Starting with Zycortal

[Walcop]

Hi Jo/all,

Walter had his 25 day blood test on Monday:
Na= 153
K= 3.7
Ratio = 41.35

10day ratio was 41.94

Initial 2.37mil of Zycortal given approx 25days ago

2nd dose of Zycortal was 2.1mil given yesterday Tues 5th July.

Daily dose of 2.5mg of preds

Walter appears well, though has increased thirst/urination. The vet suggested lowering the amount of preds being given......I was thinking this is a side effect of the Zycortal, so any thoughts are appreciated.

Regards

Steve

[kathyl1]

I have 2 Standard Poodles aged 11 and 5.  The 5 year old apricot was diagnosed with Addisons in July 2014 after a crisis.  He has been treated successfully since then with 6 tablets a day of Florinef and has lead a completely normal life, good appetite and lots of energy.   

Rueben commenced his treatment with Zycortal injection 3 weeks ago and so far with no problems.  His 10 day electrolytes were completely within the normal range. He has prescribed 1.5 tablets of Predniselone per day but I feel he may be able to take just 1 as his appetite seems to have increased quite a lot.

He will be tested again and given his next injection at 25 days.  My vet has agreed that, once he is stable, I can commence injecting him myself.

After feeling devastated at the coming change of routine after having him so stable for 2 years, I am now quietly optimistic that the Zycortal will prove to be just as effective, albeit more expensive.

I will ask my vet for specific dose levels and electrolyte results when I take him for his next injection and will post them.

[Jo CIMDA]

Hi Keith

It is great news that Max is doing well on Zycortal.

This pattern seems pretty typical going by the people that I am in contact with, and most have delayed giving a further injection until the ratio is between 27-32.  As far as I am aware this prolonged period of elevated ratios can settle down and the duration between injections may not be as long in the future, but every dog is an individual and they can process hormones differently. 

My own feeling is to establish the dose that will give the dog a ratio between 27-32 by day 25 (or per month).  Once this dose is established, the owner can give the injection subcutaneously and will only need to go to the vet for electrolyte checks every 4-6 months.  It is very likely the established dose that will last one month will be lower than 2.2mg/kg and I believe this might reduce any peaks and troughs of electrolytes throughout this period of time. 

Many thanks for the update on Max.
Jo


I  am sure you have seen the following extract taken from the Zycortal Drug sheet.

https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2c9b766a-c36b-44aa-bbd8-24fab24ca97c

Label: ZYCORTAL- desoxycorticosterone pivalate injection, suspension
•   Application
Drug Label Information
Updated March 3, 2016


Initial dose of ZYCORTAL Suspension:
The initial dose is 2.2 mg/kg (1 mg/lb) body weight, administered by subcutaneous injection.

Interim monitoring visit:
Re-evaluate the dog and measure the serum sodium/potassium ratio (Na+/K+ ratio) approximately 10 days after the first dose, which is the time to maximum concentration (Tmax) of desoxycorticosterone (see CLINICAL PHARMACOLOGY). If the dog's clinical signs have worsened or not resolved, adjust the dose of prednisone/prednisolone and/or investigate other causes of the clinical signs.

Second dose of ZYCORTAL Suspension:
At approximately 25 days after the first dose, re-evaluate the dog and repeat the Na+/K+ ratio.
o   If the dog is both clinically normal and has a normal Na+/K+ ratio on Day 25, adjust the dose based on the Day 10 Na+/K+ ratio using the guidelines in Table 1, below.

o   If the dog is clinically normal and has a Na+/K+ ratio > 32 on Day 25, either adjust the dose based on the Day 10 Na+/K+ ratio according to Table 1 or delay the dose (see Prolonging the dosing interval).

o   If the dog is either not clinically normal or if the Na+/K+ ratio is abnormal on Day 25, adjust the dose of prednisone/prednisolone or ZYCORTAL Suspension (see Subsequent doses and long-term management).

Table 1: Day 25: Administering the Second Dose of ZYCORTAL Suspension
If the Day 10 Na+/K+ ratio is:   Do not administer Dose 2 on Day 10.   25 days after the first dose, administer ZYCORTAL Suspension, as follows:

> 34      Decrease dose to: 2.0 mg/kg
> 32 to 34      Decrease dose to: 2.1 mg/kg
27 to 32      Continue 2.2 mg/kg
24 to < 27      Increase dose to: 2.3 mg/kg
< 24      Increase dose to: 2.4 mg/kg

Prolonging the dosing interval:
If the dog is clinically normal and the Day 25 Na+/K+ ratio is > 32, it is possible to prolong the dosing interval instead of adjusting the dose as described in Table 1. Evaluate the electrolytes every 3-7 days until the Na+/K+ ratio is < 32, and then administer 2.2 mg/kg of ZYCORTAL Suspension.

Subsequent doses and long-term management:
For subsequent doses, use the following guidelines if the dog is not clinically normal and/or has abnormal Na+ or K+ concentrations:

o   Clinical signs of polyuria/polydipsia: Decrease the prednisone/prednisolone dose first. If the polyuria/polydipsia persists, then decrease the dose of ZYCORTAL Suspension without changing the dosing interval.

o   Clinical signs of depression, lethargy, vomiting, diarrhea or weakness: Increase prednisone/prednisolone dose.
o   Hyperkalemia, hyponatremia or Na+/K+ ratio < 27: Decrease the ZYCORTAL Suspension dosing interval by 2-3 days.
o   Hypokalemia or hypernatremia: Decrease the ZYCORTAL Suspension dose.

Prior to a stressful situation, consider temporarily increasing the dose of prednisone/prednisolone.

[Jo CIMDA]

Hi Steve

Walters sodium and potassium ratio has remained high.  I am glad your vet has reduced the dose but I guess that it might need lowering further or prolong the dosing period until the ratio is around the early 30's before the next injection is given.

I am so pleased Walter is doing well.  It is usually the pred that causes excessive drinking and urinating, but Walter is only on a very low dose, so perhaps you should give his body time to adjust and this might settle down on its own.  Was Walter on daily pred when he was on Florinef, or just at times of stress?  Because Prednisolone has a 24 hour whole life duration of action and then 12 hour half life duration, some dogs, if they are weeing and drinking a lot might do better on an every other day dose of pred but this will have to be discussed with your vet.  Personally  2.5mg/24hrs is such a low dose I think his body will adjust. If he were mine I wouldn't want him on less at this stage.

Many thanks for the info.

Jo

[Jo CIMDA]

Hi

Great to know that Rueben is doing well.

Jo

[Keith@Yorkshire]

Hi Jo,
Thank you for your reply, all taken on board. Testing ratios again tomorrow, Saturday, I think the vets are getting a little more relaxed about Zycortal.

[Walcop]

Hi Jo,

Yes I think waiting until the ratio is approx 32 is a good idea before the next injection.

I too am aware re the preds which causes excessive drinking & weeing...as happened when many moons ago I was battling the vets to lower the preds dose. I know Walter is on a very low dose but wanted your thoughts after the vet suggested lowering the dose.

When Walter was on Florinef he only received preds at times of stress. I will see how things settle down with the Zycortal before lowering the current dose of preds as the small amount is simply replacing the glucorticoid/Pred effect that was in the florinef.

Thanks as always


Steve

[Keith@Yorkshire]

Hi Jo,
Had Max tested Tues. 19th July, 56 days on from 1st. Zycortal injection, his ratio was 34, it was 33 on Saturday 16th July. taking him back on Saturday 23rd July. Vets now looking at a dose rate of probably 1.8. for 2nd injection.
Keith.

[Jo CIMDA]

That's brilliant Keith and so useful to know.  I will add these details to Max's notes.

I am so glad your vet is going to reduce the Zycortal dose.  The next month will be interesting.

I hope Max is doing well.  Many thanks for this update.

Jo

[Keith@Yorkshire]

Hi Jo and friends,
Our 12yrs old Black Lab Max is on his second cycle of Zycortal, his first went about 55 days For his 2nd. cycle his dose was reduced from 2.2 to 1.8. After 10 days ratio was 36, at 25 days it was 33, we are to test again at 32 days.
The vets we use are in the learning curve and are very willing to discuss the ongoing situation and accept our views. I think that we should reduce the dose rate again to aim for a 28 day cycle, maybe a further reduction to 1.6/1.5.  We'll see what happens on Wednesday.
Max himself is in good form, I think he is re-acting better to Zycortal  than Florineff.

[Jo CIMDA]

Hi Keith

You must be thrilled that Max is doing so well on the Zycortal.  I will add these details to his record.

It will be very interesting to see what his levels are next Wednesday. It may be at day 32 his levels will be perfect to give another shot (27 - 32) and if they are then it might be prudent to give 1.8mg again to see if the control is the same as this time, or if it needs to be reduced further at the next due dose. Anecdotal evidence suggests that the duration may be prolonged for the first couple of times and then the duration can reduce as the body adjusts to the new treatment.

Many thanks for the update. It is useful to know.

Jo

[Keith@Yorkshire]

Hi Jo,
We had Max's ratio done on Wednesday, 24th. 32days since 1.8ml. injection.  It was 35 so we decided to leave him another week and test again. What as happen is we have reduced his preds. from 5 a day to 2.5, he was panting allot, always hungry and drinking more than usual so Laura, the vet, suggested that his steroids be reduced.

Keith.

[Jo CIMDA]

Hi Keith

I do feel you are getting there Keith.  It seems ridiculous that a science based treatment is so hit and miss, but I suppose that is the uncertainty of hormones and the individual.  Having said that, we all thought that the recommended starting dose was probably too high based on the American experience with this drug.

Thanks for the update.

Jo