Este DERMAGIC/EXPRESS es una revisión APOCALÍPTICA Y DE HONOR, porque desde que publiqué en JULIO DEL 2001 la edición: DESLORATADINA CONTRA LORATADINA, fui prácticamente "ajusticiado" por el entorno quien calificó dicha revisión como un ATENTADO CONTRA EL "PRESTIGIO" del Laboratorio Schering-Plough. Allí dije que el laboratorio tenía problemas de manufactura con tres productos (ALBUTEROL, LORATADINA CON PSEUDOEFEDRINA y DESLORATADINA) y que había sido demandado en los Estados Unidos de América por varias firmas de abogados. Desde esa fecha tenía ya en mi servidor casi todos los documentos que publico hoy, excepto los últimos, los cuales lo que hacen es ratificar que DERMAGIC/EXPRESS tenía y tiene la razón.
EDITORIAL ENGLISH 
================= 

SCHERINGH-PLOUGH should BE DEMANDED BY THE VENEZUELAN STATE BY ABOUT 500 MILLION DOLLARS to have put in venezuela DRUGS WITH BAD FACTORY. and other aspects but THAT are OBVIOUS. !!!! 

================================================================== 
REFERENCIAS BIBLIOGRAFICAS / BIBLIOGRAPHICAL REFERENCES 
================================================================== 
============================================================== 
1.) Wall Street Journal: Schering fines could total $500 million. 
2.) Schering-Plough Announces Ongoing Negotiations with FDA for Consent Decree on 
Manufacturing Issues. 
3.) Schering-Plough's new treatment for seasonal allergies now on the market. 
4.) SCHERING-PLOUGH ANNOUNCES CLARINEX (desloratadine) NOW AVAILABLE 
NATIONWIDE FOR TREATMENT OF SEASONAL ALLERGIES 
5.) FDA Oversight Of Drugs Fails To Protect Many Patients 
6.) Did Defective Inhalers Cause 17 Deaths? 
7.) Class-Action Lawsuit Filed Against Claritin's Maker 
8.) Group sues Schering-Plough over Claritin ads 
9.) Class Actions against Shering-Plough 
10.) Consumer Groups Sue Over Direct-to-Consumer Advertising by Schering-Plough 
11.) Schering-Plough Corporation, (SGP) Generic Firms Face FTC Suit Over Alleged Illegal 
Payments 
12.) Prove It Isn’t So, Sen. Ashcroft: After Taking $50,000 from Schering-Plough, Voters Need 
Action to Prove Missouri’s Junior Senator Isn’t Captured By Special Interests 
13.) Stop Claritin's Billion Dollar Patent Extension Grab! 
14.) Claritin Patent Extension Bill: Don't Be Fooled by the "R&D Scare Card" 
15.) Seven Reasons to Vote NO on S. 1172, Claritin's Special Interest Patent Extension Bill 
16.) Ranbaxy Announces Receiving Tentative Approval >From The U.S. FDA For Loratadine 10 
mg Tablets 
17.) A DIFERENCIA DE FEXOFENADINA, DESLORATADINA ES UN POTENTE 
ANTAGONISTA DE RECEPTORES MUSCARINICOS PARA ACETILCOLINA 
18.) Desloratadine stauts 
19.) Desloratadine 
20.) LORATADINE AND PREGNANCY 
============================================================== 
============================================================== 
1.) Wall Street Journal: Schering fines could total $500 million Wednesday, January 2, 2002 
06:50:47 PM - Wall Street Journal 
============================================================== 

Dec 24, 2001, (Wall Street Journal /FT Information via COMTEX) -- 
Schering-Plough Corp., the pharmaceutical company, says it may have to pay up to 
$500m in fines after a federal investigation into its manufacturing practices by 
the Food and Drug Administration. The firm also warned that this quarter's 
earnings will fail to meet analysts' forecasts. In separate news the company 
announced it has received regulatory approval to sell Clarinex, its allergy 
drug. 

Abstracted from: The Wall St Journal (US Edition) 

Schering-Plough Announces Ongoing Negotiations with FDA for Consent Decree on Manufacturing 
Issues 
Wednesday, December 26, 2001 07:46:13 PM - PR Newswire 


============================================================== 
2.) Schering-Plough Announces Ongoing Negotiations with FDA for Consent Decree on 
Manufacturing Issues 
Wednesday, December 26, 2001 07:46:13 PM - PR Newswire 
============================================================== 
SOURCE Schering-Plough Corporation 

KENILWORTH, N.J., Dec 21, 2001 /PRNewswire via COMTEX/ -- Schering-Plough 
Corporation (NYSE: SGP) today announced that it is in negotiations with the U.S. 
Food and Drug Administration (FDA) for a consent decree to resolve issues 
involving the company's compliance with current Good Manufacturing Practices 
(GMPs) at manufacturing facilities in New Jersey and Puerto Rico. 

Terms of the consent decree under negotiation include a possible payment by 
Schering-Plough to the federal government that may be as high as $500 million, 
subject to resolution of other terms of the final agreement. Schering-Plough 
intends to work closely and cooperatively with the FDA to reach a negotiated 
agreement resolving outstanding issues. However, the company notes that there 
are a number of issues being discussed and no assurances can be given that a 
negotiated agreement will be reached or as to what the terms of any such 
agreement would be. Any agreement would be subject to approval by the U.S. 
District Court for the District of New Jersey (Newark). 

DISCLOSURE NOTICE: The information in this press release includes certain 
"forward-looking" statements relating to the manufacturing process and control 
and current Good Manufacturing Practices (GMP) issues identified by the FDA, the 
company's efforts going forward to resolve those issues, remedies the FDA may 
seek with respect to those issues, and the prospect and potential terms and 
effects of a negotiated consent decree resolving the GMP issues. The resolution 
of the issues with the FDA is subject to substantial risks and uncertainties. 
Many factors could cause the resolution of those issues through a consent decree 
to differ materially from the company's forward- looking statements, including 
that the timing, scope and duration of a resolution of the manufacturing process 
and control and GMP issues will depend on the ability of the company to assure 
FDA of the quality and reliability of its manufacturing systems and controls. 
The reader of this release should understand that the failure to reach 
resolution of the GMP issues through a consent decree or otherwise could result 
in delays in approval of new products, seizure or recall of products, suspension 
or revocation of the authority necessary for the production and sale of 
products, fines and other civil or criminal sanctions. In addition, the 
forward-looking statements may also be adversely affected by general market 
factors, competitive product development, product availability, current and 
future branded, generic or OTC competition, federal and state regulations and 
legislation, the regulatory process for new products and indications, existing 
and new manufacturing issues that may arise, trade buying patterns, patent 
positions, litigation and investigations. For further details and a discussion 
of these and other risks and uncertainties, see the company's Securities and 
Exchange Commission filings, including the company's 2000 annual report on Form 
10-K and subsequent quarterly reports on Form 10-Q. 

Schering-Plough Corporation is a research-based company engaged in the 
discovery, development, manufacturing and marketing of pharmaceutical products 
worldwide. 
============================================================== 
3.) Schering-Plough's new treatment for seasonal allergies now on the market 
Tuesday, January 15, 2002 05:39:53 PM - Datamonitor 
============================================================== 
Source: The wall street journal 

Jan 14, 2002 (Datamonitor via COMTEX) -- Schering-Plough's new nonsedating 
antihistamine, Clarinex 5mg Tablets, is now available by prescription in 
pharmacies nationwide in the US, for the treatment of seasonal allergic 
rhinitis. 

Approved by the FDA on December 21, 2001, Clarinex (desloratadine)is a 
once-daily, nonsedating antihistamine that provides 24 hour relief from the 
symptoms of seasonal allergic rhinitis (SAR) in adults and children 12 years of 
age and older. In clinical trials, Clarinex Tablets significantly reduced total 
symptom scores of the nasal and non-nasal symptoms of seasonal allergies. 

"With its proven clinical benefits, Clarinex offers patients an important new 
therapy for the treatment of seasonal allergy symptoms," said to the press, 
Richard W Zahn, president of Schering Laboratories, the US prescription 
pharmaceutical marketing arm of Schering-Plough. "The launch of Clarinex is now 
under way and we look forward to working with physicians, pharmacists and other 
healthcare decision-makers to provide the millions of seasonal allergy sufferers 
in the US with an opportunity to enjoy 24 hours of non-drowsy seasonal relief." 

============================================================== 
4.) SCHERING-PLOUGH ANNOUNCES CLARINEX (desloratadine) NOW AVAILABLE 
NATIONWIDE FOR TREATMENT OF SEASONAL ALLERGIES 
============================================================== 
New Once-Daily, Nonsedating Therapy Provides 24-Hour Relief of Nasal and Non-Nasal 
Symptoms of Seasonal Allergies 

Kenilworth, N.J., Jan. 14, 2002 — Schering-Plough Corporation (NYSE: SGP) announced today 
that its new nonsedating antihistamine, CLARINEX (desloratadine) 5 mg Tablets, is now available 
by prescription in pharmacies nationwide for the treatment of seasonal allergic rhinitis (SAR). 

Approved by the U.S. Food and Drug Administration (FDA) on Dec. 21, 2001, CLARINEX is a 
once-daily, nonsedating antihistamine that provides 24-hour relief from the symptoms of SAR in 
adults and children 12 years of age and older. In clinical trials, CLARINEX Tablets significantly 
reduced total symptom scores of the nasal and non-nasal symptoms of seasonal allergies. 

"With its proven clinical benefits, CLARINEX offers patients an important new therapy for the 
treatment of seasonal allergy symptoms,” said Richard W. Zahn, president of Schering Laboratories, 
the U.S. prescription pharmaceutical marketing arm of Schering-Plough. “The launch of 
CLARINEX is now under way and we look forward to working with physicians, pharmacists and 
other healthcare decision-makers to provide the millions of seasonal allergy sufferers in the United 
States with an opportunity to enjoy 24 hours of non-drowsy seasonal relief." 

Allergies affect an estimated 45 million Americans and can have a significant impact on everyday 
activities at work, school and leisure time. The direct cost of seasonal allergies, including medications 
and physician visits, has been estimated at $4.5 billion annually. Indirect costs from absenteeism 
include the loss of an estimated 6 million workdays and 2 million school days each year. In addition, 
there is a growing body of evidence that points to an association between allergies and even more 
serious conditions such as asthma. 

CLARINEX CLINICAL STUDIES 
An H-1 receptor antagonist, CLARINEX, has been studied in four double-blind, randomized, 
placebo-controlled studies involving more than 2,300 seasonal allergic rhinitis patients in the United 
States between the ages of 12 and 75. A single 5 mg dose of CLARINEX taken once daily 
provides 24-hour relief from nasal and non-nasal symptoms of seasonal allergies. 

CLARINEX Tablets may be taken without regard to food. No clinically relevant drug-to-drug 
interactions have been observed when CLARINEX is administered with the antibiotic erythromycin 
or the antifungal ketoconazole, both of which have been linked to potentially dangerous interactions 
with some older antihistamines. 

In clinical trials, CLARINEX provided significantly greater symptom relief than placebo with a low 
incidence of side effects. The most common side effects were pharyngitis, dry mouth, somnolence 
and fatigue, with an incidence rate similar to placebo. 
A copy of the package insert for CLARINEX is available at www.clarinex.com. 

CLARINEX CONTINUES ALLERGY AND RESPIRATORY HERITAGE 
CLARINEX builds upon Schering-Plough's heritage as a leader in the discovery and development of 
allergy and respiratory products. Products from the company's research efforts include the 
CLARITIN (loratadine) family of nonsedating antihistamines, the country's leading prescription 
antihistamine, and NASONEX (mometasone furoate monohydrate), a once-daily nasal steroid for 
allergies. 

The company has received an “approvable letter” from the FDA for CLARINEX Tablets in the 
treatment of chronic idiopathic urticaria (CIU), or hives of unknown cause. A separate new drug 
application is also pending for the treatment of allergic rhinitis, which encompasses both SAR and 
perennial allergic rhinitis (PAR). 

DISCLOSURE NOTICE: The information in this press release includes certain “forward-looking” 
information relating to the market potential for CLARINEX. The reader of this release should 
understand that the extent that CLARINEX will be prescribed will be determined by market forces. 
In addition, the forward-looking statements may also be adversely affected by general market 
factors, competitive product development, product availability, current and future branded, generic 
or OTC competition, federal and state regulations and legislation, the regulatory process for new 
products and indications, existing and new manufacturing issues that may arise, trade buying patterns, 
patent positions, litigation and investigations. For further details and a discussion of these and other 
risks and uncertainties, see the company's Securities and Exchange Commission filings, including the 
company’s 2000 annual report on Form 10-K and subsequent quarterly reports on Form 10-Q. 

Schering-Plough is a research-based company engaged in the discovery, development, 
manufacturing and marketing of pharmaceutical products worldwide 

============================================================== 
5.) FDA Oversight Of Drugs Fails To Protect Many Patients 
May 23, 2001 
============================================================== 
Source: The Associated Press. 

WASHINGTON (AP) - Darlene Alber traces the painful, ugly boils she has had for the past five 
years to an injection of an alternative medicine that was contaminated with bacteria. 

This year, the Atlanta woman learned that the company which supplied her injection, Phyne 
Pharmaceuticals Inc., had distributed a second batch of defective products that left two people 
hospitalized in Pennsylvania. 

Phyne's victims say the company's ability to operate for more than two decades, despite repeated 
brushes with the law, shows lax oversight by the Food and Drug Administration of drug makers that 
supply the growing alternative medicine market. 

"Consumers are facing the same kind of environment that their great-grandparents did a hundred 
years ago when snake oil was being sold on every corner," said Larry D. Sasich, a pharmacist with 
the Public Citizen Health Research Group. 

But Phyne's president, Donna Critchlow, said the FDA has been too harsh. She took over the 
Scottsdale, Ariz., company last year after her husband, James Critchlow, pleaded guilty in the 
bacteria contamination case. 

"It's been a manhunt," she said. "It's a bad situation." Government investigators have faulted the FDA 
in recent years for taking too long to notify drug companies of manufacturing problems and not 
making sure those problems are corrected. 

The FDA has just one inspector for every 14 prescription drug makers in the U.S. Sasich says the 
FDA doesn't have enough resources to catch problems before people get hurt. Lawyers for some of 
Phyne's victims contend the agency often fails to enforce sanctions against troubled companies. 

FDA officials say their agency is understaffed but vigilant in getting unsafe and unapproved drugs off 
the market. Funds for oversight of drug makers have declined since 1980, but President Bush has 
proposed a 21 percent increase, to $58 million. 

Some examples of problems with prescription drugs: -Thomas Ronald Theodore was convicted in 
March for selling a bogus alternative cancer remedy. Prosecutors said Theodore's company made 
the product in an unregistered, unsanitary Massachusetts lab. The FDA did not inspect the plant until 
four months after a manager halted production in 1995. 

-The FDA halted sales of a clot-busting drug in 1998 and 1999 because of viral contamination 
problems at its manufacturer, Abbott Laboratories. But the FDA did not recall doses doctors 
already had, despite warning that the drug should be used only in emergencies. 

-Since 1999, drug maker Schering-Plough has faced repeated FDA warnings and recalls because of manufacturing problems. Consumer groups contend the FDA has not taken strong enough action against Schering-Plough and has not ensured that the company fix its problems quickly. 

Agency officials say two recalls and a string of court actions against Phyne - and a current 
investigation into its latest troubles - show the system is working. 

The case "is a good example of why we need a strong FDA," said David Horowitz, head of the 
FDA's compliance office. He said the FDA tries to get companies to correct problems informally, 
"but if that doesn't work, the agency will take whatever action is necessary to achieve compliance." 

Phyne distributed the latest batch of problem products - a gout medicine called colchicine - despite a 
1983 court order to stop selling unapproved drugs, a guilty plea in May 2000 to three felonies, and 
lawsuits from Alber and a dozen other victims. 

Phyne's colchicine supplier, Amram Inc., made it in a rural Idaho home with no state license or FDA 
inspection. Two Philadelphia-area women were hospitalized with overdoses in December because 
the colchicine they took was 10 times stronger than its label indicated. 

"Once we realized there was an adverse event, we made it a priority to inspect their manufacturing 
conditions," said John Taylor, director of the FDA's enforcement office. 

The FDA shut down Amram's lab after finding it was inadequate and unsanitary. 

Phyne's troubles with federal authorities date to its founding in 1979 by James Critchlow in Florida. 
Authorities sued the Critchlows and Phyne that year for selling unapproved drugs. 

The Critchlows settled the case in 1983 by agreeing to stop selling unapproved drugs. But they later 
moved the company to Arizona and began selling an unapproved drug called adrenal cortex extract, 
which infected Alber and at least 54 others in 1995 and 1996. 

Days after Alber injected the extract into her veins, she developed a severe infection that caused 
boils all over her hands, feet, arms, legs and buttocks. She was hospitalized for three months and 
had as many as 13 antibiotics constantly pumped into her body for two years. 

At 67, Alber still has outbreaks of boils. She won a $500,000 settlement in her lawsuit against Phyne 
and the Alabama pharmacy that sold her the extract. 

"This is worse than taking a gun and shooting someone," Alber said of the damage the contaminated 
extract did to her. 

Phyne recalled the contaminated extract in 1996 after the Centers for Disease Control and 
Prevention reported an outbreak linked to a Denver weight-loss doctor. 

Phyne and James Critchlow pleaded guilty last year to three federal felonies in connection with 
adrenal cortex extract sales. A federal judge fined Phyne more than $11,000 and ordered the 
company never to sell the extract or any other unapproved drug. 

Despite that ban, Edith Crawford, Amram's former owner, said she made adrenal cortex extract for 
Phyne until last fall, several months after the court order. 

Phyne lawyer Holly Gieszl denied that Phyne sold the extract in violation of its probation. But FDA 
investigators found vials of the extract in Alaska while investigating the gout drug case. 

============================================================== 
6.) Did Defective Inhalers Cause 17 Deaths? 
============================================================== 
Source: ClassActionAmerica.com 

Did Defective Inhalers Cause 17 Deaths? 
A number of possible legal actions against drug maker Schering-Plough Corp. are being investigated after reports that 17 people using the company's albuterol-based asthma inhalers died during a period of time in which potentially defective inhalers were on the market. 

A number of possible legal actions against drug maker Schering-Plough Corp. are being investigated after reports that 17 people using the company's albuterol-based asthma inhalers died during a period of time in which potentially defective inhalers were on the market.The allegations were made by consumer advocacy group Public Citizen, which reviewed records from the federal Food and Drug Administration. Public Citizen made the claims in an August 9, 2001 letter to Tommy Thompson, U.S. Secretary of Health and Human Services. 
Schering-Plough recalled a small batch of albuterol-based inhalers in September, 1999 and 58 
million more in March, 2000. According to Public Citizen, FDA records show 17 deaths for which 
this inhaler was listed as the 'primary suspect' from late 1998 through spring 2000, the period that 
potentially defective inhalers were on the market. Ten patients had used inhalers from batches later 
recalled, while identifying lot numbers aren't listed for the other seven. Albuterol-based inhalers made 
by Schering-Plough are sold under both its Proventil brand name and as a generic version from 
Warrick Pharmaceuticals, a subsidiary of Schering-Plough. 

The first death was reported to Schering-Plough on January 4, 2000, yet the company didn't expand 
the recall until March. That woman had had well-controlled asthma until abruptly dying in 
September, 1999 while using an inhaler that ultimately would be recalled. Between her death and the 
March, 2000 recall, five more inhaler users died, according to Public Citizen. 

Schering-Plough has responded that 'To date, every inhaler returned to us by a patient claiming 
injury and alleging that the canister lacked active ingredient has been tested and found to contain 
active ingredient.' 

============================================================== 
7.) Class-Action Lawsuit Filed Against Claritin's Maker 
============================================================== 
Consumer Groups Charge Schering-Plough's Ad Campaign 'Deceptive' By Jeff Levine 

Source: WebMD Medical News 

Aug. 9, 2001 (Washington) -- In what is apparently a first, a coalition of health-oriented consumer 
groups has filed a class-action lawsuit against pharmaceutical giant Schering-Plough. The complaint, 
brought to a New Jersey state court, accuses the drug company of "deceptive advertising and 
overpricing" for Claritin, America's most widely prescribed allergy drug. 


Whether it be an ad on TV, in print, or over the Internet, the plaintiffs charge that Schering-Plough 
has falsely promised Claritin users relief from their symptoms without drowsiness when relatively few 
benefit. The suit covers the period from 1997 to the present and is the creation of Prescription 
Access Litigation (PAL), an alliance of 53-activist groups around the country. 


"The scale of Schering-Plough's misleading direct-to-consumer advertising exceeds all others in 
American prescription drug history," said lead plaintiff's attorney Tom Sobol at a news conference 
announcing the suit. Sobol maintains that during the years under scrutiny, Schering-Plough has spent more than $100-million annually to promote Claritin. 


Meanwhile, allergy sufferers have paid $10 billion during the last four years for a drug that Sobol 
claims is little better than a "sugar pill." 


Some of Claritin's commercial images have become a part of American pop culture, like the woman running through the field of yellow flowers, seemingly oblivious to the onslaught of noxious pollens. 


"Claritin television advertisements are replete with images and references to celebrities [and] outdoor activities ... but ... devoid of any reference to the limited efficacy of the drug," says Sobol. PAL contends that Schering-Plough's own studies have shown the drug is effective for only half its users. 


Lisa Tyson, one of the plaintiffs, says she took Claritin for more than five years and it did nothing. 
"My doctor was very clear, telling me it was going to help me. And I just kept waiting and waiting 
for this thing to help me, and it wasn't helping me," she says. 


The suit has two basic goals: get the court to give consumers a refund for the product and put an end to the allegedly deceptive ads, which PAL says inflate rapidly rising drug costs. "Price is the key, and we believe that our contribution is to attack price," says Stephen Rosenfeld, a legal advisor to PAL. Drug inflation is the main thing that's preventing Congress from passing a prescription drug benefit for 
Medicare, he says. 


Schering-Plough spokeswoman Denise Foy says she can't comment directly on the lawsuit, since she hasn't seen it. Still, she says the company follows the FDA's rules on consumer ads. 
"Schering-Plough is committed to full compliance with all regulations, pertaining to promotional and 
education materials," Foy tells WebMD. 


She also insists that the nonsedating antihistamine is the most popular because it works. "No amount of marketing can sustain a drug that's not effective," she says. 

The plaintiffs say their suit isn't passing judgement on the FDA's effectiveness at supervising 
direct-to-consumer advertising one way or the other, even though it's an agency responsibility. Sobol says his group's goal is not to stop direct-to-consumer ads, but to focus on abuses where they exist. 


Meanwhile, WebMD has obtained a copy of a notice of violation written from the FDA to 
Schering-Plough on Aug. 18, 2000 alleging violations in two Claritin print ads. 


"The [agency] has reviewed these ads and concluded that they are misleading and violate the Federal Food, Drug and Cosmetic Act and applicable regulations and should be discontinued immediately," says the letter from Joan Hankin, JD, a consumer promotion analyst at the FDA. 


Specifically, the correspondence accuses the company of "misleading" readers by failing to list 
information on the product's side effects. TV personality Joan Lunden was featured in the magazine 
spread, which focused in part on the importance of school attendance. 


"Like all parents, I want what's best for my children, especially when it concerns their health. So 
when my daughter, Lindsay, kept sneezing and sniffling, we visited her doctor. He said seasonal 
allergies were the cause ... Once he prescribed a medication that wouldn't make her drowsy, she felt better and so did I," said Lunden in the ad. 

============================================================== 
8.) Group sues Schering-Plough over Claritin ads 
============================================================== 
Source: Reuters Health 

NEW YORK, Aug 09 (Reuters Health) - The Prescription Access Litigation project (PAL), a 
Boston-based advocacy group, on Thursday announced it has filed a class action lawsuit against 
Schering-Plough over allegedly deceptive direct-to-consumer (DTC) advertising and overpricing of 
the blockbuster allergy drug Claritin (loratadine). 

The complaint, filed in a New Jersey Superior Court, charges that Schering-Plough "falsely 
promise[s] all Claritin purchasers complete relief from their allergy symptoms, without qualification, 
when in fact a large percent of Claritin users report no benefit at all." 

The "language and imagery" of Schering-Plough's print, Internet and television promotions 
"effectively portray Claritin as the cure for everyone's allergy-related symptoms," according to the 
suit. 

The document points out that, in fact, Schering-Plough's "own studies indicate that Claritin does not work for between 50% and 55% of all potential customers." 

The company's marketing approach has helped "create an artificial and illegitimate demand" for 
Claritin products, and allowed the firm to "charge unconscionable prices" as a result of the demand, 
the complaint alleges. 

The suit seeks a declaration that the Claritin ads violate New Jersey law, injunctive relief to prevent 
similar misleading advertising by Schering-Plough in the future and a portion of the $10 billion that 
consumers have spent on the prescription drug since mid-1997, Tom Sobol, a lead attorney for PAL told Reuters Health. 

A Schering-Plough spokeswoman said the company has not been served with the lawsuit and cannot yet comment on specific charges. 

However, she did state that "Claritin is the world's leading non-sedating prescription antihistamine 
because it works. There's no amount of marketing that can sustain a drug that's not effective." 

She added, "All advertising, all promotional and educational materials that the company uses are 
used under rules and regulations established by the Food and Drug Administration (FDA)." 

In September 2000, the FDA requested that Schering-Plough pull Claritin ads that the agency said contained unsubstantiated claims about the drug's benefits and failed to adequately inform consumers about side effects. The spokeswoman was not able to comment on whether the FDA has cited the company over promotional practices for Claritin since then. 

PAL's litigation against Schering-Plough marks the latest in a string of recent legal actions taken by 
the group against the pharmaceutical industry. In June, PAL filed suits against Schering-Plough, 
American Home Products and Upsher-Smith Laboratories alleging that the companies entered into 
illegal agreements that kept inexpensive generic versions of K-Dur 20, a prescription potassium 
chloride supplement, out of the hands of patients. 

In May, PAL sued AstraZeneca and Barr Laboratories for what it claims was a collusive agreement 
that inflated the price of the breast cancer drug tamoxifen. And the advocacy group charged 
Bristol-Myers Squibb in April with illegally filing secondary patents on the anti-anxiety drug 
buspirone in order to block generic competition. 

In a recent interview with Reuters Health, PAL Director Kim Shellenberger said that the group's goal 
is to file a suit at least every couple of months. 

"Ms. Shellenberger's words were accurate then and are now," Sobol said on Thursday. He noted 
that there is a "high probability" that the group will file another suit within the next 60 days. 

"The point of filing the lawsuit is to in some way deter other pharmaceutical companies from engaging 
in [similar] conduct, and hopefully start a dialogue where some more sense could be made of the 
madness of drug prices in America," Sobol said. "Our position is...that the FDA has a regulatory role 
to fulfill, but that private, civil enforcement actions are also an additional way to make sure that 
effective and accurate communication happens to American consumers." 

"We aren't trying to preempt, or in any way affect or comment on, the FDA's role," he added. 
"We're simply trying to pursue other roles that the law not only makes available, but expects will be 
exercised." 

============================================================== 
9.) Class Actions against Shering-Plough 
============================================================== 
Source: SteveWeisman.com, Attorney and Counsellor at law. 

NewsLetter: 

Schering-Plough Corp., the maker of Claritin, the country's most widely prescribed allergy medecine is finding that class actions are nothing to sneeze at. Recently a number of consumer groups filed a class action against Schering-Plough alleging that the pervasive television ads we have all seen touting the effectiveness of Claritin as an allergy symptom fighter are deceptive and misleading. The plaintiffs allege that Claritin is effective only half of the time. 

============================================================== 
10.) Consumer Groups Sue Over Direct-to-Consumer Advertising by Schering-Plough 
============================================================== 
Source: Milberg Weiss, Berhand Hynes, and Lerach LLP. 

Maker of Claritin Misleads the Public and Illegally Inflates Prices, Complaint Alleges 
WASHINGTON, D.C., August 9 – The Boston-based Prescription Access Litigation project 
(PAL) announced today the filing of a class action lawsuit in New Jersey against Schering-Plough 
Corp. (NYSE: SGP) for deceptive advertising and overpricing of Claritin, America's most widely 
prescribed allergy drug. Plaintiffs allege that Schering-Plough has engaged in a campaign of 
misrepresentation that has artificially increased the demand and price for the drug—a drug that 
Schering-Plough's own studies have shown to be effective for only 50% of its users. 

The lawsuit was announced today a National Press Club Newsmaker news conference. The complaint, filed in state Superior Court in New Jersey, alleges that Schering-Plough's 
direct-to-consumer ads falsely depict the benefits of its drug, Claritin, and fail to disclose the limited efficacy of Claritin products, which also include Claritin-D, Claritin-D 24 Hour, Claritin Syrup, and Claritin Reditabs. The lawsuit alleges that Schering-Plough's campaign of deceptive, unfair advertising has turned it into the top-selling antihistamine in the U.S., with annual sales of over $2 billion. 

Last year, Schering-Plough spent $111 million on direct-to-consumer ads promoting the allergy 
drug, according to PAL's lawsuit, which says the ads consistently make a false promise: that Claritin 
works for everyone. In fact, medical research indicates that Claritin fails to provide allergy relief 
roughly half the time, and performs only slightly better than a placebo, i.e., a sugar pill. 

Plaintiffs in the actions, members of the PAL coalition, include Citizen Action New York, Citizen 
Action New Jersey, and Health Action New Mexico, as well as individual users of the drug. The 
plaintiffs are represented by; New York-based Milberg Weiss Bershad Hynes & Lerach LLP 
(www.milberg.com); Carey & Danis, LLC of St. Louis (www.careydanis.com); and Lieff, 
Cabraser, Heimann & Bernstein, LLP of San Francisco (www.lchb.com). 

"This is not a mere oversight," said attorney Stephen Rosenfeld, consumer advocate and PAL 
spokesman. "We believe Schering-Plough has deliberately left out any information about the drug's 
efficacy, instead serving up glowing ads to push this product in America's living rooms. This suit 
alleges that the ads are misleading, incomplete, and designed to fool the public into paying top-dollar for a drug that often as not, just doesn't work. We see this as one of the most egregious examples of inflating the prices of a drug beyond its worth." 

PAL (www.prescriptionaccesslitigation.org) was formed earlier this year on behalf of consumer 
groups to combat the tactics drug companies use to maintain artificially high prices for prescription 
drugs. The Claritin litigation is the fourth filed by PAL since April against pharmaceutical companies. 

The newest PAL lawsuit notes that during the class period, about $10 billion was spent in the US for Claritin products; a substantial portion of which, the complaint alleges, is directly attributable to 
Schering-Plough's unlawful conduct. 

"This is a case about a pharmaceutical company's direct-to-consumer advertising, and how that 
advertising distorted the market. We allege that Schering-Plough induced Americans to spend 
billions of dollars on Claritin in the belief that it would bring complete allergy relief for each user. That belief sprang from the false claims in Claritin ads and the absence in the ads of information about Claritin's true level of efficacy, the Complaint alleges, and it inflated sales and prices throughout the market," noted a PAL lead attorney, Thomas M. Sobol. "Deliberate concealment and false promises are at the heart of the New Jersey Consumer Fraud Act." 

In April, PAL filed six lawsuits alleging that Bristol-Myers Squibb illegally kept a generic version of 
BuSpar, an anti-anxiety drug, off the market. In May, PAL filed lawsuits against AstraZeneca and 
Barr Laboratories alleging price collusion over tamoxifen, a breast cancer drug that is the most 
widely prescribed anti-cancer drug in the world. In June, PAL filed suits alleging that 
Schering-Plough, Upsher-Smith Labs & American Home Products entered into illegal agreements to maintain artificially high prices of K-DUR20, potassium supplement that is the fourth most prescribed drug among the elderly. 

The Prescription Access Litigation Project was organized by Community Catalyst 
(www.communitycatalyst.org), a Boston-based nonprofit organization. PAL, comprised of more 
than 50 consumer and senior advocacy groups in 25 states, was formed earlier this year to target 
pharmaceutical companies whose unfair market conduct has pushed the cost of prescription drugs 
beyond the reach of many U.S. consumers. 

============================================================== 
11.) Schering-Plough Corporation, (SGP) Generic Firms Face FTC Suit Over Alleged Illegal 
Payments 
============================================================== 
Source: BioSpace.com 

Federal antitrust enforcers are preparing civil charges against Schering-Plough Corp. and two generic drug makers, alleging that patent settlements between the companies included illegal payments to delay a low-cost generic drug from reaching the market. The Federal Trade Commission is expected to file an administrative complaint as soon as Monday against Schering-Plough and the generic companies, the Lederle unit of American Home Products Corp. and Upsher-Smith Inc., Minneapolis, lawyers close to the case said. 

============================================================== 
12.) Prove It Isn’t So, Sen. Ashcroft: After Taking $50,000 from Schering-Plough, Voters Need Action to Prove Missouri’s Junior Senator Isn’t Captured By Special Interests 
============================================================== 
Source: Public Citizen. 

WASHINGTON, D.C. -- The consumer watchdog group Public Citizen issued a challenge Monday 
to Missouri Sen. John Ashcroft (R) to wipe away the stain of impropriety that corporate donations 
have placed on his office. 

On June 18, the Kansas City Star reported that John Ashcroft's soft-money Victory Committee 
took $50,000 from the drug firm Schering Corp., the parent company of the better-known 
Schering-Plough. The company makes Claritin, a blockbuster drug that helped the company post a 
whopping $2.1 billion in profits last year. 

The reason for Schering's generosity is obvious. Ashcroft chairs the Senate Judiciary Committee's 
subcommittee on Constitution, Federalism, and Property Rights, which oversees patent regulations. Schering has launched an unprecedented sneak attack to try and extend its Claritin patent, a move that could cost consumers $7.3 billion in continued monopoly drug prices, according to a study by the University of Minnesota's PRIME Institute. Extending the patent would delay competition for Claritin from generic drug makers and other competitors, who typically charge cheaper prices. 

"Senator Ashcroft, we need you to step up to the plate and persuade your fellow Senators not to let these sneaky riders go through," said Frank Clemente, director of Public Citizen's Congress Watch. 

Clemente was speaking on behalf of Public Citizen's 1,700 members in Missouri. 

Schering-Plough is reported to be attempting to secretly attach riders on the Military Construction supplemental appropriations bill, which is currently being conferenced between the House and Senate and is expected to be finished this week. 

"When John Ashcroft's political committee took $50,000 from a company that is attempting to use the power of government to swipe $7.3 billion from consumers' pocketbooks, he made himself immediately suspect," Clemente said. "If he wants to disabuse voters of the impression that he's totally bought and paid for, he needs to work hard to block this blatant money grab. 

"This patent extension couldn't survive the full light of day. Sen. Ashcroft needs to help make sure it 
doesn't succeed in a shadowy, back-room deal." 

In addition, Columbia University is seeking to extend its Cotransformation patent, which could give 
the university an extra $500 million in royalties for a product that was developed with taxpayer 
money. 

Schering-Plough made the $50,000 donation to Ashcroft on September 30, 1999, during a crucial period when the Claritin bill was before his subcommittee. It is the only such soft-money contribution that the company has ever given to benefit an individual Senator. This huge donation is only one part of Schering-Plough's dramatically increased lobbying on this issue. The company spent $9.2 million lobbying Congress in 1999, more than any other pharmaceutical or biotechnology firm, according to its lobby disclosure reports. That amount was up from $4.3 million in 1998. 

============================================================== 
13.) Stop Claritin's Billion Dollar Patent Extension Grab! 
============================================================== 
Bad Medicine for U.S. Consumers and Health Care Costs 
Source: Public Citizen 

Schering-Plough, a major pharmaceutical company, is pushing special interest legislation [H.R. 1598 and S. 1172] to extend monopoly patent protection for Claritin, the firm's best selling allergy drug. If successful, this high profile attack on consumer pocketbooks will have an annual cost of between $1.6 billion and $3.2 billion. 

In an effort to sell the Claritin Patent Extension Grab as a "fair process" - which it's not - the 
company appears willing to put the same kind of money into lobbying Congress that it spends on its "blue skies" TV ads that blanket the air waves. But before Congress - or the American people - buy in, let's look at the facts about the Claritin patent extension grab: 

1. Legislative history: H.R. 1598/S. 1172's proponents attempt to rewrite - and in the process 
seriously misrepresent - history by characterizing this special interest legislation as a remedy for 
"consequences unintended by Congress" in enacting the Drug Price Competition and Patent Term 
Restoration Act of 1984 [Waxman-Hatch Act]. 

2. Economic impact: H.R. 1598/S. 1172 would cost some individual American consumers hundreds of dollars more a year, and the U.S. health care system as a whole hundreds of millions of dollars more. If Schering-Plough got the full three year patent extension they are seeking, the price tag would run between $1.6 billion and $3.2 billion more during these three years. 

3. Subversion of patent system: H.R. 1598/S. 1172 subverts the drug patent system from its true 
purpose, which is to promote research and development of new pathbreaking drugs, into an 
anti-competitive shield to protect the monopoly profits of an old drug. 

4. Not a fair and open process: H.R. 1598/S. 1172 creates a "stacked deck" review process with all the aces in Schering-Plough's hand. Although S. 1172 purports to allow challenges based on "public interest," cost to consumers and the U.S. health care system is excluded from the bill's definition of "public interest." 

5. Future impact: If Schering-Plough gets away with this one, every other company with a profitable 
drug about to go off-patent will think it is entitled to the same special treatment. 

Public Citizen's analysis of H.R. 1598/S. 1172 is attached. 

Legislative History 

In opposing Schering-Plough's effort to extend Claritin's patent, Representative Waxman, the 
principal House sponsor of the 1984 Act, testified [jointly with Representative Stark] last year that 
"the Act...strikes a careful balance between promoting innovation and ensuring that consumers have timely access to affordable medicines." 

Schering-Plough's justification for this special interest legislation would upset that balance and rewrite legislative history. The company claims that the two-year patent extension granted to seven "pipeline" drugs [so-called because they were in the FDA review and approval process when the Act was under consideration], including Claritin, should be extended because the FDA review process for these drugs took much longer than average. The company claims that in order to "remedy" an "unintended consequence," Claritin should be made eligible for an additional three years of patent protection. 

This "fairness" claim rests on a clever attempt to confuse two unrelated parts of the 1984 Act: 

1. The five-year patent term restoration process. Congress made this provision of the 
Waxman-Hatch Act prospective only. It deliberately chose to exclude the pipeline drugs from this 
section because it was intended as an incentive to stimulate new research and development. Since the research and development phase for the pipeline drugs had already occurred, they were not meant to be covered by it. 

As the House Committee on Energy and Commerce report clearly stated: [Congress] "established 
different maximum periods of extension to provide greater incentive for future innovations." H.R.Rep. No.98-857, pt.1 at page 41 (1984) 

2. Special protections for pipeline drugs. This does not mean that Congress ignored the competitive situation of the pipeline drugs. Other sections of the Act provided them two types of protection: (a) two years of patent extension, and (b) a variety of special non-patent exclusivity provisions, which prevented or delayed generic competition. Claritin got the two-year patent extension to which it was entitled under the Act plus another 22.5 months extension from the Uruguay Rounds Agreement Act (URAA) of 1994, the U.S. enabling legislation for the General Agreement on Trade and Tariffs (GATT). (On average, the URAA extended pharmaceutical patents by only 14 months.) 

It is retrospective wishful thinking on Schering-Plough's part to read into Waxman-Hatch any intent 
to provide pipeline drugs with more protection that the Act gave them. If Congress had wanted to 
make the length of the FDA review and approval process a factor for pipeline drug patent extension 
terms, it could - and would - have done so. 

All interested parties signed off on the tradeoffs incorporated into the Waxman-Hatch Act. What 
would be unfair would be to permit Schering-Plough to retroactively - and unilaterally - write 
themselves a better deal at the expense of consumers and generic competitors. 


Economic Impact 

Rising prescription drug expenditures are a leading cost-driver in the U.S. health care system. 
Prescription drug expenditures rose 85% between 1993 and 1998, with double digit annual 
increases projected for the foreseeable future. The daily newspaper and the nightly news regularly 
feature stories about seniors who must choose between paying for their medicines and buying food. Moreover, out-of-control drug prices remains the chief barrier to making outpatient prescription drugs a covered benefit under Medicare. 

Legislation to clamp down on brand name prescription drug monopoly pricing abuses should be at 
the top of the Congressional agenda. Instead, H.R. 1598/S. 1172 would make things worse. Using a Congressional Research Service study, the following chart shows the potential savings to consumers and the U.S. health care system that would result from generic competition to the seven brand name "pipeline" drugs that H.R. 1598/S. 1172 would protect. 


"They are pulling out all the stops to get that extension," Clemente said. "They couldn't do it with a 
stand-alone bill so now they're trying the secretive approach, enlisting an anonymous Senator to 
insert the language. 

"This sneaky trick absolutely should not stand in a democracy. By taking such an unprecedented contribution from a special interest with business before his committee, Sen. Ashcroft has a special burden to uphold the integrity of the Senate and prevent Schering-Plough's greed from running roughshod over consumer need." 

Last year, the company enlisted its home-state Sen. Robert Torricelli (D-N.J.) to sponsor the 
Claritin patent extension as bill S.1172. The bill has since been tied up in the Judiciary Committee. 
Sen. Ashcroft remains a co-sponsor of the bill, even after fellow Sens. Conrad Burns (R-Mont.) and 
Max Cleland (D-Ga.) withdrew their support. 

"The people of Missouri deserve a Senator who will stand up for their rights as consumers, not 
conspire to help multi-billion-dollar corporations extend their monopoly power over new drugs," 
Clemente said. "Which will it be, Senator?" 

St. Louis Post-Dispatch 
Wednesday, July 5, 2000 

The Senator from Claritin 

Congress wants to do something about the unconscionable cost of prescription medicine: Increase 
it. 

Legislation now pending would extend by three years Schering-Plough's 20-year patent on the 
popular allergy medication Claritin and seven other drugs. That means less expensive generic 
versions couldn't be sold, so consumers would pony up an additional $11 billion over the next five 
years. 

You certainly can't blame Schering-Plough for trying. Claritin, which reportedly sells for $2.66 a pill 
-- so much some insurance plans won't pay for it -- is a blockbuster drug for the company. 
Schering-Plough argues it needs the extension because it waited years for FDA approval. The 
company can expect to earn $5 million a day on Claritin sales if the bill is passed. So far, it has spent a comparatively paltry $8.5 million in political donations and lobbying fees this year. 

Of that amount, $50,000 went to the Ashcroft Victory Committee, a joint fund-raising committee set up by Missouri Sen. John Ashcroft and the National Republican Senatorial Committee. By 
remarkable coincidence, Mr. Ashcroft is a co-sponsor of the bill, which his campaign spokesman 
characterized as "meritorious." 

But the Senator from Claritin is not alone in backing this odious bill. He has plenty of company on 
both sides of the aisle. Locally, Illinois Rep. Henry Hyde and Missouri Rep. Roy Blunt are 
co-sponsors in the House, as was, until recently, Rep. Jo Ann Emerson. Nor is Schering-Plough the only company bellied up to the public trough. Columbia University is seeking similar patent 
extensions on drugs developed there. 

As with many other corporate welfare bills, the patent protection act surfaced so quietly that an early version was circulated without identifying the legislation's author. Only after the Seniors Coalition ran newspaper ads offering $1,000 to anyone who could name "Senator Anonymous" did the author's identity come to light. Even then, Sen. Orrin Hatch -- who originally denied he was behind the effort 
-- blamed members of his staff for circulating the proposal. Mr. Hatch, who campaigned for president on a Schering-Plough corporate jet, insisted he never could have supported the proposal drafted by his staff. 

If nothing else, this episode proves that Claritin is represented by the same number of U.S. Senators 
as Missouri. The question, teary-eyed Midwestern allergy sufferers should be asking is, "Who 
represents us?" 

============================================================== 
14.) Claritin Patent Extension Bill: Don't Be Fooled by the "R&D Scare Card" 
============================================================== 
Source: Public Citizen 

Proponents of H.R. 1598/S. 1172, which creates a "slam dunk" patent extension process for Claritin and six other drugs that could cost consumers between $1.6 billion and $3.2 billion over three years, seek to justify this special interest legislation with two main arguments: (1) defense of "patent integrity," and (2) the "R&D Scare Card:" without enormous drug company profits, the research and development investment necessary to find and develop new medicines will stop. 

R&D Scare Card: The brand name pharmaceutical industry plays the R&D scare card every time 
Congress considers legislation to mitigate the consequences of the U.S.'s extraordinarily high 
prescription drug prices. Here it is used as an affirmative argument for granting Claritin a third patent extension.(1) Representative Ed Bryant introduced the R&D argument in his April 28, 1999, floor statement on H.R. 1598: "Drug research is...expensive...It costs more than $500 million to develop and discover one new medicine...That explains our legislation and the necessity for patent integrity." This argument is particularly absurd with respect to best-selling Claritin, which has repaid its makers' R&D costs many times over. The case of Claritin also disproves the erroneous implication that the enormous profits earned by drug companies go in large part to R&D. 

Schering-Plough's expenditures on R&D are low and its profits are high: The attached pie chart 
shows data from Schering-Plough's Annual Report on how Schering-Plough's 1998 net sales were 
allocated. Despite the rhetoric about the importance of research and development, it reveals that, 
even with a profit rate of almost 22 percent, Schering-Plough allocated a scant 12.5 percent of sales 
to R&D.(2) (see attached pie chart). 

Schering-Plough does not need three additional years of patent protection to reap ample rewards for developing Claritin: Brand name drug companies do not reveal how much they spend on bringing a new drug to market. But even at the Pharmaceutical Research and Manufacturing Association's (PhRMA) inflated figure of an average of $500 million per drug that makes it to market,(3) the investment in Claritin has been repaid many times over. 

Since Schering-Plough does not report what proportion of its net income derives from Claritin, 
Public Citizen has constructed an estimate using the rough assumption of a 1:1 relationship between Claritin's shares of Schering-Plough's net sales and net income.(4) On that basis, Claritin has earned $1.3 billion in its first five years on the market. 
Prospects for future earnings are also bright. For the next three years, 1999 - 2001, Claritin's sales 
are projected to total nearly $10 billion.(5) At Schering-Plough's current 21.7 percent profit rate,4 
Claritin could earn another $2.2 billion before its first patent expires in 2002.5 The drug will have 
earned $3.5 billion in its first eight years on the market, seven times more than PhRMA's inflated 
cost of bringing a drug to market. 
Nor will these profits cease in 2002. To the contrary: analysts expect Claritin to remain a 
blockbuster drug for Schering-Plough for many years, due to expanded sales from new formulations 
(Claritin-D 24 Hour, Claritin Syrup, and Claritin RediTabs have been introduced over the last few 
years) and a 1997 licensing agreement with Sepracor, which holds the patent for the active 
metabolite of Claritin, giving Schering-Plough patent life for some products extending as far as 
2014.5 Among the MedAdNews editors' explanations for "What makes Claritin special:" "long life 
ahead before patent expires" and "many years of growth ahead."5 
Claritin's success is based on aggressive marketing: In saluting Claritin as its 1998 brand of the year, 
MedAdNews' editors particularly noted the "aggressive promotional effort by marketer to establish 
brand identity."5 Claritin is indeed a story of aggressive marketing. Between January and June, 
1998, it led all other drugs in direct-to-consumer (DTC) ads. During that period, Schering-Plough 
spent $66.7 million on DTC ads for Claritin, an increase of 91 percent over the first half of 1997.(6) 
The company also increased its sales force, which markets to physicians, hospital formulary 
committees, and HMOs.(7) And recently Claritin's promoters have borrowed an idea from the 
tobacco industry - placing young people in blue T-shirts on downtown street corners to hand-out 
"$5 off" promotional coupons (with the necessary "ask your doctor" tagline, since Claritin is available by prescription only). 

Conclusion: H.R. 1598/S. 1172 is not about patent integrity or drug research and development. 
Above all, this bill would reward Schering-Plough's aggressive Congressional lobbying campaign 
with additional billions in profits which, if the company's past priorities are a guide, would go in large part to fuel aggressive marketing campaigns like that waged for Claritin, arguably the most aggressive in U.S. pharmaceutical history. That may be a legitimate reason for Schering-Plough stockholders to support the bill - but not for Congress to pass it. 

Attachment: Public Citizen's May 24, 1999, fact sheet, "Stop Claritin's Billion Dollar Patent 
Extension Grab," which rebuts the patent integrity argument made for H.R. 1598. It explains how 
H.R. 1598 would subvert rather than defend the integrity of the drug patent system while costing 
consumers billions of dollars. 




Rev. July 30, 1999 


-------------------------------------------------------------- 


1. Claritin received a two-year extension under the terms of the Waxman-Hatch Act, and 22 more months from the Uruguay Rounds Agreement Act (URAA) of 1994, the U.S. enabling legislation for the General Agreement on Trade and Tariffs (GATT). (On average, the URAA extended pharmaceutical patents by 14 months.) 

2. Schering-Plough 1998 Annual Report, p. 33. Explanation for "cost of sales" category comes from 6-10-99 telephone interview with Schering-Plough; no further breakdown was available for "selling, general and administrative" or "research and development" categories. 

3. The $500 million figure has a "failure rate" built in; i.e., it includes expenditures on R&D for drugs 
that are never marketed. It dates back to a paper published in 1991 by four economists with 
well-known ties to the drug industry which used data from an unaudited and confidential industry 
questionnaire. It has been used in connection with H.R. 1598/S. 1172 not only by Representative 
Bryant in his floor statement introducing the bill but also by Gerald Mossinghoff, former executive 
director of PhRMA, at a June 10, 1999 forum organized to promote H.R. 1598. For a critique of 
the studies underlying this number, see James Love, "Call for More Reliable Costs on Clinical 
Trials," Marketletter, January 13, 1997, pp. 24-25. Love's analysis of orphan drug tax credit reports 
and NIH clinical trial costs suggests that the PhRMA number is at least three times too high for the cost of clinical trials, said to be one of the most expensive components of new drug development. 

4. Claritin worldwide sales reported by Schering-Plough (6-17-99 telephone interview); corporate 
worldwide net sales and net income from 1998 Annual Report, p. 36 ($ in millions). 

Seven Reasons to Vote NO on S. 1172, Claritin's Special Interest Patent Extension Bill 

Multibillion-dollar cost to consumers and the U.S. health care system. 
Consumers would pay through the nose for a three-year patent extension for Claritin and six other 
"pipeline" drugs that would benefit from S. 1172 because cheaper generic equivalents would not be 
made available sooner. A new study by the University of Minnesota's PRIME Institute estimates the cost at $11 billion between 2002 and 2012. Of that, $2.5 billion would be paid by Medicaid, the 
Veterans Administration and other government health programs. Taxpayers' share would rise to $5 
billion if a Medicare drug benefit is approved. At a time when Congress and the Clinton 
administration are struggling with how to make a Medicare prescription drug benefit affordable, 
these bills would only add fuel to the fire of rapidly rising drug prices. 

Subverts the purpose of drug patents from research incentive to profit protection. 
The 1984 Hatch-Waxman Act deliberately distinguished between pipeline drugs such as Claritin 
(so-called because they were in the FDA approval process when the Act became law) and drugs 
that were not that far along. Hatch-Waxman granted up to two years of patent term restoration to 
the pipeline drugs but, to provide an incentive for new research and development, reserved the 
five-year restoration period for drugs that had not been submitted for FDA approval. The legislative 
history is clear: "[Congress] established different maximum periods of extension to provide greater 
incentive for future innovations." (H.R. Rep. No. 98-857, pt. 1 at page 41 (1984).) 

Claritin already has benefited from extra patent protection. 
In addition to the two-year patent term restoration, the Hatch-Waxman Act granted pipeline drugs a number of special provisions -- including additional years of market exclusivity for patenting new formulations -- which have benefited Claritin. The drug also got almost two years additional patent protection from the 1994 General Agreement on Tariffs and Trade (GATT). Who's telling the truth about FDA's review of Claritin? 

Schering-Plough claims that the FDA's review of Claritin took too long, but the company won't 
waive confidentiality requirements so the FDA can make public what took place. Rep. Henry 
Waxman (D-Calif.) and others have asked the General Accounting Office to investigate, and the that report is pending. Why not wait for the results? 

Profits, not R&D, is Schering-Plough's priority. 
Schering-Plough put more than one and-a-half times as much into profits as R&D in 1998: 22% into profits, and just 12.5% into R&D. If a three-year patent extension for Claritin is allowed, based on industry standards only 3.6% of Schering-Plough's additional revenue would be used for the 
discovery of new drugs - the rest would go into additional profits, marketing, advertising, and other 
corporate expenditures. [Stephen Schondelmeyer, Patent Extension of Pipeline Drugs: Impact on 
U.S. Health Care Expenditures, University of Minnesota, July 1999, p. 10.] 
Enacting S. 1172 opens the floodgate. 
S. 1172 amounts to Congressional forum shopping for Schering-Plough by putting the Commissioner of Patents and Trademarks -- who has no expertise in this area and has historically been a proponent of brand-name patent extensions -- in charge of a stacked-deck process that would almost inevitably result in the extension being granted. Once this process is in statute, it would invite the makers of other blockbuster drugs to ask Congress to "tweak" its terms so that they too could qualify for lucrative patent extensions. There are 20 such drugs [for example, Prozac, Prilosec, Vasotec], with annual sales of almost $20 billion, with patents due to expire between 2000 and 
2005. 
The Claritin Patent Extension Bill is opposed by dozens of consumer, labor, senior and public health groups, including Public Citizen, AARP, AFL-CIO, National Council of Senior Citizens, Consumer Federation of America, United Auto Workers, AIDS Action, American Federation of Teachers, Center on Disability and Health, National Organization for Rare Disorders (NORD), 
Communications Workers of America, Families USA, Gray Panthers, ILWU, National Senior Citizens Law Center, Neighbor to Neighbor, AFSCME, American Federation of Retired Teachers, Network - A National Catholic Social Justice Lobby, UNITE, U.S. PIRG, and United Steelworkers of America. 
November 16, 1999 


Year 


Claritin Sales 


Total S-P Sales 
Claritin Sales as % of Total S-P Sales 

S-P Net Income 
Estimated Claritin Net Income 

1993 N.A. 
$4,229 
0* 
$ 731 
0* 

1994 N.A. 
4,537 
7.7%* 
922 
$ 71 

1995 $ 789 
5,104 
15.5% 
887 
138 

1996 1,150 
5,656 
20.3% 
1,213 
246 

1997 1,726 
6,778 
25.3% 
1,444 
365 

1998 2,263 
8,077 
28.0% 
1,756 
492 

Estimated Claritin Net Income, 1994 - 1998: $1,312 


*Sales data for Claritin for 1993, the year the drug was launched, and 1994 were not available. We 
estimate Claritin's share of net sales as 0 for 1993 and 7.7% for 1994 (the midpoint between 1993 
[0] and 1995 [15.5]). This is undoubtedly a conservative assumption, since Claritin had some sales 
in 1993. 

5. MedAdNews, May 1998, pp. 14-15. 

6. Scrip, December 2, 1998, for dollar figure; MedAdNews, October 1998, p. 10, for percentage 
increase. 

7. Schering-Plough 1997 Annual Report, p. 9. 


============================================================== 
15.) Seven Reasons to Vote NO on S. 1172, Claritin's Special Interest Patent Extension Bill 
============================================================== 
Source: Public Citizen 

Multibillion-dollar cost to consumers and the U.S. health care system. 
Consumers would pay through the nose for a three-year patent extension for Claritin and six other 
"pipeline" drugs that would benefit from S. 1172 because cheaper generic equivalents would not be 
made available sooner. A new study by the University of Minnesota's PRIME Institute estimates the 
cost at $11 billion between 2002 and 2012. Of that, $2.5 billion would be paid by Medicaid, the 
Veterans Administration and other government health programs. Taxpayers' share would rise to $5 
billion if a Medicare drug benefit is approved. At a time when Congress and the Clinton 
administration are struggling with how to make a Medicare prescription drug benefit affordable, 
these bills would only add fuel to the fire of rapidly rising drug prices. 

Subverts the purpose of drug patents from research incentive to profit protection. 
The 1984 Hatch-Waxman Act deliberately distinguished between pipeline drugs such as Claritin 
(so-called because they were in the FDA approval process when the Act became law) and drugs 
that were not that far along. Hatch-Waxman granted up to two years of patent term restoration to 
the pipeline drugs but, to provide an incentive for new research and development, reserved the 
five-year restoration period for drugs that had not been submitted for FDA approval. The legislative 
history is clear: "[Congress] established different maximum periods of extension to provide greater 
incentive for future innovations." (H.R. Rep. No. 98-857, pt. 1 at page 41 (1984).) 

Claritin already has benefited from extra patent protection. 
In addition to the two-year patent term restoration, the Hatch-Waxman Act granted pipeline drugs a 
number of special provisions -- including additional years of market exclusivity for patenting new 
formulations -- which have benefited Claritin. The drug also got almost two years additional patent 
protection from the 1994 General Agreement on Tariffs and Trade (GATT). 
Who's telling the truth about FDA's review of Claritin? 
Schering-Plough claims that the FDA's review of Claritin took too long, but the company won't 
waive confidentiality requirements so the FDA can make public what took place. Rep. Henry 
Waxman (D-Calif.) and others have asked the General Accounting Office to investigate, and the that report is pending. Why not wait for the results? 

Profits, not R&D, is Schering-Plough's priority. 
Schering-Plough put more than one and-a-half times as much into profits as R&D in 1998: 22% into 
profits, and just 12.5% into R&D. If a three-year patent extension for Claritin is allowed, based on 
industry standards only 3.6% of Schering-Plough's additional revenue would be used for the 
discovery of new drugs - the rest would go into additional profits, marketing, advertising, and other 
corporate expenditures. [Stephen Schondelmeyer, Patent Extension of Pipeline Drugs: Impact on 
U.S. Health Care Expenditures, University of Minnesota, July 1999, p. 10.] 
Enacting S. 1172 opens the floodgate. 
S. 1172 amounts to Congressional forum shopping for Schering-Plough by putting the Commissioner of Patents and Trademarks -- who has no expertise in this area and has historically been a proponent of brand-name patent extensions -- in charge of a stacked-deck process that would almost inevitably result in the extension being granted. Once this process is in statute, it would invite the makers of other blockbuster drugs to ask Congress to "tweak" its terms so that they too could qualify for lucrative patent extensions. There are 20 such drugs [for example, Prozac, Prilosec, Vasotec], with annual sales of almost $20 billion, with patents due to expire between 2000 and 
2005. 
The Claritin Patent Extension Bill is opposed by dozens of consumer, labor, senior and public health 
groups, including Public Citizen, AARP, AFL-CIO, National Council of Senior Citizens, Consumer 
Federation of America, United Auto Workers, AIDS Action, American Federation of Teachers, 
Center on Disability and Health, National Organization for Rare Disorders (NORD), 
Communications Workers of America, Families USA, Gray Panthers, ILWU, National Senior 
Citizens Law Center, Neighbor to Neighbor, AFSCME, American Federation of Retired Teachers, 
Network - A National Catholic Social Justice Lobby, UNITE, U.S. PIRG, and United 
Steelworkers of America. 
November 16, 1999 

============================================================== 
16.) Ranbaxy Announces Receiving Tentative Approval >From The U.S. FDA For Loratadine 10 
mg Tablets 
============================================================== 
Friday, January 11, 2002 01:44:51 PM - PR Newswire 

Source: The wall Street Journal. 

PRINCETON, N.J., Jan 11, 2002 /PRNewswire via COMTEX/ -- Ranbaxy 
Pharmaceuticals Inc. (RPI), a wholly owned subsidiary of Ranbaxy Laboratories 
Limited (RLL) of New Delhi, India, announced today that the U.S. Food and Drug 
Administration has provided tentative approval of its abbreviated New Drug 
Application (ANDA) for Loratadine 10 mg tablets. This tentative approval was 
granted nine months after the ANDA was filed in March 2001. 

Loratadine is the generic equivalent of Schering-Plough's long-acting tricyclic 
anti-histamine agent Claritin(R), which has annual sales of $1.6 billion of 
total Loratadine sales of $2.3 billion (IMS - MAT, Dec. 2000). Loratadine is 
indicated for the relief of nasal and non-nasal symptoms of seasonal allergic 
rhinitis and for the treatment of chronic idiopathic urticaria in patients six 
years of age or older. 

Ranbaxy Pharmaceuticals Inc. will launch the product to the retail pharmacy 
market that will include chain and independent pharmacies, mass merchandisers, 
food combination outlets, wholesalers, and generic distributors. The product 
will be launched following expiration of exclusivity periods, which is scheduled to occur in June 
2003. 

===========================================================
17.) A DIFERENCIA DE FEXOFENADINA, DESLORATADINA ES UN POTENTE
ANTAGONISTA DE RECEPTORES MUSCARINICOS PARA ACETILCOLINA
===========================================================
Source:
Allergy 2OO1 XXth Congress of the European Academy of Allergology and Clin
ical Immunology. European Journal of Allergy and Clinical Immunology,
Supplement 68, Volume 56, # 642

Introducción
-------------

Pese a sus buenas afinidades por los receptores H1 periféricos para
histamina, los antihistamínicos de primera generación estaban asociados con
penetración en el sistema nervioso central (S NC) y ausencia de
selectividad. Los antihistamínicos de segunda generación han reducido
substancialmente sus efectos sobre el SNC, pero todavía persiste la
ausencia de selectividad con respecto a otros objetivos periféricos. Más
recientemente se han desarrollado metabolitos activos de antihistamínicos
de segunda generación, tales como desloratadina y fexofenadina. Uno de los
probables objetivos secundarios indeseables de los antihistamínicos es la
familia de receptores muscarínicos, dado que comparte un alto grado de
homología de secuencia con el receptor H1 para histamina 1 sin embargo,
pocos estudios han sido emprendidos acerca de las potencias relativas de
los antihistamínicos para subtipos individuales de receptores muscarínicos.


Objetivos
----------

Investigar las potencias con las cuales la desloratadina y su compuesto
antecesor loratadina, y fexofenadina y su compuesto antecesor terfenadina,
interactúan con receptores muscarinicos. También se investigaron los
efectos funcionales de desloratadina y fexofenadina.


Métodos
-------

Experimentos de unión en equilibrio:

Células COS-7 y de ovario de hámster chino (CHO) fueron transfectadas con
receptores histaminicos H1 humanos donados (expresados transitoriamente) y
receptores muscarinicos (M1, M2, M3, M4, M5) humanos donados (expresados
de manera estable), respectivamente. Se prepararon membranas celulares
mediante homogeneización seguida por centrifugación a 50.000 g durante 20
minutos.

Las membranas fueron incubadas con 1 nM de [3H]pirilamina para investigar
interacciones en el receptor H1, oO,lnM de [3H]N-metilescopolamina (NMA)
para estudiar interacciones en receptores muscarínicos. La fijación
inespecífica fue definida con 3pM de prometazina o 3 pM de atropina,
respectivamente. Los ensayos se realizaron a 250C en tampón fisiológico
(composición [mM]: NaCí: 136; KCI: 5; COCI2:2;MgSO4:1;Na2HPO4:1; Na-HEPES:
10; pH: 7,4) y los fragmentos de membrana fueron recuperados por filtracion.

Las afinidades de fexofenadina, terfenadina, desloratadina y loratadina por
los receptores fueron expresadas como la constante de inhibición K
(concentración de fármaco que ocuparía 50% de los receptores), utilizando
las concentraciones apropiadas de los radioligandos y sus afinidades.

Estudios funcionales
--------------------

Los efectos funcionales de fexofenadina y desloratadina fueron evaluados
determinando su capacidad para antago nizar la inhibición por carbachol de
la formación de AMP cíclico (CAMP) estimulada por forskolín en células CHO
intactas transfectadas de manera estable con receptores muscarinicos M2.
Las células fueron previamente marcadas con [3H]adenina y luego provocadas
con forskolín (100 pM) en presencia o ausencia de carbachol (3 uM) y los
antihistamínicos a las concentraciones indicadas. La actividad
fosfodiesterasa fue inhibida por 1 mM de IBMX.


Resultados
-----------

Experimentos de unión en equilibrio:

La fexofenadina, terfenadina, desloratadina y loratadina exhibieron todas
alta afinidad por el receptor H1 (Figura 1, Tabla 1). Sin embargo, tanto
desloratadina como loratadina exhibieron también altas afinidades por los
receptores muscarinicos, en particular el subtipo M2; la desloratadina es
sólo cinco veces más selectiva para el receptor H1 que para M2, y
loratadina sólo 11 veces más. La terfenadina es alrededor de 50 veces más
selectiva para el receptor H1 sobre M2, mientras que fexofenadina está
relativamente desprovista de actividad muscarínica, siendo 600 veces más
selectiva para el receptor H1 que para el receptor del subtipo M2. Las
afinidades de loratadina por H1 y M2 fueron 180 nM y 2 pM, respectivamente,
mientras que los valores correspondientes para terfenadina fueron 40 nM y 2
pM. En la Tabla 1 se presentan las afinidades de desloratadina y
fexofenadina por el receptor H1 y todos los subtipos muscarínicos.

Estudios funcionales:
--------------------

Ni fexofenadina ni desloratadina ejercieron por si mismas efectos
significativos sobre los niveles de cAMP estimulados por forskolín (datos
no mostrados>. Sin embargo, y como se esperaba, el agonista muscarínico
carbachol si inhibió la estimulación de cAMP por forskolin, con una CE50 de
335 nM (Figura 2A).

Incluso a una dosis suprafisiológica de 25 pM, fexofenadina no afectó la
capacidad de carbachol para inhibir la formación de cAMP (Figura 2B). En
contraste, desloratadina (25 pM) revirtió completamente la inhibición
inducida por carbachol de la formación de cAMP estimulada por forskolin.

La desloratadina revirtió el efecto del carbachol con una Cl50de 240 nM.
Mediante corrección por la concentración utilizada de carbachol (3pM), se
determinó que el valor K~ de desloratadina para el receptor M2 es 27 nM
(Figura 2C); este valor es muy próximo a la afinidad determinada en el
ensayo de unión (21 nM) y confirma que desloratadina es un antagonista
potente del receptor M2.

Discusión
---------

Cuando el metabolito activo de un producto farmacéutico presenta mejor
perfil farmacológico que el medicamento originario, es preferible
administrar el metabolito. De esta manera se pueden retener los efectos
terapéuticos mientras se eliminan los efectos indeseables del compuesto
originario. Por ejemplo, fexofenadina posee excelente potencia
antihistamínica pero no interfiere con los canales cardíacos de potasio
como lo hace su compuesto antecesor terfenadina.2 Los resultados de este
estudio sugieren que es aconsejable una cuidadosa caracterización
farmacológica de los nuevos antihistamínicos, para determinar si
representan una mejoría sobre el tratamiento existente.

Conclusiones: 
--------------------- 
1.) En ensayos de union, desloratadina es un antagonista potende del subtipo de receptor muscarinico M2 (que es el receptor cardiaco parasimpatico postsinaptico); tambien antagoniza marcadamente la inhibición inducida por carbachol de la formación de cAMP estimulada por forskolin. 

2.) Desloratadina presenta peor selectividad por H1/M2 que su compuesto antecesor loratadina. 

3.) Fexofenadina no muestra afinidad relevante por el receptor M2, con selectividad mejorada sobre su compuesto antecesor terfenadina, y estuvo desprovista de actividad muscarinica M2 en el ensayo del cAMP, incluso a dosis supra fisiológicas. 

Referencias 
----------- 

1. Vernier P Cardinaud B, Valdenaire O, Philippe H, Vincent JD. An 
evolutionary view of drug-receptor interaction: the bioamine receptor 
family. Trends Pharmacol Sci 1995; 16:375-81. 

2. Rampe D, Wible B, Brown AM, Dage RC. Effects of terfenadine and its meto 
bolites on a delayed rectifier K+ channel cloned from human heart. Mol 
Pharmacol 
1993;44: 1240-45. 

============================================================== 
18.) Desloratadine stauts 
============================================================== 
Source: 

MINUTES OF THE TWENTY-FOURTH MEETING OF THE MEDICINES 
CLASSIFICATION COMMITTEE HELD IN THE MEDSAFE CONFERENCE ROOM ON 
THE 18TH FLOOR OF GRAND PLIMMER TOWER, 4-6 GILMER TCE, WELLINGTON 
ON THURSDAY 2 NOVEMBER 2000 COMMENCING AT 9:30AM 

Desloratadine: 

This was a new chemical entity for which a classification had been deferred pending information from 
the Medicines Assessment Advisory Committee (MAAC) about its safety in comparison with that of 
loratadine. The MAAC had not found any significant problems with desloratadine. It was 
metabolised differently from loratadine and there were fewer potential problems for interactions with 
other medicines. 
Members were happy that the safety profile was satisfactory for OTC sale but questioned whether 
there were precedents for classifying a new chemical entity as a pharmacy-only medicine without a preliminary period as a prescription medicine. It was noted that fexofenadine, a metabolite of 
terfenadine, had been given immediate pharmacy-only status. The Committee agreed to make a 
similar recommendation for desloratadine. 

Recommendation 

That desloratadine should be classified as a pharmacy-only medicine. 

============================================================== 
19.) Desloratadine 
============================================================== 
(Aerius, Allex, Azomyr, DCL, Decarboethoxyloratadine, Descarboethoxyloratadine, Neoclarityn, 
Opulis, SCH 34117) 
Chemical Name: 
8-Chloro-6,11-dihydro-11-(4-piperidylidene)-5H-benzo[5,6]cyclohepta[1,2-b]pyridine 
Molecular Formula: C19 H19 Cl N2 
CAS Number: 100643-71-8 

WHO ATC Code: Antipruritics, Incl. Antihistamines, Anesthetics, Etc. (D04A); Other 
antihistamines for systemic use (R06A-X) 
EphMRA ATC Code: Anti-Pruritics (D4A); Systemic Antihistamines (R6A) 
Originator Company: Sepracor 
Licensee Company: Schering-Plough 
Last Update: 2000-11-17 
Accession Number: 10778 

Highest Development Phase: Preregistration 
Drug Development Phase: Indication Phase Country 
Allergic seasonal rhinitis Preregistration USA 
Allergic seasonal rhinitis Preregistration European Union 
Urticaria Preregistration USA 

Properties 

Mechanism of Action: Histamine H1 receptor antagonists 
Pharmacodynamics: Inhibits histamine-induced muscle contractions and skin reactions with greater potency than loratadine in preclinical studies 
Pharmacokinetic Characteristics: t�beta (h) : 19.0 - 34.6 
Route of administration: PO 
Comparative Efficacy: = naproxen (Osteoarthritis, PO); = naproxen (Rheumatoid arthritis, PO) 
Adverse Events: (Frequent) Headache 
Drug interaction: Minimal. Does not interact with alcohol; increase in gastrointestinal system 
disorders when coadministered with erythromycin; no clinically significant interaction with 
ketoconazole 

Commercial Introduction 

Desloratadine [DCL, SCH 34117, decarboethoxyloratadine, descarboethoxyloratadine] is an active 
metabolite of Schering- Plough's histamine H1 receptor antagonist loratadine [Claritin�], which is a 
leading nonsedating antihistamine. Desloratadine appears to be more potent than loratadine. 
Desloratadine has both antiallergic and decongestant effects in allergic rhinitis. Sepracor holds the 
patent rights to desloratadine and has exclusively licensed the drug to Schering-Plough. 
Schering-Plough has submitted a New Drug Application (NDA) to the US Food and Drug 
Administration (FDA) for marketing clearance for desloratadine as an orally administered agent for 
the treatment of allergic seasonal rhinitis. Approval in the US was expected in the fourth quarter of 
2000. However, the US FDA has missed the one-year deadline for determining approvability of the 
product. An analogous application has been made by Schering-Plough to the European Medicines 
Evaluation Agency (EMEA) of the European Union. The EMEA's Committee for Proprietary 
Medicinal Products has expressed a positive opinion, recommending the approval of the drug as 
Aerius™ for use as a once-daily therapy in the treatment of allergic seasonal rhinitis. Aerius will not be used as the brand name in the US. Schering-Plough has registered the name Neoclaritin™ in the US. Schering-Plough also has applications pending for desloratadine under the names Opulis™, Azomyr™, Neoclarityn™ and Allex™. 

Schering-Plough states that in addition to the development which is taking place for allergic seasonal rhinitis, desloratadine is being developed for other allergic indications and as other formulations in ongoing phase II and phase III studies. The company has filed an NDA to the US FDA for marketing clearance for the product for the treatment of chronic idiopathic urticaria (hives of unknown origin). 

The compound patent in the US for loratadine is due to expire in December 2002. Claritin� 
revenues accounted for > 25% of Schering-Plough's sales and growth in 1999. A use patent for 
desloratadine is not due to expire until April 2004. Schering-Plough has licensed from Sepracor a 
patent for the methods and compositions for treating allergic rhinitis using desloratadine, which 
expires in 2014. 

Lehman Market Analysis 

Company Indication/ Class Region Patent Expiry Launch Date Probability of Success Licensed 
Status Peak Sales Cycle 
Sepracor Allergy / Anti-histamine Wrld 2014 2000 90% Royalty $3500m (2010) Medium 
Schering Plough Allergic rhinitis / Anti-histamine US 2004 2001 90% In licensed $1000m (2009) 
Medium 
Schering Plough Allergic rhinitis / Anti-histamine ex US N/A 2001 90% In licensed $500m (2009) 
Long 
Copyright � Lehman Brothers International. All rights reserved. 

Review 

Pharmacokinetics 

In a randomised, double-blind, parallel-group study, 49 healthy volunteers received a single oral 
dose of desloratadine (5, 7.5, 10 or 20mg) or placebo. After 3 days, the same dose of desloratadine was administered once daily for 14 days. Mean t� was 19.0-34.6h for single-dose desloratadine; Cmax values (1.83- 7.08 ng/ml) and AUC0-8 values (32.5- 169 ng � h � ml-1) increased in proportion to dose. Apparent total body clearance was 114-201 L � h-1. At steady-state, after multiple dosing, Cmax values were in the range 2.18- 8.08 ng/ml. Apparent total body clearance and t� after multiple dosing were similar to single-dose values. Accumulation (multiple-dose AUC0-24h/single-doseAUC0- 8) was 1.1-1.6[1]. 
In a randomised, open-label, 4-way crossover study, 20 healthy, fasting volunteers received a single oral dose of desloratadine (5, 7.5, 10 or 20mg). There was a period = 14 days between each 
crossover arm. The slope for both Cmax vs dose and AUC0-t vs dose did not differ significantly 
from 1. The slope for AUC0-t vs dose did not differ significantly from linearity, whereas the slope 
for Cmax vs dose showed a marginal deviation from linearity (p = 0.049). This deviation was 
assessed as being of no significance for the pharmacokinetics of desloratadine[2]. 

In a randomised, open-label, 2-way crossover study, 18 healthy volunteers received a single oral 
dose of desloratadine under either fasted conditions or immediately following a high-fat, high-caloric 
meal. Each arm of the study was separated by a period of = 7 days. Cmax values for the fasted and fed states were 3.30 and 3.53 ng/ml, respectively. The relative bioavailability of desloratadine in 
fasted subjects, compared with fed subjects (based on the 90% confidence interval for the log 
transformations of the parameters Cmax and AUC) was in the range 93%-118%, demonstrating 
bioequivalence[3]. 

In an open-label, parallel-group study, 12 black men, 12 white men, 12 black women and 12 white 
women received a single oral dose of desloratadine 7.5mg, followed by once-daily administration of 
desloratadine for 14 days, beginning 3 days after the single dose. Statistical evaluation of 
log-transformed AUC and Cmax values showed that there were no clinically relevant differences for 
desloratadine pharmacokinetics between men and women. AUC and Cmax values were 32% and 
18% higher, respectively, in black subjects compared with white subjects. These differences were 
also classed as not clinically relevant[4]. 

Adverse Events 

Animal toxicology: desloratadine blocked the human cardiac K+ channel (stably expressed in a mouse cell line) in a concentration-, voltage- and time-dependent manner. It was less potent than loratadine and terfenadine[5]. In guinea- pigs, desloratadine caused QTc prolongation[6]. 

In mice, desloratadine = 300 mg/kg had no significant behavioural, neurological, or autonomic 
effects. In an analogous study in rats, oral desloratadine = 12 mg/kg had no significant effects on the same parameters. In mice, desloratadine 160 mg/kg did not protect against electroconvulsive shock. 
In mice, desloratadine and azatadine inhibited acetic acid-induced writhing with respective ED50 
values of 147 and 4.8 mg/kg. Also in mice, desloratadine = 300 mg/kg did not protect against 
physostigmine-induced lethality, whereas azatadine 2.2 mg/kg protected 50% of mice. In 
guinea-pigs, intraperitoneal desloratadine or loratadine (both 6 mg/kg) did not inhibit the binding of 
mepyramine to brain H1 receptors, indicating that desloratadine is unable to affect brain H1 
receptors associated with sedation. In vitro, desloratadine or loratadine (10 � 10-9- 10 � 10-6 
mol/L) did not significantly affect the cardiac K+ HERG channel expressed in Xenopus oocytes. 
Oral or intravenous desloratadine had no adverse effects on blood pressure, heart rate or ECG data 
in rats, guinea-pigs and monkeys. In these studies, desloratadine did not lengthen the QTc or the 
QRS interval[7]. 

In the isolated rabbit iris smooth muscle, desloratadine was a competitive antagonist of 
carbachol-induced contractions (pA2 = 6.67). When administered topically to the eye conjunctiva of conscious guinea-pigs, desloratadine caused a potent and long-lasting mydriasis (>2h at the ED50 dose of 2.3 mg/ml), whereas fexofenadine and carebastine were inactive at a dose of 10 mg/ml[8]. 

Adverse events: 

in a randomised, double-blind, 2-way crossover study, 24 healthy volunteers received an oral daily 
dose of desloratadine (45 mg/day) or placebo for 10 days. There was a washout period of 14 days 
before subjects were crossed over to the other regimen. Compared with baseline, changes in QTc 
intervals were = 6.5%; there was no statistically significant prolongation of the QTc interval by 
desloratadine. The maximum QTc intervals occurring after desloratadine and placebo treatment were 433 and 429 msec, respectively. The ventricular rate was statistically significantly higher during treatment with desloratadine, compared with placebo, but the difference (9.4 bpm) was not 
considered to be of clinical significance. The QT interval was shorter during desloratadine treatment, compared with placebo, but there was no effect on the PR or QRS intervals. The most frequent adverse event was mild-to-moderate headache; this occurred in 54% and 46% of desloratadine and placebo recipients, respectively[9]. 

In 2 randomised, parallel-group, double- blind studies in patients with allergic seasonal rhinitis for > 
2 years and moderate-to-severe symptoms (172-174 patients per group in study 1, 165-166 
patients per group in study 2), once-daily, oral desloratadine (5 or 7.5mg) or placebo was 
administered for 14 days. Headache was the most frequently reported adverse event, occurring in 
16%-24% and 14%-22% of desloratadine and placebo recipients, respectively. The incidence of 
somnolence was 2%-4% after desloratadine treatment and 2% after placebo. There were no 
changes in heart rate or in PR, QRS, QT or QTc waves. There was no effect on hepatic and renal 
function[10]. 

Drug Interactions 

In a randomised 4-way crossover study in 25 healthy volunteers, subjects received a single oral dose of desloratadine 7.5mg or placebo, both with and without alcohol. Alcohol dose was adjusted to achieve a mean blood level of 100 mg/dl. All alcohol-treated groups showed impaired performance, compared with placebo, in 4 psychomotor tests (Stanford Sleepiness Scale or SSS, Digit Symbol Substitution Test or DSST, Serial Add Subtract Reaction Time Test or ANAM Battery and Psychomotor Vigilance Test or PVT) in the first 8h after alcohol ingestion. Desloratadine was not significantly different to placebo in its effect on psychomotor performance, and desloratadine + 
alcohol was not significantly different to placebo + alcohol in psychomotor effects[11]. 

In a randomised, 2-way crossover, third-party blind study, 24 healthy volunteers received oral, 
once-daily desloratadine 7.5mg combined with either placebo or oral erythromcyin 500mg every 8h 
for 10 days. There was a washout period = 7 days separating each study period. Coadministration 
of desloratadine and erythromycin did not cause any significant change in ventricular rate or QT, PR, QRS or QTc intervals. Log-transformed Cmax and AUC values for desloratadine were 1.2- and 
1.1-fold higher, respectively, with concomitant erythromycin. The most frequent adverse events were gastrointestinal system disorders, occurring in 46% and 4% of subjects receiving desloratadine + erythromcyin and desloratadine + placebo, respectively. Dizziness and headache occurred in 25% and 17%, respectively, of desloratadine + erythromycin recipients and in 4% and 13%, respectively, of desloratadine + placebo recipients[12]. 

In a randomised, 2-way crossover, third-party blind study, 24 healthy volunteers received 
once-daily, oral desloratadine 7.5mg, combined either with placebo or oral ketoconazole 200mg 
twice-daily for 10 days. There was a washout period = 7 days separating each study period. 
Coadministration of desloratadine and ketoconazole did not cause any significant change in QT, PR, QRS or QTc intervals. Desloratadine + ketoconazole reduced the mean ventricular rate by 6.6 bpm. Log-transformed Cmax and AUC values for desloratadine were 1.45- and 1.39-fold higher, 
respectively, with concomitant ketoconazole. Headache was the most frequently reported adverse 
event, occurring in 42% and 38% of desloratadine + placebo and desloratadine + ketoconazole 
recipients, respectively[13]. 

Pharmacodynamics: 

Obstructive Airways Disease 
In vitro, desloratadine and loratadine displaced radioligand binding to the human H1 receptor with 
respective IC50 values of 51 and 721 nmol/L. The affinity of either compound for H2 or H3 
receptors was negligible. In isolated guinea-pig lung tissue, desloratadine and loratadine inhibited 
binding to peripheral H1 receptors with respective IC50 values of 840 and 3030 nmol/L. 
Desloratadine inhibited radioligand binding to human muscarinic receptor subtypes M1, M2 and M3 
with IC50 values of 48, = 250 and 125 nmol/L, respectively. Loratadine did not interact with 
muscarinic receptors. In isolated guinea-pig ileum, desloratadine inhibited histamine-induced 
contraction with 20-fold greater potency than loratadine. In vivo, orally administered desloratadine 
inhibited histamine-induced wheal and flare in guinea-pigs with = 2-fold greater potency than oral 
loratadine[14]. The histamine-induced activation of human bronchial and nasal epithelial cells in vitro was inhibited by desloratadine[15]. 

In vivo, in guinea-pigs, orally administered desloratadine was more potent than loratadine in 
providing protection against lethal histamine doses; the respective ED50 values were 0.15 and 0.37 
mg/kg. The protection provided by desloratadine lasted for = 24h. In mice, desloratadine was 4-fold 
more potent than loratadine in inhibiting histamine-induced rear paw swelling; the respective ED50 
values were 0.15 and 0.60 mg/kg. Nasally administered desloratadine, loratadine and levocabastine inhibited the nasal response to histamine in guinea-pigs with respective ED50 values of 0.9�g, 8.7�g and 0.025�g. Orally administered desloratadine 5 mg/kg significantly reduced acute antigen-induced bronchospasm in sensitised Cynomolgus monkeys. In sensitised guinea-pigs, orally administered desloratadine = 0.3 mg/kg significantly decreased the number of antigen-induced coughs[16]. 

Therapeutic Trials: 

Obstructive Airways Disease 
Treatment of allergic seasonal rhinitis: in 2 randomised, parallel-group, double-blind studies in 
patients with allergic seasonal rhinitis for > 2 years and moderate-to-severe symptoms (172-174 
patients per group in study 1, 165-166 patients per group in study 2), once-daily, oral desloratadine 
(5 or 7.5mg) or placebo was administered for 14 days. Both doses of desloratadine were 
significantly superior to placebo for the primary endpoint (patient assessment of total symptom 
severity scores using a 4-point scale ranging from 0 = none to 3 = severe). Both desloratadine doses also improved secondary endpoints (nasal, non-nasal and individual symptom severity scores and joint patient and physician evaluations)[10]. 

Decongestant effect in allergic seasonal rhinitis: in a series of randomised, parallel-group, 
double-blind studies (659-662 patients per group overall), patients with allergic seasonal rhinitis (for 
= 2 years) and moderate-to-severe symptoms received once-daily, oral desloratadine (5 or 7.5mg) 
or placebo for 14 days. The severity of congestion and stuffiness was assessed by patients using a 4-point scale (0 = none, 1 = mild, 2 = moderate, 3 = severe). Desloratadine significantly decreased nasal congestion and stuffiness at both dosage strengths, relative to placebo, as well as total symptom severity[17]. 

Effect on quality of life: in 407 patients with allergic seasonal rhinitis, the effect on quality of life 
(QOL) of 14 days of desloratadine treatment was assessed using the SF-36 Survey (to assess 
health-related QOL, or HQOL) and the Rhinoconjunctivitis QOL Questionnaire (RQLQ). The 8 
SF-36 domains were scored from 0 (worst) to 100 (best) and the 8 RQLQ domains were scored 
from 0 (not troubled) to 6 (extremely troubled). At baseline, 4 SF-36 domains were scoring less 
than for the general population: role limitations due to physical problems, bodily pain, social 
functioning and vitality, and RQLQ scores were in the range 2.9-4.3, consistent with a moderate 
disease burden. Desloratadine treatment significantly improved 2 of the SF-36 domains: social 
functioning and vitality. Desloratadine improved 4 of the RQLQ domains: practical problems, nasal 
symptoms, eye symptoms and activities, as well as overall assessment. HQOL improvements were positively correlated with therapeutic response (the latter scored jointly by investigator and patient), and the greatest improvements in SF-36 and RQLQ scores were associated with complete or major relief from disease symptoms[18]. 


References 

1.) Padhi D, Banfield C, Gupta S, Herron JM, Glue P, et al. Multiple-dose pharmacokinetics, 
safety, and tolerance of desloratadine in healthy volunteers. Journal of Allergy and Clinical 
Immunology 105: 385, Part 2, Jan 2000. [English]. Schering-Plough Research Institute, Kenilworth, 
New Jersey, USA 

2.) Herron JM, Padhi D, Affrime MB, Glue P, Gupta S, et al. Dose-proportionality, linearity, and 
pharmacokinetics of desloratadine in healthy adults. Journal of Allergy and Clinical Immunology 105: 
385, Part 2, Jan 2000. [English]. 

3.) Gupta S, Padhi D, Banfield C, Marbury T, Affrime MB. The effect of food on the oral 
bioavailability of desloratadine. Journal of Allergy and Clinical Immunology 105: 386-387, Part 2, 
Jan 2000. [English]. Schering-Plough Research Institute, Kenilworth, New Jersey, USA 

4.) Rosenberg MA, Cohen A, Padhi D, Banfield C, Gupta S, et al. Multiple-dose pharmacokinetics 
of desloratadine in subjects differing in race and gender. Journal of Allergy and Clinical Immunology 
105: 386, Part 2, Jan 2000. [English]. Peninsular Testing Corporation, Miami, Florida, USA; 
Schering-Plough Research Institute, Kenilworth, New Jersey, USA 

5.) Caballero R, Delp�n E, Valenzuela C, et al. Effect of descarboethoxyloratadine, the major 
metabolite of loratadine, on the human cardiac potassium channel Kv1.5. British Journal of 
Pharmacology 122: 796-798, Nov 1997. [English]. 

6.) Gras J, Llenas J, Palacios JM, et al. Descarboethoxyloratadine, like terfenadine, produces QTc 
prolongation in a guinea pig model of arrhythmogenesis. 1996 Annual Meeting American College of 
Allergy, Asthma & Immunology : 64, 8-13 Nov 1996. [English]. 

7.) Hey J, Anthes J, Barnett A, Tozzi S, Kreutner W. Preclinical cardiovascular and CNS safety 
profile of desloratadine, a selective and nonsedating histamine H1-receptor antagonist. Journal of 
Allergy and Clinical Immunology 105: 383, Part 2, Jan 2000. [English]. Schering-Plough Research 
Institute, Kenilworth, New Jersey, USA 

8.) Cardelus I, Anton F, Beleta J, et al. Anticholinergic effects of desloratadine, the major metabolite 
of loratadine, in rabbit and guinea-pig iris smooth muscle. European Journal of Pharmacology 374: 
249-254, 18 Jun 1999. [English]. Cardelus 
9.) I, Almirall Prodesfarma, Res Ctr, Dept Pharmacol, Cardener 68-74, Barcelona 08024, SPAIN 

10.) Banfield C, Padhi D, Glue P, Herron JM, Statkevich P, et al. Electrocardiographic effects of 
multiple high doses of desloratadine. Journal of Allergy and Clinical Immunology 105: 383, Part 2, 
Jan 2000. [English]. Schering-Plough Research Institute, Kenilworth, New Jersey, USA 

11.) Salmun LM, Lorber R, Danzig M, Staudinger H. Efficacy and safety of desloratadine in 
seasonal allergic rhinitis. Journal of Allergy and Clinical Immunology 105: 384-385, Part 2, Jan 
2000. [English]. Schering-Plough Research Institute, Kenilworth, New Jersey, USA 

12.) Scharf M, Rikken G, Salmun L, Staudinger H. Comparative effects of desloratadine and 
placebo with and without alcohol on performance measures. Journal of Allergy and Clinical 
Immunology 105: 394, Part 2, Jan 2000. [English]. Tri-state Sleep Disorders Center, Cincinnati, 
Ohio, USA; Schering-Plough Research Institute, Kenilworth, New Jersey, USA 

13.) Glue P, Banfield C, Affrime MB, Statkevich P, Reyderman L, et al. Desloratadine and 
erythromycin: pharmacokinetics and electrocardiographic pharmacodynamic effects. Journal of 
Allergy and Clinical Immunology 105: 387, Part 2, Jan 2000. [English]. Schering-Plough Research 
Institute, Kenilworth, New Jersey, USA 

14.) Affrime MB, Banfield C, Glue P, Keung A, Herron JM, et al. Desloratadine and ketoconazole: 
pharmacokinetics and electrocardiographic pharmacodynamic effects. Journal of Allergy and Clinical 
Immunology 105: 386, Part 2, Jan 2000. [English]. Schering-Plough Research Institute, Kenilworth, 
New Jersey, USA 

15.) Handley DA, McCullough JR, Fang Y, et al. Descarboethoxyloratadine, a metabolite of 
loratadine, is a superior antihistamine. 1996 Annual Meeting American College of Allergy, Asthma & 
Immunology : 65, 8-13 Nov 1996. [English]. 

16.) Vignola AM, Mondain M, Crampette L, et al. Inhibitory activity of decarboxyethoxy-loratadine 
on histamine activation of bronchial and nasal epithelial cells. Journal of Allergy and Clinical 
Immunology 93: 176, Part 2, Jan 1994. [English]. 

17.) Kreutner W, Hey JA, Anthes J, Barnett A, Tozzi S. Preclinical efficacy and antiallergic profile 
of desloratadine, a selective and nonsedating histamine H1-receptor antagonist. Journal of Allergy 
and Clinical Immunology 105: 382, Part 2, Jan 2000. [English]. 

18.) Nayak A, Lorber R, Salmun LM. Decongestant effects of desloratadine in patients with 
seasonal allergic rhinitis. Journal of Allergy and Clinical Immunology 105: 384, Part 2, Jan 2000. 
[English]. University of Illinois, Peoria, Illinois, USA; Schering-Plough Research Institute, 
Kenilworth, New Jersey, USA 

20.) Heithoff K, Meltzer EO, Mellars L, Salmun LM. Desloratadine improves quality of life in 
patients with seasonal allergic rhinitis. Journal of Allergy and Clinical Immunology 105: 383-384, 
Part 2, Jan 2000. [English]. Schering-Plough Research Institute, Kenilworth, New Jersey, USA 

Drug Development History 

17 Nov 2000 US FDA misses one-year deadline for determining approvability of desloratadine 
16 Oct 2000 Desloratadine recommended for approval in the EU as Aerius™ for the treatment of 
allergic seasonal rhinitis 
07 Sep 2000 Preregistration for Urticaria in USA (Unknown route) 
17 Aug 2000 Sales forecasts reviewed by Lehman Brothers 
19 May 2000 Phase-III for Urticaria in USA (Unknown route) 
08 Mar 2000 A preclinical study has been added to the pharmacodynamics field[16] 
06 Mar 2000 A clinical study has been added to the pharmacokinetics field[4] 
06 Mar 2000 A preclinical study has been added to the adverse events field [7] 
02 Mar 2000 Clinical studies have been added to the drug interactions field 
02 Mar 2000 Clinical studies in allergic seasonal rhinitis have been added to the therapeutic trials 
field 
02 Mar 2000 Clinical studies have been added to the adverse events field 
02 Mar 2000 Clinical studies have been added to the pharmacokinetics field 
02 Mar 2000 An in vivo study has been added to the adverse events field [8] 
17 Nov 1999 Preregistration for Allergic seasonal rhinitis in European Union (PO) 
17 Nov 1999 Preregistration for Allergic seasonal rhinitis in USA (PO) 
29 Sep 1998 New profile 
29 Sep 1998 Phase-III for Allergic rhinitis in USA (PO) 

=========================================================== 
20.) LORATADINE AND PREGNANCY 
=========================================================== 
Source: Drugs in Pregnancy and Lactation, Fifth Edition. 
by Lippincott Williams & Wilkins. 

No published reports describing the use of loratadine during human pregnancy have been located. The FDA has received six reports of adverse outcomes following exposure during pregnancy, including two cases of cleft palate, and one case each of microtia and microphthalmia, deafness, tricuspid dysplasia, and diaphragmatic hernia (F. Rosa, personal 
communication, FDA, 1996). 

Copyright 1999 by Lippincott Williams & Wilkins 

================================================================== 
DATA-MÉDICOS/DERMAGIC-EXPRESS No 4-(111)  DR. JOSÉ LAPENTA R. 
=================================================================== 

Produced by Dr. José Lapenta R. Dermatologist 
              Maracay Estado Aragua Venezuela 2.002-2026  
            Telf.: 04142976087 - 04127766810