FAQs For Veterinarians

PRASCEND® (pergolide mesylate)

  • Question 1: What is the indication for the use of PRASCEND?

    Answer: PRASCEND is indicated for the treatment of clinical signs associated with the pituitary pars intermedia dysfunction or PPID (equine Cushing's disease).

  • Question 2: What are the benefits of treatment with PRASCEND for the horse and the owner?

    Answer: Treatment with PRASCEND improves the quality of life of PPID-affected horses by managing clinical signs and decreasing the risk of complications of PPID, including those that have potential to be life threatening.

  • Question 3: What is the benefit of an FDA-approved equine pergolide?

    Answer: Unlike compounded pergolide, FDA approval gives veterinarians and horse owners the peace of mind that PRASCEND is manufactured under consistent conditions and tested to the same standards as human drugs. Strict manufacturing guidelines ensure the product is pure and consistent and potency is stable up to the validated expiration date.

  • Question 4: How is PRASCEND different from compounded pergolide?

    Answer: PRASCEND is the only FDA-approved pergolide for horses. FDA approval ensures the product has demonstrated safety and efficacy through extensive clinical trials. Strict manufacturing guidelines ensure the product is pure and consistent. Compounded pergolide is not required to undergo clinical trials or stringent testing procedures, so efficacy and consistency cannot be assured.

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PPID

  • Question 1: What is PPID?

    Answer: Pituitary pars intermedia dysfunction—PPID is the most common endocrinopathy in horses and is caused by neurodegeneration of the hypothalamic dopaminergic neurons that innervates the pars intermedia of the pituitary gland. The loss of dopamine inhibition leads to hyperplasia of the cells of the pars intermedia of the pituitary gland as well as increased production of pro-opiomelanocortin (POMC)-derived peptides, such as adrenocorticotropin hormone (ACTH). This results in an increased production of cortisol by the adrenal cortex. Cortisol is thought to cause most of the clinical signs associated with PPID.

  • Question 2: What are the most common signs of PPID?

    Answer: PPID-affected horses show a wide variety of clinical signs. Only hirsutism (hypertrichosis) is considered to be pathognomonic for advanced-stage PPID. Clinical signs that can occur in PPID horses include:

    • Hirsutism (hypertrichosis)
    • Abnormal sweating
    • Weight loss
    • Muscle wasting
    • Abnormal fat distribution
    • Lethargy
    • Laminitis
    • Polyuria/polydipsia (PU/PD)
    • Chronic/recurrent infections

  • Question 3: Are there specific breeds predisposed to developing PPID?

    Answer: Ponies and horses with equine metabolic syndrome (EMS) have been identified to be at greater risk for PPID.1 Studies are inconclusive concerning breed predilection.

  • Question 4: At what age is the onset of PPID?

    Answer: Average age at onset is 19 years of age.2 Median age of horses with PPID in studies ranged from 15 to 23 years of age.3,4 The frequency of diagnosis generally increases with age. Although PPID is rarely seen in horses younger than 10 years of age, it has been reported in a horse as young as 4 years of age.2,5

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Diagnosis

  • Question 1: How can I diagnose PPID

    Answer: In advanced cases, PPID can be diagnosed based on observation of clinical signs (eg, hirsutism [hypertrichosis]), which is considered to be pathognomonic.2,4 Diagnosis of PPID requires observation of clinical signs as well as diagnostic testing. Commonly used tests are the endogenous ACTH test and the low-dose dexamethasone suppression test (DST).4

  • Question 2: What additional clinical signs are suspicious for underlying PPID?

    Answer:

  • Question 3: What test should I use to confirm PPID?

    Answer: The most commonly used diagnostic tests are the endogenous ACTH test and the low-dose DST. If results are negative or inconclusive on DST or ACTH, and a high index of clinical suspicion exists that a horse has PPID, the horse can be retested with the other Tier 1 test, or a Tier 2 test, such as thyrotropin-releasing hormone (TRH) stimulation, can be considered.

  • Question 4: How do I conduct the ACTH test and/or the DST 6?

    Answer:

  • Question 5: What precautions are associated with ACTH/DST tests?

    Answer: Both the ACTH and DST have been associated with false-positive and false-negative results. None of the currently available tests are sensitive in detection of early disease.2 Additionally, not all laboratories use the same ACTH assay and reference ranges must be adjusted based on the assay used. ACTH, however, may be superior to DST as the reference range can be adjusted during Autumn.

    *Some general recommendations include:

    • ACTH: Collect blood for ACTH testing in a plastic tube at any time of day. Take multiple samples at 0 and 15 minutes and combine to help increase sensitivity. Centrifuge within 8 hours or at the end of the work day. Chill within 3 hours of collection. There is no need to freeze.
    • DST: This test has previously required 2 farm visits. However, this test may be simplified to a single sample test at 19 hours. Owners may administer dexamethasone on the farm. Avoid testing in autumn.

  • Question 6: How should I interpret diagnostic test results?

    Answer: This diagnostic flowchart details the recommended steps of PPID diagnosis.6


    Chart developed by the PPID Working Group on behalf of the Equine Endocrinology Summit.
    *If clinical signs persist or progress, retest 6 to 12 months later or perform a Tier 2 test.

  • Question 7: What is the most important differential diagnosis?

    Answer: Horses affected with PPID exhibit some clinical signs also observed in equine metabolic syndrome (EMS). Horses with EMS are generally younger than 15 years of age, and ponies and Morgans exhibit a higher prevalence of this syndrome. EMS is characterized by 3 main factors:

    • Obesity or regional adiposity
    • Increased predisposition to laminitis
    • Insulin resistance (IR)

    Horses with a history of EMS tend to develop PPID at an earlier age, and it has been proposed that EMS may be a risk factor for development of PPID. Horses in transition from EMS to PPID may exhibit a change in body mass from obese to lean, increased caloric needs, a worsening of IR, and present for laminitis during this time. Horses that suffer from EMS and develop PPID exhibit a poorer prognosis and may be difficult to manage with diet and medical therapy. Although they share some similarities, it is important to differentiate between EMS and PPID. The treatment for EMS is primarily diet and exercise with the goal of improving insulin sensitivity. Pergolide would not be helpful for a horse with EMS. Proper management of the horse with EMS may delay the onset of PPID.

  • Question 8: How can I distinguish PPID from EMS?

    Answer: Measurement of the endogenous ACTH concentration can be used to distinguish between PPID and EMS. In horses affected by EMS, the concentration of ACTH remains normal. IR, which is characteristic for EMS, can occur in PPID-affected horses as well.

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Therapy

  • Question 1: Can I cure PPID?

    Answer: PPID is a chronic, lifelong disease, requiring daily medical treatment. The aim of treatment is to increase the quality of life of the patient by reducing clinical signs as well as the risk of complications of PPID, including those that have potential to be life threatening.

  • Question 2: Is there a standard of care for the treatment of PPID?

    Answer: Pergolide is considered the gold standard for treatment of PPID. Pergolide, a dopamine agonist, acts to restore the inhibition to the pars intermedia, downregulating the activity of this area, thereby decreasing the production of hormones like ACTH.

  • Question 3: When should horses be treated with PRASCEND?

    Answer: A horse exhibiting clinical signs of PPID, including unexplained laminitic episodes, should undergo evaluation for PPID. A horse exhibiting clinical signs or that has positive results on ACTH or DST testing should be treated with PRASCEND. Currently available diagnostic tests are not sensitive in detection of early disease. Therefore, if test results are negative, but a high index of clinical suspicion exists that the horse suffers from PPID, a 6-month trial of PRASCEND may be instituted and response to treatment observed.

  • Question 4: Are there any contraindications for the use of PRASCEND in horses?

    Answer: PRASCEND is contraindicated in horses known to have a hypersensitivity to pergolide mesylate or other ergot derivates. It should not be used in horses younger than 2 years of age.

  • Question 5: Can PRASCEND be used in breeding, pregnant, or lactating mares?

    Answer: PRASCEND has not been evaluated in breeding, pregnant, or lactating horses. As PRASCEND is a dopamine agonist, it may interfere with reproductive hormones involved in horses. Use only after a risk/benefit assessment by the attending veterinarian.

  • Question 6: In addition to treatment with PRASCEND, what else can be done to help the horse with PPID?

    Answer: Complementary treatment should focus on the overall health of the horse and is of particular importance during the first months of the treatment period. Complementary treatment includes:

    • Dental care
    • Clipping of the hair coat
    • Regular hoof trimming
    • Deworming
    • Vaccinations
    • Appropriate diet
    • Biannual veterinary examinations, including P3 radiographs

  • Question 7: Are there any feeding recommendations for horses affected by PPID?

    Answer: The goal of nutritional management of the PPID horse is weight maintenance if the horse exhibits muscle wasting and dietary management of PPID horses with IR. Pasture grass is a dynamic source of carbohydrates (sugars) and will worsen IR. PPID-affected horses that have severe IR or are experiencing recurrent, uncontrolled laminitic episodes must be removed from pasture grass indefinitely until IR improves. Horses with mild IR may be returned to limited pasture once IR improves and maintained on a low-carbohydrate diet.

    Supplementation of the horse's diet with vitamin E may be helpful in the PPID-affected horse, as PPID is thought to occur via oxidative degeneration of dopaminergic neurons. Vitamin E may assist in support of neuronal function and slow oxidative processes.

  • Question 8: What about chasteberry?

    Answer: Chasteberry is a nutraceutical product. There is no standardization of the active ingredient available and no testing of biological activity or bioavailability in horses. Comparative studies between chasteberry and pergolide did not show a beneficial effect of chasteberry on horses with PPID.7

  • Question 9: How do I transition from a compounded pergolide to the FDA-approved PRASCEND?

    Answer: The recommended starting dose of PRASCEND is 2 mcg/kg body weight. The tablets are scored and the calculated dosage should be provided to the nearest one-half tablet increment (1 mg tablet per 750-1,249 lbs body weight). Due to the potential variability in concentrations of compounded pergolide, it is recommended to begin at the labeled starting dose, even if the patient was on a higher dose of the compounded product.

  • Question 10: Are there any side effects reported with use of PRASCEND?

    Answer: Potential adverse reactions in horses include inappetence, transient anorexia and lethargy, mild central nervous system signs, diarrhea, and colic. If signs of dose intolerance develop, treatment should be stopped for 2 to 3 days and then reinstituted at one half of the previous dose, and gradually increased over 7 to 10 days back to the recommended dose. Resistance to drug efficacy does not occur with long-term therapy.

  • Question 11: Is it possible to administer PRASCEND concurrently with other medication?

    Answer: PRASCEND is 90% plasma protein-bound. Therefore, it is possible that using PRASCEND with another highly plasma protein-bound drug may lead to lack of efficacy or increased toxicity of either product. This has not been reported in clinical cases.

  • Question 12: How long does it take until I see the first improvement?

    Answer: Normally it takes 6 to 8 weeks until clinical signs improve. Improvement of clinical signs is not necessarily correlated to an improvement of endocrinologic test results. The earliest signs are improvement in the overall attitude and behavior of the horse (eg, horses become more active) is usually observed within 30 to 60 days of treatment institution.

  • Question 13: How should I proceed if clinical signs and/or endocrinologic test results do not improve?

    Answer: If the clinical signs are not improving or if the diagnostic testing has not yet normalized (ACTH within 30 days; DST within 60 days), the total daily dose may be increased by 0.5 mg until the horse responds and only if PRASCEND is tolerated at that dosage. The total daily dose should not exceed 4 mcg/kg. Repeated samples should be taken for endocrinologic testing. If monitoring clinical signs only, re-evaluate the patient every 60 days and adjust the dose accordingly.

  • Question 14: What should be done if the horse owner has missed a dose of PRASCEND?

    Answer: If a dose is missed, the next scheduled dose should be administered as prescribed.

  • Question 15: Why should I encourage horse owners to use a daily, lifelong therapy

    Answer: PPID is not curable and therefore a daily, lifelong therapy is necessary. The aim is to improve long-term quality of life of the patient by reducing clinical signs as well as the risk of comorbidities. The cost of daily administration of PRASCEND is offset by the potential expense(s) incurred in treatment for laminitis, dental disease, and other consequences of uncontrolled PPID.

  • Question 16: Why is it important to have veterinary examinations on a biannual to annual basis?

    Answer: The approach to treatment is to titrate to the lowest effective dose per individual horse based on response to therapy. Therefore, regular veterinary exams to evaluate treatment success, as well as to monitor other health issues are necessary.

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Dose

  • Question 1: What is the recommended starting dose of PRASCEND?

    Answer: The recommending starting dose of PRASCEND is 2 mcg/kg body weight. The tablets are scored and the calculated dosage should be provided to the nearest one-half tablet increment (1 mg tablet per 750-1,249 lbs body weight). To avoid human exposure, do not crush tablets. Important human safety information. The starting dose should then be titrated according to the clinical response as well as results of diagnostic testing.

  • Question 2: How do I measure the success of treatment with PRASCEND?

    Answer: There are different ways to measure the success of treatment. Success can either be based on the improvement of clinical signs or normalization of test results. Clinical signs used for monitoring should be evaluated at 60 days following initiation of treatment. If ACTH sampling is used, retesting should be performed 30 days following initiation of treatment. If DST sampling is used, it is recommended to wait 60 days before retesting. Once disease is controlled, regular clinical assessment and diagnostic testing should be performed every 6 months to monitor treatment success.

  • Question 3: How do I determine whether the daily dose is too high?

    Answer: Signs of dose intolerance are lethargy, decreased appetite, and diarrhea.

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Administration

  • Question 1: What is the best way to administer PRASCEND?

    Answer: To avoid human exposure, tablets should not be crushed. The tablet may be administered orally by dissolving the tablet with a small amount of water and administer with a syringe or as a top-dressing on feed. After dissolving, the tablet should be administered immediately. Alternatively, tablets can be hidden in an apple or treat.

  • Question 2: Is it possible to treat dogs with PRASCEND?

    Answer: No. PRASCEND is for use in horses only. Treatment of Cushing's disease in dogs with PRASCEND is not recommended as the pathoetiology of Cushing's disease in dogs and humans differs from equine PPID. Cushing's disease in dogs and humans is a disease of the pars distalis, which results in adrenal hyperplasia and production of cortisol. PPID in horses originates from loss of dopaminergic inhibition to the pars intermedia of the pituitary. PRASCEND would not be helpful for adrenal-based disease.

  • Question 3: Is it possible to use trilostane to treat horses with PPID?

    Answer: As trilostane addresses adrenal production of cortisol, treatment of horses with trilostane would not be recommended. PPID in horses involves loss of dopaminergic inhibition to the pars intermedia of the pituitary, and adrenal disease is rare in horses.

  • Question 4: Is pergolide allowed in competition?

    Answer: At the current time, pergolide mesylate, the active ingredient of PRASCEND, is considered a forbidden substance in competition.

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Important safety information

PRASCEND is for use in horses only. Treatment with PRASCEND may cause loss of appetite. Most cases are mild. Weight loss, lack of energy, and behavioral changes also may be observed. If severe, a temporary dose reduction may be necessary. PRASCEND has not been evaluated in breeding, pregnant, or lactating horses and may interfere with reproductive hormones in these horses. Using PRASCEND at the same time as drugs known as dopamine antagonists should be avoided. These drugs may diminish the effectiveness of PRASCEND. If your horse is especially sensitive to pergolide mesylate or similar products, PRASCEND should not be used. Refer to the package insert for complete product information.

References:

  1. Frank N, Geor RJ, Bailey SR, Durham AE, Johnson PJ. Equine metabolic syndrome. J Vet Intern Med. 2010;24(3):467–475.
  2. McGowan C. Diagnostic and management protocols for equine Cushing’s syndrome. In Practice. 2003;25:586–592.
  3. Donaldson MT. Evaluation of suspected pituitary pars intermedia dysfunction in horses with laminitis. J Am Vet Med Assoc. 2004;224(7):1123–1127.
  4. Schott HC. Pituitary pars intermedia dysfunction: equine Cushing’s disease. Vet Clin North Am Equine Pract. 2002;18(2):237–270.
  5. Donaldson MT, LaMonte BH, Morresey P, Smith G, Beech J. Treatment with pergolide or cyproheptadine of pituitary pars intermedia dysfunction (equine Cushing’s disease). J Vet Intern Med. 2002;16(6):742–746.
  6. PPID Working Group on behalf of the Equine Endocrinology Summit. Diagnosis and treatment of pituitary pars intermedia dysfunction (PPID). August 2011.
  7. McFarlane D, Toribio RE. Pars intermedia dysfunction (equine Cushing’s disease). In: Reed SM, Bayly WM, Sellon DC, eds. Equine Internal Medicine. 3rd edition. St. Louis, MO: Saunders; 2010:1262–1270.