SUMMARY OF PRODUCT CHARACTERISTICS 1. NAME OF THE VETERINARY MEDICINAL PRODUCT

Ubropen 600 mg intramammary suspension for lactating cows

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each 10 g intramammary syringe contains:

Active substance:

Benzylpenicillin procaine monohydrate 600 mg (equivalent to 340.8 mg benzylpenicillin)

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Intramammary suspension.

White to yellowish, oily suspension.

4. CLINICAL PARTICULARS

4.1 Target species

Cattle (lactating cow).

4.2 Indications for use, specifying the target species

Treatment of clinical mastitis caused by penicillin susceptible streptococci or staphylococci occurring during the lactation phase.

4.3 Contraindications

Do not use in cases of hypersensitivity to the active substances, to substances of the β-lactam group or to any of the excipients.

Do not use in cases of infections with β-lactamase-forming pathogens.

4.4 Special warnings for each target species

If the product is used in treatment of mastitis caused by Staphylococcus aureus, an appropriate parenteral antimicrobial may be required.

4.5 Special precautions for use

Special precautions for use in animals

Use of the product should be based on identification and 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. Official, national and regional antimicrobial policies should be taken into account when the product is used. In some geographical areas or in some individual herds resistance to penicillin in S. aureus is widespread.

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 (penicillins and cephalosporins) due to the potential for cross-resistance.

The feeding of waste milk containing residues of antimicrobials to calves should be avoided up to the end of the milk withdrawal period (except during the colostral phase), because it could select for antimicrobial-resistant bacteria within the intestinal microbiota of the calf and increase the faecal shedding of these bacteria.

The cleaning towel should not be used in presence of teat injuries.

Care must be taken when applying the product in case of severe udder quarter swelling, milk duct swelling and/or congestion of detritus in the milk duct.

Special precautions to be taken by the person administering the veterinary medicinal product to animals

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.

• Do not handle in case of hypersensitivity to penicillins or cephalosporins or if you have been advised not to work with such preparations.

• Handle this product with great care to avoid exposure taking all recommended precautions.

• Persons handling or administering the veterinary medicinal product should wear appropriate disposable gloves. Avoid contact with the eyes. Wash exposed skin after use. In case of eye contact, wash the eyes thoroughly with copious amounts of clean running water.

• If you develop symptoms following exposure such as a skin rash, you should 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.

The cleaning towels provided contain isopropyl alcohol, which may be irritating to skin and eyes. It is recommended that disposable gloves are also worn when using the cleaning towels.

Wash hands after use.

4.6 Adverse reactions (frequency and seriousness)

Hypersensitive reactions to penicillin or procaine have been reported very rarely on post marketing safety experience and may include symptoms like oedema, dermatological changes such as urticaria, angio-oedema or erythema and anaphylactic shock.

In case adverse reactions occur, the current treatment should be withdrawn and symptomatic treatment should be initiated.

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).

4.7 Use during pregnancy, lactation or lay

Can be used during pregnancy, but not during the dry period.

4.8 Interaction with other medicinal products and other forms of interaction

Do not combine with bacteriostatic agents. Tetracyclines, macrolides, sulphonamides, lincomycin or tiamulin may inhibit the antibacterial effect of penicillins because of the rapid onset of bacteriostatic action.

4.9 Amounts to be administered and administration route

Intramammary use.

Infuse the contents of one intramammary syringe (equivalent to 600 mg benzylpenicillin procaine monohydrate) per affected udder quarter once daily after milking. The treatment is continued for 3-5 days.

Parenteral therapy may also be required depending upon the clinical presentation.

Clean and disinfect the end of the teat and teat orifice thoroughly before applying the product. Remove the cover of the tip and infuse the product gently into the teat. The intramammary syringe has a double tip. It is recommended to remove only the outer cover, revealing a tip about 5 mm long. Using the shorter tip reduces the mechanical irritation of the teat canal when the veterinary medicinal product is applied (partial insertion). If the inner cover is removed as well, a tip of about 20 mm is revealed. This can be used only exceptionally to facilitate infusion, for instance to a teat with pronounced oedema (full insertion). The partial insertion technique is preferred, whenever achievable. After infusion, the quarter is massaged so that the drug is evenly distributed.

4.10 Overdose (symptoms, emergency procedures, antidotes), if necessary

Not applicable.

4.11 Withdrawal period(s)

Milk: 6 days.

Meat and offal: 3 days.

5. PHARMACOLOGICAL PROPERTIES

Pharmacotherapeutic group: Beta-lactam antibacterials, penicillins, for intramammary use.

ATCvet code: QJ51CE09

5.1 Pharmacodynamic properties

Benzylpenicillin is a bactericidal antibiotic belonging to the betalactam group of antibiotics. It inhibits the peptidoglycan synthesis of Gram-positive bacteria. Benzylpenicillin has no effect on dormant/non-growing bacteria or on most of the Gram-negative bacteria.

Mastitis-causing streptococci are commonly susceptible to penicillin. Both

Staphylococcus aureus and coagulase-negative staphylococci may synthesise betalactamase. These strains are resistant to penicillin. Penicillin is active against betalactamase-negative bacteria. The MIC values of penicillin to susceptible pathogens are ordinarily smaller than 0.15 μg/ml.

Most resistance results from production of a beta-lactamase, although modifications of PBPs with reduced drug affinity or reduced bacterial permeability are additional and sometimes concurrent mechanisms of intrinsic and acquired resistance to penicillins.

State of resistance of the target pathogens across Europe:

According to European surveillance reports and literature published in 2009-2018 proportion of the strains susceptible/non-resistant to penicillin from the isolates tested varied from 64 to 98 % for S. aureus, from 63 to 73 % for coagulase negative staphylococci and from 97 to 100 % for streptococci. However, although resistance in streptococci is rare, decrease in susceptibility of Streptococcus uberis has been reported.

The resistance situation remained stable throughout 2002-2018.

Clinical MIC Breakpoints according to CLSI Standards have been set for the evaluation of the resistance development.

Clinical breakpoints for Benzylpenicillin procaine on penicillin-susceptible mastitis pathogens (human derived data)

Pathogen	Source: CLSI Standard VET01S
	Breakpoint (μg/mL)
	S[1]	I3	R2
Staphylococcus aureus	≤ 0.12	-	≥0.25
Coagulase negative Staphylococci	≤ 0.12	-	≥0.25
Streptococcus agalactiae	≤ 0.12	-	-
Streptococcus dysgalactiae	≤ 0.12		-
Streptococcus uberis	≤ 0.12	0.25 – 2	≥4-

above 0,15 µg/ml for at least 24 h, even when the quarter is emptied at 2 h intervals for a period of 10 h after the administration.

Most of the penicillin in the product is excreted in milk unchanged. About 40% of the drug is eliminated in the milk at the first evacuation, and about 10% at the second evacuation. Therefore, about half of the penicillin dose has been eliminated after two milkings. Penicillin absorbed systemically is excreted via the kidneys unchanged.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Wool wax alcohol ointment

Paraffin, liquid

Lecithin (E322)

6.2 Major incompatibilities

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

6.3 Shelf life

Shelf life of the veterinary medicinal product as packaged for sale: 2 years.

6.4 Special precautions for storage

Store below 25 °C.

6.5 Nature and composition of immediate packaging

White intramammary syringe (LDPE) with a double tip (LDPE) packed in a cardboard container.

Pack sizes: 3 x 10 g with 3 cleaning towels, 5 x 10 g with 5 cleaning towels, 20 x 10 g with

20 cleaning towels, 40 x 10 g with 40 cleaning towels and 100 x 10 g with 100 cleaning towels.

Not all pack sizes may be marketed.

6.6 Special precautions for the disposal of unused veterinary medicinal product or waste materials derived from the use of such products

Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal product should be disposed of in accordance with local requirements.

7. MARKETING AUTHORISATION HOLDER

Vetcare Oy

P.O. Box 99

24101 Salo Finland

8. MARKETING AUTHORISATION NUMBER

Vm 42810/4000

9. DATE OF FIRST AUTHORISATION

25 April 2016

10. DATE OF REVISION OF THE TEXT

April 2021

Approved: 15/04/21

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