Equine Medicine Compounding

Equine Canker

Equine canker is a chronic, hyperproliferative, suppurative, pyogranulomatous pododermatitis of the frog, bars, and sole and, in severe cases, the adjacent hoof wall. The lesion appears grossly as soft, whitish, cauliflower-like proliferations associated with a foul-smelling caseous exudate. Canker is commonly reported in draft horses and usually affects the rear feet, however, it has been reported in many other equine breeds and has been known to affect all four feet. Episodes of canker are known to be seasonal and the majority of cases present during July through December. Canker is associated with wet or unhygienic (or both) stall conditions and is caused by opportunistic infections by treponeme spirochetes. A recent investigation1 detected 19 different phylotypes of treponemes present in canker-infected equine hoof tissue, but did not determine antimicrobial susceptibility for the organisms found. Treatment of canker has always been extremely difficult, and mortality due to foot loss has been high. In the 2004 Proceedings of the American Association of Equine Practitioners, Dr. Stephen O’Grady presented a compounded topical therapy which has subsequently become the therapy of choice in treating equine canker.2 He details treatment and outcome for a series of 56 cases of equine canker from 1998-2004 that all experienced consistent and predictable efficacy from this treatment. The therapy consists of a topical dressing of benzoyl peroxide, acetone, and metronidazole, covered by an elastomer putty protective layer and is changed daily. Treatment was continued for weeks to months or until the hoof tissue sufficiently recornified. The therapy described by Dr. O’Grady is not commercially available, but this compound, containing highly concentrated solutions of benzoyl peroxide and acetone, can be obtained through our compounding pharmacist.

J Vet Med Sci. 2010 Feb;72(2):235-9.
Detection of treponemes in canker lesions of horses by 16S rRNA clonal sequencing analysis.
Kyaw Kyaw Moe, Takahisa Yano; Atsutoshi Kuwano; Satomi Sasaki; Naoaki Misawa.
Click here to access the PubMed abstract of this article.

Proceedings of the American Association of Equine Practitioners, 2004.
How to treat equine canker.
O’Grady S, Madison J.


Reserpine for Compulsory Stall Rest

Reserpine has clinical therapeutic value to sedate horses recovering from injuries that are confined to stall rest for long periods of time. Reserpine is a narrow therapeutic index drug. Recommended doses of reserpine range from 1-4mg/500kg horse once daily and may be administered orally or by intramuscular injection. Doses of 5-10mg/500kg horse have resulted in severe toxicity. Signs of toxicity can occur within three to six hours of administration. Initially, severe depression, sweating and flatulence are seen. There may be sporadic episodes of colic, sometimes violent, followed by somnolence. Injection frequently results in diarrhea, but both oral and parenteral routes may result in increased gastrointestinal sounds, muscle trembling, hypotension, decreased heart rate, arrhythmias, miosis, ptosis, and penile paralysis. Clinical signs will persist until norepinephrine stores are replenished which may be up to 60 hours after dosing. Reserpine may be detected by drug assay for up to 5 days after administration. No antidote is available for reserpine toxicity, although methamphetamine has been suggested as a possible therapy.

Drug interactions with reserpine can be life-threatening. Horses treated with reserpine within the previous 60 days may be at risk for profound hypotension (even death) when exposed to xylazine, detomidine or ketamine.

Reserpine is no longer commercially available as an injection, but is available in 0.1mg and 0.25mg tablets. However, reserpine has a bitter taste, and many horses will not accept these tablets voluntarily. Our compounding pharmacy is able to provide palatable oral gels and suspensions of reserpine as well as reserpine injection upon the order of a licensed veterinarian.

Equine Clinical Pharmacology. Editors Joseph Bertone, DVM, MS and Linda J. I. Horspool BVMS PhD. WB Saunders, p. 152.


Transmucosal Buprenorphine: More is Better For Dogs and Horses

The pharmacokinetic profile of a buccally-administered (transmucosal) dose of buprenorphine to cats is almost identical to that of intravenously administered buprenorphine. The unusually alkaline salivary pH of cats prevents ionization of buprenorphine, allowing it to diffuse into systemic circulation in a non-ionized form. This discovery greatly facilitated outpatient feline pain relief, allowing owners to administer this drug to cats at home, without the need for hospitalization or injection. Because the duration of analgesia from buprenorphine (4-12hrs) is longer than that provided by other opiates, buprenorphine is frequently used for provision of non-invasive, intermediate to long-term analgesia in cats. It is typically administered at doses of 10-30mcg/kg applied to the oral mucosa (inside the cheek pouch) every 8 hours for up to 5 days (many cats experience anorexia after 5 days of therapy with buprenorphine). The commercially available 300mcg/ml solution for injection (Buprenex) works well for buccal administration with most cats receiving volumes of approximately 0.066ml/kg (e.g. 0.33ml for the average 5kg cat).

Buccal absorption of buprenorphine has also been examined in dogs at approximately the same dose (20mcg/kg) utilized in cats. Absorption was low at this dose, but a dose of 120 mcg/kg administered transmucosally to dogs produced drug concentrations equivalent to an intravenous dose of 20 mcg/kg. Dogs have a relatively more acidic salivary pH than cats, resulting in more ionization of buprenorphine, reducing the amount of drug available for diffusion across membranes. At doses of 120mcg/kg, a 25kg dog would require 3000mcg or 10ml of the commercially available buprenorphine solution for injection. A canine patient would likely swallow a large portion of 10ml administered buccally, and since the oral absorption of buprenorphine is extremely low, analgesic effect would not be achieved. Recent work at NC State University (unpublished) also demonstrates that buccal buprenorphine provides effective analgesia in horses when administered at doses of 6.6mcg/kg (e.g. 11ml of the commercially available injection for a 500kg horse). Again, a significant portion of this dose is likely to be swallowed by an equine patient, precluding a full analgesic effect.

For dogs and horses, a more concentrated solution of buprenorphine is greatly desirable for transmucosal use. Compounded solutions of buprenorphine from 3-6mg/ml would allow for buccal administration of volumes of less than 1ml for both dogs and horses. Our compounding pharmacy can prepare concentrated solutions of buprenorphine for transmucosal use in dogs and horses. Please call for more information.

J Vet Pharmacol Ther. 2005; 28(5):453-460.
PK-PD modeling of buprenorphine in cats: intravenous and oral transmucosal administration
Click here to access the abstract of this article.

Vet Ther. 2008 Summer;9(2):83-93.
Pharmacokinetics of buprenorphine following intravenous and oral transmucosal administration in dogs.
Click here to access the PubMed abstract of this article.


Stability of Compounded Pergolide
Pituitary pars intermedia dysfunction (PPID) is the most common endocrine disorder in equine species.The most life-threatening clinical sign of PPID is laminitis, which is thought to be related to cortisol and other hormonal effects on glucose utilization by tissues of the hoof wall.

An integral part of PPID management is medical treatment.The most widely used drug is the dopamine agonist, pergolide. Unfortunately, pergolide was withdrawn from the human market in 2007 due to cardiovascular side effects in people. Pressured by the American Veterinary Medical Association, the American Association of Equine Practitioners, and thousands of horse owners in May 2007, the Food and Drug Administration decided to allow compounding of pergolide for horses utilizing the bulk chemical active pharmaceutical ingredient. As a result of this milestone decision, compounding pharmacists began providing various compounded dosage forms of pergolide for horses with PPID.Most horse owners prefer to utilize flavored oral suspensions of pergolide.This dosage form allows for both increased palatability to the patient, increased compliance by the horse owner, and allows for flexibility in dosage adjustment until an effective dosage is determined. Unfortunately, pergolide was never commercially available in a liquid oral dosage form.Commercial availability was limited to the tablet dosage form and until recently, no information was available to support the stability of a liquid dosage form of pergolide. In February 2009, researchers at the NC State College of Veterinary Medicine published results of a long-term stability study for aqueous suspensions of pergolide.In this study, pergolide was compounded into an aqueous formulation with a final target concentration of 1 mg/mL. Aliquots of the formulation were then stored at –20°, 8°, 25°, or 37°C without exposure to light or at 25°C with exposure to light for 35 days. Samples were assayed in triplicate by means of high-pressure liquid chromatography immediately after compounding and after 1, 7, 14, 21, and 35 days of storage.Results showed that samples exposed to light while stored at 25°C had undergone excessive degradation by day 14, samples stored at 37°C had undergone excessive degradation by day 21, and samples stored at 25°C without exposure to light had undergone excessive degradation by day 35. The decrease in expected concentration corresponded with the appearance of degradation peaks in chromatograms and with a change in color of the formulation.In light of these results, researchers concluded that compounded pergolide formulations in aqueous vehicles should be stored in a dark container, protected from light, and refrigerated and should not be used > 30 days after produced. It is also recommended that pharmacists and veterinarians do not add any excipients which would prevent an owner from detecting a color change in pergolide formulations.Formulations that have undergone a color change should be considered unstable and discarded. The results of this study should allow veterinarians and our compounding pharmacists to collaborate to provide more accurate control of this devastating equine disease.

J Am Vet Med Assoc 2009;234:385–389
Compounding and Storage Conditions on Stability of Pergolide Mesylate.
Click here to access the abstract of this article.


Sugar-Free Medications For Horses with EMS

The term “equine metabolic syndrome” (EMS) has been adopted to describe a collection of clinical signs that contribute to the development of laminitis in horses, and has previously been described as peripheral equine Cushing’s syndrome, pseudo-Cushing’s syndrome, hypothyroidism, and insulin resistance syndrome. Causes of EMS are similar to those found to cause metabolic syndrome and insulin resistance in humans. Management and prevention of EMS primarily revolves around weight control and prevention of obesity. While there is no “cure” for EMS, there exist many supportive therapies including vitamin and mineral supplements, low starch feeds, and anti-inflammatory and analgesic medications. While the horse feed industry has quickly realized the need for sugar-free feeds, any change in drug formulation requires FDA approval, so the veterinary drug industry has not been able to respond quickly to the need for sugar-free medications and supplements for horses.

Our compounding pharmacy can contribute significantly to the care of EMS horses by working with veterinarians to convert all medications and supplements to sugar-free dosage forms. Sugar-free powders and pastes of phenylbutazone, flunixin, pergolide, and vitamins are particularly valuable to veterinarians treating horses with EMS.


Pergolide for Equine Cushing’s Disease

Pergolide has proven to be a safe and effective therapy in long term management of equine Cushing’s disease. The American Association of Equine Practitioners (AAEP) has been working with the FDA to develop options to provide veterinarians with continued access to pergolide to treat equine Cushing’s patients. FDA has indicated willingness to utilize regulatory discretion to allow compounding pharmacists to provide pergolide compounded from the bulk substance until a manufactured source of pergolide can be made available.
J Vet Intern Med. 2002 Nov-Dec;16(6):742-6.
Treatment with pergolide or cyproheptadine of pituitary pars intermedia dysfunction (equine Cushing’s disease).
Click here to access the PubMed abstract of this article.


Electrolyte Paste to Restore Fluid and Acid Base Balance in Horses

“Prolonged exercise in horses, particularly when performed in hot and humid conditions, brings about large fluid and electrolyte loses which, if not restored, may impair thermoregulatory responses and result in hyperthermia.” In horses, administration of oral rehydration solutions (ORS) is problematic, because many horses refuse to drink fluids containing electrolytes. Therefore, administration of ORS typically requires placement of a nasogastric tube with its inherent risks. An alternative is to give a concentrated electrolyte mixture as a paste. Leon et al. of Department of Veterinary Clinical Sciences, University of Sydney, NSW, Australia studied six Thoroughbred geldings to determine “whether oral administration of a concentrated electrolyte paste would promote the restoration of fluid, electrolyte, and acid base balance as well as fluid and electrolyte deficits induced by furosemide administration” (a standard model which induces significant contraction of plasma volume and consistent electrolyte deficit against which the effects of treatment could be measured).
“As a general conclusion, horses that received concentrated electrolytes [and had free access] to water consumed more water, regained more weight, lost considerably less electrolytes in urine, and maintained plasma electrolyte concentrations and acid base balance closer to baseline values than did those that had ad libitum access to water only.” Administration of electrolyte paste provided a more practical source than supplementation using feed or salt blocks.

Am J Vet Res 1998 Jul;59(7):898-903
Effects of concentrated electrolytes administered via a paste on fluid, electrolyte, and acid base balance in horses.
Click here to access the PubMed abstract of this article.


Progesterone for Estrus Induction in Mares

According to Robert R. Foss, DVM, progesterone in sesame oil, 150 mg per day, IM is equally as efficacious as altrenogest. The optimal formulation is the combination of progesterone and estradiol 17-beta; the addition of estradiol provides a greater feedback than progesterone alone, so cessation produces a more dramatic response. The estradiol is somewhat protective against exacerbation of endometritis. Dr. Foss commonly uses this combination at 150 mg progesterone and 10 mg estradiol 17-beta, IM, daily for 10 days. Estrus will usually begin in 6-8 days with ovulation around day 10-12. This combination has been effective in situations where altrenogest has failed.

114th IL VMA Proceedings, February, 1996


Prednisone (Oral) Ineffective in Horses

Jackson et al. compared the effects of prednisone with environmental management to environmental management alone for the treatment of heaves (recurrent airway obstruction), and reported that oral prednisone has no additional benefit.

To be effective, oral prednisone must be absorbed and metabolized to its active form prednisolone. Robinson et al. designed a study with two objectives: 1) to compare oral prednisone with intravenous dexamethasone for the treatment of horses with heaves; and 2) to measure serum prednisolone levels in horses after oral administration of prednisone and prednisolone. Each of five horses received five drug formulations (prednisone and prednisolone in tablet and liquid form, as well as intravenous prednisolone sodium succinate as a positive control, all at a dose of 2.2 mg/kg) in a Latin square design study. Severity of airway obstruction was measured, and there were no significant differences between prednisone administration and no medication at any time. Prednisolone was detectable in serum immediately after intravenous administration, peaking at around 1000 ng/ml at 12 min. Oral administration of prednisolone tablets or liquid yielded peak serum prednisolone concentrations of 377-1032 ng/ml at 30-45 min. When horses received oral prednisone tablets or liquid, prednisolone never reached detectable levels in the serum. The authors concluded, “In order for the drug prednisone to be effective after oral administration it must be absorbed from the gastrointestinal tract and converted to the active drug prednisolone by the liver. Although trace serum levels of prednisone were detected, prednisolone never appeared in the serum. Our data do not allow us to determine if prednisone is poorly absorbed, rapidly excreted, or not converted to prednisolone by the liver. However, it is clear that prednisone is unlikely to have any anti-inflammatory effect when administered by mouth. Oral administration of prednisolone is likely to be beneficial because it is rapidly absorbed and achieves serum levels close to those that result from intravenous administration.”

Robert N. Oglesby, DVM (The Horseman’s Advisor, www.horseadvice.com) reports his reaction to hearing the above presentation at the November, 2000 meeting of the American Association of Equine Practitioners: “I was shocked and looking around me hundreds of other vets were also: oral prednisone doses are in every equine medicine text with many descriptions of its indications. Why has no one noticed the lack of effect before now? The reason is simple: no one believed it was possible that [prednisone] was not effective [in horses]. Its usefulness in other species was too well established… we did not even question its use. Looking back on it, it was the management changes that were responsible for the clinical improvement…”

Equine Vet J 2000 Sep;32(5):432-8

AAEP Proceedings, Vol. 46, 2000, pp. 266-267

Equine Vet J. 2002 May;34(3):283-7
Prednisone per os is likely to have limited efficacy in horses.
Click here for access to the PubMed abstract.

We can compound prednisolone into the most appropriate dosage form, including oral pastes or “chewies” that horses will love!


Pentoxifylline

In horses, a dose of 8.5 mg/kg orally two times daily is recommended for reducing the cytokine effects in endotoxemia. For the treatment of navicular disease, 6 g/day orally for 6 weeks should be used.

Compendium 23(7), July 2001, 603-4


Anti-Diarrheals for Foals & Horses

Treatment of diarrhea should always be based on establishing a diagnosis and correcting the basic cause. Anti-diarrheal products are not a substitute for adequate fluid and electrolyte therapy when dehydration or shock threatens. When the veterinarian deems anti-diarrheal therapy is appropriate, the following options may be considered.

According to James L. Becht, D.V.M., M.S., Diplomat ACVIM, preparations containing bismuth subsalicylate seem superior to those containing kaolin, pectin, or activated charcoal for treating the foal with diarrhea. Bismuth subsalicylate neutralizes bacterial toxins, has some antibacterial activity, and may exert an antisecretory effect. It can be administered at a dosage of 4 oz q 6h; darkened feces will result. If no effect is seen within 48 hours, continued administration is probably not indicated. (105th Ohio VMA).

Wendy E. Vaala, V.M.D., Diplomate ACVIM reports (ACVIM 16th Veterinary Medical Forum) that delayed gastric emptying and gastroduodenal dysmotility can be improved in some foals with metoclopramide (0.25-0.6 mg/kg, PO q4-6h), erythromycin (1.0-2.0 mg/kg PO q6h), or cisapride (10 mg/kg PO q6h). If colic, ileus, and gastric reflux are present, Dr. Vaala recommends an abdominal sonogram to rule out the presence of an intussusception prior to initiating prokinetic therapy. Diarrhea may be treated symptomatically with bismuth subsalicylate (1-2 ml/kg, PO, q4-6h) and may also respond to psyllium administration. Intestinal probiotics containing Lactobacillus bacteria … may be given to foals receiving antibiotics to help reestablish intestinal flora.

Adult horses may be treated with bismuth subsalicylate 1 oz per 8 kg of body weight PO TID-QID (Clark and Becht 1987).


Headshaking in Horses

may include additional signs such as nose rubbing, striking at the nose with the forelegs, or active avoidance of light, warmth, or wind on the face. Newton et al studied 20 mature horses with typical headshaking of 2 week to 7 year duration, and concluded that the etiopathology may be a trigeminal neuritis or neuralgia. In 12 of 20 horses, drug therapy was initiated. Cyproheptadine (CP) alone was ineffective but the addition of carbamazepine (CM) resulted in 80-100% improvement in 80% of cases within 3 to 4 days of beginning drug therapy. Seven cases were treated with a combination of CM (4 mg/kg, three to four times daily) and CP (0.2-0.5 mg/kg every 12 to 24 hours).

Carbamazepine alone has been effective in 88% of cases. Some headshaking horses have responded well to CM doses of 1.6 – 2.4 grams every six hours without apparent side effects. Horses are treated for 10 to 20 days and if they respond, the treatment is discontinued. If clinical signs of headshaking recur, treatment is restarted. In practice, there is a realistic possibility of controlling but not curing headshaking with carbamazepine therapy at the present time. Other studies have reported that cyproheptadine alone was beneficial in more than two thirds of treated horses.

Equine Vet J 2000 May;32(3):208-16
Headshaking in horses: possible aetiopathogenesis suggested by the results of diagnostic tests and several treatment regimes used in 20 cases.
Click here for access to the PubMed abstract.

Equine Vet J Suppl 1998 Nov;(27):28-9
Characterisation of headshaking syndrome–31 cases.
Click here for PubMed abstract.

J Am Vet Med Assoc 2001 Aug 1;219(3):334-7
Owner survey of headshaking in horses.
Click here for access to the PubMed abstract.

ISU Vet Med Sept 2000

The Pennsylvania State University Veterinary News, Dec 2000, pp 9-10

Aust Vet J. 1991 Jul;68(7):221-4
Use of phenytoin to treat horses with Australian stringhalt
Click here for access to the PubMed abstract.

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