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Secnidazole

A Review of its Antimicrobial Activity, Pharmacokinetic Properties and Therapeutic Use in the Management of Protozoal Infections and Bacterial Vaginosis

Abstract

Synopsis

Secnidazole is structurally related to the commonly used 5-nitroimidazoles metronidazole and tinidazole. These drugs share a common spectrum of activity against anaerobic micro-organisms and they appear particularly effective in the treatment of amoebiasis, giardiasis, trichomoniasis and bacterial vaginosis. Secnidazole is rapidly and completely absorbed after oral administration and has a longer terminal elimination half-life (≈17 to 29 hours) than commonly used drugs in this class.

In patients with intestinal amoebiasis or giardiasis, clinical or parasitological cure rates of 80 to 100% are achieved after treatment with a single dose of secnidazole 2g (30 mg/kg in children), similar to the response rates achieved with multiple dosage regimens of metronidazole or tinidazole. Patients with hepatic amoebiasis appears to respond well to 5- to 7-day therapy with secnidazole, but the efficacy of this drug regimen requires further evaluation in larger numbers of patients.

After administration of a single dose of secnidazole, parasitological eradication was achieved in approximately 92 to 100% of patients with urogenital trichomoniasis. Patients with bacterial vaginosis respond at least as well to a single dose of secnidazole as to single-dose tinidazole, or single- or 7-day treatment with metronidazole; clinical improvement and/or microbiological evidence of cure was attained in approximately 59 to 96% of patients.

In the clinical trials reviewed, secnidazole was well tolerated; most adverse events were gastrointestinal in nature and did not require treatment intervention or withdrawal from therapy.

In summary, available evidence suggests that secnidazole is as efficacious as other 5-nitroimidazole drugs in the treatment of protozoal infections and bacterial vaginosis. The convenience and ease of administration associated with single-dose therapy, combined with a good tolerability profile, make secnidazole a suitable option to other single-dose treatments and an attractive alternative to multiple dosage regimens with other drugs in this class.

Antimicrobial Activity

Secnidazole and other 5-nitroimidazoles possess selective activity against many anaerobic Gram-positive and Gram-negative bacteria and protozoa. In general, secnidazole and metronidazole were approximately equipotent in activity against Bacteroides fragilis, Trichomonas vaginalis and Entamoeba histolytica, in in vitro studies. In 1 study, secnidazole was more potent than metronidazole against Giardia lamblia (G. intestinalis, G. duodenalis).

Secnidazole was as effective as metronidazole and tinidazole in eradicating G. lamblia, T. vaginalis and E. histolytica from the majority of infected patients. Bacterial or protozoal resistance develops rarely to the 5-nitroimidazoles.

Pharmacokinetic Properties

Secnidazole is rapidly and completely absorbed after oral administration. Plasma drug concentrations are linear over the therapeutic dose range of 0.5 to 2g. Protein binding accounts for only about 15% of total plasma drug concentration and the volume of distribution is low (49.2L). The concentration of secnidazole which remains in the plasma for at least 48 hours after a single 2g dose appears to be well within the range corresponding to minimum inhibitory concentration values reported by most investigators for in vitro sensitivity of B. fragilis, E. histolyticaand T. vaginalis.

The metabolism of secnidazole is not well described but, as with metronidazole, the drug probably undergoes oxidation in the liver. Secnidazole and a hydroxymethyl metabolite are detected in urine as glucuronide conjugates. The parent drug is cleared slowly from the body and, in 1 trial, only 10 to 25% of a single 2g dose was recovered in urine after 72 hours. The terminal elimination half-life (t1/2β) of secnidazole ranged from about 17 to 29 hours and was longer in men (20 hours) than in women (14 hours) in 1 study. The expression of cytochrome P450 isoenzymes does not appear to be influenced by secnidazole.

Therapeutic Use

Secnidazole, usually as a single 2g dose (30 mg/kg in children), has been investigated in the treatment of amoebiasis, giardiasis, urogenital trichomoniasis and nonspecific bacterial vaginosis.

In patients with intestinal amoebiasis or giardiasis, clinical cure or parasitological eradication rates of 80 to 100% were obtained after single-dose treatment with secnidazole. These rates were similar to those observed after single-dose, or 5- or 7-day metronidazole treatment (73.3 to 100%), 2-day therapy with tinidazole (83 to 100%) or 3-day treatment with ethofamide (92.9%). Hepatic amoebiasis seemed to respond well to 5- to 7-day treatment with secnidazole, although available data are sparse and require confirmation. No difference in therapeutic efficacy was noted on the basis of patient age.

A single dose of secnidazole 2g resulted in parasitological eradication in about 92 to 100% of patients with urogenital trichomoniasis. No difference in treatment outcome was noted in patients who received a single dose of secnidazole 2g or 4-day treatment totalling 4g. Although no direct comparisons have been conducted between secnidazole and other 5-nitroimidazoles, response to secnidazole does not appear to differ markedly from those previously reported for single doses of metronidazole (82 to 97%) or tinidazole (81 to 100%).

In a randomised double-blind trial, clinical cure and/or symptom improvement rates were similar in women with bacterial vaginitis treated with a single dose of secnidazole (90.8%) or tinidazole (87.5%); and bacterial eradication rates were 81.5 and 78.5%, respectively. Data from 2 nonblind studies indicated that a single dose of secnidazole was at least as effective as 7-day treatment with metronidazole (clinical or microbiological cure rates: secnidazole 73.3 to 93.1%; metronidazole 58.5 to 95.8%).

Tolerability

The tolerability profile of secnidazole does not differ markedly from other 5-nitroimidazoles. The most commonly reported adverse events in clinical trials involved the gastrointestinal tract (nausea, vomiting, glossitis, anorexia, epigastric pain and a metallic taste) and occurred in 2 to 10% of patients. Headache and dizziness were experienced by about 2% of patients. The drug was equally well tolerated in adults and children, and no adverse event required therapeutic intervention or treatment withdrawal.

Abnormalities in leucocyte counts associated with secnidazole treatment were noted in about 25% of adult patients in 2 trials (n = 360) but were not considered clinically significant by investigators; no changes were seen in 96 paediatric patients. An increase in blood urea nitrogen occurred in some patients but values remained within normal limits.

Dosage and Administration

Adult patients with intestinal amoebiasis or giardiasis should receive a single dose of secnidazole 2g, and children should receive 30 mg/kg (or the nearest quantity of secnidazole in terms of bottles of reconstituted suspension). The World Health Organization recommends that family members and institutional contacts of persons with giardiasis also receive treatment. Hepatic amoebiasis should be treated with secnidazole 1.5 mg/day (or 30 mg/kg in children) for 5 days.

Treatment for patients with vaginal trichomoniasis consists of a single 2g dose of secnidazole; sexual partners should also be treated. There are no dosage guidelines for the treatment of patients with bacterial vaginosis; however, a single 2g dose has shown clinical efficacy.

Ingestion of alcohol during, and up to 24 hours after, therapy with secnidazole may result in a disulfiram-like reaction and should be avoided. Secnidazole may potentiate the anticoagulant effect of warfarin and should not be administered to patients with a history of blood disorders.

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Correspondence to Jane C. Gillis.

Additional information

Various sections of the manuscript reviewed by: V.R. Bagnoli, Department of Obstetrics and Gynecology, University of São Paulo, São Paulo, Brazil; D.I. Edwards, Chemotherapy Research Unit, University of East London, London, England; J. Dupouy-Camet, Laboratoire de Parasitologic, Hôpital Cochin, Paris, France; N. Katz, ‘René Rachou’ Research Centre, Belo Horizonte, Brazil; M. Müller, Laboratory of Biochemical Parasitology, The Rockefeller University, New York, New York, USA; J.D. Sobel, Division of Infectious Diseases, Wayne State University, Detroit, Michigan, USA; H. Tenenbaum, Department of Peridontology, University Louis Pasteur, Strasbourg, France; J. Turnidge, Microbiology Department & Infectious Disease Unit, Monash Medical Centre, Clayton, Victoria, Australia.

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Gillis, J.C., Wiseman, L.R. Secnidazole. Drugs 51, 621–638 (1996). https://doi.org/10.2165/00003495-199651040-00007

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Keywords

  • Metronidazole
  • Bacterial Vaginosis
  • Gingival Crevicular Fluid
  • Tinidazole
  • Giardiasis