Ortho Evra Lawsuit; Evra Lawsuit;                           
Birth Control Patch Lawsuit
InternetDrugNews.com
Explanation of why people are suing the makers of Ortho Evra and what the lawsuit is all about including the allegations that Ortho Pharmaceuticals (a subsidiary of Johnson and Johnson) failed to tell doctors that Ortho Evra exposed women to high levels of hormones that may have caused dangerous side effects; written by a famous lawyer who specializes in suing drug companies.

The Ortho Evra Birth Control Patch Lawsuit -
A complicated situation

The Ortho Evra birth control patch was approved by the Food and Drug
Administration on Nov. 20, 2001, and has been used by more than five
million women.
Click Here to read Ortho Evra's FDA approval Letter database beginning with its original approval letter from 2001

It is the only birth control product of its kind in that its hormonal
contraceptive components are delivered transdermally. Ortho-McNeil
adverytised the patch in a way that appealed to young women to get
them into using the patch as their primary method of birth control. 

While the patch has been used by women of various ages, its use is most
commonly seen in young women, women between the ages of 16 through 24.

On Nov. 10, 2005, manufacturer Ortho-McNeil Pharmaceuticals Inc.
revised the warnings for Ortho Evra, prompting a surge in litigation
against it as well as a family of Johnson & Johnson defendants.

Click Here to read the above-cited Ortho Evra Safety Alert Letter dated
11/10/05 and posted to the FDA website on 11/14/05


The lawsuits commonly allege that the patch poses an increased risk of
thromboembolic events to users when compared to alternative forms of
hormone-based birth control. 

These events include blood clots, pulmonary emboli and deep vein
thrombosis, which have caused death, strokes, heart attacks and
extensive surgical and medical intervention, including prolonged
anti-coagulant therapy.

The Ortho Evra birth control patch belongs to a category of contraceptives
known as combination hormonal contraceptives.  There are two
hormones used in the patch -- estrogen and progestin. 

The estrogen component of the patch is called ethinyl estradiol (EE) and
has been used in varying doses in oral contraceptives for many years.
The progestin component of the patch is called norelgestromin (NGMN).
 

NGMN is the active metabolite of norgestimate and is the primary
progestin compound found in many birth control pills.  Both EE and NGMN
are delivered transdermally, or through the skin and directly into the
bloodstream.

Would you like to see more information regarding Ortho Evra?

OrthoEvra.com - the official Ortho Evra website; contains prescribing
information, how to use the patch, who should use the patch, frequent a
sked questions, information on birth control, a $5.00 off coupon for the
purchase of Ortho Evra.

Prescribing Information For Ortho Evra - official (FDA approved) prescribing
information for Ortho Evra.  This is the information your doctor and
pharmacist use when they want to learn about Ortho Evra's warnings,
side effects, mechanism of action, dosing, etc. ( PDF Format - easy to print).

Picture of an Ortho Evra Patch

Recent News Concerning Ortho Evra - from Google news; news reports from
newspapers, magazines and websites regarding Ortho Evra; updated
constantly throughout the day (sorted by date; the latest stories are on
the top of the page).

Scientific Papers On Ortho Evra - from the National Institutes of Health
scientific research database; an extensive catalogue of papers regarding t
he product.

FDA Approval Letters Etc For ZZOrtho Evra …[FDA]

YourLawyer.com; extensive database of data and case-law regarding drug
liability actions including Crestor, Zyprexa, Accutane, Prem Pro, etc.


Ortho-McNeil sought and obtained FDA approval of the patch based in
large part on data generated in connection with oral contraceptives. 
he initial package insert for the patch states:

There is no epidemiological data available to determine whether safety
and efficacy with the transdermal route of administration would be
different than the oral route.

The information contained in this package insert is principally based on
studies carried out in women who used combination oral contraceptives…


The following information is derived primarily from studies of birth control
pills.  The contraceptive patch is expected to be associated with similar
risks.  Click Here to read the original Ortho Evra label cited above


How Is A Birth Control Patch Like Ortho Evra Different from Birth
Control Pills?

The patch and the birth control pill are different products with completely
different pharmacokinetic profiles.  These differences extend to how each
product is delivered, absorbed, distributed, metabolized and excreted.

Click here for a definition of the word "pharmacokinetic"


For example, the estrogen and progestin components of a typical birth
control pill are subject to what is known as first-pass metabolism
through the liver.  (First-pass metabolism refers to the absorption of an
orally taken drug through the intestinal wall, and directly to the liver
through the portal vein system). 

Drugs subject to first-pass metabolism get metabolized before reaching
the target organ. 

Unlike birth control pills, the hormones in the patch are delivered through
the skin and directly into the bloodstream. 

There is no first-pass metabolism through the liver with the Ortho Evra
patch because they bypass the digestive tract and go directly into the
bloodstream without being broken down.

A big difference between birth control pills and the Ortho Evra patch
relates to a woman's total exposure to estrogen and progestin. 
Ortho-McNeil has stated in each of the Ortho Evra package inserts that:

Women of all ages who use combination hormonal contraceptives, should
use the lowest possible dose formulation that is effective and meets the
individual patient needs. Click Here to see the a recent Ortho Evra
package insert (dated 11/10/2005)


Supposed Increased Exposure To Hormones

A woman's total exposure to hormones used in various forms of hormona
l birth control is often expressed in terms of the "Area Under The Curve,"
or AUC.  The AUC in this context simply refers to a woman's total
exposure to both estrogen and progestin. 

The AUC for estrogen and progestin with the Ortho Evra patch is
significantly higher than the AUC for estrogen and progestin with
birth control pills.

Birth control pills are taken daily.  They produce daily serum concentration
levels of estrogen and progestin in the form of "peaks and troughs." 

In other words, the amount of estrogen and progestin found in the blood
of an oral contraceptive user will vary from day-to-day with high peaks
(tops) and low troughs (bottoms).

The opposite of "peak and trough" exposure is a "constant steady state"
exposure (abbreviated as Css in the medical literature).  Css in this
context refers to a consistent, steady level of exposure to birth control
hormones. 

Unlike the "peak and trough" exposure observed in birth control pills,
Ortho Evra produces a high, consistent, steady state exposure to both
estrogen and progestin throughout the patch's wear cycle. 

Some scientists claim that this results in a noticeably greater exposure
to both estrogen and progestin in users of the patch as compared to users
of oral contraceptives (i.e. a significant increase in the AUC). 

A recent study indicated that the exposure to the estrogen component of
Ortho Evra was 1.6 times higher than the exposure seen in women who
used a contraceptive pill. (see end-note #1)

Did The New Warnings Ignore Differences Between The Pill
And The Patch?

On Nov. 10, 2005, Ortho-McNeil, in conjunction with the FDA, announced
changes to the warnings for Ortho Evra.  The focus of the new warnings
relate to an Ortho Evra user's increased exposure to estrogen compared
to typical birth control pills.
Click Here to read the above-cited Ortho Evra Safety Alert Letter dated
11/10/05 which was posted to the FDA website on 11/14/05

Estrogen is pro-thrombotic, which means the higher the dosage, the more
risk there is for thrombosis. (see endnote #2)  The new warnings
released by Ortho-McNeil contain the following language:

The pharmacokinetic (PK) profile for the ORTHO EVRA® patch is different
from the PK profile for oral contraceptives in that it has higher steady
state concentrations and lower peak concentrations. 

AUC and average concentration at steady state for ethinyl estradiol (EE)
are approximately 60% higher in women using ORTHO EVRA® compared
with women using an oral contraceptive containing EE 35 µg. 6
(µg = micrograms).

The new insert stated that women who use Ortho Evra are exposed to
about 60 percent more total estrogen in their blood than if they were
taking a typical birth control pill containing 35 micrograms of estrogen.

Ortho Evra is intended to release 20 micrograms of estrogen into the
bloodstream each day.  The warnings confirm that Ortho Evra exposes
women to 60 percent more estrogen than they would be exposed to
with a birth control pill containing 35 micrograms of estrogen. 

More Hormones Get Into The Blood - So What?

Lawyers claim that this information was never disclosed before. 
The lawyers claim that an increase in exposure to estrogen is at
the heart of the side effects that are behind the lawsuits. 


Prior to the new warnings, medical providers and users of Ortho Evra
were told only that Ortho Evra releases 20 micrograms of estrogen
into the bloodstream each day.

The new warnings seem to indicate that an Ortho Evra user is exposed
to approximately 60 percent more estrogen than they would be with a
35-microgram pill. 

This appears to equate with exposure to more than 50 micrograms of
estrogen, not the 20 micrograms originally disclosed by Ortho-McNeil.
The new warnings released by Ortho-McNeil confirm an extremely
significant and dangerous increase in exposure to a hormone that is
known to be pro-thrombotic.

The lawyers think that Ortho-McNeil's initial reliance on data from birth
control pills to obtain approval for its birth control patch was not properly
disclosed and that this lack of proper disclosure caused doctors to
prescribe Ortho Evra without being able to know the big picture including
possible risks associated with blood clots caused by big doses of
hormones.

Lawyers suing Ortho claim that Ortho-McNeil's statement to prescribing
physicians and patients that the patch is expected to have risks similar to
those of birth control pills is misleading.  They claim that the company did
not conduct any pre-market testing sufficient to draw that conclusion or expectation.

Progestin Also Plays A Role In The Lawsuit

There is another aspect to the safety profile of Ortho Evra that the lawyers
claim has not been disclosed by Ortho-McNeil or Johnson & Johnson:  the
significance of the type of progestin selected by Ortho-McNeil for use in Ortho Evra. 

Once again, the progestin component of Ortho Evra is called
norelgestromin (NGMN).  An examination of the pharmacokinetic profile
for Ortho Evra confirms that the total exposure, or the AUC, to NGMN
essentially tracks the total exposure to estrogen.

No Thrombotic Balance

Generally speaking, the body seeks to maintain a balance between factors
which cause the human blood to clot (pro-thrombotic factors) and the
factors that prevent the blood from clotting (anti-thrombotic factors).

This balance allows blood to perform its intended clotting function as
needed ( such as when you cut yourself and a blood clot is needed to stop
the bleeding).

If this balance is tipped in favor of the pro-thrombotic factors, the result
may be an increase in thrombotic risk, or a "pro-thrombotic state."
(See endnote #3)  Estrogen is a pro-thrombotic factor. 

Progestin, or progestagen, is an anti-clotting factor.  The progestin
component of combination hormonal contraceptives is designed to
counter the pro-thrombotic effects of the estrogen component.

The initial and revised warnings for Ortho Evra relate only to the increased
exposure to estrogen caused by the patch as compared to a typical birth
control pill. 

There were and are no warnings relating to NGMN, or the progestin
component of the patch.  Neither the old nor the new Ortho Evra package
inserts address the relationship between NGMN and Ortho Evra's
pro-thrombotic risks.

Third-Generation Progestins

The FDA's Medical Officer Review for the New Drug Application for Ortho
Evra states "The progestin component of Ortho EVRA™ is norelgestromin
(the generic name for 17-deacetyl-norgestimate), a new molecular entity
(NME), not yet classified, but sometimes called a third generation
progestin. . . ." (see endnote #4) 

Third-generation progestins have been shown to disturb the homeostatic
balance discussed above to a greater extent than second-generation
progestins.  The result is that third-generation progestins present an
increased risk of clotting compared to second-generation progestins.

One of the components of the clotting cascades is known as the "protein C
system." (see endnote #4) 

This system is critical to maintaining a balance between clotting and
anti-clotting factors. 

The protein C system is one of the anti-clotting factors designed to counter
the pro-thrombotic effects of estrogen.  Defects in the "protein C
pathway" are associated with an increased risk of venous
thrombo-embolism.11  Women who are born with or who develop a
resistance to  activated protein C (APC) have a considerably increased risk
of thrombosis.12

Epidemiological studies suggest that women who use oral contraceptives
with third-generation progestins have a higher risk of venous thrombosis
than women who use oral contraceptives with second-generation
progestins.13 

This is because women who use oral contraceptives with third-generation
progestins develop a resistance to APC.14  This resistance is sometimes
referred to as "acquired APC resistance." (see endnote #5)   

Acquired APC resistance disturbs the homeostatic balance discussed above
and places the body in a pro-thrombotic state.16  Some studies suggest
that women taking oral contraceptives with third-generation progestins
have APC resistance similar to that found in women who are born with a
hereditary clotting disorder known as Factor V Leiden.17 

Women who are born with the Factor V Leiden mutation who take oral
contraceptives with third-generation progestins exhibit a 30-50 fold
increase in venous thrombosis.18 

Unfortunately, the increased clotting risk posed by third-generation
progestins such as norelgestromin has never been disclosed to prescribing
physicians or patients, and is not contained in the new warnings for
Ortho Evra.

Varying Absorption Rates

Further compounding the altered exposure to the hormones with Ortho
Evra is the fact that different areas of the body have different absorption
rates. 

A recent study confirmed that placement of the patch on the abdomen,
one of the application sites recommended by Ortho-McNeil, resulted in 20
percent less absorption of the estrogen component of the patch as
compared to the arm, buttock or torso. 

Stated otherwise, a woman who uses the patch on her arm is exposed to
20 percent more estrogen than a woman who uses it on her abdomen.

In addition, there is concern that patch replacement after an adhesion
problem results in additional hormone exposure. 

There is no information provided to physicians or patients that the
application of a new patch following an adhesion problem may expose
a user to higher hormone levels in the bloodstream.

Following the warning changes for Ortho Evra, and the filing of numerous
actions against Ortho-McNeil and the family of Johnson and Johnson
defendants across the country, including many individual actions and at
least two class actions, the law firm of Parker & Waichman filed a
petition with the Judicial Panel on MultiDistrict Litigation.

The petition seeks transfer and consolidation of all federal Ortho Evra
cases for coordinated pre-trial proceedings.  The various jurisdictions
requested by parties who have appeared in the MDL proceedings include
the District of New Jersey, the Eastern District of New York, and
Northern and Southern Districts of Ohio. 

The MDL panel has docketed the Ortho Evra petition for hearing on Jan.
26, 2006.  The first Ortho Evra case filed in the United States has been
Set for trial in June 2006 in Austin, Texas.


Endnotes

1 - A graph depicting the peak and trough exposure to estrogen and
progestin with oral contraceptives can be found  at  Michiel Wilhelmus
van den Heuvel, et al., Comparison of Ethinylestradiol Pharmaco
Kinetics in Three Hormonal Contraceptive Formulations: the vaginal
ring, the transdermal patch and an oral contraceptive,
Contraception, 2005; 72: 168-174, 171. 

2 - Huib A.A.M. van Vliet, et al., Association between Sex
Hormone-Binding Globulin Levels and Activated Protein C Resistance
in Explaining the Risk of Thrombosis in Users of Oral Contraceptives
Containing different Progestogens, Human Reproduction,  2005; 20:
563-568.

3 - J. Rosing, et at., Oral Contraceptives and Venous Thrombosis:
different sensitivities to activated protein C in women using second -
and third-generation oral contraceptives, British Journal of Haematology
1997; 97: 233-238.

4   -  Medical Officer's Review: NDA 21-180 ORTHO EVRA
(noregestromin and ethinyl estradiol transdermal system), FDA
released 11/6/2001. 

5 - Jeanet M. Kemmeren, et al., Effect of Second- and Third-Generation
Oral Contraceptives on the protein C system in the absence of the factor
VLeiden mutation: a randomized trial, Hemostasis, Thrombosis, and
Vascular Biology 2004; 103: 927-33.

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