Label: VALPROIC ACID solution

  • NDC Code(s): 62559-266-16
  • Packager: ANI Pharmaceuticals, Inc.
  • Category: HUMAN PRESCRIPTION DRUG LABEL
  • DEA Schedule: None
  • Marketing Status: Abbreviated New Drug Application

Drug Label Information

Updated January 2, 2024

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  • HIGHLIGHTS OF PRESCRIBING INFORMATION
    These highlights do not include all the information needed to use VALPROIC ACID ORAL SOLUTION safely and effectively. See full prescribing information for VALPROIC ACID ORAL SOLUTION. VALPROIC ACID ...
  • Table of Contents
    Table of Contents
  • BOXED WARNING (What is this?)

    WARNING: LIFE THREATENING ADVERSE REACTIONS

    Hepatotoxicity
    General Population: Hepatic failure resulting in fatalities has occurred in patients receiving valproate and its derivatives. These incidents usually have occurred during the first six months of treatment. Serious or fatal hepatotoxicity may be preceded by non-specific symptoms such as malaise, weakness, lethargy, facial edema, anorexia, and vomiting. In patients with epilepsy, a loss of seizure control may also occur. Patients should be monitored closely for appearance of these symptoms. Serum liver tests should be performed prior to therapy and at frequent intervals thereafter, especially during the first six months [see Warnings and Precautions (5.1)].

    Children under the age of two years are at a considerably increased risk of developing fatal hepatotoxicity, especially those on multiple anticonvulsants, those with congenital metabolic disorders, those with severe seizure disorders accompanied by mental retardation, and those with organic brain disease. When valproic acid products are used in this patient group, they should be used with extreme caution and as a sole agent. The benefits of therapy should be weighed against the risks. The incidence of fatal hepatotoxicity decreases considerably in progressively older patient groups.

    Patients with Mitochondrial Disease: There is an 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 γ (POLG) gene (e.g. Alpers Huttenlocher Syndrome). Valproic acid is contraindicated in patients known to have mitochondrial disorders caused by POLG mutations and children under two years of age who are clinically suspected of having a mitochondrial disorder [see Contraindications (4)]. In patients over two years of age who are clinically suspected of having a hereditary mitochondrial disease, valproic acid should only be used after other anticonvulsants have failed. This older group of patients should be closely monitored during treatment with valproic acid for the development of acute liver injury with regular clinical assessments and serum liver testing. POLG mutation screening should be performed in accordance with current clinical practice [see Warnings and Precautions (5.1)].

    Fetal Risk
    Valproate can cause major congenital malformations, particularly neural tube defects (e.g., spina bifida). In addition, valproate can cause decreased IQ scores and neurodevelopmental disorders following in utero exposure.

    Valproate is therefore contraindicated for prophylaxis of migraine headaches in pregnant women and in women of childbearing potential who are not using effective contraception [see Contraindications (4)]. Valproate should not be used to treat women with epilepsy or bipolar disorder who are pregnant or who plan to become pregnant unless other medications have failed to provide adequate symptom control or are otherwise unacceptable.

    Valproate should not be administered to a woman of childbearing potential unless other medications have failed to provide adequate symptom control or are otherwise unacceptable. In such situations, effective contraception should be used [see Warnings and Precautions (5.2, 5.3, 5.4)].

    A Medication Guide describing the risks of valproate is available for patients [see Patient Counseling Information (17)].

    Pancreatitis
    Cases of life-threatening pancreatitis have been reported in both children and adults receiving valproate. Some of the cases have been described as hemorrhagic with a rapid progression from initial symptoms to death. Cases have been reported shortly after initial use as well as after several years of use. Patients and guardians should be warned that abdominal pain, nausea, vomiting, and/or anorexia can be symptoms of pancreatitis that require prompt medical evaluation. If pancreatitis is diagnosed, valproate should ordinarily be discontinued. Alternative treatment for the underlying medical condition should be initiated as clinically indicated [see Warnings and Precautions (5.5)].

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  • 1 INDICATIONS AND USAGE
    1.1 Epilepsy - Valproic acid oral solution is indicated as monotherapy and adjunctive therapy in the treatment of patients with complex partial seizures that occur either in isolation or in ...
  • 2 DOSAGE AND ADMINISTRATION
    2.1 Epilepsy - Valproic acid oral solution is intended for oral administration. Patients should be informed to take valproic acid oral solution every day as prescribed. If a dose is missed it ...
  • 3 DOSAGE FORMS AND STRENGTHS
    Valproic acid oral solution USP is available as a clear, red, sour cherry flavored oral solution containing the equivalent of 250 mg valproic acid per 5 mL as the sodium salt in bottles of 16 ...
  • 4 CONTRAINDICATIONS
    • Valproic acid should not be administered to patients with hepatic disease or significant hepatic dysfunction [see Warnings and Precautions (5.1)]. • Valproic acid is contraindicated in patients ...
  • 5 WARNINGS AND PRECAUTIONS
    5.1 Hepatotoxicity - General Information on Hepatotoxicity - Hepatic failure resulting in fatalities has occurred in patients receiving valproate. These incidents usually have occurred during the ...
  • 6 ADVERSE REACTIONS
    The following serious adverse reactions are described below and elsewhere in the labeling: • Hepatic failure [see Warnings and Precautions (5.1)] • Birth defects [see Warnings and Precautions ...
  • 7 DRUG INTERACTIONS
    7.1 Effects of Co-Administered Drugs on Valproate Clearance - Drugs that affect the level of expression of hepatic enzymes, particularly those that elevate levels of glucuronosyltransferases ...
  • 8 USE IN SPECIFIC POPULATIONS
    8.1 Pregnancy - Pregnancy Exposure Registry - There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs), including valproic acid oral ...
  • 10 OVERDOSAGE
    Overdosage with valproate may result in somnolence, heart block, deep coma, and hypernatremia. Fatalities have been reported; however, patients have recovered from valproate levels as high as ...
  • 11 DESCRIPTION
    Valproic acid is a carboxylic acid designated as 2-propylpentanoic acid. It is also known as dipropylacetic acid. Valproic acid has the following structure: Valproic acid (pKa 4.8) has a ...
  • 12 CLINICAL PHARMACOLOGY
    12.1 Mechanism of Action - Valproic acid dissociates to the valproate ion in the gastrointestinal tract. The mechanisms by which valproate exerts its therapeutic effects have not been ...
  • 13 NONCLINICAL TOXICOLOGY
    13.1 Carcinogenesis, Mutagenesis, and Impairment of Fertility - Carcinogenesis - Valproate was administered orally to rats and mice at doses of 80 and 170 mg/kg/day (less than the maximum ...
  • 14 CLINICAL STUDIES
    The studies described in the following section were conducted using divalproex sodium tablets. 14.1 Epilepsy - The efficacy of divalproex sodium in reducing the incidence of complex partial ...
  • 15 REFERENCES
    1. Meador KJ, Baker GA, Browning N, et al. Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): a prospective observational study. Lancet Neurology 2013; 12 ...
  • 16 HOW SUPPLIED/STORAGE AND HANDLING
    Valproic Acid Oral Solution USP is a clear, red, sour cherry flavored oral solution containing the equivalent of 250 mg valproic acid per 5 mL as the sodium salt and is available as follows: NDC ...
  • 17 PATIENT COUNSELING INFORMATION
    Advise the patient to read the FDA-approved patient labeling (Medication Guide). Hepatotoxicity - Warn patients and guardians that nausea, vomiting, abdominal pain, anorexia, diarrhea, asthenia ...
  • MEDICATION GUIDE
    Valproic (val PROE ik) Acid Oral Solution - Read this Medication Guide before you start taking valproic acid oral solution and each time you get a refill. There may be new information. This ...
  • PRINCIPAL DISPLAY PANEL
    Valproic Acid Oral Solution USP - 250 mg/5 mL - NDC 62559-266-16 - PHAMACIST: Dispense the accompanying Medication Guide to each patient. Rx only - NET CONTENTS: 16 fl. oz. (473 mL)
  • INGREDIENTS AND APPEARANCE
    Product Information