Tinidazole
M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson in Kucers’ The Use of Antibiotics, 2017
Tinidazole, 1-[2-(ethylsulfonyl)ethyl]-2-methyl-5-nitroimidazole, is a nitroimidazole drug similar to metronidazole (see Chapter 99, Metronidazole). It was synthesized in 1969 and it has an in vitro activity profile similar to that of metronidazole, including efficacy against Trichomonas vaginalis (Miller et al., 1969; Howes et al., 1970). Tinidazole is useful for the treatment of protozoal parasitic infections (Giardia lamblia [G. intestinalis], Entamoeba histolytica) and against anaerobic bacterial infections.
Candida and parasitic infection: Helminths, trichomoniasis, lice, scabies, and malaria
Hung N. Winn, Frank A. Chervenak, Roberto Romero in Clinical Maternal-Fetal Medicine Online, 2021
Trichomoniasis in pregnancy has been associated with adverse pregnancy outcomes including premature rupture of membranes and preterm delivery. A large multicenter trial was conducted to see whether treatment of asymptomatic trichomoniasis at the end of the second trimester could reduce the rate of preterm birth (51). Unfortunately, this study reported a somewhat increased rate of preterm delivery in the treated women as compared with the placebo group. This increase has not been confirmed in other studies and there has been much discussion of potential limitations of this trial (including the timing and dosage of the treatment), but to date there has been no benefit identified for treatment of asymptomatic pregnant women (52). By contrast, treatment of symptomatic pregnant women with metronidazole (single 2-g oral dose) is recommended upon diagnosis (50). Metronidazole has no evidence of teratogenicity in animal studies and extensive use during human pregnancy (pregnancy category B). Some women may prefer to await completion of the first trimester prior to treatment to avoid exposure during organogenesis. Tinidazole has evidence of increased fetal mortality in animal studies with no controlled human studies (pregnancy category C). Since tinidazole has no advantage over metronidazole with potential for increased risks, tinidazole is not recommended for use during pregnancy. Metronidazole is excreted into breastmilk at levels similar to those found in maternal plasma after oral dosing, thus the American Academy of Pediatrics recommends that women pump and discard breastmilk for 12 to 24 hours following maternal single-dose oral metronidazole therapy to reduce infant exposure (50). It should be noted that the levels seen in the infant after maternal therapy during breastfeeding are lower than levels achieved in infants directly treated with metronidazole. Tinidazole is also excreted into breastmilk at levels similar to maternal plasma following oral dosing. Since tinidazole is still detectable in breastmilk up to 72 hours after the last dose, pumping and discarding milk for 3 days are recommended to reduce infant exposure.
Trichomonas
Vincenzo Berghella in Maternal-Fetal Evidence Based Guidelines, 2022
The nitroimidazoles are the only class of drugs useful for the oral or parenteral treatment of trichomoniasis. In randomized clinical trials, oral nitroimidazoles have resulted in parasitologic cure rates of 90–95%. Metronidazole and tinidazole are most commonly used. Metronidazole can be given as a single 2-g oral dose, or 500 mg twice a day for 7 days, and can be given to symptomatic women at any gestational age [10]. Twice daily dosing may be more effective than the single oral dose in all patients (RR 0·55, 95% CI 0·34–0·70; p <0·0001) [26]. In patients with co-infection with HIV, studies have shown the twice a day dosing to be more effective and thus should be the treatment of choice. All patients, regardless of HIV status, should also be re-screened for a test of cure within 3 months of initial infection [17, 27]. This is due to the high levels of ongoing infection found in pregnant women [28] and can be done as soon as 2 weeks with PCR amplification. Multiple studies and meta-analyses have not demonstrated an association between metronidazole use during pregnancy and teratogenic or mutagenic effects in infants [29, 30, 31]. Tinidazole is given as a single 2-g oral dose. Its use is contra-indicated in the first trimester of pregnancy. Metronidazole resistance is increasingly common. The CDC estimated that 5% of clinical isolates of T. vaginalis exhibit some degree of metronidazole resistance. An escalated dosing regimen of metronidazole 2 g daily for 3–5 days has been successful in some cases of resistant infection, but in general not more than a single 2-g dose should be given to prevent possible increase in preterm birth [10]. Tinidazole is effective in treating up to 60% of metronidazole-resistant T. vaginalis infections. Concurrent treatment of sexual partners is recommended to prevent reinfection. Concurrent treatment via expedited partner treatment (EPT) has been proposed for treatment of trichomoniasis but has not shown in randomized trials to decrease reinfection rates versus partner referral [16, 32]. Currently, no clear evidence-based recommendations for EPT exist [17]. In those rare cases with a confirmed metronidazole allergy, patients should go through desensitization of their allergy before being treated with metronidazole [33].
Successes, failures, and future prospects of prodrugs and their clinical impact
Published in Expert Opinion on Drug Discovery, 2019
Antimicrobials of the 5-nitroimidazole class are the first line choice in the treatment of protozoal and some bacterial infections. Metronidazole and tinidazoleare are prodrugs with a similar proposed mechanism of action: the parent compound diffuses into the target organism and is reduced to several intermediates which cause cytotoxicity. Tinidazole is commonly prescribed for giardiasis, bacterial vaginosis, and H. pylori. Metronidazole, though, undergoes heavy hepatic metabolism producing 5 metabolites. Hydroxy-metronidazole, is an active metabolite with 30–65% of the antimicrobial activity of metronidazole [62]. Secnidazole is a second generation 5-nitroimidazole commonly prescribed for bacterial vaginosis. It is oxidized hepatically to an active hydroxyethyl metabolite. Both parent compound and its metabolite are clinically significant [61,63]. The mechanism of action of both secnidazole and its active metabolite is similar to that of metronidazole.
Controlled delivery of the antiprotozoal agent (tinidazole) from intravaginal polymer matrices for treatment of the sexually transmitted infection, trichomoniasis
Published in Pharmaceutical Development and Technology, 2019
Hevanshi Vidhushika Fernando, Li Li Chan, Nhung Dang, Diviya Santhanes, Hasini Banneheke, Sivalingam Nalliah, Allan G. A. Coombes
The current treatment options for trichomoniasis include a 500 mg oral dose of metronidazole, administered twice daily for 7 days or a single 2 g oral dose (Cudmore et al. 2004). Concerns with metronidazole treatment relate to increasing drug-resistance, the failure to eradicate infection with two consecutive courses and development of allergic reactions (Das et al. 2005). Tinidazole, a second-generation nitroimidazole and structural analogue of metronidazole, is administered orally in the form of single (2g) dose as an alternative treatment. Tinidazole exhibits an elimination half-life twice that of metronidazole (12–14 h vs. 6–7h) resulting in higher and more persistent serum concentrations at equivalent dosage. The prodrug is converted in vivo to the cytotoxic form following diffusion into cells and reduction to cytotoxic radical intermediates by ferredoxin-mediated electron transport. The radicals bind to DNA and the resulting damage (loss of helical structure, impaired template function and strand breakage) eventually leads to cell death (Nord and Kager 1983; Gardner and Hill 2001).
A pragmatic stepwise approach to the diagnosis and management of refractory acute pouchitis
Published in Expert Opinion on Pharmacotherapy, 2021
Zaid S. Ardalan, Miles P. Sparrow
Once the diagnosis of idiopathic acute pouchitis is confirmed, if a patient has failed one 2-week course of antibiotics such as metronidazole (15–20 mg/kg/day), they should be treated with a 2-week course of another antibiotic such as ciprofloxacin (500 mg twice daily) [6]. Ciprofloxacin appears to be more effective than metronidazole and with fewer adverse effects [6]. Tinidazole (500 mg twice daily) can be used as an alternative in those failing ciprofloxacin and is considered one of the most potent antibiotics for acute pouchitis. Rifaximin 500 mg twice daily is also effective, but due to its cost and low side effect profile, it is best reserved for chronic antibiotic-dependent pouchitis (CADP) requiring ongoing antibiotics [7]. Patients failing the above, should be offered longer courses of two antibiotics combined [8]. Combination therapy of ciprofloxacin and metronidazole for 4 weeks achieved clinical remission in 82% of patients in one study [9], and combination of ciprofloxacin and tinidazole achieved clinical remission in 88% of patients in another study [10]. Those intolerant to metronidazole or tinidazole can be treated with a 2–4 week course of ciprofloxacin and rifaximin, which achieved clinical response or remission in 87% of patients in an open-label study [11].
Related Knowledge Centers
- Amoeba
- Anaerobic Respiration
- Antibiotic
- Disulfiram
- Giardia
- Nitroimidazole
- Protozoan Infection
- Helicobacter Pylori Eradication Protocols
- Amoebiasis
- Trichomonas Vaginalis