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Zusammenfassung Gegenstand und Ziel Desoxycorticosteronpivalat (DOCP) ist seit 2016 mit Zycortal® das einzige in Deutschland zugelassene Medikament für die Therapie des primären Hypoadrenokortizismus (Morbus Addison) beim Hund. Der Hersteller empfiehlt als Anfangsdosis 2,2 mg/kg. Sowohl eigene Erfahrungen als auch vereinzelte bisherige Veröffentlichungen lassen vermuten, dass eine deutlich niedrigere Anfangsdosis ausreicht. Gründe für eine Dosisreduktion sind die Verringerung der beträchtlichen Kosten mit Steigerung der Besitzermotivation zur Therapie sowie die Vermeidung einer Überdosierung und damit einhergehender Nebenwirkungen. Ziel unserer retrospektiven Studie war zu zeigen, dass eine Anfangsdosis von 1,5 mg/kg DOCP ausreicht, um einen Hund mit primärem Hypoadrenokortizismus stabil einzustellen. Material und Methode Aufnahme in die Studie fanden Hunde mit primärem Hypoadrenokortizismus, die mit einer DOCP-Anfangsdosis von 1,5 mg/kg s. c. therapiert worden waren. Dokumentiert wurden die 1., 2. und letztbekannte DOCP-Dosis sowie die Elektrolytkonzentrationen zum Zeitpunkt der Diagnose, 10–14 Tage nach der ersten DOCP-Injektion, am Tag der 2. und der zuletzt dokumentierten Injektion von DOCP. Ein Hund galt als stabil eingestellt, wenn er ein ungestörtes Allgemeinbefinden hatte, Natrium- und Kaliumkonzentration im Referenzbereich lagen und der behandelnde Tierarzt keine Dosisanpassung empfahl. Ergebnisse Alle 13 in die Studie eingeschlossenen Hunde waren nach der 1. bzw. 2. Injektion stabil eingestellt. Ein Hund benötigte als letzte dokumentierte Dosis 1,6 mg/kg DOCP, alle anderen ≤ 1,5 mg/kg (Median: 1,3 mg/kg, Spanne: 0,4–1,6 mg/kg). Elf Hunde erhielten monatlich eine Injektion, 2 Hunde alle 60 Tage. Der Beobachtungszeitraum betrug mindestens 7 Monate (Median: 20 Monate, Spanne: 7–26 Monate). Schlussfolgerung und klinische Relevanz Wir konnten zeigen, dass eine Anfangsdosis von 1,5 mg/kg DOCP (Zycortal®) ausreicht, um einen Hund mit primärem Hypoadrenokortizismus stabil einzustellen, aber teilweise Dosisanpassungen vorgenommen werden müssen. Für eine korrekte Einstellung der DOCP-Dosis ist eine regelmäßige Elektrolytkontrolle jeweils 10 Tage nach DOCP-Injektion als auch nach 28–31 Tagen nötig.

Objectives To investigate kidney function by determining serum symmetric dimethylarginine (sSDMA) and serum creatinine (sCr) concentrations in dogs with primary hypoadrenocorticism (PH) receiving long-term mineralocorticoid replacement therapy. Methods Dogs with PH receiving a minimum of 12 months of either desoxycorticosterone pivalate or fludrocortisone acetate were included in the study provided that banked frozen serum samples were available for sSDMA analysis. sCr concentrations were retrieved from the medical records. In dogs still alive and presented for regular re-evaluations and in newly diagnosed patients, blood was prospectively collected for sSDMA and sCr determination. Results Thirty-two dogs met the inclusion criteria. The treatment time ranged from 12 to 146 months after initial diagnosis (median, 55.5 months). The majority of dogs had normal sSDMA and sCr concentrations throughout the hormone replacement treatment. Both sSDMA and sCr concentrations were persistently elevated in three of 32 dogs. Further workup confirmed chronic kidney disease (CKD) in all three dogs. Conclusions Based on these data, the prevalence of CKD could be higher in dogs with PH receiving long-term mineralocorticoid replacement treatment than in the general dog population. However, additional studies with a larger number of dogs are needed to confirm it.

Background Lowering the dose of desoxycorticosterone pivalate (DOCP) for the treatment of dogs with primary hypoadrenocorticism (PH) decreases costs and could lead to increased owner motivation to treat their affected dogs. Objective To evaluate the efficacy of a low-dose DOCP treatment protocol in dogs with PH. Animals Prospective study, 17 client-owned dogs with naturally occurring PH (12 newly diagnosed, 5 previously treated with fludrocortisone acetate [FC]). Methods Dogs with newly diagnosed PH were started on 1.5 mg/kg DOCP SC; dogs previously treated with FC were started on 1.0-1.8 mg/kg DOCP SC. Reevaluations took place at regular intervals for a minimum of 3 months and included clinical examination and determination of serum sodium and potassium concentrations. The DOCP dosage was adjusted to obtain an injection interval of 28-30 days and to keep serum electrolyte concentrations within the reference interval. Results Median (range) follow-up was 16.2 months (4.5-32.3 months). The starting dosage was sufficient in all but 2 dogs and had to be significantly decreased after 2-3 months to a median dosage (range) of 1.1 mg/kg (0.7-1.8). Dogs 3 years of age or younger needed significantly higher dosages compared to older dogs. None of them, however, needed the 2.2 mg/kg DOCP dosage, recommended by the manufacturer. Conclusions and clinical importance A starting dosage of 1.5 mg/kg DOCP is effective in controlling clinical signs and serum electrolyte concentrations in the majority of dogs with PH. An additional dose reduction often is needed to maintain an injection interval of 28-30 days. Young and growing animals seem to need higher dosages.

Dissertação de Mestrado Integrado em Medicina Veterinária A frequência de utilização do pivalato de desoxicorticosterona (DOCP), a dose inicialmente prescrita e as frequências de administração são variáveis entre a comunidade médico veterinária da Europa Ocidental (MVEO). Este estudo teve como objetivos averiguar a suplementação mineralocorticóide preferencial para maneio crónico do hipoadrenocorticismo (HA) e caraterizar a utilização de DOCP pela comunidade MVEO em cães diagnosticados com esta doença. Um questionário online em português, foi construído, validado e traduzido em 3 idiomas (Espanhol, Francês e Italiano), utilizando a plataforma eletrónica Google Forms. O questionário foi divulgado através de grupos exclusivos a Médicos Veterinários na rede social Facebook e via correio-eletrónico, incluindo questões sobre o regime inicial de tratamento, a dose inicial de DOCP, a monitorização clínica e eletrolítica em cães com doença de Addison. Obteve-se um total de 315 respostas em seis países (Portugal, Espanha, Itália, França, Bélgica e Luxemburgo). Dos que diagnosticaram HA recentemente, cerca de 84% utilizaram, pelos menos uma vez, DOCP e 80% preferem este fármaco ao acetato de fludrocortisona como primeira escolha para suplementação mineralocorticóide. Dos 154 que utilizaram DOCP, 63% indicaram que utilizam a dose inicial recomendada de 2,2mg/kg enquanto que, apenas 15% utilizam doses mais baixas. Após iniciarem tratamento com DOCP, cerca de 91% dos participantes monitorizam os eletrólitos duas vezes por mês e apenas 9% o fazem mensalmente até estabilização. Apenas 65% dos inquiridos se pronunciaram acerca do ajuste terapêutico. Destes, 53% privilegiam alterar a dose administrada enquanto 47% preferem aumentar o intervalo de administração. Após a primeira administração, 10% dos participantes apenas administram uma nova dose de DOCP quando o animal começa a descompensar. Em cães com valores eletrolíticos estáveis, 34% dos participantes fazem avaliações clínicas mensalmente, 44% trimestralmente, 17% duas vezes por ano e 5% anualmente. Este estudo confirma que, o DOCP é o fármaco de eleição para suplementação mineralocorticóide e que a maioria dos inquiridos segue as recomendações para a dose inicial e monitorização a curto prazo. Os ajustes terapêuticos de dose e frequência variam entre a amostra, evidenciando a necessidade de diretrizes específicas. Uma percentagem significativa dos inquiridos só administra DOCP novamente após descompensação clínica, o que pode aumentar o risco de crise addisoniana. ABSTRACT- The use of desoxycorticosterone pivalate by veterinary surgeons: A Western European perspective - The frequency of use of desoxycorticosterone pivalate (DOCP), initial doses and treatment intervals are variable among Western European Veterinary Surgeons (WEVS). This study aimed to verify which is the preferable mineralocorticoid supplementation for chronic management of hypoadrenocorticism (HA) and characterize the use of DOCP by WEVS in dogs diagnosed with this disease. An online Portuguese survey translated into three different languages (Spanish, French and Italian) was developed and validated using the electronic platform Google Forms. The survey was shared through social network veterinary groups in Facebook and mailing lists including questions focused on initial treatment regimen, DOCP starting dosage, clinical and electrolytic monitoring schedule in dogs diagnosed with Addison’s disease. Overall, a total of 315 responses were obtained in six countries (Portugal, Spain, Italy, France, Belgium and Luxembourg). Of those who had recently diagnosed HA, about 84% used DOCP at least once and 80% indicated they preferred its use over fludrocortisone acetate as first-line choice for mineralocorticoid supplementation. Among 154 respondents who had used DOCP, 63% indicated using 2.2mg/kg as initial dosage while only 15% stated using lower dosages. Following initiation of DOCP treatment, about 91% of respondents indicated monitoring electrolytes twice a month and only 9% do it once a month until stabilization. Only 65% of the respondents indicated their therapeutic adjustment. Of these, 53% prefer changing the dosage while 47% stated increasing the administration interval. Following the initial administration, 10% of respondents indicated administering subsequent DOCP injections only in case of clinical relapse. In dogs with stable electrolytes concentrations, 34% of respondents reported reassessing dogs monthly, 44% quarterly, 17% twice yearly and 5% yearly. This study states DOCP is the preferred treatment for mineralocorticoid supplementation and the majority of WEVS follow the manufacturer’s recommendations for initial dosage and short term monitoring schedule. Subsequent preferred therapeutic adjustments regarding change in dosage or dosing intervals vary among sample, reflecting how relevant specific guidelines are. Of particular concern, a significant proportion of WEVS only administer DOCP in case of clinical relapse following the initial administration, which likely increases the risk of addisonian crisis. N/A

The Thai Journal of Veterinary Medicine, 51, 1, 197

Although newly introduced to the UK and EU markets, desoxycorticosterone pivalate (DOCP) has been used successfully for the management of canine hypoadrenocorticism in the US for several decades. This article briefly reviews the history of DOCP use, as well as current dosing and monitoring recommendations, including off-label recommendations for lower initial dosing. Laboratory quality, particularly when using electrolyte ratios, is a critical component of case management.

Background Clinicians alter dosing for desoxycorticosterone pivalate (DOCP) to mitigate costs, but this practice has not been critically evaluated in a prospective clinical trial. Hypothesis/Objectives The duration of action of DOCP is longer than 30 days in dogs with primary hypoadrenocorticism (PH). Animals A total of 53 client-owned dogs with PH. Twenty-four dogs with newly diagnosed PH (Group 1) and 29 dogs with treated PH (Group 2). Methods Prospective, multicenter, clinical trial. For phase I, DOCP was administered and plasma sodium and potassium concentrations were measured until the dog developed hyponatremia or hyperkalemia at a planned evaluation, or displayed clinical signs with plasma electrolyte concentrations outside of the reference interval independent of a planned evaluation, thus defining DOCP duration of action. Plasma electrolyte concentrations then were assessed at the end of the individualized dosing interval (IDI; i.e., DOCP duration of action minus 7 days, phase II and at least 3 months after concluding phase II, phase III). Results The duration of action of DOCP in dogs in phase I with naive PH (n = 24) ranged from 32 to 94 days (median, 62 days; 95% confidence interval [CI], 57, 65) and previously treated PH (n = 29) from 41 to 124 days (median, 67 days; CI, 56, 72). Overall, the final DOCP dosing interval for all dogs that completed phase II (n = 36) ranged from 38 days to 90 days (median, 58 days; CI, 53, 61). No dog that completed phase III (n = 15) required reduction in the IDI. The DOCP duration of action, independent of group, was not significantly associated with several baseline variables. The median drug cost reduction using IDI was approximately 57.5% per year. Conclusion and Clinical Importance The duration of action of DOCP in dogs with PH is >30 days, and plasma sodium and potassium concentrations can be maintained with an IDI >30 days long term.

ADDISON'S disease or hypoadrenocorticism generally results from immune-mediated destruction of the adrenal glands and particular dog breeds appear to be overrepresented; for example, West Highland white and wheaten terriers, Portuguese water dogs, duck-tolling retrievers and great danes. Candidate genes for the disease have been identified in several breeds, although at this time the exact contribution of these genes is unclear (Short and others 2014). In most cases of ‘typical’ hypoadrenocorticism there is a lack of production of both mineralocorticoid and glucocorticoid, whereas in the rarer ‘atypical’ Addisonian only glucocorticoid deficiency manifests itself. Mineralocorticoid deficiency results in hyponatraemia and hyperkalaemia, as well as hypovolaemia, whereas glucocorticoid deficiency can lead to weakness, hypoglycaemia and gastrointestinal signs. Once typical hypoadrenocorticism has been diagnosed, both mineralocorticoid and glucocorticoid supplementation is needed. Mineralocorticoid deficiency is generally treated with either fludrocortisone or desoxycorticosterone pivalate (DOCP). There is an example of a large study of 205 dogs where 95 per cent were initially treated with fludrocortisone. Some of these dogs (14 per cent) were eventually switched to DOCP for a variety of reasons (Kintzer and Peterson 1997). In a paper summarised on p 98 of this issue of Veterinary Record , Roberts and others (2016) were also able to successfully stabilise 90 per cent of their patients with fludrocortisone. There are significant differences between both medications, including cost, and in most countries DOCP is sparingly used, because it is considerably more expensive than fludrocortisone; however, in a small number of countries …

Background Measurement of plasma renin activity (PRA) is the gold standard for monitoring mineralocorticoid treatment in humans with primary hypoadrenocorticism (PH). Objectives To compare PRA in dogs with newly diagnosed PH, dogs with diseases mimicking PH, and healthy dogs, and evaluate measurement of PRA to monitor therapeutic effects in dogs with PH treated with different mineralocorticoids. Animals Eleven dogs with newly diagnosed PH (group 1), 10 dogs with diseases mimicking PH (group 2), 21 healthy dogs (group 3), 17 dogs with treated PH (group 4). Methods In group 1, PRA was measured before treatment and at different times after initiating treatment. In groups 2 and 3, PRA was measured at initial presentation only. In group 4, no baseline PRA was obtained but PRA was measured once or every 1–6 months during treatment. Mineralocorticoid treatment consisted of fludrocortisone acetate (FC) or desoxycorticosterone pivalate (DOCP). Results Plasma renin activity before treatment was increased in dogs with PH compared to normal dogs and dogs with diseases mimicking PH with median activity of 27, 0.8, and 1.0 ng/mL/h, respectively. In dogs with PH, PRA decreased and normalized with mineralocorticoid treatment using DOCP but not with FC. In dogs treated with DOCP, PRA was lower than in dogs treated with FC. Plasma sodium concentrations were higher and potassium concentrations were lower with DOCP treatment compared to FC treatment. Conclusion and Clinical Importance Plasma renin activity is a reliable tool for monitoring mineralocorticoid treatment. DOCP treatment more effectively suppresses PRA compared to FC in dogs with PH.

The efficacy of a microcrystalline desoxycorticosterone pivalate (DOCP) injection in the management of canine hypoadrenocorticism (CHAC) was investigated in 21 dogs. On day 0 dogs previously diagnosed with CHAC were given a physical examination and an injection (2.2 mg/kg) of DOCP. This was repeated on days 25 and 50. On day 75 of the study a final physical examination was performed and the success of therapy was evaluated. Blood samples were obtained for serum chemical analysis (Na+, K+, Cl−, BUN & creatinine) on day 0 and day 75. Body weight increased steadily from a mean (± sd ) of 25.5 ± 14.2 kg on day 0 to 27.1 ± 14.8 kg on day 75. The mean serum biochemistry values on day 0 were outside normal limits for Na+ (139.3 ± 9.2 mEq/l), K+ (5.4 ± 0.9 mEq/l), and Na + K + ratio [ (26.4 ± 4.8) 1 ]. On day 75, after three injections of DOCP, the values for Na+ (148.2 ± 5.2 mEq/l), K+ (4.9 ± 0.6 mEq/l), and Na + K + [ (30.8 ± 4.2) 1 ] were normal and significantly (P All dogs in the study did well on DOCP therapy. The few side effects observed resolved with concomitant administration of prednisolone and/or adjustment of the DOCP dose. All clients elected to continue DOCP therapy after the trial ended, and the dogs continue to do well.