Safety and tolerance of rapidly infused Depacon. A randomized trial in subjects with epilepsy.
BACKGROUND
Valproate sodium injection (Depacon(R)) is an intravenous form of valproate for use in absence and complex partial seizures when circumstances preclude oral administration. Certain situations may warrant larger and more rapid infusions than permitted by the original labeling. This study evaluated the safety of more rapid infusions.


METHODS
Subjects with epilepsy were randomized in a 2:1 ratio to receive up to 15 mg/kg of valproate sodium infused at 3.0 or 1.5 mg/kg/min. Up to four infusions were allowed within 24 h to achieve target plasma valproate concentrations of 50-100 mcg/ml. Primary safety endpoints were the changes in the 5-min and minimum post-first infusion blood pressures (BPs).


RESULTS
One hundred twelve subjects were treated, (3.0 mg/kg/min group: n=72, 1.5 mg/kg/min group: n=40). No significant treatment differences were detected for changes in the primary BP endpoints. Two subjects in the 3.0 mg/kg/min group had potentially clinically significant low systolic BP values during the study. Similar proportions of subjects in the two groups reported adverse events during or within 6 h following the first infusion.


CONCLUSIONS
Valproate sodium injection dosages up to 15 mg/kg and rates of 1.5 and 3.0 mg/kg/min were well tolerated in this population.
Ramsay
R E
RE
International Center for Epilepsy, University of Miami, Professional Arts Building, 1150 NW 14th Street, Suite 410, 33136, Miami, FL, USA. cramsay@epiworld.com
Cantrell
D
D
Collins
S D
SD
Walch
J K
JK
Naritoku
D K
DK
Cloyd
J C
JC
Sommerville
K
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D044383:Black People; D001794:Blood Pressure / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000145:classification / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D014635:Valproic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D044465:White People
D000927:Anticonvulsants; D014635:Valproic Acid