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Oxcarbazepine

Usage

  • The PBS indication for oxcarbazepine is for focal or primary generalised tonic-clonic seizures that have not been satisfactorily controlled by other anti-epileptic drugs.
  • Oxcarbazepine is a structural derivative of carbamazepine that was intended to offer similar efficacy with reduced side effects.
  • The mechanism of action is thought to be similar to carbamazepine and predominantly involves blockade of voltage-dependent sodium channels. There may also be an effect on voltage-activated calcium channels.
  • Oxcarbazepine may worsen absence or myoclonic seizures.

 

Side effects

Common side effects:

  • Abdominal pain, nausea, vomiting
  • Agitation and reduced concentration
  • Constipation
  • Somnolence
  • Dizziness
  • Headache
  • Hyponatraemia (up to 46%, may be dose related, usually occurs within first few weeks)

 

Other notable side effects:

  • IMPORTANT: Oxcarbazepine may rarely cause a severe hypersensitivity reaction including Stevens-Johnson Syndrome – see section below for more detail.
  • Nystagmus
  • Vertigo
  • Ataxia
  • Tremor
  • Agranulocytosis, aplastic anaemia, pancytopenia, thrombocytopenia
  • Hypothyroidism
  • Depression
  • All anticonvulsants are potentially teratogenic and this is often dose related (see section: Pregnancy and AEDs)
  • For a complete list of adverse effects, appropriate formularies should be consulted.

 

Hypersensitivity Reactions

  • Similar to carbamazepine, oxcarbazepine is associated with an idiopathic hypersensitivity type reaction manifesting as a maculopapular skin rash.
  • In its most severe form, this can progress to Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis and can carry a significant mortality risk (10-30%).
  • Approximately 25-30% of people who experience a hypersensitivity reaction to carbamazepine will react to oxcarbazepine. Up to 71% who develop rash with oxcarbazepine will develop rash with carbamazepine. It is important to note that hypersensitivity reactions to oxcarbazepine can also occur in patients who did not experience a reaction to carbamazepine.
  • Research has shown that severe hypersensitivity reactions to carbamazepine are more common in children of South Asian, Han Chinese, Thai, Filipino, Malaysian or Korean descent with the HLA-B*15:02 genotype.
  • A similar association has been made between HLA-A*31:01 and hypersensitivity reactions in patients of European descent.
  • Although there is no direct evidence to support an association between HLA-B*15:02 or HLA-A*31:01 and oxcarbazepine hypersensitivity reactions, the similarity of the reactions and high incidence of overlap suggest that caution is needed and testing for these alleles should be considered prior to treatment in the appropriate ethnic groups.

 

Dosing

  • Initial dose: 4-5mg/kg twice daily increasing at weekly intervals by up to 5mg/kg twice daily. Slower titrations may be wise and are based on individual tolerance and drug response.
  • A recommended maintenance dose is 15mg/kg bd (maximum dose 30mg/kg or 1200mg bd)
  • Oxcarbazepine can be taken with food
  • Dosages per kilogram can only be used in children of weight approximately up to 30-40kgs. Consult appropriate formularies for higher weights and in the adult range.
  • These dosages are only a guideline and appropriate formularies should be consulted as needed

 

Preparations

  • Tablets: 150mg, 300mg, 600mg
  • Oral liquid: 60mg/mL, 250mL bottle

 

Precautions

  • Renal impairment: It is advised to halve the initial dose if the estimated GFR is less than 30mL/minute
  • Hepatic impairment: No data. Advised not to use in severe hepatic impairment and use with caution in mild-moderate impairment.
  • Oxcarbazepine has been associated with a drug hypersensitivity reaction and Stevens-Johnson syndrome.

 

 

Weaning

  • When ceasing oxcarbazepine it is important to withdraw slowly (over a minimum of several weeks, recommended rate of reduction of 5mg/kg/week) to minimize the potential of increased seizure frequency in patients with seizure disorders.

 

Pregnancy

  • Usage in pregnancy needs to be discussed with a neurologist
  • There is limited data of the safety of oxcarbazepine in pregnancy.

 

Drug Interactions

  • Oxcarbazepine is rapidly absorbed and converted to its active metabolite, licarbazepine, in the liver. Licarbazepine has a half-life of 9.5 hours.
  • Unlike carbamazepine, the metabolism of oxcarbazepine is not affected by drugs, such as erythromycin, which inhibit CYP3A4.
  • Oxcarbazepine may decrease plasma levels of carbamazepine, lamotrigine, levetiracetam, perampanel, rufinamide and topiramate and may increase plasma levels of phenobarbitone and phenytoin.
  • Oxcarbazepine decreases plasma levels of hormonal contraceptives potentially reducing effectiveness leading to contraceptive failure.

 

 

 

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