Florinef going!

RE: Florinef going!

Bob Russell — Fri, 29 Apr 2016 10:38:23 GMT

There is a nice little scam going on in the human medicine world. Companies are withdrawing so called orphan products which have set prices paid by the NHS.

The products are either transferred to another company and sold as a generic or even just sold as a generic. As there is no price control for generics, the drugs can be sold on at whatever price the seller wishes.

One example is Epanutin, made by Pfizer and cost about £20 for 30. Now made by Pfizer and sold as Phenytoin sodium (Flynn) at about £200+.

This scam is being investigated by the competitions lot:

https://www.gov.uk/cma-cases/investigation-into-the-supply-of-pharmaceutical-products

RE: Florinef going!

John Flynn — Fri, 29 Apr 2016 09:40:06 GMT

when you say generic do you mean the Aspen one that used to be squibb?

Is the increased cost of purchase not simply due to the current shortage in supply?

RE: Florinef going!

Ian Ramsey — Fri, 29 Apr 2016 09:05:09 GMT

Dear John,

Florinef has been withdrawn from the market (which is a legal step) so I don't see it coming back soon at all. Generic fludrocortisone is already on the market and easy to obtain - you just have to pay 7 x the price. Once you have started a dog on Zycortal (DOCP) then as this is the authorised drug for dogs under the Cascade you would have to show lack of efficacy before you transition them back to fludrocortisone. Moreover as the duration of action of DOCP is quite long it is not necessarily easy to know when to restart Florinef. If you start florinef too soon then you risk mineralocorticoid overdose, which could cause hypokalaemia and weakness and lethargy and in a dog with mild cardiac dysfunction could tip them over into heart failure.

Good news is that - providing owners learn to inject dogs by themselves and don't have to pay vets for this then the costs of Zycortal at 2.2.mg/kg SC q 25d (and remember many dogs will need less) are broadly similar to Florinef at 0.04mg/kg PO q12h for 25 days (though I accept many dogs need less). Point is that they are in the same ball park.

Best wishes

Ian

RE: Florinef going!

John Flynn — Fri, 29 Apr 2016 07:52:09 GMT

Presumably the fludrocortisone shortage is unlikely to last more than another couple of months - is it straightforward to transition them back on to it again from DOCP? (I have sufficient fludrocortisone for those on my books for another couple of months yet, so no problem just yet, but if the short supply continues I might be looking at this although haven't looked at cost of DOCP injection yet).

RE: Florinef going!

Ian Ramsey — Thu, 28 Apr 2016 21:40:40 GMT

Dear Chris,

You are absolutely correct - the starting doses in the licensing trial were based on dogs that were ill with hypoadrenocorticism. So dogs that are already stable on fludro are unlikely to need as much as 0.4 mg/kg so we have been using starting doses closer to 0.2mg/kg when transferring but tablet sizes mean that we thought a range of doses are better. Some - by no means all - of our patients on DOCP have had subsequent reductions in prednisolone (we usually reduce by 50%) due to Pu/Pd.

One of the questions that we hope to answer with this trial is how we can better judge these dose reductions as our worry is that another cause of Pu/Pd might cause a vet to reduce the prednisolone when in fact it needs to be maintained. It seems we have precise parameters for adjusting mineralocorticoid but at best vague parameters for adjusting glucocorticoid.

Hope this provides some fodder for discussion as we are all having to learn how to use this drug.

Best wishes

Ian

RE: Florinef going!

Christopher Saul — Thu, 28 Apr 2016 21:16:44 GMT

Dear Ian, Emma and Susanna.

Many thanks indeed for taking the time to write what is a very thorough and helpful response to this thread.

My only question is regarding the dose of prednisolone. I understand I am comparing two slightly different diseases here but in my own experience of treating 'atypical'/glucocorticoid only deficient cases of hypoadrenocorticism, most cases seem to be settle well on lower doses of glucocorticoids (usually 0.05 - 0.1 mg/kg/day prednisolone). Indeed these cases seem quite sensitive to the adverse effects of glucocorticoids and become very PU/PD on doses higher than this. I would have thought that an Addisonian patient treated with DOCP would have had similar glucocorticoid requirements to these 'atypical' cases.

I see that the mean prednisolone dose was 0.39mg/kg at the start of the trial and 0.13 at the end; I was wondering if patients receiving the higher doses at the start of the trial were clinically unwell and therefore needed higher doses due to their metabolically stressed state, and if not have you noticed if these patients were frequently PU/PD at these higher prednisolone doses or not?

I'm sorry if my question sounds argumentative; it is not meant to be I'm just genuinely interested in your experiences.

Many thanks again and best wishes,

Chris

RE: Florinef going!

Ian Ramsey — Thu, 28 Apr 2016 16:55:57 GMT

Dear all,

As others have noted, at least for the foreseeable future, cheap fludrocortisone in the form of Florinef is no longer available. A similar, though not identical, generic form of fludrocortisone is available through veterinary wholesalers but it is about 6 to 7 times more expensive and its bioavailability in dogs is not yet known.

We are currently conducting a clinical trial under an Animal Test Certificate issued by the Veterinary Medicines Directorate examining the efficacy of fludrocortisone and Zycortal. We have already successfully transferred several dogs on to DOCP as part of this clinical trial and we would like to share a protocol in cases where the owner’s supply of fludrocortisone is about to be exhausted. This is not evidence based, just experience based, and is also available from Dechra.

Day 1: Inject Zycortal at 2.2 mg/kg by subcutaneous injection once every 25 days and give the dog’s usual dose of Florinef

Day 2: Give the dog one half of the usual dose of Florinef. Start glucocorticoid (prednisolone) supplementation at 0.2 – 0.4 mg/kg by mouth once daily (or if currently on a higher dose of prednisolone then maintain that dose).

Day 3: Give the dog one quarter of the usual dose of Florinef

Day 4: No further Florinef

If there is not even sufficient fludrocortisone to perform this tapering dose then please note that in the original clinical trial dogs received their last fludrocortisone dose on the same day as their first Zycortal dose without ill effects. It is important to monitor sodium and potassium concentrations and adjust the dose according to the information available with the product.

We understand that in the USA and Europe it is standard practice to train most owners to inject their own dogs and we will be doing this after the first 2 or 3 injections (once our trial has finished). Although certain precautions need to be observed and sufficient training are necessary the risks of self-injection can be compared to the risks of owners injecting insulin into themselves when they have a diabetic pet.

It is vital that, when starting Zycortal, prednisolone or other glucocorticoid supplement is started at the same time. In the long term, it may be possible to reduce the prednisolone dose, however this will still need to be given every day (do not attempt every other day treatment as you are not trying to let the HPA axis recover). In the, as yet unpublished, clinical registration trial the mean prednisolone dose at the start of the trial was 0.39 mg/kg by mouth once daily, and the mean dose at the end of the trial was 0.13 mg/kg by mouth once daily. The prednisolone dose should be increased in times of metabolic stress such as surgery or illness by a factor of 2 to 4 times the dose (this is an empirical figure and should be adjusted according to the patient’s clinical signs).

We should also note that we are using Zycortal on a 28 day interval which is more convenient. Thus far we have identified one dog out of 10 that needs a shorter interval (21 days).

We hope that this advice is timely and helpful and reduces the number of calls to our and other hospitals. We would welcome others experiences and will be happy to share ours as it develops.

Yours sincerely

Ian Ramsey, Emma Roberts, Susanna Spence

University of Glasgow Small Animal Hospital

464 Bearsden Road

Bearsden

Glasgow

G61 1QH

RE: Florinef going!

Charlotte Marshall — Wed, 27 Apr 2016 23:38:06 GMT

Well NVS has only got the expensive stuff. I have nearly finished ringing around our clients. I still have to ring the lady who's dog is on 11 tablets a day . I'm pretty sure he's going to have to swop to the injection! I am rather dreading telling her the costof the tablets even tthough I can offer zycortal.

RE: Florinef going!

Roland Bulkyn-Rackowe — Wed, 27 Apr 2016 16:55:12 GMT

I'll be changing over to Zycortal + pred. I have used Percorten-V imported in the past and found it to be very effective and quite straightforward. The bottle is good for 120 days once broached IIRC so there should be 2 treatments or so per 20kg of dog in a bottle. The dose interval varies patient to patient with a range of about 20-40 days. My last one was every 22 or so.

I did enquire about fludrocortisone from Bristol-Myers Squibb, they stopped manufacturing it in September 2015 and passed on this to a third party. I contacted their distributer (Movianto??) who confirmed the price (£30 + vat per 30 tablets). Surely there must be a generic, it looks like it was patented in 1958!?

RE: Florinef going!

Bob Russell — Wed, 27 Apr 2016 15:32:02 GMT

India with a free 4 pack of Viagra!

RE: Florinef going!

Kate Richardson — Wed, 27 Apr 2016 15:11:34 GMT

So....am phoning round the Addisons patients to advise on the changeover and costs- one client has told me that his friend/sister's dog who is also Addisonian has been told by her vet that a) she can inject the dog and b) she can source fludrocortisone tablets cheaper than Florinef!

What are people's thoughts on owners injecting Zycortal? My initial reaction was no, but then owners inject insulin twice daily, so one they are stable, is it any worse? The guidelines just say use is restricted to use by or on the order of a vet.

And re sourcing generic fludrocortisone, so far only found it at approx £1.20 per tablet to us so am waiting with baited breath to here where this vet is getting it from!

RE: Florinef going!

Georgia Owen — Wed, 27 Apr 2016 13:14:36 GMT

Ah, I wasn't thinking of Percorten, it was whether to consider the use of Zycortal at a low dose...in fact have just had a very useful chat with Dechra. The low dose protocol is based on a single study by one author and is not all endocrinologists agree with her work.

In Zycortal trials the end dose ranged from 1.15-2.53mg/kg with a mean of 1.9mg/kg, so 1mg/kg does appear to be aspirational!

RE: Florinef going!

Bob Russell — Wed, 27 Apr 2016 12:56:22 GMT

May be a struggle to get VMD to authorise its importation in view of the arrival of Decra's product.

It is pretty pricey stuff as well!

RE: Florinef going!

Bob Russell — Wed, 27 Apr 2016 12:55:53 GMT

May be a struggle to get VMD to authorise its importation in view of the arrival of Decra's product.

It is pretty pricey stuff as well!

RE: Florinef going!

Georgia Owen — Wed, 27 Apr 2016 12:07:23 GMT

Have any of you heard (or used?) about the low dose Percorten protocol that vets have used in the states, starting at 1mg/kg.

Clients on an Addisons support group have mailed me info, but Dechra, unsurprisingly, have no info on this.

RE: Florinef going!

Kirsten Simpson — Tue, 26 Apr 2016 16:41:09 GMT

I don't know how this passed us by but we had NO idea this was going to happen until one of the bosses rang the supplier today regarding Florinef and was told it was discontinued! We (luckily) only have 4 cases just now, ranging from Lhasa to German Shepherd. The Lhasa owner has very limited funds, and another owner will be raging at having to come in more often! AAhhh dramaz!

RE: Florinef going!

Christopher Saul — Sat, 23 Apr 2016 11:59:58 GMT

[quote user="grumpyoldman"]

pred does have some mineralocorticoid activity, we have used that before as a stop gap until its re-appeared .

[/quote]

It does yes but its mineralocorticoid : glucocorticoid activity is only about 1:4. Hydrocortisone's is around 2:1 so is a better stop gap alternative. It is also available in IV form (efcortisol) which is useful in acute crises....

RE: Florinef going!

Ann Hopkirk — Thu, 21 Apr 2016 18:23:42 GMT

To continue the above (sorry-computer issues part way through reply!)

Dechra don't have any data on how early is safe but didn't think there would be a problem giving up to a week early

4\no data but would suppose a crisis would occur at some stage. Dechra are working on a reminder system.

RE: Florinef going!

Ann Hopkirk — Thu, 21 Apr 2016 18:19:00 GMT

I have managed to find the answers to these questions so thought I'd post in case useful to anyone else!

1\Yes-if dose and interval fine continue with this and run bloods on 'individual case basis'-depending how dog is, whether insured etc. Routine bloods every 3-6months (more often if owner willing)

2\No-just run d25 bloods. If Na:K ration still out of range on d25 results adjust incrementally by 0.1mg/kg until ratio noramlises

3\Good safety margin so give injection slightly early

RE: Florinef going!

Harriet Nicholson — Wed, 20 Apr 2016 10:51:43 GMT

My concern with allowing to let owners inject this is the section on the datasheet as below:

This 
product may cause adverse effects on male reproductive organs and, as a 
result, fertility.
This product may cause adverse developmental effects on unborn children and 
neonates.
Pregnant and breast-feeding women should avoid administration of this 
product.

When I emailed Dechra (who were really helpful) about conversion and the datasheet warnings they recommended pregnant and breast feeding women should avaoid the product altogether.

As such with this and the other datasheet warnings I would be concerned about the owners sefl injecting.

RE: Florinef going!

Martin Atkinson — Tue, 19 Apr 2016 18:12:33 GMT

[quote user="Emma ."]

Yes, you can!

If the licensed product is unavailable then Summit can help - give them a call

[/quote]You don't happen to work for Summit by any chance do you Emma. If you do as you've been helpful I won't post a picture of a tin of SPAM.

RE: Florinef going!

Emma . — Tue, 19 Apr 2016 16:06:44 GMT

[quote user="Martin Atkinson"]

More of an issue for me now is Amodip is out of stock and I can't get generic amlodipine from Summit anymore. Aarghhh!

[/quote]

Yes, you can!

If the licensed product is unavailable then Summit can help - give them a call

RE: Florinef going!

Martin Atkinson — Tue, 19 Apr 2016 13:31:20 GMT

Ann, there is a decent flow chart in the brouchure to address Q 1&2 but I would suggest you call Dechra for more information.

For Q3, I don't know what the storage requirements are but I would have thought that it was not beyond the wit of man to organise this and inject it themselves - what would they do with a diabetic dog? Sometimes we have to adjust our lifestyle to the circumstances we find ourselves in especially if they can afford to go on holiday for more than 25 days!!

Q4 I would have thought rather likely but if they're that disorganised what chance is there of them sticking to tablets and repeat monitoring anyway?

RE: Florinef going!

Ann Hopkirk — Tue, 19 Apr 2016 12:51:01 GMT

We have 3 Addisons cases needing to change to DOCP and I have 4 questions:-

1\If the electrolytes at d10 and d25 suggest continuing at 2.2mg/kg is this 'for life' unless clinical problems or do we have to run electrolytes every 25days? Clients already worried about increased costs.

2\If dose adjustment is required at d25 do we need to run bloods at d10 again?

3\What if someone is going on holiday and cant return for the regular injection at the correct time? Can it be given early or late? How many days early or late is considered 'safe'?

4\If an owner forgets to return for the injection, how likely is it the dog will have a crisis?

RE: Florinef going!

Andrew Kent — Sat, 16 Apr 2016 14:40:40 GMT

In most cases it's every day, if there are any steroid side effects you can try going to EOD but most dogs are fine at those low doses.

florinef had some glucocorticoid activity so most cases could be managed with that alone. DOCP has no glucocorticoid activity.

Andy