Link:  Pharm/Biotech Resources

Released by FDA:  3/30/05.  Posted by FDA:  4/14/05

John E. Presutti
President
Presutti Laboratories, Inc.
1685 Winnetka Circle Rolling
Meadows, IL 60008

Re:  NDA # 21-618, 21-681, 21-682
        Tindamax^TM (tinidazole tablets)
        MACMIS ID # 12965

Dear Mr. Presutti:

The Division of Drug Marketing, Advertising, and Communications (DDMAC) has reviewed a "Dear Doctor" Letter for Tindamax^TM (tinidazole tablets) submitted by Presutti Laboratories, Inc. (Presutti) under cover of Form FDA 2253.  The "Dear Doctor" Letter is false or misleading in that it suggests that Tindamax is safe and effective for uses for which it has not been approved by the Food and Drug Administration (FDA). Thus, the "Dear Doctor" Letter violates sections 502(a) and 502(fl(1) of the Federal Food, Drug, and Cosmetic Act (Act). 21 U.S.C. § 352(a) & (fl(1).  By promoting unapproved new uses for Tindamax, you have encouraged the potentially unsafe use of Tindamax.

Background

The Indications and Usage section of the approved product labeling (PI) for Tindamax states that Tindamax is indicated for:

Trichomoniasis:  Tindamax oral tablets are indicated for the treatment of trichomoniasis caused by T. vaginalis in both female and male patients.  The organism should be identified by appropriate diagnostic procedures.  Because trichomoniasis is a sexually transmitted disease with potentially serious sequelae, partners of infected patients should be treated simultaneously in order to prevent reinfection.

Giardiasis:  Tindamax oral tablets are indicated for the treatment of giardiasis caused by G. duodenalis (also termed G. lamblia) in both adults and pediatric patients older than three years of age.

Amebiasis:  Tindamax oral tablets are indicated for the treatment of intestinal amebiasis and amebic liver abscess caused by E. histolytica in both adults and pediatric patients older than three years of age.  It is not indicated in the treatment of asymptomatic cyst passage.

In a letter dated [deleted by FDA] the Division of Special Pathogen and Immunologic Drug Products (DSPIDP) informed Presutti that [deleted] are not approvable.

DSPIDP stated that Presutti failed to submit adequate safety and efficacy data to support the use of Tindamax for these [deleted].  The deficiencies of the data were also explained in the letter.

In a teleconference on November 15, 2004, between DDMAC and Presutti, and in a letter dated November 19, 2004, submitted by Presutti to DDMAC, Presutti acknowledged that it did not have substantial evidence or substantial clinical experience to support the claim that Tindamax is safe and effective for the treatment of metronidazole-resistant trichomoniasis, metronidazole-resistant giardiasis, or anaerobic bacteria, and that the inclusion of these claims in the "Dear Doctor" Letter was a mistake.

Promotion of an Unapproved New Use

Despite the lack of evidence, the "Dear Doctor" Letter clearly suggests that Tindamax is safe and effective for the treatment of metronidazole-resistant trichomoniasis, metronidazole-resistant giardiasis, and anaerobic bacteria.  Specifically, the "Dear Doctor" Letter states:

•  "Demonstrated utility in metronidazole resistant trichomoniasis and giardiasis at higher doses."

•  "Tindamax is the new replacement for metronidazole offering excellent efficacy with minimal side effects." (emphasis added)

•  "Greater in-vitro potency than metronidazole against most protozoa (including metronidazole resistant T. vaginalis) and anaerobic bacteria."

As we indicated in the teleconference and as acknowledged in your letter, FDA is not aware of substantial evidence or substantial clinical experience demonstrating that Tindamax is safe and effective for the treatment of metronidazole-resistant trichomoniasis, metronidazole-resistant giardiasis, or anaerobic bacteria.  In fact, the Agency found that Tindamax is not approvable for the indications of treatment of metronidazole-resistant trichomoniasis and metronidazole-resistant giardiasis.

Furthermore, by claiming that Tindamax is the new replacement for metronidazole, which is approved to treat anaerobic bacterial infections, you suggest that Tindamax is safe and effective for such infections.

Conclusion and Requested Action

Your "Dear Doctor" Letter misleadingly suggests that Tindamax is safe and effective for unapproved new uses, and therefore, misbrands the drug in violation of sections 502(a) and 502(f)(1) of the Federal Food, Drug, and Cosmetic Act (Act), 21 U.S.C. § 352(a) & (f)(1).

DDMAC requests that Presutti immediately cease the dissemination of violative promotional materials for Tindamax such as those described above.  Please submit a written response to this letter on or before April 13, 2005, stating whether you intend to comply with this request, listing all violative promotional materials for Tindamax such as those described above, and explaining your plan for discontinuing use of such materials. Because the violations described above are serious, we request, further, that your submission include a comprehensive plan of action to disseminate truthful, nonmisleading, and complete corrective messages about the issues discussed in this letter to the audience(s) that received the violative promotional material.  Please direct your response to me at the Food and Drug Administration, Division of Drug Marketing, Advertising, and Communications, HFD42, Room 8B-45, 5600 Fishers Lane, Rockville, MD 20857, facsimile at 301-594-6771.  In all future correspondence regarding this matter, please refer to MACMIS ID # 12965 in addition to the NDA numbers.  We remind you that only written communications are considered official.

The violations discussed in this letter do not necessarily constitute an exhaustive list.  It is your responsibility to ensure that your promotional materials for Tindamax comply with each applicable requirement of the Act and FDA implementing regulations.

Sincerely,

Thomas Abrams, RPh, MBA
Division Director
Division of Drug Marketing, Advertising, and
Communications