Fasigyn (tinidazole) 500 mg tablets. Fasigyn contains the active ingredient tinidazole. The structural formula of tinidazole is shown below: Chemical name: 1-(2-ethylsulfonylethyl)-2-methyl-5-nitro-imidazole Molecular formula: C8H13N3O4S Molecular weight: 247.3 CAS registry number: 19387-91-8.
Fasigyn (tinidazole) is a derivative of the substituted imidazole group of compounds. It is a pale yellow crystalline solid that is insoluble in water, but soluble in methanol and chloroform. Fasigyn tablets contain 500 mg of tinidazole. The following ingredients are also present: microcrystalline cellulose, alginic acid, maize starch, magnesium stearate, sodium lauryl sulfate, hypromellose, propylene glycol and titanium dioxide.
Fasigyn (tinidazole) has been shown to be effective against Trichomonas vaginalis, Entamoeba histolytica and Giardia lamblia. Minimum inhibitory concentration (MIC) values for Trichomonas vaginalis ranged from 1.25 to 10 ug/mL when the organism was incubated with tinidazole for 6 hours and 0.12 - 1.25 ug/mL when the incubation period was 3 days. Minimum cidal concentration (MCC) for the same organism ranged from 1.25 to 40 ug/mL and 1.25 - 2.5 ug/mL in the two studies respectively. The MIC for tinidazole against Entamoeba histolytica trophozoites after 48 hours incubation in Locke's medium was 40 ug/mL. An MIC of 6.25 ug/mL has been established for Entamoeba histolytica. In the absence of suitable laboratory techniques the MIC/MCC for Giardia lamblia is not known. Fasigyn (tinidazole) has also been shown to be effective against anaerobic bacteria including Bacteroides fragilis, other species of Bacteroides and Fusobacteria spp. Other organisms for which tinidazole is also bactericidal belong to species such as Peptococcus spp., Peptostreptococcus spp., Clostridium spp. (except C. difficile), and Eubacteria spp. Aerobic and facultative aerobic bacteria, Arachnia, propionibacteria, and actinomycetes are resistant to tinidazole.
Absorption
Following oral administration the drug is rapidly absorbed. In healthy female volunteers given a single oral 2 g dose of tinidazole, peak serum levels of 51 ug/mL were obtained 2 hours post-administration. At 24 hours mean serum concentration of tinidazole was 19 ug/mL; at 48 hours, 4 ug/mL and at 72 hours, 1.3 ug/mL. The serum half-life of tinidazole is approximately 12.7 hours.
Distribution
There is suggestive evidence that peak serum levels may be lower and serum half-life shorter in males than in females. The concentrations of tinidazole in various tissues and fluids of the female genital tract of gynaecological patients after a single 2 g oral dose have been reported. The concentrations in peritoneal fluid obtained at operation 8.5 - 15 hours after drug intake ranged between 16 - 40 ug/mL. Fallopian tube specimens yielded 15 - 26 ug/g tissue. Similar levels were obtained in specimens from myometrium, endometrium, vaginal secretions, cervix and omental fat. Cerebrospinal fluid (C.S.F.) concentrations in subjects without meningitis, were approximately 88% of the simultaneous serum concentrations. Tinidazole is bound to plasma proteins to the extent of approximately 12%.
Metabolism and Excretion
It is excreted in the urine primarily as unchanged drug. Approximately 20% of the unchanged drug appears in the urine in 24 hours.
Fasigyn is indicated for the oral treatment of:
Trichomonas vaginalis infections of the genito-urinary tract in both female and male patients. When infection with Trichomonas vaginalis has been confirmed or is suspected, simultaneous treatment of the consort is recommended.
Giardiasis.
Amoebic Dysentery and Amoebic Liver Abscess.
Acute Giardiasis and Acute Amoebic Dysentery and Amoebic Liver disease in children.
The prevention of infection of the surgical site which may be contaminated or potentially contaminated with anaerobic organisms, for example during colonic, gastro-intestinal and gynaecological surgery.
Fasigyn is contraindicated in patients with the following conditions:
Hypersensitivity to tinidazole, other 5-nitroimidazole derivatives, or any component of the tablet.
Blood dyscrasias or with a history of blood dyscrasias.
Active organic diseases of the central nervous system.
First trimester of pregnancy (see PRECAUTIONS, Use in Pregnancy).
Nursing mothers, as Fasigyn (tinidazole) is present in breast milk (see PRECAUTIONS, Use in Lactation).
Fasigyn may produce mild transient leukopenia and neutropenia. It is therefore recommended that total and differential leukocyte counts be done before and after treatment with the drug if a second course of therapy is necessary.
Alcoholic beverages should be avoided during therapy with Fasigyn and for at least 72 hours after discontinuing Fasigyn because of the possibility of a disulfiram-like reaction (abdominal cramps, vomiting, tachycardia and flushing).
If, during therapy with Fasigyn, abnormal neurological signs develop, therapy should be promptly discontinued (see ADVERSE EFFECTS).
During treatment with closely related chemical compounds, vaginal and intestinal monilial overgrowth has been reported and may necessitate treatment with nystatin.
Closely related chemical compounds enhance the activity of warfarin and if Fasigyn is to be given to patients receiving this or other anticoagulants, the dosage of the latter should be recalibrated (see INTERACTIONS WITH OTHER MEDICINES).
It is recommended that tablets be taken during or after a meal.
Category B3. Tinidazole crosses the placental barrier and enters the foetal circulation. Fasigyn is contraindicated during the first trimester of pregnancy. Animal studies suggest that tinidazole may have teratogenic potential. Benefit and risk from its use should, therefore, be carefully assessed and the drug may be used during the second and third trimester with caution and discretion and only if in the judgement of the attending physician the expected benefits outweigh the potential risk.
Tinidazole is secreted in breast milk. In view of its mutagenic potential, breast feeding is not recommended. Tinidazole may continue to appear in breast milk for more than 72 hours after administration. Women should not breast feed until at least three days after having discontinued Fasigyn.
Experience in treating paediatric patients with this drug is relatively limited and information on safety is still incomplete.
Because the drug is excreted in the urine caution should be exercised in patients with impaired renal function if administering a second or additional doses.
As with other agents in the 5-nitroimidazole class, tinidazole has been reported to produce testicular and spermatogenic adverse effects in male rats.
In vitro mutagenicity results with tinidazole were mixed (positive and negative). Tinidazole is mutagenic in the Ames test and was positive for in vivo genotoxicity in the mouse micronucleus assay.
Animal carcinogenic studies are inadequate to exclude tumorigenic potential. However, as other drugs of this class have been shown to be tumorigenic in animals, the benefits and risks from the use of tinidazole should be carefully assessed in each case, particularly in relation to the severity of the disease, the age of the patient or if a longer than usual treatment period is required.
The effect of tinidazole on the ability to drive or operate heavy machinery has not been studied.
Concurrent use of tinidazole and alcohol may produce a disulfiram-like reaction and should be avoided (see PRECAUTIONS, Disulfiram-like Reaction).
Drugs of similar chemical structure have been shown to potentiate the effects of oral anticoagulants. Prothrombin times should be closely monitored and adjustments to the dose of the anticoagulant should be made as necessary (see PRECAUTIONS, Interactions with Anticoagulants).
Mild adverse reactions have been reported in about 15% of patients of which the most common were gastrointestinal. Reported mild side effects have generally been infrequent and self-limiting. All adverse reactions are presented in the table below by system organ class and frequency.
| System Organ Class | Common >=1/100 to <1/10 | Frequency not known (cannot be estimated from available data) |
| Blood and the lymphatic system disorders | Leukopenia, neutropenia | |
| Immune system disorders | Drug hypersensitivity | |
| System Organ Class | Common >=1/100 to <1/10 | Frequency not known (cannot be estimated from available data) |
| Metabolism and nutrition disorders | Decreased appetite | |
| Nervous system disorders | Headache | Convulsions, neuropathy peripheral, paraesthesia, hypoaesthesia, sensory disturbances, ataxia, dizziness, dysgeusia |
| Ear and labyrinth disorders | Vertigo | |
| Vascular disorders | Flushing | |
| Gastrointestinal disorders | Vomiting, diarrhoea, nausea, abdominal pain | Glossitis, stomatitis, constipation, tongue discolouration |
| Skin and subcutaneous tissue disorders | Dermatitis allergic, pruritis | Angioedema, urticaria |
| Renal and urinary disorders | Chromaturia | |
| General disorders and administration site conditions | Pyrexia, fatigue, malaise | |
| Investigations | Blood urea increased, aspartate aminotransferase increased, eosinophil count increased, haemoglobin decreased, blood bilirubin increased | |
| CIOMS III categories: Common 1/100 to 1/10 ( 1% and <10%), Not known:frequency cannot be estimated from available data | ||
Trichomoniasis
Adult: 2 g (4 x 500 mg tablets) orally as a single stat dose.
Giardiasis
Adult: 2 g orally as a single stat dose. Children: 50 mg/kg of body weight given as a single dose, up to a maximum of 2 g. It may be necessary to repeat this dose once in some cases.
Acute Amoebic Dysentery
Adult: 2 g orally as a single dose for 2 to 3 days. (In the occasional instance when a three day course is ineffective, treatment may be continued for ten days). Children: 50 mg/kg of body weight up to a maximum of 2 g, given as a single daily dose on each three successive days.
Amoebic Liver Abscess
Adult: 2 g orally as a single daily dose for 3 days. (In the occasional instance when a three day course is ineffective, treatment may be continued for five days). Total dosage varies according to the virulence of the Entamoeba histolytica between 4.5 to 10 g. Children: 50 mg/kg of body weight, up to a maximum of 2 g, given as a single daily dose on each of five successive days. In amoebic involvement of the liver the aspiration of pus may be required in addition to therapy with Fasigyn.
Prevention of Postoperative Infections
Adult: A single oral dose of 2 g approximately 12 hours before surgery. Children: There is no data available to allow dosage recommendations for children below the age of 12 in the prophylaxis of anaerobic infections.
Dosage adjustments in patients with impaired renal function are generally not necessary. However, because tinidazole is easily removed by haemodialysis, patients may require additional doses of tinidazole to compensate.
Reports of overdoses in humans with tinidazole are anecdotal and do not provide consistent data regarding the signs and symptoms of overdose.
There is no specific antidote for the treatment of overdosage with tinidazole. Treatment is symptomatic and supportive. Tinidazole is easily dialysable. Contact the Poisons Information Centre on 13 11 26 for advice on the management of an overdose.
Fasigyn is supplied as white, round, biconvex, film coated oral tablets engraved with "FAS 500" on one side and plain on the other, each containing 500 mg tinidazole base, in blister packs of 4.
Store below 25oC.
S4 (Prescription Only Medicine).
Pfizer Australia Pty Ltd ABN 50 008 422 348 38-42 Wharf Road West Ryde NSW 2114.
2 April 1993.
20 November 2013
(r) Registered trademark.