TINIDAZOLE- tinidazole tablet, film coated
Roxane Laboratories, Inc
WARNING: POTENTIAL RISK FOR CARCINOGENICITY
Carcinogenicity has been seen in mice and rats treated chronically with metronidazole, another nitroimidazole agent (13.1). Although such data have not been reported for tinidazole tablets, the two drugs are structurally related and have similar biologic effects. Its use should be reserved for the conditions described in INDICATIONS AND USAGE (1).
1 INDICATIONS AND USAGE
1.1 Trichomoniasis
Tinidazole Tablets are indicated for the treatment of trichomoniasis caused by Trichomonas vaginalis. 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 re-infection[see Clinical Studies (14.1)].
1.2 Giardiasis
Tinidazole Tablets are indicated for the treatment of giardiasis caused by Giardia duodenalis (also termed G. lamblia) in both adults and pediatric patients older than three years of age [see Clinical Studies (14.2)].
1.3 Amebiasis
Tinidazole Tablets are indicated for the treatment of intestinal amebiasis and amebic liver abscess caused by Entamoeba histolytica in both adults and pediatric patients older than three years of age. It is not indicated in the treatment of asymptomatic cyst passage [see Clinical Studies (14.3, 14.4)].
1.4 Bacterial Vaginosis
Tinidazole Tablets are indicated for the treatment of bacterial vaginosis (formerly referred to as Haemophilus vaginitis, Gardnerella vaginitis, nonspecific vaginitis, or anaerobic vaginosis) in non-pregnant women [see Use in Specific Populations (8.1) and Clinical Studies (14.5)].
Other pathogens commonly associated with vulvovaginitis such as Trichomonas vaginalis, Chlamydia trachomatis, Neisseria gonorrhoeae, Candida albicans and Herpes simplex virus should be ruled out.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Tinidazole Tablets and other antibacterial drugs, Tinidazole Tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
2 DOSAGE AND ADMINISTRATION
2.1 Dosing Instructions
It is advisable to take tinidazole with food to minimize the incidence of epigastric discomfort and other gastrointestinal side-effects. Food does not affect the oral bioavailability of tinidazole [see Clinical Pharmacology (12.3)].
Alcoholic beverages should be avoided when taking tinidazole and for 3 days afterwards [see Drug Interactions (7.1)].
2.2 Compounding of the Oral Suspension
For those unable to swallow tablets, tinidazole tablets may be crushed in artificial cherry syrup to be taken with food.
Procedure for Extemporaneous Pharmacy Compounding of the Oral Suspension: Pulverize four 500 mg oral tablets with a mortar and pestle. Add approximately 10 mL of cherry syrup to the powder and mix until smooth. Transfer the suspension to a graduated amber container. Use several small rinses of cherry syrup to transfer any remaining drug in the mortar to the final suspension for a final volume of 30 mL. The suspension of crushed tablets in artificial cherry syrup is stable for 7 days at room temperature. When this suspension is used, it should be shaken well before each administration.
2.3 Trichomoniasis
The recommended dose in both females and males is a single 2 g oral dose taken with food. Since trichomoniasis is a sexually transmitted disease, sexual partners should be treated with the same dose and at the same time.
2.4 Giardiasis
The recommended dose in adults is a single 2 g dose taken with food. In pediatric patients older than three years of age, the recommended dose is a single dose of 50 mg/kg (up to 2 g) with food.
2.5 Amebiasis
Intestinal: The recommended dose in adults is a 2 g dose per day for 3 days taken with food. In pediatric patients older than three years of age, the recommended dose is 50 mg/kg/day (up to 2 g per day) for 3 days with food.
Amebic Liver Abscess: The recommended dose in adults is a 2 g dose per day for 3-5 days taken with food. In pediatric patients older than three years of age, the recommended dose is 50 mg/kg/day (up to 2 g per day) for 3-5 days with food. There are limited pediatric data on durations of therapy exceeding 3 days, although a small number of children were treated for 5 days without additional reported adverse reactions. Children should be closely monitored when treatment durations exceed 3 days.
2.6 Bacterial Vaginosis
The recommended dose in non-pregnant females is a 2 g oral dose once daily for 2 days taken with food or a 1 g oral dose once daily for 5 days taken with food. The use of tinidazole in pregnant patients has not been studied for bacterial vaginosis.
3 DOSAGE FORMS AND STRENGTHS
250 mg tablets are white to off white, round, biconvex, film coated tablets, with �54 524? debossed on one side and scored on the other
500 mg tablets are white to off white, modified oval, film coated tablets, with �54 455? debossed on one side and scored on the other.
4 CONTRAINDICATIONS
The use of Tinidazole Tablets are contraindicated:
In patients with a previous history of hypersensitivity to tinidazole or other nitroimidazole derivatives. Reported reactions have ranged in severity from urticaria to Stevens-Johnson syndrome [see Adverse Reactions (6.1,6.2)].
During first trimester of pregnancy [see Use in Specific Populations (8.1)].
In nursing mothers: Interruption of breast-feeding is recommended during Tinidazole Tablets therapy and for 3 days following the last dose [see Use in Specific Populations (8.3)].
5 WARNINGS AND PRECAUTIONS
5.1 Neurological Adverse Reactions
Convulsive seizures and peripheral neuropathy, the latter characterized mainly by numbness or paresthesia of an extremity, have been reported in patients treated with tinidazole. The appearance of abnormal neurologic signs demands the prompt discontinuation of tinidazole therapy.
5.2 Vaginal Candidiasis
The use of tinidazole may result in Candida vaginitis. In a clinical study of 235 women who received tinidazole for bacterial vaginosis, a vaginal fungal infection developed in 11 (4.7%) of all study subjects [see Clinical Studies (14.5)].
5.3 Blood Dyscrasia
Tinidazole should be used with caution in patients with evidence of or history of blood dyscrasia [see Drug Interactions (7.3)].
5.4 Drug Resistance
Prescribing tinidazole in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
DESCRIPTION
Tinidazole is a synthetic antiprotozoal and antibacterial agent. It is 1-[2-(ethylsulfonyl)ethyl]-2-methyl-5-nitroimidazole, a second-generation 2-methyl-5-nitroimidazole
Tinidazole tablets contain 250 mg or 500 mg of tinidazole. In addition to tinidazole, each tablet contains the following inactive ingredients: colloidal silicon dioxide, copovidone, croscarmellose sodium, magnesium stearate, polyvinyl alcohol, polyethylene glycol, silicified microcrystalline cellulose, titanium dioxide and talc.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Tinidazole is an antiprotozoal, antibacterial agent.
Microbiology
Mechanism of Action: Tinidazole is an antiprotozoal, antibacterial agent. The nitro- group of tinidazole is reduced by cell extracts of Trichomonas. The free nitro- radical generated as a result of this reduction may be responsible for the antiprotozoal activity. Chemically reduced tinidazole was shown to release nitrites and cause damage to purified bacterial DNA in vitro. Additionally, the drug caused DNA base changes in bacterial cells and DNA strand breakage in mammalian cells. The mechanism by which tinidazole exhibits activity against Giardia and Entamoeba species is not known.
Antibacterial: Culture and sensitivity testing of bacteria are not routinely performed to establish the diagnosis of bacterial vaginosis [see Indications and Usage (1.4)]; standard methodology for the susceptibility testing of potential bacterial pathogens, Gardnerella vaginalis, Mobiluncus spp. or Mycoplasma hominis, has not been defined. The following in vitro data are available, but their clinical significance is unknown. Tinidazole is active in vitro against most strains of the following organisms that have been reported to be associated with bacterial vaginosis:
Bacteroides spp.
Gardnerella vaginalis
Prevotella spp.
Tinidazole does not appear to have activity against most strains of vaginal lactobacilli.
Antiprotozoal: Tinidazole demonstrates activity both in vitro and in clinical infections against the following protozoa:Trichomonas vaginalis; Giardia duodenalis (also termed G. lamblia); and Entamoeba histolytica.
For protozoal parasites, standardized susceptibility tests do not exist for use in clinical microbiology laboratories.
Drug Resistance: The development of resistance to tinidazole by G. duodenalis, E. histolytica, or bacteria associated with bacterial vaginosis has not been examined.
Cross-resistance: Approximately 38% of T. vaginalis isolates exhibiting reduced susceptibility to metronidazole also show reduced susceptibility to tinidazole in vitro. The clinical significance of such an effect is not known.
ATIENT COUNSELING INFORMATION
17.1 Administration of Drug
Patients should be told to take Tinidazole Tablets with food to minimize the incidence of epigastric discomfort and other gastrointestinal side-effects. Food does not affect the oral bioavailability of Tinidazole Tablets.
17.2 Alcohol Avoidance
Patients should be told to avoid alcoholic beverages and preparations containing ethanol or propylene glycol during Tinidazole Tablets therapy and for 3 days afterward because abdominal cramps, nausea, vomiting, headaches, and flushing may occur.
17.3 Drug Resistance
Patients should be counseled that antibacterial drugs including Tinidazole Tablets should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Tinidazole Tablets is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Tinidazole Tablets or other antibacterial drugs in the future.
