Adult Dosing
Complex Partial Seizures
Monotherapy (Initial Therapy)
- Initial: 10-15 mg/kg/day IV
- Titer: Increase 5-10 mg/kg/wk IV to achieve optimal response; [Max: 60 mg/kg/day]
Conversion to Monotherapy
- Initial: 10-15 mg/kg/day IV
- Titer: Increase 5-10 mg/kg/wk IV to achieve optimal response; [Max: 60 mg/kg/day]
- Reduce concomitant antiepilepsy drug (AED) dosage by approx 25% q2 wks
Adjunctive Therapy
- Start: 10-15 mg/kg/day IV
- Titer: Increase 5-10 mg/kg/wk IV to achieve optimal response; [Max: 60 mg/kg/day]
Simple and Complex Absence Seizures
- Initial: 15 mg/kg/day IV
- Titer: Increase 5-10 mg/kg/day IV qwk until seizures are controlled; [Max: 60 mg/kg/day]
Note:
- Use valproate IV for maximum 14 days
- Give IV infusion of valproate sodium for 60 mins (not more than 20 mg/min)
- Patients should be switched from IV to oral dose (valproic acid) as soon as possible
Status Epilepticus [Non-FDA Approved]@
- 25 mg/kg IV infused over 5-10 minutes [Max 1500 mg]
- Note some references recommend an infusion rate maximum of 50 mg/min
Pediatric Dosing
Complex Partial Seizures (
10 yrs)
Monotherapy
- Initial: 10-15 mg/kg/day IV
- Titer: Increase 5-10 mg/kg/wk IV to achieve optimal response; [Max: 60 mg/kg/day]
Conversion to Monotherapy (10 yrs)
- Initial: 10-15 mg/kg/day IV
- Titer: Increase 5-10 mg/kg/wk IV to achieve optimal response; [Max: 60 mg/kg/day]
- Reduce concomitant antiepilepsy drug (AED) dosage by approx 25% q2 wks
Adjunctive Therapy (10 yrs)
- Start: 10-15 mg/kg/day IV
- Titer: Increase 5-10 mg/kg/wk IV to achieve optimal response; [Max: 60 mg/kg/day]
Simple and Complex Absence Seizures (10 yrs)
- Initial: 15 mg/kg/day IV
- Titer: Increase 5-10 mg/kg/day IV qwk until seizures are controlled; [Max: 60 mg/kg/day]
Note:
- Use valproate IV for maximum 14 days
- Give IV infusion of valproate sodium for 60 mins (not more than 20 mg/min)
- Patients should be switched from IV to oral (valproic acid) dose as soon as possible
Status Epilepticus [Non-FDA Approved]@
- 25 mg/kg IV infused over 5-10 minutes [Max 1500 mg]
- Note some references recommend an infusion rate maximum of 50 mg/min
[Outline]
See Supplemental Patient Information
- Fatal hepatic failure has occurred in patients receiving valproic acid especially in the first six month of treatment. Closely monitor the patients and perform LFT at base line and at frequent interval during the treatment [US Black box warning]
- Valproate and any other antiepleptic drug causes teratogenic effect such as neural tube defect in fetus. Use cautiously in pregnancy and women with child bearing age only if potential benefit to mother outweighed against the risk to the fetus.
- Therapy can also cause decreased IQ scores following in utero exposure [US Black box warning]
- Do not discontinue the antiepileptic drug abruptly in patients with major seizures as it can precipitate status epilepticus with attendant hypoxia and threat to life
- Valproate causes clotting disorder, low fibrinogen level. Use of valproate in pregnancy causes afribrinogenemia in infant leading to the death due to hemorrhage
- Maternal use of valproate during pregnancy causes hepatotoxicity in infants
- Life threatening pancreatitis have occurred in both children and adults receiving valproate [U.S Black box warning]
- Avoid use of valproate in patients with known urea cycle disorders, as it causes hyperammonemic encephalopathy in such patients
- Before starting valproate therapy evaluate for urea cycle disorders (UCD) in patients with a history of unexplained encephalopathy or coma, pregnancy-related or postpartum encephalopathy, unexplained mental retardation, or history of elevated plasma ammonia or glutamine, cyclical vomiting and lethargy, episodic extreme irritability, ataxia, low BUN, or protein avoidance, family history of UCD or a family history of unexplained infant deaths. Immediately discontinue the drug if patient develops unexplained hyperammonemic encephalopathy and provide prompt treatment
- Monitor the patient receiving any antiepileptic drug including valproate for the signs of depression suicidal thoughts or behavior, and/or any unusual changes in mood or behavior, as antiepileptic drugs increase the risk of suicidal tendencies in the patients
- Concomitant use of carbapenem antibiotic with valproate reduce serum valproic acid concentrations to subtherapeutic levels, resulting in loss of seizure control
- Valproate causes somnolence in elderly patients and also dehydration and weight loss. Use valproate cautiously in elderly patients and increase dosage slowly, with regular monitoring for fluid and nutritional intake, dehydration, somnolence, and other adverse events
- Thrombocytopenia occurs with total valproate concentrations of 110 mcg/mL (female) - 135 mcg/mL (male). Monitor platelet counts and coagulation before starting the treatment and periodically
- Valproate causes hypothermia; discontinue the drug on development of hypothermia manifested by lethargy, confusion, coma, and significant alterations in other major organ systems such as the cardiovascular and respiratory systems. Monitor blood ammonia levels
- Multi-organ hypersensitivity reactions have occurred with valproate therapy in adult and pediatric patients
- Valproate is partially eliminated as ketometabolite in the urine and lead to false interpretation of urine ketone test and also alters the thyroid function test
- Patients developing unexplained lethargy and vomiting or changes in mental status, hyperammonemic encephalopathy, hypothermia should be evaluated for hyperammonemia. Discontinue the drug if high ammonia level and initiate hyperammonemia treatment
- Concomitant use of topiramate and valproate causes hyperammonemia with or without encephalopathy
- Increased risk of lower cognitive function has been reported in children born to mothers exposed to valproate sodium or related products throughout their pregnancy, as compared to the children born to mothers exposed to other anti-seizure medications
Cautions: Use cautiously in
- Renal impairment
- History of liver disease
- Pediatric patients
- Infants and young children
- Organic brain disease
- Head injury
- Hx of depression
- Mental retardation with seizure disorder
- Congenital metabolic disorders
- Taking multiple anticonvulsants (increased hepatotoxicity)
- Myelosuppression
- Bleeding tendencies
- Elderly patients
Supplemental Patient Information
- As valproate causes CNS depression patients are advised not to drive an automobile or operate dangerous machinery
- Women those who are planning to become pregnant or have become pregnant should inform their doctors as valproate is known to cause teratogenic effect in fetus
- Patients should immediately report to the physician if there is fever associated with other organ system involvement (rash, lymphadenopathy, etc.) during the treatment
Pregnancy Category:D
Breastfeeding: Low level of valproic acid is excreted in breastmilk; no unquestionable adverse reactions to valproic acid have been reported during breastfeeding. Monitoring infant serum valproate levels, platelets and liver enzymes during maternal therapy as breastfed infants are at risk for valproate induced hepatotoxicity and thrombocytopenia. Monitor infants for jaundice and other signs of liver damage, unusual bruising or bleeding. Combination therapy with sedating anticonvulsants or psychotropics may result in infant sedation or withdrawal reactions. This information is based upon LactMed database (available at http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT) last accessed 13th December 2010). However manufacturer advises to discontinue nursing when valproate is administered to a nursing woman.
US Trade Name(s)
US Availability
valproate sodium (generic)
Depacon
- INJ: 100 mg/mL (5 mL vial)
Canadian Trade Name(s)
Canadian Availability
UK Trade Name(s)
UK Availability
Epilim
- PWDR for INJ: 400 mg/vial
Episenta
- INJ: 100 mg/mL (3, 10 mL amp)
Australian Trade Name(s)
Australian Availability
Epilim IV
- PWDR for INJ: 400 mg/vial
[Outline]