U.S. Food and Drug Administration
FDA Consumer magazine
November-December 2000
Table of Contents

Prescriptions for Healthier Animals: Pets and People Frequently Fight Disease with Similar Drugs

by Linda Bren

Tina and Baron have both seen better days. Tina Gilliam, of Gaithersburg, Md., slowly gets out of bed in the morning and carefully pulls on her socks to avoid the pain she feels when she tries to move too fast. Her golden retriever, Baron, also lifts himself slowly from the floor next to her bed. As he limps after her to the medicine cabinet, his gait is much like hers--slow, stiff and deliberate--for like Gilliam, Baron suffers from arthritis.

Gilliam shakes a pill out of a bottle, and swallows it with a few sips of water. She shakes another pill out of a different bottle, pops it into Baron's mouth, and massages his throat while he swallows it. Soon, the pain and stiffness for both will lessen, and the two companions will go out for their morning walk.

Gilliam has just taken Lodine, and Baron has taken EtoGesic. The pills are different sizes, shapes, and colors. But if Gilliam were to check the label on each, she would find the same active ingredient: etodolac.

Gilliam and Baron are part of an increasingly common phenomenon in which humans and animals often take similar drugs for similar diseases.

Admittedly, the animal drug's active ingredient may be in a concentration different from that found in the human drug. The animal drug might even have different inactive ingredients. But that drug can alleviate the same pain, eliminate the same symptoms, and cure the same illness in pets as its counterpart can in people.

Veterinarians have been prescribing approved animal drugs that are similar to human drugs for years. And, since the passing of the Animal Medicinal Drug Use Clarification Act of 1994 (AMDUCA), it has been legal for vets to treat pets with human drugs that have not been approved for animals. Veterinarians also prescribe drugs not approved for humans, such as flea control medications.

Veterinary science is working doggedly to keep up with the expectations of pet owners, who represent the majority of Americans. More than 37 percent of American households own dogs, 34 percent own cats, and 16 percent own both, according to consumer marketing firm NPD Group Inc.

These guardians of 58 million dogs and 72 million cats want first-rate treatment for their four-legged friends. "As people are seeing more complex and sophisticated drugs for themselves, they want that same quality for their pets," says Melanie Berson, DVM, director of the Division of Therapeutic Drugs for Non-Food Animals within the Food and Drug Administration's Center for Veterinary Medicine (CVM).

Recognizing this need, animal pharmaceutical companies continue to submit applications to CVM, the organization within FDA that approves drugs designed for animals. The applications fall into three drug categories: an existing animal drug to be used for a different illness, an existing animal drug to be used for a different type of animal, and an entirely new animal drug.

Drugs Approved for Animals

Nearly 300 drugs currently on the market have been approved by FDA for dogs, cats, and horses--otherwise known as companion animals. Many of these have the same active ingredient found in their human drug counterparts.

Drugs for animals are given new trade names to distinguish them from the human drugs, and different companies may manufacture them. GastroGard, for example, used to treat stomach ulcers in horses, has the same active ingredient as Prilosec, used to treat severe and persistent heartburn in people. GastroGard is made by Merial Limited in London, while Prilosec is a product of AstraZeneca PLC, also in London.

"The approval process for a new companion animal drug is similar to the approval of a new human drug," says Berson. "The major difference is that the size of the clinical trials for animal drugs is many times smaller." A human clinical trial typically involves thousands of test subjects, but an animal trial involves only hundreds, according to Berson.

Despite their smaller clinical trials, pet drugs must meet standards similar to those for human drugs. And pet drug manufacturers "must apply the same rigorous scientific standards to studies and the manufacturing processes must be in accordance with Good Manufacturing Practices," says Ann Stohlman, VMD, a veterinary medical officer at CVM.

Drugs Used But Not Approved for Animals

The practice of giving animals drugs that have been approved for humans but not for animals is known as prescribing "off-label," or "extralabel." Extralabel use can also mean prescribing a drug to a different species, for a different condition, or in a different dosage than that for which the drug was approved. For example, a veterinarian may prescribe a lower dose of an arthritis drug approved for dogs to a feline with an inflamed joint.

FDA restricts extralabel use of human drugs in food-producing animals. This precaution is taken to prevent drug residues in animals from entering the human food chain and threatening public health. But extralabel use of human drugs in companion animals is not as restricted.

While these human drugs have been tested in some animals before being tested in humans, they have not gone through the comprehensive studies FDA requires to approve them for use in animals. And drug manufacturers cannot advertise to veterinarians or pet owners a drug that has not been approved for animals.

Even so, it is a long-standing veterinary practice to treat pets with the latest human drugs. "In vet medicine we've relied on human drugs for years," says Michael Bassett, DVM, owner and medical director of Pet Dominion Animal Hospital in Rockville, Md. "They don't develop new drugs for animals fast enough."

Veterinarian Daniel Negola tries to rely on the animal drugs when possible. "We use the drugs approved for animals first," says the owner of Negola's Ark Veterinary Hospital in Gaithersburg, Md. "Only when they're not working or if they're not available for a specific problem do we go to the next source--human drugs."

How do vets know how much of a human drug to prescribe to an animal when it is not approved for animal use? The veterinary research community shares study results through published papers, seminars, and books, says Neal Bataller, a veterinarian in CVM's Office of Surveillance and Compliance. Formulations found to be effective are documented in numerous veterinary drug handbooks and textbooks.

The handbooks provide such information as the drug's indications and usage, contraindications, dosage, precautions, and adverse reactions. There are also veterinary handbooks and texts that explain what drugs to use to treat other pets --such as lizards, rabbits, and birds--for which specific FDA approvals do not exist, adds Bataller.

Informed Consent

Much as they do in managing their own health-care, people need to weigh the benefits and risks of a drug prescribed for their pet. It's the veterinarian's responsibility to explain the risks and benefits of each drug to clients, and give them printed information, particularly for the drugs that aren't approved for animal use, says Karen Overall, VMD, Ph.D., professor of behavioral medicine and director of the small animal behavior clinic at the Veterinary School of the University of Pennsylvania. "It's important that we have the informed consent of our clients."

Pet owners should ask their vet questions about any drug being prescribed for their animal--especially in the absence of printed information. Although manufacturers provide a label, or printed information, with each drug they give to veterinarians, says Bataller, "in repackaging the drug at a veterinary facility, the label often does not get passed on to clients. And if the drug is prescribed extralabel, the label would be of limited value to the pet owner."

FDA has helped two animal pharmaceutical companies develop consumer-friendly labels that explain the benefits and risks of their osteoarthritis drugs for dogs. Fort Dodge Animal Health of Overland Park, Kan., distributes a "client information sheet" with EtoGesic (the generic drug etodolac). Pfizer Animal Health, Inc., of Exton, Pa., gives out a client information sheet with Rimadyl (carprofen). Both drugs are non-steroidal anti-inflammatory drugs (NSAIDs).

Pfizer provided the Rimadyl information at CVM's request following a high volume of adverse events, including deaths, reported by owners whose dogs were treated with the drug. The angry owners, who were not properly informed of the drug's risk, prompted the new labeling that will better help other pet owners decide if the drug is appropriate for their dogs.

Although pet owners are becoming better educated and informed about animal treatments, it is still unwise for them to medicate their animals without veterinary supervision, warns Bataller. "Different species metabolize drugs differently. A dog is not a small human, and a cat is not a small dog," he says. "Some drugs may be better tolerated in a dog than in a human, while other drugs may have the reverse effect. Dogs are generally more sensitive to aspirin than humans, and Tylenol (acetaminophen) can readily kill a cat."

A Brave New Behavioral Frontier

"Behavior is an emerging area of vet medicine," notes CVM's Berson, and "improving the quality of life for geriatric pets" is an area of strong veterinary and public interest.

In 1999, the veterinary community and pet owners celebrated the introduction of the first FDA-approved drugs for behavioral conditions in pets: Clomicalm to treat separation anxiety in dogs, and Anipryl to treat the symptoms of canine cognitive dysfunction syndrome (CDS).

Anipryl has the same active ingredient as Eldepryl (selegiline hydrochloride), which FDA approved in 1989 to treat Parkinson's disease in humans.

Clomicalm has the same active ingredient as the human anti-depressant Anafranil (clomipramine hydrochloride), which was approved by FDA in 1989 to treat obsessive-compulsive disorders in humans.

Aging Dogs and Cognitive Decline

FDA first approved Pfizer's Anipryl in 1997 to treat canine Cushing's disease, a common endocrine disorder, and in 1999 approved it to treat canine CDS. This age-related decline of cognitive ability can cause a dog to become disoriented, appear confused or lost in the house or yard, be unresponsive to familiar people, forget previous learned behavior (such as housetraining), bark and whine more, and change its sleep-wake cycle.

"Anipryl really made a difference in my dog's life," says Bobbi Mallace of northern California. Mallace's lively little 10-pound dog, dubbed Miss Piggy because of her pudginess, had a sudden onset of confusion at age 15. "She didn't know what to do with her food," says Mallace, "and she would go under a table and couldn't figure how to get out." After starting on Anipryl, Miss Piggy improved in just three to four days, according to Mallace. "She knew where her food was and how to eat it again. It seemed to clear her head."

Although Mallace was warned by her veterinarian that Anipryl doesn't work in all cases, she calls it a "miracle drug" because it brought her dog's quality of life "almost back to normal."

"[Anipryl] can work a miracle in about one-third of cases, says Nicholas Dodman, BVMS. "It can be useful in about one-third, and it doesn't work in one-third," adds the professor and director of the Behavior Clinic at Tufts University School of Veterinary Medicine.

Some researchers liken the brain of an older animal with CDS to that of an older human. A loss of neurotransmitters has been found in both. And amyloid plaques, or lesions, similar to those that cause damage in the geriatric human brain, have been found in the brains of older dogs and cats. Animal behaviorist Overall says that Anipryl "won't fix the existing plaques, but it will improve the effectiveness of the neurons wrapped up in plaque."

As in diagnosing age-related cognitive decline in people, CDS in dogs should not be diagnosed until all other medical problems have been ruled out. Anipryl cannot cure CDS, but it can alleviate the symptoms and enhance the pet's quality of life.

Distressed Dogs and Separation Anxiety

The only other FDA-approved drug for animal behavioral problems currently on the market is Clomicalm, manufactured by Novartis Animal Health US, Inc., of Greensboro, N.C. Clomicalm is to be used as part of a behavior modification program to treat separation anxiety in dogs older than six months.

Although not a tranquilizer, Clomicalm can lessen anxiety by increasing the serotonin levels in the brain. Increased serotonin can make a dog more receptive to positive behavior modification and less likely to overreact to an owner's absence.

While few dogs are happy when their owners leave, some show extreme anxiety, resulting in destructive behavior, soiling the house, excessive salivation, or constant barking and whining. In severe cases, dogs mutilate themselves, eat furniture, jump through windows, or claw through walls.

"If your dog is tunneling through your wall, that dog is going to be dead soon," says Overall, who sees many rescued dogs with separation anxiety in her clinic. She attributes these cases in part to the "pet recycling" process. "Cute animals get adopted, they go home, they don't behave as expected so they go back, get readopted, and go home again. As they get recycled, separation anxiety increases."

Overall cautions owners that they cannot simply pop a pill in their pet's mouth and expect to come home to a perfectly calm dog and intact house. Treating a dog for separation anxiety requires hard work on the part of the whole family to modify the pet's behavior. "I know everybody wants magic from science, but I try to get across to my clients that you're not going to solve anything with just a pill," says Overall. "The people who work the hardest get the biggest change--regardless of the severity of the condition."

Whitley, a mixed terrier-poodle, is a testimony to the success of behavior modification combined with medication. The 10-year-old dog, known for her spirited but sweet disposition, suddenly became anxious and destructive after her owner left for work. "She chewed up clothes, doors, furniture, and electrical cabling--to the point where her gums were bleeding," says owner Mark Oumedian of Livonia, Mich.

Under the supervision of his veterinarian, Oumedian put Whitley on Clomicalm. At the same time, he practiced behavior modification techniques--exercises to help learn positive behaviors--with Whitley. But Whitley went through an entire bottle of Clomicalm with no effect. Oumedian's initial discouragement turned to delight when halfway through the second bottle--about 45 days after the dog began taking the drug--Whitley started to show results. Soon after, he became a happy, well-adjusted pooch once again.

And Oumedian was relieved that his spunky dog's character remained unchanged. "It was so amazing to me that there were no personality changes or side effects," he said. "It would have broken my heart if there were."

Animal behaviorist Dodman emphasizes the grim consequences of behavior problems. "Behavior problems are probably the leading cause of mortality in the canine population," he says. "It's estimated that at least one-and-a-half million dogs are needlessly euthanatized each year because of behavior problems, which is three times as many as die of cancer."

Some veterinarians predict that the use of drugs for behavioral problems will result in a decrease in the number of animals euthanized or relinquished to shelters. "Oftentimes, success in treating a behavioral problem like separation anxiety can mean the difference between having to put an animal to sleep or being able to live with the pet," says Stephen Sundlof, DVM, director of FDA's CVM . "Having drugs like this available can really make a tremendous difference."

New psychotropic drugs to treat animal behavioral problems and geriatric conditions may be just ahead. Meanwhile, pets can continue to have the best of both worlds--a host of human and animal drugs to treat their ailments and keep them healthy and active for many years.

Linda Bren is a staff writer for FDA Consumer.

Vet Medicine Promotes Progress in Human Medicine

While advances in human medicine can mean new drugs to treat pets, veterinary medical advances can also benefit humans. The creation of a blood substitute is an example of this potential. Scientists have been searching for an effective oxygen-carrying blood substitute for more than 50 years.

In 1998, FDA approved Oxyglobin, the first blood substitute to reach the market, for the treatment of anemia in dogs. Anemia, a deficiency of red blood cells or the protein hemoglobin within red blood cells, kills millions of dogs each year. Treatment for canine anemia is difficult because of the lack of donated dog blood, the resources required to refrigerate the blood for storage and warm it prior to use, and the need to use it within its 35-day shelf life. Also, typing and cross-matching must be done to accommodate the eight blood types of dogs.

Oxyglobin is the first alternative solution to donated blood. A chemically modified bovine hemoglobin solution, Oxyglobin picks up oxygen in the lungs and carries it to cells throughout the body. "The product quickly delivers oxygen into tissue and organs and buys time for the dog's own regenerative red blood cells to come back," says Robert Murtaugh, DVM, principal investigator for the canine clinical trials at Tufts University School of Veterinary Medicine.

Biopure Corp., the manufacturer of Oxyglobin, along with Tufts University, is testing a similar blood substitute, Hemopure, for humans as a treatment for sickle cell anemia and as a replacement for donated blood during surgery. Unlike stored blood, Hemopure requires no refrigeration, is compatible with all blood types, and has minimal potential to transmit viruses or bacteria.

FDA's Center for Biologics and Evaluation (CBER) is currently evaluating this human blood substitute to determine its safety and effectiveness. "Hemopure is subjected to a higher level of scrutiny," says Abdu Alayash, Ph.D., a research chemist in CBER, "particularly in light of recent clinical failures with other hemoglobin-based products intended for human use."

The implications of a human blood substitute are significant: Emergency medical personnel can carry out transfusions in the field, for example at the site of an accident or in a war zone, without the worry of blood-typing, cross-matching, or transmitting infectious diseases.

L.B.

Drugs That Do Double Duty

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