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Valproic acid Disease Interactions

There are 5 disease interactions with valproic acid:


Valproate (Includes Valproic acid) ↔ Liver Disease

Severe Potential Hazard, High plausibility

Applies to: Liver Disease, Brain Anomalies - Congenital, Mental Retardation, Metabolic Disorder - Congenital

The use of valproate derivatives is contraindicated in patients with hepatic disease or significant hepatic dysfunction. Serious and potentially fatal hepatotoxicity has been reported in patients treated with these agents. The risk appears to be greatest in children less than 2 years of age--particularly those on multiple anticonvulsants and those with congenital metabolic disorders, severe seizure disorders accompanied by mental retardation, or organic brain disease--and decreases considerably in progressively older patient groups. Therapy with valproate products should be administered with extreme caution and as a sole agent in patients with risk factors for valproate-related hepatotoxicity. In reported cases, the onset has generally been within the first 6 months of treatment and may be preceded by nonspecific symptoms such as malaise, weakness, lethargy, facial edema, anorexia, nausea, vomiting, and a loss of seizure control. Patients should be monitored closely for appearance of these symptoms, and therapy withdrawn immediately if significant hepatic dysfunction occurs. Liver function tests should be performed prior to initiating therapy and at frequent intervals thereafter, especially during the first 6 months. However, clinicians should bear in mind that transient, dose-related, asymptomatic elevations in serum transaminase, amylase and ammonia levels may commonly occur and often return to normal with or without dosage adjustment.


  1. Palm R, Silseth C, Alvan G "Phenytoin intoxication as the first symptom of fatal liver damage induced by sodium valproate." Br J Clin Pharmacol 17 (1984): 597-9
  2. Powell-Jackson PR, Tredger JM, Williams R "Hepatotoxicity to sodium valproate: a review." Gut 25 (1984): 673-81
  3. Tennison MB, Miles MV, Pollack GM, et al "Valproate metabolites and hepatotoxicity in an epileptic population." Epilepsia 29 (1988): 543-7
View all 14 references

Antiepileptics (Includes Valproic acid) ↔ Suicidal Tendency

Moderate Potential Hazard, Moderate plausibility

Applies to: Depression, Psychosis

Antiepileptic drugs (AEDs) have been associated with an increased risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Pooled analyses of 199 placebo-controlled clinical studies involving the use of 11 different AEDs across multiple indications in either monotherapy or adjunctive therapy for a median treatment duration of 12 weeks (up to a maximum of 24 weeks) showed that patients receiving AEDs had approximately twice the risk of suicidal thinking or behavior compared to patients receiving placebo. The estimated rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% for 16,029 placebo-treated patients, representing an increase of approximately one case for every 530 patients treated. There were four suicides in AED-treated patients and none in placebo-treated patients, although the number is too small to establish any causal relationship. The increased risk of suicidal thoughts or behavior was observed as early as one week after starting AEDs and persisted for the duration of treatment assessed. The risk did not vary substantially by age (5 to 100 years) in the clinical trials analyzed. Therapy with AEDs should be administered cautiously in patients with depression or other psychiatric disorders. The risk of suicidal thoughts and behavior should be carefully assessed against the risk of untreated illness, bearing in mind that epilepsy and many other conditions for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Patients, caregivers, and families should be alert to the emergence or worsening of signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts or behavior. For clinically significant or persistent symptoms, a dosage reduction or treatment withdrawal should be considered. If patients have symptoms of suicidal ideation or behavior, treatment should be discontinued.


Valproate (Includes Valproic acid) ↔ Thrombocytopenia

Moderate Potential Hazard, Moderate plausibility

Applies to: Thrombocytopenia, Bleeding, Coagulation Defect, Thrombocytopathy, Vitamin K Deficiency

The use of valproate derivatives may be associated with dose-related thrombocytopenia, the incidence of which is generally low but has been reported at up to 27% in one study using high dosages (approximately 50 mg/kg/day of valproic acid). In that study, platelet counts returned to normal in all patients, some despite continued treatment. Valproate may also inhibit the secondary phase of platelet aggregation, although this effect is unlikely to be of clinical significance except during the concomitant use of other drugs that affect coagulation. However, altered bleeding time, ecchymosis, petechiae, bruising, hematoma formation, epistaxis, and frank hemorrhage have been reported rarely. Hypofibrinogenemia has also been observed. Therapy with valproate products, particularly at high dosages, should be administered cautiously in patients with significant active bleeding or a hemorrhagic diathesis, including hemostatic and/or coagulation defects associated with hemophilia, vitamin K deficiency, hypoprothrombinemia, thrombocytopenia, thrombocytopathy, or severe hepatic impairment. The manufacturers recommend platelet counts and coagulation tests prior to initiating therapy and at periodic intervals thereafter, as well as before planned surgery. The dosage should be reduced or the drug withdrawn if clinical evidence of hemorrhage, bruising, or a disorder of hemostasis or coagulation occurs.


  1. Brichard B, Vermylen C, Scheiff JM, Ninane J, Cornu G "Haematological disturbances during long-term valproate therapy." Eur J Pediatr 153 (1994): 378-80
  2. Smith FR, Boots M "Sodium valproate and bone marrow suppression." Ann Neurol 8 (1980): 197-9
  3. American Medical Association, Division of Drugs and Toxicology "Drug evaluations annual 1994." Chicago, IL: American Medical Association; (1994):
View all 6 references

Valproate (Includes Valproic acid) ↔ Thyroid Function Tests

Moderate Potential Hazard, Low plausibility

Applies to: Thyroid Disease

The manufacturers state that there have been reports of altered thyroid function tests associated with the use of valproate. However, no specific information is given. Clinicians should be cognizant of this potential effect when prescribing or administering valproate products to patients with thyroid disease.


  1. "Product Information. Depakene (valproic acid)." Abbott Pharmaceutical, Abbott Park, IL.
  2. "Product Information. Depakote (divalproex sodium)." Abbott Pharmaceutical, Abbott Park, IL.

Valproate (Includes Valproic acid) ↔ Urine Ketone Test

Moderate Potential Hazard, High plausibility

Applies to: Diabetes Mellitus

Valproate is partially eliminated in the urine as a ketone-containing metabolite, which may lead to a false interpretation of the urine ketone test. Clinicians should be cognizant of this interaction when prescribing or administering valproate products to patients with diabetes.


  1. "Product Information. Depakote (divalproex sodium)." Abbott Pharmaceutical, Abbott Park, IL.
  2. "Product Information. Depakene (valproic acid)." Abbott Pharmaceutical, Abbott Park, IL.
  3. American Medical Association, Division of Drugs and Toxicology "Drug evaluations annual 1994." Chicago, IL: American Medical Association; (1994):

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There are 2 alcohol/food interactions with valproic acid

Drug Interaction Classification

The classifications below are a general guideline only. It is difficult to determine the relevance of a particular drug interaction to any individual given the large number of variables.

Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.

Do not stop taking any medications without consulting your healthcare provider.

Disclaimer: Every effort has been made to ensure that the information provided by Multum is accurate, up-to-date and complete, but no guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource beyond the date hereof. This material does not endorse drugs, diagnose patients, or recommend therapy. Multum's information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill, knowledge, and judgement of healthcare practitioners in patient care. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective, or appropriate for any given patient. Multum Information Services, Inc. does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. Copyright 2000-2016 Multum Information Services, Inc. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse, or pharmacist.