Dear Committee Members,

I want to applaud the FDA concerning the action they have taken to protect the public by the with-drawl of Proheart 6.

The adverse reactions that I have witnessed fall into three categories; Neuro-toxicity manifesting in the form of seizures, pulmonary symptoms including massive pulmonary thromboembolisms, and allergic reactions including hemorrhagic gastroenteritis and frequently progressing to disseminated intravascular coagulation.

I pose that the following questions need to be answered before this drug can be returned to the market.

1. Are these problems due to an inherent problem with the drug moxidectin, instability of the microspheres, allergy to the micorpsphere coating, or are they due to mis-handleding of the drug by Veterinarians or some of both?

2. If Proheart 6 is injected thru too small of a gauge needle, or if the bottle of reconstituted drug is shaken vigorously after several nights of refrigeration could this cause disruption of the microspheres? Could disruption of the micropspheres cause pre-mature release of the moxidectin, moxidectin overdose, and result in seizures? Or could this be a manufacturing problem?

3. We know moxidectin is a more potent filaracide than ivermectin or milbemycim. In a letter I have from Dr Toni Triego whose patient died from an adverse reaction to proheart 6, she states that Dr La Roch at Ft Dodge told her they knew Proheart 6 could kill L4 larvae. Does the death of L4, newly emerged young adult larvae and possibly migrating intestinal worm larvae, all of which cannot be detected by available testing methods, pose a fatal risk to our patients? How can this risk be avoided?

4. How does proheart 6 cause hemorrhagic gastroenteritis? Is this due to death of migrating larvae or is this a manifestation of an allergic reaction?

5. Are dogs allergic to the microsphere coating? Is the number of dogs allergic to this drug excessive necessitating withdrawal? Why do these anaphylactic reactions this result in DIC?

6. If microspheres are injected into a dog do some of them inter the circulation? What is the impact of circulating microspheres on the kidneys and lungs? Studies have shown microspheres can cause pulmonary hypertention in some species.

I have a suggestion which could increase product safety. Unit dosing would help to prevent many of the mis-handling and storage errors. This has been widely mandated for human drugs.

I want to express dismay at the method in which Ft Dodge marketed this product. Please help me to understand why a company would choose a person whose presentations use so much profanity? Dr Whitford is not a Board certified cardiologist, parasitologist or pharmacologist. He has nothing to qualify him to educate DVMs on the use of a drug. In his presentation he focused on one point. Veterinarians will go broke due to competition form Pet Med Express if they do not switch their clients to this product. He repeatedly said that none of the Adverse Drug experiences reported to the DFDA were due to Proheart 6. He stated that all allergic reactions could be treated with benadryl. Since when is benadryl the standard of care for DIC? In my humble opinion Ft Dodge is responsible for the mi-handling of this drug by Veterinarians and the deaths of pets that have resulted because they failed to warn Veterinarians about the side effects, they failed to adequately inform DVMs on the proper handling of the drug, the consequences of not following label directions, and how to diagnose or treat adverse reactions. This lack of responsibility is not in the best interest of Ft Dodge, it is not in the best interest of our patients, and it is not in the best interest of the Veterinary profession.

I made several calls to Ft Dodge about adverse reactions to Proheart 6. I was told by a Veterinarian in research and development that marketing has a larger budget than research and development and that the marketing does not ask questions of or even talk to research and development. When I called to report an adverse reaction, I was told that FDA ADEs are not filtered. That if a dog was hit by a car the day after an injection of Proheart 6 it would be recorded as an adverse reaction. In looking at the ADEs reported I don’t see and "hit by cars" or any adverse reaction reports that are lacking in common sense.

There is nothing urgent about the need to return Proheart 6 to the market. We have several heartworm preventatives available with excellent safety records. Our primary doctrine is “Above all, do no harm.” I hope the FDA will take time to insure that the safety of our patients is insured.

Sincerely,

Dr Bob Rogers