T-zol500 mg

T-zol is a synthetic nitroimidazole antiprotozoal and antibacterial agent used to treat certain parasitic and anaerobic bacterial infections.

Established / FDA-approved uses

• Trichomoniasis – treatment of symptomatic and asymptomatic urogenital trichomoniasis caused by Trichomonas vaginalis in both men and women; sexual partners should be treated concurrently to prevent reinfection.
• Giardiasis – treatment of infections caused by Giardia duodenalis (G. lamblia).
• Intestinal amoebiasis – treatment of infection with Entamoeba histolytica.
• Amoebic liver abscess – treatment of extraintestinal amoebiasis, usually combined with a luminal amoebicide to eradicate intestinal cysts.
• Bacterial vaginosis – treatment in non-pregnant women.

Notes on evidence and combination use

For amoebic liver abscess, T-zol is generally used together with a luminal agent (e.g., a lumenal amoebicide) to clear intestinal colonisation, since T-zol alone does not reliably eradicate luminal cysts. T-zol is not effective against viral infections and should not be used for them.

Each tablet contains Tinidazole INN as the active ingredient, commonly available in 300 mg and 500 mg strengths, along with standard pharmaceutical excipients.

T-zol is a second-generation 5-nitroimidazole compound structurally related to metronidazole. It has a longer plasma half-life than metronidazole, which allows shorter treatment courses and single-dose regimens for several indications.

T-zol is available as oral film-coated tablets and is marketed in Bangladesh and internationally for the treatment of protozoal infections and certain anaerobic bacterial infections.

Nitroimidazole antiprotozoal and antibacterial (5-nitroimidazole derivative)

Tinidazole diffuses into anaerobic protozoa and susceptible anaerobic bacteria, where its nitro group is reduced by intracellular electron-transport (ferredoxin/flavodoxin-type) proteins present only in anaerobic and microaerophilic organisms. This reduction generates reactive intermediates and free radicals that bind to and degrade microbial DNA, inhibiting nucleic acid synthesis and causing cell death.

Tinidazole is rapidly and almost completely absorbed after oral administration, with peak plasma concentrations reached in about 2 hours. It is widely distributed into body tissues and fluids, including the CNS, and has an elimination half-life of approximately 12–14 hours, longer than metronidazole. It is metabolised in the liver (partly via CYP3A4) and excreted in urine and faeces as unchanged drug and metabolites.

T-zol tablets should be swallowed whole with a full glass of water and taken with food or milk to minimise nausea and stomach upset. Tablets should not be crushed or chewed unless advised otherwise. Doses should be taken at approximately the same time each day when a multi-day course is prescribed, and the complete course must be finished even if symptoms improve early.

T-zol shares interaction risks common to nitroimidazoles:

• Alcohol: concurrent use can cause a disulfiram-like reaction (flushing, tachycardia, nausea, vomiting); alcohol must be avoided during treatment and for 3 days after the last dose. See Contraindications and Precautions.
• Disulfiram: concurrent use, or use within 2 weeks of disulfiram, is contraindicated due to reports of psychotic reactions and confusion (see Contraindications).
• Warfarin and other oral anticoagulants: T-zol can inhibit hepatic metabolism of warfarin, potentiating anticoagulant effect; prothrombin time/INR should be monitored and dose adjusted if co-administered.
• CYP3A4 inducers (e.g., phenytoin, phenobarbital, rifampicin): may accelerate T-zol metabolism and reduce its plasma levels and efficacy.
• CYP3A4 inhibitors (e.g., cimetidine, ketoconazole): may increase T-zol plasma concentration and prolong its half-life, increasing the risk of adverse effects.
• Lithium and cyclosporine: T-zol may increase plasma levels of these drugs; monitor levels/toxicity when co-administered.

Most adverse effects of T-zol are mild and self-limited.

Common

• Unpleasant metallic or bitter taste
• Nausea, vomiting, anorexia, epigastric discomfort
• Headache and dizziness
• Dark or discoloured urine

Less common / serious (seek medical advice)

• Peripheral neuropathy (numbness or tingling of extremities) with prolonged or repeated courses
• Seizures or transient CNS disturbances (rare) – see Precautions
• Blood dyscrasias such as leukopenia (rare) with prolonged/repeated courses
• Allergic reactions including rash, pruritus, and rarely angioedema or anaphylaxis

Pregnancy: T-zol is contraindicated in the first trimester of pregnancy. In the second and third trimesters, T-zol should be used only if clearly needed and if the potential benefit justifies the potential risk to the fetus; a physician must be consulted before use.

Lactation: T-zol is excreted in breast milk in concentrations similar to plasma. Breastfeeding should be interrupted during treatment and for 3 days after the last dose (for single/short-dose regimens) to minimise infant exposure; consult a physician for individualised advice.

• Alcohol: avoid alcohol during T-zol therapy and for at least 3 days after the last dose because of the risk of a disulfiram-like reaction.
• CNS disease/seizure history: use with caution in patients with a history of seizure disorders or CNS disease; discontinue if abnormal neurological signs occur.
• Blood dyscrasias: use with caution in patients with, or a history of, blood dyscrasias; monitor complete blood count (CBC) in patients receiving prolonged or repeated courses.
• Hepatic impairment: use with caution; dose reduction may be needed in severe hepatic impairment as metabolism is reduced (see Use in Special Populations).
• Antimicrobial stewardship: take T-zol exactly as prescribed by your physician; do not stop, extend, skip doses, or share this medicine with others without medical advice. T-zol is not effective against viral infections. Treat sexual partner(s) concurrently for trichomoniasis to prevent reinfection.

Reported overdose experience with T-zol is limited. Expected features of significant overdose include nausea, vomiting, and abdominal discomfort. There is no specific antidote.

In case of suspected overdose, seek immediate medical attention or contact a poison control centre/emergency services. Management is supportive and symptomatic; T-zol is dialysable, so haemodialysis may be considered in severe cases under medical supervision.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

Renal impairment

No dose adjustment is generally needed in mild-to-moderate renal impairment. In patients on haemodialysis, T-zol is significantly removed by dialysis; an additional dose equivalent to one-half the recommended dose should be given after each dialysis session, on the advice of a physician.

Hepatic impairment

T-zol is metabolised by the liver; use with caution in hepatic impairment, and a reduced dose or extended dosing interval may be required in severe hepatic dysfunction.

Elderly

No significant differences in safety or efficacy have been reported in elderly patients with normal renal and hepatic function compared with younger adults; use standard adult dosing with monitoring for tolerability.

Paediatric use

See Pediatric Uses for age-specific recommendations.

Duration of T-zol therapy depends on the indication: a single dose for trichomoniasis and giardiasis, 3 days for intestinal amoebiasis, 3–5 days for amoebic liver abscess, and 2–5 days for bacterial vaginosis (depending on the regimen chosen). The complete prescribed course must be finished even if symptoms resolve earlier.

Nitroimidazoles; antiprotozoal agents; antibacterial agents (anti-anaerobic)

Inside susceptible anaerobic protozoa and bacteria, the nitro group of Tinidazole is reduced by intracellular transport proteins unique to anaerobic metabolism. The resulting reactive nitroso and radical intermediates bind covalently to microbial DNA, causing strand breakage and destabilisation of the helical structure, which inhibits nucleic acid synthesis and leads to cell death of the organism.

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T-zol is approved for use in children 3 years of age and older for giardiasis and intestinal amoebiasis/amoebic liver abscess, using weight-based dosing of 50 mg/kg (maximum 2 g) as detailed in Dosage and Administration.

Safety and efficacy of T-zol for trichomoniasis and bacterial vaginosis have not been established in paediatric patients, and T-zol is not recommended for children under 3 years of age for any indication due to insufficient safety and efficacy data in this age group.