ESTRUMATE SYNTHETIC PROSTAGLANDIN FOR CATTLE AND HORSES
APVMA Approval No:
ESTRUMATE SYNTHETIC PROSTAGLANDIN FOR CATTLE AND HORSES
PRESCRIPTION ANIMAL REMEDY
KEEP OUT OF REACH OF CHILDREN
FOR ANIMAL TREATMENT ONLY
250 ug/ml CLOPROSTENOL AS THE SODIUM SALT
A luteolytic agent for clinical use and the control of the bovine and equine oestrous cycles.
ESTRUMATE a synthetic prostaglandin analogue for use in cattle and horses, is
structurally related to Prostaglandin F2a (PGF2a). Each mL of the colourless aqueous
solution contains 263ug of cloprostenol sodium equivalent to 250ug cloprostenol. The
solution also contains 2% benzyl alcohol Ph. Eur. as a bactericide.
Action: ESTRUMATE is a potent luteolytic agent, i.e. it causes functional and morphological
regression of the corpus luteum (luteolysis) in a variety of circumstances. Luteolysis is
usually followed by return to oestrus two to four days after treatment, and normal ovulation.
10 x 20mL
Directions for Use:
For use by or under direction of a registered veterinarian
DIRECTIONS FOR USE
ESTRUMATE should not be administered to pregnant animals where the foetus is not to be
aborted, since luteolysis at some stages of gestation will result in the loss of the foetus.
ESTRUMATE should not be administered by intravenous injection.
Note: There is a refractory period of four to five days after ovulation when cattle are
insensitive to the luteolytic effect of prostaglandins. ESTRUMATE has a good safety margin
and does not impair fertility. No deleterious effects have been reported on the progeny
conceived at the oestrus following treatment.
In cattle adverse reactions have not been seen at up to 80 times the effective
recommended dose (500μg). The only clinically apparent effect was mild and transient
In horses adverse reactions including sweating (occurring within about 20 minutes of
treatment), increased respiratory and cardiac rates, signs of abdominal discomfort,
watery diarrhoea and depression may occur when exceptionally high doses are given.
However adverse reactions are usually mild and transient. ESTRUMATE should NOT be
Mares suffering from acute or sub-acute disorders of the gastrointestinal tract.
Mares suffering from acute or sub-acute respiratory disease. (This is a precautionary
measure because in some species of animals, dosing with prostaglandins can result in
acute respiratory distress.)
Pregnant mares, since luteolysis at some stages of gestation will result in the loss of the
Use the contents within 28 days after first broaching the vial. Discard unused portion.
This section contains file attachment.
MEAT (CATTLE, HORSES): DO NOT USE less than one day before slaughter for human
MILK: Zero (0) days.
EXPORT SLAUGHTER INTERVAL (ESI): An ESI has not been established for this product.
Note-observing the meat withholding period may not be sufficient to mitigate potential risks
to export trade. Trade advice should be sought from Intervet/MSD Animal Health on 1800
033 461 before using this product.
First Aid Instructions:
If poisoning occurs, contact a doctor or Poisons Information Centre. Phone Australia 13 11
First Aid Warnings:
ESTRUMATE can be absorbed through the skin and therefore, care should be taken when
handling this product, especially by women of child bearing age and also by asthmatics. In
case of accidental spillage on skin, wash immediately with water.
Prostaglandins of the F2a type may cause broncho-spasm in man, although the
possible incidence of this effect with ESTRUMATE is not known. Should respiratory
embarrassment result from accidental inhalation or injection, a rapid acting broncho-dilator,
e.g. isoprenaline or salbutamol by inhalation is indicated.
Dispose of empty container by wrapping in paper and putting in garbage.
Store below 30°C (Room Temperature). PROTECT from light.
A single intramuscular dose of ESTRUMATE is likely to be highly effective in the following clinical
conditions of the cow.
Suboestrus (or non-detected oestrus - NDO):
This condition occurs in heavy yielding cows, usually at peak lactation, which have normal ovarian
cyclicity but in which behavioural manifestations of oestrus are either very mild, transient or absent.
Such animals can be treated with ESTRUMATE following
palpation and then closely observed for oestrus. Those showing heat should be inseminated. Some
animals may have been treated during the refractory period of the cycle and therefore will not
respond. Animals not showing heat should receive a further single injection 11 days after the first and
be inseminated 72 and 96 hours later.
Termination of Normal but Unwanted Pregnancies:
Pregnancy can be terminated from one week after conception until the 150th day of gestation. Before
100 days gestation, abortion can be induced rapidly and efficiently. Between 100 and 150 days of
gestation results are less reliable, probably because a proportion of cattle may become progressively
less dependent upon the corpus luteum for the maintenance of pregnancy. Abortion should not be
induced after day 150 of gestation. Treated animals should be kept under supervision until expulsion
of the foetus and the placental membranes is complete, as an occasional animal may develop metritis
following abortion. Most cows will abort in 3-5 days; if an animal has not aborted by the eighth day, a
second injection should be given.
Termination of Abnormal Pregnancy
Removal of mummified foetus:
Death of the conceptus may be followed by its dehydration and degeneration. Induction of luteolysis
at any stage of pregnancy will result in the expulsion of this mummified foetus from the uterus into the
vagina. Manual removal from the vagina may be necessary. Normal cyclical activity should then
Hydrops of the Foetal Membranes:
Pathological accumulation of placental fluids - hydramnios or hydrallantois - can cause severe
physiological complications and death. Surgical drainage is not usually successful in alleviating the
condition. A single dose of ESTRUMATE may be used to induce parturition in such cases, success
has been achieved as early as the sixth month of pregnancy.
Chronic endometritis (Pyometra):
Damage to the reproductive tract at calving or post-partum retention of the placenta, frequently lead to
infection and inflammation of the uterus. Acute or sub-acute endometritis occurring shortly after
parturition may require both local and systemic antibiotic treatment and this often results in resolution
of the condition. However, under certain circumstances the endometritis may progress until, at a few
weeks post-partum the uterus is very swollen, of a soft doughy consistency and full of purulent
discharge. This is characterised by a lack of cyclical oestrus behaviour and the presence of a
persistent corpus luteum. This condition can be successfully treated by induction of luteal regression.
Where necessary, treatment may be repeated at 10 to 14 day intervals.
Induction of Parturition:
Induction of parturition should take place as close to the predicted calving date as possible and not
more than 10 days before. Induction should not be attempted before day 270 of gestation measured
from the confirmed day of conception. All treated animals must receive adequate supervision. In
common with all other methods of shortening the gestation period a higher than usual incidence of
retention of the foetal membranes is to be expected. It is now recognised that there may be a
reduced survival rate in calves born as a result of early induction. Any increased mortality is due to
lack of viability as a result of prematurity rather than any effect from the prostaglandins.
Ovarian Luteal Cysts:
Where cystic ovaries associated with persistent luteal tissue and absence of oestrus are diagnosed,
ESTRUMATE has proved effective in correcting the condition and bring about a return of cycling.
Accurate diagnosis is essential if completely satisfactory results are to be achieved.
Controlled Breeding Programmes in Cattle.
The luteolytic activity of ESTRUMATE can be harnessed to control the breeding patterns of cattle. A
variety of treatment regimes exists from which it is possible to choose the most appropriate for the
characteristics and objectives of each particular individual, group or herd. ESTRUMATE can be used
to complement oestrus detection input or animals may be bred “on schedule” during critical times of
the breeding season, without reference to oestrus detection. Use one of the following programs:
At the usual time, relative
to detected heat OR
At about 72 hours and 96
Hours post-injection OR
Mass AI at 72 hours, with
re-insemination of those in
Oestrus over the next 2 to 3
All animals with
Detect heat and
Day 11: All animals
Detect heat for 6
days and breed.
Day 6: All animals
Best results obtained where heat detection is utilised. This is generally assisted by the use of
Identification of animals is important.
Conception rate may be about 20% less if insemination is carried out en masse 72 hours after
injection with no following insemination.
ESTRUMATE can also be used in systems which include other treatment regimes. e.g. CIDR.
To control oestrus in the individual animal giving better control of the calving index by allowing
artificial insemination without oestrus detection. The number of cows culled as barren is consequently
To synchronise oestrus in groups of cows to promote management of the herd in groups of
suitable size for feeding, A.I. and ‘drying off’. The chances of maintaining a strictly seasonal calving
herd are improved and the number of barren cows at the end of the breeding programme is reduced.
To permit the use of A.I. in dairy heifers which, in turn, allows the speeding up of the breeding
programme, the use of a bull known to produce few dystocia problems, better control of heifer
management, and steaming up prior to calving.
To facilitate the use of A.I. improving the progeny through the use of genetically superior bulls. The
problems of oestrus detection are avoided and the labour involved in carrying out an A.I. programme
is reduced by allowing groups of cattle to be presented instead of single animals.
To permit better management at conception and calving: The calving pattern is altered, resulting
in greater average age and weight of calves at weaning. The peak calving period can be forecast
more accurately in relation to other events in the farm calendar and there is an improved potential for
‘flushing’ the cows prior to A.I.
Dosage and Administration
Single or repeat doses of 2 mL (500
g cloprostenol) by intramuscular injection.
ESTRUMATE as a potent luteolytic agent causes regression of the corpus luteum in MARES, in a
variety of circumstances. Luteolysis is usually followed by oestrus, appearing 2 to 4 days after
treatment, with ovulation during the induced oestrus. This sequence of events is seen, for example,
in mares treated with ESTRUMATE during dioestrus (the progestational) phase of the oestrus cycle,
but it should be noted that there is a refractory period of 4 to 5 days after ovulation when mares are
not responsive to the luteolytic action of prostaglandins.
ESTRUMATE has a wide margin of safety and has no deleterious effect on foals conceived and born
as a result of mares being covered at the induced oestrus. This property of shortening the life-span of
the corpus luteum makes ESTRUMATE of clinical value in:-
Induction of Luteolysis following early foetal death and resorption: About 8 to 10 per cent of all
mares which conceive lose the conceptus during the first 100 days of pregnancy. Persistence of
luteal function in the ovary precludes an early return of oestrus. Treatment before day 45 is
recommended. After that time no response may be obtained due to the presence of circulating
Termination of Pseudopregnancy: Some mares covered at normal oestrus and subsequently
found to be empty (but not having lost or resorbed a conceptus) display clinical signs of pregnancy.
These animals are said to be ‘pseudopregnant’.
Treatment of Lactation anoestrus: Failure of lactating mares to cycle again for several months after
exhibiting an early ‘foal heat’ can be avoided in most cases. Some variability does however occur.
Barren and maiden mares: Some of these animals will be found, on examination, to have a
functional corpus luteum and are either suffering from abnormal persistence of luteal function or are
simply failing to exhibit normal oestrus behaviour (‘silent heat’) while ovarian cyclicity continues.
Synchronisation of oestrus: Under some circumstances this may be a desirable objective in stud
management. Treatment during dioestrus usually induces oestrus after 2 to 4 days, with ovulation
occurring 8 to 12 days after treatment.
Nomination of the time of service: Mares may be brought into oestrus at will, simply as an aid to
successful and economic management of stallions during the breeding season.
Dosage and Administration
A single intramuscular injection of 0.5 to 1.0 mL for animals up to 400 kg bodyweight. 1.0 to 2.0 mL
for horses weighing 400 kg and above.