How To Give Percorten Injection For Dogs
Desoxycorticosterone Pivalate for Dogs With Addison'due south Disease
Enquiry studies show that DOCP injectable suspension is a safe and effective therapy for dogs with Addison'south disease.
February 24, 2021 |
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Desoxycorticosterone pivalate (DOCP) is a mineralocorticoid replacement therapy for dogs with primary hypoadrenocorticism (Addison's affliction). This commodity covers its mechanism of action, dosing, monitoring, effectiveness, and safe and discusses clinical applications for both available formulations of the drug: Percorten-V (Elanco, elanco.com ) and Zycortal (Dechra, dechra.com ).
DOCP Machinery of Action
DOCP is a long-interim analog of desoxycorticosterone, an endogenous steroid hormone and precursor to aldosterone. When administered parenterally, it produces the aforementioned physiologic effects equally endogenous aldosterone, increasing sodium retention in the distal tubule and renal collecting ducts through active sodium resorption and upregulated sodium/potassium exchange.1 Thus, DOCP increases serum sodium and chloride concentrations, promotes potassium excretion, and results in enhanced osmotic renal water retention. It is by and large considered to have no glucocorticoid activeness, though some have suggested weak activity,2 and should be used in conjunction with appropriate glucocorticoid replacement therapy for addisonian patients exhibiting both glucocorticoid and mineralocorticoid deficits. The manufacturers of both formulations recommend accompanying DOCP with prednisone or prednisolone at a starting dose of 0.two to 0.4 mg/kg/day.3,iv
DOCP Formulations
Percorten-V was approved for canine use by the U.South. Nutrient and Drug Administration (FDA) in 1998, and Zycortal was approved for use by the European Medicines Agency in 2015 and the FDA in 2016. Both products incorporate 25 mg desoxycorticosterone per milliliter and are formulated as microcrystalline suspensions, allowing for slow dissolution and prolonged drug release.i,4 They differ in their employ of preservative and surfactant.1 Percorten-Five is labeled for intramuscular injection but is often given subcutaneously in clinical do. Zycortal is labeled for subcutaneous injection. Pharmacokinetic studies constitute that Zycortal demonstrated a longer half-life (17 days) when administered subcutaneously equally opposed to intramuscularly (8 days).one
DOCP Effectiveness
Two well-controlled clinical field trials found that, at doses of two.2 mg/kg administered once every 25 days, Percorten-V provided good control of clinical signs of hypoadrenocorticism, resulting in normalization of serum sodium, potassium, and blood urea nitrogen (BUN) concentrations, as well equally body weight increases, although adjustments of the dose or dose frequency were sometimes needed.v
In a double-blind field trial, 152 dogs with primary adrenocortical insufficiency were randomized to treatment with either Percorten-V or Zycortal. Zycortal was found to be noninferior to Percorten-V in both management of clinical signs and command of serum sodium and potassium concentrations as evaluated at 90 days and 180 days after initiation of handling.6,7
DOCP Prophylactic
Condom trials conducted past the manufacturer of Percorten-V concluded that DOCP was tolerated without significant morbidity or bloodshed at doses up to xv times the recommended dose of ii.2 mg/kg when administered intramuscularly every 28 days to clinically normal beagles for a period of six months.v,8 Noted adverse effects included polyuria, polydipsia, decreased serum potassium and BUN concentration, decreased urine creatinine, and weight loss.viii
Boosted rubber studies conducted by the manufacturer of Zycortal found no serious agin effects in healthy beagles receiving up to v times the recommended handling dose every 21 days for 6 months (9 injections).1,half dozen Treated dogs exhibited decreased urine specific gravity, increased serum sodium and globulins, and decreased serum potassium and BUN, consequent with the pharmacologic effects of the drug.i,6 Injection site reactions were the nearly common agin outcome.ane,6
In effectiveness field studies, commonly reported adverse events for both Percorten-Five and Zycortal included polydipsia, polyuria, and inappropriate urination.v,6 In the Zycortal field effectiveness study, languor/low was reported more commonly with Zycortal than Percorten-V (9.vii% versus 2.6%), while diarrhea was reported more ordinarily with Percorten-V (seven.7% versus 2.vii%).half-dozen Other adverse effects from field studies of both drugs included 1 dog with a preexisting heart murmur that developed congestive centre failure,half dozen 2 dogs with loss of hormonal control requiring a shorter dosage interval, and 1 dog that collapsed after the get-go dose, possibly from inadvertent intravenous drug administration.five
Both the Percorten-Five and Zycortal production labels include cautions for use in patients with preexisting congestive middle failure, severe renal disease, or edema (Percorten-V recommends non using the drug at all in these patients), and both products are not recommended for utilize in pregnancy.iii,4 The Zycortal characterization also includes a caution for patients with principal hepatic failure.iii
DOCP Comparison to Fludrocortisone Acetate
An alternative mineralocorticoid replacement therapy, fludrocortisone acetate, is available for use in dogs with adrenal insufficiency. Fludrocortisone acetate is an oral mineralocorticoid typically given twice daily. In dissimilarity to DOCP, information technology possesses significant glucocorticoid activity. Thus, in some patients treated with fludrocortisone, supplemental glucocorticoid therapy may not be needed. However, this additional glucocorticoid activity may contribute to dose-dependent agin furnishings, including polyuria, polydipsia, and polyphagia. As DOCP has minimal glucocorticoid activity, its dose and dosing interval tin can be adjusted to effect without affecting glucocorticoid delivery.
Studies comparing the effectiveness of DOCP and fludrocortisone are express. The available data suggest the 2 drugs provoke a similar clinical response; patients that take persistent polyuria/polydipsia when treated with fludrocortisone may feel fewer agin furnishings from DOCP. A 1997 report of 200 dogs with primary hypoadrenocorticism found no meaning departure in clinical response to treatment or median survival times between patients treated with DOCP and patients treated with fludrocortisone.9 However, treatment was inverse from fludrocortisone to DOCP in 27 dogs due to the development of adverse furnishings, poor clinical response, or possessor convenience/finances.ix
A 2014 study compared plasma renin activity (PRA) in dogs with hypoadrenocorticism treated with fludrocortisone or DOCP.10 PRA is considered the gold standard in human medicine for monitoring response to mineralocorticoid therapy, every bit information technology is increased in people with adrenocortical insufficiency and decreases with mineralocorticoid replacement therapy. In studied dogs, increased baseline PRA levels normalized after treatment with DOCP merely not with fludrocortisone. Serum sodium and potassium were also more commonly in the reference range in dogs treated with DOCP. Five dogs were switched from fludrocortisone to DOCP due to adverse glucocorticoid effects or poor clinical response to handling.10
Almost clinicians consider DOCP the preferred mineralocorticoid for replacement therapy in dogs with hypoadrenocorticism, although fludrocortisone is a reasonable option for owners when oral therapy is strongly preferred or DOCP injections are not tolerated.
DOCP Dosing and Monitoring
DOCP dosing protocols are tailored to the private based on clinical response to therapy after administration of an initial starting dose. Parcel inserts for Percorten-V and Zycortal differ slightly in their dosing and monitoring recommendations, and existing clinical studies take taken varied approaches to dose adjustment in their studied patient populations.
DOCP Manufacturer Recommendations
Both Percorten-V and Zycortal are labeled for a starting dose of 2.2 mg DOCP/kg body weight, administered once every 25 days.3,4 Elanco recommends evaluating serum electrolytes at 14 days and 25 days after administration of Percorten-V. Patients are considered well controlled, with no adjustments recommended to dose or dosing interval, if serum electrolyte levels are normal or just slight hyponatremia and slight hyperkalemia exist at both xiv and 25 days. In dogs with more than pregnant hyperkalemia or hyponatremia, guidelines land that the dosage interval should be decreased past ii to 3 days. Elanco advises that most patients are well controlled with a dose range of one.65 to 2.2 mg/kg given every 21 to 30 days.4 Dechra recommends serum sodium/potassium ratios be measured at 10 and 25 days after initial administration of Zycortal to make up one's mind changes in recommended dose and dosing interval, equally described in the packet insert.3
DOCP Culling Aligning Protocols
Culling monitoring and dose adjustment protocols take been described in the literature. In about described protocols, serum electrolyte (sodium and potassium) concentrations are measured at 2 time points after initial injection. Concentrations measured at the start time point (typically 10 to xiv days postinjection) are used to make up one's mind necessary dosage adjustments, while those measured at the 2nd time point (typically 25 to 30 days postinjection) are used to determine necessary changes in dosing interval.
A 2010 review suggests that, if hyperkalemia or hyponatremia is present at the initial recheck (mean solar day 12), the next DOCP dose should exist increased past 5% to x%, while if hypokalemia or hypernatremia is present, the adjacent dose should exist decreased by 5% to 10%. If the patient is hyperkalemic or hyponatremic at the subsequent recheck (mean solar day 25), the dosing interval can be decreased by one day.eleven Other authors let for farther dosage reduction and interval extension in a clinically normal patient to let for titration to the lowest effective dose.10 Following institution of a maintenance dose and dosing interval, subsequent monitoring of electrolyte levels once every iii to vi months is typically recommended.
DOCP Alternative Dosing Protocols
As primary hypoadrenocorticism necessitates lifelong mineralocorticoid replacement therapy, cost of treatment is oft a significant hurdle to delivery of care. Also, excessive mineralocorticoid supplementation may have deleterious effects. A number of studies have evaluated alternative dosing regimens in an attempt to narrate the success of lower-cost and lower-dose protocols in controlling clinical signs of disease. These studies take demonstrated that adept clinical control of disease can exist achieved for many patients at doses lower than the 2.2 mg/kg starting dose recommended by the manufacturers.
DOCP Dose Reduction
A 2019 prospective report of 17 dogs with newly diagnosed primary hypoadrenocorticism plant that a starting dose of 1.5 mg/kg of Zycortal was sufficient to control clinical signs and maintain normal serum electrolyte concentrations in all merely ii patients.12 Farther dosage reductions were used to attain an injection interval of 28 to thirty days (median dose at 2 to 3 months, 1.ane mg/kg) in nigh dogs, and no dogs required the recommended two.ii mg/kg dose. Further analysis of these results suggested that young, growing dogs might require higher initial doses that can exist reduced over fourth dimension.12
A like retrospective written report of 13 dogs with principal hypoadrenocorticism constitute a ane.5 mg/kg starting dose to be constructive in all but 1 canis familiaris that required a dose of i.6 mg/kg.xiii A 2013 retrospective report of 49 dogs institute that initial DOCP doses less than 2.2 mg/kg were effective at decision-making clinical signs of hypoadrenocorticism, with a hateful final dose of 1.3 mg/kg.14 In the 1997 study comparing DOCP with fludrocortisone, just 18% of the 33 dogs treated with DOCP required doses of 2.ii mg/kg or higher, with a final median dose of ane.69 mg/kg and a median dosing interval of xxx days.nine
DOCP Dosing Interval Extension
Extending the interval between doses is some other approach to reducing cost of handling, and recent evidence suggests that a longer dosing interval may yet achieve effective disease control. A 2017 prospective clinical trial of 53 dogs plant that the duration of action of DOCP (one.4 to 2.6 mg/kg/dose) ranged from 32 to 94 days (median, 62 days) in dogs with newly diagnosed primary hypoadrenocorticism and from 41 to 124 days (median, 67 days) in dogs that had received previous treatment. The report ended that a final acceptable treatment interval that maintained serum potassium and sodium concentrations within the reference interval for all studied patients ranged from 38 to 90 days (median, 58 days).15
Although this approach is effective, some clinicians prefer to prioritize dose reduction since owner compliance may be college with more standard monthly drug assistants.
Conclusion
DOCP is a rubber and effective mineralocorticoid replacement therapy when used in dogs with primary hypoadrenocorticism. Recent research suggests that lower doses and longer dosing intervals than those recommended in manufacturer guidelines may, for many patients, remain effective in controlling both serum electrolyte levels and clinical signs of illness. No current consensus exists regarding the near effective monitoring and dosing protocols. Further inquiry is needed to ameliorate characterize clinically appropriate starting doses and evaluate the efficacy of the diverse dose adjustment and monitoring protocols used in clinical do.
References
ane. European Medicines Agency. CVMP cess report for Zycortal (EMEA/ V/C/003782/0000). September 10, 2015. ema.europa.eu/en/documents/cess-report/zycortal-epar-public-assessment-report_en.pdf. Accessed October 2020.
2. Vinson GP. The mislabelling of deoxycorticosterone: making sense of corticosteroid structure and part. J Endocrinol 2011;211(1):three-16. doi: 10.1530/JOE-11-0178
3. Zycortal suspension (desoxycorticosterone pivalate injectable intermission) [parcel insert]. Overland Park, KS: Dechra Ltd; 2016.
iv. Percorten-V (desoxycorticosterone pivalate injectable interruption) [package insert]. Greenfield, IN: Elanco; 2011.
5. Percorten™-Five Freedom of Information Summary. January 12, 1998. animaldrugsatfda.fda.gov/adafda/app/search/public/document/downloadFoi/3622. Accessed Oct 2020.
6 Zycortal suspension Freedom of Data Summary. February 17, 2016. animaldrugsatfda.fda.gov/adafda/app/search/public/certificate/downloadFoi/936. Accessed October 2020.
7. Farr H, Bricklayer BL, Longhofer SL. Randomised clinical non-inferiority trial comparing ii formulations of desoxycortone pivalate for the handling of canine chief hypoadrenocorticism. Vet Rec 2020;187(2):e12. doi: 10.1136/vr.105328
8. Chow E, Campbell WR, Turnier JC, et al. Toxicity of desoxycorticosterone pivalate given at high dosages to clinically normal beagles for vi months. Am J Vet Res 1993;54(eleven):1954-1961.
9. Kintzer PP, Peterson ME. Treatment and long-term follow-upwardly of 205 dogs with hypoadrenocorticism. J Vet Intern Med 1997;xi:43-49. doi: 10.1111/j.1939-1676.1997.tb00072.10
10. Baumstark M, Nussberger J, Boretti F, et al. Use of plasma renin activity to monitor mineralocorticoid treatment in dogs with primary hypoadrenocorticism: desoxycorticosterone versus fludrocortisone. J Vet Intern Med 2014;28:1471-1478. doi: 10.1111/jvim.12426
11. Klein SC, Peterson ME. Canine hypoadrenocorticism: part Ii. Can Vet J 2010;51(2):179-184.
12. Sieber-Ruckstuhl NS, Reusch CE, Hofer-Inteeworn N, et al. Evaluation of a low-dose desoxycorticosterone pivalate treatment protocol for long-term management of dogs with primary hypoadrenocorticism. J Vet Intern Med 2019;33:1266-1271. doi: ten.1111/jvim.15475
13. Münch 50, Münch M, Paul H, et al. Therapie des primären Hypoadrenokortizismus beim Hund mit niedrig dosiertem Desoxycorticosteronpivalat [Therapy of chief hypoadrenocorticism in dogs with low dose desoxycorticosterone pivalate]. Tierarztl Prax Ausg Grand Kleintiere Heimtiere 2020;48(3):171-175. doi:
10.1055/a-1166-8800
fourteen. Bates J, Shott S, Schall W. Lower initial dose desoxycorticosterone pivalate for treatment of canine primary hypoadrenocorticism. Aust Vet J 2013;91:77-82. doi: 10.1111/avj.12019
15. Jaffey J, Nurre P, Cannon A, et al. Desoxycorticosterone pivalate elapsing of action and individualized dosing intervals in dogs with primary hypoadrenocorticism. J Vet Intern Med 2017;31:1649-1657. doi: 10.1111/jvim.14828
Source: https://todaysveterinarypractice.com/pharmacology/desoxycorticosterone-pivalate-for-dogs-with-addisons-disease/
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