Lupron Demystified

I don't usually have time to write posts, but I felt it was important to clarify some confusion surrounding the different forms and dosages of Lupron®, and briefly discuss adrenal tumors.

There have been some inaccuracies in some posts and emails that I've read about the forms in which Lupron comes. I have done extensive research in this area and will try to pass on some of the key information. The protocol information sheet for veterinarians that Beth Comarow (Miskabc@aol.com) is distributing for me is the result of treating more than 150 ferrets with the drug and not based upon hearsay or a few cases, so I think the information is accurate.

I urge you to exercise caution before acting on unsubstantiated information or claims that you may read.

The treatment of choice for this condition is surgical removal of the adrenal tumor. The adrenal tumor produces an excess of testosterone and/or estrogen which results in all of the symptoms we see, including but not limited to: hair loss, males straining to urinate, swollen vulva, lethargy and return-to-male sexual behavior or aggression.

Approximately 25% of adrenal tumors are malignant; therefore, surgical removal is the best treatment. Medical treatment is reserved for ferrets who are not good surgical candidates - too weak or otherwise sick to tolerate surgery well, or when surgery cannot be done..

The medical treatment for this condition involves drugs that block and decrease the production of estrogen and testosterone. Therefore, these medical treatments are unlikely to affect the adrenal tumor(s) themselves, but they can reverse all of the symptoms.

None of the new medical treatments are approved for ferrets, although they appear to be safe, and long term treatment results are not available. (I should point out that most drugs, from Amoxi-drops to Lysodren, have not been specifically studied and approved for the ferret either.)

Lupron is available in several forms that last different amounts of time in the body. Lupron is available as an injection that lasts 24 hours, 1 month, 3 months and 4 months. Each is a different preparation that lasts for different amounts of time, so it's important to know which form you are using: 1-month, 3-month or 4-month.

The reason we use the 4-month form is for convenience and cost. The monthly injection given 4 months in a row is more expensive that one 4-month shot. (No matter how high a dose you give of the 1-month shot, it will only last 1 month - so when you talk about what dosage you are giving you must say which form you are using.)

Example: Two ferrets receive the same dosage of Lupron, but one gets the 4-month shot and one gets the 1-month shot. The ferret who gets the 1-month shot receives a 500 microgram (mcg) shot each month for 4 months. The ferret receiving the 4-month shot receives one shot of 2000/mcg (2 milligrams or mg). Therefore, both ferrets are receiving the same amount of the drug per month, but when you say one ferret got a 2000/mcg shot and one got a 500/mcg shot, it doesn't sound like the same dosage - but it is the same per month. I have found that at the same dosage, the 4-month shot is the less expensive form.

The Lupron in both cases is time released, called a "depot." In the 1-month shot the Lupron depot is released over the period of 1 month, and in the 4-month shot, over 4 months.

The 24-hour form of Lupron comes in a pre-made liquid. Since it only lasts 24 hours in the ferret after being injected, it would have to be given every day to be effective, so is not worth discussing.

The other forms (1-, 3- and 4-month) come in two vials - a liquid and a powder. They are mixed together, and then immediately injected. Stability after mixing has never been studied. I am looking at the stability of the solution once mixed and stored in a standard freezer.

Why is this important to understand? Each human dose of Lupron is large enough to treat many ferrets. If a veterinarian who wants to treat one ferret is forced to buy a human-sized dose, storage can be a problem, since after the Lupron is mixed it should be injected immediately, or it could become ineffective very quickly. But the veterinarian may not have, for example, 15 ferrets who need the injection at the same time. So it can be cost prohibitive to be forced to buy a dose that could treat that many ferrets but only use it for one.

The good news is that we recently found a pharmacy which, under sterile conditions, will separate the powder into individual ferret-sized dosages and ship directly to the veterinarian. A veterinarian can now call the pharmacy and buy one ferret-sized dose of the drug. The veterinarian mixes the liquid and powder together, and gives the injection immediately.

I should mention that I receive no money from the pharmacy! I'm giving out their name because they are capable and willing to separate out the powder and liquid in a sterile environment for us.

Lupron is so new that no one yet knows the lowest dosage we can use to reverse all symptoms. The dosage I have found to be the most effective so far is 2000/mcg (2/mg) of the 4-month depot, or 500/mcg of the 1-month depot.

This dosage is virtually 100% effective in reversing all symptoms. To date we have not seen any toxicity, although long-term studies have not yet been performed. In a small number of ferrets we have seen local reactions - a bump where the shot was given. The reactions can occur 2-4 weeks after the injection, and resolves without treatment in 4-6 weeks. If they are removed or biopsied, some or all of the Lupron will be removed, so they should be left alone. They do not seem to bother the ferret. There are lower dosages recommended by some. Although I have not used lower dosages, I have heard of approximately 20 cases and seen several for a second opinion, where lower dosages did not reverse symptoms. In cases where male ferrets have enlarged prostates and are straining to urinate, life threatening blockages can occur.

(A word on urinary blockages: straining to urinate means that the adrenal tumor is secreting the hormone testosterone, which causes the prostate (not the tumor) to swell and block or partially block the urinary tract. Treating with a high enough dose of Lupron can stop the testosterone secretion, so the swelling of the prostrate is reduced.)

I consider the treatment effective if all symptoms reverse (hair grows back, vulva goes down to normal size, no straining to urinate, no lethargy, reversal of male aggression, reversal of return-to-male sexual behavior, etc.). If your ferret is receiving Lupron and all of the symptoms do not completely reverse, then the dosage may be too low. In my experience the 4-month shot at the dosage we are using is very effective and lasts for 5-6 months with some ferrets symptom-free for 7 months.

Again, you can have your veterinarian buy a 1-ferret dose of the 4-month Lupron depot from Professional Arts Pharmacy. Their number is 1-800-832-9285. There may be other pharmacies that offer this service but this is the one with which I've worked.

It's critical that a pharmacy work in a sterile hood and understand the protocol. My wife is a pharmacist, and agrees that the varied forms of Lupron can be confusing. Also, Lupron is often administered in a hospital setting, so retail pharmacists don't frequently work with it. I've heard about mistakes such as using unapproved diluent (the liquid) or dispensing 24-hour Lupron as the 1-month depot. It's also easy to confuse 1- and 4-month Lupron depot and think that 2000/mcg (2/mg) of 1-month depot lasts 4 months. But remember, the 1- and 4-month depots are different forms, and 2000/mcg of the 1-month depot only lasts 1 month! I've spoken at length to all of the pharmacists at Professional Arts, provided them with my protocol, and they have been compounding and shipping it to veterinarians.

If you would like a copy of the Lupron, Casodex® and Arimidex® protocols for your veterinarian, contact Beth Comarow at Miskabc@aol.com and request "Medical Treatment of Hyperadrenocorticism in the Ferret," or simply "the protocol sheet."

Finally, I'd like to thank the ferret-owning community for their generosity and dedication, which has helped spark my enthusiasm to continue treating and searching for new treatments for this wonderful species.

Note: This information sheet may only be copied or reprinted in its entirety, with credit given to the author.