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valproic acid (Rx)Brand and Other Names:Depakene, Stavzor, more...Depacon

 
 
 

Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

capsule (Depakene)

  • 250mg

capsule, delayed-release (Stavzor)

  • 125mg
  • 250mg
  • 500mg

syrup (Depakene)

  • 250mg/5mL

injectable solution (Depacon as valproate sodium)

  • 100mg/mL
more...

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

IV (valproate sodium): 10-15 mg/kg/day IV divided q12hr infused over 1 hr; maximum dose 60 mg/kg/day; do not exceed 14 days (switch to PO as soon as possible) 

PO: 10-15 mg/kg/day PO initially; increase by 5-10 mg/kg/day at weekly intervals; may increase dose up to 60 mg/kg/day

Simple & Complex Absence Seizures

Also indicated for use as sole and adjunctive therapy in the treatment of simple and complex absence seizures, and adjunctively in patients with multiple seizure types that include absence seizures

IV (valproate sodium): 10-15 mg/kg/day IV divided q12hr infused over 1 hr; maximum dose 60 mg/kg/day; do not exceed 14 days (switch to PO as soon as possible) 

PO (Depakene, Stavzor): 15 mg/kg/day PO initially, divided q6-12hr; increase by 5-10 mg/kg/day at weekly intervals; may increase dose up to 60 mg/kg/day

Migraine

Indicated for prophylaxis of migraine headaches; there is no evidence of use for acute treatment

Stavzor: 250 mg PO q12hr; 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 PO in divided doses; adjust dose as rapidly as possible to desired therapeutic effect; not to exceed 60 mg/kg/day

Dosage Modifications

Renal impairment

  • 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 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

Fragile X Syndrome (Orphan)

Orphan indication sponsor

  • Neuropharm Ltd; Fetcham Park House; Surrey KT22 9HD; UK

Familial Adenomatous Polyposis (Orphan)

Orphan indication sponsor

  • Topotarget A/S; Fruebjergvej 3; DK-2100; Copenhagen; Denmark

Dosage Forms & Strengths

capsule (Depakene)

  • 250mg

capsule, delayed-release (Stavzor)

  • 125mg
  • 250mg
  • 500mg

syrup (Depakene)

  • 250mg/5mL

injectable solution (Depacon as valproate sodium)

  • 100mg/mL
more...

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

<10 years: Safety and efficacy not established

(IV) valproate sodium: 10-15 mg/kg/day IV divided q12hr infused over 1 hr; maximum dose 60 mg/kg/day; do not exceed 14 days (switch to PO as soon as possible) 

PO (Depakene or Stavzor): 10-15 mg/kg/day PO initially; increase by 5-10 mg/kg/day at weekly intervals; may increase dose up to 60 mg/kg/day

Simple & Complex Absence Seizures

Indicated for use as sole and adjunctive therapy in the treatment of simple and complex absence seizures, and adjunctively in patients with multiple seizure types that include absence seizures

<10 years: Safety and efficacy not established

≥10 years

  • IV (valproate sodium): 10-15 mg/kg/day IV divided q12hr infused over 1 hr; maximum dose 60 mg/kg/day; do not exceed 14 days (switch to PO as soon as possible) 
  • Stavzor: 250 mg PO q12hr; adjust dose based on clinical response up to 1000 mg/day

Dosage Modifications

Renal impairment

  • 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 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

Wolfram Syndrome (Orphan)

Orphan designation for treatment of Wolfram syndrome

Sponsor

  • The University of Birmingham; Birmingham Research Park - Vincent Drive; Birmingham B15 2SQ

Administer as in adults, but may need to initiate at lower dose; the increment in dose should also be slow

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Interactions

Interaction Checker

valproic acid and

No Results

     
     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            Sort by :  
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            Adverse Effects

            >10%

            Nausea (31%)

            Headache (<31%)

            Increased bleeding time (26-30%)

            Thrombocytopenia (26-30%)

            Tremor (25%)

            Alopecia (<24%)

            Asthenia (16-20%)

            Infection (16-20%)

            Somnolence (16-20%)

            Amblyopia (11-15%)

            Diarrhea (11-15%)

            Diplopia (11-15%)

            Dizziness (11-15%)

            Dyspepsia (11-15%)

            Nystagmus (11-15%)

            Tinnitus (11-15%)

            Vomiting (11-15%)

            1-10%

            Ataxia (<8%)

            Increased appetite (<6%)

            Rash (<6%)

            Abdominal pain (<5%)

            Tremor (<5%)

            Back pain (<5%)

            Mood changes (<5%)

            Anxiety (<5%)

            Confusion (<5%)

            Abnormal gait (<5%)

            Paresthesia (<5%)

            Hallucinations (<5%)

            Catatonia (<5%)

            Dysarthria (<5%)

            Tardive dyskinesia (<5%)

            Vertigo (<5%)

            Irregular menses (<5%)

            Weight gain (4%)

            Frequency Not Defined

            Anorexia

            Acute pancreatitis (may be life-threatening)

            Hepatic toxicity

            Hyperammonemia

            Weight loss

            Fractures

            Osteoporosis

            Osteopenia

            Decreased bone mineral density

            Cerebral pseudoatrophy

            Postmarketing Report

            Hair texture change

            Hair color change

            Photosensitivity

            Erythema multiforme

            Toxic epidermal necrolysis

            Stevens-Johnson syndrome

            Elevated testosterone level

            Hyperandrogenism

            Hirsutism

            Nail and nailbed disorders

            Weight gain

            Aspermia, azoospermia, decreased sperm count, decreased spermatozoa motility, male infertility, and abnormal spermatozoa morphology

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            Warnings

            Black Box 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 (eg, 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 antiseizure 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

            Contraindications

            Hypersensitivity

            Liver disease, significant hepatic impairment

            Urea cycle disorder

            Mitochondrial disorders caused by mutations in mitochondrial DNA polymerase-gamma (POLG; eg, Alpers-Huttenlocher Syndrome) and children <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

            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 <2 years, higher risk of fatal hepatotoxicity); evaluate high risk populations and monitor serum liver tests; see Black Box Warnings

            POLG mutations; see Contraindications and Black Box 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 Black Box Warnings)

            Pancreatitis, including fatalities reported (see Black Box Warnings)

            Porphyria may occur

            May produce false-positive urine ketone test and alter TFTs

            May cause 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

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            Pregnancy & Lactation

            Pregnancy category: D for seizures or manic episodes associated with bipolar disorder that are unresponsive to other treatments

            Pregnancy category: X for migraine headache prevention

            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

            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

            Lactation: Excreted in milk; use caution (AAP and ACOG say compatible)

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

            more...
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            Pharmacology

            Mechanism of Action

            May increase levels of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in brain; may enhance or mimic action of GABA at postsynaptic receptor sites; may also inhibit sodium and calcium channels

            Absorption

            Bioavailability: Extended-release 81-89% of delayed-release

            Peak plasma time: 2 hr (Stavzor)

            Peak plasma concentration: 115-145 mcg/mL (IV)

            Distribution

            Protein bound: 80-90%

            Vd: 92 L/1.73 m²

            Metabolism

            Metabolized by liver

            Enzymes inhibited: CYP2C9

            Metabolites: 2-propyl-3-ketopentanoic acid

            Elimination

            Half-life: 7-13 hr (>2 months); 9-16 hr (adults)

            Dialyzable: Yes

            Total body clearance: 4.6 L•hr/1.73 m² (50% higher in children <10 years)

            Excretion: Urine (30-50%)

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            Administration

            IV Preparation

            Dilute with at least 50 mL of compatible diluent (eg, D5W; NS; LR)

            Stable for at least 24 hr when stored in glass or PVC at 15-30°C (59-86°F)

            IV Administration

            Infuse over 60 min at <20 mg/min

            Has been administered as rapid infusion over 5-10 min (1.5-3 mg/kg/min) (not per label; rapid infusion associated with increased AE risk, but in limited studies was well-tolerated) 

            Oral Administration

            Swallow whole, do not chew or crush

            Capsules may be opened and sprinkled on spoonful of soft food immediately before administration

            If dose is skipped, do not double next dose

            If daily oral dose >250 mg/day, give as divided dose

            Storage

            Store vials at 15-30°C (59-86°F)

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            Images

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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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