Epival

Monotherapy & adjunctive therapy in the treatment of complex partial seizures occurring 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 including absence seizures in adults & childn ≥10 yr. Treatment of acute manic or mixed episodes associated w/ bipolar disorder. Prophylaxis of migraine headaches.

Mania Initially 750 mg daily in divided doses. 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 250 mg bid. Some may benefit from doses up to 1,000 mg/day. 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. Give in divided doses if total daily dose exceeds 250 mg. 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. Give in divided doses if the total daily dose exceeds 250 mg.

Should be taken with food: Swallow whole, do not chew/crush.

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 acute liver failure & liver-related deaths in patients w/ hereditary neurometabolic syndromes caused by POLG mutations; 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. 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 studied in childn <18 yr for treatment of acute mania; & in childn <16 yr for prophylaxis of migraines. 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

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

Rx