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Tinidazole


General


Pronunciation

(tye NI da zole)


Brand Names: U.S.

  • Tindamax

Indications


Use: Labeled Indications

Treatment of trichomoniasis caused by T. vaginalis; treatment of giardiasis caused by G. duodenalis (G. lamblia); treatment of intestinal amebiasis and amebic liver abscess caused by E. histolytica; treatment of bacterial vaginosis caused by Bacteroides spp, Gardnerella vaginalis, and Prevotella spp in nonpregnant females


Contraindications


Hypersensitivity to tinidazole, nitroimidazole derivatives (including metronidazole), or any component of the formulation; pregnancy (1st trimester); breast-feeding


ALERT: U.S. Boxed Warning

Carcinogenic:

Carcinogenicity has been seen in mice and rats treated chronically with metronidazole, another nitroimidazole agent. Although such data have not been reported for tinidazole, the 2 drugs are structurally related and have similar biologic effects. Reserve its use only for the conditions for which it is indicated.


Dosing and Administration


Dosing: Adult

Amebiasis, intestinal: Oral: 2 g/day for 3 days

Amebiasis, liver abscess: Oral: 2 g/day for 3-5 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

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])


Dosing: Geriatric

Refer to adult dosing.


Dosing: Pediatric

Amebiasis, intestinal: Oral: Children >3 years: 50 mg/kg/day for 3 days (maximum dose: 2 g/day)

Amebiasis, liver abscess: Oral: Children >3 years: 50 mg/kg/day for 3-5 days (maximum dose: 2 g/day)

Giardiasis: Oral: Children >3 years: 50 mg/kg as a single dose (maximum dose: 2 g)

Prophylaxis against sexually transmitted diseases following sexual assault (off-label use): Adolescents: Refer to adult dosing.


Dosing: Renal Impairment

No dosage adjustment necessary.

Hemodialysis: 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 a dialysis days.


Dosing: Hepatic Impairment

No dosage adjustment provided in manufacturer 's labeling (has not been studied). Use with caution.


Administration

Administer with food


Dietary Considerations

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


Storage

Store at controlled room temperature of 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F). Protect from light.


Dosage Forms/Strengths


Dosage Forms

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

Tablet, Oral:

Tindamax: 250 mg [scored; contains fd&c red #40 aluminum lake, fd&c yellow #6 aluminum lake]

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

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

Generic: 250 mg, 500 mg


Extemporaneously Prepared

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 to a uniform paste; mix while adding cherry syrup in incremental proportions to almost 30 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 30 mL. Label shake well". Stable for 7 days.

Tindamax ‚ ® prescribing information, Mission Pharmacal Company, San Antonio, TX, 2007. Available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021618s003lbl.pdf

Drug Interactions

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

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


Lab Test Interferences


Test Interactions

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


Adverse Reactions


1% to 10%:

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

Endocrine & metabolic: Menorrhagia (>2%)

Gastrointestinal: Metallic/bitter taste (4% to 6%), nausea (3% to 5%), anorexia (2% to 3%), appetite decreased (>2%), flatulence (>2%), dyspepsia/cramps/epigastric discomfort (1% to 2%), vomiting (1% to 2%), constipation ( ≤1%)

Genitourinary: Candida vaginitis (5%), painful urination (>2%), pelvic pain (>2%), urine abnormality (>2%), vaginal odor (>2%), vulvovaginal discomfort (>2%)

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

Renal: Urinary tract infection (>2%)

Respiratory: Upper respiratory tract infection (>2%)

Frequency not defined:

Cardiovascular: Flushing, palpitation

Central nervous system: Ataxia, coma (rare), confusion (rare), depression (rare), drowsiness, fever, giddiness, insomnia, seizure, vertigo

Dermatologic: Angioedema, pruritus, rash, urticaria

Gastrointestinal: Abdominal pain, diarrhea, furry tongue (rare), oral candidiasis, salivation, stomatitis, thirst, tongue discoloration, xerostomia

Genitourinary: Urine darkened, vaginal discharge increased

Hematologic: Leukopenia (transient), neutropenia (transient), thrombocytopenia (reversible; rare)

Hepatic: Transaminases increased

Neuromuscular & skeletal: Arthralgia, arthritis, myalgia, peripheral neuropathy (transient, includes numbness and paresthesia)

Respiratory: Bronchospasm (rare), dyspnea (rare), pharyngitis (rare)

Miscellaneous: Burning sensation, Candida overgrowth, diaphoresis

Postmarketing and/or case reports: Acute hypersensitivity reaction (severe), erythema multiforme, Stevens-Johnson syndrome


Warnings/Precautions


Concerns related to adverse effects:

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

- CNS effects: Seizures and peripheral neuropathy have been reported with tinidazole and other nitroimidazole derivatives; use with caution in patients with CNS diseases.

- 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:

- Amebiasis: Appropriate use: When used for amebiasis, not indicated for the treatment of asymptomatic cyst passage.

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

- Hepatic impairment: Use with caution in patients with current or a history of hepatic impairment.


Pregnancy Risk Factor

C


Pregnancy Considerations

The manufacturer contraindicates use of tinidazole during the first trimester of pregnancy. Adverse events have been observed in some animal reproduction studies. Tinidazole crosses the human placenta and enters the fetal circulation. 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]).


Actions


Pharmacology

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


Absorption

Rapid and complete


Distribution

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


Metabolism

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


Excretion

Urine (20% to 25%); feces (12%)


Time to Peak

1.6 hours (fasting, delayed ~2 hours when given with food)


Half-Life Elimination

13 hours


Protein Binding

12%


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience nausea, vomiting, or bad taste. Have patient report immediately to prescriber burning or numbness feeling, seizures, vaginitis, bruising, or bleeding (HCAHPS).

- Educate patient about signs of a significant reaction (eg, 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. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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