|
As far back as October 23, 1998, Arava (leflunomide) manufacturer
was sent a letter from the Department of Health and Human
Services notifying them that The Division of Drug Marketing,
Advertising and Communications reviewed their submissions
and found they had violated the Federal Food, Drug,
and Cosmetic Act. The Arava materials were cited because
of the following reasons:
Fair Balance- Pregnancy/Risk to Fetus
The materials are misleading because they lack fair balance
and/or minimize the importance of serious risk information
included in the approved product labeling (PI) for Arava concerning
pregnancy and the potential risks to the fetus. Specifically,
the PI for this product includes a prominent boxed contraindication
and warning stating that pregnancy must be excluded before
the start of treatment with Arava. Arava is also contraindicated
in pregnant women and 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 risk to the fetus. Pregnancy must be avoided during
Arava treatment or prior to the completion of a specific drug
elimination procedure after Arava treatment. It is recommended
that all women of childbearing potential undergo this elimination
procedure upon discontinuing Arava. These warnings and contraindications
are due to the fact that Arava 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 while taking this drug, the patient should
be apprised of the potential hazard to the fetus. In addition,
men wishing to father a child should consider discontinuing
use of Arava and taking cholestyramine 8 grams 3 times daily
for 11 days to minimize any possible risk to the fetus. The
disclosure of this information should be preceded by a signal
that both emphasizes the importance of this information and
provides adequate prominence for disclosure of these risks
and related material facts.
Fair Balance – Hepatoxicity
The materials are misleading because they lack fair balance
and/or minimize the importance of serious risk information
included in PI for Arava regarding hepatoxicity. The WARNINGS
section of the PI indicates that Arava was associated with
elevations of liver enzymes, primarily ALT and AST, in a significant
number of patients enrolled in clinical trials. Although these
effects were generally reversible with dose reduction or discontinuation
of treatment, marked elevations (greater than three times
the upper limit of normal) occurred as well. Therefore, at
minimum, ALT measurements should be performed at baseline
and monitored initially at monthly intervals, then, if stable,
at intervals determined by the individual clinical situation.
In addition, Arava should not be used in patients with significant
hepatic impairment or positive hepatitis B or C serologies,
given the risk of increased hepatoxicity.
Superiority Claim
“The treatments we have now are good but many patients
either have an incomplete response or don’t’ have
a response and need a choice  such
as Arava.”
This claim is misleading because it suggests Arava is more
effective than current treatment options for rheumatoid arthritis
(RA) when such has not bee demonstrated by substantial supporting
evidence. The PI for Arava states that Arava was statistically
significantly superior to placebo in reducing the signs and
symptoms of RA and reducing the progression of the disease.
However, the PI also states that no consistent differences
were demonstrated between Arava and methotrexate or between
Arava and sulfasalazine in these efficacy parameters.
These FDA violations of Arava materials led the Division
of Drug Marketing, Advertising and Communications to recommend
that Arava manufacturer take the following actions:
1. Immediately discontinue the use of this, and all other
promotional materials for this product that contain the same
or similar violations.
2. Provide to DDMAC, in writing, HMR’s intent to comply
with #1 above. Your response should be received by November
6, 1998.
3. This response should include a list of all similarly violative
promotional materials and HMR’s method for discontinuing
their use.
To the Top
|
