Dec. 20, 2002 THE FOOD & DRUG LETTER Issue No. 666 Dec. 20, 2002 CLARITIN APPROVAL MARKS SIGNIFICANT SHIFT IN RX-TO-OTC SWITCHES
The switch of Schering-Plough’s Claritin to over-the-counter (OTC) status set new precedents whose
implications will reach far beyond drugstore shelves and affect the pharmaceutical industry for years.
FDA’s Nov. 27 approval of OTC Claritin, the non-sedating antihistamine (loratadine) culminated an
extraordinary odyssey through the regulatory system. The small tablet is at the confluence of powerful interests– drug companies, regulators, payers and consumers.
Previously one of the nation’s top-selling prescription drugs, Claritin is the latest in a number of prescrip-
tion drugs that have switched to OTC status (see “Rx Drugs Switched to OTC,” Page 3). Some industryobservers have forecast a rising tide of Rx-to-OTC switches, and indeed a slew of drugs are reportedlywaiting in the wings to seek OTC status (see “Rx-to-OTC Switch Candidates,” Page 3).
Switching a product from prescription to OTC involves critical decisions for drug makers. A properly
executed Rx-to-OTC switch can maximize a company’s revenue from a drug, and may provide an additionalbonus of exclusivity. But the transition to OTC is also fraught with risks and may not always be in the bestinterests of pharmaceutical companies or patients, experts say. Opening Of OTC Floodgates Uncertain
Whether the OTC approval of Claritin heralds an opening of the floodgates remains to be seen. What’s
clear is that the rules of the game are changing. In this issue, The Food & Drug Letter explores some of thelessons gleaned from the Claritin switch and examines key issues facing drug makers eyeing switches.
Claritin has been a success since its approval as a prescription-only drug in April 1993. One of the first
of a new generation of antihistamines, Claritin is less likely to cause drowsiness than traditional antihista-mines based on diphenhydramine. Its safety profile offers important benefits for the 10 percent to 30 percentof adult Americans who suffer from seasonal allergy symptoms. Claritin generated $3.1 billion in salesannually for Schering-Plough. That figure represented almost one-third of the company’s revenue.
Other second-generation antihistamines include Aventis’ Allegra (fexofenadine) and Pfizer’s Zyrtec (certirizine).
On July 22, 1998, Wellpoint Health Networks petitioned the FDA to
EDITOR’S NOTE: The
switch Claritin, Zyrtec and Allegra from prescription to OTC status. Formed
in 1992 by Blue Cross of California’s managed care business, Wellpoint is
not be published Jan. 2. Thenext issue will be Jan. 8.
(SeeOTC SWITCH, Page 2) THE FOOD & DRUG LETTER Dec. 20, 2002 OTC SWITCH, fromPage 1
without the consent of the drug company sponsor?
one of the nation’s largest health insurers, provid-
The definitive answer, according to some of the
ing benefits for more than 40 million members.
nation’s top experts surveyed by The Food & DrugLetter: Maybe.
In its petition, Wellpoint argued that the
second-generation antihistamines were safer and
more effective than antihistamines currently soldOTC, and therefore do not meet the criteria for
prescription status. The insurer said that consumers
(FDCA), a drug is presumed available OTC unless
want easy access to affordable healthcare and
it has toxic effects, requires a doctor’s supervision,
would prefer to use less expensive medications
or there is some other compelling reason to protect
that don’t require an office visit for a prescription.
the public health. For a drug to be sold OTC, apatient must be able to safely diagnose his or her
condition, understand the drug regimen and use the
Claritin or a generic, is in the best interest of
drug appropriately without professional guidance.
allergy sufferers nationwide,” said Robert
Also, the drug itself must not have any significant
Seidman, Wellpoint’s chief pharmacy officer. “It
lowers the cost and eases access. Any memberwho feels they need to consult with a physician can
There are three ways that a prescription drug
consult today just like they did yesterday.”
Wellpoint’s interests also include financial
The FDA can remove prescription restrictions
considerations. The OTC switch of the third-
if it determines they are not necessary to
generation antihistamines is expected to save the
protect public health and if it deems the drug
company about $90 million – $45 million from
safe and effective for self-medication.
prescription costs and $45 million for copays.
Any “interested person” – usually a drugsponsor – can file a supplemental new drug
“Our responsibility, whether to an employer
application (NDA) for an approved prescrip-
group or an individual subscriber, is to provide
broad access to pharmaceuticals in an affordable
Any interested person who wants an Rx-to-
manner,” said Seidman. “We’re going to take every
OTC switch can file a citizen petition asking
opportunity to encourage our members who have
the FDA to consider changing a drug’s status.
chronic diseases to stay on their meds, to thinkabout gold standard generic drugs, and we’re going
Wellpoint’s petition seeking the OTC switch
to foster conversion of safe and effective drugs
for Claritin, made under the third of the above
from prescription to OTC status. It’s a complicated
options, drew fire from Schering-Plough and other
but complete strategy to protect the affordability of
Wellpoint’s move took many in the pharma-
ceutical industry by surprise. Never before had a
Allergy Drugs Advisory Committees, which met
payer group asked that a class of drugs be
to consider the OTC switch of second-generation
designated OTC. When such a request is filed
antihistamines, Schering-Plough contended that
with FDA, it is typically from a drug company
switching Claritin to OTC would not be in the
that also provides scientific data to back up the
best interest of patients. Changing the prescrip-
claim that the product is safe for OTC use as
tion status of Claritin would force patients to
labeled – none of which Wellpoint submittedwith its petition.
(SeeOTC SWITCH, Page 4) Dec. 20, 2002 THE FOOD & DRUG LETTER Rx DRUGS SWITCHED TO OTC Rx-TO-OTC SWITCH CANDIDATES
Nasonex (mometasone furoate monohydrate) Schering-Plough
THE FOOD & DRUG LETTER Dec. 20, 2002 OTC SWITCH, fromPage 2
received. However, the FDA is unlikely to take suchdramatic unilateral action, agency officials said.
diagnose themselves, self-treat and pay theentire cost of their allergy medications.
“There is something in the law that if a drug
can be sold without a prescription, it should be,”
“We believe that prescription status of these
said David Hilfiker, project manager in the Drug
medications is necessary to protect and optimize
Center’s Division of Over-the-Counter Products.
public health,” Robert Spiegel, the company’s
“We traditionally haven’t put ourselves in the
chief medical officer, told the committees.
position to force a company to take a drug [OTC].”
Other drug company officials also tried to
Pharmaceutical Research and Manufacturers
poke holes in Wellpoint’s arguments. Francois
Nader, senior vice president for North American
Wellpoint petition and the strategy of switching by fiat.
medical and regulatory affairs at Aventis, said thatwhile Wellpoint described sedating antihistamines
“We believe that’s inappropriate,” said spokes-
as “dangerous,” the insurer’s own formulary
man Jeff Trewhitt. “FDA should take a drug over the
reserved the second-generation antihistamines for
counter only in active collaboration with the sponsor-
patients “who have failed or are unable to tolerate
ing company. It’s the company that took this through
the 12-15-year drug approval process, generating anNDA with as many as 100,000 pages of scientific
Schering-Plough and Aventis also argued that
data. They truly know the medicine best.”
improper use of OTC second-generation antihista-mines could lead to health problems by masking
If Wellpoint succeeds, observers have forecast
serious illness, since sniffling and sneezing could
a flood of citizen petitions requesting OTC switch-
be symptoms of asthma or other conditions. Among
ing for a range of drugs, including those for asthma,
others that opposed the switch was the National
diabetes, osteoporosis, oral herpes infection and
Consumers League, which contended that the OTC
switch would eliminate an entire class ofnonsedating antihistamines. Making the drugs OTC
Wellpoint has no plans to target any other
would reduce consumers’ choice to self-medica-
drugs. “There aren’t any other easy home-run hits,”
tion with less expensive sedating drugs, putting
them in danger of accidents. Others against theswitch were:
However, the insurer has asked that Schering-
Plough’s therapeutic follow-up to Claritin, Clarinex
! The American Academy of Asthma, Allergy
(desloratadine), also be switched to OTC status.
! The American Academy of Otolaryngic Allergy
Battles Against Generics
! The patient advocacy group Asthma Network/
Claritin, whose patent expired Dec. 19. A growing
By a vote of 19 to 4, the committee over-
list of competitors announced plans to launch
generic versions of loratadine, and the new
Allegra, Claritin and Zyrtec. More than a year
Clarinex was meant to lay claim to the market
later, the FDA, which usually follows the recom-
mendations of its advisory committees, still has notissued a decision on the Wellpoint petition.
But the Clarinex launch was delayed by an FDA
investigation into Schering-Plough’s manufacturing
In theory, the agency could grant Wellpoint’s
petition based on safety and efficacy data already
(SeeOTC SWITCH, Page 5) Dec. 20, 2002 THE FOOD & DRUG LETTER OTC SWITCH, fromPage 4
mine market. The absence of drowsiness andcholinergic effects are powerful selling points that
practices, leaving the door open for generic competi-
experts have said will give diphenhydramine-
tors to win over Claritin users before the brand maker
based antihistamines a run for their money.
could convert them to Clarinex, which was finallyapproved in February 2002.
OTC Claritin enjoyed a full 10 days of market
exclusivity after its introduction Dec. 10 before
Potential generic competitors got a jump on
generic competitors hit the market. Wyeth received
Claritin several years before its patent expiration.
tentative approval for the ANDA on its version of
Geneva filed an abbreviated new drug application
loratadine, which will be sold as Alavert and
could hit the shelves by the end of December.
Schering’s patents were unenforceable. Four othergeneric manufacturers submitted ANDAs for
Wyeth also plans to launch its version of
loratadine in 1999, three in 2000 and five the follow-
Claritin-D (loratadine/pseudoephedrine sul-
ing year, including McNeil Consumer Health Care. In
fate) in 12-hour and 24-hour formulations in
2001, Whitehall-Robbins, now Wyeth, filed an
early 2003. Novartis also has a loratadine
ANDA for its version of loratadine, also contending
version waiting in the wings and generic maker
Schering’s patents were invalid and unenforceable.
Andrx is considering selling the drug in theprivate label market.
By mid-2002, Schering-Plough had launched
15 lawsuits against generic companies to defend its
Competitive Market Expected
loratadine patents, and lost key rounds in court.
Clarinex gave Schering-Plough a foothold in
market will be flooded with loratadine products
both the OTC and prescription markets for second-
starting in early 2003. Competition from generic
generation antihistamines. “The approval of
versions of loratadine is expected to drive the
Clarinex provided us with the opportunity to move
price from the prescription rate of more than $2
Claritin to the OTC category while still maintain-
per pill down to about $1 per pill, comparable
ing a presence in the prescription field,” said
to currently available OTC antihistamines.
company spokesman William O’Donnell.
Health insurers are expected to drop coverage
Faced with a losing battle, Schering-Plough
for second-generation OTC antihistamines.
capitulated and filed its own supplemental NDA
Wellpoint already has. Aetna, the nation’s second-
to switch Claritin to OTC March 8, 2002. After
largest health insurer, said it will no longer cover
contending that OTC Claritin posed a risk to the
Allegra, Claritin or Zyrtec unless a doctor makes a
public health before the FDA’s advisory commit-
special request. Several other insurers have
tees the previous year, the company switched
gears and made the case that the drug was safe touse OTC when directed by the label.
According to industry sources, health plans
intend to encourage a trial of OTC loratadine by
The FDA approved all five formulations of
making sure patients’ out-of-pocket copayment for
Claritin for OTC sale for allergic rhinitis. Based on
Rx versions plus the physician office copay is not
additional data provided by the company, FDA
appreciably less than the amount they pay for OTC
subsequently approved Claritin for the OTC treatment
of chronic idiopathic urticaria. However, Schering isfar from alone in the market for OTC antihistamines.
Other drug companies also are closely watch-
ing the Wellpoint petition as they maneuver the Rx-
Industry observers expect the introduction of
OTC loratadine to shake up the consumer antihista-
(SeeOTC SWITCH, Page 6) THE FOOD & DRUG LETTER Dec. 20, 2002 OTC SWITCH, fromPage 5
would be the only OTC drug available at prescrip-tion strength for the prevention of heartburn.
to-OTC switch for their products. One drug in asituation similar to Claritin is AstraZeneca’s
Several companies are champing at the bit to get
Prilosec (omeprazole), one of a new generation of
OTC approval for cholesterol-lowering statin drugs,
proton pump inhibitors that treat gastroesophageal
a huge potential market. In July 2000, an FDA advi-
reflux and ulcers. Prilosec’s move to OTC will
sory committee rejected OTC switch applications for
follow a similar shift for the earlier generation of
Merck’s Mevacor (lovastatin) and Bristol-Myers
H2 blockers that switched to OTC status in the
Squibb’s Pravachol (pravastatin). The committee
mid-1990s, including Tagamet (cimetidine) and
asked for the firms to provide more studies to demon-
strate the public’s ability to self-diagnose the need forstatin therapy, and to show that consumers can use the
world for several years, Prilosec is key toAstraZeneca’s financial health. It generated $3.7
Merck is reportedly ready to try for approval
billion in worldwide sales for the company, or
again, and has formed a joint venture with Johnson
nearly 35 percent of AstraZeneca’s revenues
& Johnson for the OTC switch of Mevacor.
from continuing operations. AstraZeneca foundits patents challenged by generic-drug compa-
One of the stumbling blocks to the OTC approval
nies in theU.S. and Europe. Despite winning
of statin drugs is the need to monitor serum choles-
U.S. court challenges, five companies pounced
terol and lipid levels, which involves office visits for
with generic versions in the United Kingdom
blood tests. Among the solutions being bandied about
after a court overturned its omeprazole patent.
is for pharmacists to become more involved inmonitoring drug treatment, taking a greater role in the
management of cholesterol-lowering and anticoagu-
AstraZeneca sold OTC rights to Prilosec to Johnson
lant therapy. Statins are among the candidates for a
& Johnson in 1997. Both companies have declined to
proposed third class of regulated drug, between
disclose the details of their arrangement.
prescription and OTC (see related story, Page 9).
The FDA approved the first generic form of
Dual Regulatory Status
omeprazole Nov. 4, giving the nod to an ANDAfrom KUDCO, the U.S. unit of Schwarz Pharma.
When a product goes OTC, the manufacturer
KUDCO, the only firm to emerge from litigation
typically discontinues its prescription counterpart.
with AstraZeneca with a valid patent for the drug,
There are cases in which it makes more sense for a
is marketing its version of omeprazole in agree-
prescription version to remain available in certain
ment with generic makers Genpharm and Andrx.
strengths or for certain indications. “Dual regula-tory status” refers to drugs with the same molecule
With the patent noose tightening, AstraZeneca
and the same brand name sold simultaneously in
filed a supplemental NDA for an OTC version of
Prilosec. A joint session of the FDA’s Nonpre-scription Drugs Advisory Committee and the
Prescription drugs may differ from their OTC
Gastroenterological Drugs Advisory Committee
versions in strength, dosing, indication, packaging
recommended the approval of OTC Prilosec June
or other factors. Typically, OTC drugs are sold at a
21. Johnson & Johnson received an “approvable”
lower dose than their prescription counterparts.
letter from the FDA Aug. 8, with a request for
Dual regulatory status was the strategy used for
products such as Imodium (loperamide) andPepcid (famotidine).
If fully approved, an OTC version of Prilosec
is expected to be on the market by mid-2003. It
(SeeOTC SWITCH, Page 7) Dec. 20, 2002 THE FOOD & DRUG LETTER OTC SWITCH, fromPage 6
patients can self-diagnose, according to saidregulatory strategist Thomas Blake, who has been
involved in the Rx-to-OTC switches of such
seeking dual regulatory status offers advantages and
products as Acutrim (phenylpropanolamine), Gyne-
disadvantages to drug companies. Dual regulatory
Lotrimin and Lotrimin AF (clotrimazole) and
status can extend patent protection and market exclu-
Nicorette (nicotine polacrilex). “Theoretically,
sivity while taking full advantage of brand recognition
most prescription drugs can be switched,” he said.
created by direct-to-consumer advertising.
In the case of antacids, companies are better
With dual status, however, companies risk spread-
served by avoiding an indication such as duode-
ing their resources too thin over different markets. “Do
nal ulcer or gastroesophageal reflux, which a
you want to be competing against both prescription and
patient is not able to recognize, and sticking to
OTC products?” asked Richard Tinsley of the pharma
easy-to-understand signs and symptoms such as
consulting firm Putnam and Associates.
heartburn. “You don’t really switch a drug, youswitch the labeling,” Blake said.
Thus, for financial as well as regulatory
reasons, industry experts advise that drug makers
should consider carefully whether it is worth it to
prescription restrictions on topical antifungals
for the treatment of vaginal yeast infection wasthat women may not be able to accurately
To Go OTC Or Not
diagnose their condition and may not recognizethe signs of other serious pelvic disease.
usually been on the prescription market for at
appropriate health care or mask the symptoms
least five years and have been taken by large
“There’s a certain amount of time we like to
infection drugs, we had concerns that using the
see prescription products on the market, to get a
drug would mask the symptoms of something
level of comfort with the safety reporting experi-
else,” said Blake. “We did a ton of research to
ence as a prescription product,” said the Drug
show that the itch of candidiasis is not dupli-
(SeeOTC SWITCH, Page 8)
The FDA considers a number of factors in an
Rx-to-OTC switch to determine whether consumers
Timetable for OTC Switches
can use a drug safely. The safety of a drug when usedin an OTC setting is a complex issue involving far
more than the toxicity of the compound itself.
“We look at whether the condition that the
product is intended to be used for can be perceived
by consumers, whether they recognize that they
indeed have that condition and no other,” Hilfiker
said. “We want to make sure there won’t be any
harm come to the consumer as a result of misdiag-
nosis of their condition or use of the product.”
The secret to a successful OTC switch is to make
the indications and labeling sufficiently clear so that
THE FOOD & DRUG LETTER Dec. 20, 2002 OTC SWITCH, fromPage 7
uct backed by the momentum of brand identity inthe OTC setting. There are cases, however, in
cated by the other vaginal infections, so the label
which a company chooses not to take the OTC
was geared toward that indication. And just to
route, for whatever reason. As the Wellpoint
be sure, we put on the label for the new OTC
case illustrates, other companies may find
drug that if you don’t see relief in three days, see
themselves in a situation similar to Pfizer,
The process of switching a drug to OTC can
Avoiding the Switch
take years, and should begin early in the product’slife cycle (see “Timetable for OTC Switches,”
According to industry experts, drug companies
Page 7). Preparations for the switch include label
can employ a number of strategies to delay or
comprehension studies in which subjects are tested
derail efforts to take product OTC against the
on their ability to read a product label and explain
their intent to follow specific label instructions. “You present the label to the consumer and ask
! Health care attorney Susan Burke suggests that
them questions about it,” explained Hilfiker. “You
drug makers develop their marketing efforts
refine the label until it’s something you’re confi-
with an eye towards OTC implications.
Pharmaceutical companies should review theirmarketing and advertising materials to make
An in-use study may be required to deter-
sure the health insurer’s position in favor of
mine consumer usage patterns, including compli-
self-diagnosis and self-medication is not
ance with dosage directions, concurrent use of
supported. Marketing materials should give a
OTC and prescription drugs, effectiveness and
prominent role to the doctor and reenforce the
the occurrence of rare side effects. In an in-use
importance of his diagnosis and care.
study, patients are presented with a drug andasked to determine whether it’s appropriate for
! Drug makers should foster contacts with physi-
them, then given the drug, sent home and told to
cian, medical and consumer groups that oppose
use it according to the label. “We look for use
OTC switches without the manufacturers’
patterns, whether consumers use it appropriately
consent. The more grassroots consumer support
or run into any problems when trying to follow
for keeping a prescription status, the less likely
the label instructions,” said Hilfiker.
the FDA is to buy the insurer’s claim that it iswidening consumers’ access to effective and
affordable drugs, according to Burke.
products to OTC, it’s important for them to appre-ciate the ethical, marketing and clinical challenges
! Firms can find a scientific issue that will
posed by the nonprescription market.
give the FDA pause, Blake suggests. “Dredge safety data that may show a differ-
“Bottom line, when you make a drug over
ent light on the product,” Blake said. This
the counter, you have to find ways to take the
place of the physician,” said Blake. “With
prescription drugs, you have the physician
nonsedating antihistamines. Aventis argued
buffer, so the drugs can be more toxic and have
monitoring built in. The challenge to the industry
unintended health and safety consequences,
is taking the place of the physician. That is a
still undergoing post-approval safety andeffectiveness trials and post-marketing
Taking a drug over the counter often makes
good sense, particularly for an innovative prod-
(SeeOTC SWITCH, Page 10) Dec. 20, 2002 THE FOOD & DRUG LETTER REGULATORS CONTINUE TO EYE
counter grew in the 1990s. The matter was ad-dressed again by a 1995 report by the General
POSSIBLE THIRD CLASS OF DRUGS
When the topic of switching drugs from prescrip-
tion to over-the-counter (OTC) comes up, the idea of
“Other countries’ experiences do not support a
creating a third class of FDA-regulated drugs be-
fundamental change in the drug distribution of the
tween prescription and OTC often accompanies it.
U. S., such as creating an intermediate class ofdrugs,” the GAO report said. “The evidence that
While the U.S. has traditionally used a two-
does exist tends to undermine the contention that
tiered system, a third class exists in many other
major benefits are being obtained in countries with
western nations, including Canada and Europe.
A third class for drugs “is certainly something
The prospect for a third class of drugs next arose
that has been talked about a lot at recent meetings,”
in 2000 during FDA public hearings on OTC
said David Hilfiker, advisory project manager in
switches. Proponents of a three-tier system argue that
the Drug Center’s Division of OTC Drug Products.
the third class could facilitate the OTC transition of
“The interest is to possibly creating new opportu-
drugs, such as cholesterol-lowering statins, several of
nities for converting additional drug categories to
which are in line for nonprescription status. A major
something other than prescription, such as choles-
obstacle to approval of OTC statins is patients’
inability to self-diagnose their cardiovascular healthand monitor the course of therapy. Regular visits to a
The proposal for a third class of drug under FDA
doctor are necessary for monitoring and blood tests.
purview was first raised in 1974. The third classwould cover drugs available without a prescription,
Statins As Third Class Candidates
but only through a pharmacist, similar to the Canadianand European systems. Drugs in the third class would
The third class has strong support within the
not be sold in other retail stores, convenience stores
pharmacy community, which has long advocated a
or supermarkets that lack a pharmacy.
more central role for the pharmacist in the healthmanagement of patients, particularly in chronic
disease areas such as diabetes, high blood pres-sure, asthma and high cholesterol.
Although several medical groups supported
the proposal, the U.S. Department of Justice
Lining up against a third class of drugs are
objected that a third class would restrict competi-
Pharmaceutical Research and Manufacturers of
tion, limit consumer availability and choice, and
Products Association (CHPA), the AmericanMedical Association (AMA) and a long list of
FDA analysis of the issue revealed that “no
controlled studies or other adequate research datahave been supplied to support the position that any
While the issue isn’t dead, it is unlikely that the
class of OTC drugs must be dispensed only by
FDA will move to a three-class system any time soon.
pharmacists to ensure their safe use.” The agencyconcluded, “There is at this time no public healthconcern that would justify the creation of a third
“It’s being discussed and considered still,
class of drugs to be dispensed only by a pharmacist
but there are issues that are making us pause,”
said Hilfiker. “There are logistical consider-ations, and the entire health care industry would
The issue regained currency as the number of
have to invest a considerable amount of money
formerly prescription products going over-the-
THE FOOD & DRUG LETTER Dec. 20, 2002 OTC SWITCH, from Page 8
associated with self-diagnosis and self-treatmentof asthma, and some potential for misuse of the
product, the benefits of easy availability to con-
quested the assessment of unanticipatedadverse reactions in pediatric patients, and
In addition, the agency suggested that labels
had also asked that electrocardiographs be
for the inhalers warn that the product should be
used only after a physician diagnoses asthma.
The FDA’s Pulmonary-Allergy Drugs Advi-
! When all else fails, firms can stall, Blake
sory Committee discussed the switch at a public
recommends. “If a company doesn’t want to
meeting in May 1983. After lengthy debate
switch a drug, the way you handle it is by
among committee members, invited experts and
dragging your feet,” he said. “The onus is on
the public, the panel recommended that FDA
the company to create labeling. It may take a
rescind its proposal to make metaproterenol a
week or it may take 10 years. The ball is
nonprescription drug, which the agency did a
And even when a decision to make the switch
has been reached, the transition from Rx to OTC
when the agency was considering Hoechst’s
status will not necessarily be smooth.
nonsedating antihistamine Seldane (terfenadine) forOTC status. Approved on a prescription basis in
1985, Seldane appeared safe when used alone but
switch was in October 1982, when it proposed
was associated with potentially fatal cardiac
OTC availability for the bronchodilator Alupent
arrhythmia when taken with certain other drugs.
(metaproterenol) in a metered-dose inhalationaerosol for asthmatics. The agency’s proposal –
Hoechst, now Aventis, developed a related
formulated without input from an advisory commit-
compound, Allegra (fexofenadine), which pro-
tee, drug companies or the public – met with
vides the same benefits of terfenadine without
the risk of arrhythmia. Allegra was approved asa prescription drug in 1997, and the following
year all products containing terfenadine were
claimed that improper use of metaproterenol
voluntarily withdrawn from the market. Now
inhalers could harm young children. The FDA’s
Allegra is among the products on deck for an
position was that while there were some risks
Cynthia Carter Annette Licitra Susan Cunningham Elizabeth Tilley-Hinkle J.T. Hroncich Bruce Goldfarb Copyright 2002 by Washington Business Information, Inc. All rights reserved. The Food & Drug Letter(ISSN 0362-6466), an in-depth analysis of regulations and issues affecting the pharmaceutical and biologics industries, is published biweekly, 24 issues, for $1,095 per year. Photocopying or reproducing in any form, including electronic or facsimile transmission, scanning or electronic storage is a violation of federal copyright law and is strictly prohibited without the publisher’s express written permission. Subscribers registered with the Copyright Clearance Center (CCC) may reproduce articles for internal use only. For more information, contact CCC at www.copyright.com or call (978) 750-8400.
8272 Moss Landing Road Moss Landing, CA 95039 EDUCATION BA Biology Truman State University, Kirksville, MO Moss Landing Marine Laboratories, Moss Landing, CA Research in phycology and community ecology OTHER RELEVANT COURSEWORK 2001 Oregon Institute of Marine Biology, Charleston, OR Graduate coursework in Marine Ecology and Animal Behavior RESEARCH EXPERIENCE 2002 - present MS
AN INFORMATION THEORETIC APPROACH TO JOINT PROBABILISTIC FACE DETECTION AND TRACKING Department of InformaticsUniversity of ThessalonikiE-mail: eloutas,nikou,pitas @zeus.csd.auth.gr ABSTRACT Head orientation is calculated by using either feature basedmethods [6, 7] or appearance based methods [8, 9]. The latter rely A joint probabilistic face detection and tracking algorithm for com-