Clinical medicine profile
Tinidazole
Nitroimidazole Antimicrobial [EPC]
- Route
- ORAL / IV / TOPICAL / VAGINAL
- Schedule
- POM
- ATC
- Not assigned
- PPB status
- registered
Safety essentials
The information most likely to change a prescribing or dispensing decision.
WARNING: POTENTIAL RISK FOR CARCINOGENICITY Carcinogenicity has been seen in mice and rats treated chronically with metronidazole, another nitroimidazole agent [see Nonclinical Toxicology ( 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 [see Indications and Usage ( 1.1 , 1.2 , 1.3 )]. Avoid chronic use [see Warnings and Precautions ( 5.1 )]. 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 ).
Contraindications
- 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 intiation of metronidazole, another nitroimidazole drug, structurally related to tinidazole, in patients with Cockayne syndrome [see Adverse Reactions ( 6.2 )] Prior history of hypersensitivity to tinidazole or other nitroimidazole derivatives ( 4, 6.1, 6.2 ) Patients with Cockayne Syndrome ( 4 , 6.2 )
Precautions
- reported.
- Discontinue Tinidazole Tablets if abnormal neurologic signs develop ( 5.1 ) Vaginal candidiasis may develop with Tinidazole Tablets and require treatment with an antifungal agent ( 5.2 ) Use Tinidazole Tablets with caution in patients with blood dyscrasias.
- Tinidazole Tablets may produce transient leukopenia and neutropenia ( 5.3, 7.3 ) 5.1 Potential for Genotoxicity and Carcinogenicity Carcinogenicity has been seen in mice and rats treated chronically with nitroimidazole derivatives, which are structurally related to tinidazole [see Nonclinical Toxicology ( 13.1 )] .
- Although such data have not been reported for tinidazole, the two drugs are structurally related and have similar biologic effects.
- However, it is unclear if the positive tumor findings in lifetime rodent studies indicate a risk to patients taking a short course or single dose of Tinidazole Tablet.
- Use should be limited to approved indications only.
- Avoid chronic use. 5.2 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. 5.3 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 )]. 5.4 Blood Dyscrasia Tinidazole should be used with caution in patients with evidence of or history of blood dyscrasia [see Drug Interactions ( 7.3 )]. 5.5 Development of Drug-Resistant Bacteria Prescribing Tinidazole Tablets 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.
Dosing matrix
Population and organ-function guidance, shown together for faster comparison.
Trichomoniasis: a single 2 g oral dose taken with food. Treat sexual partners 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 days without additional reported adverse reactions. Children should be closely monitored when treatment durations exceed 3 days. 2.6 Bacterial Vaginosis The recommended dose 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.
8.4 Pediatric Use Other than for use in the treatment of giardiasis and amebiasis in pediatric patients older than three years of age, safety and effectiveness of tinidazole in pediatric patients have not been established. Pediatric Administration: For those unable to swallow tablets, tinidazole tablets may be crushed in artificial cherry syrup, to be taken with food [see Dosage and Administration ( 2.2 )].
Metabolites accumulate in renal failure; review dosing in ESRD.
- CrCl 0–120: Confirm renal dosing in product SmPC / primary label.
Hepatic metabolism — reduce dose in severe liver disease.
Use, effects & interactions
Indications
- 1 INDICATIONS AND USAGE Tinidazole Tablet 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 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. 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, local epidemology and susceptibility patterns may contribute to the empiric selection of therapy.
Adverse effects
- 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 Rising Pharma Holdings, Inc. at 1-844-874-7464 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.
Drug interactions
Open multi-drug checker ↗- Cornerstone for anaerobic coverage and protozoa (giardia, amoeba, trichomonas).
- Combine with other agents for mixed aerobic–anaerobic infections as indicated.
- Warn every patient about alcohol.
Mechanism & disposition
It is a selective for anaerobic bacteria due to their ability to intracellularly reduce imidazole which covalently binds to DNA, disrupt its helical structure, inhibiting bacterial nucleic acid synthesis.
Read complete mechanism
It is a selective for anaerobic bacteria due to their ability to intracellularly reduce imidazole which covalently binds to DNA, disrupt its helical structure, inhibiting bacterial nucleic acid synthesis.
1–2 hours
8–24 hours
ORAL / IV / TOPICAL / VAGINAL
After oral administration, tinidazole is rapidly and completely absorbed. A bioavailability study of Tinidazole tablets was conducted in adult healthy volunteers. All subjects received a single oral dose of 2 g (four 500 mg tablets) of Tinidazole following an overnight fast. Oral...
Tinidazole is distributed into virtually all tissues and body fluids and also crosses the blood-brain barrier. The apparent volume of distribution is about 50 liters. Plasma protein binding of tinidazole is 12%.
Tinidazole is significantly metabolized in humans prior to
half-life (T 1/2 ) was 13.2 (±1.4) hours. Mean plasma levels decreased to 14.3 µg/mL at 24 hours, 3.8 µg/mL at 48 hours and 0.8 µg/mL at 72 hours following administration. Steady-state conditions are reached in 2½ - 3 days of multi-day dosing. Administration of Tinidazole tablets...
(T 1/2 ) was 13.2 (±1.4) hours. Mean plasma levels decreased to 14.3 µg/mL at 24 hours, 3.8 µg/mL at 48 hours and 0.8 µg/mL at 72 hours following administration. Steady-state conditions are reached in 2½ - 3 days of multi-day dosing. Administration of Tinidazole tablets with food...
Pregnancy, lactation & diet
8.1 Pregnancy Risk Summary Available published data from a case-control study and case report with Tinidazole Tablets 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).
8.3 Females and Males of Reproductive Potential Infertility Infertility Males Based on findings in rodents, Tinidazole may impair fertility in males of reproductive potential. It is not known whether effects on fertility are reversible [see Nonclinical Toxicology (13.1) ].
Brands & loaded prices
| Brand | Manufacturer | Pack | Observed price |
|---|---|---|---|
| TINIZEN 500 | ZAIN PHARMA LIMITED | Tablet | Unavailable |
Sources & review state
Decision support only. Confirm patient-specific decisions against the current product SmPC, Kenya STG/EML, and professional judgement.