Aventis Welcomes FDA Denial of Public Citizen Petition Regarding Arava(R) (leflunomide) Tablets

Aventis Welcomes FDA Denial of Public Citizen Petition Regarding
Arava(R) (leflunomide) Tablets
Decision Supports Safety and Efficacy Profile 


BRIDGEWATER, N.J., April 1  /PRNewswire-FirstCall/ -- Aventis today welcomed the
U.S. Food and Drug Administration's (FDA) denial of the Public Citizen Health
Research Group's citizen petition seeking to remove the company's rheumatoid
arthritis drug Arava(R) (leflunomide) Tablets from the U.S. market.  In a March
23, 2004 letter sent to Public Citizen, the agency said it concluded that, based
upon thorough evaluation of extensive available data, the benefits of Arava
outweigh the risks associated with the product. The letter states that "Arava's
continued availability is important and justified".   While the petition was
under review, Aventis provided the FDA with safety and efficacy data from
clinical trials, post-marketing experience, and large epidemiology studies.

(Logo:  http://www.newscom.com/cgi-bin/prnh/20000501/NYM197 )

"Weare pleased that the FDA has denied the petition and that Arava will
continue to be available to patients in the U.S. who need it," said Francois
Nader, M.D., Senior Vice President, Medical Affairs, Aventis North America.
"Arava is a much needed drug among the limited number of rheumatoid arthritis
therapies, and it is an important option for physician choice and patient care. 
We were confident that an objective review and assessment of the extensive data
available on Arava would lead to this result."

The petition denial follows a March 5, 2003 FDA Arthritis Advisory Committee
meeting in which committee members unanimously concluded that the benefit to
risk profile for Arava is acceptable for its current indications. The committee
also voted to recommend approval of an expanded indication for improvement in
physical function in patients with rheumatoid arthritis, which was subsequently
approved by the FDA on June 13, 2003.

Arava(R) (leflunomide), an oral disease-modifying antirheumatic drug (DMARD), is
a first-line therapy to reduce signs and symptoms, inhibit structural damage as
evidenced by X-ray erosions and joint space narrowing, and improve physical
function in active rheumatoid arthritis in adults. Rheumatoid arthritis is one
of the most common forms of arthritis, a potentially crippling autoimmune
disease that affects more than two million Americans, 70 percent of whom are
women.

Safety Information

Pregnancy Contraindication: Pregnancy must be excluded before the start of
treatment with Arava.  Arava is contraindicated in pregnant women or women of
childbearing potential who are not using reliable contraception.  Before
starting treatment with Arava, patients must be fully counseled on the potential
for serious risks to the fetus.  Pregnancy must be avoided during Arava
treatment or prior to the completion of a drug elimination procedure with
cholestyramine after Arava treatment.  It is recommended that all women of
childbearing potential undergo this elimination procedure upon discontinuing
Arava as the drug may increase the risk of fetal death or teratogenic effects
when administered to a pregnant woman.

If this drug is used during pregnancy or if the patient becomes pregnant when
taking this drug, the patient should be apprised of potential hazard to the
fetus.  In addition, men wishing to father a child should consider discontinuing
use of Arava and taking cholestyramine eight grams three times daily for 11 days
to minimize any possible risk to the fetus.

Important hepatic information:  Rare cases of severe liver injury, including
cases with fatal outcome, have been reported during treatment with leflunomide. 
Most cases of severe liver injury occur within 6 months of therapy and in a
setting of multiple risk factors for hepatotoxicity (liver disease, other
hepatotoxins).

Arava is not recommended in patients with significant hepatic impairment or
evidence of infection with hepatitis B or C viruses given the risk of increased
hepatotoxicity.

Arava was associated with elevations in liver enzymes, primarily ALT and AST, in
a significant number of patients in clinical trials.  Although these effects
were generally reversible with dose reductions or discontinuation of treatment,
marked elevations (greater than three times the upper limit of normal) occurred
as well.  Therefore, at minimum, ALT levels must be measured at the beginning of
therapy (baseline) and monitored initially at monthly intervals during the first
six months, then, if stable, every 6 to 8 weeks thereafter.

Arava is not recommended for patients with severe immunodeficiency, bone marrow
dysplasia, or severe, uncontrolled infections.  Rarely, severe infections
including sepsis, which may be fatal, have been reported. Rare cases of
pancytopenia, agranulocytosis, thrombocytopenia, Stevens-Johnson syndrome, and
toxic epidermal necrolysis have been reported in post-marketing experience.  At
minimum, patients taking Arava should have platelet, white blood cell count and
hemoglobin or hematocrit monitored at baseline and monthly for six months
following initiation of therapy and every 6 to 8 weeks thereafter.

Adverse reactions associated with the use of Arava in clinical trials include
diarrhea, elevated liver enzymes (ALT and AST), alopecia, and rash.

  Prescribing information is available by visiting http://www.arava.com/.

  About Aventis


Aventis is dedicated to treating and preventing disease by discovering and
developing innovative prescription drugs and human vaccines. In 2003, Aventis
generated sales of euro 16.79 billion (US $18.99), invested euro 2.86 billion
(US $3.24) in research and development and employed approximately 69,000 people
in its core business. Aventis corporate headquarters are in Strasbourg, France. 
The company's prescription drugs business is conducted in the U.S. by Aventis
Pharmaceuticals Inc., which is headquartered in Bridgewater, New Jersey.  For
more information, please visit: http://www.aventis-us.com/.

Statements in this news release containing projections or estimates of revenues,
income, earnings per share, capital expenditures, capital structure, or other
financial items; plans and objectives relating to future operations, products,
or services; future economic performance; or assumptions underlying or relating
to any such statements, are forward-looking statements subject to risks and
uncertainties.  Actual results could differ materially depending on factors such
as the timing and effects of regulatory actions, the results of clinical trials,
the company's relative success developing and gaining market acceptance for new
products, the outcome of significant litigation, and the effectiveness of patent
protection.  Additional information regarding risks and uncertainties is set
forth in the current Annual Report on Form 20-F of Aventis on file with the
Securities and Exchange Commission and in the current Annual Report --"Document
de Reference"- on file with the "Autorite des marches financiers" in France.

Pursuant to Article 7 of the COB Regulation no. 2002-04, this press release was
transmitted to the Autorite des marches financiers before its release. 

http://www.newscom.com/cgi-bin/prnh/20000501/NYM197DATASOURCE: Aventis



CONTACT:  Corinne Hoff of Aventis Media Relations, [phone],

; or Jason Ford of Aventis Global Product

Communications, [phone], ; or Terri Pedone of

Aventis U.S. Product Communications, [phone],





Web site:  http://www.aventis.com/

http://www.aventis-us.com/

http://www.arava.com/ 

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