Valpros Pedia

Monotherapy & adjunctive therapy in the treatment of patients w/ complex partial seizures that occur either in isolation or in association w/ other types of seizures; simple & complex absence seizures. Adjunct in patients w/ multiple seizure types that include absence seizures.

Initially 15 mg/kg/day, increased at 1-wk intervals by 5-10 mg/kg/day, until seizures are controlled or when occurrence of adverse effects prevent further dose increase. Max: 60 mg/kg/day. Should be given in divided regimen if the total daily dose exceeds 250 mg.

Should be taken with food.

Hypersensitivity to Na valproate or valproic acid. Pre-existing, acute, or chronic hepatic dysfunction or history of severe hepatic dysfunction, especially drug-related. Mitochondrial disorders caused by mutations in mitochondrial DNA polymerase γ (POLG; eg, Alpers-Huttenlocher syndrome) & childn <2 yr who are suspected of having a POLG-related disorder. Urea cycle disorders (UCD). Porphyria. Pregnant women.

Risk of major congenital malformations particularly neural tube defects (eg, spina bifida), & decreased IQ scores following in utero exposure; valproate-induced acute liver failure & resultant deaths in patients w/ hereditary neurometabolic syndromes caused by DNA mutations of the mitochondrial DNA POLG gene (eg, Alpers-Huttenlocher syndrome). Possible sudden alterations in plasma conc resulting to recurrence of symptoms; gradually w/draw treatment to avoid or minimize potential for seizures or increased seizure frequency. Reports of severe liver damage, including hepatic failure, usually in the 1st 6 mth of treatment; perform serum liver tests at baseline & at regular intervals thereafter during the 1st 6 mth of treatment, especially at patients at most risk & those w/ history of liver disease. High teratogenic potential. Discontinue treatment upon diagnosis of pancreatitis; if multi-organ hypersensitivity reaction is suspected; significant hepatic dysfunction (suspected or apparent) has occurred; serum ammonia levels are increased; signs of brain atrophy are suspected; blood creatine phosphokinase levels are significantly elevated, or if signs & symptoms indicative of rhabdomyolysis occurred; patients develop hypothermia; signs of brain atrophy are suspected. Stimulates replication of HIV & cytomegalovirus (CMV) under certain experimental conditions; consider when interpreting results from regular monitoring of viral load in HIV-infected patients treated w/ valproate or when following CMV-infected patients clinically. Monitor patients for emergence of worsening depression, & signs of suicidal ideation & behavior. Cases of hyperammonemic encephalopathy, some fatal, in patients w/ UCD, particularly ornithine transcarbamylase deficiency; increased serum thyroid-stimulating hormone or decreased serum thyroxine levels. Measurement of CBC, & coagulation tests are recommended prior to treatment & at periodic intervals thereafter. Monitor blood counts & coagulation parameters prior to planned surgery, during pregnancy, & in case of spontaneous bruising or bleeding. Routinely monitor motor & cognitive functions during therapy. Caution in patients on anticoagulant therapy. Not recommended in concurrent use w/ carbapenem antibiotics. Periodic plasma conc of valproate & of concurrent enzyme inducers are recommended during early course of therapy. False interpretation of urine ketone test may occur. Altered thyroid function tests. Use only in female childn if other treatment options are ineffective or not tolerated. May affect ability to drive or operate machines. Reports of amenorrhea, polycystic ovaries, & increased testosterone levels in women. May impair male fertility. Not to be administered to a woman of childbearing potential unless other medications have failed to provide adequate symptoms control or are otherwise unacceptable. Abstain from breastfeeding or discontinue therapy. Women should not breastfeed during treatment & for 1 mth after treatment discontinuation. Monitor breastfed infant for signs of liver damage (eg, jaundice) & unusual bruising or bleeding. Use only in childn <2 yr w/ extreme caution as monotherapy. Somnolence in the elderly. Perform dose selection w/ caution in the elderly.

Nausea, vomiting, tremor, headache, abdominal pain & indigestion.

Risk of encephalopathy &/or hyperammonemia w/ acetazolamide. Reduced plasma conc of both valproic acid & phenytoin in a child on short-term oral aciclovir therapy. May potentiate CNS depressant action of alcohol. Decreased plasma clearance of amitriptyline & net clearance of nortriptyline. Reduced plasma conc & increased intrinsic clearance w/ antiepileptics w/ enzyme-inducing effects. Increased metabolism w/ anti-malarial agents eg, mefloquine, chloroquine. Plasma level may be reduced w/ antiretroviral agents (eg, ritonavir, lopinavir, zidovudine, lamivudine). Decreased clearance of zidovudine in patients seropositive for HIV. May decrease oxidative hepatic metabolism of some benzodiazepines. May induce absence seizures w/ clonazepam in patients w/ history of absence type of seizures. Displaces diazepam from plasma binding sites & inhibits its metabolism. May increase free plasma levels of midazolam. Reduced serum conc w/ carbapenem antibiotics (eg, ertapenem, imipenem, meropenem). Reduced absorption & plasma levels w/ cholestyramine. Inhibited metabolism w/ chlorpromazine. Reduced hepatic metabolism w/ cimetidine. Competitive protein binding may potentiate an increase in levels of either clozapine or valproate when concomitantly administered. Increased clearance w/ CYP450 inducers eg, phenytoin, carbamazepine, & phenobarb (or primidone). CYP450 inhibitors (eg, antidepressants) are expected to have little effect in valproate clearance. Clearance may be increased & plasma levels decreased w/ drugs affecting hepatic microsomal enzymes, particularly those that elevate levels of glucuronosyltransferases (eg, ritonavir). Serum levels may be altered w/ drugs w/ extensive protein binding. Decreased protein binding & inhibited metabolism w/ aspirin at antipyretic doses (11-16 mg/kg) in childn. May displace carbamazepine from protein binding sites & inhibit its metabolism. Inhibited hepatic metabolism of phenobarb; phenytoin. Increased metabolism w/ phenobarb. Increased plasma levels of primidone. Increased unbound fraction of tolbutamide. Increased anticoagulant effect of vit K-dependent factor anticoagulants. Plasma levels may be increased w/ erythromycin. Clearance may be increased w/ estrogen-containing hormonal contraceptives. Inhibited metabolism of ethosuximide. Increased mean conc w/ felbamate in patients w/ epilepsy. Free plasma levels may be increased w/ highly protein-bound agents eg, aspirin. Reduced metabolism of lamotrigine. May potentiate effect of MAOIs, TCAs, & other antipsychotics, & may enhance CNS depression & lower seizure threshold. Increased plasma conc of nimodipine. Reduced C_max & AUC of olanzapine. May inhibit metabolism of propofol & increase its blood levels. Increased oral clearance w/ rifampicin. Decreased clearance of rufinamide. Increased risk of neutropenia & leukopenia w/ quetiapine. Inhibited metabolism w/ SSRIs. Risk of hyperammonemia w/ or w/o encephalopathy w/ topiramate. May inhibit metabolism of TCAs. False interpretation of urine ketone test may occur. Altered thyroid function tests.

Anticonvulsants

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

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