Oseltamivir phosphate use in domestic animals and wildlife

Article From Dr. Broadhurst's Web site: www.JackBroadhurstDVM.com
Inserts by Annette King Tucker

On April 24, 2004, the concept of treating Parvoenteritis in dogs with a neuraminidase inhibitor (oseltamivir phosphate) was introduced on the Veterinary Information Network’s Infectious Disease Board. Since then, oseltamivir phosphate has been used successfully by veterinarians, shelter workers and rescue groups to treat Parvoenteritis in thousands of dogs, cats and raccoons throughout the world.

oseltamivir phosphate: Oseltamivir is one of two commercially available sources of a neuraminidase inhibitor that has been used successfully in treating infectious parvoenteritis.

Neuraminidase: An enzyme that is produced by both bacteria and viruses. It is considered a virulence factor in viral and bacterial infections that require neuraminidase to remove biological barriers that protect the host.

Super infections: Any infection that requires both a virus and bacteria to produce an infection that is more pathogenic than either infectious agent can produce alone. Veterinary examples: canine and feline Parvo, canine kennel cough and influenza, feline URI, parvoenteritis in raccoons, and bloody scowls in deer.

The use of oseltamivir phosphate in canine, feline, and raccoon parvoenteritis: The success of using a neuraminidase inhibitor in treating canine and feline Parvo is due to the suppression the production of bacterial neuraminidase, and has no effect on the Parvovirus' ability to replicate. Puppies can still develop myocarditis and CHF...kittens can still develop cerebellar hypoplasia...the patient’s feces will still contain the viral antigen even while the animal is recovering. oseltamivir phosphate does not interfere with the replication of the Parvovirus, and as a result, no mutant or resistant strains of the Parvovirus will be created from the use of oseltamivir phosphate.

oseltamivir phosphate should never be used to treat any animal that does not test (+) using the fecal antigen test. All of the guidelines for using oseltamivir phosphate have been developed in cases that have had a (+) fecal Parvo test.

Dose: 1mg/lb that dose given every 12 hours for 10 consecutive treatments...requires a (+) fecal antigen test.... There is a direct relationship between clinical response and the time treatment is started…oseltamivir phosphate should be given w/in 48 hrs of onset of clinical signs...if no response after the first dose...double to 2mg/lb for the second, third dose, etc.

Specific Breeds of Dogs: Dobies, Rotties, Retrievers, Pit Bulldogs, and Alaskan sled dogs...all require at least 2mg/lb as the starting dose as these breeds respond poorly to Parvo infections...

As a preventive: Animals have been exposed, but are not currently showing any clinical signs should be given 1mg/lb once a day for 5 days...if these animals develop one or more clinical signs (vomiting/bloody diarrhea/anorexia)...treatment should be changed so that they are given 1mg/lb every 12 hr for a total of 10 treatments.

Animals requiring IV support: Animals sick enough to require IV support (fluids/antibiotics/antiemetics) respond poorly to oseltamivir phosphate. Their clinical condition is the result of a damaged GI tract with the introduction of GI bacteria and toxins beyond oseltamivir phosphate’s ability to protect the patient. If used, oseltamivir phosphate can be started at 2mg/lb and the dose adjusted according to the patient’s response every 12 hours.

Animals that vomit after being given oral oseltamivir phosphate: These patients can be given the same dose as an enema. You can also divide the contents of a 75mg capsule into lines and mix the appropriate amount into pancake syrup or honey and place under the tongue or in the lip fold.

oseltamivir phosphate Products: There is a suspension that you add 23 cc of water to get 25cc of 12mg/cc. There is also a flat of ten 75 mg capsules.

To use capsules to treat a 5 lb puppy: (INSERT: "or any mammal") Mix the contents of 1 capsule into 10 cc of a liquid diet like Canine Rebound..(INSERT: Plain water works fine to mix-then pull up syrup or honey to flavor capsule suspension as it is very bitter) this will create a 10cc suspension with a concentration of 7.5mg/cc....Refrigerate and shake well and give 1cc q. 12 hrs x 10 treatments.... do not mix capsules with water as this water suspension is very bitter and can cause the patient to vomit. One can also use liquid VAL or similar vitamin prep.

(INSERT: KEEP SUSPENTION REFRIGERATED AND SHAKE WELL BEFORE DOSING. GOOD FOR 30 DAYS AFTER SUSPENDING)

INSERT: Small wildlife; dose 1/10th cc of the 7.5 mg per ml suspension per lb, with the smallest dose for animals under 1 lb. being no less than 2/10ths cc.

To use the suspension (12mg/cc) to treat a 5 lb puppy: Shake well and give the puppy 0.5cc of the suspension q. 12 hrs x 10 treatments. Refrigerate the suspension after adding water and between treatments.

oseltamivir phosphate and FDA: On March 20, 2006, the FDA banned the use of oseltamivir phosphate and other neuraminidase inhibitors in treating chickens, ducks, turkeys and other birds...goes into effect in June 2006.... you can still use oseltamivir phosphate in dogs, cats, and raccoons.

In the emergency clinics or private clinics that are presented with cases whose disease course is unknown or have exceeded the 48 hrs time-frame: The professional staff should make the client aware of the poor response to oseltamivir phosphate due to the high levels of bacterial neuraminidase currently present in the patient's GI tract, and the presence of GI pathology created prior to presentation. oseltamivir phosphate will only prevent future pathology, and cannot reverse any pathology created prior to treatment.

Treating Parvo requires the same mental process used in treating Diabetes Mellitus.... The DVM begins with a standard initial dose of oseltamivir phosphate or insulin and then uses professional judgment to adjust the following doses required to get a clinical response.

In an uncomplicated case, presented within 48 hrs. of the onset of clinical signs, one should see no vomiting after the first dose...no diarrhea after the 2nd...and alert/eating after the 3rd dose. If there is no clinical response after the 3rd dose...you have either started using oseltamivir phosphate too late, have a secondary medical problem that needs to be addressed, or have the wrong diagnosis.

In summary, the introduction of the concept of using a neuraminidase inhibitor to treat canine, feline and raccoon Parvoenteritis, has opened many new doors into the understanding of the pathobiology and treatment of this disease. Prior to April 24, 2004, Parvovirus was thought of as viral enteritis. Based on this concept, vaccines were developed to help prevent or reduce the severity of the clinical disease.

Once the disease was diagnosed, treatment protocols were all designed to address the various end products produced during the disease. The presence of vomiting and/or diarrhea usually dictated that most drugs were given intravenously. Animals that are hospitalized usually remain 3-7 days with unpredictable prognosis. This is because none of the treatments address the core problem of excessive GI bacterial neuraminidase. Drugs are given to address all of the various reactions such as: vomiting, endotoxic shock, pain, bacterial septicemia, GI mucosal ulcerations and general organ failure. This approach requires many drugs and man-hours to treat the multiple pathological processes associated with viral Parvoenteritis.

With the introduction of using a neuraminidase inhibitor (oseltamivir phosphate), we established that Parvoenteritis is not a viral enteritis, but a super infection that requires the presence of bacterial neuraminidase. When a neuraminidase inhibitor is use under the strict guidelines developed since April 24, 2004, the disease is not allowed to develop into the clinical disease currently known as viral Parvoenteritis. The commensal bacteria do not transform into pathologic bacteria, and the patient’s disease is not allowed to progress as described in the veterinary literature. In order to achieve this reversal, there has to be a definitive diagnosis and the neuraminidase inhibitor has to be given according to established guidelines.

Please keep in mind that any recommendations given in this article are not FDA approved. They are offered to help educate and guide those anticipating using Oseltamivir therapy in the future. Roadrunner Pharmacy is currently in the process of acquiring Oseltamivir powder to be compounded into the various formulations and concentrations requested by our clients.

Jack Broadhurst

The following comments and updates are by Annette King Tucker, the Director of Wild Heart Ranch Wildlife Rescue, where use of oseltamivir phosphate in wildlife was first tried, and the clinical studies of its use in wildlife began;

Road Runner Pharmacy has oseltamivir phosphate kits available for animals. One kit treats 50 lbs of animal and sells for around $100. Contact 877-518-4589. Must be ordered by a DVM!

There is NO FDA BAN on treating mammals with oseltamivir phosphate. Fear of causing resistant or mutating strains are unfounded since oseltamivir phosphate works on the body's response to the virus, not the virus itself. In order for an animal to be "oseltamivir phosphate resistant" the animal itself would have to be infected and treated with oseltamivir phosphate repeatedly in order for its body chemistry response to the virus to change. Animals treated for parvo virus and saved with oseltamivir phosphate are naturally immune. Since the virus is NOT stopped from replicating by oseltamivir phosphate, the animal builds immunities naturally and will not get the virus again. Tamilfu works on the body's pathogenic response to the virus. (overgrowing deadly bacteria) Releasing rehabilitated groups of immune animals into the wild will actually reduce the spread of the deadly virus.

Fear of contaminating our environment with oseltamivir phosphate is also unfounded. oseltamivir phosphate completely leaves the body after 12 hours of dosing. As long as animals are not released within 12 hours of treatment, (which is unlikely as they are still recovering) they cannot contaminate the outside environment with oseltamivir phosphate. This fear is much more likely to happen with humans on oseltamivir phosphate using our water system to eliminate rather than animals receiving treatment in wildlife facilities.

Opposition within the wildlife rehabilitation profession is uninformed of the way this drug works in animals, and has yet to contact Dr. Broadhurst (a pathologist and THE leading specialist on oseltamivir phosphate use in animals) to obtain details of its effect and outcome.

oseltamivir phosphate is also very helpful with bacterial problems in squirrels, skunks and even scours in fawns. Since oseltamivir phosphate is safe to use, the same dosage can be tried when experiencing an obvious virus outbreak in small mammals. Typical symptoms are lack of appetite, lethargy, diarrhea in some cases. ONLY certain diseases will respond to oseltamivir phosphate, and most bacterial problems. If this is the case, you will see a marked improvement after one or two doses. If not, you need to seek a diagnosis and appropriate treatment.

oseltamivir phosphate DOES NOT KILL BACTERIA or assist in parasitic infestations! It is an inhibitor, not an antibiotic. If you have a bacterial issue in your animal, you make need an appropriate antibiotic to assist with treatment. In early diagnosis in a case that oseltamivir phosphate is effective, the body's own immune system will respond and clean up bacteria before it becomes pathogenic. Exposed animals can be treated and recover without ever showing symptoms. At my facility, in exposed cages, as soon as appetites are affected, we begin treatment and the outbreak is completely stopped. Prevention dose is once every 24 hours unless symptoms begin, then every 12 hours for 5 days.

In fawns, 1 cc daily for 3 days will often stop scours without need of other therapy. If after the first dose you do not see improvement, continue the 3 day dosage, but use your probiotics and fluid therapy as well. A target condition will almost completely clear up after 1 dose, but requires the additional 2 doses not to return.

Records of case studies need reported for the gathering of clinical data. A simple description of symptoms, treatment and outcome can be emailed along with any clinical diagnostic information, and will be forwarded to Dr. Broadhurst.

I will forward all case information to Dr. Broadhurst and answer any treatment questions you may have. He has worked very hard to make this treatment available to wildlife rehabilitators, and has spent countless hours counseling and instructing them on its use. Today, only a handful of wildlife rehabilitators in the Country are still reporting results in wildlife, even thought this treatment is being widely used because I hear about it continuously. I would like to save Dr. Broadhurst continued aggravation teaching this treatment without the benefit of receiving case reports. I am going to advise on treatment in wildlife in any way I can and then follow up to obtain results. Anything I am not trained to assist with will be forwarded to Dr. Broadhurst.

I am working under the constant supervision and instruction of my wildlife veterinarian who has been enrolled in Dr. Broadhursts clinical trial since it's inception. I do not claim to have any formal training in virology and veterinary medicine, however, I have personally treated and saved hundreds of animals from formerly deadly viruses with oseltamivir phosphate in my rehabilitation facility and have Dr. Broadhursts confidence to advise of its use in wildlife.

Thank you,
Annette King Tucker
Wild Heart Ranch Wildlife Rescue
A 501(c)(3) Non Profit Association
Rogers County Oklahoma
www.wildheartranch.org
wheartrnch@aol.com

My own excerpts from an email advising a new oseltamivir phosphate user for wildlife rehab:

Have your vet prescribe a script of 10 of the 75 mg capsules of oseltamivir phosphate. (about $13 per pill..worth every penny!) You will suspend one capsule into 10 ccs of water. (7.5 mg per ml) You will dose at 1 cc per 10 lbs, no less than .2 cc for any small animal under 2 lbs. Refrigerate, shake well before dosing, discard suspension after 30 days.

It has a bitter taste. I always use it with amoxicillin. One reason for bacteria, and two, if they vomit, its pink. (use white bedding for one you suspect is vomiting..helps) I pull up the amoxicillin, then the oseltamivir phosphate, then I pull up an equal amount of pancake syrup (generic). The sugar helps them with lethargyy and the syrup kills the bitter taste. If you have a vomiter, you can give oseltamivir phosphate rectally (alone) and I double the dose. If you have an animal that does not respond after the first dose, double the dose during treatment.

You will dose EVERY 12 HOURS WITHOUT FAIL for 5 days. You CANNOT be late on a dose. Better to be early and overdose. You can also adjust your dosing schedule this way to be more convenient. There are no drug interactions with oseltamivir phosphate and no effects from over dosing. oseltamivir phosphate leaves the body in 12 hours and the virus immediately begins to replicate. As long as the oseltamivir phosphate is in the body, pathogenic bacteria (what kills our animals in parvo) cannot replicate. Its stops the process that kills the animal while the virus runs its course safely. The animal is still full blown parvo (or distemper) and is contagious. They are naturally immune after recovery. DO NOT VACCINATE or release for 30 days after treatment is completely. Treat everything else as you would with a virus, decontamination, negative air flow, etc, even though you may have a completely normal animal, eating and drinking, playing etc, after the first dose. If you vaccinate wildlife, your vaccines may render oseltamivir phosphate useless if the vaccine causes the outbreak. Many people who battle parvo have learned not to vaccinate anything until everyone has had parvo and recovered. They cannot get it again, ever. In early parvo cases, you wont need anything but the oseltamivir phosphate. In severe cases, sub q fluids, heat, sugar, and we also sometimes use traditional supportive treatments along with the oseltamivir phosphate.

Distemper is not as easy as parvo. You need to continue with all the usual treatments (I use oral clavamox, traditional supportive therapy and treatments including sub q fluids and sugar, babies on heat, etc) and you may have to stay on the oseltamivir phosphate for a few weeks in a severe case. You will notice all your symptoms will disappear in the first few days except for the neurological. Those will improve slowly. If there are seizures, dont continue. You will stop the virus, but your animal will have brain damage if they survive the seizures.

If you take in fawns, this treatment will change your life!! Scours are treated with a half cc once daily for 3 days in a newborn, and 1 cc daily for 3 days in a juvenile. I still do the probiotics with it, but you dont have too. It stops the scours. You will notice your fawn may not have a bowel movement after the first dose, and wont for a few days. THAT IS NORMAL. The next bowel might be pellets. You will fall over in shock!

Does the same thing for diarrhea in anything. Because there are no side effects and oseltamivir phosphate is safe, we no longer have to know what we are treating to treat it in wildlife rehab. If there is a bacterial problem in the mucous membranes of the body (any of them) oseltamivir phosphate will help, if not fix it, and if it doesn't, you most likely have something non bacterial, like a parasite or micro organism.