FDA approves treatment for bacterial vaginosis

May 28 2007

Mission Pharmacal has announced that the U.S. Food and Drug Administration (FDA) approved Tindamax (tinidazole) for the treatment of bacterial vaginosis (BV), the most common vaginal infection among women of childbearing age in the United States.

Tindamaxis the first new oral therapy to be approved for the treatment of BV in a decade, and provides a shorter course oral treatment, with fewer doses per day and a better tolerability profile, than the current standard of care. Tindamaxis the only FDA approved treatment for both BV and trichomoniasis, two conditions which are highly prevalent and often overlap. Trichomoniasis is the most common curable sexually transmitted disease in the United States.

As the most widespread form of vaginal infection, BV affects almost one- third of women in the United States (29.2 percent) and is one of the main causes of the 10 million doctor visits for vaginitis in the country annually. BV is caused when the normal balance of bacteria in the vagina is disturbed and replaced by an overgrowth of certain bacteria. Many women with BV do not experience any symptoms; when they do, symptoms include abnormal vaginal discharge with an unpleasant odor, burning during urination, or itching in the genital area.

Tindamaxis administered as one gram (two tablets) once daily for five days or two grams (four tablets) once daily for two days, compared to the twice- daily, seven day oral dosing of metronidazole, the current standard of care.

"We are extremely pleased to be able to provide women with the first new oral treatment for BV in a decade," said Neil Walsdorf, Jr., President of Mission Pharmacal. "Because Tindamax provides a shorter course of therapy with a better tolerability profile, we are confident it will set a new standard of care in oral therapy for the treatment of BV."

Unlike intravaginal treatments, Tindamax treats the entire reproductive tract, including the upper tract, where BV has been shown to migrate. According to the Centers for Disease Control and Prevention (CDC), if left untreated, BV can increase a woman's susceptibility to sexually transmitted diseases such as chlamydia, gonorrhea, and HIV, if she is exposed to these diseases. The untreated bacteria also may infect other female organs and cause serious complications such as pelvic inflammatory disease and cervicitis. In pregnant women, BV is associated with an increased risk of early pregnancy loss, premature delivery, and delivery of a low-birth-weight baby.

The FDA approval of Tindamax for BV is supported by data from a randomized, placebo-controlled, double-blind multi-center trial evaluating two dosing regimens of Tindamax. In the study, 235 women with BV were randomized to one of three treatment arms: two grams of Tindamax once daily (four tablets) for two days, one gram of Tindamax (two tablets) once daily for five days, or placebo. Both Tindamax regimens exhibited superior efficacy than placebo, with a cure rate of 27.4 percent in the two grams once daily for two days group and 36.8 percent in the one gram once daily for five days group, compared to a cure rate of 5.1 percent in the placebo group. Cure rate was defined using the FDA Guidance Criteria, the most rigorous criteria available.

"Compared with other oral treatments for BV currently recommended, Tindamax therapy reduces the total number of treatment doses by more than half. Shorter courses of therapy have been shown to improve patient compliance, which is important when treating a condition like BV," said Jeanne Marrazzo, M.D., MPH, Associate Professor of Medicine, Department of Infectious Diseases, University of Washington in Seattle.

In the pivotal trials, adverse events in patients treated with Tindamax were minimal and comparable across both treatment groups and the placebo group, and included metallic taste and nausea. Tindamax is associated with a low incidence of gastrointestinal side effects.

Tindamax, a second-generation 5-nitroimidazole compound, is indicated in the United States for the treatment of bacterial vaginosis, trichomoniasis, the intestinal infections giardiasis and intestinal amebiasis, and amebic liver abscess. It has been approved for use in the United States since May 2004 and is recognized as one of the drugs of choice for the treatment of trichomoniasis by the CDC.

Tindamax has been found to have a favorable side effect profile with a low incidence of nausea and vomiting. In clinical trials of patients treated with a single two gram dose of tinidazole for trichomoniasis and giardiasis, adverse effects experienced by more than one percent of patients included metallic or bitter taste, nausea, anorexia, abdominal discomfort, vomiting, constipation, diarrhea, general weakness or fatigue, dizziness, and headache.

Carcinogenicity has been seen in mice and rats treated chronically with metronidazole, another nitroimidazole agent. Although such data have not been reported for tinidazole, the two drugs are structurally related and have similar biologic effects. Use should be limited to approved indications only.

The use of tinidazole in pregnant patients has not been studied. Tindamax should not be administered to women in their first trimester of pregnancy.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Tindamax and other antibacterial drugs, Tindamax should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

As the most widespread form of vaginal infection, affecting nearly one- third of women in the United States, BV is one of the main causes of the 10 million doctor visits for vaginitis in the country annually. Approximately 4.5 million prescriptions are written for BV treatment each year in the United States.

BV symptoms include a foul or fishy odor in varying degrees and a milk- like vaginal discharge. Signs of BV also include a vaginal pH level exceeding 4.5 and the presence of clue cells seen in a microscopic evaluation of vaginal discharge. Clue cells are vaginal epithelial cells coated with bacteria. BV is caused by an overgrowth of anaerobic bacteria in the vagina, with a concomitant decrease in protective lactobacilli.