Tinidazole

(BAN, USAN, rINN)
Tinidazole Chemical formula
Synonyms: CP-12574; Tinidatsoli; Tinidazol; Tinidazolas; Tinidazolum; Tynidazol. 1-[2-(Ethylsulphonyl)ethyl]-2-methyl-5-nitroimidazole.
Cyrillic synonym: Тинидазол.

💊 Chemical information

Chemical formula: C8H13N3O4S = 247.3.
CAS — 19387-91-8.
ATC — J01XD02; P01AB02.
ATC Vet — QJ01XD02; QP51AA02.

Pharmacopoeias.

In Chin., Eur., Jpn, and US.

Ph. Eur. 6.2

(Tinidazole). An almost white or pale yellow, crystalline powder. Practically insoluble in water; soluble in acetone and in dichloromethane; sparingly soluble in methyl alcohol. Protect from light.

USP 31

(Tinidazole). An almost white or pale yellow crystalline powder. Practically insoluble in water; soluble in acetone and in dichloromethane; sparingly soluble in methyl alcohol. Store in airtight containers. Protect from light.

💊 Adverse Effects and Precautions

Breast feeding.

The American Academy of Pediatrics1 considers that the use of tinidazole by mothers during breast feeding may be of concern, since it is mutagenic in vitro. After singledose therapy, breast feeding may be stopped for 12 to 24 hours to allow excretion of the dose.
1. American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 2001; 108: 776–89. Correction. ibid.; 1029. Also available at: http://aappolicy.aappublications.org/cgi/content/full/pediatrics %3b108/3/776 (accessed 03/06/04)

Porphyria.

Tinidazole is considered to be unsafe in patients with porphyria because it has been shown to be porphyrinogenic in in-vitro systems.

Shock.

An acute severe toxic reaction, considered not to be allergic, occurred in a healthy subject shortly after the intravenous infusion of tinidazole 1.6 g over 80 minutes.1 He fainted for about 10 seconds and low blood pressure, nausea, and tiredness persisted for several hours. Spasms in the left arm were also experienced but no generalised convulsions. Anaphylactic shock has also been reported,2 with severe bronchospasm and subsequent development of Stevens-Johnson syndrome, in a patient who had reactions of increasing severity after 3 separate exposures to tinidazole.
1. Aase S, et al. Severe toxic reaction to tinidazole. Eur J Clin Pharmacol 1983; 24: 425–7
2. Singbal SS, Rataboli PV. Anaphylaxis and hypersensitivity syndrome reactions in increasing severity following repeated exposure to tinidazole. J Postgrad Med 2005; 51: 243–4.

💊 Interactions

Tinidazole may, like metronidazole, produce a disulfiram-like reaction with alcohol.

💊 Pharmacokinetics

The pharmacokinetics of tinidazole resemble those of metronidazole although the half-life is longer. Tinidazole is rapidly and almost completely absorbed after oral doses and, typically, a peak plasma concentration of about 40 micrograms/mL is achieved 2 hours after a single 2-g dose, falling to about 10 micrograms/mL at 24 hours and 2.5 micrograms/mL at 48 hours; concentrations above 8 micrograms/mL are maintained by daily maintenance doses of 1 g. Comparable concentrations are achieved with equivalent intravenous doses. The plasma elimination half-life of tinidazole is 12 to 14 hours. Tinidazole is widely distributed and concentrations similar to those in plasma have been achieved in bile, breast milk, CSF, saliva, and a variety of body tissues; it crosses the placenta readily. Only 12% is reported to be bound to plasma proteins. An active hydroxy metabolite has been identified. Unchanged drug and metabolites are excreted in the urine and, to a lesser extent, in the faeces.
1. Wood BA, et al. The pharmacokinetics, metabolism and tissue distribution of tinidazole. J Antimicrob Chemother 1982; 10 (suppl A): 43–57
2. Karhunen M. Placental transfer of metronidazole and tinidazole in early human pregnancy after a single infusion. Br J Clin Pharmacol 1984; 18: 254–7
3. Evaldson GR, et al. Tinidazole milk excretion and pharmacokinetics in lactating women. Br J Clin Pharmacol 1985; 19: 503–7
4. Wood SG, et al. Pharmacokinetics and metabolism of C-tinidazole in humans. J Antimicrob Chemother 1986; 17: 801–9.

Renal impairment.

Single-dose studies indicate that the pharmacokinetics of tinidazole in patients with chronic renal failure are not significantly different from those in healthy subjects and that no modification of tinidazole dosage is necessary. However, tinidazole is rapidly removed by haemodialysis.1,2
1. Flouvat BL, et al. Pharmacokinetics of tinidazole in chronic renal failure and in patients on haemodialysis. Br J Clin Pharmacol 1983; 15: 735–41
2. Robson RA, et al. Tinidazole pharmacokinetics in severe renal failure. Clin Pharmacokinet 1984; 9: 88–94.

💊 Uses and Administration

Tinidazole is a 5-nitroimidazole derivative. It has the antimicrobial actions of metronidazole and is used similarly in the treatment of susceptible protozoal infections and in the treatment and prophylaxis of anaerobic bacterial infections. It has also been used in regimens for the eradication of Helicobacter pylori in peptic ulcer disease. Tinidazole is usually given as a single daily oral dose with or after food; it is also given by intravenous infusion and as vaginal pessaries. In invasive amoebiasis, tinidazole is usually given with a luminal amoebicide. In intestinal amoebiasis, a single daily dose of 2 g is given orally for 2 or 3 days; in hepatic amoebiasis, 1.5 to 2 g as a single daily dose may be given for 3 days or occasionally up to 6 days. Children are given 50 to 60 mg/kg daily for 3 or 5 days respectively. A single dose of tinidazole 2 g is given orally in the treatment of giardiasis, trichomoniasis, and acute necrotising ulcerative gingivitis; 50 to 75 mg/kg as a single dose is given to children with giardiasis or trichomoniasis. It may sometimes be necessary to repeat this dose once. In trichomoniasis, sexual partners should also be treated. In bacterial vaginosis, a single 2-g dose of tinidazole is usually given orally, although higher cure rates have been achieved with a 2-g dose on 2 successive days or 1 g daily for 5 days. For the treatment of most anaerobic bacterial infections, tinidazole is given orally, usually for 5 or 6 days, in an initial dose of 2 g followed on subsequent days by 1 g daily or 500 mg twice daily. If oral therapy is not possible, tinidazole may be given intravenously, 800 mg being infused as 400 mL of a 2 mg/mL solution at a rate of 10 mL/minute; this initial dose is followed by 800 mg daily or 400 mg twice daily until oral therapy can be substituted. For the prevention of postoperative anaerobic bacterial infections, 2 g is given by mouth about 12 hours before surgery. Alternatively 1.6 g is given as a single intravenous infusion before surgery. In regimens for the treatment of peptic ulcer disease, tinidazole 500 mg twice daily has been given with clarithromycin and omeprazole for 7 days.
1. Manes G, Balzano A. Tinidazole: from protozoa to Helicobacter pylori—the past, present and future of a nitroimidazole with peculiarities. Expert Rev Anti Infect Ther 2004; 2: 695–705
2. Fung HB, Doan TL. Tinidazole: a nitroimidazole antiprotozoal agent. Clin Ther 2005; 27: 1859–84
3. Nailor MD, Sobel JD. Tinidazole for bacterial vaginosis. Expert Rev Anti Infect Ther 2007; 5: 343–8.

Administration in renal impairment.

The elimination of tinidazole is largely unchanged in patients with impaired renal function (see under Pharmacokinetics, above) and dosage adjustment is not generally considered necessary. However tinidazole is removed by haemodialysis, and patients may need additional doses to compensate.

💊 Preparations

Proprietary Preparations

Arg.: Fasigyn; Gynormal; Ladylen Duo; Austral.: Fasigyn; Simplotan; Belg.: Fasigyn; Braz.: Amplium; Facyl; Fasigyn; Ginosutin; Pletil; Tinoral; Trinizol†; Chile: Fasigyn; Triconidazol†; Troxxil; Fr.: Fasigyne; Ger.: Simplotan†; Gr.: Fasigyn; Hong Kong: Fasigyn; India: Amebamagma; Enidazol; Fasigyn; Tiniba; Tinidafyl; Tinidol†; Tinifas; Tinvista; Indon.: Fasigyn; Flatin; Israel: Fasigyn; Protocide; Ital.: Fasigin; Trimonase; Malaysia: Fasigyn†; Tindol; Mex.: Amebysol; Ametricid†; Estovyn-T; Fasigyn; Induken†; Trinigyn; Triseptil; Neth.: Fasigyn†; NZ: Dyzole; Port.: Fasigyn; Rus.: Fasigyn (Фазижин); Tiniba (Тиниба); S.Afr.: Fasigyn; Singapore: Fasigyn; Spain: Tricolam; Swed.: Fasigyn; Switz.: Fasigyne; Thai.: Asiazole-TN; Fasigyn; Funida; Idazole; Sporinex; Tinazole; Tini†; Tonid; Trichonas; Tricogyn; Tricozone; Trigyn†; UK: Fasigyn; USA: Tindamax; Venez.: Cinabel†; Fasigyn; Pangamil. Multi-ingredient: Arg.: Aduar; Fasigyn Nistatina; Gynormal; Helmint Compuesto; Ladylen; Mebutar Compuesto; Nistinol; Tru Compuesto; Braz.: Amplium-G; Anfugine; Cartrax; Colpolase; Duozol; Facyl M; Ginec†; Gino Pletil; Ginometrim Oral†; Ginosutin M; Gynomax; Gynopac; Poliginax; Seczol; Takil; Tizonil M†; Travogyn; Trinizol M†; Chile: Doxifen; Famidal; Famidal Ad†; Ginecopast; Ginecopast Dual; Ginedazol; Ginedazol Dual; Medidos; Mizonase; India: Biocip-TZ; Bioflox-TZ; Candizole-T; Cipgen TZ; Ciplox TZ; Ciptini; Citizol; Entrolate†; Forcan TZ; Genflox TZ; Helipac; Nor T; Norflox TZ; Normax TZ; Ofler-TZ; Oflox TZ; Olfi TZ; OTC HP Kit; Parabact; Pylokit; Tinidafyl Plus; Tinvista-CF; Tinvista-NF; Wotinex; Indon.: Fasigyn-Nystatin; Ital.: Fasigin N; Malaysia: Pylobact Combi; Mex.: Afumix; Fasigyn VT; Mebeciclol; Rus.: Pylobact (Пилобакт).
Published December 25, 2018.