1 ml contains:

Ceftiofur ........ 50 mg (as Ceftiofur Hydrochloride)

Suspension for injection.

A white or yellowish oily suspension

Pigs and Cattle

Infections associated with bacteria sensitive to Ceftiofur:

- Treatment of bacterial respiratory disease associated with Pasteurella multocida, Actinobacillus pleuropneumoniae and Streptococcus suis.

- For the treatment of bacterial respiratory disease associated with Mannheimia haemolytica, Pasteurella multocida and Histophillus somni.

- For the treatment of acute interdigital necrobacillosis (panaritium, foot rot) associated with Fusobacterium necrophorum and Bacteroides melaninogenicus (Phorphyromonas asaccharolytica).

- For the treatment of the bacterial component of acute post-partum (puerperal) metritis within 10 days after calving associated with Escherichia coli, Arcanobacterium pyogenes and Fusobacterium necrophorum. (restricted to cases where treatment with another antimicrobial has failed).

Do not administer to an animal previously found to be hypersensitive to Ceftiofur and other β-lactam antibiotics.

Do not inject intravenously.

Do not use in poultry (including eggs) due to risk of spread of antimicrobial resistance to humans.

None known.

Shake the bottle well before use to bring the product back into suspension.

In case of the occurrence of allergic reaction the treatment should be withdrawn.

Inappropriate use of the product may increase the prevalence of bacteria resistant to cephalosporins.

Use of the product should be based on susceptibility testing and take into account official and local antimicrobial policies.

Do not use for disease prevention or as a part of herd health programmes. Treatment of groups of animals should be strictly restricted to ongoing disease outbreaks according to the approved conditions of use.

Do not use as prophylaxis in case of retained placenta.

Penicillins and cephalosporins may cause hypersensitivity (allergy) following injection, inhalation, ingestion or skin contact. Hypersensitivity to penicillins may lead to cross reactions to cephalosporins and vice versa. Allergic reactions to these substances may occasionally be serious.

People with known hypersensitivity to penicillins or cephalosporins should avoid contact with the product.

In the case of accidental self-injection or following exposure, if you develop symptoms such as a skin rash, seek medical advice immediately and show the package leaflet or the label to the physician.

Swelling of the face, lips or eyes or difficulty with breathing are more serious symptoms and require urgent medical attention.

Hypersensitivity reactions unrelated to dose can occur. Allergic reactions (e.g. skin reactions, anaphylaxia) may occasionally occur.

In swine, mild reactions at the injection site, such as discoloration of the fascia or fat, have been observed in some animals for up to 20 days after injection.

In cattle, mild inflammatory reactions at the injection site, such as tissue oedema and discoloration of the subcutaneous tissue and/or fascial surface of the muscle may be observed. Clinical resolution is reached in most animals by 10 days after injection although slight tissue discoloration may persist for 28 days or more.

Studies in laboratory species have not produced any evidence of teratogenic, foetotoxic or maternotoxic effects. Safety has not been established in the target species during pregnancy. Use only according to the benefit/risk assessment by the responsible veterinarian.

The bacterial properties of β-lactams are neutralised by simultaneous use of bacteriostatic antibiotics (macrolides, sulphonamides and tetracyclines).

3 mg Ceftiofur/kg bw/day for 3 days by intramuscular injection, i.e. 1 ml of the product /16 kg bw/day.

Treatment of respiratory disease: 1 mg Ceftiofur/kg bw/day for 3 to 5 days by subcutaneous injection, i.e. 1 ml of the product /50 kg bw/day.

Treatment of acute interdigital necrobacillosis: 1 mg Ceftiofur/kg bw/day for 3 days by subcutaneous injection, i.e. 1 ml of the product/50 kg bw/day.

Acute post-partum metritis within 10 days after calving: 1 mg Ceftiofur/kg bw/day for 5 consecutive days by subcutaneous injection, i.e. 1 ml of the product /50 kg bw/day.

Subsequent injections must be given at different sites.

In case of acute post-partum metritis, additional supportive therapy might be required in some cases.

Shake well before use.

The low toxicity of Ceftiofur has been demonstrated in swine using Ceftiofur sodium at doses in excess of 8 times the recommended daily dose of Ceftiofur intramuscularly administered for 15 consecutive days.

In cattle, no signs of systemic toxicity have been observed following substantial parenteral overdosages.

Swine:

- Meat and offal: 5 days.

Cattle:

- Meat and offal: 8 days

- Milk: zero days.

Pharmacotherapeutic group: Antibacterials for systemic use, ATCvet code: QJ01DD90.

Ceftiofur is a late generation cephalosporin, which is active against Gram-positive and Gram-negative bacteria. Like all beta-lactam antibiotics, ceftiofur inhibits bacterial cell wall synthesis, thereby exerting bactericidal properties.

Cell wall synthesis is dependent on enzymes that are called penicillin-binding proteins (PBP´s). Bacteria may develop resistance to cephalosporins by 1) having penicillin binding proteins insensitive to an otherwise effective β-lactam; 2) altering cell permeability to β-lactams; 3) producing β-lactamases that cleave the β-lactam ring of the antibiotic, or 4) active efflux.

Some β-lactamases, documented in Gram-negative enteric organisms, may lead to varying degrees of cross resistance between cephalosporins, as well as with penicillins, ampicillins and β-lactam inhibitor combinations.

Ceftiofur is active against the following microorganisms which are involved in respiratory diseases in swine: Pasteurella multocida, Actinobacillus pleuropneumoniae and Streptococcus suis. Bordetella bronchiseptica is intrinsically non-susceptible to ceftiofur.

It is also active against bacteria involved in respiratory disease in cattle: Pasteurella multocida, Mannheimia haemolytica, Histophillus somni; bacteria involved in acute bovine foot rot (interdigital necrobacillosis): Fusobacterium necrophorum, Bacteroides melaninogenicus (Porphyromonas asaccharolyitica); and bacteria associated with acute post-partum (puerperal) metritis in cattle: Escherichia coli, Arcanobacterium pyogenes and Fusobacterium necrophorum.

The following Minimum Inhibitory Concentrations (MIC) have been determined for ceftiofur in European isolates of target bacteria:

* No range; all isolates yielded the same value. ND: not determined.

The following breakpoints are recommended by NCCLS for bovine and porcine respiratory pathogens:

No breakpoints have been determined to date for the pathogens associated with foot rot or acute post-partum metritis in cows.

After administration, ceftiofur is quickly metabolised to desfuroylceftiofur, the principal active metabolite.

Desfuroylceftiofur has an equivalent anti-microbial activity to ceftiofur against the bacteria involved in respiratory disease in animals. It is reversibly bound to plasma proteins and as a result, the metabolite concentrates at sites of infection. It remains active in the presence of necrotic tissue and debris.

A single intramuscular dose of the product at 3 mg ceftiofur/kg body weight resulted in mean Cmax of approximately 9 microgram/mL after about 1 hour. The terminal elimination half-life (t1/2) of desfuroylceftiofur was about 23 hours. No accumulation of desfuroylceftiofur has been observed after a dose of 3 mg ceftiofur/kg bw/day administered daily over 3 days.

Elimination occurs mainly via the urine (more than 70%); 12-15 % is eliminated via faeces.

Ceftiofur is completely bioavailable following intramuscular administration.

A single subcutaneous dose of the product at 1 mg ceftiofur/kg resulted in mean Cmax of approximately 2 microgram/mL after about 2.5 hours. After administration of the product, the terminal elimination half-life (t1/2) of desfuroylceftiofur in cattle is approximately 18 hours.

In other studies in healthy cows, a mean Cmax of approximately 2.25 microgram/mL was reached in the endometrium about 5 hours after a single administration of cefiofur. Maximum mean concentrations reached in caruncles and lochiae of healthy cows were about 1 microgram/mL.

No accumulation of desfuroylceftiofur has been observed after a daily treatment of ceftiofur over 5 days. Elimination occurs mainly via the urine (more than 55%). 31% is eliminated in the faeces.

Ceftiofur is completely bioavailable following subcutaneous administration.

Aluminium monostearate

Sorbitan oleate

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: 2 years

Shelf life after first opening the immediate packaging: 28 days

Do not store above 25 ºC

Do not refrigerate or freeze

Keep the PET bottles in the outer carton in order to protect from light

50, 100 or 250 ml Type II glass vials with Type I bromobutyl closure and aluminium cap.

One bottle of 50 ml, 100 ml or one bottle of 250 ml is available in a cardboard box.

The 250 ml bottle has a colourless plastic package as a protective measure in order to avoid glass bottle breaking when it is being used.

Also clinical pack sizes are available: 10x100 ml and 12x100ml

Not all pack sizes may be marketed.

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

LABORATORIOS HIPRA, S.A.

Avda. La Selva, 135

17170- AMER (Girona) SPAIN

Tel. +34 972 430660

Fax. +34 972 430661

E-mail: hipra@hipra.com

07.01.2009

May 2015

Nil