Portal latinoamericano de toxicología
Florida Polo Horse Deaths & sodium selenite
12 May, 2009
Biodyl, Franck’s Pharmacy, and Florida Polo Horse Deaths: Guaranteed It’s the Decimal.scienceblogs.com. April 24, 2009, by Abel Pharmboy. Last weekend, 21 Venezuelan polo horses collapsed and died at the US Open championship match at the International Polo Club Palm Beach in Wellington, Florida (AP, CNN). The deaths have now been associated with injection of a veterinary mineral supplement produced by a compounding pharmacy in Ocala, Florida. Located in central Florida about 45 min south of the University of Florida, Ocala is well-known for its density of equestrian farms and training centers.Read also related notices: Selenium Overdose Caused Deaths of Polo Horses & Polo needs drug testing for horses, Humane Society says (CNN)
Precisely how this supplement killed the animals is not yet known but I can guarantee that it was a calculation error involving an errant decimal point, the bane of any professor in the STEM disciplines.
The compounding pharmacy that provided the supplement was apparently trying to reproduce the formula of a swine and equine supplement sold worldwide under the brand name, Biodyl. Biodyl is produced by Merial, an animal health product company run as a joint venture of Merck and Sanofi-Aventis. Merial conducts business in about 150 countries and lists annual sales at $2.6 billion; while they have operations in Duluth, Georgia, the Biodyl product is not sold in the US and their pressroom site does not have any information on this case as of this afternoon.
However, and to be clear, the product in question was not made by Merial. Rather, it was a custom formulation apparently commissioned by a veterinarian from Franck’s Pharmacy, a compounding pharmacy that has been in the business for over 25 years. Compounding pharmacies do what comes to mind when one thinks of an old-fashioned pharmacist in a Norman Rockwell painting.
Today, compounding pharmacies continue to play an important role in human and veterinary medicine in providing specialty products made to specific doses not available commercially, free of preservatives or potential allergens, or otherwise meet individual patient needs. The International Academy of Compounding Pharmacists has an excellent primer on the role of this practice of pharmacy.
The practice of compounding, however, has come under attack by FDA in recent years as some operations skirt the law and sometime produce what the agency calls unapproved drugs: preparations of compounds not currently approved in other forms. For example, compounding pharmacies the subject of FDA action for hormone creams defined as unapproved drug products or topical local anesthetics with inadequate labeling for use and safety.
So where do I think things went wrong? Well, what is in the Biodyl supplement and what is it used for?
The supplement contains sodium selenite, vitamin B12, and salts of potassium and magnesium. From their Philippine product site:
Biodyl (VR-1683)Injection solution containing metabolic constituents (adenosine triphosphoric acid or ATP, magnesium and potassium aspartate, sodium selenite and vitamin B12) for debility, convalescence and myopathies.
It is used to prevent a type of rhabdomyolysis, or life-threating skeletal muscle degradation, that can follow physical exertion after a period of inactivity (as one might expect for horses being transported to south Florida from Venezuela. Also known as equine rhabdomyolysis syndrome (EMS), tieing-up, or azoturia, the syndrome has been associated with high carbohydrate diet and selenium deficiency. I don’t quite understand the inclusion of ATP in the supplement since it does not readily cross cell membranes.
I must offer a mega hat tip: much of the information provided here today came from PharmGirl, MD. She dug up a lot of this info while I was on a plane yesterday and then while I was asleep and she wasn’t. I keep telling her to start her own blog.
However, we have differing opinions on the compound whose content was mistakenly calculated.
Having been trained originally as a toxicologist, my money is on the sodium selenite. Selenium is an essential element but is toxic at surprisingly low doses; as a trace element, adults only need about 55 micrograms per day (abbreviated mcg or µg). Methinks it would be quite easy for a pharmacist to mistake mcg or µg for mg or milligrams. So my bet is that the supplement had 1000 times the amount of sodium selenite than intended. The LD50 for sodium selenite in rodents and rabbits via the oral, intravenous, subcutaneous, or intraperitoneal routes is in the range of 2 to 7.5 mg per kg body weight (LD50 is an experimental term used to describe a dose of chemical required to kill 50% of animals in a given sample size)
Dr PharmGirl contends that the deaths were due to a miscalculation of either the magnesium or potassium, with potassium being the more likely culprit. Intravenous potassium chloride is one of three chemicals used for execution by lethal injection. Potassium, together with sodium, are among the most exquisitely regulated cations in physiology. The oral LD50 of potassium chloride, for example, is 1500 mg/kg in the mouse and 2600 mg/kg in the rat but I am unable to find these figures for injection.
What’s your guess?
Regardless of the cause, this is an extremely sad case that will draw much attention to the practice of pharmacy compounding. I wrote two years ago about a fatality in an Oregon integrative medicine clinic due to a 10-fold error in an injectable colchicine product that was being used unconventionally for back pain.
Compounding pharmacies that operate ethically provide an important service for physicians and their patients. And, sadly, contacts I have inform me that Franck’s Pharmacy in Ocala has a very good reputation in veterinary circles.
These cases should give the profs among our readers more fuel to respond to students about placement of decimal points and the importance of calculations in their respective careers.
The compounding pharmacy that provided the supplement was apparently trying to reproduce the formula of a swine and equine supplement sold worldwide under the brand name, Biodyl. Biodyl is produced by Merial, an animal health product company run as a joint venture of Merck and Sanofi-Aventis. Merial conducts business in about 150 countries and lists annual sales at $2.6 billion; while they have operations in Duluth, Georgia, the Biodyl product is not sold in the US and their pressroom site does not have any information on this case as of this afternoon.
However, and to be clear, the product in question was not made by Merial. Rather, it was a custom formulation apparently commissioned by a veterinarian from Franck’s Pharmacy, a compounding pharmacy that has been in the business for over 25 years. Compounding pharmacies do what comes to mind when one thinks of an old-fashioned pharmacist in a Norman Rockwell painting.
Today, compounding pharmacies continue to play an important role in human and veterinary medicine in providing specialty products made to specific doses not available commercially, free of preservatives or potential allergens, or otherwise meet individual patient needs. The International Academy of Compounding Pharmacists has an excellent primer on the role of this practice of pharmacy.
The practice of compounding, however, has come under attack by FDA in recent years as some operations skirt the law and sometime produce what the agency calls unapproved drugs: preparations of compounds not currently approved in other forms. For example, compounding pharmacies the subject of FDA action for hormone creams defined as unapproved drug products or topical local anesthetics with inadequate labeling for use and safety.
So where do I think things went wrong? Well, what is in the Biodyl supplement and what is it used for?
The supplement contains sodium selenite, vitamin B12, and salts of potassium and magnesium. From their Philippine product site:
Biodyl (VR-1683)Injection solution containing metabolic constituents (adenosine triphosphoric acid or ATP, magnesium and potassium aspartate, sodium selenite and vitamin B12) for debility, convalescence and myopathies.
It is used to prevent a type of rhabdomyolysis, or life-threating skeletal muscle degradation, that can follow physical exertion after a period of inactivity (as one might expect for horses being transported to south Florida from Venezuela. Also known as equine rhabdomyolysis syndrome (EMS), tieing-up, or azoturia, the syndrome has been associated with high carbohydrate diet and selenium deficiency. I don’t quite understand the inclusion of ATP in the supplement since it does not readily cross cell membranes.
I must offer a mega hat tip: much of the information provided here today came from PharmGirl, MD. She dug up a lot of this info while I was on a plane yesterday and then while I was asleep and she wasn’t. I keep telling her to start her own blog.
However, we have differing opinions on the compound whose content was mistakenly calculated.
Having been trained originally as a toxicologist, my money is on the sodium selenite. Selenium is an essential element but is toxic at surprisingly low doses; as a trace element, adults only need about 55 micrograms per day (abbreviated mcg or µg). Methinks it would be quite easy for a pharmacist to mistake mcg or µg for mg or milligrams. So my bet is that the supplement had 1000 times the amount of sodium selenite than intended. The LD50 for sodium selenite in rodents and rabbits via the oral, intravenous, subcutaneous, or intraperitoneal routes is in the range of 2 to 7.5 mg per kg body weight (LD50 is an experimental term used to describe a dose of chemical required to kill 50% of animals in a given sample size)
Dr PharmGirl contends that the deaths were due to a miscalculation of either the magnesium or potassium, with potassium being the more likely culprit. Intravenous potassium chloride is one of three chemicals used for execution by lethal injection. Potassium, together with sodium, are among the most exquisitely regulated cations in physiology. The oral LD50 of potassium chloride, for example, is 1500 mg/kg in the mouse and 2600 mg/kg in the rat but I am unable to find these figures for injection.
What’s your guess?
Regardless of the cause, this is an extremely sad case that will draw much attention to the practice of pharmacy compounding. I wrote two years ago about a fatality in an Oregon integrative medicine clinic due to a 10-fold error in an injectable colchicine product that was being used unconventionally for back pain.
Compounding pharmacies that operate ethically provide an important service for physicians and their patients. And, sadly, contacts I have inform me that Franck’s Pharmacy in Ocala has a very good reputation in veterinary circles.
These cases should give the profs among our readers more fuel to respond to students about placement of decimal points and the importance of calculations in their respective careers.
Read also related news: Mineral overdose may have led to horse deaths, says veterinarian. guardian.co.uk. April 28, 2009. Dr Thomas J Holt says toxicology tests show 21 polo horses in Florida had significantly increased selenium levels. Florida’s top veterinarian today blamed the deaths of 21 elite polo horses on an overdose of a common mineral that helps muscles recover from fatigue.
Florida’s state veterinarian, Dr Thomas J Holt, said toxicology tests on the dead horses showed significantly increased selenium levels.
The horses from the Venezuelan-owned Lechuza Caracas team began collapsing 19 April as they were unloaded from trailers at the International Polo Club Palm Beach in Wellington before a championship match. Some died at the scene, others hours later.
"Signs exhibited by the horses and their rapid deaths were consistent with toxic doses of selenium," Holt said.
The team was preparing to play in the sport’s US Open and was seen as a top contender.
A Florida pharmacy that mixed a brew of vitamins and minerals for the team on order from its Florida veterinarian said today that the strength of selenium was incorrect. Jennifer Beckett, chief operating officer for Franck’s Pharmacy in Ocala, Florida, would not say whether the incorrect amount was specified in the veterinarian order or was a pharmacy error.
"We continue to cooperate fully with the authorities as their investigations proceed," she said. "We cannot discuss further details."
Lechuza had no comment on the toxicology report.
The polo team had hoped to get a compound similar to a name-brand supplement known as Biodyl. The supplement is used around the world but hasn’t been approved by the Food and Drug Administration for use in the US.
Veterinarians often turn to compounding pharmacies like Franck’s for medications that can’t be found on shelves, but the dispensaries generally can only recreate unapproved drugs in limited circumstances, such as for health reasons.
The FDA and state authorities are investigating.
Biodyl is a supplement made in France by Duluth, Georgia-based animal pharmaceutical firm Merial Limted. It wasn’t clear how close Franck’s mixture came to the name-brand drug. Lechuza said what they ordered was supposed to contain vitamin B, potassium, magnesium and selenium.
The injections provided by Franck’s were given to the horses just hours before their deaths.
Dr Murl Bailey, a toxicology professor at Texas A&M University’s college of veterinary medicine & biomedical sciences, said selenium is a common mineral needed in small doses by humans and animals for growth and tissue stabilisation. It can also help muscles recover from fatigue.
"It’s a naturally occurring mineral in the Earth’s crust," Bailey said. But he said it was generally not needed as a supplement since most people and animals get it in their food.
Bailey said an overdose of selenium can cause the veins in the body to dilate, "so there’s really no blood coming back to the heart".
"The horses go into shock," he said. Necropsies previously revealed bleeding in the horses’ lungs.
Dr Tam Garland, division head of the toxicology and drug testing section at Texas A&M’s veterinary medical diagnostic laboratory, said the horses’ deaths would likely have been painful, and irreversible after the overdose.
"Haemorrhaging in the lungs tells me these horses couldn’t breathe," Garland said.
Florida’s state veterinarian, Dr Thomas J Holt, said toxicology tests on the dead horses showed significantly increased selenium levels.
The horses from the Venezuelan-owned Lechuza Caracas team began collapsing 19 April as they were unloaded from trailers at the International Polo Club Palm Beach in Wellington before a championship match. Some died at the scene, others hours later.
"Signs exhibited by the horses and their rapid deaths were consistent with toxic doses of selenium," Holt said.
The team was preparing to play in the sport’s US Open and was seen as a top contender.
A Florida pharmacy that mixed a brew of vitamins and minerals for the team on order from its Florida veterinarian said today that the strength of selenium was incorrect. Jennifer Beckett, chief operating officer for Franck’s Pharmacy in Ocala, Florida, would not say whether the incorrect amount was specified in the veterinarian order or was a pharmacy error.
"We continue to cooperate fully with the authorities as their investigations proceed," she said. "We cannot discuss further details."
Lechuza had no comment on the toxicology report.
The polo team had hoped to get a compound similar to a name-brand supplement known as Biodyl. The supplement is used around the world but hasn’t been approved by the Food and Drug Administration for use in the US.
Veterinarians often turn to compounding pharmacies like Franck’s for medications that can’t be found on shelves, but the dispensaries generally can only recreate unapproved drugs in limited circumstances, such as for health reasons.
The FDA and state authorities are investigating.
Biodyl is a supplement made in France by Duluth, Georgia-based animal pharmaceutical firm Merial Limted. It wasn’t clear how close Franck’s mixture came to the name-brand drug. Lechuza said what they ordered was supposed to contain vitamin B, potassium, magnesium and selenium.
The injections provided by Franck’s were given to the horses just hours before their deaths.
Dr Murl Bailey, a toxicology professor at Texas A&M University’s college of veterinary medicine & biomedical sciences, said selenium is a common mineral needed in small doses by humans and animals for growth and tissue stabilisation. It can also help muscles recover from fatigue.
"It’s a naturally occurring mineral in the Earth’s crust," Bailey said. But he said it was generally not needed as a supplement since most people and animals get it in their food.
Bailey said an overdose of selenium can cause the veins in the body to dilate, "so there’s really no blood coming back to the heart".
"The horses go into shock," he said. Necropsies previously revealed bleeding in the horses’ lungs.
Dr Tam Garland, division head of the toxicology and drug testing section at Texas A&M’s veterinary medical diagnostic laboratory, said the horses’ deaths would likely have been painful, and irreversible after the overdose.
"Haemorrhaging in the lungs tells me these horses couldn’t breathe," Garland said.