Receptal Information Brochure - MSD Animal Health New Zealand

ACTIVE CONSTITUENTS:
BUSERELIN 4 µg per ml
PRESENTATION:
A ready-to-use colourless, aqueous injection solution for parenteral administration,
containing synthetic releasing hormone analogue of both the luteinising and follicle
stimulating hormones (GnRH equivalent to LH/FSH-RH).
Each ml contains 4 µg Buserelin and 10 mg benzyl alcohol, Ph.Eur., as antimicrobial
preservative. Buserelin is equivalent to the natural LH/FSH releasing hormone
produced in the hypothalamus. It causes simultaneous release of luteinizing hormone
(LH) and follicle stimulating hormone (FSH) from the anterior pituitary.
Cattle:
Horses:
Dosage
Dosage
DIRECTIONS FOR USE:
Cows:
Mares:
For the treatment of anovulatory anoestrous in dairy cows when used in
conjunction with a progesterone device and a PGF 2α analogue with luteolytic activity
Anovulatory anoestrous
2 mL
Synchronisation of oestrous
2 mL
5 mL
For the treatment of delayed ovulation in cows
Follicular and Luteal cysts with
or without prolonged signs of
nymphomania
For the treatment of cystic ovaries in cows
Delayed ovulation
5 mL
Improvement in pregnancy rate
of cows
2.5 mL
For the synchronisation of oestrous in cows and heifers when used in
conjunction with a PGF 2α analogue with luteolytic activity and with or without a
progesterone device as part of a 10 day fixed time insemination regime.
For the improvement of pregnancy rate in cows
To induce ovulation of a mature follicle and thereby to synchronise ovulation
more closely with mating in mares
For the treatment of cystic ovaries and anoestrous in mares
PRECAUTIONS
Following withdrawal of the first dose, use the product within 14 days.
Discard unused material. Observe aseptic precautions.
DOSAGE AND ADMINISTRATION
Receptal® is preferably given by intramuscular injection. However, the
intravenous or subcutaneous routes may also be used if desired. Syringes and
needles should be from gamma irradiated packs or freshly sterilised by boiling
for 20 minutes, but no alcohol or disinfectant should be used for this procedure.
DISPOSAL:
Dispose of empty container by wrapping with paper and putting in garbage.
STORAGE:
SPECIAL NOTES
Follicular cysts
In the treatment of follicular cysts in cattle, it is unnecessary and contraindicated
to manually express the cysts. A corpus luteum will usually be clearly
detectable on either the affected or the normal ovary within about 8 days
after administration of Receptal®. The ‘healthy corpus luteum’ can be left to
spontaneously resolve or the time to the next oestrous can be shortened by
giving a PGF 2α analogue with luteolytic activity 7 – 9 days after the Receptal®
injection. Artificial insemination or service should take place during the first
oestrous after treatment. Oestrous should occur within 21 days of Receptal®
injection, if not re-examine and retreat if a further cyst has developed.
Delayed ovulation
Store below 25°C (Air conditioning). Protect from light.
May be treated at the time of artificial insemination or service, or up to 6 – 8
hours before. Ovulation is usually induced within 24 hours of treatment.
FIRST AID:
Note
If poisoning occurs, contact a doctor or the National Poisons Centre
(0800 POISON).
The induction of ovulation is not possible in the presence of a functional
corpus luteum.
Cystic changes of the ovaries with
or without prolonged or permanent
oestrous
10 mL
To induce ovulation of a mature follicle
and thereby to synchronise ovulation
more closely with mating in mares
5 mL twice, with an interval of
24 hours
Anoestrous
5 mL twice, with an interval of
24 hours
In cystic changes of the ovaries, a single treatment is usually sufficient. If 10-14
days after treatment no response (i.e. regression of the cysts or remission of the
prolonged or permanent oestrous) is seen, the treatment should be repeated.
In anoestrous mares if no oestrous occurs within 10 days, Receptal® should be
administered again on the 11th and 12th day after the first treatment.
To induce ovulation of a mature follicle and thereby to synchronise ovulation more
closely with mating.
Receptal® should be administered on the first day on which the follicle has reached
its maximum size, this being determined by previous clinical history and rectal
examinations.
*
Receptal® is best given approximately 6 hours prior to service. This may be
achieved by administering Receptal® in the morning with service in the afternoon
of the same day, or alternatively with the injection given in the early afternoon and
service in the evening.
The mare should be served again the next morning if she is still in oestrous.
If ovulation has not occurred within 24 hours after treatment, then the injection
should be repeated.
Registered to and distributed by: Intervet Ltd, 12 Shakespeare Ave, Upper Hutt. New Zealand, Phone: 0800 447 838 www.intervet.co.nz
Receptal® is registered pursuant to the ACVM Act 1997, No. A4062. Prescription Animal Remedy (P.A.R.) Class 1 for use only under the authority or prescription of a veterinarian.
See www.nzfsa.govt.nz/acvm/ for registration conditions.
Not all GnRH are the same
Receptal® is the only veterinary GnRH with the highly potent Buserelin as its active constituent.
The New Zealand dairy industry has a major problem with anoestrous cows, treating
around 500,000 cows annually to increase pregnancy rates.
Two fertility programmes for the treatment of anoestrous cows are recommended using Intervet’s
Receptal – a synthetic gonadotrophin releasing hormone (GnRH), in conjunction with a progesterone
device and prostaglandin analogue to stimulate the cow into oestrous prior to artificial insemination. The
Fixed Time Insemination programme can also be used for synchronisation of oestrous cows and heifers.
• 1 dose (2.0ml) Receptal
• Insert progesterone device
®
-3
-1
Hormone levels during the oestrous cycle of a cow
Buserelin – a unique active with unrivalled potency
® has the highly potent Buserelin as its active constituent. Buserelin acts the same as the natural
hormone
Receptal
level
LH/FSH releasing hormone
LH
LH produced in the hypothalamus. It causes simultaneous release of luteinising
Progesterone
hormone (LH) and follicle stimulating hormone (FSH) from the pituitary.
Ovulation
•is an international benchmark, enjoying world wide perception as the gold standard for GnRH
based products
Oestrous
• 1 dose (2.0ml) Receptal®
Inter-relationships in the control of female reproductive function
D E T E C T I O N O F O E S T R O U S P ro g r a m m e
-2
0
+1
Ovulation
*Nawito et al. (1977); Reeves et al. (1980); Loumaye et al. (1982); Chenault et al. (1990).
Hypothalamus
• 1 dose (2.0ml) Receptal®
• Insert progesterone device (CIDR)
• Remove progesterone device (CIDR)
• Inject Prostaglandin (PGF2α) analogue
at recommended luteolytic dose
• Inseminate on detection of oestrous
• 1 dose (2.0ml) Receptal® to non-detected cows
• Fixed time artificial insemination
immediately or within 24 hours
Oestradiol
positive
feedback
Using a GnRH?
– Receptal®
is your most
potent option
Inhibin
negative
feedback
Pituitary gland
FSH
Follicle
Progesterone
negative
feedback
LH
Luteolysis
Corpus
Luteum
Maturation
Oestrogens
PGF2 α
Luteinization
Oxytocin
Ovulation
•As LH release is stimulated by GnRH, it is in fact
the ability of a GnRH analogue to stimulate the
release of LH from pituitary gland that decides
about its efficacy
Progesterone
Why is Buserelin so potent?
•Gonadorelin is identical in structure to
natural GnRH
•Buserelin has one amino-acid difference
•this gives it higher affinity for the GnRH
receptors in the pituitary gland
Uterus
•which results in higher levels of FSH/LH
released
Oestradiol
Ovulation
The table below shows results from selected trials summarising the effect on
pregnancy rate of administering GnRH 11-13 days post-insemination
Ovulation
Author
Oestrous
•The main uses of GnRH analogues in the
management of reproduction in cattle rely
on their ability to induce ovulation of the
responsive ovarian follicle(s) present on the
ovary at the time of injection.
•The final stimulus that triggers the ovulation
comes in the form of the maximal
concentrations of LH (so called preovulatory
LH peak)
A New Zealand cost benefit analysis indicates that returns on this programme
are around 200%, based on milk production gains alone.
PGF2α
– a question of potency
•It therefore makes sense to use the most potent
analogues on the market to ensure the efficient
ovulation induction
Ovary
Growth
FSH
Receptal®
Oestrous
GnRH
-9
Progesterone
•was involved in the majority of the fundamental works on the application of GnRH in cattle
– internationally
and in New Zealand
Luteal phase
Foll. phase
Foll. phase
•Fixed time Artificial Insemination 16 – 20
hours after final Receptal® injection
LH
LH
•is at least 50 – 60 timesFSH
more effective than Gonadorelin, the alternative GnRH active* (as measured
in FSH and LH response)
Interrelationships in the control of female reproductive function
0
hormone
level
Receptal® containing Buserelin:
•is the most potent GnRH analogue of standard formulation on the vet market
• Remove progesterone device (CIDR)
• Inject Prostaglandin (PGF2α) analogue
at recommended luteolytic dose
MacMillan et al, (1986), investigated this effect in lactating dairy cows of
mixed breed in seasonally calving dairy herds in New Zealand. Treatment with
Receptal® (10µg) increased pregnancy rate to first insemination by 11.5%.
Sheldon and Dobson (1993), conducted a trial across 19 commercial dairy farms
(1040 cows) in seasonal calving herds in the UK where the use of Receptal®
(10ug) on day 11 post-service improved pregnancy rate by 9.4% compared to
paired control cows. Other trials by Sheldon 1990/91 using Receptal® (10µg)
showed a post service improved pregnancy rate of 13.2% when used on 2nd
service repeat breeding cows, 28.3% and 30.0% when used on 3rd and 3rd plus
service repeat breeding cows respectively.
Hormone levels during the oestrous cycle of a cow
PGF2αand better support ofOestradiol
•stimulates high production of LH for efficient induction of ovulation
corpus
luteum formation and early luteal function
F i X E D T I M E I N S E M I N A T I O N P R O G R AMM E
-10
Hormone levels during the oestrous cycle of a cow
Not
all GnRH are the same:
Luteal phase
Foll. phase
This involved investigating the LH and FSH response of Holstein heifers to fertirelin
acetate, gonadorelin and buserelin, aimed at: Hypothalamus
GnRHof the induction of FSH
“Response to the treatment with GnRH analogues in terms
and LH release was measured as average areaPituitary
under curve
and determination of
gland
Results
Service
Time of GnRH
administration
Post
insemination
Improvement
in preg rate
cf controls
MacMillan et al
225
1
11-13 days
11.5%
Sheldon and
Dobson 1993
1040
1
11days
9.4%
Drew and
Peters 1994
643
1
12 days
12.0%
Adas 1989/90
660
1
12 days
12.0%
Sheldon
1990/91
272
2
11days
13.2%
Sheldon
1990/91
134
3
11days
28.3%
Sheldon
1990/91
80
3+
11days
30.0%
Foll. phase
Synchronisation of oestrous cows and heifers
TheInter-relationships
Chenault trial – Chenault
et al.
(1990):of female reproductive
The benefits
of high FSH/LH
in the
control
function
Inhibin
Oestradiol
differences
in bioequivalence
negative
positive
feedback
feedback
Sample size
Oestrous
between three molecules tested.”
FSH
LH
•10μg of buserelin stimulated the largest release of LH in comparison to any
Follicle
Ovary
of the doses of gonadorelin used
Luteolysis
LH
•efficient induction of ovulation
•better support for the formation of corpus luteum
•better early luteal function
FSHProgesterone
negative
feedback
•supports
the selection and maturation of dominant follicle
Reference
•The largest dose (500μg)
Growth of gonadorelin recommended in cattle,
Corpus
Luteum
released significantly less FSH and LH as compared to
the lowest dose of PGF2 α
Nawito et al. (1977)
Maturation
buserelin used (10μg)
Luteini-
Potency of buserelin in relation to gonadorelin
In vivo (cattle)
50x
zation
•Standard recommended dose of buserelin was proven to be the most
Chenault et al. (1990)
Oxytocin
Oestrogens
Progesterone
efficient in terms of LH release and duration
of action than any of the GnRH
Ovulation
analogues tested
Reeves et al. (1980)
Uterus
Loumaye et al. (1982)
60x
In vitro — cell lines
50x
60x
Receptal®, when used as part of a 10 day fixed time oestrous synchronisation
and insemination regime, will increase submission rates and significantly reduce
the calving to conception interval. The regime requires Receptal® to be used in
conjunction with a PGF 2α analogue with luteolytic activity and a progesterone
implant device (see Fixed Time Insemination Programme).
When using fixed time insemination regimes, it is recommended that cows
showing signs of oestrous after prostaglandin treatment should be inseminated
when observed in oestrous rather than completing the synchronisation
programme.
Prevention of early embryonic mortality
Use of Receptal® at 11-12 days post-insemination
Early embryonic mortality is regarded as a major cause of reproductive failure in
cattle; some estimates suggest that 25% of bovine embryos are lost during the
first 3 weeks of life, with luteolysis suspected as a major cause. Studies show that
the administration of GnRH at 11-13 days post-service suppresses oestradiol17ß and PGF 2α, possibly representing a mechanism for a direct anti-luteolytic
and embryo protective effect of GnRH. This effect has been demonstrated in a
number of species including cattle, horses, sheep and rabbits.