Secnidazole: a treatment for trichomoniasis in adolescents and adults

Figures & data

Figure 1. Chemical structure of secnidazole, metronidazole, and tinidazole.

Figure 2. A single 2-g oral dose of secnidazole reaches peak plasma concentrations at 4 h, and with its long half-life, remains above the minimum inhibitory concentration for several days as opposed to oral metronidazole 500 mg, which requires repeat dosing. (Adapted from Lupin Pharmaceuticals [data on file] and Ashiq B, et al. 2011 [40]).

Table 1. Microbiological cure rate in women with trichomoniasis at the TOC visit (mITT*)

	Secnidazole 2-g	Placebo	Treatment difference
	n/N (%)	n/N (%)	(95% CI)^†
Microbiological cure^‡	59/64 (92.2)	1/67 (1.5)^§	90.7 (80.7, 96.5)
			p < 0.001^¶

CI: confidence interval; mITT: modified intent to treat population; STI; sexually transmitted infection; TOC: test of cure. *Defined as all randomized patients who were culture positive for T. vaginalis and negative for other STIs. ^†Exact CI from Score Method. ^‡InPouch^TM TV test negative for T. vaginalis; patients with no test results were assumed to be positive (1 SEC- and 3 placebo-treated patients).

^§In placebo-treated patients with a positive T. vaginalis culture at TOC, receiving delayed SEC showed a comparable microbiological cure rate 7–12 days later (88.9% [56/63]); 95% CI: 78.4%, 95.4%) compared with the 92.2% cure rate for patients initially treated with SEC. ^¶P-value derived using a Cochran–Mantel–Haenszel test adjusted for clinical symptoms (present/absent) of trichomoniasis at baseline.

Table 2. Studies of SEC in men

Citation(Location)	Treatment	M/F	Cure rate	Adverse events
Siboulet 1977 [43] (France)	SEC 2 g SD PO	76/104	95.6%*	Nausea/gastralgia: 9% Gastric burning: 1%
Videau 1978 [38] (France)	SEC 2 g SD PO	56/84	97.1%^†	Nausea: 4%
Özbilgin 1994 [42] (Turkey)	SEC 2 g SD PO MTZ 250 mg TID PO (7 d) ORZ 500 g BID PO (5 d)	30/0 29/0 26/0	100% 100% 100%	NR
Dyudyun 2016 [44] (Ukraine)	SEC 2 g SD PO^§ SEC 2 g MD PO (3 d)^¶	49/38	97.0%^‡	Dyspepsia: 0.5% Metallic taste: NR

BID: twice daily; F: female; M: male; MD: multiple doses; MTZ: metronidazole; NR: not reported; ORZ: ornidazole; PO: by mouth; SD: single dose; SEC: secnidazole; TID: thrice daily.

*Microbiological cure (wet mount and culture: Siboulet, Videau; wet mount, culture, and molecular test: Dyudyun). ^†Symptomatic cure. ^‡Microbiological and symptomatic cure. ^§Treatment for patients experiencing their first occurrence of T. vaginalis. ^¶Treatment for patients with persistent trichomoniasis.

Table 3. Summary of TEAEs* (SAF)

	Secnidazole 2-g (n = 74)		Placebo (n = 73)
	Patients^† n (%)	Events, n	Patients^† n (%)	Events, n
Any TEAE	11 (14.9)	13	16 (21.9)	20
Nausea	2 (2.7)	2	3 (4.1)	3
Abdominal pain	1 (1.4)	1	1 (1.4)	1
Diarrhea	1 (1.4)	1	2 (2.7)	2
Vomiting	1 (1.4)	1	1 (1.4)	1
Vulvovaginal candidiasis	2 (2.7)	2	0	0
Vulvovaginalmycotic infection	1 (1.4)	1	0	0
Productive cough	1 (1.4)	1	0	0
Upper-airwaycough syndrome	1 (1.4)	1	0	0
Myalgia	1 (1.4)	1	0	0
Back pain	0	0	1 (1.4)	1
Headache	1 (1.4)	1	5 (6.8)	5
Vulvovaginal pruritus	1 (1.4)	1	0	0
Dysmenorrhea	0	0	2 (2.7)	2
Irregular Menstruation	0	0	1 (1.4)	1
Thirst	0	0	1 (1.4)	1
Pruritus	0	0	1 (1.4)	1

TEAE: treatment-emergent adverse event; SAF: safety population; TOC: test of cure. *Includes all TEAEs during the primary phase (start date on or before the TOC visit). ^†Patients experiencing multiple TEAEs are counted only once within a given cell.

Table 4. Characteristics of secnidazole, metronidazole, and tinidazole

	Secnidazole [64]	Metronidazole [65]	Tinidazole [66]
Drug family	5-nitroimidazole	5-nitroimidazole	5-nitroimidazole
Formula	C7H11N3O3	C6H9N3O3	C8H13N3O4S
Molecular mass	185.18	171.15	247.27
Dose	2 g	500 mg	2 g
Treatment course for T. vaginalis	Single dose	BID x 7 days	Single dose
Route of administration	Oral granules	Oral	Oral
Half-life (t1/2) in women	17–19 h	7.3 h	11.7 ± 1 h
Half-life (t1/2) in men	20.2 ± 3.1 h [43]	7.3 h [43]	13.6 ± 1.2 h [43]
Time to peak concentration (Tmax)	4 h	1–2 h	1.6 ± 0.7 h
Peak concentration (Cmax)	45.4 mcg/mL	12 mcg/mL	47.7 ± 7.5 mcg/mL
Minimum lethal concentration	5.9 ± 13.2 μg/mL	13.5 ± 26.9 μg/mL	0.8 μg/mL
Contraindications	Hypersensitivity to SEC or other nitroimidazole derivatives Cockayne syndrome*: severe irreversible hepatotoxicity/acute liver failure with fatal outcomes have been reported after initiation of MTZ [64].	Hypersensitivity to MTZ or other nitroimidazole derivatives Psychotic reaction with disulfiram: in alcoholic patients using disulfiram concurrently; MTZ should not be administered to patients who have taken disulfiram within the last 2 weeks. Interaction with alcohol: MTZ associated with disulfiram-like reaction to alcohol; discontinue consumption of alcohol or products containing propylene glycol during and for ≥3 days after MTZ. Cockayne syndrome*: severe irreversible hepatotoxicity/acute liver failure with fatal outcomes have been reported [65].	Hypersensitivity: to TDZ Cockayne syndrome*: severe irreversible hepatotoxicity/acute liver failure with fatal outcomes have been reported after initiation of MTZ [67].
Alcohol Interaction	In vitro studies showed that secnidazole had no effect on aldehyde dehydrogenase activity [64]. Alcoholic beverages and preparations containing ethanol or propylene glycol should be avoided during therapy and for 2 days after treatment is stopped. (post-marketing) [64]. Updated data suggest that refraining from alcohol use while taking 5-nitroimidazoles is unnecessary [2,68].	Associated with a disulfiram-like reaction to alcohol, including abdominal cramps, nausea, vomiting, headaches, and flushing. Alcohol or products containing propylene glycol should be discontinued during and for ≥3 days after treatment is stopped [65]. Updated data suggest that refraining from alcohol use while taking 5-nitroimidazoles is unnecessary [2,68].	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. Updated data suggest that refraining from alcohol use while taking 5-nitroimidazoles is unnecessary [2,68].
Pregnancy	Limited available data on use in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes. No evidence of adverse developmental outcomes in animal studies [64,69].	No adequate studies in pregnant women. However, no evidence of teratogenicity or mutagenic effects among infants has been reported in multiple cross-sectional, case-control, and cohort studies of pregnant women. No evidence of harm to the fetus in animal studies [70–72]. Updated data indicate that MTZ poses a low risk to the developing fetus. No evidence of teratogenicity or mutagenic effects in infants has been found in multiple studies of pregnant women taking single- or multiple-dose MTZ regimens [2].	Available published data from a case-control study [73] and case report with TDZ use [74] in pregnant women are insufficient to identify a risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. However, additional preclinical data indicate that TDZ poses a moderate risk. Thus, TDZ should be avoided for pregnant women [2].
Breastfeeding	No data on the presence of SEC in human milk, the effects on the breast- fed child, or the effects on milk production. Breastfeeding is not recommended during treatment and for 96 hours after administration [64].	Present in human milk. Decision should be made whether to discontinue nursing or to discontinue the drug, considering the importance of the drug to the mother. Clinicians sometimes advise deferring breastfeeding for 12–24 hours after maternal treatment with MTZ.	No reports of adverse effects in breastfed infants and no information on effects on milk production. Due to the potential for serious adverse reactions, including tumorigenicity, breastfeeding is not recommended during therapy and for 3 days after the last dose [66]. Breastfeeding should be deferred for 72 hours after a single 2-g oral dose of tinidazole [2].

*Cockayne syndrome: is an inherited form of dwarfism diagnosed according to the presence of (1) growth retardation (ie, short stature), abnormal sensitivity to light, and prematurely aged appearance (progeria).

Ashiq B, Usman M, Ashraf M, et al. Comparative pharmacokinetics of metronidazole in healthy volunteers and in patients suffering from amoebiasis. Pak J Pharm. 2011;24. 41–46.

 Google Scholar

Siboulet A, Catalan F, Videau D, et al. La trichomonase urogénitale. Essais d’un imidazole à demi-vie longue: le secnidazole. Médecine et Maladies Infectieuses. 1977;7(9):400–404.

 Google Scholar

Videau D, Niel G, Siboulet A, et al., Secnidazole. A 5-nitroimidazole derivative with a long half-life. Br J Vener Dis. 54(2): 77–80. 1978.

 PubMedGoogle Scholar

Özbilgin A, Özbel Y, Alkan MZ, et al. Trichomoniasis in non-gonococcic urethritis among male patients. J Egypt Soc Parasitol. 1994;24(3):621–625.

 PubMedGoogle Scholar

Dyudyun AD, Polyon NM, Gorbuntsov VV. Secnidazole in complex treatment of patients with urogential trichomoniasis. Dermatovenerol Cosmetol Sexopathol. 2016;1(4):287–292.

 Google Scholar

Lupin Pharmaceuticals Inc. SOLOSEC® (secnidazole): full Prescribing Information. 2022.

 Google Scholar

Pfizer Inc. FLAGYL® (metronidazole): full prescribing Information. 2021.

 Google Scholar

Mission Pharmacal Inc. TINDAMAX® (tinidazole): full prescribing Information. 2019.

 Google Scholar

ClinicalKey® [Internet]. Elsevier. 2022. [cited May 1, 2022]. Available from: https://www.elsevier.com/solutions/clinicalkey.

 Google Scholar

Workowski KA, Bachmann LH, Chan PA, et al., Sexually transmitted infections treatment guidelines, 2021. MMWR Recomm Rep. 70(4): 1–187. 2021.

 PubMed Web of Science ®Google Scholar

Fjeld H, Raknes G. Is combining metronidazole and alcohol really hazardous? Tidsskr Nor Laegeforen. 2014;134(17):1661–1663.

 PubMedGoogle Scholar

Pentikis H, Eder S, Kaufman G, et al. Secnidazole, an approved single dose drug for bacterial vaginosis, does not cause reproductive toxicity in animals. American Academy of Obstetricians and Gynecologists: Seattle WA. 2020 April 24-27.

 Google Scholar

Czeizel AE, Kazy Z, Vargha P. Oral tinidazole treatment during pregnancy and teratogenesis. Int J Gynaecol Obstet. 2003;83(3):305–306.

 PubMedGoogle Scholar

Subramanian C, Sobel JD. A case of high-level metronidazole-resistant trichomoniasis in pregnancy successfully treated. J Low Genit Tract Dis. 2011;15(3):248–249.

 PubMedGoogle Scholar