SUMMARY OF PRODUCT CHARACTERISTICS

1. NAME OF THE VETERINARY MEDICINAL PRODUCT

Promone E 50 mg/ml Suspension for injection

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each ml of injectable suspension contains 50 mg Medroxyprogesterone Acetate

Active substance:

Medroxyprogesterone Acetate 50 mg

Excipients:

Methylparahydroxybenzoate 1.30 mg

Propylparahydroxybenzoate 0.14 mg

For full list of excipients, see Section 6.1.

3. PHARMACEUTICAL FORM

Suspension for injection.

4. CLINICAL PARTICULARS

4.1 Target species

Canine.

4.2 Indications for use, specifying the target species

For the prevention of oestrus in anoestrual bitches for which breeding, whelping or ovariohysterectomy involves a high risk to the animal's life or from which litters are not desired or are optional.

4.3 Contraindications

Not for bitches primarily intended for breeding purposes.

Use in pro-oestrus, oestrus or metoestrus of the oestrus cycle.

Bitches before first oestrus.

Gravid bitches.

Previous history of genito-urinary disease.

Persistent or abnormal vaginal discharge.

False pregnancy or prior history of false pregnancy, in some instances.

Mammary tumours which may be stimulated under the influence of progestational activity.

Irregular heat periods or nymphomania.

Bitches in which previous administration of Promone E gave rise to mammary swelling and lactation.

Animals with abnormal uterine bleeding, mammary tumours, or mammary enlargement until a definite diagnosis has been established and the possibility of neoplasia has been eliminated.

Other recognisable abnormalities of the endocrine or reproductive system.

4.4 Special warnings for each target species

Clinical testing indicates that medroxyprogesterone acetate may produce mammary swelling and lactation in certain bitches; therefore, this product should not be administered a second time to such individuals. The degree of mammary enlargement varies from very slight to some cases where the development may be undesirable. Although this syndrome has been reported in individuals of several breeds, the effects has been considered most undesirable in Greyhound bitches which are intended for racing. Such individuals are not candidates for continued therapy.

Some bitches exposed to high levels of progestational steroids have been shown to develop mammary nodules. Animals under therapy should be examined periodically to determine if nodules are developing and an appropriate course of action should be instituted. Some individuals may have a tendency toward obesity while under treatment. Such individuals should be examined for other possible causes and appropriate action taken. Nutritional adjustments should be considered. Compounds with marked corticoid-like activity may cause a worsening of diabetes mellitus. Therefore, do not use in animals that are under treatment for diabetes mellitus without close observation to determine that adverse reactions are not developing.

Cystic endometrial hyperplasia has been noted in some animals following use. This condition in bitches treated in accord with the aforementioned recommendations will differ from the corresponding condition found in untreated bitches by the absence of corpora lutea on the ovaries. The owners of bitches for breeding purposes should be warned that a possible sequel of the cystic endometrial hyperplasia-pyometra complex may be the need for ovariohysterectomy.

When injections are not continued at the recommended interval of six months, animals in which the product has been used for long-term prevention of oestrus will return to oestrual cycling at various intervals. The time between the last injection and the next oestrus varies markedly between individual bitches; it usually being at least six months, but in some bitches may be three years or longer.

The owner should be informed of this variable lag period to return to cycling. At the present time, no recommendations can be made as to methods to initiate cycling in bitches anoestrual due to medroxyprogesterone acetate treatment. Attempts to induce cyclic activity using gonadotrophin (FSH, LH) and oestrogens are definitely contra-indicated as these compounds in conjunction with a progestogen may, in theory, increase the probability of endometrial hyperplasia.

This is not a suitable preparation for use in attempting to synchronise heat periods in groups of animals or individual animals. Bitches should not be bred until the second normal heat following injection. Vaginal smears may be used to establish the normality of the heat period.

Due to individual variation in the absorption and metabolism of medroxyprogesterone acetate, some animals may return to cycling as soon as five months after treatment while others may not recycle for 36 months and, possibly more, in isolated cases. In general, the earliest breeding date for bitches would occur approximately one year following injection but may be as much four years or more following injection. Bitches have been maintained in continuous anoestrus for as long as 48 months with repeated injections.

Injection results in the deposition of an amorphous mass of the drug at the site of injection. Because a semi-permanent bleb or thinning of the skin or change in hair colour may result, the subcutaneous injection in bitches should be made in an inconspicuous area. The inner surface of the thigh or the inner fold of the flank is recommended for these subcutaneous injections.

4.5 Special precautions for use

i. Special precautions for use in animals

Clinical testing indicates that the product may produce mammary swelling and lactation in certain bitches; therefore, this product should not be administered a second time to such individuals. The degree of mammary enlargement varies from very slight to some cases where the development may be undesirable. Although this syndrome has been reported in individuals of several breeds, the effects has been considered most undesirable in Greyhound bitches which are intended for racing. Such individuals are not candidates for continued therapy.

Some bitches exposed to high levels of progestational steroids have been shown to develop mammary nodules. Animals under therapy should be examined periodically to determine if nodules are developing and an appropriate course of action should be instituted. Some individuals may have a tendency toward obesity while under treatment. Such individuals should be examined for other possible causes and appropriate action taken. Nutritional adjustments should be considered. Compounds with marked corticoid-like activity may cause a worsening of diabetes mellitus. Therefore, do not use in animals that are under treatment for diabetes mellitus without close observation to determine that adverse reactions are not developing.

Cystic endometrial hyperplasia has been noted in some animals following use. This condition in bitches treated in accord with the aforementioned recommendations will differ from the corresponding condition found in untreated bitches by the absence of corpora lutea on the ovaries. The owners of bitches for breeding purposes should be warned that a possible sequel of the cystic endometrial hyperplasia-pyometra complex may be the need for ovariohysterectomy.

When injections are not continued at the recommended interval of six months, animals in which the product has been used for long-term prevention of oestrus will return to oestrual cycling at various intervals. The time between the last injection and the next oestrus varies markedly between individual bitches; it usually being at least six months, but in some bitches may be three years or longer.

The owner should be informed of this variable lag period to return to cycling. At the present time, no recommendations can be made as to methods to initiate cycling in bitches anoestrual due to medroxyprogesterone acetate treatment.

Attempts to induce cyclic activity using gonadotrophin (FSH, LH) and oestrogens are definitely contra-indicated as these compounds in conjunction with a progestogen may, in theory, increase the probability of endometrial hyperplasia.

The product is not a suitable preparation for use in attempting to synchronise heat periods in groups of animals or individual animals. Bitches should not be bred until the second normal heat following injection. Vaginal smears may be used to establish the normality of the heat period.

Due to individual variation in the absorption and metabolism of medroxyprogesterone acetate, some animals may return to cycling as soon as five months after treatment while others may not recycle for 36 months, and possibly more, in isolated cases.

In general, the earliest breeding date for bitches would occur approximately one year following injection but may be as much four years or more following injection. Bitches have been maintained in continuous anoestrus for as long as 48 months with repeated injections.

Injection results in the deposition of an amorphous mass of the drug at the site of injection. Because a semi-permanent bleb or thinning of the skin or change in hair colour may result, the subcutaneous injection in bitches should be made in an inconspicuous area. The inner surface of the thigh or the inner fold of the flank is recommended for these subcutaneous injections.

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

Women who are pregnant or are intending to become pregnant should avoid handling the product.

Accidental spillage or splashing to the skin or eyes should be removed by flushing with water. In the event of accidental self injection seek medical advice, taking the product literature to show the doctor.

4.6 Adverse reactions (frequency and seriousness)

Clinical testing indicates that the product may produce mammary swelling and lactation in certain bitches; therefore, this product should not be administered a second time to such individuals. The degree of mammary enlargement varies from very slight to some cases where the development may be undesirable. Although this syndrome has been reported in individuals of several breeds, the effect has been considered most undesirable in Greyhound bitches which are intended for racing. Such individuals are not candidates for continued therapy.

Some bitches exposed to high levels of progestational steroids have been shown to develop mammary nodules. Animals under therapy should be examined periodically to determine if nodules are developing and an appropriate course of action should be instituted. Some individuals may have a tendency toward obesity while under treatment with. Such individuals should be examined for other possible causes and appropriate action taken. Nutritional adjustments should be considered. Compounds with marked corticoid-like activity may cause a worsening of diabetes mellitus. Therefore, do not use in animals that are under treatment for diabetes mellitus without close observation to determine that adverse reactions are not developing.

Cystic endometrial hyperplasia has been noted in some animals following treatment. This condition in bitches treated in accord with the aforementioned recommendations will differ from the corresponding condition found in untreated bitches by the absence of corpora lutea on the ovaries. The owners of bitches for breeding purposes should be warned that a possible sequel of the cystic endometrial hyperplasia-pyometra complex may be the need for ovariohysterectomy.

When injections are not continued at the recommended interval of six months, animals in which the product has been used for long-term prevention of oestrus will return to oestrual cycling at various intervals. The time between the last injection and the next oestrus varies markedly between individual bitches; it usually being at least six months, but in some bitches may be three years or longer.

The owner should be informed of this variable lag period to return to cycling. At the present time, no recommendations can be made as to methods to initiate cycling in bitches anoestrual due to medroxyprogesterone acetate treatment. Attempts to induce cyclic activity using gonadotrophins (FSH, LH) and oestrogens are definitely contra-indicated as these compounds in conjunction with a progestogen may, in theory, increase the probability of endometrial hyperplasia.

The product is not a suitable preparation for use in attempting to synchronise heat periods in groups of animals or individual animals. Bitches should not be bred until the second normal heat following injection. Vaginal smears may be used to establish the normality of the heat period.

Due to individual variation in the absorption and metabolism of medroxyprogesterone acetate, some animals may return to cycling as soon as five months after treatment while others may not recycle for 36 months, and possibly more, in isolated cases. In general, the earliest breeding date for bitches would occur approximately one year following injection but may be as much four years or more following injection. Bitches have been maintained in continuous anoestrus for as long as 48 months with repeated injections.

Injection results in the deposition of an amorphous mass of the drug at the site of injection. Because a semi-permanent bleb or thinning of the skin or change in hair colour may result, the subcutaneous injection in bitches should be made in an inconspicuous area. The inner surface of the thigh or the inner fold of the flank is recommended for these subcutaneous injections.

4.7 Use during pregnancy, lactation or lay

Not applicable.

4.8 Interaction with other medicinal products and other forms of interaction

Gonadotrophins (FSH, LH) and oestrogens must not be used to attempt induction of cycling as this will increase the probability of endometrial hyperplasia.

4.9 Amounts to be administered and administration route

Shake before using.

For subcutaneous use only.

1 ml (50 mg medroxyprogesterone acetate) is administered during anoestrus, repeated at six month intervals.

Due to the possibility of thinning of the skin, or change in hair colour, at the site of deposition of the drug, subcutaneous injections are best made in an inconspicuous area, e.g. the inner surface of the thigh.

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

Any overdosing can probably be surgically removed, if discovered soon enough after dosing.

4.11 Withdrawal period(s)

Not applicable.

5. PHARMACOLOGICAL PROPERTIES

Medroxyprogesterone acetate (MPA) is a synthetic progestagen. It has pharmacodynamic actions similar to those of endogenous progesterone. The production of follicle stimulating hormone (FSH) and luteinizing hormone (LH) by the anterior pituitary is inhibited by progesterone thus preventing follicular growth, maturation, secretion and ovulation. The sub-cutaneous depot injection of 1 ml Promone E in anoestrus serves to provide sufficient exogenous progestagen to prevent oestrus occurring over a long period of time, usually for at least 6 months and sometimes for up to three years or longer. For continued effect, the treatment should be repeated at six month intervals.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Methyl parahydroxybenzoate

Propyl parahydroxybenzoate

Sodium chloride

Polyethylene Glycol 3350

Polysorbate 80

Hydrochloric acid

Sodium hydroxide

Water for Injections

6.2 Incompatibilities

None known

6.3 Shelf life

5 years.

Single dose container, discard unused material.

6.4. Special precautions for storage

Do not store above 25ºC. Do not freeze. For single use only. Discard unused material.

6.5 Nature and composition of immediate packaging

1 ml uncoloured single glass vial sealed with bromobutyl rubber bung and aluminium cap. Packaged in cardboard carton.

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

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

7. MARKETING AUTHORISATION HOLDER

Zoetis UK Limited

5th Floor, 6 St. Andrew Street

London

EC4A 3AE

8. MARKETING AUTHORISATION NUMBER

Vm 42058/4115

9. RENEWAL OF THE AUTHORISATION

Date: 22^nd August 2003

10. DATE OF REVISION OF THE TEXT

Date: July 2013

Approved: 30/07/2013