Sodium Valproate interactions

Food & lifestyle

• alcohol

  Moderate

  Synergy

  Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

  What to do: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

  4 sources

  1. Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc. (1990):
  3. "Product Information. Fycompa (perampanel)." Eisai Inc (2012):
  4. "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc (2015):

Conditions

Conditions in which Sodium Valproate needs care, as documented in this source.

• Depressive Disorder

  Major

  Antiepileptic drugs can increase depression and suicidal thoughts or behaviors in patients receiving these drugs for any indication. Patients should be monitored for the emergence or worsening of depression, suicidal thoughts and unusual changes in mood or behavior. Caregivers and family should be alert for the emergence or worsening of symptoms. Behaviors of concern should be reported immediately to the healthcare providers.

  9 sources

  1. "Product Information. Tegretol (carbamazepine)." Novartis Pharmaceuticals (2002):
  2. "Product Information. Depakene (valproic acid)." Abbott Pharmaceutical (2001):
  3. "Product Information. Depakote (divalproex sodium)." Abbott Pharmaceutical (2001):
  4. "Product Information. Lamictal (lamotrigine)." Glaxo Wellcome (2001):
  5. "Product Information. Magnesium Sulfate (magnesium sulfate)." Abbott Pharmaceutical (2001):
  6. "Product Information. Trileptal (oxcarbazepine)." Novartis Pharmaceuticals (2001):
  7. "Product Information. Vimpat (lacosamide)." UCB Pharma Inc (2008):
  8. "Product Information. Banzel (rufinamide)." Eisai Inc (2008):

  Show all 9 sourcesShow fewer sources

  9. "Product Information. Aptiom (eslicarbazepine)." Sunovion Pharmaceuticals Inc (2013):

• Liver Diseases

  Major

  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 intellectual disability, 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.

  14 sources

  1. Bach N, Thung S, Schaffner F, Tobias H "Exaggerated cholestasis and hepatic fibrosis following simultaneous administration of chlorpromazine and sodium valproate." Dig Dis Sci 34 (1989): 1303-7
  2. Itoh S, Yamaba Y, Matsuo S, et al. "Sodium valproate-induced liver injury." Am J Gastroenterol 77 (1982): 875-9
  3. Zaret BS, Backner RR, Marini AM, et al. "Sodium valproate-induced hyperammonemia without clinical hepatic dysfunction." Neurology 32 (1982): 206-8
  4. Powell-Jackson PR, Tredger JM, Williams R "Hepatotoxicity to sodium valproate: a review." Gut 25 (1984): 673-81
  5. Tennison MB, Miles MV, Pollack GM, et al. "Valproate metabolites and hepatotoxicity in an epileptic population." Epilepsia 29 (1988): 543-7
  6. Anderson GD, Acheampong AA, Wilensky AJ, Levy RH "Effect of valproate dose on formation of hepatotoxic metabolites." Epilepsia 33 (1992): 736-42
  7. Kondo T, Kaneko S, Otani K, et al. "Associations between risk factors for valproate hepatotoxicity and altered valproate metabolism." Epilepsia 33 (1992): 172-7
  8. 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

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  9. Marini AM, Zaret BS, Beckner RR "Hepatic and renal contributions to valproic acid-induced hyperammonemia." Neurology 38 (1988): 365-71
  10. "Product Information. Depakene (valproic acid)." Abbott Pharmaceutical (2001):
  11. Kulick SK, Kramer DA "Hyperammonemia secondary to valproic acid as a cause of lethargy in a postictal patient." Ann Emerg Med 22 (1993): 610-2
  12. Caparros-Lefebvre D, Lecomte-Houcke M, Pruvot FR, Declerck N, Paris JC, Petit H "Unusual electronmicroscopic changes in valproate-associated liver failure." Lancet 341 (1993): 1604
  13. "Product Information. Depakote (divalproex sodium)." Abbott Pharmaceutical (2001):
  14. American Medical Association, Division of Drugs and Toxicology "Drug evaluations annual 1994." Chicago, IL: American Medical Association; (1994):

• Urea Cycle Disorders, Inborn

  Major

  Valproic acid and derivative products are contraindicated in patients with known urea cycle disorders (UCD), as hyperammonemic encephalopathy, sometimes fatal, has been reported on these patients following the initiation of treatment. Prior to the initiation of therapy, the evaluation for UCD should be considered in patients with history of unexplained encephalopathy or comma, encephalopathy associated with a protein load, pregnancy- related or postpartum encephalopathy, unexplained intellectual disability, or history of elevated plasma ammonia or glutamine. Also, those with family history of UCD or family history of unexplained infant deaths. Patients who develop symptoms of hyperammonemic encephalopathy while receiving valproate therapy should receive prompt treatment including treatment discontinuation and be evaluated for underlying urea cycle disorders.

  2 sources

  1. "Product Information. Depakene (valproic acid)." Abbott Pharmaceutical (2001):
  2. "Product Information. Depakote (divalproex sodium)." Abbott Pharmaceutical (2001):

• Depressive Disorder

  Moderate

  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 showed that patients receiving AEDs had approximately twice the risk of suicidal thinking or behavior compared to patients receiving placebo. 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. If patients have symptoms of suicidal ideation or behavior, a dosage reduction or treatment discontinuation should be considered.

  16 sources

  1. "Product Information. Tegretol (carbamazepine)." Novartis Pharmaceuticals (2002):
  2. "Product Information. Klonopin (clonazepam)." Roche Laboratories (2001):
  3. "Product Information. Dilantin (phenytoin)." Parke-Davis (2001):
  4. "Product Information. Cerebyx (fosphenytoin)." Parke-Davis (2001):
  5. "Product Information. Mysoline (primidone)." Elan Pharmaceuticals (2001):
  6. "Product Information. Lyrica (pregabalin)." Pfizer U.S. Pharmaceuticals Group (2005):
  7. "Product Information. Sabril (vigabatrin)." Lundbeck Inc (2009):
  8. "Product Information. Potiga (ezogabine)." GlaxoSmithKline (2011):

  Show all 16 sourcesShow fewer sources

  9. "Product Information. Qsymia (phentermine-topiramate)." Vivus Inc (2012):
  10. "Product Information. Fycompa (perampanel)." Eisai Inc (2012):
  11. "Product Information. Briviact (brivaracetam)." UCB Pharma Inc (2016):
  12. "Product Information. Diacomit (stiripentol)." Biocodex USA (2018):
  13. "Product Information. Epidiolex (cannabidiol)." Greenwich Biosciences LLC (2018):
  14. "Product Information. Xcopri (cenobamate)." SK Life Science, Inc. (2020):
  15. "Product Information. Fintepla (fenfluramine)." Zogenix, Inc (2020):
  16. "Product Information. Ztalmy (ganaxolone)." Marinus Pharmaceuticals, Inc (2022):

• Diabetes Mellitus

  Moderate

  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.

  3 sources

  1. "Product Information. Depakene (valproic acid)." Abbott Pharmaceutical (2001):
  2. "Product Information. Depakote (divalproex sodium)." Abbott Pharmaceutical (2001):
  3. American Medical Association, Division of Drugs and Toxicology "Drug evaluations annual 1994." Chicago, IL: American Medical Association; (1994):

• HIV Infections

  Moderate

  Some in vitro studies suggest that valproate stimulates the replication of the HIV and CMV viruses under certain experimental conditions. The clinical consequences are unknown, and the relevance of these findings is uncertain for patients receiving maximally suppressive antiretroviral therapy. However, this should be borne in mind when interpreting the results from regular monitoring of the viral load in HIV infected patients receiving valproate or when following CMV infected patients clinically.

  2 sources

  1. "Product Information. Depakene (valproic acid)." Abbott Pharmaceutical (2001):
  2. "Product Information. Depakote (divalproex sodium)." Abbott Pharmaceutical (2001):

• Thrombocytopenia

  Moderate

  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.

  6 sources

  1. Smith FR, Boots M "Sodium valproate and bone marrow suppression." Ann Neurol 8 (1980): 197-9
  2. Morris N, Barr Rd, Pai KR, Kelton JG "Valproic acid and thrombocytopenia." Can Med Assoc J 125 (1981): 63-4
  3. "Product Information. Depakene (valproic acid)." Abbott Pharmaceutical (2001):
  4. Brichard B, Vermylen C, Scheiff JM, Ninane J, Cornu G "Haematological disturbances during long-term valproate therapy." Eur J Pediatr 153 (1994): 378-80
  5. "Product Information. Depakote (divalproex sodium)." Abbott Pharmaceutical (2001):
  6. American Medical Association, Division of Drugs and Toxicology "Drug evaluations annual 1994." Chicago, IL: American Medical Association; (1994):

• Thyroid Diseases

  Moderate

  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.

  2 sources

  1. "Product Information. Depakene (valproic acid)." Abbott Pharmaceutical (2001):
  2. "Product Information. Depakote (divalproex sodium)." Abbott Pharmaceutical (2001):