Image of Incurin from Europe

Incurin ( estriol / oestriol ) is the newest drug available in the USA to treat dog incontinence

Incurin is the brand name for a new form of estriol (or oestriol if you’re in Europe) now approved for use in estrogen-responsive urinary incontinence in ovariohysterectomized (spayed) female dogs. Incurin is manufactured by Intervet, Inc. of Summit, New Jersey and will be made available through veterinarians at a later date.

Urinary incontinence (involuntary urine leakage) can be caused by different medical conditions. Hormone-based urinary incontinence is a common problem in middle-aged and elderly spayed female dogs. The pet can urinate normally, but they leak urine while resting. Frequently the dogs are not aware that they are leaking urine. Physical examination and blood and urine tests are usually normal in these pets. Hormone-responsive incontinence can occur months to years after a dog is spayed.

Incurin will be FDA labelled for the treatment of estrogen-responsive urinary incontinence in dogs

Incurin ( estriol / oestriol ) in its current form has been used in Europe since 2000.

Incurin will likely become the most widely used drug for hormone responsive incontinence in dogs as it is an “on-label” treatment for this problem, and veterinarians are supposed to use FDA-labelled drugs first before turning to off-label drugs.

*UPDATE: PRN Pharmaceutical has received FDA approval for Proin® - http://www.prnpharmacal.com/pressreleases/proin.php

Long-term safety of Incurin has not been established

Incurin is a natural estrogen hormone. Estrogens increase the resting muscle tone of the urethra in females, especially those with low natural estrogen levels after being spayed.

Side effects of Incurin include estrogenic (swollen, reddened, bleeding or licking of vulva, and swollen or licking of mammary glands) and gastrointestinal (inappetence and vomiting) effects. According to initial safety studies, These effects were most often noted at the beginning of drug administration when higher doses of estriol were used. These effects usually improved after the dose was decreased.

Those same studies named additional possible side effects of Incurin including hyperpigmentation and lichenification of the vulva, vaginal hemorrhage, anemia, leukopenia and thrombocytopenia, possible uterine stump pyometra, and increase in epileptic seizures. During those studies, three dogs receiving estriol in US extended-use studies were euthanized due to aggressive behavior after 180, 306, and 320 days of therapy, respectively.

It’s clear that Incurin DOES have hormone related side effects.

I suspect the main selling point of Incurin will be that Estriol is a short acting “natural” compound, hopefully without the cummulative affects more likely seen with longer acting estrogens. Unfortunately, research on this hypothesis is still underway, and no long-term safety studies have been completed.

Another potential benefit of Incurin is its dosing schedule – Incurin is intended to be dosed once daily. For comparison, phenylpropanolamine ( Proin®, PRN Pharmaceutical, a drug I’ll talk about in a moment ) must be dosed up to three times daily. DES, an old discontinued drug that I also discuss later, used to be given once or twice a week.

Incurin is NOT more effective than phyenylpropanolamine / PPA / Proin

During a two-phase American field trial of 226 dogs, Incurin was only found to be 66% effective, compared to 37% of dogs who improved after receiving ONLY PLACEBO (interesting!).

A similar study of 129 dogs from the Netherlands showed better success – according to the veterinary practitioners in this study, 83 per cent of the dogs either became continent or improved.

Clearly, Incurin is more effective for the treatment of estrogen-responsive incontinence than is NO treatment at all…

However…

Most American veterinarians these days use a drug called phenylpropanolamine ( also known as PPA or Proin or Propalin) to treat urinary incontinence in dogs. Phenylpropanolamine is an amphetamine-type drug containing norephedrine and norpseudoephedrine. It used to be available on the American OTC market as Accutrim for weight loss, and in various decongestants, until studies found it caused an increase in stroke in young women (but NOT IN DOGS) and was pulled off the market.

Although Proin is now a prescription drug, it is NOT FDA LABELLED NOW FDA LABELLED to treat canine urinary incontinence (although it has years and years of veterinary experience). Proin works by stimulating the bladder sphincter muscle to contract, thereby helping control urine leakage. Proin is NOT a hormone, and therefore has ZERO hormone side effects.

While most veterinarians consider Proin “safe”, side effects of phenylpropanolamine do exist and include vasoconstriction, increased heart rate and coronary blood flow, increased blood pressure and mild CNS stimulation. As a result, this medication should be used with caution in animals with glaucoma, prostatic hypertrophy, hypertension, hyperthyroidism, diabetes mellitus and cardiovascular disorders.

Many American studies have been done on phenylpropanolamine for use in incontinent dogs. One study of phenylpropanolamine at label doses has been found it to be 89.7% effective to treat the same dogs that Incurin would aim to treat.

Older hormone alternatives to Incurin like DES or megestrol acetate (Ovaban) are no longer commercially available (but can still be obtained from compounding pharmacies)

In the past, veterinarians treated estrogen-responsive incontinence with a drug called diethylstilbestrol ( DES ) which is now unavailable. DES use has been discontinued in recent years because of a high incidence of bone marrow suppression, aplastic anemia and severe illness in long-term high-dose treated dogs.

My primary concern, and I suspect that of other veterinarians, will be that Incurin may also end up causing bone marrow suppression, and estrogen-like side effects in treated dogs, just as DES and megestrol acetate did in the past.

Not only that, we’ve got a good, safe alternative drug. Phenylpropanolamine is currently available to veterinarians (though not labelled for this indication) and doesn’t have any hormone side effects at all.

Both drugs appear equally effective.

So really, Incurin isn’t going to be a BETTER drug than Proin. They’re both 70-90% effective for controlling incontinence in dogs. True, Incurin is once daily while Proin is three times daily, but many pet owners only give the Proin in the evening since most incontinence episodes happen during sleep, so I don’t think that’s a big selling point.

The difference will be in patient selection. If your dog has a history of heart disease, diabetes or glaucoma, avoid Proin and choose Incurin instead.

Or, if your dog is one of the 10-20% that Proin DOESN’T work on, you can try ADDING Incurin and see if that helps.

Before starting your pet on any new drug therapy for urinary incontinence, whether it be Incurin or Proin , please discuss everything with your veterinarian.