To : Jeannie Fisher
Re :  Midrin, Migraines

        Midrin is a rather poor antimigraine product, that just barely
passed FDA approval,  and is listed as "Possibly" effective,  a rather poor
indication of its efficacy.  It contains a sympathomimetic
drug(vasoconstrictive) isometheptene mucate which is only marginally
effective.  We know little to nothing of its transfer into human milk.  Due
to its activity in the CNS, I would surmise that it has a relatively high
Milk:plasma ratio.

        Migraine headaches are generally believed to be caused by an
intense, but brief vasoconstriction in a very localized region of the
brain.  The aura is believed due to the relative ischemia induced by this
brief, regional vasoconstriction.  Soon after, due to the ischemia, local
vasodilating substances are released by the tissues that produce a profound
vasodilation in the region.  The ergot drugs,  alone with this drug are
aimed at reducing the secondary vasodilation.  The ergots are definitely
contraindicated in breastfeeding moms.

        Other useful products that are more commonly used,  and have proven
efficacy, include propranolol and 'some' other beta blockers, and the newer
sumatriptan(Imitrex).  Of these agents, the beta blocker propranolol is
probably the safest in breastfeeding moms,  although the CNS depression,
and generalized fatigue induced by this product does not make many users
very happy. Tricyclic antidepressants are also quite effective in patients
with chronic migraines.  We have little to no experience using sumatriptan
in lactating mothers.

        Sumatriptan(Imitrex) levels in human breast milk have not been
published, but rat studies indicate a relatively high milk:plasma ratio,
but a rather low absolute level of this product in their milk.  This
product is available both orally, and IM.  The plasma half-life is
short(2.5 hrs),  and the milk level at 1.2 hours following an IV dose was
only 114 nanograms/ml of milk.  This suggests to me that the product is
rapidly distributed to other body compartments(and not the plasma), thus
ensuring a rather reduced milk level over time.  In addition, oral
bioavailability of sumatriptan is very poor(15%) suggesting poor absorption
by a breastfeeding infant.  But again, we have little experience with this
product in breastfeeding moms.



TWH