Politics and Medicine - Add Statins to Birth Defects Ipledge program established for Accutane

Author

Add Statins to Birth Defects Ipledge program established for Accutane

Sharon Hope

2005-08-16, 8:58 am

FDA has taken action to mitigate the risk of birth defects from the Acne
medication Accutane (Isotretinoin).
http://www.fda.gov/bbs/topics/NEWS/2005/NEW01218.html

Why stop there? Why not add statins to the birth defects risk mitigation
registry and procedures?

Birth defects can be caused by the cholesterol-lowering Statin drugs, which
include Atorvastatin (aka Lipitor), fluvastatin (aka Lescol), lovastatin
(aka Mevacor), pravastatin (aka Pravachol), simvastatin (aka Zocor),
rosuvastatin (aka Crestor), and cerivastatin (Baycol), and now Vytorin
(Zocor and Zetia (ezetimibe/simvastatin) combination).

Statins are the largest selling class of drugs in the world, and in history.
Lipitor is the largest selling of all drugs. Lowering the threshold for
cholesterol treatment by statins has increasingly resulted in statins
prescribed to patients of childbearing ages.

Why hasn't the FDA added statins to the Ipledge registry they have recently
established for Accutane?

"To obtain the drug, in addition to registering with iPLEDGE, patients must
comply with a number of key requirements that include completing an informed
consent form, obtaining counseling about the risks and requirements for safe
use of the drug, and, for women of childbearing age, complying with required
pregnancy testing."

Adding statins to this established registry is the responsible thing to do,
and the additional cost would be minimal and the risk mitigation.

http://www.ncbi.nlm.nih.gov/entrez/...6153&query_hl=8
Am J Med Genet A. 2004 Dec 15;131(3):287-98.
Mechanistic and epidemiologic considerations in the evaluation of adverse
birth outcomes following gestational exposure to statins.

Edison RJ, Muenke M.

Medical Genetics Branch, National Human Genome Research Institute, National
Institutes of Health, Department of Health and Human Services, Bethesda,
Maryland 20892-3717, USA.

The cholesterol-lowering "statin" drugs are contraindicated in pregnancy,
but few data exist on their safety in human gestation. We reviewed case
reports for patterns suggesting drug-related effects on prenatal development
and considered a variety of mechanisms by which such effects, if confirmed,
might occur. This uncontrolled case series included all FDA reports of
statin exposures during gestation, as well as others from the literature and
from manufacturers. Exposures and outcomes were reviewed and were tabulated
by individual drug. Age-specific rates of exposure to each drug among women
of child-bearing age were estimated. Of 214 ascertained pregnancy exposures,
70 evaluable reports remained after excluding uninformative cases. Among 31
adverse outcomes were 22 cases with structural defects, 4 cases of
intrauterine growth restriction, and 5 cases of fetal demise.

There were two principal categories of recurrent structural defects:

cerivastatin and lovastatin were associated with four reports of severe
midline CNS defects;

simvastatin, lovastatin, and atorvastatin were all associated with reports
of limb deficiencies, including two similar complex lower limb defects
reported following simvastatin exposure.

There were also two cases of VACTERL association among the limb deficiency
cases.

All adverse outcomes were reported following exposure to cerivastatin,
simvastatin, lovastatin, or atorvastatin, which are lipophilic and
equilibrate between maternal and embryonic compartments. None were reported
following exposure to pravastatin, which is minimally present in the embryo.

Statins reaching the embryo may down-regulate biosynthesis of cholesterol as
well as many important metabolic intermediates, and may have secondary
effects on sterol-dependent morphogens such as Sonic Hedgehog.

The reported cases display patterns consistent with dysfunction of
cholesterol biosynthesis and Sonic Hedgehog activity. Controlled studies are
needed to investigate the teratogenicity of individual drugs in this class.

PMID: 15546153 [PubMed - indexed for MEDLINE]

SJ Doc

2005-08-16, 11:58 am

On Tue, 16 Aug 2005 00:44:20 -0700, "Sharon Hope" wrote:

>Why stop there? Why not add statins to the birth defects risk
>mitigation registry and procedures?

I have to keep repeating that "There are no stupid questions"
mantra, but - damn it - I just can't hold onto my temper this
morning. That's a stupid question.

Cystic acne - the condition for which the retinoids (i.e.,
Accutane and its congeners) are used - occurs during the
childbearing years. The common use of the HMG-CoA
reductase inhibitors (the "statins") is in the later decades of
life. Except in relatively rare congenital disorders such as
the hyperlipoproteinemias, the statin drugs are not commonly
prescribed to women during the early decades of their
adult lives.

And it's not just the HMG-CoA reductase indicators that
are not to be used indiscriminately in women who might
become pregnant. Many commonly-prescribed classes of
drugs are considered relatively or absolutely contraindicated
during pregnancy. If you'll follow the arguments of conscien-
tious drug safety advocates like David Graham of the FDA,
Accutane and the retinoids present a special case, chiefly
because the use of these products - heavily driven by pharma
marketing - is disproportionate, indiscriminate, and simply
too goddam promiscuous.

Cystic acne is pretty damned bad, but it's not terribly common.
Plain old acne vulgaris is eminently susceptible to treatment with
topical therapy and with systemic medications that have very
little risk as teratogens (i.e., proclivity for causing birth defects)
compared with the retinoids. Too many cement-headed members
of my profession have been prescribing Accutane without
thinking too clearly, and too many patients have been "doctor-
shopping" to get Accutane because concerning their physical
appearance, women in their childbearing years altogether too
thoroughly fit that description from *As Good as It Gets*
("I think of a man, and I take away reason and accountability").

Putting Accutane and the other systemic retinoids on a
national registry similar to that established for thalidomide
(Thalomid, Celgene) is a recognition of the above-mentioned
fact. It's also a way to get both doctors and patients to
*think* about using these products before they do so.

As opposed to the statin drugs, the angiotensin converting
enzyme (ACE) inhibitors, the angiotensin receptor blockers
(ARBs), the fluoroquinolone antibiotics, the tetracyclines,
chloramphenicol, warfarin, and a bunch of other medications
about which both doctors and patients tend to think much
more clear-headedly, probably because patient demand for
these products is not driven by vanity.

Or have you got some sort of idiot fixation on the HMG-CoA
reductase inhibitors, you pharmacological illiterate?

--------------------------
Hygiene is the corruption of medicine by morality. It is
impossible to find a hygienist who does not debase his
theory of the healthful with a theory of the virtuous.
The whole hygienic art, indeed, resolves itself into an
ethical exhortation. This brings it, at the end, into
diametrical conflict with medicine proper. The true aim
of medicine is not to make men virtuous; it is to safeguard
and rescue them from the consequences of their vices. The
physician does not preach repentence; he offers absolution.

-- H.L. Mencken, The Smart Set, May 1919

Herman Rubin

2005-08-16, 5:57 pm

In article <SpidnWnhQsnNBJzeRVn-iw@comcast.com>,
Sharon Hope <shope@anet.net> wrote:
>FDA has taken action to mitigate the risk of birth defects from the Acne
>medication Accutane (Isotretinoin).
>http://www.fda.gov/bbs/topics/NEWS/2005/NEW01218.html

I wonder why they have not done this earlier. It was known
when Accutane was introduced to treat acne.

>Why stop there? Why not add statins to the birth defects risk mitigation
>registry and procedures?

Every TV commercial I have seen for statins say not to take
it if pregnant or might become pregnant.
--
This address is for information only. I do not claim that these views
are those of the Statistics Department or of Purdue University.
Herman Rubin, Department of Statistics, Purdue University
hrubin@stat.purdue.edu Phone: (765)494-6054 FAX: (765)494-0558

Sharon Hope

2005-08-18, 8:58 am

"SJ Doc" <predone@NOSPAMeticomm.net> wrote in message
news:n504g11slt4uo3dhbdmn9t7oer7o7r73bv@4ax.com...
> On Tue, 16 Aug 2005 00:44:20 -0700, "Sharon Hope" wrote:
>
>
> I have to keep repeating that "There are no stupid questions"
> mantra, but - damn it - I just can't hold onto my temper this
> morning. That's a stupid question.
>
> Cystic acne - the condition for which the retinoids (i.e.,
> Accutane and its congeners) are used - occurs during the
> childbearing years. The common use of the HMG-CoA
> reductase inhibitors (the "statins") is in the later decades of
> life. Except in relatively rare congenital disorders such as
> the hyperlipoproteinemias, the statin drugs are not commonly
> prescribed to women during the early decades of their
> adult lives.

Check the latest cholesterol guidelines. There are women in their 20s being
put on statins.

Clearly, statins were prescribed for childbearing women, or the data on
birth defects caused by statins would not exist.

>
> And it's not just the HMG-CoA reductase indicators that
> are not to be used indiscriminately in women who might
> become pregnant. Many commonly-prescribed classes of
> drugs are considered relatively or absolutely contraindicated
> during pregnancy. If you'll follow the arguments of conscien-
> tious drug safety advocates like David Graham of the FDA,
> Accutane and the retinoids present a special case, chiefly
> because the use of these products - heavily driven by pharma
> marketing - is disproportionate, indiscriminate, and simply
> too goddam promiscuous.
>

Lipitor is the most prescribed drug in the world. Statins are the most
prescribed class of drugs in the world. Statins are the most prescribed
class of drugs in history.

> Cystic acne is pretty damned bad, but it's not terribly common.
> Plain old acne vulgaris is eminently susceptible to treatment with
> topical therapy and with systemic medications that have very
> little risk as teratogens (i.e., proclivity for causing birth defects)
> compared with the retinoids. Too many cement-headed members
> of my profession have been prescribing Accutane without
> thinking too clearly, and too many patients have been "doctor-
> shopping" to get Accutane because concerning their physical
> appearance, women in their childbearing years altogether too
> thoroughly fit that description from *As Good as It Gets*
> ("I think of a man, and I take away reason and accountability").
>
> Putting Accutane and the other systemic retinoids on a
> national registry similar to that established for thalidomide
> (Thalomid, Celgene) is a recognition of the above-mentioned
> fact. It's also a way to get both doctors and patients to
> *think* about using these products before they do so.
>
> As opposed to the statin drugs, the angiotensin converting
> enzyme (ACE) inhibitors, the angiotensin receptor blockers
> (ARBs), the fluoroquinolone antibiotics, the tetracyclines,
> chloramphenicol, warfarin, and a bunch of other medications
> about which both doctors and patients tend to think much
> more clear-headedly, probably because patient demand for
> these products is not driven by vanity.
>

Expanding tracking to other drugs is not a bad thing, particularly if it
prevents birth defects.

> Or have you got some sort of idiot fixation on the HMG-CoA
> reductase inhibitors, you pharmacological illiterate?
>
> --------------------------
> Hygiene is the corruption of medicine by morality. It is
> impossible to find a hygienist who does not debase his
> theory of the healthful with a theory of the virtuous.
> The whole hygienic art, indeed, resolves itself into an
> ethical exhortation. This brings it, at the end, into
> diametrical conflict with medicine proper. The true aim
> of medicine is not to make men virtuous; it is to safeguard
> and rescue them from the consequences of their vices. The
> physician does not preach repentence; he offers absolution.
>
> -- H.L. Mencken, The Smart Set, May 1919