Valproic acid

Valproic acid oral solution is indicated for: Monotherapy and adjunctive therapy of complex partial seizures; sole and adjunctive therapy of simple and complex absence seizures; adjunctive therapy in patients with multiple seizure types that include absence seizures ( 1 ) 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 association with other types of seizures. …

• Valproic acid oral solution is intended for oral administration
• Simple and Complex Absence Seizures: Start at 10 to 15 mg/kg/day, increasing at 1 week intervals by 5 to 10 mg/kg/week until seizure control or limiting side effects Safety of doses above 60 mg/kg/day is not established 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 should be taken as soon as possible, unless it is almost time for the next dose
• If a dose is skipped, the patient should not double the next dose
• Valproic acid is indicated as monotherapy and adjunctive therapy in complex partial seizures
• In adults and pediatric patients down to the age of 10 years, and in simple and complex absence seizures
• As the valproic acid dosage is titrated upward, concentrations of clonazepam, diazepam, ethosuximide, lamotrigine, tolbutamide, phenobarbital, carbamazepine, and/or phenytoin may be affected [see Drug Interactions ]
• Complex Partial Seizures For adults and children 10 years of age or older. Monotherapy (Initial Therapy) Valproic acid oral solution has not been systematically studied as initial therapy
• Patients should initiate therapy at 10 to 15 mg/kg/day
• The dosage should be increased by 5 to 10 mg/kg/week to achieve optimal clinical response
• Ordinarily, optimal clinical response is achieved at daily doses below 60 mg/kg/day. …

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 fluid ounces (473 mL). Oral solution: Equivalent of 250 mg valproic acid per 5 mL as the sodium salt ( 3 )

• Experience has indicated that pediatric patients under the age of two years are at a considerably increased risk of developing fatal hepatotoxicity, especially those with the aforementioned conditions [see Boxed Warning]
• When valproic acid is used in this patient group, it should be used with extreme caution and as a sole agent
• The benefits of therapy should be weighed against the risks
• Above the age of 2 years, experience in epilepsy has indicated that the incidence of fatal hepatotoxicity decreases considerably in progressively older patient groups. …

No patients above the age of 65 years were enrolled in double-blind prospective clinical trials of mania associated with bipolar illness. In a case review study of 583 patients, 72 patients (12%) were greater than 65 years of age. A higher percentage of patients above 65 years of age reported accidental injury, infection, pain, somnolence, and tremor. Discontinuation of valproate was occasionally associated with the latter two events. …

• 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, and/or jaundice can be symptoms of hepatotoxicity and, therefore, require further medical evaluation promptly [see Warnings and Precautions ]
• Pancreatitis Warn patients and guardians that abdominal pain, nausea, vomiting, and/or anorexia can be symptoms of pancreatitis and, therefore, require further medical evaluation promptly [see Warnings and Precautions ] . …

• Valproic acid should not be administered to patients with hepatic disease or significant hepatic dysfunction [see Warnings and Precautions ]
• Valproic acid is contraindicated in patients known to have mitochondrial disorders caused by mutations in mitochondrial DNA polymerase γ (POLG; e.g., Alpers-Huttenlocher Syndrome) and children under two years of age who are suspected of having a POLG-related disorder [see Warnings and Precautions ] . …

Hepatic enzyme-inducing drugs (e.g., phenytoin, carbamazepine, phenobarbital, primidone, rifampin) can increase valproate clearance, while enzyme inhibitors (e.g., felbamate) can decrease valproate clearance. Therefore increased monitoring of valproate and concomitant drug concentrations and dosage adjustment are indicated whenever enzyme- inducing or inhibiting drugs are introduced or withdrawn ( 7.1 ) Aspirin, carbapenem antibiotics, estrogen-containing hormonal contraceptives: Monitoring of valproate concentrations is recommended ( 7.1 ) Co-administration of valproate can affect the pharmacokinetics of other drugs (e.g. …

Hepatotoxicity; evaluate high risk populations and monitor serum liver tests ( 5.1) Birth defects, decreased IQ, and neurodevelopmental disorders following in utero exposure; should not be used to treat women with epilepsy or bipolar disorder who are pregnant or who plan to become pregnant or to treat a woman of childbearing potential unless other medications have failed to provide adequate symptom control or are otherwise unacceptable. …

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 ( 5.2 )] Decreased IQ following in utero exposure [see Warnings and Precautions ( 5.3 )] Pancreatitis [see Warnings and Precautions ( 5.5 )] Hyperammonemic encephalopathy [see Warnings and Precautions ( 5.6 , 5.9 , 5.10 )] Suicidal behavior and ideation [see Warnings and Precautions ( 5.7 )] Bleeding and other hematopoietic disorders [see Warnings and Precautions ( 5.8 )] Hypothermia [see Warnings and Precautions ( 5.11 )] Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan hypersensi …

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 solution, during pregnancy. Encourage women who are taking valproic acid during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling toll-free 1-888-233-2334 or visiting the website, http://www.aedpregnancyregistr …

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 2,120 mcg/mL. In overdose situations, the fraction of drug not bound to protein is high and hemodialysis or tandem hemodialysis plus hemoperfusion may result in significant removal of drug. The benefit of gastric lavage or emesis will vary with the time since ingestion. General supportive measures should be applied with particular attention to the maintenance of adequate urinary output. …

Take it when you remember, unless it is nearly time for the next dose. Then skip the missed one. Never take two doses at once to make up for it. Check your leaflet, as some medicines are different.