Depakote ER

Monotherapy & adjunctive therapy in the treatment of complex partial seizures that occur either in isolation or in association w/ other types of seizures in adults & childn ≥10 yr. Sole & adjunctive therapy in the treatment of simple & complex absence seizures & adjunctively in multiple seizure types that include absence seizures in adults & childn ≥10 yr. Treatment of acute manic or mixed episodes associated w/ bipolar disorder. Prophylaxis of migraine headaches.

Mania Initially 25 mg/kg/day once daily. Dose should be increased as rapidly as possible to achieve the lowest therapeutic dose that produces the desired clinical effect or range of plasma conc. Max: 60 mg/kg/day. Migraine prophylaxis Initially 500 mg once daily for 1 wk, thereafter increased to 1,000 mg once daily. Adult & childn ≥10 yr Monotherapy for complex partial seizure or conversion to monotherapy Initially 10-15 mg/kg/day, increased by 5-10 mg/kg/wk. Adjunctive therapy for complex partial seizure Initially 10-15 mg/kg/day, increased by 5-10 mg/kg/wk. Simple & complex absence seizure Initially 15 mg/kg/day, increased at 1-wk interval by 5-10 mg/kg/day. Max: 60 mg/kg/day.

Should be taken with food: Swallow whole & should not be crushed or chewed.

Hypersensitivity. Mitochondrial disorders caused by mutations in mitochondrial DNA polymerase γ (POLG; eg, Alpers-Huttenlocher syndrome) & childn <2 yr suspected of having POLG-related disorder; systemic primary carnitine deficiency w/ uncorrected hypocarnitinemia; urea cycle disorders (UCD); porphyria. Hepatic disease or significant hepatic dysfunction. Women of childbearing potential unless measures for prevention of pregnancy are met. Treatment of epilepsy: Pregnancy, unless there is no suitable alternative treatment. Treatment of mania & prophylaxis of migraine attacks: Pregnancy.

Not to be used for prophylaxis of post-traumatic seizures in patients w/ acute head trauma. Risk of hepatotoxicity/hepatic dysfunction. Reports of life-threatening pancreatitis; increased risk of suicidal thoughts or behavior; hyperammonemia; hyperammonemic encephalopathy, sometimes fatal, in patients w/ UCD, particularly ornithine transcarbamylase deficiency; hypothermia; brain atrophy; thrombocytopenia; multi-organ hypersensitivity reactions (rare); medication residue in the stool (rare). Increased risk of neurodevelopmental disorders in childn born to men treated w/ valproate in the 3 mth prior to conception. Discontinue if pancreatitis occurs; ammonia is increased; suspected or apparent signs of brain atrophy are present. May trigger occurrence or worsening of hypocarnitinemia that can result in hyperammonemia. Patients w/ inborn errors of metabolism or reduced hepatic mitochondrial activity may be at increased risk for hyperammonemia w/ or w/o encephalopathy. Some patients may experience a reversible worsening of convulsion frequency & severity, or onset of new types of convulsions. Risk of rhabdomyolysis in patients w/ underlying carnitine palmitoyltransferase type II deficiency. Perform LFTs prior to therapy & at frequent intervals thereafter, especially during the 1st 6 mth. Monitor platelet count & coagulation parameters prior to planned surgery, before initiating therapy & at periodic intervals. Should not be abruptly discontinued in patients in whom the drug is administered to prevent major seizures. Concomitant use w/ drugs which are capable of enzyme induction. Not recommended in concomitant use w/ carbapenems or pivalate-conjugated medicines. False interpretation of urine ketone test. Reports of altered thyroid function test. Patients w/ rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine. May affect ability to drive or operate machinery. Caution in patients w/ prior history of hepatic disease. High teratogenic potential. Women of childbearing potential must use effective contraception w/o interruption during entire treatment. Reports of amenorrhea, polycystic ovaries & increased testosterone levels in women. May impair fertility in men. Male patients should not donate sperm during treatment & for 3 mth after stopping treatment. Discontinue breast-feeding or discontinue/abstain from therapy. Use w/ extreme caution & as a sole agent in childn <2 yr. Safety & effectiveness have not been established in childn <18 yr for prophylaxis of migraines; & in childn <10 yr for the treatment of complex partial seizures, simple & complex absence seizures, & multiple seizures types that include absence seizures. Increase dose more slowly in elderly patients, w/ regular monitoring for fluid & nutritional intake, dehydration, somnolence, & other adverse events. Insufficient safety & effectiveness information for the prophylaxis of migraines in elderly >65 yr.

Somnolence, tremor; nausea; asthenia. Thrombocytopenia; decreased/increased wt; amnesia, ataxia, dizziness, dysgeusia, headache, nystagmus, paresthesia, speech disorder; tinnitus; abdominal pain, constipation, diarrhea, dyspepsia, flatulence, vomiting; alopecia, ecchymosis, pruritus, rash; decreased/increased appetite; gait disturbance, peripheral edema; abnormal dreams, affect lability, confusional state, depression, insomnia, nervousness, abnormal thinking; amblyopia, diplopia; infection; injury.

Clearance may be increased w/ enzyme-inducing drugs (eg, ritonavir, phenytoin, carbamazepine, phenobarb, primidone); estrogen-containing hormonal contraceptives. Decrease in protein-binding & inhibition of metabolism w/ aspirin. Significant reduction in serum conc w/ carbapenem antibiotics (eg, ertapenem, imipenem, meropenem). Increased mean peak conc w/ felbamate. Increased oral clearance w/ rifampin. Decreased plasma level w/ PIs (eg, lopinavir, ritonavir) or cholestyramine. Decreased serum levels w/ metamizole or MTX. Decreased plasma clearance of amitriptyline. Decreased net clearance of nortriptyline. Decreased serum levels of carbamazepine & increased serum levels of carbamazepine-10,11-epoxide (CBZ-E). May induce absence status w/ clonazepam in patients w/ history of absence type seizures. Reduced plasma clearance & vol of distribution of free diazepam. Inhibited metabolism of ethosuximide; phenobarb/primidone. Increased elimination t_1/2 of lamotrigine. Valproate displaces phenytoin from its plasma albumin binding sites & inhibits its hepatic metabolism. Valproic acid metabolites levels may be increased w/ phenytoin or phenobarb. Risk of hypocarnitinemia w/ pivalate-conjugated medicines that decrease carnitine levels (eg, cefditoren pivoxil, adefovir dipivoxil, pivmecillinam & pivampicillin). Increased blood level of propofol. May increase plasma conc of nimodipine. Increased unbound fraction of tolbutamide or warfarin. Increased ALT >3 times ULN w/ cannabidiol. Encephalopathy &/or hyperammonemia w/ topiramate or acetazolamide. Decreased clearance of zidovudine. Increased risk of neutropenia/leucopenia w/ quetiapine. May decrease plasma conc of olanzapine. May increase plasma level of rufinamide.

Anticonvulsants / Antimigraine Preparations

N03AG01 - valproic acid ; Belongs to the class of fatty acid derivatives antiepileptic.

Rx