Prascend (Canada)

This page contains information on Prascend for veterinary use.
The information provided typically includes the following:

Prascend Indications
Warnings and cautions for Prascend
Direction and dosage information for Prascend

Prascend

This treatment applies to the following species:

Horses

Company: Boehringer Ingelheim Animal Health

Pergolide (as pergolide mesylate) 1 mg tablets for horses

Veterinary Use Only

DIN 02412217

Description

Prascend^® is a dopamine receptor agonist for oral use in horses. Prascend^® tablets are rectangular light red colored, half-scored tablets.

Prascend Indications

For the control of clinical signs associated with Pituitary Pars Intermedia Dysfunction (Equine Cushing’s Disease) in horses.

Active Ingredient

Each tablet contains 1 mg pergolide (as pergolide mesylate).

Dosage and Administration

Administer orally at a starting dose of 2 mcg/kg once daily. Dosage may be adjusted to effect, up to 4 mcg/kg daily (see “Animal Safety” section). To facilitate the administration, one or more tablets may be dissolved with a small amount of water and/or mixed with molasses or other sweetener. In this case, the dissolved tablets should be administered with a syringe. The entire amount should be administered immediately. The tablets should not be crushed.

The tablets are scored and the calculated dosage should be provided to the nearest one-half tablet increment (see Table 1).

Table 1- Dosing Table
Body weight	Starting dose 2 mcg/kg (in tablets)	Dosage range (in mcg/kg)
136 - 340 kg	0.5 tablets	1.5 - 3.7
341 - 567 kg	1 tablet	1.8 - 2.9
568 - 795 kg	1.5 tablets	1.9 - 2.6
796 - 1022 kg	2 tablets	2.0 - 2.5

Appropriate endocrine laboratory tests (e.g., dexamethasone suppression test or ACTH test) should be conducted as well as an evaluation of the clinical signs in order to establish a diagnosis of Pituitary Pars Intermedia Dysfunction (PPID). Following initial diagnosis, repeat the endocrine test at intervals of 4 - 6 weeks for dose titration until results and/or clinical signs have improved or stabilized. Following stabilization, a clinical assessment and endocrine testing should be performed every 6 months to monitor long-term treatment response. Dosing should be titrated according to the individual horse response to achieve the lowest effective dose. Where there is no apparent response to treatment, the diagnosis should be reevaluated.

If signs of dose intolerance develop, treatment should be stopped for 2 - 3 days and re-instated at one-half of the previous dose. The total daily dose can be titrated back up by 0.5 mg increments (half-tablets) every 2 - 4 weeks until the desired clinical effect is achieved.

Contraindications

Prascend^® is contraindicated in horses with known hypersensitivity to pergolide mesylate or other ergot derivatives.

Cautions: Do not use in horses younger than 3 years of age, and in breeding, pregnant, or lactating horses, as Prascend^® has not been evaluated in these animals. In mice, pergolide mesylate has been shown to inhibit prolactin secretion, a hormone linked to milk and colostrum production.

Pergolide mesylate is approximately 90% associated with plasma proteins in humans and laboratory animals. Use caution if administering Prascend^® with other drugs that affect protein binding. Dopamine antagonists, such as neuroleptics (phenothiazines, domperidone) or metoclopramide, should not be administered concurrently with Prascend^® (a dopamine agonist) since these agents may diminish the effectiveness of Prascend^®.

Warnings: Keep out of reach of children. Pergolide, like other ergot derivatives, may cause emesis, dizziness, lethargy or low blood pressure. Prascend^® should not be administered by persons who have had adverse reactions to ergotamine or other ergot derivatives. Pregnant or nursing women should wear gloves when administering this product. Pergolide tablets may cause eye irritation, an irritating smell, or headache when Prascend^® tablets are split or crushed. Prascend^® tablets should not be crushed due to the potential for increased human exposure and care should be taken to minimize exposure when splitting tablets. Avoid contact with skin or eyes. In case of contact with skin, wash exposed skin with water. In the event of exposure to the eye, flush the affected eye immediately with water and get medical advice.

Do not ingest the product. Store this product separately away from human medicinal products and handle this product with great care to avoid accidental ingestion. In case of accidental ingestion, seek medical advice immediately and show the package insert to the physician. Avoid driving or operating machinery following ingestion of this product.

Do not use in horses intended for human consumption. Owners and handlers should monitor for any changes in balance or behaviour of horses on this medication.

Adverse Reactions

Although all adverse reactions are not reported, the following information is based on voluntary post-approval drug experience reporting. It is generally recognized that this results in significant underreporting. The adverse events listed here reflect reporting and not necessarily causality. Adverse events are listed by body system, in decreasing order of frequency:

Systemic disorders: anorexia (inappetence), lethargy, lack of efficacy, weight loss

Musculoskeletal disorders: laminitis, lameness

Digestive tract disorders: diarrhea, abdominal pain/colic

Skin and appendages disorders: hair change/alopecia, hyperhidrosis

Neurological disorders: ataxia, seizure, muscle tremors

Behavioural disorders: behavioural changes, aggression (to other horses and humans), hyperactivity (anxiety, agitation)

Death (including euthanasia) has been reported.

The above adverse events were reported in some horses at starting dose levels, while in the others following a dose increase.

Clinical Pharmacology

Pergolide mesylate is a synthetic ergot derivative and is a potent dopamine receptor agonist. The chemical name of pergolide mesylate is 8β-[(Methylthio) methyl]-6-propylergoline monomethanesulfonate.

The chemical structure is:

As with other dopamine agonists, pergolide inhibits the release of prolactin which suggests that it may interfere with lactation. In horses with PPID, pergolide is believed to exert its therapeutic effect by stimulating dopamine receptors, and has been shown to decrease the plasma levels of adrenocorticotropic hormone (ACTH), melanocyte stimulating hormone (MSH), and other pro-opiomelanocortin peptides.

Pharmacokinetic information in the horse is based on a study using single oral doses of 10 mcg/kg in six healthy mares between 3 and 17 years of age. Pergolide was rapidly absorbed; the mean maximum concentration (C_max) was 2.11 ± 0.38 ng/mL with the median time to maximum concentration (T_max) being 0.33 hours. The area under the curve (AUC) was 8.44 ± 1.33 hr•ng/mL. The mean half-life (T_1/2) was 26.84 ± 10.2 hours; the mean apparent oral clearance (CL/F) was 1417.96 mL/kg/hr; and the mean apparent volume of distribution (V/F) was 39739.01 ± 10285.42 mL/kg.

Safety and Efficacy Study Information:

Animal Safety: In a six month target animal safety study healthy adult horses received Prascend^® administered orally, once daily, at doses of either 0 mcg/kg, 4 mcg/kg, 6 mcg/kg, or 8 mcg/kg (0X, 1X, 1.5X, or 2X the maximum recommended dose). There were eight healthy horses (four males and four females) in each treatment group. Doses were prepared by dissolving tablets in approximately 10 mL of a 50% sugar water solution.

Prascend^® treated groups had lower mean heart rates than the control group. Mean heart rates were statistically significantly different for geldings in all treated groups (4, 6 and 8 mcg/kg) and for mares in the 2X (8 mcg/kg). Mean heart rate was reduced by approximately 10 (1X group), 18 (1.5X group) and 16 (2X group) beats per minute for geldings and 8 beats per minute for mares in the 2X group.

Mares in the 1X and 1.5X groups also had numerically lower mean heart rates; however, the differences were not statistically significant. The minimum heart rates for individuals in all treated groups were within the normal range (24 - 44 beats per minute). Horses in all treatment groups also had higher mean temperatures when compared to the control group. However, maximum temperatures remained below 101.5°F (38.6°C). One 1.5X horse experienced a mild episode of spasmodic colic on Day 3 that resolved after treatment with flunixin meglumine.

Statistically significant decreases in mean red blood cell counts and hemoglobin values were present in all Prascend^® treated groups (4, 6 and 8 mcg/kg) as compared to the control group. Other hematology parameters including hematocrit, white blood cells, absolute neutrophils, and absolute lymphocytes exhibited mild, transient decreases as compared to the control group. The hematology parameters generally decreased over the first 30 to 60 days after treatment initiation and then returned to values similar to pretreatment levels. No treatment related alterations were identified on histopathology evaluation of bone marrow.

The safety analysis was conducted with the results of all 122 horses included in this field study and treated with Prascend^® for six months.

Table 2 - Summary of the most common adverse reactions (N=122)
Clinical sign	# Cases	Cases (%)
Decreased appetite	40	32.8
Lameness	22	18.0
Diarrhea/Loose stool	12	9.8
Colic	12	9.8
Lethargy	12	9.8
Abnormal Weight Loss	11	9.0
Laminitis*	10	8.2
Heart murmur	10	8.2
Death	8	6.6
Tooth disorder	8	6.6
Skin abscess	7	5.7
Musculoskeletal pain	6	4.9
Behavior change	6	4.9

*Three new cases and 7 pre-existing, recurring cases

Inappetance or decreased appetite occurred at one or more meals in 40 of 122 horses treated with Prascend^®. At the baseline evaluation 1.6% of owners reported a history of inappetence or decreased appetite as compared to the 32.8% of horses that experienced inappetence or decreased appetite during the study. Most cases of inappetence were transient and occurred during the first month of treatment; however, some horses experienced sporadic inappetence throughout the study. Two horses required a temporary reduction in dose due to inappetence during the first month of the study. Both horses returned to their original dose within 30 days.

Weight loss occurred in more than half of the horses in this study; however, weight loss that was considered abnormal was only reported in 11 horses.

Lethargy was reported in 9.8% of horses during the study, and was not reported in any horses at the baseline evaluation.

Behavioural changes were noted in 6 horses including aggression, kicking, agitation, nervous behaviour and increased activity. One horse required a temporary reduction in dose due to energetic behaviour during the first month of the study and increased back to original dose 9 days later.

Eight horses died or were euthanized during the study due to worsening of pre-existing conditions (laminitis, dental disease, septic tenosynovitis), or colic (strangulating lipomas, large colon volvulus).

One mare was inadvertently enrolled in the study while pregnant and experienced dystocia due to malpositioning resulting in the death of the foal.

Efficacy: An open-label, historical control, field study evaluated the effectiveness of Prascend^® for the control of clinical signs of PPID. A total of 122 horses with PPID were enrolled in the study, 113 of which were included in effectiveness evaluations. The success of each horse was based on results of endocrinology testing (dexamethasone suppression test or endogenous ACTH test) and/or improvement in clinical signs related to PPID (hirsutism, hyperhidrosis, polyuria/polydypsia, abnormal fat distribution, and/or muscle wasting) on the Day 180 evaluation. Based on endocrine testing and investigators’ clinical assessment scores, 86 (76.1%) of the 113 evaluable cases were treatment successes.

Table 3 - Proportion of Treatment Successes on Day 180
Percent success	Lower bound: one-sided 95% confidence interval
76.1% (86/113)	67.2%

Enrolled horses were diagnosed with PPID based on the presence of hirsutism and an abnormal pre-study endocrine test result. All horses were treated with 2 mcg/kg Prascend^® (to the nearest one-half tablet) orally once daily for the first three months. If the endocrine test result on Day 90 was normal or adequately improved, the horse continued on the same dose through Day 180. If the endocrine test result on Day 90 was abnormal, the dose increased to 4 mcg/kg given once daily through Day 180. Forty-seven (41.6%) of the 113 horses included in the effectiveness database required a dose increase at Day 90.

Improvement was noted in scores for all clinical sign categories and in mean results for endocrine tests.

Table 4 - Percent of Animals with Improvement in Clinical Signs Relative to Baseline Scores
Clinical sign	Day 90±7	Day 180±7
Hirsutism	32.7%	89.2%
Hyperhidrosis	27.4%	42.3%
Polyuria / polydypsia	31.0%	34.2%
Abnormal fat distribution	21.2%	33.3%
Muscle wasting	36.3%	46.0%

Table 5 - Endocrine test results (mean values)
Test	# Animals	Baseline	Day 90	Day 180
ACTH (pg/mL)	20	73.53	51.12	45.08
DST** (mcg/dL)	93	3.12	1.39	1.47

** Dexamethasone suppression test: Post dexamethasone cortisol concentration

Storage

Store at or below 25°C. Do not freeze. Store the blister in the original carton.

Presentation: Prascend^® (pergolide mesylate) tablets are available in 1 mg strength - packaged 10 tablets per blister and 60 or 160 tablets per carton.

Boehringer Ingelheim Animal Health Canada Inc., 5180 South Service Road, Burlington ON L7L 5H4

Prascend^® is a registered trademark of Boehringer Ingelheim Vetmedica GmbH used under license.

Revised: 09-2021

51746635-03/22

CPN: 1182191.0

BOEHRINGER INGELHEIM ANIMAL HEALTH CANADA INC.
5180 SOUTH SERVICE ROAD, BURLINGTON, ON, L7L 5H4

Customer Care No.:		1-800-567-1885
Technical Services No.:		1-877-565-5501
Website:		www.boehringer-ingelheim.ca

THIS SERVICE AND DATA ARE PROVIDED "AS IS". Animalytix assumes no liability, and each user assumes full risk, responsibility, and liability, related to its use of the Animalytix service and data. See the Terms of Use for further details.