca Williams, Pharm.D.
Regulatory Review Officer
Division of Drug Marketing,
       Advertising, and Communications

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¹ Aerobic gram-positive microorganisms: Corynebacterium species, Staphylococcus aureus (methicillin-susceptibile strains only), Staphylococcus epidermidis, (methicillin-susceptibile strains only), Streptococcus pneumoniae, Streptococcus (Groups CIF), Streptococcus (Group G), Viridans group streptococci); and aerobic gram-negative microorganisms: Acinetobacter Iwoffii, Haemophilus influenzae, Serratia marcescens.