Names and pronunciation
(dye-val′proh-ex) Depakote, Depakote ER, Depakote Sprinkle, Epival
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Drug reference
(dye-val′proh-ex) Depakote, Depakote ER, Depakote Sprinkle, Epival
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Func. class.: Anticonvulsant, vascular headache suppressant
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Chem. class.: Carboxylic acid derivative
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ACTION: Increases levels of γ-ami nobutyric acid (GABA) in the brain, which decreases seizure activity
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USES: Simple (petit mal), complex (petit mal), absence, mixed seizures; manic episodes associated with bipolar disorder, prophylaxis of migraine, adjunct for schizophrenia, tardive dyskinesia, aggression in children with ADHD, organic brain syndrome, mania, migraines; tonic-clonic (grand mal), myoclonic seizures
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CONTRAINDICATIONS: Hyper sensitivity, urea cycle disorders, mito chondrial disease, hepatic disease Precautions: Breastfeeding, geriatric patients, abrupt discontinuation, carni tine deficiency, coagulopathy, depres sion, diarrhea, encephalopathy, head trauma, organic brain syndrome, HIV, renal disease, suicidal ideation, sur gery, thrombocytopenia
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Black Box Warning: Children <2 yr, con traception requirements, hepatotoxicity, pancreatitis, pregnancy Black Box Warning: Hepatotoxicity: AST, ALT, bilirubin, ammonia baseline and peri odically during 6 mo or more, discontinue if hyperammonemia occurs; hepatic failure has occurred; monitor for fever, anorexia, vomiting, lethargy, jaundice of skin, eyes that may occur during treatment; those with organic brain disorders, mental retardation, children <2 yr are at greater risk • DRESS: eosinophilia, changes in lab work, fever, rash, lymphadenopathy if present and condition confirmed, discon- tinue immediately, do not restart • Suicidal thoughts/behaviors: usually occurs during beginning of therapy, limit amount of product that is given to the pa- tient, assess for increasing suicidal thoughts, behaviors, anxiety, restlessness, hostility may proceed destructive behaviors • Hyperammonemic encephalopathy: can be fatal in those with urea cycle dis- orders (UCD); lethargy, confusion, coma, CV, respiratory changes; discontinue • Trough/peak: serum blood levels: therapeutic level 50-125 mcg/mL Black Box Warning: Pancreatitis: may be fatal; report immediately nausea, vomiting, anorexia, abdominal pain; may occur anytime during treatment or for several months/years after discontinu ing treatment, check risk factors before starting • Beers: avoid in older adults unless safer alternative is unavailable; ataxia, impaired psychomotor function may occur Black Box Warning: Pregnancy/ breastfeeding: do not use in pregnancy (migraine prophylaxis), use only in preg nancy (epilepsy, manic episodes) if other alternatives are unavailable; major mal formations may occur; enroll pregnant patients in the North American Anti epileptic Drug Pregnancy Registry, 888- 233-2334; cautious use in breastfeeding, excreted in breast milk Black Box Warning: To report visual disturbances, rash, diarrhea, abdomi nal pain, light-colored stools, jaun dice, protracted vomiting, weakness to prescriber • DRESS: to report fever, swelling of lymph glands, rash • Hepatotoxicity: to report immediately, anorexia, nausea, vomiting, abdominal pain, fever • That continuing follow-up exams and blood work will be needed • To carry an emergency ID with condi tion, medications taken • Overdose symptoms: Heart block, coma Black Box Warning: Pancreatitis: to report immediately; may be fatal, abdomi nal pain, nausea, vomiting, anorexia • To report immediately suicidal thoughts/ behaviors, increased depression, changes in mood, anxiety, hostility Black Box Warning: Pregnancy/breast- feeding: To use contraception while tak ing this product; to notify prescriber if pregnancy is planned or suspected
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SIDE EFFECTS CNS: Sedation, drowsiness, dizziness, headache, depression, behavioral changes, tremors, aggression, weakness, coma, suicidal ideation, hypothermia CV: Peripheral edema EENT: Visual disturbances, taste perversion GI: Nausea, vomiting, constipation, diarrhea, dyspepsia, anorexia, pancreati- tis, stomatitis, weight gain, dry mouth, hepatotoxicity HEMA: Thrombocytopenia, leukopenia INTEG: Rash, alopecia, photosensitivity, dry skin, DRESS META: Hyperammonemia, SIADH
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INTERACTIONS Increase: valproic acid toxicity level— erythromycin, felbamate, salicylates, NSAIDs, rifampin, carBAMazepine, cimetidine Increase: CNS depression—alcohol, anti depressants, benzodiazepines, opioids, bar biturates, antihistamines, MAOIs, sedative/ hypnotics V Increase: action of, possible toxicity— phenytoin, carBAMazepine, ethosuxi mide, barbiturates, zidovudine, LORaze pam, rufinamide, lamoTRIgine Increase: bleeding—warfarin Decrease: valproate levels—carBAMaze pine, cholestyramine, estrogen, hormonal contraceptives, carbapenem antibiotics Drug/Lab Test False positive: ketones, urine Interference: thyroid function tests Increase: LFTs, bleeding time, ammonia Decrease: sodium
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DOSAGE AND ROUTES Simple/absence seizures • Adult/adolescent/child ≥10 yr: PO/ IV Initially, 10-15 mg/kg/day; increase by 5-10 mg/kg/day weekly, max 60 mg/ kg/day Acute mania • Adult: PO (delayed-release dival- proex). Initially, 750 mg/day in divided doses, then increase to the lowest effec tive dose, max 60 mg/kg/day; PO (ex- tended-release divalproex). Initially, 25 mg/kg/day, to achieve the desired clinical effect For migraine prophylaxis • Adult ≤65 yr: PO (delayed-release divalproex). Initially, 250 mg bid, ti trate as needed up to a max 500 mg bid; PO (extended-release divalproex); initially, 500 mg/day × 1 wk, then in creasing to 1000 mg/day, max 1000 mg/ day
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Available forms: Valproate: inj 100 mg/mL; valproic acid: caps 250, 500 mg; syrup 250 mg/5 mL; dival proex: del rel tabs 125, 250, 500 mg; ext rel tabs 250, 500 mg; sprinkle cap 125 mg
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Administer: PO route • Do not confuse different forms • Swallow tabs or caps whole; do not break, crush, or chew ext rel or del rel tabs • Sprinkle cap contents on food • Syrup: Do not dilute with carbon ated beverage; do not give syrup to patients with sodium restrictions, shake before use • Give with food or milk to decrease GI symptoms • Conversion from Depakote to Depakote ER, the ER product should be higher than immediate release • Do not discontinue abruptly IV Infusion route • Dilute dose with ≥50 mL D5W, NS, LR (2 mg/mL) • Run over 60 min (20 mg/min) • Draw drug level • Use in those that cannot use PO • Y-site compatibilities: cefepime, ceftazadime, cloxacillin, naloxone
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Assess: • Seizure disorder: location, aura, activ ity, duration; seizure precautions should be in place • Mental status: bipolar disorder: mood, activity, sleeping/eating, behavior; sui- cidal thoughts/behaviors • Migraines: frequency, intensity, allevi ating factors • Blood studies: Hct, HB, RBC, serum folate, PT/PTT, serum ammonia, platelets, vit D if patient receiving long-term therapy, throm bocytopenia may occur at higher doses
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Evaluate: • Therapeutic response: decreased sei zures
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • To avoid driving, other activities that require alertness • To drink plenty of fluids • To discuss all OTC, Rx, herbals, supple ments taken with health care professional • Not to discontinue medication quickly after long-term use, seizures may result; to take as directed; not to skip, double doses; not to chew capsules; to take with milk for GI upset • That syrup may be mixed with fluids that are not carbonated; sprinkle cap can be opened and sprinkled on applesauce or soft food, and swallowed
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PHARMACOKINETICS Absorption complete (IV) well (PO); dis tribution widely, crosses blood-brain bar rier. Metabolized by liver; excreted by kidneys, in breast milk; crosses placenta; half-life 6-16 hr; 90% protein binding; PO: Peak 4 hr (regular rel); 4-17 hr (ext rel)
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• Adult/adolescent/child ≥10 yr: PO/ IV Initially, 10-15 mg/kg/day; increase by 5-10 mg/kg/day weekly, max 60 mg/ kg/day Acute mania
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