Valproic Acid (Adverse effects)

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

If you wish to know all the substances that we analyze in our DNA test, please consult the pharmacological or pharmacogenetic compatibility section.

CONTRAINDICATIONS

Hypersensitivity to sodium valproate.

Acute hepatitis, chronic hepatitis, personal or family history of severe hepatitis, hepatic porphyria, previous or current liver disease and/or severe liver or pancreatic dysfunction, disorders of branched amino acid metabolism or the urea cycle, known mitochondrial disorders caused by mutations in the nuclear gene encoding the mitochondrial polymerase gamma enzyme, such as Alpers-Huttenlocher syndrome. It is contraindicated in children under 2 years of age suspected of having a gamma polymerase-related disorder.

PRECAUTIONS

Renal insufficiency. In systemic lupus erythematosus assess benefit-risk. Severe hepatic insufficiency has been reported, maximum risk in infants and children under 3 years of age with brain damage, psychic retardation or metabolic or genetic degenerative disease: evaluate hepatic function before starting treatment and monitor it periodically during the first 6 months of treatment.

In children under 3 years of age it is recommended in monotherapy and concomitant use with salicylates should be avoided due to risk of hepatic toxicity. Suspend in case of pancreatitis. Perform hematological tests before initiating treatment, surgical intervention and in case of spontaneous hematomas or hemorrhages.

Do not drink alcohol. In case of suspicion of an enzymatic deficiency of the urea cycle, perform metabolic tests.

Possible weight gain at the beginning of treatment. Changes in treatment or gradual discontinuation.

Do not administer to girls, adolescent women, women of childbearing age and pregnant women unless alternative treatments are not effective or not tolerated, the teratogenic potential and the risk of developing developmental disorders in children in utero are high. Women of childbearing potential should use an effective method of contraception and the risks in case of pregnancy should be explained to them. If pregnancy occurs, an assessment of the benefits and risks of continuing treatment should be made and other therapeutic alternatives should be considered.

Monitor for signs of suicidal ideation and behavior.

In patients with suspected or present mitochondrial disease (may trigger or worsen clinical signs of these underlying mitochondrial diseases caused by mutations in mitochondrial DNA as well as in the nuclear gene encoding gamma polymerase) test for gamma polymerase mutations in accordance with current clinical practice for diagnostic evaluation of such disorders.

SIDE EFFECTS

Anemia, thrombocytopenia, weight gain, tremor, extrapyramidal disorders, stupor, somnolence, convulsions, memory failure, headache, nystagmus, dizziness after injection, deafness, nausea, abdominal pain, diarrhea, hypersensitivity, alopecia (transient, dose-related), hyponatremia, hemorrhage, liver injury, dysmenorrhea, confusion, aggressiveness, agitation and attention disorders.

PHARMACOLOGICAL INTERACTIONS

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

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

Serum concentrations of valproic acid are decreased 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 with anticoagulants and ASA.

Risk of seizures with mefloquine.

Hepatic toxicity exacerbated by alcohol.

Adjust dose if prescribed concomitantly with rifampicin.

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

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

Taking VPA can give false positives in ketone body excretion tests.

BRAND NAMES

• Depakine®
• Valproic acid®.