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