As a carer, I have observed what may have been a connection between
missing regular medication for epilepsy and life-threatening hospitalisation with a
severe seizure three days later. The oral medication was missed due to
vomiting. Is there any evidence of a connection? If there is some
evidence of a connection, is it possible, practical or desirable to
give the medication by other methods when it cannot be given orally?

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Request for Question Clarification by synarchy-ga on 14 Sep 2003 17:35 PDT

Hi - the answer to the first part of your question is an emphatic
'yes'; however, in order to give you references, and to answer the
second part of your question (is it possible to give the drug other
than orally), I would need to know which drug it is.

synarchy

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Clarification of Question by mowerman-ga on 15 Sep 2003 14:45 PDT

The medication is Epilim Chrono Controlled Release (Sodium
valproate/valproic acid) 600mg in the morning and 600mg in the
evening. Living in UK.

Hello -

While I am a physician, only your treating physician can make an
accurate diagnosis and should be the only one to modify the medication
regime.

I know that you know that missed medications are a common cause of
seizure relapse:
http://odmrdd.state.oh.us/Includes/alertdocuments/Seizure_Triggers.htm
http://www.epinet.org.au/info/seizure.html

The timing of three days to seizure fits fairly well with the
half-life of valproate (around 16 hours) - usually 3 half-lives are
sufficient for near total elimination of a drug which would put this
at 48hours after the effect of the last dose, so, 64 hours total, or
almost three days (note, other drugs may also affect the metabolism,
and thus the half-life of the drug):
http://www.pharmacynetworkgroup.com/c/depacon-pharmacology.htm


Valproic acid can be given in other than oral form, although, another
approach would be to attempt an elixir form that might decrease nausea
associated with administration.  Intravenous preparations are
available, although this would likely require hospitalization or at
least, training in the administration of intravenous medications at
home (available in the US; I'm not sure about the UK, you could check
with your local physician).
http://www.mgh.harvard.edu/pharmacy/ICU%20Guidelines/valproate.htm

Alternatively, and very common when vomitting is preventing oral
medication delivery, is rectal administration.  While the extended
release pills would not be ideal for this purpose (though they
presumably would work if it's possible to keep them in place long
enough for them to dissolve), the elixir form diluted 1:1 with water
appears to be better tolerated.  A reference:
http://www.medicineau.net.au/clinical/palliativecare/palliativec1259.html

Epilim is available is both liquid and elixir forms:
http://emc.medicines.org.uk/emc/assets/c/html/displaydoc.asp?documentid=6781#PRODUCTINFO

A side effect of valproic acid can be nausea:
http://www.wholehealthmd.com/print/view/1,1560,DR_628,00.html#Common_Side_Effects
- it might be worth checking with your physician if:
1) the valproate level goes too high with drug administration, leading
to nausea, preventing further dosing and thus leading to a seizure
2) the patient is very sensitive to the nausea inducing potential of
valproate, in which case another drug may be a better solution (there
are many others available).

Please let me know if I can further tailor this answer to your needs.

synarchy

Google search for references:
valproate half-life
valproate UK

A great help at a worrying time.