Introduction

Company name: CEVA Animal Health Ltd

Address: 90 The Broadway

Chesham

Buckinghamshire

HP5 1EG

Telephone: 01494 781510

Fax: 01494 781519

Email: cevauk@ceva.com

Website: www.ceva.uk.com

Presentation

A clear sterile aqueous solution for injection. Enzaprost® contains dinoprost 5 mg/ml present as 6.71 mg/ml of dinoprost tromethamine (THAM salt) with 1.65% benzyl alcohol as preservative. Dinoprost is the synthetic, naturally occurring prostaglandin F2α (PGF2α).

Uses

Enzaprost® is indicated for its luteolytic and/or oxytocic effect in cattle and pigs.

The indications for use are:

Cattle

To more effectively control the time of oestrus in cycling cows.

To treat cows which have a functional corpus luteum, but do not express behavioural oestrus (sub-oestrus or silent heat).

To induce abortion.

To induce parturition.

For treatment of chronic metritis and pyometra.

For controlled breeding (oestrus synchronisation).

Pigs

Induction of parturition.

To reduce the weaning to oestrus interval (WOI) and the weaning to fertile service interval (WFSI) in sows in herds with reproductive problems.

Notes:

1. Oestrus control in cycling cattle: Individual cows or heifers treated during dioestrus will normally return to oestrus and ovulate within two to four days after treatment.

This may be employed to advantage as an effective aid towards managing oestrus and breeding in individual animals. (Note: Administration of Enzaprost® to cattle within four days after oestrus is unlikely to result in luteolysis of the corpus luteum.

Administration within 48 hours before the onset of the next oestrus may not influence the timing of the oestrus after treatment).

2. Treatment of sub-oestrus (no visible oestrus) in cattle Individual cattle may have normal cyclical ovarian activity, without detectable behavioural oestrus; this occurs most frequently in the winter months, at peak lactation in high producing dairy cows and in beef suckler cows. If a corpus luteum is present and ovulation has not occurred in the previous four days, administration of Enzaprost® will result in corpus luteum regression followed by return to oestrus and ovulation.

Breeding of cattle treated with Enzaprost® for the above indication may be by natural service, artificial insemination at the usual time in relation to observed oestrus, or by fixed time insemination (78 hours or 72 and 90 hours post-treatment).

3. Induction of abortion: Enzaprost® may be used to terminate pregnancy in cattle through its luteolytic effect during those stages of pregnancy in which the corpus luteum is sensitive to its action and in which maintenance of pregnancy is dependent upon the corpus luteum as the sole source of progesterone.

Stage of gestation in cattle is an important factor influencing response. The percentage of animals responding to a single intramuscular injection decreases as the gestation period increases. Approximate percentages responding are 90% within the first 100 days of gestation, 60% within 101-150 days of gestation and 40% in animals beyond 150 days of gestation. In the early stages of gestation, abortion will usually occur within one week, but as gestation length increases, the period to abortion following injection may also increase.

4. Induction of parturition in cattle and pigs: Cattle: Enzaprost® has been used to induce parturition on or after day 270 of gestation. The interval from administration to parturition is one to eight days (average three days). Induction of parturition in cattle is indicated where there is a risk of oversize calves or where early parturition is desired. In addition, induction is indicated where pregnancies are complicated by miscellaneous conditions such as mummified or macerated foetuses, hydrops amnii, hydroallantois, etc. Enzaprost® is indicated for expulsion of a dead foetus.

Pigs: Enzaprost® may be used to induce parturition in pigs within 3 days of the normal predicted farrowing date. Response to treatment by individual animals varies within a range of 24-36 hours from administration to parturition. This can be advantageously employed to control the time of farrowing in sows and gilts in late gestation. Treatment earlier than 3 days prior to predicted farrowing date may produce weak piglets resulting in reduced survival. It is recommended that treatment be given in the early morning following feeding. A lack of response had been noted in a small proportion of pigs, the specific reason for which has not yet been determined.

5. Treatment of metritis or pyometra in cattle: In the cow chronic metritis frequently occurs as a sequel to an acute or sub-acute endometritis in the first two or three weeks post-partum; typically, there is an intermittent purulent or mucopurulent discharge. Pyometra is characterised by the retention of purulent fluid within the uterus.

Luteal regression through the administration of Enzaprost® is followed by oestrus, during which the uterine environment is relatively unfavourable to the bacteria involved in the infection. Treatment may have to be repeated after 10-12 days where the condition is longstanding.

6. Controlled breeding in cattle: Enzaprost® is indicated for its luteolytic effect in cattle. This luteolytic effect can be utilised to control the timing of oestrus in cycling cattle that have a corpus luteum. For normally-cycling cows, at least 35 days after calving, the identified activity of Enzaprost® permits a wide range of oestrus control programmes.

Programme 1

1. Inject 5 ml Enzaprost® intramuscularly;

2. Repeat the injection in 11 (10 to 12) days; then

3. Inseminate 78 (75 to 80) hours after the second Enzaprost® injection. No oestrus detection or observation is required if animals were cycling normally when injected.

This programme is recommended for most herds with successful A.I. experience where females are known to be cycling.

Programme II

1. Inject 5 ml Enzaprost® intramuscularly;

2. Repeat the injection in 11 (10 to 12) days; then

3. Inseminate 72 (70 to 74) hours and 90 (88 to 96) hours after the second Enzaprost® injection. No oestrus detection or observation is required if animals were cycling normally when injected.

Double insemination has demonstrated increased pregnancy rates in some herds.

Programme III*

1. Inject 5 ml Enzaprost® intramuscularly;

2. Repeat the injection in 11 (10 to 12) days; then

3. Inseminate upon detected oestrus.

Programme IV*

1. Inject 5 ml Enzaprost® intramuscularly;

2. Inseminate upon detected oestrus.

* If it is unknown whether most animals to be treated are cycling, Programmes III and IV calling for oestrus detection should be followed rather than Programmes I and II calling for timed insemination. A follow up bull may be used following any Enzaprost® programme, or the service may be repeated at the next oestrus, one cycle later, in animals that did not conceive at first service.

Practical application of these programmes will vary depending upon many factors, and in many cases these programmes may be altered to meet the requirements of the specific operation. For example, some veterinary surgeons may wish to design their own programmes for specific situations and schedules. The activity of Enzaprost® may be easily adapted for such individualised approach. These changes should be carefully evaluated to ensure that they do not detrimentally affect the success of the breeding programme.

7. To reduce the weaning to oestrus interval (WOI) and the weaning to fertile service interval (WFSI) in sows in herds with reproductive problems: PGF2α has a stimulating effect on uterine contractions, leading to better post-partum evacuation of the uterus. Field clinical trials in herds with reproductive problems confirmed that treatment with Enzaprost® resulted in a more rapid return to oestrus and fertile service after farrowing.

Dosage and administration

A single injection of the recommended dose of dinoprost activity is luteolytic provided a functional corpus luteum is present. Administer by intramuscular injection. Full aseptic precautions must be taken. Use a sterile syringe and needle and make the injection through an area of clean dry skin. Care should be taken to avoid injections through wet or dirty areas of skin.

Cattle: The dose rate for all indicated uses in cattle is 5 ml Enzaprost® (25 mg dinoprost).

Pigs

1. Induction of parturition: 2 ml Enzaprost® (10 mg dinoprost) within 3 days of expected parturition.

2. Use post-partum: 2 ml Enzaprost® (10 mg dinoprost) 24 to 48 hours after parturition.

Contra-indications, warnings, etc

Prostaglandins of the F2α type can be absorbed through the skin and may cause bronchospasm or miscarriage.

Care should be taken when handling the product to AVOID SELF-INJECTION OR SKIN CONTACT.

Women of child-bearing age, asthmatics and persons with bronchial or other respiratory problems should avoid contact with, or wear disposable plastic gloves when administering the product.

Accidental spillage on the skin should be washed off immediately with soap and water.

Localised post injection bacterial infections that may become generalised have been reported. Aggressive antimicrobial therapy should be employed at the first sign of infection. Careful aseptic techniques should be employed to decrease the possibility of post injection bacterial infections.

Animals should not be treated if they suffer from either acute or sub-acute disorders of the vascular system, gastro-intestinal tract or respiratory system.

Pregnancy status should be determined prior to injection since Enzaprost® has been demonstrated to result in abortion or parturition induction when administered at sufficiently high doses to many animal species.

Do not administer by the intravenous route.

Enzaprost® is ineffective when administered prior to day five after ovulation.

If pregnant, the unlikely possibility of uterine rupture should be borne in mind, especially if cervical dilation does not occur.

Induction of parturition in pigs earlier than 72 hours prior to predicted farrowing date may result in reduced piglet viability.

For animal treatment only. Keep out of reach and sight of children.

Side-effects

Cattle: The most frequently observed side-effect is increased rectal temperature at a 5x or 10x overdose. However, rectal temperature changes have been transient in all cases observed and have not been detrimental to the animal. Limited salivation has been seen in some instances.

Pigs: Transient side-effects consisting of increased body temperature, increased respiratory rate, increased salivation, stimulation of defecation and urination, flushing of the skin and restlessness (arching of back, pawing, and rubbing and gnawing the crate) occur occasionally following the administration of dinoprost in pregnant sows and gilts. These effects tend to parallel the signs exhibited by sows prior to normal parturition, only they appear to be condensed in time. These effects are usually seen within 15 minutes of injection and disappear within one hour.

Withdrawal periods

Animals must not be slaughtered for human consumption during treatment.

Cattle may be slaughtered for human consumption only after 3 days since last treatment.

Pigs may be slaughtered for human consumption only after 2 days since last treatment.

It is unnecessary to discard milk for human or animal consumption.

Pharmaceutical precautions

Store below 25°C.

Avoid the introduction of contamination during use. Should apparent growth or discolouration occur, the product should be discarded. Following withdrawal of the first dose, the product should be used within 28 days. Discard any unused material.

Legal category

POM-V

Packaging Quantities

Enzaprost® is supplied in 30 ml vials and packs of 5 x 10 ml vials.

Further information

Many factors contribute to the success and failure of reproduction management, and these are important when the time of breeding is to be regulated with Enzaprost®. Some of these factors are:

1. Cattle must have a corpus luteum on the ovary of about five days or more of age in order for Enzaprost® to be luteolytic; i.e. they are healthy and are undergoing normal oestrus cycles.

2. Semen of high fertility must be inseminated.

3. Semen must be inseminated properly.

4. Oestrus must be detected accurately if timed A.I. is not employed.

5. Physical facilities must be adequate to allow cattle handling without being detrimental to the animal.

6. Nutritional status must be adequate prior to and during the breeding season as this has a direct effect on conception and the initiation of oestrus in heifers or return of oestrous cycles in cows following calving.

Marketing authorisation number

Vm 15052/4015.