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PHARMACOLOGICAL COMPATIBILITY*

Response to Valproic Acid and adverse effects

Valproic acid (VPA), also known as sodium valproate, magnesium valproate or simply valproate is an antiepileptic drug and mood stabilizer that is used in the treatment of diseases such as epilepsy or bipolar disorder. VPA increases brain levels of GABA, decreases levels of excitatory amino acids and modifies potassium conductance.

CONTRAINDICATIONS

Hypersensitivity to sodium valproate.

VPA is contrindicated in cases of acute hepatitis, chronic hepatitis, personal or family history of severe hepatitis, hepatic porphyria, previous or current liver disease, and/or severe liver or pancreas dysfunction, disorders of branched-chain amino acid metabolism or urea cycle, known mutation-induced mitochondrial disorders in the nuclear gene encoding the mitochondrial enzyme gamma polymerase, such as Alpers-Huttenlocher syndrome. VPA is also contraindicated in children younger than 2 years old who are suspected of having a gamma-polymerase-related disorder.

CAUTIONS

Cautions should be taken in patients with renal insufficiency. Extrem precautions in patients with systemic lupus erythematosus and value benefit-risk. Cautions in patients with severe hepatic impairment, maximum risk in infants and children under 3 years old with brain injury, psychic retardation, or metabolic or degenerative genetic disease has been reported: prior to initiating treatment, liver function should be monitored and monitored periodically during the first 6 months of treatment.

In children under 3 years old, monotherapy is recommended and concomitant use with salicylates should be avoided because of the risk of hepatic toxicity. Suspend in case of pancreatitis. Perform hematological tests before starting treatment, surgical intervention and in case of bruising or spontaneous hemorrhages.

Do not ingest alcohol. On suspicion of an enzymatic deficiency of the urea cycle, perform metabolic tests.

Possible weight gain at the start of treatment. Changes in treatment or discontinuation should be performed gradually.

Do not administer to girls, adolescent women, women on childbearing age and pregnant women unless alternative treatments are not effective or are not tolerated, the teratogenic potential and the risk of developing developmental disorders in children in the uterus are high. Women on childbearing age should use an effective contraceptive method and must be explained the risks in case of pregnancy. If you become pregnant, an evaluation of the benefits and risks of continuation of treatment will be made, considering other therapeutic alternatives.

Monitor the appearance of signs of suicidal ideation and behavior

In patients in whom mitochondrial disease is suspected or present (clinical signs of these underlying mitochondrial diseases caused by mitochondrial DNA mutations as well as the nuclear gene encoding gamma polymerase may be triggered or worsened) test for polymerase mutations gamma according to current clinical practice for the diagnostic evaluation of such disorders

SIDE EFFECTS

Anemia, thrombocytopenia, weight gain, tremor, extrapyramidal disorders, stupor, drowsiness, seizures, memory failure, headache, nystagmus, dizziness after injection, deafness, nausea, abdominal pain, diarrhea, hypersensitivity, alopecia (transient, dose related) , hyponatremia, haemorrhage, hepatic injury, dysmenorrhea, confusion, aggression, agitation and attention disorders.

PHARMACOLOGICAL INTERACTIONS

VPA potentiates the effect of neuroleptics, MAOIs, antidepressants and benzodiazepines.

Intake of VPA increases plasma concentrations of phenobarbital, free phenytoin, primidone, carbamazepine, lamotrigine, zidovudine, nimodipine and ethosuximide

Serum valproic acid concentrations are reduced by: phenytoin, phenobarbital, carbamazepine and carbapenems.

Serum valproic acid concentrations are increased by: felbamate, cimetidine, fluoxetine and erythromycin.

VPA decreases the clearance of felbamate. There is a risk of bleeding if prescribed together with anticoagulants and ASA.

Risk of convulsions with mefloquine.

Hepatic toxicity exacerbated by alcohol.

Adjust dose if prescribed concomitantly with rifampicin.

Risk of encephalopathy and/or hyperammonemia if taken together with topiramate.

VPA increases the exposure of propofol, so it is recommended to reduce propofol doses during treatment with valproic.

Taking VPA may render false positives in ketone body excretion tests.

BRAND NAMES

  • Depakine ®
  • Ácido valpróico ®

GENE OR REGION STUDIED


  • POLG

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