Valproic Acid and Derivatives

• 2-Propylpentanoic Acid
• 2-Propylvaleric Acid
• Dipropylacetic Acid
• Divalproex Sodium
• DPA
• Valproate Semisodium
• Valproate Sodium
• Valproic Acid
• Valproic Acid Derivative

• Anticonvulsant, Miscellaneous
• Antimanic Agent
• Histone Deacetylase Inhibitor

Clearance is decreased with liver impairment. Hepatic disease is also associated with decreased albumin concentrations and 2- to 2.6-fold increase in the unbound fraction. Free concentrations of valproate may be elevated while total concentrations appear normal.

Oral capsules:

Depakene: Store at 15°C to 25°C (59°F to 77°F).

Stavzor: Store at 25°C (77° F); excursions are permitted between 15°C and 30°C (59°F and 86°F).

Oral sprinkle capsules (Depakote): Store below 25°C (77°F).

Oral solution (Depakene): Store below 30°C (86°F).

Oral tablets:

Depakote: Store below 30°C (86°F).

Depakote ER: Store tablets at 25°C (77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F).

Epival [Canadian product]: Store at 15°C and 25°C (59°F and 77°F). Protect from light.

IV: Store at controlled room temperature 15°C to 30°C (59°F to 86°F). Stable in D5W, NS, and LR for at least 24 hours when stored in glass or PVC.

Amdinocillin: Valproate Products may enhance the adverse/toxic effect of Amdinocillin. Specifically, the risk for carnitine deficiency may be increased. Avoid combination

Barbiturates: Valproate Products may increase the serum concentration of Barbiturates. Barbiturates may decrease the serum concentration of Valproate Products. Monitor therapy

CarBAMazepine: Valproate Products may increase serum concentrations of the active metabolite(s) of CarBAMazepine. Parent carbamazepine concentrations may be increased, decreased, or unchanged. CarBAMazepine may decrease the serum concentration of Valproate Products. Monitor therapy

Carbapenems: May decrease the serum concentration of Valproate Products. Management: Concurrent use of carbapenem antibiotics with valproic acid is generally not recommended. Alternative antimicrobial agents should be considered, but if a concurrent carbapenem is necessary, consider additional anti-seizure medication. Consider therapy modification

ChlorproMAZINE: May increase the serum concentration of Valproate Products. Monitor therapy

Cholestyramine Resin: May decrease the serum concentration of Valproic Acid and Derivatives. Management: Separate administration of valproic acid and cholestyramine by at least 3 hours whenever possible in order to minimize the potential for a significant interaction. Consider therapy modification

Contraceptives (Estrogens): May decrease the serum concentration of Valproate Products. Monitor therapy

Cosyntropin: May enhance the hepatotoxic effect of Valproate Products. Management: Avoid concomitant use of Synacthen Depot (dosage form available in Canada) with valproic acid. Avoid combination

Ethosuximide: May decrease the serum concentration of Valproate Products. Valproate Products may increase the serum concentration of Ethosuximide. Monitor therapy

Felbamate: May increase the serum concentration of Valproate Products. Consider therapy modification

Fosphenytoin-Phenytoin: Valproate Products may decrease the protein binding of Fosphenytoin-Phenytoin. This appears to lead to an initial increase in the percentage of unbound (free) phenytoin and to a decrease in total phenytoin concentrations. Whether concentrations of free phenytoin are increased is unclear. With long-term concurrent use, total phenytoin concentrations may increase. Fosphenytoin-Phenytoin may decrease the serum concentration of Valproate Products. Monitor therapy

GuanFACINE: May increase the serum concentration of Valproate Products. Monitor therapy

LamoTRIgine: Valproate Products may enhance the adverse/toxic effect of LamoTRIgine. Valproate Products may increase the serum concentration of LamoTRIgine. Consider therapy modification

Lesinurad: Valproate Products may increase the serum concentration of Lesinurad. Avoid combination

LORazepam: Valproate Products may increase the serum concentration of LORazepam. Consider therapy modification

Mefloquine: May diminish the therapeutic effect of Anticonvulsants. Mefloquine may decrease the serum concentration of Anticonvulsants. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of convulsions. Monitor anticonvulsant concentrations and treatment response closely with concurrent use. Consider therapy modification

Methylfolate: May decrease the serum concentration of Valproate Products. Monitor therapy

Mianserin: May diminish the therapeutic effect of Anticonvulsants. Monitor therapy

Minoxidil (Systemic): Valproate Products may increase the serum concentration of Minoxidil (Systemic). Monitor therapy

OLANZapine: Valproate Products may decrease the serum concentration of OLANZapine. Monitor therapy

Orlistat: May decrease the serum concentration of Anticonvulsants. Monitor therapy

OXcarbazepine: Valproate Products may decrease the serum concentration of OXcarbazepine. Monitor therapy

Paliperidone: Valproate Products may increase the serum concentration of Paliperidone. Monitor therapy

Primidone: Valproate Products may decrease the metabolism of Primidone. More specifically, the metabolism of phenobarbital, primidone's primary active metabolite, may be decreased. Primidone may increase the serum concentration of Valproate Products. Monitor therapy

Propofol: Valproate Products may enhance the therapeutic effect of Propofol. Monitor therapy

Protease Inhibitors: May decrease the serum concentration of Valproate Products. Monitor therapy

RifAMPin: May decrease the serum concentration of Valproate Products. Consider therapy modification

RisperiDONE: Valproate Products may enhance the adverse/toxic effect of RisperiDONE. Generalized edema has developed. Monitor therapy

Rufinamide: Valproate Products may increase the serum concentration of Rufinamide. Management: Initiate rufinamide at a dose less than 10 mg/kg/day (children) or 400 mg/day (adults) in patients receiving valproic acid. In patients receiving rufinamide, initiate valproic acid at a low dose and titrate based on clinical response. Consider therapy modification

Salicylates: May increase the serum concentration of Valproate Products. Monitor therapy

Sodium Oxybate: Valproate Products may increase the serum concentration of Sodium Oxybate. Management: Consider a sodium oxybate dose reduction of at least 20% if combined with valproic acid. Consider therapy modification

Temozolomide: Valproate Products may enhance the adverse/toxic effect of Temozolomide. Valproate Products may increase the serum concentration of Temozolomide. Monitor therapy

Topiramate: May enhance the adverse/toxic effect of Valproate Products. Monitor therapy

Tricyclic Antidepressants: Valproate Products may increase the serum concentration of Tricyclic Antidepressants. Monitor therapy

Urea Cycle Disorder Agents: Valproate Products may diminish the therapeutic effect of Urea Cycle Disorder Agents. More specifically, Valproate Products may increase plasma ammonia concentrations and thereby increase the doses of Urea Cycle Disorder Agents needed to maintain concentrations in the target range. Monitor therapy

Vorinostat: Valproate Products may enhance the thrombocytopenic effect of Vorinostat. This may increase the risk of gastrointestinal bleeding. Monitor therapy

Zidovudine: Valproate Products may increase the serum concentration of Zidovudine. Monitor therapy

May cause a false-positive result for urine ketones (valproate partially eliminated as a keto-metabolite in the urine); may alter thyroid function tests

Liver enzymes (at baseline and frequently during therapy especially during the first 6 months), CBC with platelets (baseline and periodic intervals), PT/PTT (especially prior to surgery), serum ammonia (with symptoms of lethargy, mental status change), serum valproate levels; suicidality (eg, suicidal thoughts, depression, behavioral changes); motor and cognitive function (for signs or symptoms of brain atrophy)

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience headache, nausea, vomiting, dizziness, fatigue, constipation, diarrhea, abdominal pain, insomnia, lack of appetite, increased hunger, weight gain, weight loss, anxiety, or hair loss. Have patient report immediately to prescriber signs of infection, signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), signs of pancreatitis (severe abdominal pain, severe back pain, severe nausea, or vomiting), signs of depression (suicidal ideation, anxiety, emotional instability, or confusion), signs of a high ammonia level (abnormal heartbeat, abnormal breathing, confusion, pale skin, bradycardia, seizures, vomiting, or twitching), angina, swelling of arms or legs, vision changes, memory impairment, severe loss of strength and energy, change in balance, abnormal gait, bruising, bleeding, purple or red spots on skin, urinary retention, change in amount of urine passed, enlarged lymph nodes, muscle pain, muscle weakness, joint pain, joint edema, tremors, seizures, behavioral changes, involuntary eye movements, tinnitus, severe fatigue, or cold sensation (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.