Pharmacology Update

Tinidazole tablets (Tindamax™ )

By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD

The FDA has approved a 5-nitroimidazole for the treatment of trichomoniasis, giardiasis, and amebiasis. Tinidazole, a second-generation nitroimidazole antiprotozoal agent, is marketed as Tindamax™ by Presutti Laboratories.

Indications

Tinidazole is indicated for the treatment of trichomoniasis caused by Trichomonas vaginalis in both females and males. It is also indicated for the treatment of giardiasis and amebiasis (intestinal and amoebic liver abscess) caused by E. histolytica. It is not indicated for the treatment of asymptomatic cyst passage.1

Dosage

For the treatment of trichomoniasis, the recommended dose is a single 2 g dose taken with food. The sexual partner should be treated with the same dose at the same time.

For giardiasis, the adult dose is a single 2 g dose taken with food. In pediatric patients (older than 3 years of age), the dose is a single 50 mg/kg dose (up to 2 g).

For intestinal amebiasis, the adult dose is 2 g daily for 3 days with food, and for pediatric patients, 50 mg/kg/d (up to 2 g) for 3 days. For amoebic liver abscess, the recommended dose is 50 mg/kg/d with food (up to 2 g) for 3-5 days.

Alcoholic beverages should be avoided while on tinidazole, and for 3 days thereafter.

Tinidazole is available as 250 mg and 500 mg tablets. The tablets can be ground to a fine powder and made into a suspension with artificial cherry syrup for pediatric use.1

Potential Advantages

Tinidazole has good in vitro activity against both metronidazole and metronidazole-resistant T. vaginalis and shown effectiveness against metronidazole-refractory vaginal trichomoniasis.2,3 The elimination half-life of tinidazole is 12-14 hours, about twice that of metronidazole (6-7 hours), and may be better tolerated.4

Potential Disadvantages

As with metronidazole, tinidazole is contraindicated during the first trimester of pregnancy. Convulsive seizures and peripheral neuropathy has also been reported with these drugs. Approximately 38% of T. vaginalis isolates showed cross-resistance to metronidazole.

Drugs that may interact with metronidazole may also interact with tinidazole (eg, alcohol, lithium, phenytoin, fosphenytoin, cyclosporine, tacrolimus fluorouracil, rifampin, phenobarbital, cholestyramine). Similar to metronidazole, tinidazole may produce transient leucopenia and neutropenia although no persistent hematological abnormalities have been observed in clinical trials. Total and differential leukocyte counts are recommended if retreatment is needed.1 Common side effects include metallic/bitter taste, dyspepsia, weakness/ fatigue/malaise, and vomiting.1

Comments

Tinidazole is a second generation 5-nitroimidazole similar to metronidazole. It has been established as an effective drug against trichomoniasis, giardiasis, and amebiasis.

The cure rate for trichomoniasis for a single 2-g dose ranged from 80% to 100%.1,5-8 The cure rate for tinidazole ranged from 80% to 100% for giardiasis, 86% to 93% for intestinal amebiasis, and 81% to 100% for amoebic liver abscess.1,9,10 In general, tinidazole was equal to, or more effective than, metronidazole. In addition, these agents share similar side effects although some studies suggest that tinidazole is better tolerated.4,8 The average wholesale cost for a 2-g dose of tinidazole is $18.24 which is significantly more expensive than generic metronidazole.

Clinical Implications

Trichomoniasis is a common sexually transmitted disease. It is estimated that there are about 7.4 million cases annually. Current treatment is metronidazole as a single 2 g dose. For patients that are not responsive, options have included an increase in the dose of metronidazole or multiple doses of the drug (eg, 500 mg twice daily ´ 7 days or 2 g for 3-5 days).11 Tinidazole provides an effective alternative for patient intolerant of or not responsive to metronidazole. Tinidazole is also a convenient single dose alternative to metronidazole and furazolidone for giardiasis.

Dr. Elliott, MD, FACP, is Chair of the Formulatory Committee at Northern California Kaiser Permanente and Assistant Clinical Professor of Medicine at the University of California, San Francisco. Dr. Chan, PharmD, PhD, is Pharmacy Quality and Outcomes Manager for Kaiser Permanente, Oakland, CA.

References

1. Tindamax™ Product Information. Presutti Laboratories, Inc. May 2004.

2. Sobel JD, et al. Clin Infect Dis. 2001;33:1341-1346.

3. Crowell AL, et al. Antimicrob Agents Chemother. 2003;1407-1409.

4. Hager WE. Sex Transm Dis. 2004;31(6):343-345.

5. O-Prasertsawat P, Jetsawangari T. Sex Transm Dis. 1992;19(5):295-297.

6. Gabriel G, et al. J Int Med Res. 1982;10(2):129-130.

7. Lyng J, Christensen J. Acta Obstet Gynecol Scand. 1981;60(2):199-201.

8. Anjaeyulu R, et al. J Int Med Res. 1977;5(6):438-441.

9. Gazder AJ, Banerjee M. Curr Med Res Opin. 1977; 5(2):164-168.

10. Swami B, et al. Cur Med Res Opin. 1977;5(2):152-156.

11. Bartlett JG. Pocket Book of Infectious Disease Therapy. Philadelphia, Pa:Lippincott Williams & Wilkins; 2004.