Tinidazole

Tinidazole is a Nitroimidazole derivative belonging to Antiprotozoal / Antibiotic.

Tinidazole is a Nitroimidazole used to treat trichomoniasis, giardiasis, amebiasis, and bacterial vaginosis.

Rapidly and almost completely absorbed from the GI tract. Food may delay absorption. Time takes to reach peak plasma concentration is 2 hours. It is widely distributed into body tissues and fluids. Crosses the placenta and blood-brain barrier; enters breast milk. Volume of distribution: 50 L. The plasma protein binding is approximately 12%. Hepatic, mainly via CYP3A4. Tinidazole, like metronidazole, is significantly metabolized in humans prior to excretion. Tinidazole is partly metabolized by oxidation, hydroxylation and conjugation. Tinidazole is excreted mainly via urine (20-25%) as unchanged drug and metabolites and faeces (12%).

Tinidazole shows side effects like Sharp, unpleasant metallic taste, upset stomach, vomiting, nausea, loss of appetite, constipation, stomach pain or cramps, headache, tiredness or weakness, dizziness.

Tinidazole is available in the form of Oral Tablet.

Tinidazole is available in India, Canada, US, Spain, Germany, France, Italy, China, and Australia.

Tinidazole belongs to the Antiprotozoal / Antibiotic acts as a Nitroimidazole derivative.

Tinidazole is a prodrug and antiprotozoal agent. The nitro group of tinidazole is reduced in Trichomonas by a ferredoxin-mediated electron transport system. The free nitro radical generated because of this reduction is believed to be responsible for the antiprotozoal activity. It is suggested that the toxic free radicals covalently bind to DNA, causing DNA damage and leading to cell death. The mechanism by which tinidazole exhibits activity against Giardia and Entamoeba species is not known, though it is probably similar.

The Data of Onset and duration of action of Tinidazole is not clinically established.

The Tmax of Tinidazole is within 1.6 hour.

Tinidazole is available in the form of Oral Tablet.

Tinidazole tablet is taken orally, usually once in a day.

Tinidazole is an antiprotozoal which helps in treating infections in the stomach, genital areas. Take this medicine with food to minimize gastric irritation.

Tinidazole is a Nitroimidazole derivative belonging to Antiprotozoal / Antibiotic.

Tinidazole, a 5-nitroimidazole derivative w/ antimicrobial actions similar to metronidazole, is active against both protozoa (e.g. Trichomonas vaginalis, Entamoeba histolytica and Giardia lamblia) and obligate anaerobic bacteria. It damages DNA strands or inhibits DNA synthesis in microorganism.

Tinidazole is approved for use in the following clinical indications

Adult indication

• Amebiasis, intestinal
• Amebiasis, liver abscess
• Bacterial vaginosis
• Giardiasis
• Helicobacter pylori eradication

Pediatric indication

• Amebiasis, intestinal
• Amebiasis, liver abscess
• Bacterial vaginosis
• Blastocystis hominis infection
• Giardiasis
• Helicobacter pylori infection
• Trichomoniasis
• Urethritis, nongonococcal

Adult Dose

• 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: 1 g once daily for 5 days or 2 g once daily for 2 days; some experts prefer 1 g once daily for 5 days due to improved efficacy and tolerability.

• Giardiasis

Oral: 2 g as a single dose.

• Helicobacter pylori eradication

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.

Pediatric Dose

• 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.

• 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.

• Blastocystis hominis infection

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

• Giardiasis

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

• Helicobacter pylori infection

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.

• Trichomoniasis

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.

• Urethritis, nongonococcal

Adolescents: Oral: 2,000 mg as a single dose.

Tinidazole is available in the form of Oral tablet.

Tinidazole is contraindicated in patients with

• In patients with a previous history of hypersensitivity to tinidazole or other nitroimidazole derivatives. Reported reactions have ranged in severity from urticaria to Stevens-Johnson syndrome.
• During first trimester of pregnancy.
• In nursing mothers: Interruption of breast-feeding is recommended during tinidazole therapy and for 3 days following the last dose.

• Neurological Adverse Reactions

Convulsive seizures and peripheral neuropathy, the latter characterized mainly by numbness or paresthesia of an extremity, have been reported in patients treated with tinidazole. The appearance of abnormal neurologic signs demands the prompt discontinuation of tinidazole therapy.

• Vaginal Candidiasis

The use of tinidazole may result in Candida vaginitis. In a clinical study of 235 women who received tinidazole for bacterial vaginosis, a vaginal fungal infection developed in 11 (4.7%) of all study subjects.

• Blood Dyscrasia

Tinidazole should be used with caution in patients with evidence of or history of blood dyscrasia.

• Drug Resistance

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

Consumption of alcohol is not recommended in patients with Tinidazole. It can lead to symptoms of the fast heartbeat, warmth, headache, and breathing difficulty.

Tinidazole is excreted in breast milk in concentrations similar to those seen in serum. Tinidazole can be detected in breast milk for up to 72 hours following administration. Interruption of breast-feeding is recommended during tinidazole therapy and for 3 days following the last dose.

The use of tinidazole in pregnant patients has not been studied. Since tinidazole crosses the placental barrier and enters fetal circulation it should not be administered to pregnant patients in the first trimester. Embryo-fetal developmental toxicity studies in pregnant mice indicated no embryo-fetal toxicity or malformations at the highest dose level of 2,500 mg/kg (approximately 6.3-fold the highest human therapeutic dose based upon body surface area conversions). In a study with pregnant rats a slightly higher incidence of fetal mortality was observed at a maternal dose of 500 mg/kg (2.5-fold the highest human therapeutic dose based upon body surface area conversions). No biologically relevant neonatal developmental effects were observed in rat neonates following maternal doses as high as 600 mg/kg (3- fold the highest human therapeutic dose based upon body surface area conversions). Although there is some evidence of mutagenic potential and animal reproduction studies are not always predictive of human response, the use of tinidazole after the first trimester of pregnancy requires that the potential benefits of the drug be weighed against the possible risks to both the mother and the fetus.

Common Adverse effects

• Heavy menstrual bleeding, Abdominal cramps, anorexia, constipation, decreased appetite, dyspepsia, epigastric discomfort, flatulence, nausea, vomiting, Dysuria, pelvic pain, urinary tract infection, urine abnormality, vulvovaginal candidiasis, vulvovaginal disease (discomfort or odor), Bitter taste, dizziness, fatigue, headache, malaise, metallic taste, Asthenia, Upper respiratory tract infection, Hairy tongue, Thrombocytopenia, Coma, confusion, depression, Bronchospasm, dyspnea, pharyngitis, Flushing, palpitations, Diaphoresis, pruritus, skin rash, urticaria, Increased thirst, Abdominal pain, diarrhea, dysgeusia, oral candidiasis, salivation, stomatitis, tongue discoloration, xerostomia, Dark urine, vaginal discharge, Leukopenia, neutropenia, Increased serum transaminases, Angioedema, Candidiasis (overgrowth), Ataxia, burning sensation, drowsiness, insomnia, peripheral neuropathy (transient; includes numbness and paresthesia), seizure, vertigo, Arthralgia, arthritis, myalgia, Fever.

Rare Adverse effects

• Erythema multiforme, Stevens-Johnson syndrome, Hypersensitivity reaction.

• Warfarin and Other Oral Coumarin Anticoagulants

As with metronidazole, tinidazole may enhance the effect of warfarin and other coumarin anticoagulants, resulting in a prolongation of prothrombin time. The dosage of oral anticoagulants may need to be adjusted during tinidazole coadministration and up to 8 days after discontinuation.

• Alcohols, Disulfiram

Alcoholic beverages and preparations containing ethanol or propylene glycol should be avoided during tinidazole therapy and for 3 days afterward because abdominal cramps, nausea, vomiting, headaches, and flushing may occur. Psychotic reactions have been reported in alcoholic patients using metronidazole and disulfiram concurrently. Though no similar reactions have been reported with tinidazole, tinidazole should not be given to patients who have taken disulfiram within the last two weeks.

• Lithium

Metronidazole has been reported to elevate serum lithium levels. It is not known if tinidazole shares this property with metronidazole, but consideration should be given to measuring serum lithium and creatinine levels after several days of simultaneous lithium and tinidazole treatment to detect potential lithium intoxication.

• Phenytoin, Fosphenytoin

Concomitant administration of oral metronidazole and intravenous phenytoin was reported to result in prolongation of the half-life and reduction in the clearance of phenytoin. Metronidazole did not significantly affect the pharmacokinetics of orally administered phenytoin.

• Cyclosporine, Tacrolimus

There are several case reports suggesting that metronidazole has the potential to increase the levels of cyclosporine and tacrolimus. During tinidazole co-administration with either of these drugs, the patient should be monitored for signs of calcineurin-inhibitor associated toxicities.

• Fluorouracil

Metronidazole was shown to decrease the clearance of fluorouracil, resulting in an increase in side-effects without an increase in therapeutic benefits. If the concomitant use of tinidazole and fluorouracil cannot be avoided, the patient should be monitored for fluorouracil-associated toxicities.

The common side effect of Tinidazole include the following

Common

• Sharp, unpleasant metallic taste, upset stomach, vomiting, nausea, loss of appetite, constipation, stomach pain or cramps, headache, tiredness or weakness, dizziness.

Rare

• Seizures, numbness or tingling of hands or feet, rash, hives, swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs, hoarseness, difficulty swallowing or breathing.

• Pregnancy

Pregnancy Category C

Teratogenic effects

The use of tinidazole in pregnant patients has not been studied. Since tinidazole crosses the placental barrier and enters fetal circulation it should not be administered to pregnant patients in the first trimester. Embryo-fetal developmental toxicity studies in pregnant mice indicated no embryo-fetal toxicity or malformations at the highest dose level of 2,500 mg/kg (approximately 6.3-fold the highest human therapeutic dose based upon body surface area conversions). In a study with pregnant rats a slightly higher incidence of fetal mortality was observed at a maternal dose of 500 mg/kg (2.5-fold the highest human therapeutic dose based upon body surface area conversions). No biologically relevant neonatal developmental effects were observed in rat neonates following maternal doses as high as 600 mg/kg (3- fold the highest human therapeutic dose based upon body surface area conversions). Although there is some evidence of mutagenic potential and animal reproduction studies are not always predictive of human response, the use of tinidazole after the first trimester of pregnancy requires that the potential benefits of the drug be weighed against the possible risks to both the mother and the fetus.

• Nursing Mothers

Tinidazole is excreted in breast milk in concentrations similar to those seen in serum. Tinidazole can be detected in breast milk for up to 72 hours following administration. Interruption of breast-feeding is recommended during tinidazole therapy and for 3 days following the last dose.

• Pediatric Use

Other than for use in the treatment of giardiasis and amebiasis in pediatric patients older than three years of age, safety and effectiveness of tinidazole in pediatric patients have not been established.

• Geriatric Use

Clinical studies of tinidazole did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

There is no specific antidote for the treatment of over dosage with tinidazole; therefore, treatment should be symptomatic and supportive. Gastric lavage may be helpful. Hemodialysis can be considered because approximately 43% of the amount present in the body is eliminated during a 6-hour hemodialysis session.

Pharmacodynamic

Tinidazole is a synthetic antiprotozoal agent. Tinidazole demonstrates activity both in vitro and in clinical infections against the following protozoa: Trichomonas vaginalis, Giardia duodenalis (also termed G. lamblia), and Entamoeba histolytica. Tinidazole does not appear to have activity against most strains of vaginal lactobacilli.

Pharmacokinetics

• Absorption

Rapidly and almost completely absorbed from the GI tract. Food may delay absorption. Time takes to reach peak plasma concentration is 2 hr.

• Distribution

Widely distributed into body tissues and fluids. Crosses the placenta and blood-brain barrier; enters breast milk. Volume of distribution: 50 L. Plasma protein binding: 12%.

• Metabolism and Excretion

Hepatic, mainly via CYP3A4. Tinidazole, like metronidazole, is significantly metabolized in humans prior to excretion. Tinidazole is partly metabolized by oxidation, hydroxylation and conjugation. Excreted mainly Via urine (20-25%) as unchanged drug and metabolites and faeces (12%).

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