COLI-OX 200 ® (powder for oral administration)

Powder ranging in colour from white to light yellow.

Composition

1 g of the product contains active substances:

- oxytetracycline hydrochloride – 100,0 mg;

- colistin sulphate – 1 200 000 IU.

Excipients: citric acid, sorbitol.

ATC vet classification code: QA07A – antimicrobial veterinary medicinal products used in intestinal infections. QA07AA98 – Colistin, combinations with other antimicrobials.

COLI-OX 200 is a combination product containing two antibiotics.

Oxytetracycline is an antibiotic belonging to the tetracycline group. Its mechanism of action consists in inhibition of protein synthesis by binding to the 30S ribosomal subunit of microorganisms sensitive to the product, thus preventing the association of ribosomes with aminoacyl-transfer RNA. It is also considered that oxytetracycline reversibly binds to 50S ribosomes and alters the permeability of the cytoplasmic membrane of sensitive microorganisms.

Oxytetracycline has a broad spectrum of activity against gram-positive (Streptococcus spp., Erysipelothrix spp.) and gram-negative (Clostridium spp., Corynebacterium spp., Brucella spp., Haemophilus spp., E. coli, Pasteurella spp., Klebsiella spp., Fusobacterium spp., Salmonella spp.) microorganisms, as well as against protozoa (Protozoa spp.), mycoplasmas (Mycoplasma spp.), rickettsiae (Rickettsia spp.) and chlamydiae (Chlamydia spp.).

Colistin is an antibiotic of the polymyxin group. It has a bactericidal effect on gram-negative bacteria (E. coli, Salmonella spp., Pseudomonas spp.) by binding to the phospholipids of the cytoplasmic membrane, increasing its permeability both for intracellular and extracellular components, which leads to destruction of cellular barriers. In addition, colistin binds phospholipid A and neutralises the biological effect of bacterial endotoxin.

After oral administration oxytetracycline is rapidly and almost completely absorbed from the gastrointestinal tract. The bioavailability of oxytetracycline is approximately 60–80%. The half-life of oxytetracycline is 4,3–9,7 hours in cattle, 6,7 hours in pigs and 3,6 hours in sheep. Oxytetracycline penetrates practically into all organs and tissues, but the highest levels are observed in the lungs, liver, bile, reproductive organs and kidneys. In low concentrations, oxytetracycline is found in the cerebrospinal fluid, but its concentration does not reach a therapeutic level. Oxytetracycline does not form metabolites. It is eliminated from the body in urine and bile.

Colistin is poorly absorbed after oral administration to calves and pigs, since its concentrations in the tissues and serum of these species are generally not detectable. In chickens, residues in serum are found for 6 hours after oral administration with drinking water. In contrast to the low concentrations of colistin in blood serum and tissues, high and constant concentrations are always present in different parts of the gastrointestinal tract. Colistin is stable in an acidic environment and is not destroyed by peptidases and proteases in the gastrointestinal tract. Higher concentrations are observed in the large intestine and caecum. It is excreted mainly with faeces.

Treatment of pigs, poultry (broiler chickens and replacement pullets, turkeys), lambs, calves and kids (up to 8 weeks of age) for diseases of the gastrointestinal and respiratory tracts caused by microorganisms sensitive to oxytetracycline and colistin.

- lambs, calves and kids (up to 8 weeks of age): 0,5 g of the product per 10 kg body weight twice daily (daily dose – 10 mg of oxytetracycline hydrochloride and 120 000 IU of colistin sulphate per 1 kg body weight) for 5–7 days.

- poultry (broiler chickens and replacement pullets, turkeys): 100 g of the product per 50–100 l of drinking water, or 100 g of the product per 50 kg of feed for 5–7 days, or 0.2–0.4 g of the product per 1 kg body weight of birds, which corresponds to 20–40 mg of oxytetracycline hydrochloride and 240 000–480 000 IU of colistin sulphate per 1 kg body weight.

- pigs: 1–2 g of the product per 10 kg body weight (10–20 mg of oxytetracycline hydrochloride and 120000–240000 IU of colistin sulphate per 1 kg body weight) with drinking water or feed for 5–7 days.

Depending on the recommended dose and body weight of the animals to be treated, the exact daily amount of the product should be calculated according to the following formula:

where:

M – mg of the product per litre of drinking water or per kg of feed;

X – dose of the product (mg per 1 kg body weight);

m – average body weight (kg) of the animals to be treated;

V – average daily water (l) or feed (kg) consumption per animal.

To prepare a solution, the required amount of the product is placed into a small container and warm water is added while continuously stirring. The concentrate prepared in this way (product : drinking water – 1:40) is immediately added to the required amount of drinking water in accordance with the water supply norms for the respective age groups of birds. Fresh solution of the product should be prepared daily.

Hypersensitivity to oxytetracycline and colistin.

Do not administer to animals with impaired renal and hepatic function.

Do not administer concurrently with bactericidal antibiotics such as penicillins, cephalosporins, aminoglycosides.

Do not administer with products containing divalent and trivalent cations such as Mg2+, Al3+, Ca2+, Zn2+, Bi3+, Fe3+.

Do not administer together with non-steroidal anti-inflammatory drugs.

Do not administer to laying hens whose eggs are intended for human consumption.

Do not administer to ruminants with functionally developed forestomachs.

At recommended doses adverse reactions are not observed. In individual cases allergic reactions may occur (skin rash, pruritus and oedema). In young animals the product may cause tooth discolouration.

Initially the product should be administered to a small group (7–8 heads) of animals. If no complications are observed within 2–3 days, the product is administered to the whole herd.

When using products containing colistin, generally accepted principles regarding the use of antimicrobial agents should be taken into account. It should be borne in mind that colistin is used in human medicine for the treatment of infections caused by multiresistant microorganisms. Therefore, it should be used only considering the results of susceptibility testing of microorganisms. Use of products in violation of the instructions given in this short product description may lead to an increase in the number of bacteria resistant to it and to a decrease in the effectiveness of treatment with other antimicrobials due to cross-resistance.

Use in pregnant animals is not recommended, as a neurotoxic effect is possible. The product should only be used following a benefit-risk assessment by the responsible veterinarian.

The product must not be administered concurrently with bactericidal products such as penicillins, cephalosporins, aminoglycosides.

When administered concurrently with products containing divalent and trivalent cations such as Mg2+, Al3+, Ca2+, Zn2+, Bi3+, Fe3+, oxytetracycline forms chelate complexes, which prevents its absorption.

The product increases the bioavailability of digoxin, which may lead to intoxication.

When administered together with theophylline (euphyllin), the product may cause adverse effects from the gastrointestinal tract (vomiting, anorexia or diarrhoea).

The product enhances the nephrotoxic effect of methoxyflurane.

When administered concurrently with anticoagulants, dose adjustment of the latter is required, as the product inhibits plasma prothrombin activity.

The slaughter of animals and poultry for meat is allowed 11 days after the last administration of the product. Meat obtained before the specified period should be disposed of or fed to non-food-producing animals, depending on the opinion of the veterinary surgeon.

Bags made of polyethylene film according to GOST 10354 or other polymer film containing 1, 10, 50, 100, 500 g and 1 kg of the product, and bags of 25 kg.

Polymer containers of 100 g, 500 g, 1 kg.

Store in a dry, dark place out of the reach of children at a temperature from 5 °C to 25 °C.

2 years.

Shelf life after first opening of the immediate packaging, if storage conditions are observed and the package with the product is subsequently tightly closed, is equal to the shelf life of the product.

Shelf life after dilution of the solution: 24 hours.