Valproic acid

Generic Name : valproic acid , sodium valproate , valproate acid ,divalproex sodium Brand Name:

Apo-Valproic Acid (CAN), Gen-Valproic (CAN), Novo-Valproic (CAN), Nu-Valprox (CAN), ratio-Valproic (CAN) Capsules: Depakene Syrup: Depakene Injection: Depacon, Epiject (CAN) Tablets, enteric coated: Depakote, Depakote ER, Depakote Sprinkle, Divalproex, Epival (CAN)

Classification: Antiepileptic Pregnancy Category D

Dosage & Route

ADULTS Dosage is expressed as valproic acid equivalents. Initial dose is 1015 mg/kg/day PO, increasing at 1-wk intervals by 510 mg/kg/day until seizures are controlled or side effects preclude further increases. Maximum recommended dosage is 60 mg/kg/day PO. If total dose > 250 mg/day, give in divided doses.

Acute mania or bipolar disorder: Initially, 25 mg/kg/day PO once daily. Dose should be increased rapidly to achieve the lowest therapeutic dose. Maximum dose 60 mg/kg/day PO (Depakote ER only). Bipolar mania: 750 mg PO daily in divided doses; do not exceed 60 mg/kg/day (Divalproex DR tablets only). Migraine: 250 mg PO bid; up to 1,000 mg/day has been used (Divalproex DR tablets); 500 mg ER tablet once a day.

PEDIATRIC PATIENTS > 10 YR

10-15 mg/kg/day PO.

PEDIATRIC PATIENTS

Use extreme caution. Fatal hepatotoxicity has occurred. Children < 2 yr are especially susceptible. Monitor all children carefully.

Therapeutic actions
Mechanism of action not understood: antiepileptic activity may be related to the metabolism of the inhibitory neurotransmitter, GABA; divalproex sodium is a compound containing equal proportions of valproic acid and sodium valproate.

Indications
Sole and adjunctive therapy in simple (petit mal) and complex absence seizures Depakote ER: Treatment of epilepsy in children > 10 yr; treatment of acute manic or mixed episodes associated with bipolar disorder, with or without psychotic features Adjunctive therapy with multiple seizure types, including absence seizures Depakote ER: Treatment of bipolar mania Depakote, Depacote ER: Prophylaxis of migraine headaches Divalproex, sodium valproate injection: Treatment of complex partial seizures as monotherapy or with other antiepileptics Unlabeled uses: Adjunct in symptom management of schizophrenia, treatment of aggressive outbursts in children with attention-deficit hyperactivity disorder, organic brain syndrome

Adverse effects
CNS: Sedation, tremor (may be dose-related), emotional upset, depression, psychosis, aggression, hyperactivity, behavioral deterioration, weakness Dermatologic: Transient increases in hair loss, rash, petechiae GI: Nausea, vomiting, indigestion, diarrhea, abdominal cramps, constipation, anorexia with weight loss, increased appetite with weight gain, life-threatening pancreatitis, hepatic failure GU: Irregular menses, secondary amenorrhea Hematologic: Slight elevations in AST, ALT, LDH; increases in serum bilirubin, abnormal changes in other LFTs, altered bleeding time; thrombocytopenia; bruising; hematoma formation; frank hemorrhage; relative lymphocytosis; hypofibrinogenemia; leukopenia, eosinophilia, anemia, bone marrow suppression

Contraindications
Contraindicated with hypersensitivity to valproic acid, hepatic disease or significant hepatic impairment. Use cautiously with children < 18 mo; children < 2 yr, especially with multiple antiepileptics, congenital metabolic disorders, severe seizures accompanied by severe mental retardation, organic brain disorders (higher risk of developing fatal hepatotoxicity); pregnancy (fetal neural tube defects; do not discontinue to prevent

major seizures; discontinuing such medication is likely to precipitate status epilepticus, hypoxia and risk to both mother and fetus); lactation.

Nursing considerations
CLINICAL ALERT! Confusion has occurred between delayed-release Depakote and Depakote ER. Dosage is very different and serious adverse effects can occur; use extreme caution. Assessment

History: Hypersensitivity to valproic acid; hepatic impairment; pregnancy, lactation Physical: Weight; skin color, lesions; orientation, affect, reflexes; bowel sounds, normal output; CBC and differential, bleeding time tests, LFTs, serum ammonia level, exocrine pancreatic function tests, EEG

Interventions

Give drug with food if GI upset occurs; substitution of the enteric-coated formulation also may be of benefit; have patient swallow SR tablet whole; do not cut, crush, or chew. WARNING: Reduce dosage, discontinue, or substitute other antiepileptics gradually; abrupt discontinuation of all antiepileptics may precipitate absence seizures. BLACK BOX WARNING: Arrange for frequent LFTs; discontinue drug immediately with significant hepatic impairment, suspected or apparent significant hepatic impairment; continue LFTs to determine if hepatic impairment progresses in spite of drug discontinuation. WARNING: Arrange for patient to have platelet counts, bleeding time determination before therapy, periodically during therapy, and prior to surgery. Monitor patient carefully for clotting defects (bruising, blood-tinged toothbrush). Discontinue if there is evidence of hemorrhage, bruising, or disorder of hemostasis. Monitor ammonia levels, and discontinue if there is clinically significant elevation in level. Monitor serum levels of valproic acid and other antiepileptic drugs given concomitantly, especially during the first few weeks of therapy. Adjust dosage on the basis of these data and clinical response. BLACK BOX WARNING: Arrange for counseling for women of childbearing age who wish to become pregnant; drug may be teratogenic. BLACK BOX WARNING: Discontinue drug at any sign of pancreatitis. WARNING: Evaluate for therapeutic serum levelsusually 50100 mcg/mL.

Teaching points

Take this drug exactly as prescribed. Do not chew tablets or capsules before swallowing them. Swallow them whole to prevent local irritation of mouth and throat. Sprinkle tablets may be opened and sprinkled on applesauce or pudding.

Do not discontinue this drug abruptly or change dosage, except on the advice of your health care provider. Avoid alcohol and sleep-inducing and over-the-counter drugs. These could cause dangerous effects. Have frequent checkups, including blood tests, to monitor your drug response. Keep all appointments for checkups. Use contraceptive techniques at all times. If you want to become pregnant, consult your health care provider. Wear a medical ID tag to alert emergency medical personnel that you have epilepsy and are taking antiepileptic medication. If you have diabetes, this drug may interfere with urine tests for ketones. You may experience these side effects: Drowsiness (avoid driving or performing other tasks requiring alertness; take at bedtime); GI upset (take with food or milk, eat frequent small meals; if problem persists, substitute enteric-coated drug); transient increase in hair loss. Report bruising, pink stain on the toothbrush, yellowing of the skin or eyes, pale feces, rash, pregnancy; abdominal pain with nausea, vomiting, anorexia.