I found some stuff on google, couldn't get the website to cut and paste. the
following info may be useful re the drug's pharmacokinetics. probably little
data on its use w/ bf but drug levels could be done on the mom and babies,
and monitoring of side effects etc.
Oxcarbazepine (Trileptal)
Oxcarbazepine is a keto-analogue of carbamazapine. The modification to the
molecular structure prevents it from being metabolized by oxidation to
CBZ-10,11-epoxide, which is the metabolite that is thought to be responsible
for much of the toxicity of CBZ. OCB is metabolized by conjugation rather
than by oxidation, and largely excreted by the kidney. See e.g. Lloyd et al.
It has been on the market for over 10 years in various countries. The
neurologists that I have spoken to seem to regard it as exactly equivalent
to CBZ for seizure control ("It's Tegretol without the toxicity"). The
clinical efficacy for seizure control of OCB compares favorably with CBZ in
clinical trials, and there are case reports of its efficacy for bipolar
disorder, and a very small placebo-controlled 1983 study (interestingly,
this study was one of the early favorable reports for the use of VPA in
mania). More recently, other studies have compared OCB (favorably) to
lithium and to haloperidol, and at the 2001 APA meeting Reinstein presented
a poster reporting equal effectiveness compared to valproate for acute
mania. There have been no instances of marrow suppression in 7000 cases
according to one citation. Compared with CBZ, P450 enzyme induction is
greatly reduced; there is only a moderate induction of CYP3A4 and other
isoenzymes seem not to be affected. It seems to be less prone to causing
cognitive impairment than CBZ (see Grant & Faulds 1992). When switching from
CBZ to OCB, one should be aware that the previous induction of CYP enzymes
will be considerably decreased, and as a result the serum levels of other
drugs may rise. The only medical issue of note is its occasional side effect
of hyponatremia.
Summary:
Half-life: the parent compound is rapidly and extensively metabolized to a
monohydroxy derivative (MHD), which is responsible for the therapeutic
effect; MHD is eliminated with a half-life of about 8-10 h
Metabolism: ~ 27% of the dose is recovered in the urine as unchanged MHD and
a further 49% as a glucuronide conjugate of MHD. It appears that the
kinetics of OCB should not be affected by impaired liver function. Impaired
kidney function does not affect the kinetics of MHD, but the glucuronide
conjugate will accumulate in these patients.
Maintenance therapeutic range: N/A; it is unclear if eventually serum levels
will be useful
Dosage: 800-1800mg/day. When converting from CBZ to OCB, multiply CBZ dose
by 1.5 to get an approximately equivalent OCB dose.
Drug interactions: mild induction of CYP3A4 — watch for some decrease (may
be subclinical) in 3A4 substrates such as estrogens and progesterone (watch
for effects on OCPs!), the dihydropyridine calcium-channel blockers
(nimodipine, amlodipine, felodipine, isradipine), pimozide, quinidine,
alprazolam, diazepam, haloperidol, lovastatin, trazodone. When switching
from CBZ to OCB expect relative de-induction of CYP enzymes, including 3A4,
so, e.g., lamotrigine levels may rise, as may those of many other drugs.
Side effects: in monotherapy (incidence greater than or equal to 5 percent)
were dizziness, nausea, headache, diarrhea, vomiting, upper respiratory
tract infection, constipation, dyspepsia, ataxia and nervousness
Cautions: hyponatremia (2.5% incidence in controlled clinical trials) —
usually asymptomatic and did not usually require dose adjustments, but fluid
restriction might be necessary
Routine laboratory monitoring: none; serum sodium levels might be checked
for elderly patients or those at risk for hyponatremia (see Smith 2001).
Laurie Wheeler, IBCLC, MN, RN
New Orleans Louisiana, s.e. USA
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