Lepsio

Valproic acid

Monotherapy & adjunctive therapy in the treatment of complex partial seizures. Sole therapy & adjunctive therapy in the treatment of simple & complex absence seizures & adjunctively in patients w/ multiple seizures that include absence seizures.

Adult & childn ≥10 yr Complex partial seizures: Monotherapy, conversion to monotherapy & adjunctive therapy Initially 10-15 mg/kg/day. Increase dose by 5-10 mg/kg/wk to achieve optimal clinical response. Daily doses of <60 mg/kg/day may achieve optimal clinical response. Simple & complex absence seizures Initially 15 mg/kg/day, increasing at 1 wk intervals by 5-10 mg/kg/day until seizures are controlled or side effects preclude further increases. Max of 250 mg in divided doses.

May be taken with or without food.

Hypersensitivity. Hepatic disease or significant hepatic dysfunction. Mitochondrial disorders caused by mutations in mitochondrial DNA polymerase γ (POLG; eg, Alpers-Huttenlocher syndrome) & childn <2 yr who are suspected of having POLG-related disorder. Urea cycle disorders (UCD). Porphyria. Not for use in prophylaxis of migraine in pregnant women.

Hepatotoxicity, prior history of hepatic disease, patients on multiple anticonvulsants, congenital metabolic disorders, severe seizure disorders accompanied by mental retardation, organic brain disease; valproate-induced acute liver failure & liver-related deaths in patients w/ hereditary neurometabolic syndromes caused by mutations in the gene for mitochondrial DNA polymerase γ (POLG eg, Alpers-Huttenlocher syndrome), family history or suggestive symptoms of POLG-related disorder; pancreatitis. History of unexplained encephalopathy or coma, encephalopathy associated w/ a protein load, pregnancy-related or postpartum encephalopathy, unexplained mental retardation, or history of elevated plasma ammonia or glutamine; cyclical vomiting & lethargy, episodic extreme irritability , ataxia, low BUN, protein avoidance; family history of UCD or of unexplained infant deaths (particularly males); those w/ other signs or symptoms of UCD. Increased risk of suicidal thoughts or behaviour w/ AEDs; loss of seizure control w/ concomitant use of carbapenems; somnolence in elderly; thrombocytopenia; hepatic dysfunction; concomitant administration w/ topiramate (hyperammonemia w/ or w/o encephalopathy); reversible or irreversible cerebral & cerebellar atrophy. Monitor platelet count & coagulation parameters prior to surgery. Multi-organ hypersensitivity reaction. May affect ability to drive or operate machinery. Women of childbearing potential, pregnancy & lactation. Childn. Elderly.

Headache, asthenia, fever, back & chest pain, malaise. Tachycardia, HTN, palpitation. Nausea, vomiting, abdominal pain, diarrhea, anorexia, dyspepsia, constipation, increased appetite, flatulence, hematemesis, eructation, pancreatitis, periodontal abscess. Thrombocytopenia, ecchymosis, petechiae. Wt gain/loss, peripheral edema, increased SGOT/SGPT. Myalgia, twitching, arthralgia, leg cramps, myasthenia. Somnolence, tremor, dizziness, diplopia, amblyopia/blurred vision, ataxia, nystagmus, emotional lability, abnormal thinking, amnesia, nervousness, depression, anxiety, confusion, abnormal gait, paresthesia, hypertonia, incoordination, abnormal dreams, personality disorder. Flu syndrome, infection, bronchitis, rhinitis, pharyngitis, dyspnea, sinusitis, increased cough, pneumonia, epistaxis. Rash, pruritus, dry skin, alopecia. Tinnitus, taste perversion, abnormal vision, deafness, otitis media. Urinary incontinence, vaginitis, dysmenorrhea, amenorrhea, urinary frequency.

May increase clearance w/ ritonavir; phenytoin, carbamazepine, phenobarb, primidone. May decrease protein binding & inhibition of metabolism w/ aspirin. Reduced serum valproic acid conc to subtherapeutic levels (loss of seizure control) w/ carbapenems (eg, ertapenem, imipenem, meropenem). May increase/decrease mean valproate peak conc w/ felbamate. May increase oral clearance w/ rifampin. Increase in trough plasma levels w/ chlorpromazine. Decrease in plasma clearance w/ amitriptyline/nortriptyline. Decrease in serum levels w/ carbamazepine. May induce absence status in patients w/ history of absence seizures w/ clonazepam. Inhibition of metabolism of diazepam, ethosuximide, phenobarb, primidone, phenytoin. Increased t_½ w/ lamotrigine.  Associated w/ hyperammonenia w/ or w/o encephalopathy & hypothermia w/ topiramate. Increased unbound fraction of warfarin. Decreased clearance of zidovudine.

Anticonvulsants

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

Rx