Protogyn is indicated for the treatment of the following infections:

• Eradication of Helicobacter pylori associated with duodenal ulcers, in the presence of antibiotic and acid suppressant therapy (see section 4.2).
•  Anaerobic infections such as:
•  Intraperitoneal infections: peritonitis, abscess.
• Gynaecological infections: endometritis, endomyometritis, tube-ovarian abscess.
• Bacterial septicaemia.
• Post-operative wound infections.
• Skin and soft tissue infections.
• Upper and lower respiratory tract infections: pneumonia, empyema, lung abscess.
• Non-specific vaginitis.
• Acute ulcerative gingivitis.
• Urogenital trichomoniasis in both male and female patients.
• Giardiasis.
• Intestinal amoebiasis.
• Amoebic involvement of the liver.
• Prophylaxis: The prevention of post-operative infections caused by anaerobic bacteria, especially those associated with colonic, gastro-intestinal and gynaecological surgery.

Route: Oral administration during or after a meal.
Posology
Eradication of H. pylori associated with duodenal ulcers:
Adults: the usual dose of tinidazole is 500mg twice daily coadministered with omeprazole 20mg twice daily and clarithromycin 250mg twice daily for 7 days.
Clinical studies using this 7 day regimen have shown similar H. pylori eradication rates when omeprazole 20mg once daily was used. For further information on the dosage for omeprazole see Astra data sheet.
Anaerobic infections:
Adults: an initial dose of 2g the first day followed by 1g daily given as a single dose or as 500mg twice daily. Treatment for 5 to 6 days will generally be adequate but clinical judgement must be used in determining the duration of therapy, particularly when eradication of infection from certain sites may be difficult. Routine clinical and laboratory observation is recommended if it is considered necessary to continue therapy for more than 7 days.
Children: < 12 years – there is no data available.
Non-specific vaginitis:
Adults: non-specific vaginitis has been successfully treated with a single oral dose of 2g. Higher cure rates have been achieved with 2g single doses on 2 consecutive days (total dose 4g).

Acute Ulcerative Gingivitis:
Adults: a single oral dose of 2g.
Urogenital trichomoniasis: (When infection with Trichomonas vaginalis is confirmed, simultaneous treatment of the consort is
recommended).
Adults: a single dose of 2g.
Children: a single dose of 50 to 75mg/kg of body weight. It may be necessary to repeat this dose.
Giardiasis:
Adults: a single dose of 2g.
Children: a single dose of 50 to 75mg/kg of body weight. It may be necessary to repeat this dose.
Intestinal Amoebiasis:
Adults: a single daily dose of 2g for 2 to 3 days.
Children: a single daily dose of 50 to 60mg/kg of body weight on each of 3 successive days.
Amoebic involvement in the liver:
Adults: total dosage varies from 4.5 to 12g, depending on the virulence of the Entamoeba histolytica.
For amoebic involvement of the liver, the aspiration of pus may be required in addition to therapy with
Protogyn.
Initiate treatment with 1.5 to 2g as a single oral daily dose for three days. Occasionally when a three
day course is ineffective, treatment may be continued for up to six days.
Children: a single dose of 50 to 60 mg/kg of body weight per day for five successive days.
Use in Renal impairment
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.
Prevention of post-operative infection:
Adults: a single dose of 2g approximately 12 hours before surgery.
Children: < 12 years – there is no data available.
It is recommended that tinidazole be taken during or after a meal.
Use in the elderly: there are no special recommendations for this age group.
Method of administration:
Oral administration. Swallow tablets whole with a glass of water during or after a meal.

Protogyn tablets are contraindicated: - In patients with hypersensitivity to tinidazole or to any of the excipients listed in section 6.1. - As with other drugs of similar structure, tinidazole is contraindicated in patients having, or with a history of, blood dyscrasia, although no persistent haematological abnormalities have been noted in clinical or animal studies. Tinidazole should be avoided in patients with organic neurological disorders. Tinidazole, other 5-nitroimidazole derivatives or any of the components of this product should not be administered to patients with known hypersensitivity to the drug. Use of tinidazole is contraindicated during the first trimester of pregnancy and in nursing mothers (see section 4.6 ).

As with related compounds, alcoholic beverages should be avoided during tinidazole therapy because of the possibility of a disulfiram-like reaction (flushing, abdominal cramps, vomiting, tachycardia). Alcohol should be avoided until 72 hours after discontinuing tinidazole.
Drugs of similar chemical structure have also produced various neurological disturbances such as dizziness, vertigo, incoordination and ataxia. If during therapy with tinidazole abnormal neurological signs develop, therapy should be discontinued.
Carcinogenicity has been seen in mice and rats treated chronically with metronidazole, another nitroimidazole agent. Although carcinogenicity data is not available for tinidazole, the two drugs are structurally related and therefore there is a potential for similar biologic effects. Mutagenicity results with tinidazole were mixed (positive and negative). The use of tinidazole for longer treatment than usually required should be carefully considered.

Alcohol: concurrent use of tinidazole and alcohol may produce a disulfiram-like reaction and should be avoided, (see section 4.4, Special warnings and precautions for use).
Anticoagulants: drugs of similar chemical structure have been shown to potentiate the effects of oral anticoagulants. Prothrombin time should be closely monitored and adjustments to the dose of the anticoagulants should be made as necessary.

Pregnancy:
Fertility studies in rats receiving 100mg and 300mg tinidazole/kg had no effect on fertility, adult and pup weights, gestation, viability or lactation. There was a slight, not significant, increase in resorption rate at the 300mg/kg dose. Tinidazole crosses the placental barrier. Since the effects of compounds of this class on foetal development are unknown, the use of tinidazole during the first trimester is contraindicated. There is no evidence that tinidazole is harmful during the latter stages of pregnancy, but its use during the second and third trimesters requires that the potential benefits be weighed against possible hazards to mother or foetus.
Breast-feeding:
Tinidazole is excreted in breast milk. Tinidazole may continue to appear in breast milk for more than 72 hours after administration. Women should not nurse until at least 3 days after having discontinued taking tinidazole.

No special precautions should be necessary. However, drugs of similar chemical structure, including tinidazole, have been associated with various neurological disturbances such as dizziness, vertigo, ataxia, peripheral neuropathy (paraesthesia, sensory disturbances, hypoaesthesia) and rarely convulsions. If any abnormal neurological signs develop during tinidazole therapy, the drug should be discontinued.

Reported side effects have generally been infrequent, mild and self-limiting. The reported undesirable effects are listed below according to MedDRA system organ class classification and frequency.
Within each frequency category, the ADRs are presented in the order of clinical importance. 1i Frequencies are defined using the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data).

Blood and the lymphatic system disorders : Not known: Leukopenia.

Immune system disorders : Not known: Drug hypersensitivity.

Metabolism and nutrition disorders : Common: Decreased appetite.

Nervous system disorders : Common: Headache.

Not known: Convulsions , Neuropathy peripheral , Paraesthesia , Hypoaesthesia , Sensory disturbances , Ataxia , Dizziness,Dysgeusia.

Ear and labyrinth disorders Common: Vertigo.

Vascular disorders : Not known: Flushing .

Gastrointestinal disorders : Common:  Vomiting , Diarrhoea, Nausea, Abdominal pain.

Not known: Glossitis , Stomatitus , Tongue discolouration.

Skin and subcutaneous tissue disorders : Common: Dermatitis allergic , Pruritis.

Not known: Angioedema , Urticaria.

Renal and urinary disorders : Not known: Chromaturia.

General disorders and administration site conditions : Not known: Pyrexia , Fatigue. 

In acute animal studies with mice and rats, the LD50 for mice was >3600mg/kg and >2300mg/kg for oral and intraperitoneal administration respectively. For rats, the LD50 was >2000mg/kg for both oral and intraperitoneal administration. Signs and symptoms of overdosage: There are no reported overdoses in humans with tinidazole.
Treatment for overdosage: There is no specific antidote for treatment of overdosage with tinidazole.
Treatment is symptomatic and supportive. Gastric lavage may be useful. Tinidazole is easily dialysable.

Pharmacotherapeutic group: Antiinfectives for systemic use, ATC code: J 01XD02
Tinidazole is active against both protozoa and obligate anaerobic bacteria. The activity against protozoa involves Trichomonas vaginalis, Entamoeba histolytica and Giardia lamblia.
The mode of action of tinidazole against anaerobic bacteria and protozoa involves penetration of the drug into the cell of the micro-organism and subsequent damage of DNA strands or inhibition of their synthesis. Tinidazole is active against Helicobacter pylori, Gardnerella vaginalis and most anaerobic bacteria including Bacteroides fragilis, Bacteroides melaninogenicus, Bacteroides spp., Clostridium spp., Eubacterium spp., Fusobacterium spp., Peptococcus spp., Peptostreptococcus spp. and
Veillonella spp.
Helicobacter pylori (H.pylori) is associated with acid peptic disease including duodenal ulcer and gastric ulcer in which about 95% and 80% of patients respectively are infected with this agent. H.pylori is also implicated as a major contributing factor in the development of gastritis and ulcer recurrence in such patients. Evidence suggests a causative link between H.pylori and gastric carcinoma.
Clinical evidence has shown that the combination of tinidazole with omeprazole and clarithromycin eradicates 91-96% of H.pylori isolates.
Various different H.pylori eradication regimens have shown that eradication of H.pylori  heals duodenal ulcers and reduces the risk of ulcer recurrence.

Tinidazole is rapidly and completely absorbed following oral administration. In studies with healthy volunteers receiving 2g tinidazole orally, peak serum levels of 40-51 micrograms/ml were achieved within two hours and decreased to between11-19 micrograms/ml at 24 hours. Healthy volunteers who received 800mg and 1.6g tinidazole IV over 10-15 minutes achieved peak plasma concentrations that ranged from 14 to 21mcg/ml for the 800mg dose and averaged 32mcg/ml for the 1.6g dose. At 24 hours post infusion, plasma levels of tinidazole decreased to 4-5mcg/ml and 8.6mcg/ml respectively, justifying once daily dosing. Plasma levels decline slowly and tinidazole can be detected in plasma at concentrations of up to 1 microgram/ml at 72 hours after oral administration. The plasma elimination half-life for tinidazole is between 12-14 hours.
Tinidazole is widely distributed in all body tissues and also crosses the blood brain barrier, obtaining clinically effective concentrations in all tissues. The apparent volume of distribution is about 50 litres. About 12% of plasma tinidazole is bound to plasma protein.
Tinidazole is excreted by the liver and kidneys. Studies in healthy patients have shown that over 5 days, 60-65% of an administered dose is excreted by the kidneys with 20-25% of the administered dose excreted as unchanged tinidazole. Up to 5% of the administered dose is excreted in the faeces.
Studies in patients with renal failure (creatinine clearance <22ml/min) indicate that there is no statistically significant change in tinidazole pharmacokinetic parameters in these patients, ( see section 4.2 ).

Tinidazole has been shown to be mutagenic in some bacterial strains tested in vitro (with and without metabolic activation). Tinidazole was negative for mutagenicity in a mammalian cell culture system utilising Chinese hamster lung V79 cells (HGPRT test system) and negative for genotoxicity in the Chinese hamster ovary (CHO) sister chromatid exchange assay. Tinidazole was positive for in vivo genotoxicity in the mouse micronucleus assay.

• Sodium lauryl sulfate.
• Povidone.
• Microcrystalline cellulose.
• Croscarmellose sodium.
• Talc.
• Opadry white.
• FD & C yellow Number 6.

Not applicable

36 month(s)

Store below 30◦C

PVC/Aluminum blisters containing film coated tablets.
Pack size for 500 mg tablets: 4 as commercially available

Any unused product or waste material should be disposed of in accordance with local requirements.