E-DRUG: Otitis media: Pfizer vs CDC (fwd)

[Robert Marshall <marshalr@OHSU.EDU>]

---------- Forwarded message -----------------
E-drug: Otitis media: Pfizer vs CDC
-----------------------------------

August 3, 1999

Donna Shalala 
Secretary 
Department of Health and Human Services 
200 Independence Avenue, SW 
Washington, DC

Dear Secretary Shalala:

We are writing to make you aware of an apparent effort by Pfizer, Inc. to 
counter the CDC guidelines for the treatment of ear infections in children
and cause millions of dollars of unnecessary spending on antibiotics.
According to an internal company document that we have obtained (see
attached), Pfizer appears to have launched a campaign to convince doctors
to ignore Centers for Disease Control and Prevention (CDC) recommendations
favoring the effective and inexpensive antibiotic amoxicillin
(full course for 10 kg child = $18.98, retail, CVS) over Pfizer's drug 
azithromycin (full course for 10 kg child = $34.69, retail). The
Pfizer document explicitly states the purpose of the campaign: "The focus
is to counter the CDC guidelines." We urge you to inform the nation's
pediatricians, family practitioners and nurse practitioners of this
campaign so they are not duped into draining the Medicaid program of needed
resources and of wasting large amounts of money on treating other patients
with this needlessly expensive and second rate drug for ear infections.

At issue are CDC recommendations developed after consultation with a
working group of national experts and published in the Pediatric Infectious
Disease Journal in January 1999.(1)

The recommendations address treatment options at a time of increasing 
antibiotic resistance to the most important cause of ear infections, the
bacteria pneumococcus. The CDC concluded that:

* Amoxicillin, the most commonly used and least expensive of antibiotics 
considered, remains the first choice for the treatment of uncomplicated ear
infections. The experts recommended increasing the dosage of amoxicillin
for some children to overcome drug-resistant pneumococcus, saying "no oral
antimicrobial agent currently available would be expected to consistently
eradicate penicillin nonsusceptible pneumococcus better than amoxicillin."

* When amoxicillin fails, appropriate treatment options are drugs that
treat both resistant pneumococcus and other possible causes of ear
infections. These include certain other drugs in the penicillin and 
cephalosporin families. One of these drugs is given as an injection and can
achieve higher levels of drug in the middle ear than amoxicillin.

* Drugs in the family of macrolides (such as azithromycin), however, offer 
no advantage over amoxicillin in initial treatment of ear infections and
are unproven for treatment failures.

In the months since publication of the CDC-sponsored recommendations, no
new research or significant opposition from experts have undermined these
conclusions.

Yet we have become aware of an apparent national campaign by Pfizer, the 
maker of the macrolide drug azithromycin (known as Zithromax) to counter
the CDC guidelines, evidently by encouraging physicians and other primary
caregivers of children to listen to inaccurate presentations by
teleconference. 

Pfizer's financial motive to counter the CDC guidelines is as massive as it
is obvious. Ear infections are responsible for about 25 million office
visits in the United States--more than for any other diagnosis in
pediatrics.(2) Over the past several years, Pfizer has aggressively
marketed azithromycin to pediatricians, distributing the drug's mascot (a
zebra) as dolls and attachments to stethoscopes and using wrap-around
advertisements that arrive covering major pediatric publications such as
American Academy of Pediatric News. Pfizer is well known as a company that
sponsors countless promotional events and lunches for physicians. At
least one of these events violated the drug manufacturers code of marketing
ethics.(3)

The overall zithromax campaign has paid off handsomely for Pfizer--to the 
tune of about $1 billion each year worldwide (including its use for
conditions besides ear infections).(4)

So what to do when a consensus panel of experts says your drug doesn't work
consistently enough to be recommended for the most common condition of
childhood?

According to information we've obtained, the answer is to fight back--hire 
your own experts and encourage practitioners to listen to Pfizer-sponsored
presentations that illegitimately criticize the CDC recommendations (see
attached document).

We tuned in to one such presentation that ran for over one month to the 
beginning of July to hear Dr. Russell Steele, a pediatric infectious
disease specialist at the Louisiana State University School of Medicine
claim:

1. "If we increase the amoxicillin resistance to what we are seeing today, 
that is to between 50 and 60 percent, then the failure rate [for
amoxicillin] anticipated would be 1 in 4 to 1 in 3."

Dr. Steele cites no evidence to support his claim that 25 to 33 percent of 
all children with ear infections will not respond to amoxicillin. That's
because there have not been any such data published or presented.

Looking only at cases of the most highly resistant pneumococcus, if 
amoxicillin fails in a significant proportion of cases, other oral
antimicrobial drugs (such as macrolides) will also fail. That's because, as
the CDC noted, amoxicillin is the best available oral antibiotic for
resistant pneumococcus.

Indeed, the most recent available evidence suggests that Pfizer's drug 
azithromycin may have a microbiological failure rate of as high as 60
percent. Data presented from an international multicenter trial in May 1999
at the European Society for Pediatric Infectious Diseases conference showed
that azithromycin killed the bacteria in just 39 percent of ear infections
in children.(5)

2. "If the failure rate [of amoxicillin] is unacceptable, then macrolides 
and cephalosporins would be considered."

This suggestion to use macrolides for resistant pneumococcus is
unjustifiable. As the consensus panel makes clear, macrolides do not have
proven efficacy against resistant pneumococcus and are not recommended when
amoxicillin fails. In fact, the potential for increasing resistance to
macrolides is a very serious concern. A recent study of pneumococcus in the
noses of healthy Italian children found a rate of macrolide resistance of
40 percent, compared to a rate of penicillin (or amoxicillin) resistance of
just 5 percent.(6)

3. "Another option is starting with a macrolide or cephalosporin as first 
line therapy."

This is an indefensible and expensive proposition. Indefensible, because 
azithromycin and other macrolides have poor proven efficacy against
resistant pneumococcus. Expensive, because only about 5 percent of initial
ear infections are now treated with azithromycin--compared to about 65
percent with amoxicillin.(7) Because azithromycin is at least 50 to 100
percent more expensive than amoxicillin (depending on the dosing), using
azithromycin as a first line therapy would add millions of dollars of
needless expense to the health care system.

4. "Most children will respond to macrolides even if the laboratory tells 
you [the bacteria] is resistant."

Since most ear infections clinically resolve on their own, with or without 
antibiotic therapy,(8)  it is true that most children taking azithromycin
will also feel better. This isn't saying very much about the drug, however.
>From a microbiologic point of view, as noted above, the most recent
evidence suggests that azithromycin frequently fails to successfully
eradicate the organisms that cause ear infections.

Moreover, the CDC recommendations state: "Unlike the graded resistance to 
[penicillin and cephalosporin antibiotics], which may be overcome by
increasing the dose, when macrolide resistance is present these agents
should not be used."

5. "With the way things are going, I think we'll have to probably abandon 
even the high dosage [of amoxicillin]."

Less than six months after the CDC concluded that "amoxicillin is the best 
oral antimicrobial agent in clinical use for treating [resistant
pneumococcus]," a Pfizer sponsored presenter is predicting, without
presenting any evidence, that the drug will have to be abandoned! Of
course, the use of high-dose amoxicillin may eventually lead to the
development and spread of significant pneumococcal resistance. (The use of
any antibiotic carries the risk of resistance.)

But the CDC, after reviewing the recommendations of experts from around the
country, has concluded that amoxicillin remains the best oral treatment for
ear infections in children, with azithromycin offering no additional
advantage. In summary, Pfizer appears to have launched an unprecedented
campaign to counter the CDC recommendations for treatment of ear
infections, a campaign that if successful, would leave children no better
off but would cost the health care system millions of dollars. We urge
you to defend these recommendations and protect the Medicaid budget and 
total health expenditures by informing primary care providers of children
of this inappropriate marketing campaign.

cc: David Satcher, M.D., Ph.D. 
Surgeon General of the United States

Sincerely,

Joshua Sharfstein, M.D. 
Fellow in General Pediatrics 
Boston Medical Center

Sidney M. Wolfe, M.D., Director 
Public Citizen's Health Research Group


1. Dowell S, et al. Acute otitis media: management and surveillance in an 
era of pneumococcal resistance. Pediatric Infect
Disease Journal 1999;18(1):1-9.

2. Otitis Media. Behrman: Nelson Textbook of Pediatrics, 15th ed., W. B. 
Saunders Company, 1996, p. 1814.

3. Sharfstein J. Pfizer Night at Boston Billiards. New England Journal of 
Medicine 1997; 337(2):134.

4. Galewitz P. SmithKline's Augmentin beats Pfizer's Zithromax in
antibiotic battle. AP business wire, May 4, 1999.

5. Leibovitz E, Dagan R, Jacobs MR, et al. Bacteriological and clinical 
response in acute otitis media: amoxicillin/clavulanic acid
vs. azithromycin. Paper presented at the 17th annual meeting of the
European Society for Pediatric Infectious Diseases in Greece,
May 19-21, 1999.

6. Principi N, et al. Risk factors for the carriage of respiratory
pathogens in the nasopharynx of healthy children. Pediatric
Infectious Disease Journal 1999;18: 517-23.

7. Thompson D, et al. Management of otitis media among children in a large 
health insurance plan. Pediatric Infectious Disease Journal 1999;8: 239-44.

8. Berman S. Otitis Media in Children. New England Journal of Medicine 
1995;332:1560-5.



Larry D. Sasich, Pharm.D., M.P.H., FASHP
Research Analyst
Public Citizen Health Research Group
1600 20th Street, NW
Washington, DC, 20009
USA 
Phone: 202-588-7782
FAX: 202-588-7796
Web Site: www.citizen.org/hrg

Email: lsasich@citizen.org  [added manually, WB]

[USD 18.98 retail cost for amoxicillin treatment!? That's a rip-off!
UNICEF sells a 100ml bottle of 25mg/mL generic amoxicillin syrup for just
51 dollarcents, and a box of 1000 250mg amoxicillin tablets for only 
USD 20.98 - this means 42 dollarcents per 20 tablets! Azithromycin is not
listed in the MSH price indicator guide 1998. WB]
 
--