BOVIKEN® (solution for injection)

A liquid ranging from light yellow to dark yellow in colour.

1 ml of the product contains active substances:

- marbofloxacin – 40,0 mg,

- ketoprofen – 60,0 mg.

Excipients: sodium metabisulphite (E223), L-arginine, citric acid, propylene glycol, benzyl alcohol, water for injections.

ATCvet code: QJ01 — Antibacterials for systemic use. QJ01RV — Combinations of antibacterials.

The active substances of the product are the antibiotic marbofloxacin, a fluoroquinolone antibiotic, and ketoprofen, a non-steroidal anti-inflammatory drug (NSAID).

Marbofloxacin is active against Gram-negative (Escherichia coli, Salmonella Typhimurium, Citrobacter freundii, Enterobacter cloacae, Serratia marcescens, Morganella morganii, Proteus spp., Klebsiella spp., Shigella spp., Pasteurella spp., Haemophilus spp., Moraxella spp., Pseudomonas spp.) and Gram-positive (Staphylococcus spp.) microorganisms, as well as against mycoplasmas (Mycoplasma bovis, Mycoplasma hyopneumoniae). The mechanism of action of marbofloxacin consists in inhibition of bacterial DNA gyrase (topoisomerase II), which stops inhibits bacterial DNA replication and synthesis.

Ketoprofen is an arylpropionic acid derivative with non-steroidal anti-inflammatory properties. It has analgesic, anti-inflammatory and antipyretic effects and inhibits platelet aggregation. The mechanism of action is associated with inhibition of prostaglandin synthesis through an effect on the cyclo-oxygenase (COX) pathway of arachidonic acid metabolism. In addition, ketoprofen inhibits lipoxygenase and causes marked suppression of neutrophil activity. Ketoprofen stabilises lysosomal membranes and inhibits the release of enzymes from them that contribute to tissue destruction in chronic inflammation. The analgesic effect of ketoprofen is related to inhibition of bradykinin-induced pain by blocking bradykinin receptors at nociceptive nerve endings. In addition to its anti-bradykinin activity, ketoprofen acts on the central nervous system by suppressing pain perception.

After parenteral administration, marbofloxacin is rapidly absorbed and reaches a maximum plasma concentration (Cmax: 1.5 mg/ml) in less than 1 hour.

Its bioavailability is close to 100%. Marbofloxacin binds weakly to plasma proteins (less than 10% in pigs, 30% in cattle) and is well distributed; in most tissues (liver, kidneys, skin, lungs, uterus) it reaches higher concentrations than in plasma. Marbofloxacin is slowly eliminated from the body of calves (t1/2 = 5–9 hours) and pigs (t1/2 = 8–10 hours), and more rapidly from adult cattle (t1/2 = 4–7 hours), mainly unchanged via urine and faeces.

Ketoprofen is rapidly absorbed from the injection site and reaches a maximum plasma concentration within 30–40 minutes. The bioavailability of ketoprofen after intramuscular administration in cattle and pigs is 90–100%. More than 98% of ketoprofen binds to plasma proteins and accumulates in inflamed tissues. Its half-life after intramuscular administration is 2–3 hours.

Ketoprofen is metabolised in the liver by microsomal enzymes to biologically inactive metabolites, and 90% is excreted in urine as glucuronide conjugates, 10% with faeces.

Treatment of cattle and pigs with respiratory diseases accompanied by inflammation or fever and caused by microorganisms susceptible to marbofloxacin (Pasteurella multocida, Mannheimia haemolytica, Mycoplasma bovis, Actinobacillus pleuropneumoniae, Mycoplasma hyopneumoniae); treatment of cows with acute mastitis (caused by Escherichia coli), as well as sows with MMA syndrome (metritis-mastitis-agalactia) caused by microorganisms susceptible to marbofloxacin.

Cattle: Administer 0.5 ml per 10 kg body weight by intramuscular injection (equivalent to 2 mg marbofloxacin and 3 mg ketoprofen per kg body weight) once daily for 3 consecutive days.

Pigs: Administer 0.5 ml per 10 kg body weight by intramuscular injection (equivalent to 2 mg marbofloxacin and 3 mg ketoprofen per kg body weight) once daily for 3 consecutive days.

Hypersensitivity to marbofloxacin and ketoprofen.

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

Do not use in animals with haematological disorders or coagulation disorders.

Do not use in cases where strains of pathogenic microorganisms resistant to quinolones have been identified.

Do not use concomitantly with diuretics, anticoagulants and nephrotoxic agents, as well as with other non-steroidal anti-inflammatory drugs.

Do not use concomitantly with tetracycline antibiotics, erythromycin, chloramphenicol or theophylline.

Intramuscular administration may cause transient local reactions such as pain, swelling at the injection site, pain on palpation and inflammatory lesions, which resolve within one week after cessation of treatment.

Fluoroquinolones should be reserved for the treatment of clinical conditions that have not responded to, or are expected to respond poorly to other classes of antimicrobials or are expected to respond poorly to other classes of antimicrobials.

Before using the product, it is recommended to perform susceptibility testing of microorganisms isolated from diseased animals to marbofloxacin.

Use of the product not in accordance with the instructions in the package leaflet may increase the prevalence of bacteria resistant to fluoroquinolones and may reduce the effectiveness of treatment with other quinolones due to possible cross-resistance.

Studies in laboratory animals (rats, rabbits) did not reveal any teratogenic, embryotoxic effects or toxic effects of marbofloxacin on the maternal organism.

The safety of the product has been studied in pregnant cows.

Use during lactation: the safety of the product has been demonstrated in piglets and calves when it was administered to sows and cows during lactation.

The product can be used in animals during pregnancy and lactation.

Do not use concomitantly with diuretics, anticoagulants and nephrotoxic agents.

Do not use concomitantly with other non-steroidal anti-inflammatory drugs or diuretics.

Do not use concomitantly with tetracycline antibiotics, erythromycin, chloramphenicol, macrolides or theophylline.

Meat and offal:

Pigs: 6 days

Cattle: 7 days.

Milk for human consumption: 5 days after last treatment.

Meat and milk obtained before the end of these periods must be discarded or used for feeding non-food-producing animals, as advised by the veterinarian.

Neutral glass vials of type NS-1, NS-2, USP-1, Type I glass (Ph.Eur.) closed with rubber stoppers and sealed with aluminium caps, containing 10, 20, 50 or 100 ml.

Secondary packaging – cardboard box.

Store in a dry place, protected from light, out of reach of children. Storage temperature: 5–25 °C.

3 years.

Shelf life after first opening the immediate packaging: 14 days, provided the product is withdrawn aseptically and subsequently stored at 10–15 °C.