Tinidazole

Pronunciation

Pronunciation: tye-NYE-da-zole
Class: Antiprotozoal, Antibacterial agent

Trade Names

Tindamax
- Tablets 250 mg
- Tablets 500 mg

Pharmacology

Unknown; however, may be related to action of free nitro radical generated as a result of reduction by cell extracts. Tinidazole also causes DNA base changes in bacterial cells and DNA strand breakage in mammalian cells.

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Pharmacokinetics

Absorption

Rapid and complete after oral administration. C max is 47.7 mcg/mL; T max is 1.6 h; AUC is 901.6 mcg•h/mL at 72 h. Steady-state conditions reached in 2.5 to 3 days.

Distribution

Distributed to virtually all tissues and body fluid and crosses the blood-brain barrier. Vd is about 50 L. Protein binding is 12%.

Metabolism

Partly metabolized by oxidation, hydroxylation, and conjugation. Metabolized by CYP3A4.

Elimination

Plasma t ½ is 12 to 14 h. Elimination t ½ is 13.2 h. About 20% to 25% excreted unchanged in urine and 12% in feces.

Indications and Usage

Treatment of trichomoniasis caused by Trichomonas vaginalis , giardiasis caused by Giardiasis duodenalis , and amebiasis caused by Entamoeba histolytica ; treatment of bacterial vaginosis in nonpregnant women.

Contraindications

First trimester of pregnancy; breast-feeding mothers; hypersensitivity to nitroimidazole derivatives (eg, metronidazole) or to any component of product.

Dosage and Administration

Amebiasis
Intestinal Adults

PO 2 g dose daily for 3 days with food.

Children older than 3 yr of age

PO 50 mg/kg daily (max, 2 g/day) for 3 days with food.

Amebic Liver Abscess Adults

PO 2 g dose daily for 3 to 5 days with food.

Children older than 3 yr of age

PO 50 mg/kg daily (max, 2 g/day) for 3 to 5 days with food.

Bacterial Vaginosis
Adults

PO Nonpregnant women: 2 g once daily for 2 days with food or 1 g once daily for 5 days with food.

Giardiasis
Adults

PO Single 2 g dose with food.

Children older than 3 yr of age

PO Single 50 mg/kg (max, 2 g) dose with food.

Trichomoniasis
Adults

PO Single 2 g dose with food. Treat sexual partners at same time.

Renal Function Impairment

PO No dosage adjustment are needed in severe renal failure (CrCl less than 22 mL/min). However, in hemodialysis patients, if administered on the same day as or prior to hemodialysis, it is recommended that an additional dose, equivalent to 50% of the recommended dose, be administered after the end of hemodialysis.

General Advice

  • Compounding of oral suspension: pulverize four 500 mg tablets and add approximately 10 mL of cherry syrup to the powder and mix until smooth. Transfer suspension to a graduated amber container, using several small rinses of cherry syrup to transfer remaining drug for a final volume of 30 mL.
  • Shake compounded suspension well before use.

Storage/Stability

Store tablets and extemporaneous suspension at controlled room temperature (59° to 86°F). Protect from light. Discard any unused suspension after 7 days.

Drug Interactions

The following interactions were reported with metronidazole, which is chemically-related to tinidazole.

Alcohol, disulfiram

Avoid during tinidazole use and for 3 days afterward because cramps, nausea, vomiting, headaches, and flushing may occur.

Anticoagulants, oral (eg, warfarin)

Anticoagulant effects may be increased. Anticoagulant dose may need to be adjusted during coadministration and for up to 8 days after discontinuation.

Cholestyramine

Bioavailability of tinidazole may be decreased.

Cyclosporine, lithium, tacrolimus

Levels may be elevated by tinidazole, increasing the risk of toxicity.

Drugs that induce CYP3A4 (eg, fosphenytoin, phenobarbital, phenytoin, rifampin)

May increase metabolism of tinidazole, decreasing plasma levels and therapeutic effect.

Drugs that inhibit CYP3A4 (eg, cimetidine, ketoconazole)

May prolong t ½ and decrease tinidazole Cl, increasing plasma levels and risk of adverse reactions.

Fluorouracil

Cl may be decreased by tinidazole, increasing the risk of adverse reactions.

Fosphenytoin, phenytoin

The t ½ may be prolonged and Cl reduced by tinidazole, increasing the risk of adverse reactions.

Oxytetracycline

Therapeutic effect of tinidazole may be decreased.

Laboratory Test Interactions

May interfere with chemical analysis for AST, ALT, LDH, triglycerides, and hexokinase glucose; zero values may occur. All assay interferences have involved enzymatic coupling of the assay to oxidation-reduction of nicotinamide adenine dinucleotide.

Adverse Reactions

Cardiovascular

Palpitation.

CNS

Decreased appetite (more than 2%); weakness/fatigue/malaise (2%); dizziness, headache (1%); ataxia, convulsions, drowsiness, giddiness, insomnia, transient peripheral neuropathy (including numbness and paresthesia), vertigo.

Dermatologic

Erythema multiforme, Stevens-Johnson syndrome (postmarketing).

GI

Metallic bitter taste (6%); nausea (5%); anorexia (3%); flatulence (more than 2%); dyspepsia/cramps/epigastric discomfort, vomiting (2%); constipation (1%); diarrhea, oral candidiasis, stomatitis, tongue discoloration.

Genitourinary

Candida vaginitis (5%); menorrhagia, painful urination, pelvic pain, urine abnormality, UTI, vaginal odor, vulvovaginal discomfort (more than 2%); dark urine, increased vaginal discharge.

Hematologic-Lymphatic

Transient leukopenia, transient neutropenia.

Hepatic

Hepatic abnormalities, including elevated transaminase levels.

Hypersensitivity

Angioedema, burning sensation, dryness of mouth, flushing, pruritus, rash, salivation, sweating, thirst, urticaria.

Musculoskeletal

Arthralgia, arthritis, myalgia.

Respiratory

Upper respiratory tract infection (more than 2%).

Miscellaneous

Candida overgrowth.

Precautions

Warnings

Carcinogenicity has been seen in mice and rats treated chronically with another nitroimidazole (metronidazole).


Pregnancy

Category C . Contraindicated in the first trimester.

Lactation

Excreted in breast milk. Interrupt breast-feeding during therapy and for 3 days following the last dose.

Children

Other than use in giardiasis and amebiasis in children older than 3 yr of age, safety and efficacy not established.

Elderly

Use with caution because of the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant diseases or other drug therapy.

Hepatic Function

Use with caution.

Blood dyscrasias

Use with caution in patients with history of blood dyscrasias.

Neurologic effects

Convulsive seizures and peripheral neuropathy have occurred. Use with caution.

Overdosage

Symptoms

No reported overdoses.

Patient Information

  • Instruct patient to take exactly as prescribed and not to change the dose or discontinue therapy unless advised by health care provider.
  • Advise patient to take prescribed dose with food to minimize GI adverse reactions.
  • Caution patient to avoid alcoholic beverages while taking tinidazole and for at least 3 days following completion of therapy.
  • Advise patient that metallic taste is a common adverse reaction of therapy but that this will resolve when therapy has been completed.
  • Advise patient to report any other bothersome adverse reactions to health care provider and to immediately report any abnormal neurologic signs or symptoms (eg, abnormal skin sensations, extremity numbness, seizures).

Copyright © 2009 Wolters Kluwer Health.

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