Brand name: Tindamax
Drug class:

Medically reviewed by Drugs.com on Apr 10, 2024. Written by ASHP.

Introduction

Antiprotozoal and antibacterial; nitroimidazole derivative.

Uses for Tinidazole

Amebiasis

Treatment of intestinal amebiasis and amebic liver abscess caused by Entamoeba histolytica in adults and children >3 years of age. Designated an orphan drug by FDA for treatment of amebiasis.

Oral tinidazole or oral metronidazole followed by a luminal amebicide (iodoquinol, paromomycin) is the regimen of choice for symptomatic intestinal disease and for amebic hepatic abscess.

Not recommended alone for treatment of asymptomatic cyst passers; these patients require treatment with a luminal amebicide such as iodoquinol, paromomycin, or diloxanide furoate (not commercially available in the US).

Giardiasis

Treatment of giardiasis caused by Giardia duodenalis (also known as G. lamblia or G. intestinalis) in adults and children >3 years of age. Designated an orphan drug by FDA for treatment of giardiasis.

Drugs of choice are metronidazole, tinidazole, or nitazoxanide; alternatives are paromomycin (especially in pregnant women), furazolidone (not commercially available in US), or quinacrine (not commercially available in US).

Trichomoniasis

Treatment of symptomatic and asymptomatic trichomoniasis in men and women in whom Trichomonas vaginalis has been demonstrated by an appropriate diagnostic procedure.

Drugs of choice are metronidazole or tinidazole. Tinidazole may be effective in some patients who do not respond to metronidazole, but some T. vaginalis isolates with reduced susceptibility to metronidazole may also have reduced susceptibility to tinidazole.

Goal of treatment is to provide symptomatic relief, achieve microbiologic cure, and reduce transmission. Because trichomoniasis is a sexually transmitted disease with potential for serious sequelae, treat individuals known to be infected with T. vaginalis regardless of symptomatology and treat sexual partner(s) presumptively to avoid reinfection.

Single-dose metronidazole or tinidazole regimens not recommended for retreatment unless the recurrent infection is likely to be caused by reinfection. A multiple-dose metronidazole or tinidazole regimen may be indicated if treatment failure occurs.

Persistent trichomoniasis may require treatment with alternative regimens and management in consultation with an expert. Clinicians can contact CDC at 404-718-4141 or [Web] for assistance regarding in vitro susceptibility testing of T. vaginalis and management of persistent infections, including use of alternative regimens.

Bacterial Vaginosis

Treatment of bacterial vaginosis (formerly called Haemophilus vaginitis, Gardnerella vaginitis, nonspecific vaginitis, Corynebacterium vaginitis, or anaerobic vaginosis) in nonpregnant women.

Bacterial vaginosis is a polymicrobial syndrome that can occur when normal vaginal hydrogen peroxide-producing Lactobacillus are replaced by overgrowth of various anaerobic bacteria (e.g., Prevotella, Mobiluncus, Atopobium vaginae), G. vaginalis, Ureaplasma urealyticum, Mycoplasma hominis, or other bacteria.

Treatment of bacterial vaginosis recommended in symptomatic women to relieve signs and symptoms of infection; routine treatment of male sexual partner(s) not usually recommended.

Regimens of choice are 7-day regimen of oral metronidazole, 5-day regimen of intravaginal metronidazole gel, or 7-day regimen of intravaginal clindamycin cream. Alternative regimens are 2- or 5-day regimen of oral tinidazole, 7-day regimen of oral clindamycin, or 3-day regimen of intravaginal clindamycin suppositories. Preferred regimens for pregnant women are the oral or intravaginal metronidazole or clindamycin regimens.

Relapse or recurrence is common, regardless of treatment regimen used. Retreatment with the same or an alternative regimen (e.g., oral therapy when topical was used initially) can be effective for initial recurrences. Maintenance suppressive therapy with intravaginal metronidazole for 4–6 months may reduce recurrences, but benefit may not persist after suppressive therapy discontinued.

Nongonococcal Urethritis

Treatment of recurrent and persistent urethritis in certain men with nongonococcal urethritis^{† [off-label]} (NGU) who have already been treated with a recommended regimen.

NGU can be caused by various organisms (e.g., Chlamydia, M. genitalium, T. vaginalis, Ureaplasma, enteric bacteria) and is treated presumptively at time of diagnosis.

CDC recommends a single oral dose of azithromycin or a 7-day regimen of doxycycline for treatment of NGU; alternatives are a 7-day regimen of oral erythromycin base or ethylsuccinate or 7-day regimen of oral ofloxacin or oral levofloxacin. To minimize transmission and reinfection, instruct patients to abstain from sexual intercourse until they and their sexual partner(s) have been adequately treated (i.e., 7 days after initiation of treatment).

Patients with persistent or recurrent NGU who were not compliant with the treatment regimen or were reexposed to untreated sexual partner(s) can be retreated with the initial regimen. In other patients, symptoms alone (without documentation of signs or laboratory evidence of urethral inflammation) are not sufficient basis for retreatment.

If patient with persistent or recurrent urethritis has sex with women and is in an area where T. vaginalis is prevalent, CDC recommends presumptive treatment with a single oral dose of metronidazole or tinidazole and referral of their sexual partners(s) for evaluation and appropriate treatment.

Prophylaxis in Sexual Assault Victims

Empiric anti-infective prophylaxis in sexual assault victims^{† [off-label]}; used in conjunction with other anti-infectives.

CDC recommends a 3-drug prophylaxis regimen of ceftriaxone, azithromycin, and metronidazole (or tinidazole) to provide coverage against gonorrhea, chlamydia, and trichomoniasis.

Helicobacter pylori Infection

Although safety and efficacy not established, has been used as a component of various multiple-drug regimens for treatment of infections caused by Helicobacter pylori ^{† [off-label]}.

Has been used in 3-drug regimens that include a proton-pump inhibitor, clarithromycin, and tinidazole or 4-drug regimens, including sequential regimens, that include a proton-pump inhibitor, amoxicillin, clarithromycin, and a nitroimidazole (either tinidazole or metronidazole). Also has been used in sequential regimens that include a proton-pump inhibitor, bismuth subsalicylate, amoxicillin, and levofloxacin.

Tinidazole Dosage and Administration

Administration

Oral Administration

Administer orally with food.

Administration with meals does not affect oral bioavailability but may reduce incidence of adverse GI effects.

Do not consume alcohol during treatment and for 3 days after last dose of tinidazole.

For children and other patients unable to swallow tablets, an extemporaneous oral suspension may be prepared using the tablets.

Extemporaneous Oral Suspension

To prepare an oral suspension containing 66.7 mg/mL, grind 2 g (four 500-mg tablets) to a fine powder with a mortar and pestle. Add approximately 10 mL of cherry syrup to the powder and mix until smooth. Transfer suspension to a graduated amber container; use several small rinses of the cherry syrup to transfer any remaining drug in the mortar to provide a suspension with a final volume of 30 mL.

Shake suspension well prior to administration.

Dosage

Pediatric Patients

Amebiasis

Entamoeba histolytica Infections

Oral

Children >3 years of age (intestinal amebiasis): 50 mg/kg (up to 2 g) once daily given for 3 days; follow-up with an oral luminal amebicide (e.g., iodoquinol, paromomycin).

Children >3 years of age (amebic liver abscess): 50 mg/kg (up to 2 g) once daily given for 3–5 days (see Pediatric Use under Cautions); follow-up with an oral luminal amebicide (e.g., iodoquinol, paromomycin).

Giardiasis

Oral

Children >3 years of age: 50 mg/kg (up to 2 g) given as a single dose.

Trichomoniasis† [off-label]

Oral

Children^{† [off-label]}: 50 mg/kg (up to 2 g) given as a single dose.

Adults

Amebiasis

Entamoeba histolytic Infections

Oral

Intestinal amebiasis: 2 g once daily given for 3 days; follow-up with an oral luminal amebicide (e.g., iodoquinol, paromomycin).

Amebic liver abscess: 2 g once daily for 3–5 days; follow-up with an oral luminal amebicide (e.g., iodoquinol, paromomycin).

Giardiasis

Oral

2 g given as a single dose.

Trichomoniasis

Oral

2 g given as a single dose.

Treat sexual partner(s) of the patient simultaneously using same dosage.

For treatment failure following recommended metronidazole regimens (e.g., single 2-g dose of oral metronidazole, 7-day regimen of oral metronidazole 500 mg twice daily), CDC states retreatment with tinidazole 2 g once daily for 7 days can be considered. (See Trichomoniasis under Uses.)

Bacterial Vaginosis

Nonpregnant Women

Oral

2 g once daily for 2 days or 1 g once daily for 5 days.

Nongonococcal Urethritis†

Oral

For recurrent and persistent urethritis in certain men with NGU (see Nongonococcal Urethritis under Uses), CDC recommends retreatment with a single 2-g dose of tinidazole.

Prophylaxis in Sexual Assault Victims†

Oral

2 g given as a single dose in conjunction with ceftriaxone (single 250-mg IM dose) and azithromycin (single 1-g oral dose) recommended by CDC.

Helicobacter pylori Infection†

Oral

500 mg twice daily has been given when used as a component of various multiple-drug regimens. (See Helicobacter pylori Infection under Uses.)

Prescribing Limits

Pediatric Patients

Oral

Children >3 years of age: Maximum 50 mg/kg (up to 2 g) daily or as a single dose.

Special Populations

Hepatic Impairment

Data not available regarding use in patients with hepatic impairment. Manufacturer states use usual dosage with caution. Some clinicians state not recommended in patients with severe hepatic impairment (Child-Pugh class C). (See Hepatic Impairment under Cautions.)

Renal Impairment

Dosage adjustments not needed (including in those with Cl_cr <22 mL/minute), unless patient is undergoing hemodialysis.

Hemodialysis patients: If given on same day as and prior to hemodialysis, administer an additional dose (equivalent to 50% of the recommended dose) after the hemodialysis session. (See Elimination under Pharmacokinetics.)

Geriatric Patients

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.

Cautions for Tinidazole

Contraindications

• History of hypersensitivity to tinidazole or other nitroimidazole derivatives.

• First trimester of pregnancy. (See Pregnancy under Cautions.)

• Breast-feeding. (See Lactation under Cautions.)

Warnings/Precautions

Warnings

Carcinogenicity

Carcinogenicity reported in mice and rats treated chronically with oral metronidazole (a chemically related nitroimidazole anti-infective). (See Boxed Warning.) Similar animal studies using tinidazole not reported to date.

Because of potential risks, reserve tinidazole for FDA-labeled indications only and avoid unnecessary use.

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions (e.g., urticaria, pruritus, rash, flushing, sweating, dryness of mouth, fever, burning sensation, thirst, salivation, angioedema, bronchospasm, dyspnea, Stevens-Johnson syndrome, erythema multiforme) reported. Anaphylaxis reported rarely.

Severe, acute hypersensitivity reactions reported with initial or subsequent tinidazole treatment.

Cross-allergenicity between tinidazole and metronidazole reported.

Other Warnings/Precautions

Nervous System Effects

Convulsive seizures and peripheral neuropathy (characterized by numbness or paresthesia of an extremity) reported with tinidazole and other nitroimidazoles (e.g., metronidazole).

Other CNS effects reported include vertigo, ataxia, giddiness, insomnia, and drowsiness.

If abnormal neurologic signs develop, promptly discontinue drug.

History of Blood Dyscrasia

Use with caution in patients with evidence or history of blood dyscrasia.

As with other nitroimidazoles (e.g., metronidazole), transient leukopenia and neutropenia may occur; persistent hematologic abnormalities not reported to date.

If retreatment necessary, perform total and differential leukocyte counts.

Vulvovaginal Candidiasis

Vaginal candidiasis reported; treat with an appropriate antifungal.

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of tinidazole and other antibacterials, use only for treatment of infections proven or strongly suspected to be caused by susceptible organisms.

Prescribing tinidazole in the absence of proven or strongly suspected infection or for a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of development of drug-resistant organisms.

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing. In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.

Specific Populations

Pregnancy

Contraindicated during first trimester.

Crosses placenta and enters fetal circulation.

Safety and efficacy not evaluated in pregnant women, including use for treatment of bacterial vaginosis in pregnant women.

CDC recommends avoiding use of tinidazole for treatment of trichomoniasis or bacterial vaginosis in pregnant women.

Lactation

Distributed into human milk in concentrations similar to serum concentrations; can be detected in milk for up to 72 hours after administration.

Contraindicated in breast-feeding women. Interrupt breast-feeding during tinidazole treatment and for 3 days (72 hours) following the last dose.

Pediatric Use

Safety and efficacy not established in pediatric patients ≤3 years of age. Some data available regarding safety and efficacy for treatment of giardiasis in pediatric patients <3 years of age^†.

Safety and efficacy in pediatric patients >3 years of age established only for treatment of amebiasis or giardiasis.

Monitor pediatric patients closely if duration of therapy is >3 days (e.g., for treatment of amebic liver abscess) since only limited data available.

Adverse effects reported in pediatric patients generally similar in nature and frequency to those reported in adults.

Geriatric Use

Experience in those ≥65 years of age insufficient to determine whether they respond differently than younger adults.

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.

Hepatic Impairment

Use usual dosage with caution; pharmacokinetics not evaluated.

Some clinicians state tinidazole not recommended in patients with severe hepatic impairment (Child-Pugh class C).

Studies using metronidazole (a chemically related nitroimidazole) indicate reduced elimination and increased plasma concentrations in severe hepatic dysfunction.

Renal Impairment

Pharmacokinetics in patients with severe renal impairment (Cl_cr <22 mL/minute) similar to that reported in healthy individuals.

Dosage adjustment not needed unless patient is undergoing hemodialysis. (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

GI effects (metallic/bitter taste, nausea, anorexia, dyspepsia/cramps/epigastric discomfort, vomiting, constipation), nervous system effects (weakness/fatigue/malaise, dizziness, headache).

Drug Interactions

Metabolized principally by CYP3A4.

Does not inhibit CYP1A2, 2B6, 2C9, 2D6, 2E1, or 3A4 in vitro.

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Inhibitors of CYP3A4: Potential pharmacokinetic interactions (increased plasma tinidazole concentrations).

Inducers of CYP3A4: Potential pharmacokinetic interactions (decreased plasma tinidazole concentrations).

Specific Drugs and Laboratory Tests

No formal drug interaction studies performed with tinidazole to date; interactions reported with metronidazole (a chemically related nitroimidazole) may also occur with tinidazole.

Tinidazole Pharmacokinetics

Absorption

Bioavailability

Estimated oral bioavailability >90%.

Rapidly absorbed following oral administration; peak plasma concentrations attained within about 2 hours.

Pharmacokinetic parameters reported with extemporaneous oral suspension containing 66.7 mg/mL (prepared using crushed 500-mg tablets and cherry syrup) in healthy individuals after an overnight fast similar to those reported with tablets swallowed whole under fasted conditions.

Food

Administration with food delays time to peak plasma concentrations by approximately 2 hours and decreases peak plasma concentrations by 10%, but does not affect AUC or elimination half-life.

Distribution

Extent

Well distributed into body tissues and body fluids, including saliva, female reproductive tract, gallbladder, bile, bowel, prostate tissue.

Crosses blood-brain barrier.

Crosses placenta and is distributed into breast milk.

Plasma Protein Binding

12%.

Elimination

Metabolism

Extensively metabolized prior to elimination.

Partially metabolized via oxidation, hydroxylation, and conjugation. Metabolized principally by CYP3A4.

Present in plasma principally as unchanged drug with small amounts of the 2-hydroxymethyl metabolite.

Elimination Route

Eliminated by the liver and kidneys.

Excreted in urine as unchanged drug (20–25%) and in feces (12%).

Removed by hemodialysis. (See Renal Impairment under Dosage and Administration.)

Not known whether removed by CAPD.

Half-life

Approximately 12–14 hours.

Special Populations

Hepatic impairment: Pharmacokinetics not evaluated. Studies using metronidazole (a chemically related nitroimidazole) indicate reduced elimination and increased plasma concentrations in severe hepatic impairment.

Severe renal impairment: Pharmacokinetics not affected by severe impairment (Cl_cr <22 mL/min).

Hemodialysis patients: Clearance increased and elimination half-life decreased (from 12 hours to 4.9 hours) during hemodialysis. (See Renal Impairment under Dosage and Administration.)

Stability

Storage

Oral

Tablets

20–25°C (may be exposed to 15–30°C); protect from light.

Extemporaneous Oral Suspension

Suspension containing 66.7 mg/mL: Stable for 7 days at room temperature. (See Extemporaneous Oral Suspension under Dosage and Administration.)

Actions and Spectrum

• A 5-nitroimidazole antiprotozoal and antibacterial agent.

• Amebicidal, trichomonacidal, and bactericidal.

• Tinidazole is a prodrug that is activated after entry into cells of susceptible organisms where the nitro group is reduced to form short-lived radical anions. Although exact mechanism of action not fully elucidated, the free radicals are believed to interfere with cellular DNA.

• Studies using cell extracts of Trichomonas indicate the nitroimidazole group of tinidazole is reduced within the cells and generates the free nitro radical, which appears to be responsible for the drug’s anti-infective activity. Similarly, the nitro group is reduced within anaerobic bacteria resulting in reactive intermediates; chemically reduced tinidazole releases nitrites and causes damage to purified bacterial DNA in vitro. Specific information on mechanism of activity against Giardia and Entamoeba histolytica not available.

• Protozoa: Active in vitro and in clinical infections against T. vaginalis, G. duodenalis (also known as G. lamblia or G. intestinalis), and E. histolytica. Although clinical importance unclear, appears to have some in vitro activity against Dientamoeba fragilis.

• Anaerobes: Active in vitro against many anaerobic bacteria, including some Bacteroides (e.g., B. fragilis, B. melaninogenicus ), some Clostridium (e.g., C. difficile, C. perfringens ), Fusobacterium, Gardnerella vaginalis, Peptococcus, Peptostreptococcus, Prevotella (including P. amnii, P. timonensis ), and Veillonella.

• Other organisms: Active against some strains of Helicobacter pylori.

• In one study that evaluated in vitro susceptibility of vaginal isolates, Anaerococcus tetradius, Finegoldia magna, Megasphaera-like type I/II, Megeeibacillus indolicus, Peptoniphilus, and Porphyromonas were susceptible to tinidazole; Atopobium vaginae, Lactobacillus (L. gasseri, L. iners, L. jensenii), and Mobiluncus (M. curtisii, M. mulieris) were resistant.

• Potential for development of resistance in Giardia, E. histolytica, or bacteria associated with bacterial vaginosis not evaluated.

• In vitro studies indicate some T. vaginalis isolates with reduced susceptibility to metronidazole also have reduced susceptibility to tinidazole.

• Although clinical importance unclear, H. pylori resistant to tinidazole reported with increasing frequency in some regions of the world; rate of resistance to tinidazole reported to be as high as 87% in some areas.

Advice to Patients

• Importance of taking with food to reduce the incidence of adverse GI effects (e.g., epigastric discomfort).

• Advise patients to avoid alcoholic beverages and preparations containing alcohol or propylene glycol during treatment and for at least 3 days after last dose of tinidazole since abdominal cramps, nausea, vomiting, headaches, and flushing could occur.

• Advise patients that antibacterials (including tinidazole) should not be used to treat viral infections (e.g., the common cold).

• Importance of completing full course of treatment, even if feeling better after a few days. Advise patients that skipping doses or not completing the full course of treatment may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with tinidazole or other antibacterials in the future.

• Advise patients to promptly discontinue tinidazole and contact clinicians if abnormal neurologic signs occur.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and any concomitant illnesses.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of advising patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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