Oxcarbazepine
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Oxcarbazepine
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| Systematic (IUPAC) name | |
| 10,11-Dihydro-10-oxo-5 H -dibenz(b,f)azepine-5-carboxamide | |
| Identifiers | |
| CAS number | |
| ATC code | N03 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C15H12N2O2 |
| Mol. mass | 252.268 g/mol |
| SMILES | & |
| Pharmacokinetic data | |
| Bioavailability | > 95% |
| Protein binding | ? |
| Metabolism | Hepatic (Cytosolic Enzymes & Glucuronic Acid) |
| Half life | 1-5 hours (healthy adults) |
| Excretion | Renal |
| Therapeutic considerations | |
| Pregnancy cat. |
C(US) |
| Legal status | |
| Routes | Oral (Tablets or Suspension) |
Oxcarbazepine (marketed as Trileptal by Novartis or Trexapin by Taro) is an anticonvulsant and mood stabilizing drug, used primarily in the treatment of epilepsy and bipolar disorder. As of October 2007, Trileptal has also been available as a generic drug in the United States.
Oxcarbazepine is structurally a derivative of carbamazepine, adding an extra oxygen atom on the dibenzazepine ring. This difference helps reduce the impact on the liver of metabolizing the drug, and also prevents the serious forms of anemia or agranulocytosis occasionally associated with carbamazepine. Aside from this reduction in side effects, it is thought to have the same mechanism as carbamazepine - sodium channel inhibition (presumably, the main mechanism of action) - and is generally used to treat the same conditions. Oxcarbazepine has recently been found associated with a greater enhancement in mood and reduction in anxiety symptoms than other drugs employed to treat epilepsy.[1]
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[edit] Side effects
Oxcarbazepine causes dizziness, drowsiness, blurred or double vision, fatigue and may cause headaches, nausea, and vomiting. It can also cause hyponatremia (2.7% of patients), so blood sodium levels should be tested if the patient complains of severe fatigue. Some of these side effects (such as headache) are more pronounced shortly after a dose is taken and tend to fade with the passage of time (generally 60 to 90 minutes). A craving for salty foods (such as potato chips) and increased impulsiveness have also been noted. The frequency of adverse effects rises after dosage above 1200mg/d.
Concentration loss is also reported to be a frequent side effect. Its appearance seems correlated to whether the patients actually make use of their concentration; for example, people working in areas related to mathematical reasoning seem to have trouble in almost every case[citation needed]. This tends to be noticed only by people whose life actually depends on their reasoning capabilities.[citation needed]
[edit] History
First synthesized in 1966,[citation needed] it was approved for use as an anticonvulsant in Denmark in 1990. It was approved in Spain in 1993, in Portugal in 1997, and eventually for all other EU countries in 1999. It was approved in the US in 2000.
[edit] Other information
Oxcarbazapine may cause oral hormonal contraceptives to be less effective.
Increased incidences of fetal structural abnormalities and other manifestations of developmental toxicity (embryolethality, growth retardation) were observed in the offspring of animals treated with either oxcarbazepine or its active 10-hydroxy metabolite (MHD) during pregnancy at doses similar to the maximum recommended human dose.
When pregnant rats were given oxcarbazepine (30, 300, or 1000 mg/kg) orally throughout the period of organogenesis, increased incidences of fetal malformations (craniofacial, cardiovascular, and skeletal) and variations were observed at the intermediate and high doses (approximately 1.2 and 4 times, respectively, the maximum recommended human dose [MRHD] on a mg/m2 basis). Increased embryofetal death and decreased fetal body weights were seen at the high dose. Doses ≥ 300 mg/kg were also maternally toxic (decreased body weight gain, clinical signs), but there is no evidence to suggest that teratogenicity was secondary to the maternal effects.
In a study in which pregnant rabbits were orally administered MHD (20, 100, or 200 mg/kg) during organogenesis, embryofetal mortality was increased at the highest dose (1.5 times the MRHD on a mg/m2 basis). This dose produced only minimal maternal toxicity.
In a study in which female rats were dosed orally with oxcarbazepine (25, 50, or 150 mg/kg) during the latter part of gestation and throughout the lactation period, a persistent reduction in body weights and altered behavior (decreased activity) were observed in offspring exposed to the highest dose (0.6 times the MRHD on a mg/m2 basis). Oral administration of MHD (25, 75, or 250 mg/kg) to rats during gestation and lactation resulted in a persistent reduction in offspring weights at the highest dose (equivalent to the MRHD on a mg/m2 basis).
There are no adequate and well-controlled clinical studies of Trileptal in pregnant women; however, Trileptal is closely related structurally to carbamazepine, which is considered to be teratogenic in humans. Given this fact, and the results of the animal studies described, it is likely that Trileptal is a human teratogen. Trileptal should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
[edit] Labor and Delivery
The effect of Trileptal on labor and delivery in humans has not been evaluated.
[edit] Nursing Mothers
Oxcarbazepine and its active metabolite (MHD) are excreted in human breast milk. A milk-to-plasma concentration ratio of 0.5 was found for both. Because of the potential for serious adverse reactions to Trileptal in nursing infants, a decision should be made about whether to discontinue nursing or to discontinue the drug in nursing women, taking into account the importance of the drug to the mother.
[edit] References
- ^ Mazza M, Della Marca G, Di Nicola M, Martinotti G, Pozzi G, Janiri L, Bria P, Mazza S. Oxcarbazepine improves mood in patients with epilepsy. Epilepsy Behav. 2007 May;10(3):397-401. Epub 2007 Feb 14. PMID 17300991
- ChemicalLand21.com: Oxcarbazepine
- Trileptal Story
- Trileptal.com(Novartis)
- Prescribing Information(PDF)
[edit] External links
- RxList entry
- http://www.psycheducation.org/depression/meds/moodstabilizers.htm
- http://www.psycheducation.org/depression/meds/trileptal.htm
- DrugBank entry
