What is Lysodren?
Lysodren is a drug approved to treat cancer in humans that some veterinarians use “off-label” to treat Cushing’s disease in dogs. “Off-label” means using a drug for a different purpose than what the U.S. Food and Drug Administration approved. The active ingredient in Lysodren is mitotane, which works by destroying the layers of the adrenal glands that produce excessive cortisol. The goal is to erode just enough adrenal cells to restore cortisol to a normal level. Lysodren is a powerful drug that can have toxic side effects if it’s not used correctly and with very careful monitoring.
Comparison to Vetoryl
Vetoryl (trilostane) and Lysodren are both used for treating Cushing's disease.
Vetoryl is a newer drug and more commonly prescribed than Lysodren.
Vetoryl is more expensive.
For the adrenal form of Cushing's, some experts recommend using Vetoryl rather than Lysodren. Adrenal tumors are highly resistant to Lysodren unless a very high dose is used, which increases the chance of side effects.
Administering Lysodren
Lysodren is given to dogs by mouth in the form of a tablet. It should be given with food, preferably one high in fat, because food helps the medicine to be absorbed by the body and helps to prevent stomach upset. If you’re struggling to administer Lysodren to your dog, please contact your veterinarian.
Induction (Initiating) Phase
Treatment with Lysodren involves a short-term induction (initiating) phase and a long-term maintenance phase. For the induction phase, dogs are given a split dose of Lysodren in 8 or 12 hour intervals each day. This is done until cortisol levels return to normal, which takes 5 to 9 days for most dogs. Every dog is different, however. Some dogs will be finished in less time, and some will take more time.
It’s VERY important to carefully observe your dog, so that you’ll know when he or she has reached the end of the induction phase. Generally, a decrease in water consumption OR appetite means a dog is finished with induction. It doesn’t have to be a major decrease; a slight change in appetite is enough, such as finishing dinner in 45 seconds instead of 20, pausing halfway through a meal to drink water, or leaving a small amount of food in the bowl. If you have any questions at all about whether your dog has reached the end of the induction phase, contact your veterinarian immediately. If your dog hasn’t responded to Lysodren after a week, the vet may need to conduct an ACTH stimulation test to check cortisol values.
Once you suspect that your dog has finished the induction phase, the protocol is to immediately stop giving the drug and contact your veterinarian. Your veterinarian will measure cortisol values with an ACTH stimulation test and determine whether your dog is ready to enter Lysodren’s maintenance phase.
Maintenance Phase
This is the long-term phase that will last for the rest of a dog’s life. Lysodren is given at a much lower dose in this phase. Instead of being given every day, it’s usually given two times a week. However, careful observation and regular check-ups are still needed. The protocol is for a veterinarian to conduct an ACTH stimulation test 30 days after the maintenance phase has started to make sure everything is going well. If so, the ACTH stimulation test is repeated in 3 months and then every 4 to 6 months. In addition to monitoring cortisol, your veterinarian should monitor other values, such as liver and kidney values, blood cell counts, blood sugar levels, and blood electrolytes.
Potential Side Effects
As mentioned above, Lysodren can have severe side effects, especially if someone doesn’t monitor their dog carefully and continues to give a high dose past the end of the induction phase. The most common side effects are vomiting and diarrhea. Other side effects include lack of appetite, neurologic signs, lethargy, incoordination, weakness, or yellowing of the skin, gums, or whites of the eyes. Any of these symptoms can be signs of a life-threatening emergency. If your dog develops any of these symptoms, seek veterinary care immediately. Many veterinarians provide dog owners with a small supply of a drug called Prednisone to use in an emergency.
Precautions for Dogs
Lysodren should not be given to dogs that are allergic to it, dogs that are sick, weak, or frail, or those that are pregnant or lactating. It should be used cautiously in dogs with diabetes, as it can potentially change insulin requirements. Additional caution should be used in dogs with decreased kidney or liver function or disease. Dogs that are injured or undergoing a stressful event while taking Lysodren may be at risk for developing Addison’s disease; during these times, your dog may need to be supplemented with a corticosteroid.
Drug Interactions
The following medications should be used with caution when given with Lysodren: central nervous system depressants, fentanyl, insulin, midazolam, phenobarbital, selegiline, spironolactone, or warfarin.
Precautions for Humans
Anyone administering Lysodren should wear gloves and not allow it to come into contact with their skin, eyes, or mouth. Gloves should also be worn when handling your pet’s urine, feces, or vomit, as the drug may be present. Don't handle this medication if you're pregnant.