Add Statins to Birth Defects Ipledge program established f..

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/query.fcgi?cmd=Retrieve&db=pubmed&d...=Abstra
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]