Valproic Acid (Adverse effects)

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

Valproic acid is used to treat disorders such as epilepsy and bipolar disorder. Although it is very effective in controlling seizures, its use must be carefully monitored due to side effects and interactions with other medications.

If you wish to know all the substances we analyze in our DNA test, consult the drug compatibility section or pharmacogenomics.

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, branched-chain amino acid or urea cycle metabolism disorders, known mitochondrial disorders caused by mutations in the nuclear gene encoding the mitochondrial enzyme polymerase gamma, such as Alpers-Huttenlocher syndrome. It is contraindicated in children under 2 years of age suspected of having a polymerase gamma-related disorder.

PRECAUTIONS

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

In children under 3 years of age, monotherapy is recommended, and concomitant use with salicylates should be avoided due to the risk of liver toxicity. Discontinue in case of pancreatitis. Perform hematological tests before starting treatment, before surgical intervention, and in case of spontaneous bruises or hemorrhages.

Do not consume alcohol. In case of suspected urea cycle enzyme deficiency, perform metabolic examinations.

Possible weight gain at the start 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 tolerated; the teratogenic potential and the risk of developing developmental disorders in children in utero are high. Women of childbearing potential must use an effective contraceptive method, 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, considering other therapeutic alternatives.

Monitor for signs of suicidal ideation and behavior.

In patients suspected of or presenting with mitochondrial disease (clinical signs of these underlying mitochondrial diseases caused by mitochondrial DNA mutations, as well as the nuclear gene encoding polymerase gamma, may be triggered or worsened), perform polymerase gamma mutation tests in accordance with current clinical practice for the diagnostic evaluation of such disorders.

SIDE EFFECTS

Valproic acid can cause anemia, thrombocytopenia, weight gain, tremor, extrapyramidal disorders, stupor, somnolence, seizures, memory failure, headache, nystagmus, dizziness after injection, deafness, nausea, abdominal pain, diarrhea, hypersensitivity, alopecia (transient, dose-related), hyponatremia, hemorrhage, liver injury, dysmenorrhea, confusional state, aggression, agitation, and attention disorders. In some cases, cognitive function may be impaired, especially with long-term treatment.

DRUG INTERACTIONS

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

VPA intake 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 concentrations of valproic acid are increased by: felbamate, cimetidine, fluoxetine, and erythromycin.

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

The antibiotic mefloquine is contraindicated with the use of valproic acid due to the risk of seizures, which can aggravate the patient's condition.

Liver toxicity exacerbated by alcohol.

Adjust dose if prescribed concomitantly with rifampicin.

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

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

VPA intake may give false positives in ketone body excretion tests.

BRAND NAMES

• Depakine®
• Valproic acid®.