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Valproic Acid

Medical and Pharmacy Editor:

Brand Name: Depakene, Stavzor, Depacon

Generic Name: Valproic Acid

Drug Class: Anticonvulsants, Other

What Is Valproic Acid and How Does It Work?

Valproic acid is an antiepileptic used to treat various types of seizure disorders. Valproic acid is sometimes used together with other seizure medications.

Valproic acid is available under the following different brand names: Depakene, Stavzor, and Depacon.

Dosages of Valproic Acid

Adult and Pediatric Dosage Forms and Strengths

Capsule (Depakene)

Capsule, delayed-release (Stavzor)

  • 125 mg
  • 250 mg
  • 500 mg

Syrup (Depakene)

  • 250 mg/5mL

Injectable solution (Depacon as valproate sodium)

  • 100 mg/mL

Dosage Considerations – Should be Given as Follows:

Complex Partial Seizures

  • Indicated as monotherapy and adjunctive therapy for complex partial seizures that occur either in isolation or in association with other types of seizures

Adult

  • Intravenous (IV) (valproate sodium): 10-15 mg/kg/day IV divided every 12 hours infused over 1 hour; maximum dose 60 mg/kg/day; do not exceed 14 days (switch to orally as soon as possible)
  • Oral: 10-15 mg/kg/day orally initially; increase by 5-10 mg/kg/day at weekly intervals; may increase dose up to 60 mg/kg/day

Pediatric

  • Intravenous (IV) (valproate sodium): 10-15 mg/kg/day IV divided every 12 hours infused over 1 hour; maximum dose 60 mg/kg/day; do not exceed 14 days (switch to orally as soon as possible)
  • Oral: (Depakene or Stavzor): 10-15 mg/kg/day orally initially; increase by 5-10 mg/kg/day at weekly intervals; may increase dose up to 60 mg/kg/day
  • Children under 10 years: Safety and efficacy not established

Simple and Complex Absence Seizures

Adult

  • Intravenous (IV) (valproate sodium): 10-15 mg/kg/day IV divided every 12 hours infused over 1 hour; maximum dose 60 mg/kg/day; do not exceed 14 days (switch to oral as soon as possible)
  • Oral (Depakene, Stavzor): 15 mg/kg/day orally initially, divided every 6-12 hours; increase by 5-10 mg/kg/day at weekly intervals; may increase dose up to 60 mg/kg/day

Pediatric

Children 10 years and older

  • Intravenous (IV) (valproate sodium): 10-15 mg/kg/day IV divided every 12 hours infused over 1 hour; maximum dose 60 mg/kg/day; do not exceed 14 days (switch to oral as soon as possible)
  • Stavzor: 250 mg orally every 12 hours; adjust dose based on clinical response up to 1000 mg/day
  • Children under 10 years: Safety and efficacy not established

Migraine

  • Indicated for prophylaxis of migraine headaches; there is no evidence of use for acute treatment
  • Stavzor: 250 mg orally every 12 hours; adjust dose based on clinical response, not to exceed 1000 mg/day

Bipolar Mania

  • Indicated for treatment of manic episodes associated with bipolar disorder
  • Stavzor: 750 mg/day orally in divided doses; adjust dose as rapidly as possible to desired therapeutic effect; not to exceed 60 mg/kg/day

Dosage Modifications

Renal impairment

  • Moderate (CrCl 30 to less than 50 mL/min): Observe closely and promptly evaluate any signs or symptoms of blood loss in patients with moderate renal impairment
  • Severe (CrCl less than 30 mL/min): Avoid use, due to expected increase in valproic_acid exposure and pharmacodynamic effects
  • If acute renal failure develops while on valproic_acid, discontinue treatment

Renal impairment (nonvalvular AF)

  • No adjustment necessary; protein binding is reduced and may cause measurement of total valproate concentrations to be inaccurate

Hepatic impairment

  • Administer lower doses
  • Contraindicated in severe impairment

Dosing Considerations

Monitor liver function tests (LFT's)

Therapeutic range

  • Low serum albumin levels may cause an increase in unbound drug (while total concentration may appear normal)
  • Epilepsy: 50-100 mcg/mL total valproate
  • Mania: 50-125 mcg/mL total valproate

What Are Side Effects Associated with Using Valproic Acid?

Common side effects of valproic_acid include:

Other side effects of valproic acid include:

Serious side effects of valproic acid include:

Postmarketing side effects of valproic acid reported include:

This is not a complete list of side effects and other serious side effects may occur. Call your doctor for information and medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What Other Drugs Interact with Valproic Acid?

If your doctor has directed you to use this medication for your condition, your doctor or pharmacist may already be aware of any possible drug interactions or side effects and may be monitoring you for them. Do not start, stop, or change the dosage of this medicine or any medicine before getting further information from your doctor, healthcare provider or pharmacist first.

Valproic acid has no known severe interactions with other drugs.

Serious interactions of valproic acid include:

  • doripenem
  • ertapenem
  • imipenem/cilastatin
  • lesinurad
  • meropenem
  • nitazoxanide
  • sodium oxybate
  • sodium phenylacetate
  • vorinostat

Valproic acid has moderate interactions with at least 44 different drugs.

Valproic acid has mild interactions with at least 54 different drugs.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

What Are Warnings and Precautions for Valproic Acid?

Warnings

Hepatotoxicity

  • Hepatic failure resulting in fatalities has occurred
  • Children younger than 2 years are at increased risk for fatal hepatotoxicity, particularly patients on multiple anticonvulsants, as well as those with congenital metabolic disorders, severe seizure disorders accompanied by mental retardation, or organic brain disease
  • Increased risk of valproate-induced acute liver failure and resultant deaths in patients with hereditary neurometabolic syndromes caused by DNA mutations of the mitochondrial DNA polymerase-gamma (POLG) gene (e.g., Alpers Huttenlocher Syndrome)
  • If used in children with these conditions, it should be administered with extreme caution as a sole agent
  • Hepatotoxicity usually occurs during the first 6 months of treatment and may be preceded by malaise, weakness, lethargy, facial edema, anorexia, and vomiting

Teratogenicity

  • Do not use in women of childbearing age unless the drug is essential to the management of the medical condition; all non-pregnant women of childbearing potential should use effective birth control if taking valproate products (see Contraindications and Pregnancy sections)
  • May cause neural tube defects
  • Children exposed in utero have increased risk for lower cognitive test scores compared with those exposed in utero to other anti-seizure medications
  • Alternative medications that have a lower risk for adverse birth outcomes should be considered
  • Patients should not stop taking valproate without talking to a health-care professional

Pancreatitis

  • Cases of life-threatening pancreatitis have been reported in children and adults
  • Some cases have been described as hemorrhagic with a rapid progression from initial symptoms to death
  • This medication contains valproic acid. Do not take Depakene, Stavzor, or Depacon if you are allergic to valproic acid or any ingredients contained in this drug.

This medication contains valproic_acid. Do not take Xarelto if you are allergic to valproic_acid or any ingredients contained in this drug.

Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Contraindications

  • Hypersensitivity
  • Liver disease, significant hepatic impairment
  • Urea cycle disorder
  • Mitochondrial disorders caused by mutations in mitochondrial DNA polymerase-gamma (POLG; e.g., Alpers-Huttenlocher Syndrome) and children under 2 years of age who are suspected of having a POLG-related disorder
  • Migraine headache prevention in women who are pregnant or plan to become pregnant

Effects of Drug Abuse

No information available

Short-Term Effects

  • See "What Are Side Effects Associated with Using Valproic Acid?"

Long-Term Effects

  • See "What Are Side Effects Associated with Using Valproic Acid?"

Cautions

  • Probability of thrombocytopenia increases significantly at total trough valproate plasma concentrations exceed 110 mcg/mL in females and 135 mcg/mL in males.
  • Bleeding and other hematopoietic disorders may occur; monitor platelet counts and coagulation tests.
  • Hepatotoxic (age under 2 years, higher risk of fatal hepatotoxicity); evaluate high risk populations and monitor serum liver tests; see Warnings.
  • POLG mutations; see Contraindications and Warnings.
  • Discontinue if hyperammonemia occurs; check ammonia level if emesis occurs or if the patient displays lethargy or abnormal behavior; evaluate patient for urea cycle disorder (see Contraindications) or hepatotoxicity (see Warnings).

Pancreatitis, including fatalities reported (see Warnings)

  • Porphyria may occur.
  • May produce false-positive urine ketone test and alter thyroid function tests (TFTs).
  • May cause central nervous system (CNS) depression, which may impair physical or mental to perform tasks requiring mental alertness.
  • Birth defects and decreased IQ following in utero exposure compared with 3 other common AEDs (carbamazepine, lamotrigine, phenytoin); only use to treat pregnant women with epilepsy if other medications are unacceptable; should not be administered to a woman of childbearing potential unless essential; reversible and irreversible cerebellar atrophy reported; monitor motor and cognitive function routinely.
  • Drug reaction with eosinophilia and systemic symptoms (DRESS)/multiorgan hypersensitivity reaction reported; discontinue therapy; monitor for possible disparate manifestations associated with lymphatic, renal, hepatic, and/or hematologic organ systems.
  • Not recommended for post-traumatic seizure prophylaxis in patients with acute head trauma (may increase mortality).
  • Hypothermia reported during valproate therapy with or without associated hyperammonemia; this adverse reaction can also occur in patients using concomitant topiramate.
  • Somnolence in the elderly can occur; valproic acid dosage should be increased slowly and with regular monitoring for fluid and nutritional intake.

Pregnancy and Lactation

  • Use valproic acid during pregnancy for seizures or manic episodes associated with bipolar disorder that are unresponsive to other treatments in LIFE-THREATENING emergencies when no safer drug is available.
  • There is positive evidence of human fetal risk.
  • Do not use in valproic acid pregnancy for migraine headache prevention. The risks involved outweigh potential benefits. Safer alternatives exist.
  • Results from epidemiologic studies concluded that children born to women who take valproate sodium or related products (valproic acid, divalproex sodium) during pregnancy have an increased risk for lower cognitive test scores, compared with children exposed to other antiseizure medications during pregnancy.
  • Valproic acid is known to cause neural tube defects; evidence suggests that folic acid supplementation prior to conception and during the first trimester decreases risk for congenital neural tube defects.
  • Valproic acid is excreted in milk; use caution if breastfeeding. The American Academy of Pediatrics (AAP) and the American College of Obstetricians and Gynecologists (ACOG) say valproic acid is compatible with nursing.
Reviewed on 1/23/2018


Medscape. Valproic Acid.
https://reference.medscape.com/drug/depakene-stavzor-valproic-acid-343024
DailyMed. Depakene.
https://www.rxlist.com/depakene-side-effects-drug-center.htm

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