RANDLABSPRING 2018 NEWSLETTER SPRING 2018 NEWSLETTER
ALTRENOGEST has been used in performance fillies and mares for over 20 years. So why is its use now being restricted?
In no mood to work. Mares behaving badly. Randlab’s Global Technical Veterinarian, Dr Michael Robinson, presents the facts behind the current Altrenogest debate KEY POINTS Altrenogest is still able to be used in performance mares that are: · Racing in NSW (oral only and not within one clear day of racing). · Not competing in official Equestrian Australia/FEI events · Non-competition fillies and mares · Pleasure/recreational fillies and mares · Breeding mares
Under the Australian Rules of Racing and FEI Clean Sport For Horses Regulations, it is illegal to use Altrenogest in male horses.
Altrenogest injection delivers a peak concentration that is approximately seven times that achieved by daily oral administration of Altrenogest.
All current formulations of Altrenogest contain a low level of background impurities including trenbolone and trendione.
The higher peaks obtained with Altrenogest injection may also result in higher peaks of any impurities and may lead to a positive swab.
Altrenogest injections maintain plasma levels above those of daily oral Altrenogest for a period of 5-7 days following injection.
This may be compounded by repeated weekly injections which results in plasma levels that are sustained for longer.
Nothing has changed with the oral formulations of Altrenogest as there was one clear day between administration and racing (ie Thursday for over 20 years. However, its use has recently been brought administration for a Saturday race). into question by racing authorities. So why the change? Racing NSW continues to allow the use of oral Altrenogest up until one clear As most veterinarians are now aware, Racing Victoria issued a notice on 19 day from racing. June warning Victorian racehorse trainers and veterinarians against the use of Altrenogest. This unanticipated warning applied to both the oral and injectable On 26 July Equestrian Australia also circulated a notice to participants in equestrian formulations of the drug. sports advising that “Injectable Altrenogest should not be used and that oral Altrenogest products should also not be administered close to or during an event”. The warning was issued in response to the detection of the prohibited substances Table 1 shows a summary of all current (01 October 2018) Altrenogest warnings. trenbolone and trendione (both anabolic androgenic steroids) from two racing mares in Victoria in September 2017 and January 2018. The source of these positive swabs had been traced to the injectable form of Altrenogest (specifically AUTHORITY WARNING Ceva’s Readyserve Injection). Racing Victoria Do not use oral or injectable Altrenogest Oral Altrenogest may be used up until one clear day Nothing has changed in the ORAL Altrenogest formulations over the Racing NSW past 20 years. Trenbolone and trendione have always been in there at of racing low background levels that would have no therapeutic effect. For the past Racing Qld Do not use oral or injectable Altrenogest 20 years, oral Altrenogest has been routinely used in the racing industry Oral Altrenogest may be used up until one clear day Racing WA and other competitive equestrian sports and has not presented a doping of racing problem to regulatory officials. Racing SA Do not use oral or injectable Altrenogest Anabolic steroids are prohibited substances under the Australian Rule of Racing Racing Tas Do not use oral or injectable Altrenogest (AR.178H) which states that; “A horse must not, in any manner, at any time, be administered an anabolic androgenic steroid”. This ban applies from birth until Harness Racing Authority Do not use oral or injectable Altrenogest the end of the horse’s racing career. Penalties for offenders are harsh with a Do not use injectable Altrenogest. mandatory disqualification of the horse from racing for a minimum period of 12 Equestrian Australia / FEI Oral Altrenogest should not be used close to or months and a minimum of a two-year disqualification for those incriminated in during an event. the administration of the anabolic. Oral Altrenogest may be used up until one clear day NZTR & HRNZ of racing at the listed label dose rate. Racing NSW subsequently (22 June 2018) issued a similar notice against the use of injectable Altrenogest. However, the Racing NSW warning differed from TABLE 1: Current Altrenogest Warnings as of 01 October 2018. that of Racing Victoria in that oral Altrenogest could continue to be used as long
AUSTRALIAN OWNED AUSTRALIAN MADE www.randlab.com.au 7/85 Alfred Road, Chipping Norton NSW 2170 Australia • Phone: (61-2) 9728 3505 • Fax: (61-2) 9728 4352 • Email: [email protected] www.randlab.com.au QUALITYAUSTRALIAN • SERVICEOWNED • VALUEAUSTRALIAN • CARE MADE 1 ) $,.:/!D)(/1A()")(5;;"+:)14)"%%).5++0#3)L?[)C0230;&0+)>?FOM)6%3+0#170(3)A"+#-#7(8) 6%3+0#170(3)-()#13).1#<0+30$)31)0-3/0+)I+0#&1%1#0)1+)I+0#$-1#0)-#)<-<18) ) ) Q#K0.3"&%0)A00^%:)6%3+0#170(3)/"()&00#)"<"-%"&%0)"()"#)6SE,6R+07-(30+0$)2+1$5.3)-#)65(3+"%-")41+) $"E#&!DF!G15/0A!":A/07B/-A!H,5030B-!I,-!76!=D!*/4A/8./5!<=DJK! "22+1J-;"30%:)3A1):0"+(8)I/0)+0.1;;0#$0$)$1(0)+"30)41+)-#K0.3"&%0)6%3+0#170(3)-()?8_;7`^78))I/0) "L$M(%N$O!F!!!!!!!!!!H"%'N')! +0.1;;0#$0$)$"-%:)$1(0)+"30)41+)1+"%)6%3+0#170(3)-()?8?aa);7`^78))))) %,930B!P39A753,F)*1)#13)5(0)1+"%)1+)-#K0.3"&%0)6%3+0#170(3) ) %,930B!'*HF)9+"%)6%3+0#170(3);":)&0)5(0$)52)5#3-%)1#0).%0"+)$":)14)+".-#7) I/5()3/0)$1(0)14)-#K0.3"&%0)6%3+0#170(3)-()"22+1J-;"30%:)(0<0#)3-;0()3/"3)14)3/0)$"-%:)1+"%)$1(08))) I/-()-()"%(1)+04%0.30$)-#)3/0)2%"(;")6%3+0#170(3)%0<0%(=)A/-./)20"^)A-3/-#)3/0)4-+(3)F>)/15+()"#$) %,930B!Q:2F)*1)#13)5(0)1+"%)1+)-#K0.3"&%0)6%3+0#170(3) +0;"-#)/-7/)41+)"22+1J-;"30%:)aO)/15+()"430+)"$;-#-(3+"3-1#)L(00)\-75+0)>M8) %,930B!H"F)9+"%)6%3+0#170(3);":)&0)5(0$)52)5#3-%)1#0).%0"+)$":)14)+".-#7) ) %,930B!*"F)*1)#13)5(0)1+"%)1+)-#K0.3"&%0)RANDLAB6%3+0#170(3) ) TN)L%&!
) $5/,A8/0A!"!Y!":A5/07B/-A!30X/9A370!I=?Z8BSWBK!,02!$5/,A8/0A!E!Y!(5,:!":A5/07B/-A!I=?=[[8BSWBK8))))))) FIGURE)*"3").15+30(:)14) 2: Mean*+)H":;0)b1: plasma)>?FO =)P/"+%0()C35+3)c#-<0+(-3:8 concentrations following) weekly injections and) daily oral dosing with Altrenogest in ovariectomised mares. TreatmentI/0(0)/-7/0+)2%"(;")%0<0%() A = AltrenogestA-3/)3/0)-#K0.3"&%0)41+;5%"3-1#) injection (0.3mg/kg)"+0)"%(1)2+1&"&%:)+04%0.30$)-#)")/-7/0+) and Treatment B = .1#.0#3+"3-1#)14)3/0)-;25+-3-0()-#)3/0)&%11$8)))Q4)3/0)/1+(0)A0+0)30(30$)A-3/-#)aO)/15+()14) Oral"$;-#-(3+"3-1#)14) Altrenogest3/0)6%3+0#170 (0.044mg/kg).(3)-#K0.3-1#=)-3)-()%-^0%:)3/"3)")/-7/0+)%0<0%)14)-;25+-3-0( Presumably the pharmacokinetics)A15%$)&0) of any$030.30$= chemically)"#$)3/-();": similar)&0)0#157/)31 impurities)+0(5%3)-#)")21(-3-<0)(A"&8 will mimic )the Altrenogest data. Data courtesy) of Jaymie Loy 2018, Charles Sturt University. )) ) ) c#$0+)3/0)2+0<"-%-#7)65(3+"%-"#)!5%0()14)!".-#7=)"$;-#-(3+"3-1#)14)6%3+0#170(3)-#K0.3-1#)-#)4-%%-0()"#$) ) These;"+0()52)5#3-% higher)1#0 ).%0"+)$": plasma)14)+".-#7 levels)A"()20+;-330$8 with the ) injectable formulation are also I/-()./0;-."%)(-;-%"+-3:);0"#()3/"3)-#);1(3)L-4)#13)"%%M)(";2%0()14)6%3+0#170(3)3/0+0)A-%%)&0)")(;"%%) )) FIGURE";15#3)14)-;25+-3-0()-#.%5$-#7)3+0#&1%1#0)"#$)3+0#$-1#08))I:2-."%%: 1: The androgenic anabolic steroids trenbolone)3/0(0)"+0)2+0(0#3)-#)%0<0%() and trendione probably!".-#7)E-.31+-")-().5++0#3%:)(3-%%)-#<0(3-7"3-#7) reflected in a higher 3/0).-+.5;(3"#.0()"+15#$)3/0)E-.31+-"#)21(-3-<0)concentration of the impurities in the are&0%1A)?8?[ closely])"#$= chemically)"()(5./=)"3)%0<0% related()3/"3)"+0) &13/)(5&3/0+"2053-. to Altrenogest.=)-#.1#(0B50#3-"%) Altrenogest"#$)&0%1A)#1+;"%) is not blood.3+0#&1%1#0`3+0#$-1#0 If the horse)(A"&(8)) were6%3/157/)3/0)(15+.0)-() tested within 48%-^0%:)31)&0 hours)3/0) of!0"$:(0+<0) administration6%3+0#170(3 of) the metabolised$030.3-1#)%-;-3(8 ))to) either trenbolone or trendione in vivo. Altrenogest injection, it is likely that a higher level of impurities would be detected, and this may be enough to result in a positive swab. This chemical similarity means that in most (if not all) samples of Altrenogest there will be a small amount of impurities including Under the prevailing Australian Rules of Racing, administration of trenbolone and trendione. Typically these are present in levels Altrenogest injection in fillies and mares up until one clear day of below 0.05% and, as such, at levels that are both subtherapeutic, racing was permitted. inconsequential and below normal detection limits. Altrenogest is not converted to either trenbolone or trendione in vivo.
Winx not winks
Injectable weekly Altrenogest has been available as an APVMA- registered product in Australia for approximately two years. The recommended dose rate for injectable Altrenogest is 0.3mg/kg. The recommended daily dose rate for oral Altrenogest is 0.044 mg/kg. Mares in season represent a constant and unwanted distraction to colts and stallions. Thus the dose of injectable Altrenogest is approximately seven times that of the daily oral dose. In addition, the bioavailability of the injectable Racing Victoria is currently still investigating the circumstances around formulation is likely to be much higher than the oral formulation. The the Victorian positive trenbolone/trendione swabs. Although the combination of the higher dose and increased bioavailability will source is likely to be the Altrenogest injection, other factors may have ultimately result in higher plasma and urine levels of Altrenogest and contributed to these positives, as there have been no other reported presumably any impurities that may be in the formulation. positives and hundreds of other racing fillies are likely to have received Altrenogest injections in the same time period. The recent positive swabs to trenbolone and trendione out of Victoria are due to a unique set of circumstances that can easily be Although Randlab’s Ovu-Mate injection has not been incriminated avoided in the future with some knowledge of the pharmacokinetic in the current round of positives, Randlab has been assisting Racing and pharmacodynamic data of the two Altrenogest formulations. Victoria and other racing Authorities with their investigations.
Randlab is also investing in strategies to reduce the levels of impurities The higher and more sustained levels of Altrenogest obtained with the below the current industry standard. injectable formulation compared with the oral was shown in a small study in ovariectomised mares conducted by Jaymie Loy from Charles Sturt University (unpublished data). However, it becomes a philosophical and somewhat abstract argument as to what analytical screening limit actually constitutes This shows injectable Altrenogest levels peaking within the first 12 a perceived zero level of detectability. That is, if the impurity is hours, remaining high for approximately 48 hours and remaining below the limits of detectability using the latest, most advanced above the oral levels for approximately 96 hours (Figure 2). analytical methods, does this constitute a zero level?
2 AUSTRALIAN OWNED AUSTRALIAN MADE www.randlab.com.au The Annual Meeting of Racing Australia’s Veterinarians and Analysts (01/10/18) Committee was held in Victoria on 17 September. No doubt the The current situation hottest topic on the table was the continuing Altrenogest debate. The In response to the current Altrenogest controversies, Racing NSW conclusions of the meeting have yet to be made publicly available. introduced a new Local Rule of Racing (LR 44A) on 13th August. This rule deals with the detection of nonconsequential trace levels Meanwhile, the rest of the racing world watches in nervous anticipation of trenbolone/trendione (when detected along with Altrenogest). The as to how Australia will respond to the Altrenogest/Trenbolone issue. rule introduces new screening limits such that, if these substances are The very first Altrenogest-derived trenbolone positive was actually detected in urine and plasma at levels below 1ng/mL, then no action detected in the USA in 2017. will be taken (at the discretion of The Stewards). The British Horse Horseracing Authority (BHA) recently conducted Racing NSW introduced a Local Rule of Racing (LR44A) which their own investigation into Regu-Mate Oral Solution and found it allows for the continued use of oral Altrenogest up until one clear contained traces of trendione. They subsequently issued a notice on day from racing. 11 September advising that, “The possession, use or attempted use, Racing NSW continues to advise trainers not to use injectable and administration or attempted administration of Regumate® Equine Altrenogest products and not to use oral Altrenogest within one clear could amount to breaches of the Rules of Racing. As such, at this time, day of racing. we would advise trainers and other industry participants to remove Regumate® Equine from all licensed premises, and not to administer In response to this new local rule, Racing Victoria emailed veterinarians this product. Further work is ongoing to gain a greater understanding on 04 September advising them that their warning against the use of all of this issue and updated information will be provided to the industry formulations of Altrenogest in racing fillies and mares remains in place. when it becomes available.” This prompted a barrage of media shout outs from prominent Victorian trainers such as David Hayes, Peter Moody, Mick Price, Mick Kent, Tony McEvoy, etc. All trainers produced convincing arguments supporting the ongoing use of Altrenogest in racing fillies and mares. Arguments largely focused on the role of Altrenogest in keeping fillies and mares racing consistently and on the heightened OH&S risks of managing “in season” fillies and mares in a racing stable environment.
“Peter Moody used Regu-Mate with Black Caviar and Lee Freedman attributed Makybe Diva’s third Melbourne Cup to the calming effect of the treatment.”
Tail up and tailed off. Mares in season may behave erratically, perform inconsistently and represent a potential OHS hazard to their handlers. Racing Australia is expected to make a decision on the ongoing use of Altrenogest in the coming weeks. Any new rule will override the new Racing NSW rule. Ultimately, it will be easier and far simpler to ban all future use of Altenogest in racing stables and not have to deal with notional issues of anabolic administration, the potential of higher levels of trenbolone/trendione being found in out of competition testing swabs and the unfortunate but ever-present potential for misuse by the few that knowingly chose to abuse the system. Other regulatory bodies (such as Equestrian Australia / FEI) are likely to follow the Australian racing authorities’ lead.
In many ways, the loss of Altrenogest from use in mares engaged in equestrian sports is likely to have a bigger impact on performance, especially as competitions may run over several days.
Altrenogest has been shown to cross the placental barrier and is actually concentrated in the plasma of neonatal foals (mare: 2.6ng/mL vs foal: 5.6ng/mL)*. Given that AR.178H states that: “A horse must not, in any manner, at any time, be administered an anabolic androgenic steroid” if the use of Altrenogest were to be banned in racehorses because of its trace levels of trenbolone/trendione, it would also be technically illegal to administer Altrenogest to pregnant broodmares due to its inadvertent and unavoidable administration to the foetal foal. Will pragmatism ultimately prevail and the use of Altrenogest be restored (plus screening limits for trenbolone and trendione)? This would allow a return to the status quo of the past 20 years with the permitted use of ORAL Altrenogest up until one clear day of racing. Or will the racing purists’ strict no anabolic steroid policy ultimately lead to a ban of all formulations of Altrenogest from racing stables forever and amore? Stay tuned.
*Concentrations of altrenogest in plasma of mares and foals and in allantoic and amniotic fluid at parturition. Palm FM et al. Theriogenology (2010) 74:2 229-235.
If you would like any further information regarding Immortal Queens of the Turf: Winx, Makybe Diva and Black Caviar. the use of Altrenogest please contact Randlab’s Possibly the best three horses to race in Australia over the past technical veterinarian Dr Michael Robinson on 20 years. According to press reports, all three were regularly maintained on Altrenogest. 0451 481 050 or [email protected].
All images are for illustrative purposes only.
AUSTRALIAN OWNED AUSTRALIAN MADE 3 SPRING 2018 NEWSLETTER Randlab welcomes new WA Territory Manager Rebecca Puvanendran
With a passion also for the horse racing industry, Rebecca and her husband have shares in three Thoroughbreds including the 2015 Group 2 WA Guineas winner, Man Booker. He is the winner of 9 of his 19 starts and over $830K in prizemoney thus far and Rebecca describes his Guineas win as a “massive thrill”. Unfortunately, Man Booker sustained an injury whilst preparing for the WA Summer racing carnival last year and had to be sent for a lengthy spell. He recently resumed on the first day of Spring with an outstanding second at Belmont and followed that up with a 4L win in a listed race at Belmont a fortnight later. “We are very much looking forward to the Spring Carnival here with Man Booker and hope to have the other two young horses hit the track this Spring too”.
Rebecca, her husband and two children reside on a small horse property in the Southern Rural pocket of Darling Downs, where they “keep too many animals to mention”. She counts herself blessed to have a great network of friends, both old and new, within the horse industry within close vicinity.
Having spent the last 13 years in sales and In this issue Randlab welcomes its new traipsing half way around the State to fulfil their marketing, Rebecca believes she found her Western Australian Territory Manager, Ms daughter’s desire to compete as often as possible. “dream job” when she joined Randlab in June. Rebecca Puvanendran. Rebecca explains Rebecca once again found success in Eventing “It allows me to combine my love of all things how a life-long love of all things equestrian over many years and feels humbled to have had equine with my love of meeting people and has led her to her ultimate job at Randlab. some of Australia’s best-known Olympic medal- providing great customer service. I was delighted winning equestrians as coaches. to be offered a position with Randlab as their WA Born and raised in the southern rural suburbs of Territory manager”. WA, Rebecca literally learnt to ride before she After a lengthy break whilst she had her two could walk and was a proud owner of her own children, Rebecca once again returned to her “So far it has been a wonderful experience. I pony by the time she was four. horse passion in 2015. With two young children have met some great people, get to visit all the in tow, Rebecca no longer felt she needed the top equine veterinary clinics and have been lucky Young Rebecca and pony were constant pony adrenalin rush of Eventing and returned to the to learn more about horse health in the last few club attendees, competing in a variety of show hack ring. months than I have in the last 38 years (and we disciplines, until the attraction of all things bright thought you were in your 20’s!). And best of all, and beautiful soon saw her enter the glamorous With her attention to detail and being a self- I get to talk horses all day, every day with some world of the showring. Rebecca successfully confessed “Style Queen”, Rebecca has once amazing people! With Randlab’s special interest competed at her first Perth Royal Show when again shown her skills on the equine catwalks of in managing gastric ulcers and joint problems in only 6yo and returned every year for many years WA. “Over the past few years I have been lucky performance horses, I am looking forward to my thereafter. “Back in those days if you competed enough to compete with some stunning ponies for future as part of the Randlab team and expanding at the Royal Show you had really made it”, she friends and now I have two lovely young horses my knowledge even further”. joked (we think). (OTT thoroughbreds) to work with at home”. She is hopeful that at least one of them will make it to We too are excited to welcome Rebecca to Rebecca’s teenage years saw her turn her hand to the show ring for the 2019 season. Randlab as a permanent presence in WA. With Eventing. Her parents soon purchased Rebecca her extensive equine experience and knowledge, her own eventer and so began the weekly vigil of So far it has been a we know that you will enjoy dealing with Bec. wonderful experience. Whether it be in the showring or on the racetrack we wish Rebecca the best of luck with her equine I have met some great pursuits this Spring. people, get to visit all the top equine veterinary Rebecca can be clinics and have been contacted by mobile lucky to learn more about 0420 349 301 horse health in the last or by email few months than I have in [email protected]. the last 38 years! Don’t be a stranger.
www.randlab.com.au AUSTRALIAN OWNED AUSTRALIAN MADE 4 SPRINGRANDLAB 2018 NEWSLETTER Randlab’s new products for 2018 Randlab was excited to launch its new product range for 2018 at this year’s Bain Fallon Lectures. Most of the products are already available. As well as the products below, we also have new pack sizes for Equine Bute Paste (30ml multidose syringe and 250mL tub). New pack sizes for Sedator (20mL) and Ovu-Mate oral (2L) will also be available soon.
SED-Ace™ SEDATOR™ ORAL TRANQUILISER INJECTION FOR HORSES ACTIVE CONSTITUENT: ACTIVE CONSITUENT: Each mL contains ACEPROMAZINE MALEATE 12 mg 10 mg/mL DETOMIDINE HYDROCHLORIDE An aid in quieting For mild to heavy sedation of excitable, nervous, horses and for all analgesia, unruly or hard to including colic handle horses. APVMA Approval No. 80410/100822 | ACVM No. A011152 APVMA Approval No. 82623/106271 | ACVM No. A011244 Ovu-Mate® Meloxicam™ INJECTION PASTE FOR HORSES ACTIVE CONSTITUENT ACTIVE CONSTITUENT Altrenogest 50 mg/mL Meloxicam 20 mg/mL For the suppression of oestrus A non-steroidal anti-inflammatory in normally cycling mares analgesic - antipyretic for use in horses
APVMA Approval No. 83216/107741 | ACVM No. A11475 APVMA Approval No 82561/106068 | ACVM No. A011118
® ® Ovu-Late Cattle-Mate INJECTION FOR Gonadorelin CATTLE AND Injection HORSES ACTIVE CONSTITUENT Gonadorelin (as acetate) 100 μg/mL ACTIVE CONSTITUENT Cloprostenol (as the sodium salt) 250 µg/mL For the treatment of cystic ovaries, prevention of delayed For luteolysis of functional corpora ovulation and improvement of lutea in cows and mares postpartum fertility in cattle APVMA Approval No. 80077/100160 | ACVM No. A011124 APVMA Approval No. 81105/102328 | ACVM No. A11104
Product Supplied Under Permit Only Product Supplied Under Permit Only Zoldronic™ Acid Equine Bisphosphonate Injection ™ for Horses Metronidazole PASTE COMING SOON ACTIVE CONSTITUENT Metronidazole 500mg/g ACTIVE CONSTITUENT Zoledronic acid (as monohydrate) 0.45 mg/mL For the treatment of protozoal and A bisphosphonate for animals anaerobic bacterial infections caused with skeletal complications by metronidazole-sensitive organisms in horses APVMA Permit No. 81385 APVMA Permit No. 84510
Contact our sales team, email [email protected] or visit www.randlab.com.au for more info
5 AUSTRALIAN OWNED AUSTRALIAN MADE www.randlab.com.au SPRING 2018 NEWSLETTER Randlab at 2018 Bain Fallon in Sydney
Randlab Australia Sales and TechNICAL Support Alex Macpherson VIC/TAS/SA Andrew Grant QLD/NT Ian Saunders COMMERCIAL MANAGER Mobile 0421 829 101 Mobile 0426 407 117 Mobile 0416 776 991 Email [email protected] Email [email protected] Email [email protected]
John Dalton NSW/ACT Rebecca Puvanendran WA Dr Michael Robinson BVSc PhD Mobile 0404 221 776 Mobile 0420 349 301 Global Technical Director Email [email protected] Email [email protected] Mobile 0451 481 050 Email [email protected] AUSTRALIAN OWNED AUSTRALIAN MADE www.randlab.com.au 7/85 Alfred Road, Chipping Norton NSW 2170 Australia • Phone: (61-2) 9728 3505 • Fax: (61-2) 9728 4352 • Email: [email protected] www.randlab.com.au QUALITYAUSTRALIAN • SERVICEOWNED • VALUEAUSTRALIAN • CARE MADE 6