METACIN FORTE (powder for oral use)

Powder ranging in colour from light yellow to yellow-brown, with the odour of its components.

1 g of the product contains the following active substances:

- doxycycline hyclate — 500 mg;

- colistin sulphate — 4,800,000 IU.

Excipient: tartaric acid.

ATC vet classification code QJ01 — antibacterial veterinary medicinal products for systemic use. QJ01RA95 — Polymyxins, combinations with other antimicrobial agents.

Doxycycline is a bacteriostatic antibiotic belonging to the tetracycline group. The mechanism of action of doxycycline is associated with inhibition of protein synthesis. Doxycycline blocks the attachment of aminoacyl-tRNA to the acceptor site, thereby preventing the addition of new amino acids to the peptide chain and thus inhibiting protein synthesis. The product has a broad spectrum of antimicrobial activity against gram-positive (Staphylococcus spp., Diplococcus pneumoniae, Streptococcus spp., Pneumococcus spp., Bacillus anthracis, Clostridium tetani, Clostridium perfringens, Listeria monocytogenes, Actinomyces spp.) and gram-negative (Haemophilus influenzae, Pasteurella spp., Actinobacillus pleuropneumoniae, E. coli, Enterobacter spp., Klebsiella spp., Salmonella spp., Shigella spp., Yersinia spp.) bacteria, as well as mycoplasmas (Mycoplasma spp.), rickettsiae (Rickettsia spp.), and chlamydiae (Chlamydia spp.).

Colistin is an antibiotic of the polymyxin group, synthesised by the aerobic spore-forming rod Bacillus polymyxa. It acts bactericidally against gram-negative bacteria (non-invasive E. coli, Salmonella spp., Pseudomonas spp.) by binding to the phospholipids of the cytoplasmic membrane, increasing its permeability to both intracellular and extracellular components, which leads to disruption of cell barriers and lysis of the bacterial cell.

Following oral administration, colistin is absorbed from the gastrointestinal tract of calves in very small amounts. Colistin was not detected in the serum of calves. In the serum of chicks, colistin was detected at a low concentration 6 hours after administration via drinking water. Colistin does not accumulate in the organs and tissues of animals, is not broken down by digestive enzymes, and as a result, a high concentration of the antibiotic is established in the gastrointestinal tract. In contrast to the low concentrations of colistin in serum and tissues, high and sustained concentrations are consistently present throughout the various sections of the gastrointestinal tract. Higher concentrations are observed in the large intestine and caecum. Colistin is excreted primarily unchanged in the faeces.

Doxycycline is well absorbed following oral administration, with a bioavailability of 90%. The presence of feed in the gastrointestinal tract does not affect the absorption of doxycycline, unlike other tetracyclines. Doxycycline penetrates well into tissues and inflammatory foci; the concentration in the lungs of calves and pigs is approximately twice that in blood plasma. Following oral administration, doxycycline is absorbed from the gastrointestinal tract of poultry at 93–100% and is rapidly distributed throughout the body. The half-life of the product is 4–9 hours in cattle, 10 hours in horses, 7 hours in pigs, and 3 hours in sheep. Doxycycline penetrates virtually all organs and tissues; however, the highest levels are found in the lungs, liver, bile, reproductive organs, and kidneys. Doxycycline is detected at low concentrations in cerebrospinal fluid, but its concentration does not reach therapeutic levels. The maximum serum concentration is reached within 2–4 hours, and the therapeutic concentration is maintained for 18–24 hours.

Doxycycline undergoes virtually no metabolism and is excreted from the body primarily in the faeces in the form of inactive complexes and, to a lesser extent, in the urine.

Calves up to 8 weeks of age, pigs: treatment of animals suffering from septicaemia, as well as diseases of the respiratory tract (bronchopneumonia, pleuropneumonia, atrophic rhinitis, and others) and the gastrointestinal tract (colibacillosis, salmonellosis) caused by micro-organisms susceptible to doxycycline and colistin.

Domestic poultry (broiler chickens, replacement pullets, turkeys): treatment of poultry suffering from colibacillosis, salmonellosis, chlamydiosis, septicaemia, and respiratory tract diseases caused by micro-organisms susceptible to doxycycline and colistin.

- calves up to 8 weeks of age — 1,0 g of the product per 100 kg body weight (5 mg doxycycline and 48,000 IU colistin sulphate per 1 kg body weight) twice daily via drinking water, feed, milk, or milk replacer for 5 days;

- pigs — 2,0 g of the product per 100 kg body weight (10 mg doxycycline and 96,000 IU colistin sulphate per 1 kg body weight) once daily, or 200 g of the product per 1,000 L of drinking water daily for 5 days;

- domestic poultry (broiler chickens, replacement pullets, turkeys) — 0,4–0,5 g of the product per 10 kg body weight per day (20–25 mg doxycycline and 192,000–240,000 IU colistin sulphate per 1 kg body weight per day), or 100 g of the product per 500–1,000 L of drinking water daily for 5 days.

To prepare the solution, measure the required amount of the product into a small container and, stirring continuously, add drinking water, preferably warm. The concentrate prepared in this way (product-to-water ratio 1:20) is then immediately added to the required volume of drinking water, in accordance with the water allowance for the respective age group of poultry. When administering the product to a group, pigs and poultry must receive only water containing the medicinal product. A fresh solution must be prepared daily.

Prior to group administration, each batch of the product should first be tested on a small group (5–10 animals). If no adverse reactions are observed within 2–3 days, the product may be used for the entire stock.

Hypersensitivity to tetracycline-group products or colistin.

Do not use concomitantly with antibiotics of the penicillin or cephalosporin groups, quinolones, or cycloserine.

Do not use in animals with severe hepatic or renal impairment.

Do not use in laying hens producing eggs intended for human consumption.

Do not use in ruminants with a functional rumen, or in horses.

Do not use when resistant strains of the causative agent have been identified.

Do not use for prophylactic purposes.

Do not use concomitantly with products containing cations Mg²⁺, Al³⁺, or Ca²⁺, as these bind to doxycycline and impair its absorption.

No adverse reactions are observed at the recommended doses.

In isolated cases, allergic reactions (skin rash, pruritus, and oedema) and gastrointestinal disturbances (anorexia, vomiting, diarrhoea) may occur. Should these arise, administration of the product must be discontinued and desensitisation therapy initiated.

High doses or prolonged use of the product may cause a neurotoxic effect (e.g., ataxia).

Use of the product must be discontinued if resistance of micro-organisms to the active substances is detected. Microbiological confirmation of the diagnosis and susceptibility testing of the causative agents should be performed prior to prescribing the product.

The product is not recommended for use in animals during pregnancy or lactation due to the potential for neurotoxic effects. Use of the product is permissible only when it is evident that the benefits of treatment outweigh the potential risks.

No data are available regarding the embryotoxic, teratogenic, or mutagenic effects of doxycycline or colistin.

It is recommended that an interval of 1–2 hours be maintained between the use of this product and any other product containing polyvalent cations, as these limit the absorption of tetracyclines (doxycycline).

Doxycycline potentiates the effect of anticoagulants.

The product is not recommended to be mixed with other medicinal products.

Slaughter of animals for meat is permitted 8 days (pigs), 7 days (poultry), and 14 days (calves) after the last administration of the product. Meat obtained prior to the expiry of the specified withdrawal period must be disposed of or fed to non-productive animals, depending on the decision of the veterinary practitioner.

Polyethylene film pouches in accordance with GOST 10354 or other polymer film, containing 1, 2, 5, 10, 50, 100, 500 g, and 1 kg; bags of 25 kg.

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

Store in a dry, dark place out of reach of children at a temperature between 15 °C and 25 °C. Store in the original packaging.

2 years.

Shelf life after first opening of the packaging: 14 days, provided the open container is stored at a temperature between 15 °C and 25 °C in a dry, light-protected place.

Shelf life after dissolution in drinking water: 24 hours.