FDA Reproductive Health Drug Advisory Committee Meeting August 29, 2006 Gaithersburg, Maryland

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FDA Reproductive Health Drug Advisory Committee
MeetingAugust 29, 2006Gaithersburg, Maryland
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New Drug Application for Gestiva 17
alpha-hydroxyprogesterone caproate (17 P)

• Theresa Grossklaus, RN, BA, BSN
• Current Master of Science of Nursing Student

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Before approving NDA 21-945

• consider lessons learned from 17 Ps prior use
  under the brand name
• Delalutin

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Prior use of 17 P

• 1980s 3 pregnancies
• Treatment of different condition
• Use during different gestation weeks of pregnancy

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Delalutin
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Treatment of Suspected Corpus Luteum Insufficiency
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Supplement confirmed pregnancy with progesterone

• Progesterone vaginal suppositories
• Weekly injections of Delalutin (17 P ) 250 mg IM
• Gestation weeks 5-9 or 5-12
• Modified gestation weeks 5-17, 5-18

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Outcome 3 children
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Concerns Delalutin (17 P)
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Possible adverse interaction between alcohol and
17 P when used for treatment of corpus luteum
insufficiency during gestation weeks 5-18
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A most peculiar pregnancy characterized by 4
problems

• Congenital cardiac condition
• Primary microcephaly
• Intrauterine growth retardation
• A maternal drinking problem

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Our son, 1986 1991
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1991

• Conducted a review of literature on birth defects
  associated with progestins, and with alcohol,
  possible mechanisms of teratogenesis, congenital
  cardiac conditions, microcephaly, behavioral
  teratology, intrauterine growth retardation,
  alcohol metabolism, addiction, more

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Subjective experience

• addiction to alcohol by 15-17 weeks
• No intoxication
• Sensation of fetal growth restriction within 1
  week of addiction
• Symptoms diminish between 18-21 weeks
• Symptoms accelerate after 21 weeks
• Intense compulsive drinking problem erupts 26
  weeks
• Its all my fault for drinking in the 3rd
  trimester

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Oversimplified logical explanation

• Alcohol is a 2 tiered psychotropic drug which
  requires transformation from ethanol to
  acetaldehyde
• Ethanol is metabolized but the metabolism of
  acetaldehyde is restricted

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Possible explanation

• Acetaldehyde accumulates in moms brain, liver,
  and serum
• Acetaldehyde serves as a teratogen, a fetal
  growth inhibitor, a disruptor of steroid hormone
  biosynthesis, an addicting substance for mom, and
  an inhibitor of fetal brain growth

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Treatment of corpus luteum insufficiency with 17
alpha-hydroxyprogesterone caproate (17 P) with
probable complications due to prenatal alcohol
consumption a 1991 perspective
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Request delay of approval of NDA 21-945 until a
designated medical researcher can review this
manuscript(gt600 pages) and assess applicability
to this newer use of 17 P
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Birth defects are usually associated with first
trimester exposure to teratogens

• Brain growth and migration of neurons can be
  inhibited by alcohol during pregnancy (including
  2nd 3rd trimesters)
• Maternal addiction to alcohol might be possible
  at any time during pregnancy

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If either of our 2 daughters were pregnant and
17 P supplementation was recommended to them, I
would want them to be very well informed about
this possible outcome, and be given a very
specific warning not to consume one bit of
alcohol while on 17 P.
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Consider protection forFetusMotherPrescribing
physicianPharmaceutical mfg.
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Pregnancy Exposure Registry

• Prospective means of capturing outcomes of
  pregnancies exposed to progesterone
• Uniform, specific warning could be communicated
  to pregnant patients to avoid alcohol while on 17
  P while obtaining a signed consent
• Adverse effects could be closely monitored
• Longitudinal data could be tracked

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Before approving NDA-21-945

• if a pregnant woman on 17 P became addicted
  and developed a drinking problem how could a
  professional identify this?
• how could this professional treat or intervene?

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I am grateful for the opportunity to bear three
children