Powder and solvent for suspension for injection.

1 ml of the reconstituted suspension contains:

Penethamate hydriodide 236.3 mg (equivalent to 182.5 mg penethamate)

Equivalent to 250,000 IU of penethamate hydriodide

Penethamate hydriodide 9452 mg (equivalent to 7299 mg of penethamate)

Equivalent to 10,000,000 IU of penethamate hydriodide

Total amount of reconstituted solution 40 ml

Treatment of mastitis in lactating cows caused by Streptococcus uberis, Streptococcus dysgalactiae, Streptococcus agalactiae and Staphylococcus aureus (beta-lactamase non-producing), susceptible to penicillin.

For deep intramuscular injection.

Directions for use: Reconstitute the suspension using the entire contents of the solvent vial.

Shake well after reconstitution. A minimum of 10 inversions of vials can be necessary.

Each ml of suspension contains 250,000 IU (236.3 mg) of penethamate hydriodide.

Dose: 15,000 IU (14.2 mg) of penethamate hydriodide per kg of body weight / day (equivalent to 6 ml of reconstituted medicinal product / 100 kg body weight) for three to four consecutive days. Shake well before use.

Administer the recommended daily dose every 24 hours, for three to four consecutive administrations.

To ensure administration of a correct dose, body weight should be determined as accurately as possible.

The recommended maximum volume to be administered at a single injection site is 20 ml.

The stopper should not be punctured more than 10 times.

Do not use in cases of hypersensitivity to penicillins, cephalosporins, and/or any of the excipients.

Do not administer intravenously.

Do not use in lagomorphs and rodents such as guinea pigs, hamsters or gerbils.

Do not administer to animals with renal disease including anuria or oliguria.

Treatment should be carried out during lactation.

This veterinary medicinal product does not contain any antimicrobial preservative.

Using penethamate hydriodide for the treatment of mastitis must be accompanied by hygienic measures to prevent reinfection.

Use of the product should be based on susceptibility testing of the bacteria isolated from the animal. If this is not possible, therapy should be based on local (regional, farm level) epidemiological information about susceptibility of the target bacteria.

The veterinary medicinal product is not effective against beta-lactamase producing organisms.

Official national and regional antimicrobial policies should be taken into account when the product is used.

Use of the product deviating from the instructions given in the SPC may increase the prevalence of bacteria resistant to benzylpenicillin and may decrease the effectiveness of treatment with other beta-lactam antimicrobials due to the potential for cross‑resistance.

• 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, cephalosporins or any of the excipients should avoid contact with the veterinary medicinal product.

• Handle this product with great care to avoid exposure. Wear gloves when handling the veterinary medicinal product to avoid contact sensitization.

• In case of accidental self-injection or if you develop symptoms following exposure such as a skin rash, you should seek medical advice and show the package leaflet or the label to the doctor. Swelling of the face, lips or eyes or difficulty with breathing are more serious symptoms and require urgent medical attention.

• Wash hands after use.

In very rare cases the symptoms of adverse reactions range from mild skin reactions such as urticaria and dermatitis to severe reactions such as anaphylactic shock with tremors, vomiting, salivation, gastrointestinal disorders and laryngeal oedema.

In some situations the treatment may lead to secondary infections due to overgrowth of non-target organisms.

The frequency of adverse reactions is defined using the following convention:

- very common (more than 1 in 10 animals treated displaying adverse reaction(s))

- common (more than 1 but less than 10 animals in 100 animals treated)

- uncommon (more than 1 but less than 10 animals in 1,000 animals treated)

- rare (more than 1 but less than 10 animals in 10,000 animals treated)

- very rare (less than 1 animal in 10,000 animals treated, including isolated reports).

Can be used during pregnancy and lactation.

The product should not be administered with antibiotics that have a bacteriostatic mode of action.

Anti-inflammatories such as salicylates, produce an increase in the elimination half-life of penethamate (iohydrate). In case of joint administration, adjust the dose of the antibacterial

In cases of overdose, adverse reactions such as those described in Adverse Reactions may occur.

Meat and offal: 4 days

Milk: 2.5 days (60 hours)

Keep out of the sight and reach of children.

Do not use this veterinary medicinal product after the expiry date which is stated on the label after EXP. The expiry date refers to the last day of that month This veterinary medicinal product does not require any special storage conditions.

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

Before reconstitution, the powder and solvent vials do not require any special storage conditions.

The reconstituted suspension should be stored in the refrigerator (2-8°C). Shelf life after reconstitution according to directions: 24 hours.

Pharmacotherapeutic group: Antibacterials for systemic use, beta- lactam antibacterials, penicillins.

ATCvet code: QJ01CE90

The active substance, penethamate hydriodide, is a prodrug which releases benzylpenicillin. Chemically, it is a diethylaminoethanol ester of penicillin.

Benzylpenicillin works by blocking the biosynthesis of the bacterial cell wall. Benzylpenicillin covalently attaches to and subsequently inactivates penicillin-binding proteins (PBPs), which are located on the inner surface of the bacterial membrane. The PBPs (transpeptidase, carbopeptidasas, endopeptidases) are enzymes involved in the terminal stages of bacterial cell-wall synthesis. Penicillins are only active against bacteria in the multiplication phase.

The antimicrobial spectrum of the active substance corresponds to that of benzylpenicillin which is effective against beta-lactamase negative Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus uberis and Staphylococcus aureus.

The most frequent mechanism is producing beta-lactamases (more specifically penicillinase especially in S. aureus), which break the beta-lactam ring of penicillins making them inactive.

Following intramuscular administration to dairy cows, Cmax is rapidly achieved in blood and milk (3 and 7 hours respectively). Ninety percent of the antibiotic is hydrolysed in blood and 98% in milk. As a result of hydrolysis, diethylaminoethanol and benzylpenicillin are produced, with the latter being the therapeutically active molecule. The distribution is rapid within the organism, with particular affinity for lung and mammary gland tissues. It crosses the placenta and enters the foetal circulation slowly.

DIVASA-FARMAVIC S.A.

Ctr. San Hipolit, Km 71

08503 Gurb-Vic (Barcelona)

Spain