Re: Drug Interaction - Adverse Reaction

Can the drug combination of Indocen and Celebrex cause a person to
develope a permanent seizure disorder ?

Thank you - Geo Sachs

George,

Yes, either of these medications alone, and especially in combination
can result in a permanent seizure disorder - under the right
circumstances.

Permanent (as opposed to acute) seizure disorders are usually caused
by brain damage. So far as I can tell, these drugs, used singly or in
combination, have not been reported to produce acute seizures when
used at normal dosage levels. On the other hand, each can produce
abnormalities of blood clotting and composition that could lead to
hemorrhagic (bleeding) or, though less likely, thrombotic (clotting)
stroke. They could also aggravate a stroke that was precipitated by
other factors.

Permanent seizure disorders are a complication of stroke, so in this
way, they could lead to permanent seizures. These medications should
be used with caution in people at risk for a stroke, and their use may
be inappropriate during a stroke or in the immediate recovery phase.

I found one paper about research carried out in mice suggesting that
the endogenous prostaglandins produced in acute neuronal death may
have an anticonvulsant (anti-seizure) effect. Both celecoxib and
indomethacin reduce levels of prostaglandins, so this is indirect
evidence that they may aggravate seizures after a brain injury such as
a stroke. Whether or not they lead to an increased risk of permanent
seizure disorder by this mechanism has not been established.

One last thing: having one seizure tends to predispose someone to more
seizures, possibly because of a "learning" effect. This means that a
single seizure induced by hematological (blood) derangement caused by
celecoxib and/or indomethacin could lead to a permanent seizure
disorder, but so far as we know this is not related to either of the
medications.

Alan Kali

Read more at:

http://www.rxlist.com/cgi/generic/coxib.htm
http://www.rxlist.com/cgi/generic/indometh.htm
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10528118

Geo,

Reading over my answer again, I feel I should clarify two points for a
non-medical audience:

1) Seizure disorder can be a complication of stroke, but this is not
necessarily or even frequently the case. I mention stroke (damage to
the brain caused by inadequate blood flow, either because of bleeding
from or blockage of blood vessels) because it may result from, or be
aggravated by, blood dyscrasias (an abnormality of blood; NOT the
band) and blood dyscrasias may be caused by non-steroidal
anti-inflammatory medications (the whole class - not just indomethacin
and celecoxib). This is only a possible means for these medications to
result in a permanent seizure disorder, not necessarily a likely or
common means.

2) Other than the paper I mentioned, I can find no evidence to suggest
that celecoxib and indomethacin in combination would cause either
stroke or seizure disorder (either temporary or permanent) by means of
a specific drug interaction or a direct physiological effect upon the
brain.

Can these medications cause or aggravate stroke? Possibly. Can stroke
lead to permanent seizures? Possibly. Can the combination have more
significant effects than either alone? Possibly. Is this common?
Probably not.

Alan Kali

Thanks to alkali-ga for your most interesting information.  Any
further information or comments is always appreciated.

Thank you.

Geo Sachs

Once again, thank you to Alkali-ga for the additional information and comments.

George Sachs