Each mL contains

Metronidazole 125 mg

Butylhydroxytoluene (E321) 0.2 mg

Oral suspension.

Flavoured oily suspension with brown visible particles.

Dogs

Treatment of infections of the gastrointestinal tract caused by Giardia spp. and Clostridium spp. (i.e. C. perfringens or C. difficile). Treatment of infections of the urogenital tract, oral cavity, throat and skin caused by obligate anaerobic bacteria (e.g. Clostridium spp.) susceptible to metronidazole.

Do not use in case of hepatic disorders.

Do not use in case of hypersensitivity to the active substance or to any of the excipients.

None

Due to the likely variability (time, geographical) in the occurrence of metronidazole resistant bacteria, bacteriological sampling and susceptibility testing are recommended.

Whenever possible, the product should only be used based on susceptibility testing. Official, national and regional antimicrobial policies should be taken into account when the veterinary medicinal product is used.

Metronidazole has confirmed mutagenic and genotoxic properties in laboratory animals as well as in humans. Metronidazole is a confirmed carcinogen in laboratory animals and thus may have carcinogenic effects in humans as well. However, there is inadequate evidence in humans for the carcinogenicity of metronidazole.

The product can cause skin sensitisation. In case of known hypersensitivity to metronidazole or other nitroimidazole derivatives or one of the components of the product, avoid contact with the veterinary medicinal product.

Avoid contact with the skin or mucous membranes including hand-to-mouth contact. To avoid such contact wear impervious gloves when handling the product and/or for direct administration into the animal's mouth.

Do not allow treated dogs to lick persons immediately after intake of the medication.

Wash hands after use.

In case of skin contact, wash thoroughly the affected area.

Metronidazole may cause adverse (neurological) effects.

Avoid accidental ingestion.

Do not drink, eat or smoke when administering the product.

Close the bottle immediately after use to avoid the child gaining access to the contents. Do not leave a syringe containing solution in the sight or reach of children. In order to prevent children from getting access to used syringes, keep the syringes in the original packaging after use.

In case of accidental ingestion, seek-medical advice immediately and show the package leaflet or the label to physician.

Avoid the access of children to the dog’s medicated food. In order to prevent children from getting access to the dog’s medicated food, pour it over a part of the feed and wait until the animal has completely consumed the medicated feed, then administer the rest of the feed. Give the treatment out of the sight and reach of children. Any uneaten medicated food must be removed immediately and the bowl washed thoroughly; wear gloves and wash hands when handling the product and cleaning the contaminated food bowl.

The following adverse reactions may occur after administration of metronidazole: vomiting, hepatotoxicity and neutropenia. In very rare cases, neurological signs may occur especially after prolonged treatment with metronidazole.

Studies in laboratory animals have shown inconsistent results with regard to teratogenic/embryotoxic effects of metronidazole. Therefore, use of this product during pregnancy is not recommended. Metronidazole is excreted in milk and use during lactation is therefore not recommended.

Metronidazole may have an inhibitory effect on the degradation of other drugs in the liver, such as phenytoin, cyclosporine and warfarin.

Cimetidine may decrease the hepatic metabolism of metronidazole resulting in increased serum concentration of metronidazole.

Phenobarbital may increase hepatic metabolism of metronidazole resulting in decreased serum concentration of metronidazole.

Oral use.

The recommended dose is 50 mg metronidazole per kg bodyweight per day (i.e. 0.4 mL per kg bodyweight), preferably given in two equally divided doses (i.e. 25 mg equivalent to 0.2 mL per kg bodyweight twice daily) for 5-7 days.

To ensure a correct dosage body weight should be determined as accurately as possible to avoid underdosing and overdosing. The dosage table is intended as a guide to dispensing the product at the volume corresponding to either 25 mg/kg for administration twice daily or 50 mg/kg for administration once daily.

Examples of bodyweight (kg)	Volume to administer twice daily for 25mg/kg	Volume to administer once daily for 50mg/kg
1		0.4ml
2	0.4ml	0.8ml
3	0.6ml	1.2ml
4	0.8ml	1.6ml
5	1.0ml	2.0ml
10	2.0ml	4.0ml
15	3.0ml	6.0ml
20	4.0ml	8.0ml
25	5.0ml	10.0ml
30	6.0ml	12.0ml
35	7.0ml	14.0ml
40	8.0ml	16.0ml

For doses requiring more than two filled syringes, the dosing should be twice daily in order to minimize counting and dosing errors.

The oral suspension is delivered through the package described below:

Administer the product by pouring it over a part of the feed or by direct administration into the animal's mouth. Wear impervious gloves when handling the product and/or administering the product into the animal's mouth.

When administered over the feed, wait until the animal has completely consumed the medicated feed, then administer the rest of the feed.

Administer the product by pouring it over a part of the feed or by direct administration into the animal's mouth. Wear impervious gloves when handling the product and/or administering the product into the animal's mouth. When administered over the feed, wait until the animal has completely consumed the medicated feed, then administer the rest of the feed.

Adverse events are more likely to occur at doses and treatment durations in excess of the recommended treatment regimen. If neurological signs occur, treatment should be discontinued and the patient should be treated symptomatically.

Not applicable

Pharmacotherapeutic group: Agent against protozoal disease, nitroimidazole derivative.

ATCvet code: QP51AA01.

After metronidazole has penetrated the bacteria the molecule is reduced by the sensitive bacteria (anaerobe). The metabolites that are created have a toxic effect on the bacteria through binding to the bacterial DNA. In general metronidazole is bactericidal for sensitive bacteria in concentrations equal to or a little higher than the minimum inhibiting concentration (MIC).

Minimum Inhibitory Concentrations (MICs) have been determined for metronidazole in European isolates of target bacteria, isolated from dogs with gastrointestinal disease in 2016.

Species	MIC range (μg/ml)	MIC50 (μg/ml)	MIC90 (μg/ml)
Clostridium spp. (C.difficile & C.perfringens)	0.5 - 2	1	1

The MICs of the collected pathogens showed mono-modal distribution profiles with good susceptibility towards metronidazole. Clinical breakpoints* for metronidazole are established for anaerobes: susceptible: ≤8 µg/ml; intermediate: 16 µg/ml; resistant: ≥32 µg/ml.

According to these breakpoints no clinical resistant strains of Clostridium spp. pathogens were observed.

*(CLSI, 2017. Performance Standards for Antimicrobial Susceptibility Testing -Twenty-Seventh Edition M100. Clinical and Laboratory Standards Institute (CLSI), Wayne, PA 19087-1898 USA)

Clinically metronidazole does not have any relevant effect on facultative anaerobe, obligate aerobe and microaerophilic bacteria.

Metronidazole is also active in protozoa. In Giardia spp. in particular, metronidazole primarily targets the trophozoites (active replication of the parasite) resulting in their death and by consequence leading to dramatic decrease in cyst shedding.

After administration of the higher dose (50 mg/day/kg of bw), the absolute bioavailability is 98 % in fasted dog. The mean maximum concentration (Cmax) was 62.4 µg/mL +/- 9.7 (mean +/- SD) in plasma and occurs between 0.25 and 4 hours after dosing (Tmax). Food was shown to decrease the oral bioavailability which remains high in fed dogs with relative F of 81% (with F fasted = 100%). Metronidazole penetrates into the tissues and bodily fluids, such as saliva, milk, vaginal secretions and semen. Metronidazole is metabolised in the liver, by side chain oxidation and glucuronide synthesis. Both metabolites and unchanged drug are eliminated in the urine (mostly) and faeces. Elimination half-life is between 3 to 5 hours.

Butylhydroxytoluene (E321)

Aluminium stearate

Stearic acid (E570)

Poultry liver powder

Triglycerides medium chain

In the absence of compatibility studies, this veterinary medicinal product must not be mixed with other veterinary medicinal products.

Shelf life of the veterinary medicinal product as packaged for sale: 3 years.

Shelf life after first opening the immediate packaging:

30 ml bottle: 3 months.

100 ml bottle: 6 months.

Store below 30° C.

Opaque white polyethylene terephthalate bottle closed with a plastic dispenser cap. Carton box containing a 30 ml or 100 ml bottle and a 3 ml graduated syringe.

Not all pack sizes may be marketed.

Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal product should be disposed of in accordance with local requirements.

VIRBAC, 1ère avenue – 2065m – LID, 06516 Carros, France

Vm 05653/4210

10 April 2018

August 2022