Tinidazole

P01A - Agents against amoebiasis and other protozoal diseases ATC P01AB02 Small molecule approved 2004 Oral Natural product Black-box warning

JFDA label: Protogyn F.C.Tab

⚠ Black-Box Warning

Carcinogenic:

Mechanism of Action

Disrupting Agent of DNA — DNA disrupting agent

Target	Action	Gene / class
DNA efficacy	DISRUPTING AGENT

Indications

Approved

Amebiasis
Bacterial vaginosis
Giardiasis
Trichomoniasis

Off-label

Helicobacter pylori eradication
Prophylaxis against sexually transmitted diseases following sexual assault
Urethritis, nongonococcal (persistent and recurrent)

Antimicrobial Spectrum

Expected / intrinsic spectrum (EUCAST breakpoints & labels) — not local resistance. Source: openfda-label.

Protozoa

Organism	Activity	MIC
Candida albicans	Active	—
Chlamydia trachomatis	Active	—
Entamoeba histolytica	Active	—
Giardia duodenalis	Active	—
Haemophilus vaginitis	Active	—
Mycoplasma hominis	Active	—
Neisseria gonorrhoeae	Active	—
Trichomonas vaginalis	Active	—

Contraindications

Source: Lexicomp

Hypersensitivity to tinidazole, nitroimidazole derivatives, or any component of the formulation Absolute
breast-feeding Absolute
pregnancy (first trimester) Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (2)

Not Known Flushing · palpitations

Nervous system disorders (11)

Common dizziness · Fatigue · headache · malaise

Not Known Ataxia · burning sensation · drowsiness · insomnia · peripheral neuropathy (transient; includes numbness and paresthesia) · seizure · vertigo

Hepatobiliary disorders (1)

Not Known Increased serum transaminases

Renal and urinary disorders (8)

Common dysuria · pelvic pain · Urinary tract infection · urine abnormality · Vulvovaginal candidiasis · vulvovaginal disease (discomfort)

Not Known Dark urine · vaginal discharge

Blood and lymphatic system disorders (2)

Not Known Leukopenia (transient) · neutropenia (transient)

Immune system disorders (1)

Not Known Angioedema

Metabolism and nutrition disorders (2)

Common Hypermenorrhea

Not Known Increased thirst

Gastrointestinal disorders (17)

Common abdominal cramps · anorexia · constipation · decreased appetite · Dysgeusia · dyspepsia · epigastric distress · flatulence · nausea · vomiting

Not Known Abdominal pain · diarrhea · oral candidiasis · salivation · stomatitis · tongue discoloration · xerostomia

Skin and subcutaneous tissue disorders (5)

Common Body odor

Not Known Diaphoresis · pruritus · skin rash · urticaria

Musculoskeletal and connective tissue disorders (4)

Common Weakness

Not Known Arthralgia · arthritis · myalgia

Infections and infestations (1)

Not Known Candidiasis (overgrowth)

General disorders and administration site conditions (1)

Not Known Fever

Respiratory, thoracic and mediastinal disorders (1)

Common Upper respiratory tract infection

Dosing

Source: Lexicomp

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: 2 g once daily for 2 days or 1 g once daily for 5 days Bacterial vaginosis, recurrent (off-label dose): Oral: 500 mg twice daily for 7 days followed by intravaginal therapy with boric acid, followed by intravaginal metronidazole suppressive therapy (CDC [Workowski 2015]) Giardiasis: Oral: 2 g as a single dose Helicobacter pylori eradication (off-label use): Oral: American College of Gastroenterology guidelines (Chey 2007; Chey 2017): 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. Prophylaxis against sexually transmitted diseases following sexual assault (off-label use): Oral: 2 g as a single dose in combination with azithromycin plus ceftriaxone (CDC [Workowski 2015]) Trichomoniasis: Oral: 2 g as a single dose; sexual partners should be treated at the same time Trichomoniasis, persistent or recurrent (ie, treatment failure of nitroimidazole [eg, metronidazole]) (index case; treatment of sex partner; off-label dose): Oral: 2 g once daily for 7 days (CDC [Workowski 2015]) Urethritis, nongonococcal (recurrent or persistent urethritis in men who have sex with women and who live in regions where T. vaginalis is prevalent; off-label use): Oral: 2 g as a single dose. Note: Compliance with initial regimen and lack of reexposure to an untreated sex partner should be excluded prior to use (CDC [Workowski 2015])

(For additional information see "Tinidazole: Pediatric drug information") Amebiasis, intestinal: Oral: Children >3 years and Adolescents: 50 mg/kg/day for 3 days (maximum dose: 2 g/day) Amebiasis, liver abscess: Oral: Children >3 years and Adolescents: 50 mg/kg/day for 3 to 5 days (maximum dose: 2 g/day) Giardiasis: Oral: Children >3 years and Adolescents: 50 mg/kg as a single dose (maximum dose: 2 g) Prophylaxis against sexually transmitted diseases following sexual assault (off-label use): Adolescents: Refer to adult dosing.

Refer to adult dosing.

No dosage adjustment necessary. Hemodialysis: An additional dose equal to 1/2 the usual dose, should be administered at the end of hemodialysis if tinidazole is administered prior to hemodialysis on a dialysis days.

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); use with caution.

Warnings & Precautions

Source: Lexicomp

Carcinogenic

Carcinogenicity has been observed with another nitroimidazole derivative (metronidazole) in animal studies; use should be reserved for approved indications only.

CNS effects

Seizures and peripheral neuropathy (eg, extremity numbness and paresthesia) have been reported with tinidazole and other nitroimidazole derivatives; discontinue treatment if abnormal neurologic signs or symptoms occur.

Superinfection

Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD), pseudomembranous colitis, and/or vaginal candidiasis. CDAD has been observed >2 months postantibiotic treatment. Disease-related concerns:

Blood dyscrasias

Use with caution in patients with current or a history of blood dyscrasias.

Hepatic impairment

Use with caution in patients with current or a history of hepatic impairment.

Pregnancy & Lactation

Pregnancy

FDA category C

The manufacturer contraindicates use of tinidazole during the first trimester of pregnancy. Adverse events have been observed in some animal reproduction studies. Tinidazole crosses the human placenta and enters the fetal circulation. The safety of tinidazole for the treatment of bacterial vaginosis or trichomoniasis in pregnant women has not been well evaluated. Other agents are preferred for use during pregnancy (CDC [Workowski 2015]).

Lactation

Contraindicated

Tinidazole is excreted into breast milk in concentrations similar to those in the maternal serum and can be detected for up to 72 hours after administration. Tinidazole is contraindicated in nursing mothers unless breast-feeding is interrupted during therapy and for 3 days after the last dose.

Chemistry & Properties

Formula	C8H13N3O4S
Molecular weight	247.28 g/mol
IUPAC name	1-(2-ethylsulfonylethyl)-2-methyl-5-nitroimidazole
CAS	19387-91-8
PubChem CID	5479
InChIKey	`HJLSLZFTEKNLFI-UHFFFAOYSA-N`
logP	0.53 (XLogP -0.4)
Polar surface area	95.1 Å²
H-bond acceptors / donors	6 / 0
Drug-likeness (QED)	0.56
Lipinski violations	0

SMILES

CCS(=O)(=O)CCn1c([N+](=O)[O-])cnc1C

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	10.0%
Half-life	1.718 h
Volume of distribution	0.721 L/kg
Protein binding	17.7%
BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP2C19	Substrate	—
CYP2C9	Substrate	—
CYP3A4	Substrate	—

Transporters

BCRP (Inhibitor)BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)MRP3 (Inhibitor)MRP4 (Inhibitor)OATP1B1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OCT1 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)

Drug–drug interactions (100+, DDInter)

Interacting drug	Severity	Management
Amprenavir	major
Typhoid vaccine (live)	major
Vibrio cholerae CVD 103-HgR strain live antigen (live)	major
Abametapir (topical)	moderate
Adalimumab	moderate
Amiodarone	moderate
Amobarbital	moderate
Anisindione	moderate
Apalutamide	moderate
Atorvastatin	moderate
Auranofin	moderate
Aurothioglucose	moderate
Benznidazole	moderate
Berotralstat	moderate
Bexarotene	moderate
Boceprevir	moderate
Bortezomib	moderate
Brentuximab vedotin	moderate
Brigatinib	moderate
Butabarbital	moderate
Butalbital	moderate
Cabazitaxel	moderate
Capecitabine	moderate
Carboplatin	moderate
Carfilzomib	moderate
Cenobamate	moderate
Cerivastatin	moderate
Certolizumab pegol	moderate
Chloramphenicol	moderate
Chloroquine	moderate
Cholestyramine	moderate
Cisplatin	moderate
Colchicine	moderate
Conivaptan	moderate
Crizotinib	moderate
Cyclosporine	moderate
Dabrafenib	moderate
Dapsone	moderate
Darunavir	moderate
Deferasirox	moderate

Showing 40 of 100+.

Registered Products (5)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Protogyn F.C.Tab	Film-Coated Tablet 500 mg	4 tab pack varies	Hayat Pharmaceutical Industries CO.PLC/JORDAN	2.140
Tinogyn	Tablet 500 mg	4 tab pack varies	JORDAN RIVER PHARMA.IND(JORIVER)/JORDAN	2.140
FASIGYN TABS	Tablet 500 mg	4 tab	Khoury Drug Store	2.670
Protogyn F.C.Tab	Film-Coated Tablet 500 mg	12 tab pack varies	Hayat Pharmaceutical Industries CO.PLC/JORDAN	6.020
Tinogyn	Tablet 500 mg	12 tab pack varies	JORDAN RIVER PHARMA.IND(JORIVER)/JORDAN	6.020