Bacterial vaginosis
A randomized, double-blind, placebo-controlled clinical trial in 235 non-pregnant women was conducted to evaluate the efficacy of tinidazole for the treatment of bacterial vaginosis. A clinical diagnosis of bacterial vaginosis was based on Amsel's criteria and defined by the presence of an abnormal homogeneous vaginal discharge that (a) has a pH of greater than 4.5, (b) emits a "fishy" amine odor when mixed with a 10% KOH solution, and (c) contains ≥20% clue cells on microscopic examination. Clinical cure required a return to normal vaginal discharge and resolution of all Amsel's criteria. A microbiologic diagnosis of bacterial vaginosis was based on Gram stain of the vaginal smear demonstrating (a) markedly reduced or absent Lactobacillus morphology, (b) predominance of Gardnerella morphotype, and (c) absent or few white blood cells, with quantification of these bacterial morphotypes to determine the Nugent score, where a score ≥4 was required for study inclusion and a score of 0-3 considered a microbiologic cure. Therapeutic cure was a composite endpoint, consisting of both a clinical cure and microbiologic cure. In patients with all four Amsel's criteria and with a baseline Nugent score ≥4, tinidazole oral tablets given as either 2 g once daily for 2 days or 1 g once daily for 5 days demonstrated superior efficacy over placebo tablets as measured by therapeutic cure, clinical cure, and a microbiologic cure.
| Outcome | Tindamax® 1 g × 5 days |
Tindamax® 2 g × 2 days |
Placebo |
|---|---|---|---|
| Therapeutic Cure | |||
| Percent cure | 36.8% | 27.4% | 5.1% |
| Difference‡ | 31.7% | 22.3% | |
| 97.5% CI§ | (16.8, 46.6) | (8.0, 36.6) | |
| Clinical Cure | |||
| Percent cure | 51.3% | 35.6% | 11.5% |
| Difference‡ | 39.8% | 24.1% | |
| 97.5% CI§ | (23.3, 56.3) | (7.8, 40.3) | |
| Nugent Score Cure | |||
| Percent cure | 38.2% | 27.4% | 5.1% |
| Difference‡ | 33.1% | 22.3% | |
| 97.5% CI§ | (18.1, 48.0) | (8.0, 36.6) | |
| n | 76 | 73 | 78 |
|
† Modified Intent-to-Treat defined as all patients randomized with a baseline Nugent score of at least 4 ‡ Difference in cure rates (Tindamax®-placebo) § CI: confidence interval p-values for both Tindamax® regimens vs. placebo for therapeutic, clinical and Nugent score cure rates for both 2 and 5 days <0.001 |
Table 1 | ||
The therapeutic cure rates reported in this clinical study conducted with Tindamax were based on resolution of 4 out of 4 Amsel's criteria and a Nugent score of <4. The cure rates for previous clinical studies with other products approved for bacterial vaginosis were based on resolution of either 2 or 3 out of 4 Amsel's criteria. At the time of approval for other products for bacterial vaginosis, there was no requirement for a Nugent score on Gram stain, resulting in higher reported rates of cure for bacterial vaginosis for those products than for those reported here for tinidazole.
Trichomoniasis
Tinidazole (2 g single oral dose) use in trichomoniasis has been well documented in 34 published reports from the world literature involving over 2,800 patients treated with tinidazole. In four published, blinded, randomized, comparative studies of the 2 g tinidazole single oral dose where efficacy was assessed by culture at time points post-treatment ranging from one week to one month, reported cure rates ranged from 92% (37/40) to 100% (65/65) (n=172 total subjects). In four published, blinded, randomized, comparative studies where efficacy was assessed by wet mount between 7-14 days post-treatment, reported cure rates ranged from 80% (8/10) to 100% (16/16) (n=116 total subjects). In these studies, tinidazole was superior to placebo and comparable to other anti-trichomonal drugs. The single oral 2 g tinidazole dose was also assessed in four open-label trials in men (one comparative to metronidazole and 3 single-arm studies). Parasitological evaluation of the urine was performed both pre- and post-treatment and reported cure rates ranged from 83% (25/30) to 100% (80/80) (n=142 total subjects).
Giardiasis
Tinidazole (2 g single dose) use in giardiasis has been documented in 19 published reports from the world literature involving over 1,600 patients (adults and pediatric patients). In eight controlled studies involving a total of 619 subjects of whom 299 were given the 2 g × 1 day (50 mg/kg × 1 day in pediatric patients) oral dose of tinidazole, reported cure rates ranged from 80% (40/50) to 100% (15/15). In three of these trials where the comparator was 2 to 3 days of various doses of metronidazole, reported cure rates for metronidazole were 76% (19/25) to 93% (14/15). Data comparing a single 2 g dose of tinidazole to usually recommended 5-7 days of metronidazole are limited.
Intestinal amebiasis
Tinidazole use in intestinal amebiasis has been documented in 26 published reports from the world literature involving over 1,400 patients. Most reports utilized tinidazole 2 g/day × 3 days. In four published, randomized, controlled studies (1 investigator single-blind, 3 open-label) of the 2 g/day × 3 days oral dose of tinidazole, reported cure rates after 3 days of therapy among a total of 220 subjects ranged from 86% (25/29) to 93% (25/27).
Amebic liver abscess
Tinidazole use in amebic liver abscess has been documented in 18 published reports from the world literature involving over 470 patients. Most reports utilized tinidazole 2 g/day × 2-5 days. In seven published, randomized, controlled studies (1 double-blind, 1 single-blind, 5 open-label) of the 2 g/day × 2-5 days oral dose of tinidazole accompanied by aspiration of the liver abscess when clinically necessary, reported cure rates among 133 subjects ranged from 81% (17/21) to 100% (16/16). Four of these studies utilized at least 3 days of tinidazole.
Important Safety Information
WARNING: POTENTIAL RISK FOR CARCINOGENICITY
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. Its use should be reserved for the conditions described in INDICATIONS AND USAGE.
Tindamax® is a prescription antibiotic used to treat certain infections caused by bacteria and parasites. It is approved for treating trichomoniasis, also known as "trich," and bacterial vaginosis, or "BV" (in non-pregnant, adult women). It is also approved for treating giardiasis, also known as "giardia," amebiasis, and amebic liver abscess in patients age 3 and older.
Important Safety Information
Tindamax® is not for everyone. You should not take Tindamax® if you are in the first trimester of pregnancy. If you are nursing, Tindamax® can pass through your breast milk, so you should not take it unless you stop breastfeeding during your prescription and for 3 days after your last dose.
Tindamax® can lead to a temporary reduction in your white blood cells, so if you have been diagnosed with a blood disorder, talk to your doctor before starting a prescription.
Do not take Tindamax® if you have a history of sensitivity to tinidazole or related drugs in the nitroimidazole family. Reactions can range from mild itching, hives, or fever to Stevens-Johnson syndrome, which is a rare, life-threatening skin condition.
Certain drugs may interact with Tindamax®, so always tell your doctor about the medications you're taking before you start a prescription.
Take each dose of Tindamax® with food to lessen the risk of stomach upset and other GI side effects. Avoid any alcoholic beverages while taking Tindamax® and for 3 days afterward.
If you are undergoing hemodialysis while taking Tindamax® on the same day, consult your doctor for the appropriate dose of Tindamax®. An additional half-dose of Tindamax® at the end of dialysis may be recommended.
Antibacterial drugs, including Tindamax®, do not treat viral infections such as the common cold. When taking Tindamax® to treat a bacterial infection, it is very common to feel better early in your prescription; however, you should keep taking the medication as directed and for as long as directed by your doctor. Skipping doses or not taking all of your medication can make Tindamax® less effective. It can also allow the bacteria to build up resistance to the drug, so that it won't be treatable with Tindamax® or similar drugs in the future.
The most common side effects of Tindamax® are a metallic or bitter taste, nausea, weakness, fatigue, discomfort, indigestion, cramps, vomiting, loss of appetite, headache, dizziness, and constipation.
Some patients taking Tindamax® may also develop a yeast infection, which can require treatment with an anti-fungal drug. Talk to your doctor if you notice any unusual symptoms.
Certain patients taking Tindamax® have experienced seizures or nerve problems, with symptoms such as numbness or tingling of the hands or feet. Other side effects included vertigo, unsteady movements, insomnia, or drowsiness. Stop taking Tindamax® if you develop any abnormal symptoms.
Tinidazole, the key ingredient in Tindamax®, is related to a drug called metronidazole, which has been linked to cancer in lab rats and mice that received the drug over long periods of time. Although these effects have not been reported for tinidazole, the two drugs are chemically related and have similar effects on the body. Therefore, Tindamax® should only be used to treat infections it has been approved to treat.
To report negative side effects, contact Mission Pharmacal Company at 1-800-298-1087 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
