Tinidazole

FDA Drug Information • Also known as: Tindamax, Tindazole, Tinidazole

Brand Names: Tindamax, Tindazole, Tinidazole
Drug Class: Nitroimidazole Antimicrobial [EPC]
Route: ORAL
Dosage Form: TABLET
Product Type: HUMAN PRESCRIPTION DRUG

⚠ Boxed Warning (Black Box)

WARNING: POTENTIAL RISK FOR CARCINOGENICITY WARNING: POTENTIAL RISK FOR CARCINOGENICITY See full prescribing information for complete boxed warning 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, the two drugs are structurally related and have similar biologic effects. Limit use of tinidazole tablets to approved indications only ( 1.1 , 1.2 , 1.3 ). Avoid chronic use. ( 5.1 ) 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, 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 ). Limit use of tinidazole to approved indications only [see Indications and Usage (1.1, 1.2, 1.3)]. Avoid chronic use [see Warnings and Precautions ( 5.1 )].

Description

11 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, which has the following chemical structure: Tinidazole pink oral tablets contain 250 mg or 500 mg of tinidazole. Inactive ingredients include pregelatinized starch NF, croscarmellose sodium NF, magnesium stearate NF, microcrystalline cellulose NF, polyvinyl alcohol-part hydrolyzed USP, titanium dioxide USP, polyethylene glycol 3000 NF, talc USP, and FD&C red # 40 aluminum lake. structure

What Is Tinidazole Used For?

1 INDICATIONS & USAGE Tinidazole Tablets is a nitroimidazole antimicrobial indicated for: Trichomoniasis ( 1.1 ) Giardiasis: in patients age 3 and older ( 1.2 ) Amebiasis: in patients age 3 and older ( 1.3 ) Bacterial Vaginosis: in adult women ( 1.4 , 8.1 ) 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 tinidazole tablets are proven or strongly suspected to be caused by bacteria (1.5). 1.1 Trichomoniasis Tinidazole is 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 is 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 is 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 is indicated for the treatment of bacterial vaginosis (formerly referred to as Haemophilus vaginitis, Gardnerella vaginitis, nonspecific vaginitis, or anaerobic vaginosis) in adult 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. 1.5 Usage 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,...

Dosage and Administration

2 DOSAGE & ADMINISTRATION Trichomoniasis: a single 2 g oral dose taken with food. Treat sexual partner s with the same dose and at the same time ( 2.3 ) Giardiasis: Adults: a single 2 g dose taken with food. Pediatric patients older than three years of age: a single dose of 50 mg/kg (up to 2 g) with food ( 2.4 ) Amebiasis, Intestinal: Adults: 2 g per day for 3 days with food. Pediatric patients older than three years of age: 50 mg/kg/day (up to 2 g per day) for 3 days with food ( 2.5 ). Amebic liver abscess: Adults: 2 g per day for 3-5 days with food. Pediatric patients older than three years of age: 50 mg/kg/day (up to 2 g per day) for 3-5 days with food ( 2.5 ). Bacterial vaginosis: Adult women: 2 g once daily for 2 days taken with food, or 1 g once daily for 5 days taken with food ( 2.6 ) 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...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS Most common adverse reactions for a single 2 g dose of tinidazole (incidence >1%) are metallic/bitter taste, nausea, weakness/fatigue/malaise, dyspepsia/cramps/epigastric discomfort, vomiting, anorexia, headache, dizziness and constipation ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Lupin Pharmaceuticals, Inc. at 1-866-403-7592 or or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Studies Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Among 3669 patients treated with a single 2 g dose of tinidazole, in both controlled and uncontrolled trichomoniasis and giardiasis clinical studies, adverse reactions were reported by 11.0% of patients. For multi-day dosing in controlled and uncontrolled amebiasis studies, adverse reactions were reported by 13.8% of 1765 patients. Common (≥ 1% incidence) adverse reactions reported by body system are as follows. (Note: Data described in Table 1 below are pooled from studies with variable designs and safety evaluations.) Other adverse reactions reported with tinidazole include: Central Nervous System: Two serious adverse reactions reported include convulsions and transient peripheral neuropathy including numbness and paresthesia [see Warnings and Precautions ( 5.1 )] . Other CNS reports include vertigo, ataxia, giddiness, insomnia, drowsiness. Gastrointestinal: tongue discoloration, stomatitis, diarrhea Hypersensitivity: urticaria, pruritis, rash, flushing, sweating, dryness of mouth, fever, burning sensation, thirst, salivation, angioedema Renal: darkened urine Cardiovascular: palpitations Hematopoietic: transient neutropenia, transient leukopenia Other: Candida overgrowth, increased vaginal discharge, oral candidiasis, hepatic abnormalities including raised transaminase level, arthralgias, myalgias, and arthritis. Table 1. Adverse Reactions Summary of Published Reports 2 g single dose Multi-day dose GI: Metallic/bitter taste 3.7% 6.3% Nausea 3.2% 4.5% Anorexia 1.5% 2.5% Dyspepsia/cramps/epigastric discomfort 1.8% 1.4% Vomiting 1.5% 0.9% Constipation 0.4% 1.4% CNS: Weakness/fatigue/malaise 2.1% 1.1% Dizziness 1.1% 0.5% Other: Headache 1.3% 0.7% Total patients with adverse reactions 11.0% (403/3669) 13.8% (244/1765) Rare reported adverse reactions include bronchospasm, dyspnea, coma, confusion, depression, furry tongue, pharyngitis and reversible thrombocytopenia. Adverse Reactions in Pediatric Patients: In pooled pediatric studies, adverse reactions reported in pediatric patients taking tinidazole were similar in nature and frequency to adult findings including nausea, vomiting, diarrhea, taste change, anorexia, and abdominal pain. Bacterial vaginosis: The most common adverse reactions in treated patients (incidence >2%), which were not identified in the trichomoniasis, giardiasis and amebiasis studies, are gastrointestinal: decreased appetite, and flatulence; renal: urinary tract infection, painful urination, and urine abnormality; and other reactions including pelvic pain, vulvo-vaginal discomfort, vaginal odor, menorrhagia, and upper respiratory tract infection [ See Clinical Studies ( 14.5 ) ]. 6.2 Postmarketing Experience The following adverse reactions have been identified and reported during post-approval use of tinidazole tablets. Because the reports of these reactions are voluntary and the population is of uncertain size, it is not always possible to reliably estimate the frequency of the reaction or establish a causal relationship to drug exposure. Tinidazole tablets Severe acute hypersensitivity reactions have been reported on initial or subsequent exposure to tinidazole. Hypersensitivity reactions may include urticaria, pruritis, angioedema, Stevens-Johnson syndrome and erythema multiforme. Metronidazole, Another...

Drug Interactions

7 DRUG INTERACTIONS The following drug interactions were reported for metronidazole, a chemically-related nitroimidazole and may therefore occur with tinidazole: Warfarin and other oral coumarin anticoagulants: Anticoagulant dosage may need adjustment during and up to 8 days after tinidazole therapy ( 7.1 ) Alcohol-containing beverages/preparations: Avoid during and up to 3 days after tinidazole therapy ( 7.1 ) Lithium: Monitor serum lithium concentrations ( 7.1 ) Cyclosporine, tacrolimus: Monitor for toxicities of these immunosuppressive drugs ( 7.1 ) Fluorouracil: Monitor for fluorouracil-associated toxicities ( 7.1 ) Phenytoin, fosphenytoin: Adjustment of anticonvulsant and/or tinidazole dose(s) may be needed ( 7.1 , 7.2 ) CYP3A4 inducers/inhibitors: Monitor for decreased tinidazole effect or increased adverse reactions ( 7.2 ) Although not specifically identified in studies with tinidazole, the following drug interactions were reported for metronidazole, a chemically-related nitroimidazole. Therefore, these drug interactions may occur with tinidazole. 7.1 Potential Effects of Tinidazole on Other Drugs Warfarin and Other Oral Coumarin Anticoagulants: As with metronidazole, tinidazole may enhance the effect of warfarin and other coumarin anticoagulants, resulting in a prolongation of prothrombin time. The dosage of oral anticoagulants may need to be adjusted during tinidazole co-administration and up to 8 days after discontinuation. Alcohols, Disulfiram: Alcoholic beverages and preparations containing ethanol or propylene glycol should be avoided during tinidazole therapy and for 3 days afterward because abdominal cramps, nausea, vomiting, headaches, and flushing may occur. Psychotic reactions have been reported in alcoholic patients using metronidazole and disulfiram concurrently. Though no similar reactions have been reported with tinidazole, tinidazole should not be given to patients who have taken disulfiram within the last two weeks. Lithium : Metronidazole has been reported to elevate serum lithium levels. It is not known if tinidazole shares this property with metronidazole, but consideration should be given to measuring serum lithium and creatinine levels after several days of simultaneous lithium and tinidazole treatment to detect potential lithium intoxication. Phenytoin, Fosphenytoin: Concomitant administration of oral metronidazole and intravenous phenytoin was reported to result in prolongation of the half-life and reduction in the clearance of phenytoin. Metronidazole did not significantly affect the pharmacokinetics of orally-administered phenytoin. Cyclosporine, Tacrolimus : There are several case reports suggesting that metronidazole has the potential to increase the levels of cyclosporine and tacrolimus. During tinidazole co-administration with either of these drugs, the patient should be monitored for signs of calcineurin-inhibitor associated toxicities. Fluorouracil : Metronidazole was shown to decrease the clearance of...

Contraindications

4 CONTRAINDICATIONS Prior history of hypersensitivity to tinidazole or other nitroimidazole derivatives ( 4 , 6.1 , 6.2 ) Patients with Cockayne syndrome ( 4 , 6.2 ) The use of tinidazole is 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 ) ]. In patients with Cockayne syndrome. Severe irreversible hepatotoxicity/acute liver failure with fatal outcomes have been reported after initiation of metronidazole, another nitroimidazole drug, structurally related to tinidazole, in patients with Cockayne syndrome [see Adverse Reactions ( 6.2 )]

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary Available published data from a case-control study and case report with tinidazole use in pregnant women are insufficient to identify a risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. There are risks associated with untreated lower genital tract infections during pregnancy (see Clinical Considerations). In animal reproduction studies, oral administration of tinidazole to pregnant mice and rats during organogenesis at 6 and 3 times, respectively, the maximum recommended human dose (based on body surface area comparison) showed a slight increase in fetal mortality in rats at the highest dose, with no other adverse fetal effects noted in either species (see Data). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data Embryo-fetal developmental toxicity studies in pregnant mice administered oral tinidazole on gestation days (GD) 7 to 12 indicated no embryo-fetal toxicity or malformations at the highest dose level of 2,500 mg/kg (approximately 6.3-fold the highest human therapeutic dose based upon body surface area conversions). In a study with pregnant rats administered oral tinidazole on GD 9 to 14, a slightly higher incidence of fetal mortality was observed at a maternal dose of 500 mg/kg (2.5-fold the highest human therapeutic dose based upon body surface area conversions). No biologically relevant neonatal developmental effects were observed in surviving rat neonates following maternal doses as high as 600 mg/kg (3-fold the highest human therapeutic dose based upon body surface area conversions).

Overdosage

10 OVERDOSAGE There are no reported overdoses with tinidazole in humans. Treatment of Overdosage : There is no specific antidote for the treatment of overdosage with tinidazole; therefore, treatment should be symptomatic and supportive. Gastric lavage may be helpful. Hemodialysis can be considered because approximately 43% of the amount present in the body is eliminated during a 6-hour hemodialysis session.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING Tinidazole Tablets 250 mg tablets are pink, round, scored tablets, debossed with "N" scored "L" on one side and "550" on the other side, supplied in bottles with child-resistant caps as: NDC 43386-550-04 Bottle of 40 Tinidazole Tablets 500 mg tablets are pink, oval, scored tablets, debossed with "N" scored "L" on one side and "551" on the other side, supplied in bottles with child-resistant caps as: NDC 43386-551-06 Bottle of 60 NDC 43386-551-02 Bottle of 20 Storage: Store at controlled room temperature 20-25° C (68-77° F); excursions permitted to 15-30° C (59-86° F) [see USP]. Protect contents from light.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.