Oxcarbazepine Risk Summary
Risk Factor: CMClass: Central nervous system drugs / Anticonvulsants
Fetal Risk Summary
Oxcarbazepine is an orally active anticonvulsant agent used either as monotherapy or adjunctive therapy in the treatment of partial seizures. The chemical structure of oxcarbazepine is closely related to that of another anticonvulsant, carbamazepine. Oxcarbazepine is rapidly metabolized to an active 10-monohydroxy metabolite (10-hydroxy-10,11-dihydrocarbamazepine; MHD) that is primarily responsible for the anticonvulsant activity.
In fertility studies with the active metabolite (MHD), an oral dose, 2 times the maximum recommended human dose on a mg/m2 basis (MRHD), administered to rats before and during mating and during early gestation caused disruption of the estrous cyclicity and a reduction in the numbers of corpora lutea, implantations, and live embryos (1). In pregnant rats, the administration of oral oxcarbazepine during organogenesis, at doses approximately 1.2 and 4 times the MRHD, caused increased incidences of fetal malformations (craniofacial, cardiovascular, and skeletal) and variations (1). Developmental toxicity (embryo/fetal death and growth retardation) was observed with oxcarbazepine at 4 times the MRHD. Oxcarbazepine (0.6 times the MRHD) or its active metabolite (1 times the MRHD) given during the latter part of gestation and throughout lactation were associated with persistent reductions in offspring body weights and, in the case of oxcarbazepine, altered behavior (decreased activity). Embryo and fetal death but no birth defects were observed in rabbits given oral doses of the active metabolite (1.5 times the MRHD) during organogenesis (1).
In a strain of mice susceptible to the teratogenic effects of carbamazepine, the highest tolerable oral dose of oxcarbazepine (1100 mg/kg/day) produced a lower incidence of teratogenicity (8% vs. 5% in controls; n.s.) than the epoxide metabolite of carbamazepine (14%27% vs. 6% in controls; p<0.05) (2). Concurrent treatment with phenobarbital did not increase the incidence of congenital malformations over that observed with oxcarbazepine alone.
In agreement with the relatively low molecular weight (about 252) of the parent drug, oxcarbazepine and its metabolite have been found in the fetus (3,4). In a woman who was taking oxcarbazepine monotherapy (300 mg 3 times daily) throughout gestation, maternal and term newborn plasma concentrations of the drug and its metabolite (MHD) were approximately equal (3). The healthy, 3700-g female infant had mild facial dysmorphism with a discrete epicanthus and a broad nasal bridge. Her development at 13 months of age was normal without signs of mental retardation or neurologic deficit.
In three women taking oxcarbazepine (6001800 mg/day; time of last dose not specified), maternal and cord blood were obtained at delivery and analyzed for parent drug, active metabolite (MHD), and the inactive metabolite of MHD (4). The three agents were detected in all samples. In another part of the study, oxcarbazepine was metabolized to MHD in a dual recirculating human placental perfusion system, suggesting that the same metabolic process occurs in vivo (4). MHD, however, was not metabolized to the inactive metabolite by the placenta. No placental metabolism of carbamazepine was observed in the perfusion system.
The author of a 1994 report very briefly reviewed the pregnancy outcomes of 27 women treated with oxcarbazepine (5). The outcomes included 1 infant born with some dysmorphic features (which disappeared later in life), 3 spontaneous abortions, 1 infant with spina bifida (whose mother also received valproate), 1 newborn with amniotic bands, and 22 normal infants (including 1 set of twins).
A 1996 review discussed the effects of oxcarbazepine and other anticonvulsants (6). Compared with carbamazepine, oxcarbazepine causes less induction of the cytochrome P450 enzyme system. However, oxcarbazepine may compromise the efficacy of hormonal contraception (6). The outcomes of 12 pregnancies treated with oxcarbazepine (3 spontaneous abortions and 9 normal newborns) were listed without further details.
In summary, oxcarbazepine is embryo and fetal toxic and teratogenic in some animal species. Although no major congenital malformations have been reported, with the possible exception of one case, mild facial defects have been observed. Of note, carbamazepine has also been associated with neural tube defects and minor craniofacial malformations (see Carbamazepine). The combined human data, however, are too limited to assess the absolute risk to the fetus. The effect of oxcarbazepine on folic acid levels or metabolism is unknown (6). Until this information is available, the safest course is to give folic acid supplementation with oxcarbazepine, as is done with other antiepileptic agents. In addition, metabolism of oxcarbazepine does not result in epoxide metabolites (4,6,7). Because these intermediate arene oxide metabolites have been associated with teratogenicity (see Carbamazepine, Phenytoin, and Valproic Acid), this may indicate a lower risk of teratogenicity with oxcarbazepine compared to the other agents.
Breast Feeding Summary
Only one published report describing the use of oxcarbazepine during human lactation has been located (3). In a woman who took oxcarbazepine (900 mg/day) throughout gestation and during lactation (see case discussion above), the milk:plasma ratios of the drug and its active metabolite (MHD) were 0.5 (3). No adverse effects in the nursing infant from the exposure were mentioned. The manufacturer also states that the milk:plasma ratio for both agents is 0.5 (1). Because the American Academy of Pediatrics considers carbamazepine to be compatible with breast feeding (see Carbamazepine), oxcarbazepine can probably be similarly classified.
References
- Product information. Trileptal. Novartis Pharmaceuticals, 2001.
- Bennett GD, Amore BM, Finnell RH, Wlodarczyk B, Kalhorn TF, Skiles GL, Nelson SD, Slattery JT. Teratogenicity of carbamazepine-10,11-epoxide and oxcarbazepine in the SWV mouse. J Pharmacol Exp Ther 1996;279:123742.
- Bulau P, Paar WD, von Unruh GE. Pharmacokinetics of oxcarbazepine and 10-hydroxy-carbazepine in the newborn child of an oxcarbazepine-treated mother. Eur J Clin Pharmacol 1988;34:3113.
- Pienimaki P, Lampela E, Hakkola J, Arvela P, Raunio H, Vahakangas K. Pharmacokinetics of oxcarbazepine and carbamazepine in human placenta. Epilepsia 1997;38:30916.
- Andermann E. Pregnancy and oxcarbazepine. Epilepsia 1994;35(Suppl 3):S26.
- Morrell MJ. The new antiepileptic drugs and women: efficacy, reproductive health, pregnancy, and fetal outcome. Epilepsia 1996;37(Suppl 6):S34S44.
- Grant SM, Faulds D. Oxcarbazepine. A review of its pharmacology and therapeutic potential in epilepsy, trigeminal neuralgia and affective disorders. Drugs 1992;43:87388.
Questions and Answers
is there an enzyme in oxcarbazepine that stops clopixal from working. Where can i find this information?, I'm trying to find this info as part of my nursing degree. Have been told there definately is but cannot seem to find any websites giving me this info.
Oxcarbazepine is a small molecule drug with chemical formula 10,11-Dihydro-10-oxo-5 H -dibenz(b,f)azepine-5-carboxamide. This is not an enzyme.
The formulations of Trileptal (oxcarbazepine) tablets and oral suspension manufactured by Novartis do not contain enzymes, either.
To answer your question: No, there is not an enzyme in oxcarbazepine that stops clopixal from working.
does oxcarbazepine inhibit acetylcholine or cholinergic system activation in brain?,
nope
does oxcarbazepine inhibit extracellular glutamate in epileptic brain?,
Studies support that they do. Oxcarbazepine inhibit veratrine-induced neurotransmitter such as extracellular glutamate release from rat brain slices in concentrations corresponding to those reached in plasma or brain in experimental animals or humans after anticonvulsant doses, presumably due to their sodium channel blocking properties.
what is oxcarbazepine used for beside preventing seizures?,
You can check with either your doctor or your pharmacist (chemist) with regards to oxcarbazepine and what it is prescribed for, but the following site indicates that, besides being prescribed for seizures (as in epilepsy), it may also be used for the treatment of Bipolar Disorder.
Ask your doctor!
Is there anything in oxcarbazepine that prevents clopixol from working?, While in my practice placement, the nurse informed my that there is evidence to suggest that oxcarbazipine can prevent clopixol from working. I have had no luck in trying to find this information. Can anyone direct me to a website giving me answers on this question.
There is no information about the possible interaction on BNF. I think this is a fairly new way of thinking and has yet to be properly researched and documented;
what is the mechanism of action of drug Oxcarbazepine?,
The pharmacological activity of Trileptal (oxcarbazepine) is primarily exerted through the 10-monohydroxy metabolite (MHD) of oxcarbazepine. The precise mechanism by which oxcarbazepine and MHD exert their antiseizure effect is unknown; however, in vitro electrophysiological studies indicate that they produce blockade of voltage-sensitive sodium channels, resulting in stabilization of hyperexcited neural membranes, inhibition of repetitive neuronal firing, and diminution of propagation of synaptic impulses. These actions are thought to be important in the prevention of seizure spread in the intact brain. In addition, increased potassium conductance and modulation of high-voltage activated calcium channels may contribute to the anticonvulsant effects of the drug.
what is the difference between oxcarbazepine & trileptal?,
It's the same drug
does oxcarbazepine inhibit norepinephrine, serotonin or acetylcholine?,
acetylcholine
Explain this:Interaction between detrol (tolterodine) and Trileptal (oxcarbazepine)?, What does this mean in laymans terms:
tolterodine and oxcarbazepine (Moderate Drug-Drug)
MONITOR: Based on in vitro data, coadministration with oxcarbazepine may decrease the plasma concentrations of drugs that are substrates of the CYP450 3A4 and 3A5 isoenzymes. The mechanism is accelerated clearance due to induction of CYP450 3A activities by oxcarbazepine. In one study, a single dose of oxcarbazepine (600 mg) had no effect on the pharmacokinetics of felodipine, a CYP450 3A4 substrate, while repeated doses (450 mg twice a day) decreased the peak plasma concentration and area under the concentration-time curve of felodipine (10 mg once daily) by 34% and 28%, respectively. Likewise, in a single case study, cyclosporine trough concentrations decreased to subtherapeutic levels a little over 2 weeks after addition of oxcarbazepine in a renal transplant patient. These results indicate that enzymatic induction occurs after multiple doses.
MANAGEMENT: Caution is advised if oxcarbazepine must be used concurrently with medications that undergo metabolism by CYP450 3A4 and/or 3A5, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever oxcarbazepine is added to or withdrawn from therapy.
The CYP450s are enzymes that are made by the liver. Their job is to get rid of toxins. Any drug, even good ones, is considered a toxin by the body. Sometimes drugs (e.g. oxcarbazepine) stimulate the body to make even more CYP450s to handle these new "toxins" that are suddenly on the scene. The more CYPs you have the more some OTHER drugs can get degraded. Sometimes this can make the level of these drugs can get too low. So the doctor or pharmacist has to be careful with someone getting oxcarbazepine if that patient is on other drugs as well. The patients other drug-level might drop too low.
Continue reading here: Mefenamic Acid Risk Summary
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