Tinidazole

Pharmacologic Category

Amebicide; Antibiotic, Miscellaneous; Antiprotozoal, Nitroimidazole

Dosing: Adult

Amebiasis, intestinal: Oral: 2 g once daily for 3 days

Amebiasis, liver abscess: Oral: 2 g once daily for 3 to 5 days

Bacterial vaginosis: Oral: 2 g once daily for 2 days or 1 g once daily for 5 days

Bacterial vaginosis, recurrent (off-label dose): Oral: 500 mg twice daily for 7 days followed by intravaginal therapy with boric acid, followed by intravaginal metronidazole suppressive therapy (CDC [Workowski 2015])

Giardiasis: Oral: 2 g as a single dose

Helicobacter pylori eradication (off-label use): Oral:

American College of Gastroenterology guidelines (Chey 2007; Chey 2017):

Concomitant regimen: 500 mg twice daily in combination with clarithromycin 500 mg twice daily, amoxicillin 1 g twice daily, and a standard-dose proton pump inhibitor twice daily; continue regimen for 10 to 14 days.

Sequential regimen: Amoxicillin 1 g twice daily plus a standard-dose proton pump inhibitor twice daily for 5 to 7 days; then follow with clarithromycin 500 mg twice daily, tinidazole 500 mg twice daily, and a standard-dose proton pump inhibitor daily for 5 to 7 days.

Hybrid regimen: Amoxicillin 1 g twice daily plus a standard-dose proton pump inhibitor twice daily for 7 days; then follow with amoxicillin 1 g twice daily, clarithromycin 500 mg twice daily, tinidazole 500 mg twice daily, and a standard-dose proton pump inhibitor twice daily for 7 days.

Prophylaxis against sexually transmitted diseases following sexual assault (off-label use): Oral: 2 g as a single dose in combination with azithromycin plus ceftriaxone (CDC [Workowski 2015])

Trichomoniasis: Oral: 2 g as a single dose; sexual partners should be treated at the same time

Trichomoniasis, persistent or recurrent (ie, treatment failure of nitroimidazole [eg, metronidazole]) (index case; treatment of sex partner; off-label dose): Oral: 2 g once daily for 7 days (CDC [Workowski 2015])

Urethritis, nongonococcal (recurrent or persistent urethritis in men who have sex with women and who live in regions where T. vaginalis is prevalent; off-label use): Oral: 2 g as a single dose. Note: Compliance with initial regimen and lack of reexposure to an untreated sex partner should be excluded prior to use (CDC [Workowski 2015])

* See Dosage and Administration in AHFS Essentials for additional information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment: Adult

No dosage adjustment necessary.

Hemodialysis: An additional dose equal to ½ the usual dose, should be administered at the end of hemodialysis if tinidazole is administered prior to hemodialysis on a dialysis day.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); use with caution.

Dosing: Pediatric

Amebiasis, intestinal: Children >3 years and Adolescents: Oral: 50 mg/kg/dose once daily for 3 days; maximum daily dose: 2,000 mg/day; for patients with severe and extraintestinal disease, administer for 5 days (Red Book [AAP 2018]).

Amebiasis, liver abscess: Children >3 years and Adolescents: Oral: 50 mg/kg/day for 3 to 5 days; maximum daily dose: 2,000 mg/day.

Bacterial vaginosis: Adolescents: Oral: 2,000 mg once daily for 2 days or 1,000 mg once daily for 5 days (CDC [Workowski 2015]).

Blastocystis hominis infection: Limited data available: Children ≥3 years and Adolescents: Oral: 50 mg/kg as a single dose; maximum dose: 2,000 mg (Red Book [AAP 2018]).

Giardiasis: Children >3 years and Adolescents: Oral: 50 mg/kg as a single dose; maximum dose: 2,000 mg.

Helicobacter pylori infection: Limited data available: Children >3 years and Adolescents: Oral: 20 mg/kg/day in 1 to 2 divided doses for 5 to 7 days in combination with other agents; some studies have used a longer duration of 2 to 6 weeks; maximum daily dose: 1,000 mg/day (Francavilla 2005; Moshkowitz 1998; Nijevitch 2000; Oderda 1992).

Trichomoniasis (CDC [Workowski 2015]):

Primary therapy: Adolescents: Oral: 2,000 mg as a single dose; sexual partners should be treated concomitantly.

Persistent, recurrent, after metronidazole treatment failure: Adolescents: Oral: 2,000 mg once daily for 7 days. Note: Ensure reinfection has not occurred prior to initiation.

Urethritis, nongonococcal (recurrent or persistent urethritis in males who have sex with females and who live in regions where T. vaginalis is prevalent): Adolescents: Oral: 2,000 mg as a single dose. Note: Compliance with initial regimen and lack of reexposure to an untreated sex partner should be excluded prior to use (CDC [Workowski 2015]).

Dosing: Renal Impairment: Pediatric

Children >3 years and Adolescents: No dosage adjustment necessary

Hemodialysis: Approximately 43% removed during a 6-hour session; an additional dose equal to 1/2 the usual dose should be administered at the end of hemodialysis if tinidazole is administered prior to hemodialysis on dialysis days

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use with caution.

Use: Labeled Indications

Amebiasis: Treatment of intestinal amebiasis and amebic liver abscess caused by Entamoeba histolytica in adults and pediatric patients older than 3 years.

Limitations of use: Not indicated for the treatment of asymptomatic cyst passage.

Bacterial vaginosis: Treatment of bacterial vaginosis (formerly referred to as Haemophilus vaginitis, Gardnerella vaginitis, nonspecific vaginitis, or anaerobic vaginosis) in adult women.

Giardiasis: Treatment of giardiasis caused by Giardia duodenalis (also termed Giardia lamblia) in adults and pediatric patients older than 3 years.

Trichomoniasis: Treatment of trichomoniasis caused by Trichomonas vaginalis; treat partners of infected patients simultaneously to prevent reinfection.

* See Uses in AHFS Essentials for additional information.

Use: Off-Label: Adult

Helicobacter pylori eradicationLevel of Evidence [G]

Based on the American College of Gastroenterology Clinical Guideline for the Treatment of Helicobacter pylori Infection, tinidazole is an effective and recommended component of a multiple-drug regimen for the treatment of this condition.

Prophylaxis against sexually transmitted diseases following sexual assaultLevel of Evidence [G]

Based on the Centers for Disease Control and Prevention (CDC) sexually transmitted diseases treatment guidelines, tinidazole, in combination with ceftriaxone and azithromycin, is a recommended regimen for prophylaxis against sexually transmitted diseases following sexual assault in adolescents and adults.

Urethritis, nongonococcal (persistent and recurrent)Level of Evidence [G]

Based on the CDC sexually transmitted diseases treatment guidelines, tinidazole is effective and recommended as treatment for recurrent and persistent urethritis for men who have sex with women and who live in areas where T. vaginalis is prevalent. Compliance with initial regimen and lack of reexposure to an untreated sex partner should be excluded prior to use. Sex partners should be referred for evaluation and appropriate treatment.

Level of Evidence Definitions

Level of Evidence Scale

Comparative Efficacy

• TINIDAZOLE

Clinical Practice Guidelines

Sexually-Transmitted Disease:

CDC, “Sexually Transmitted Diseases Treatment Guidelines,” June 2015.

Helicobacter pylori Infection:

“ACG Guideline on the Management of Helicobacter pylori Infection,” August 2007

“ACG Guideline on the Treatment of Helicobacter pylori Infection,” February 2017

Administration: Oral

Administer with food.

Administration: Pediatric

Oral: Administer with food to minimize gastrointestinal adverse effects.

Dietary Considerations

The manufacturer recommends that ethanol be avoided during treatment and for 3 days after therapy is complete.

Storage/Stability

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light.

Extemporaneously Prepared

67 mg/mL oral suspension:

A 67 mg/mL suspension may be made with tablets and cherry syrup. Crush four 500 mg tablets in a mortar and reduce to a fine powder. Add 10 mL cherry syrup and mix until smooth; transfer to a graduated bottle. Rinse mortar with cherry syrup several times to transfer any remaining drug into the bottle, and add additional cherry syrup to the bottle to a final volume of 30 mL. Label "shake well". Stable for 7 days at room temperature.

Tindamax (tinidazole) [prescribing information]. San Antonio, TX: Mission Pharmacal Company; June 2019.

Medication Patient Education with HCAHPS Considerations

What is this drug used for?

• It is used to treat infections.

Frequently reported side effects of this drug

• Nausea

• Bad taste

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Burning or numbness feeling

• Seizures

• Vaginal pain, itching, and discharge

• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Contraindications

Hypersensitivity to tinidazole, nitroimidazole derivatives, or any component of the formulation.

Warnings/Precautions

Concerns related to adverse effects:

• Carcinogenic: [US Boxed Warning]: Carcinogenicity has been observed with another nitroimidazole derivative (metronidazole) in animal studies; use should be reserved for approved indications only. Avoid chronic use.

• CNS effects: Seizures and peripheral neuropathy (eg, extremity numbness and paresthesia) have been reported with tinidazole and other nitroimidazole derivatives; discontinue treatment if abnormal neurologic signs or symptoms occur.

• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD), pseudomembranous colitis, and/or vaginal candidiasis. CDAD has been observed >2 months postantibiotic treatment.

Disease-related concerns:

• Blood dyscrasias: Use with caution in patients with current or a history of blood dyscrasias.

• Hepatic impairment: Use with caution in patients with hepatic impairment.

* See Cautions in AHFS Essentials for additional information.

Pregnancy Considerations

Tinidazole crosses the human placenta and enters the fetal circulation (Karhunen 1984).

The safety of tinidazole for the treatment of bacterial vaginosis or trichomoniasis in pregnant women has not been well evaluated. Other agents are preferred for use during pregnancy (CDC [Workowski 2015]).

Breast-Feeding Considerations

Tinidazole is present in breast milk.

Breast milk concentrations of tinidazole are similar to those in the maternal serum and decline by 72 hours after the last maternal dose (Evaldson 1985; Männistö 1983; Wood 1982). Due to the potential for adverse events, the manufacturer does not recommend breastfeeding during therapy or for 72 hours after the last tinidazole dose.

Lexicomp Pregnancy & Lactation, In-Depth

• Tinidazole

Briggs' Drugs in Pregnancy & Lactation

• Tinidazole

Adverse Reactions

1% to 10%:

Central nervous system: Fatigue (≤2%), malaise (≤2%), dizziness (≤1%), headache (≤1%)

Dermatologic: Body odor (vaginal: >2%)

Endocrine & metabolic: Hypermenorrhea (>2%)

Gastrointestinal: Dysgeusia (bitter taste, metallic taste: 4% to 6%), nausea (3% to 5%), anorexia (2% to 3%), decreased appetite (>2%), flatulence (>2%), dyspepsia (≤2%), abdominal cramps (≤2%), epigastric distress (≤2%), vomiting (1% to 2%), constipation (≤1%)

Genitourinary: Vulvovaginal candidiasis (5%), dysuria (>2%), pelvic pain (>2%), urine abnormality (>2%), vulvovaginal disease (discomfort) (>2%)

Neuromuscular & skeletal: Weakness (1% to 2%)

Renal: Urinary tract infection (>2%)

Respiratory: Upper respiratory tract infection (>2%)

Frequency not defined:

Cardiovascular: Flushing, palpitations

Central nervous system: Ataxia, burning sensation, drowsiness, insomnia, peripheral neuropathy (transient; includes numbness and paresthesia), seizure, vertigo

Dermatologic: Diaphoresis, pruritus, skin rash, urticaria

Endocrine & metabolic: Increased thirst

Gastrointestinal: Abdominal pain, diarrhea, oral candidiasis, salivation, stomatitis, tongue discoloration, xerostomia

Genitourinary: Dark urine, vaginal discharge

Hematologic & oncologic: Leukopenia (transient), neutropenia (transient)

Hepatic: Increased serum transaminases

Hypersensitivity: Angioedema

Infection: Candidiasis (overgrowth)

Neuromuscular & skeletal: Arthralgia, arthritis, myalgia

Miscellaneous: Fever

<1%, postmarketing, and/or case reports: Bronchospasm, coma, confusion, depression, dyspnea, erythema multiforme, hairy tongue, hypersensitivity reaction (acute, severe), pharyngitis, Stevens-Johnson syndrome, thrombocytopenia (reversible)

* See Cautions in AHFS Essentials for additional information.

Allergy and Idiosyncratic Reactions

• Nitroimidazole Allergy

Metabolism/Transport Effects

Substrate of CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions Open Interactions

Alcohol (Ethyl): Tinidazole may enhance the adverse/toxic effect of Alcohol (Ethyl). A disulfiram-like reaction may occur. Risk X: Avoid combination

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination

Disulfiram: Tinidazole may enhance the adverse/toxic effect of Disulfiram. Risk X: Avoid combination

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Risk D: Consider therapy modification

Food Interactions

Peak antibiotic serum concentration lowered and delayed, but total drug absorbed not affected. Management: Administer with food.

Test Interactions

May interfere with AST, ALT, triglycerides, glucose, and LDH testing

Advanced Practitioners Physical Assessment/Monitoring

Assess results of culture and sensitivity tests prior to beginning therapy. Obtain CBC with differential and liver function tests in patients on prolonged therapy. Assess patient for peripheral neuropathy or seizure activity; discontinue drug if abnormal neurologic signs develop. Assess for effectiveness of treatment. Test for C. difficile if patient develops diarrhea.

Nursing Physical Assessment/Monitoring

Check lab results and report abnormalities. Monitor for severe or bloody diarrhea and send a specimen to the lab for C. difficile. Monitor for improvement with infection. Monitor patient for numbness or paresthesia of extremities, seizures, or other CNS abnormalities; instruct patient to report.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet, Oral:

Tindamax: 500 mg [DSC] [scored; contains fd&c red #40 aluminum lake, fd&c yellow #6 aluminum lake]

Generic: 250 mg, 500 mg

Anatomic Therapeutic Chemical (ATC) Classification

• J01XD02
• P01AB02

Generic Available (US)

Yes

Pricing: US

Tablets (Tinidazole Oral)

250 mg (per each): $5.08

500 mg (per each): $10.15 - $12.69

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

After diffusing into the organism, it is proposed that tinidazole causes cytotoxicity by damaging DNA and preventing further DNA synthesis.

Pharmacodynamics/Kinetics

Absorption: Rapid and complete

Distribution: Vd: ~50 L; distributes to most body tissues and fluids; crosses the blood-brain barrier

Protein binding: 12%

Metabolism: Hepatic via CYP3A4 (primarily); undergoes oxidation, hydroxylation and conjugation; forms a metabolite

Half-life elimination: 13.2 hours

Time to peak, plasma: 1.6 hours (fasting, delayed ~2 hours when given with food)

Excretion: Urine (~20% to 25%); feces (~12%)

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Dental Health Professional Considerations

Although this drug is a member of the metronidazole family, there is no specific dental indication for its use. Just as with metronidazole, alcohol in any form is contraindicated while the patient is on this medication because of the danger of a disulfiram-type reaction.

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Xerostomia and changes in salivation (normal salivary flow resumes upon discontinuation), metallic/bitter taste, oral candidiasis, tongue discoloration, stomatitis, furry tongue. See Dental Health Professional Considerations.

Effects on Bleeding

No information available to require special precautions

FDA Approval Date

May 17, 2004

References

American Academy of Pediatrics (AAP). In: Kimberlin DW, Brady MT, Jackson MA, Long SA, eds. Red Book: 2018 Report of the Committee on Infectious Diseases. 31st ed. Itasca, IL: American Academy of Pediatrics; 2018.

Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG clinical guideline: treatment of Helicobacter pylori infection. Am J Gastroenterol. 2017;112(2):212-239. doi: 10.1038/ajg.2016.563.[PubMed 28071659]

Chey WD, Wong BC; Practice Parameters Committee of the American College of Gastroenterology. American College of Gastroenterology guideline on the management of Helicobacter pylori infection. Am J Gastroenterol. 2007;102(8):1808-1825. doi: 10.1111/j.1572-0241.2007.01393.x.[PubMed 17608775]

Evaldson GR, Lindgren S, Nord CE, Rane AT. Tinidazole milk excretion and pharmacokinetics in lactating women. Br J Clin Pharmacol. 1985;19(4):503-507. doi: 10.1111/j.1365-2125.1985.tb02676.x.[PubMed 4039599]

Francavilla R, Lionetti E, Castellaneta SP, et al. Improved efficacy of 10-day sequential treatment for Helicobacter pylori eradication in children: a randomized trial. Gastroenterology. 2005;129:1414-1419.[PubMed 16285942]

Karhunen M. Placental transfer of metronidazole and tinidazole in early human pregnancy after a single infusion. Br J Clin Pharmacol. 1984;18(2):254-257. doi: 10.1111/j.1365-2125.1984.tb02465.x.[PubMed 6487467]

Lamp KC, Freeman CD, Klutman NE, “Pharmacokinetics and pharmacodynamics of the nitroimidazole antimicrobials,” Clin Pharmacokinet, 1999, 36(5):353-73.[PubMed 10384859]

Li XQ, Bjorkman A, Andersson TB, et al, “Identification of Human Cytochrome P(450)s that Metabolise Anti-Parasitic Drugs and Predictions of in vivo Drug Hepatic Clearance from in vitro Data,” Eur J Clin Pharmacol, 2003, 59(5-6):429-42.[PubMed 12920490]

Männistö PT, Karhunen M, Koskela O, Suikkari AM, Mattila J, Haataja H. Concentrations of tinidazole in breast milk. Acta Pharmacol Toxicol (Copenh). 1983;53(3):254-256.[PubMed 6356785]

Moshkowitz M, Reif S, Brill S, Ringel Y, Arber N, Halpern Z, Bujanover Y. One-week triple therapy with omeprazole, clarithromycin, and nitroimidazole for Helicobacter pylori infection in children and adolescents. Pediatrics. 1998;102(1):e14.[PubMed 9651466]

Nijevitch AA, Farztdinov KM, Sataev VU, et al. Helicobacter pylori infection in childhood: results of management with ranitidine bismuth citrate plus amoxicillin and tinidazole. Journal of Gastroenterology and Hepatology. 2000;15:1243-1250.[PubMed 11129216]

Odera G, Vaira D, Ainley C, et al. Eighteen month follow up of Helicobacter pylori positive children treated with amoxicillin and tinidazole. Gut. 1992;33:1328-1330.[PubMed 1446854]

Tindamax (tinidazole) [prescribing information]. San Antonio, TX: Mission Pharmacal Company; June 2019.

Wood BA, Faulkner JK, Monro AM. The pharmacokinetics, metabolism and tissue distribution of tinidazole. J Antimicrob Chemother. 1982;10(suppl A):43-57. doi: 10.1093/jac/10.suppl_a.43.[PubMed 7118775]

Workowski KA, Bolan GA; Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2015 [published correction appears in MMWR Recomm Rep. 2015;64(33):924]. MMWR Recomm Rep. 2015;64(RR-03):1-137.[PubMed 26042815 ]

Brand Names: International

Amibiol (CO); Asgin (TW); Astiba (ET); Cachtin (ET); Dyzole (NZ); Estovit-T (MX); Fasdol (EC); Fasigin (IT, PL); Fasigyn (AE, AR, AT, BE, BG, BH, BZ, CH, CL, CO, CR, DO, EG, GR, GT, HN, IN, JO, KW, LB, LU, MX, NI, NL, PA, PE, PK, PT, QA, RU, SA, SE, SG, SI, SV, TH, UA, UY, VE, VN, ZA); Fasigyne (FR); Induken (CR, DO, GT, HN, MX, NI, PA, SV); Jie Li (CN); Protocide (IL); Protogyn (AE, BD, JO, LB, QA, SA); Protozole (BH, EG, ET); Simplotan (AT); Su (TW); T-Zol (BD); Tindol (MY); Tiniba (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZM, ZW); Tinidan (EC); Tinidazine (KR); Tinidol (EG); Tinirem (ET, TR); Tinizol (BD, RO); Tinoral (BR); Tiprogyn (RO); Tricolam (ES); Tricor 500 (PY); Trinigyn (BB, BM, BS, GY, JM, SR, TT); Troxxil (PY)

Last Updated 4/16/20