|Valproic Acid and Derivatives
|Drugs search, click the first letter of a drug name: | A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | 1 | 2 | 3 | 4 | 5 | 6 | 8 | 9
Valproic Acid and Derivatives( Sodium Valproate , Divalproex Sodium ) Pronouncation: (VAL-pro-ik acid)
Class: Anticonvulsant Sodium Valproate
PMS-Valproic Acid (Canada)
Rhoxal-valproic EC (Canada)
Mechanism of Action
Believed to work by increasing brain levels of gamma-aminobutyric acid (GABA). It may also inhibit catabolism of GABA, potentiate postsynaptic GABA responses, and affect potassium channels or directly stabilize membranes.
Valproic acid is rapidly absorbed in the GI tract. Divalproex dissociates into valproic acid in the GI tract. T max is 4 to 17 hr (extended-release tablets).
Vd of total or free valproic acid is 11 and 92 L per 1.73 m 2 , respectively. 80% to 90% protein bound (concentration-dependent).
Metabolized primarily in the liver.
30% to 50% excreted as glucuronide conjugate in the urine. The t ½ is 9 to 16 hr for valproate.
Special PopulationsRenal Function Impairment
Protein binding in renal failure patients is substantially reduced.Hepatic Function Impairment
Cl may be decreased and unbound fraction of valproate may be increased.Elderly
Intrinsic Cl is reduced 39%; the free fraction is increased 44%.
Indications and Usage
Sole and adjunctive therapy in simple (petit mal) and complex absence seizures; adjunctive therapy in multiple seizure types, including absence seizures; monotherapy and adjunctive therapy in complex partial seizures that occur in isolation or with other seizure types; manic episodes associated with bipolar disorder (divalproex sodium delayed-release tablets); prophylaxis of migraine headaches (divalproex sodium delayed-release and extended-release [ER] tablets).
Treatment of atypical absence, myoclonic, and tonic-clonic (grand mal) seizures and atonic, elementary partial, and infantile spasm seizures; prevention of recurrent pediatric febrile seizures; intractable status epilepticus in patients who have not responded to other therapies; treatment of minor incontinence after ileoanal anastomosis (subchronic administration); management of anxiety disorders and panic attacks.
Hepatic disease dysfunction; known urea cycle disorders; hypersensitivity to the drug.
Dosage and Administration
Therapeutic serum levels for most patients with seizures range from 50 to 100 mcg/mL; however, a good correlation has not been established between daily dose, serum level, and therapeutic effect.Complex Partial Seizures
Adults and children 10 yr of age and older Monotherapy
PO/IV Start at 10 to 15 mg/kg daily and increase by 5 to 10 mg/kg per wk to achieve optimal clinical response, which usually occurs below 60 mg/kg daily.Conversion to monotherapy
PO/IV Start at 10 to 15 mg/kg daily and increase by 5 to 10 mg/kg per wk to achieve optimal clinical response, which usually occurs below 60 mg/kg daily. Concomitant antiepilepsy drug dosage can usually be reduced approximately 25% q 2 wk. The reduction may be started at initiation of therapy or delayed by 1 to 2 wk if there is a concern that reductions may result in seizures. If the total daily dose exceeds 250 mg, administer in divided doses.Adjunctive therapy
PO/IV Divalproex sodium or valproic acid may be added to the patient"s regimen at a dosage of 10 to 15 mg/kg daily. The dosage may be increased by 5 to 10 mg/kg per wk to achieve optimal response, which usually occurs below 60 mg/kg daily. If the total daily dose exceeds 250 mg, administer in divided doses.Conversion from Depakote to Depakote ER
Adults and children 10 yr of age and older
Patients with epilepsy previously receiving Depakote should be administered Depakote ER daily using a dose that is 8% to 20% higher than the daily dose of Depakote . For patients whose Depakote total daily dose cannot be directly converted to Depakote ER , consideration may be given, at the clinician"s discretion, to an increase in the patient"s Depakote total daily dose to the next higher dosage before converting to the appropriate total daily dose of Depakote ER .Mania (Divalproex Sodium Delayed-Release Tablets)
PO 750 mg daily in divided doses. Increase dose as rapidly as possible to achieve the lowest therapeutic dose that produces the desired clinical effect (max, 60 mg/kg daily).Migraine (Divalproex Sodium)
Divalproex sodium delayed-release tablets
PO Start with 250 mg bid (max, 1,000 mg daily).Divalproex sodium ER tablets
PO Start with 500 mg daily for 1 wk, thereafter increasing to 1,000 mg daily.Simple and Complex Absence Seizures
PO/IV Start at 15 mg/kg daily, increasing at 1-wk intervals by 5 to 10 mg/kg daily until seizures are controlled or side effects preclude further increases (max, 60 mg/kg daily). If the total daily dose exceeds 250 mg, administer in divided doses.
Store syrup, tablets, and unopened injection vials at controlled room temperature (59° to 86°F). Store capsules and sprinkle capsules at temperature less than 77°F. Diluted injection may be stored at controlled room temperature for up to 24 hr.
Drug InteractionsAlcohol, CNS depressants
Enhanced CNS depression.Amitriptyline/Nortriptyline, barbiturates, diazepam, ethosuximide
May increase levels and actions of these drugs.Carbamazepine, hydantoins
May result in increased levels of these drugs and reduced efficacy of valproic acid.Charcoal, cholestyramine
May reduce absorption of valproic acid.Chlorpromazine, cimetidine, erythromycin, rifampin, salicylates
May increase valproic acid levels.Clonazepam
May increase risk of absence status in patients with history of absence-type seizures.Felbamate
Increased valproic acid levels.Lamotrigine
Decreased valproic acid levels; increased lamotrigine levels.Meropenem
May decrease valproic acid levels.Zidovudine
Increased AUC of zidovudine.
Laboratory Test Interactions
Valproic acid may yield false-positive results on urine ketone tests; altered thyroid function tests.
Hypertension, hypotension, postural hypotension, palpitation, tachycardia, bradycardia (more than 1% and less than 5%).
Tremor (57%); somnolence (30%); asthenia (21%); dizziness (18%); insomnia (15%); nervousness (11%); amnesia (7%); headache (5% or more); depression (5%); ataxia, emotional lability, abnormal thinking, paresthesia (1% to 5%); anxiety, confusion, abnormal gait, hypertonia, incoordination, abnormal dreams, personality disorder, agitation, catatonic reaction, dysarthria, hallucinations, hypokinesia, increased reflexes, tardive dyskinesia, speech disorder, vertigo (more than 1% and less than 5%).
Alopecia (7%); rash (6%); dry skin, pruritus, petechiae, discoid lupus erythematosus, furunculosis, maculopapular rash, seborrhea (more than 1% and less than 5%); erythema multiforme, photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis (rare).
Pharyngitis, amblyopia, blurred vision (8%); nystagmus, tinnitus (7%); diplopia, taste perversion (1% to 5%); abnormal vision, deafness, otitis media, conjunctivitis, dry eyes, ear pain/disorder, eye pain (more than 1% and less than 5%).
Nausea (34%); diarrhea, vomiting (23%); dyspepsia (13%); abdominal pain (12%); anorexia (11%); increased appetite (6%); constipation (1% to 5%); flatulence, hematemesis, eructation, periodontal abscess, fecal incontinence, gastroenteritis, glossitis, periodontal abscess, dry mouth, GI disorder, stomatitis, tooth disorder (more than 1% and less than 5%).
Amenorrhea, dysmenorrhea, urinary frequency, urinary incontinence, vaginitis, cystitis, metrorrhagia, vaginal hemorrhage (more than 1% and less than 5%).
Thrombocytopenia (24% [high dose]); ecchymosis (5%); frank hemorrhage; relative lymphocytosis; macrocytosis; leucopenia; eosinophilia; anemia; bone marrow suppression; pancytopenia; aplastic anemia; acute intermittent porphyria.
Increase ALT, AST, LDH, bilirubin.
Weight gain (9%); edema (more than 1% and less than 5%); hyperammonemia; Fanconi syndrome (primarily in children); hyperglycemia.
Arthralgia, leg cramps, myalgia, myasthenia, twitching arthrosis (more than 1% and less than 5%).
Infection (20%); flu-like syndrome (12%); rhinitis; dyspnea (1% to 5%); epistaxis, pneumonia, sinusitis, increased cough (more than 1% and less than 5%).
Infection (15%); back pain (8%); injection site pain (3%); injection site reaction (2%); fever, chest pain, vasodilation, peripheral edema, accidental injury, chills, face edema, viral infection (1% to 5%); malaise (more than 1% and less than 5%); lupus erythematosus; anaphylaxis.
Category D .
Excreted in breast milk.
Use with extreme caution in children younger than 2 yr of age (see Warning box). Safety and efficacy of divalproex sodium for treatment of acute mania have not been established in patients younger than 18 yr of age. Safety and efficacy of divalproex sodium for the prophylaxis of migraines have not been established in patients younger than 16 yr of age. Safety and efficacy of divalproex sodium ER tablets for the prophylaxis of migraine headaches in pediatric patients have not been established. Safety and efficacy of divalproex ER for the treatment of complex partial seizures, simple and complex absence seizures, and multiple seizure types that include absence seizures have not been established in pediatric patients younger than 10 yr of age. Safety and efficacy of valproate sodium injection have not been established in children younger than 2 yr of age.
Reduce starting dose and base therapeutic dose on clinical response.
Acute head injuries
Because IV valproic acid has been associated with a higher incidence of death than IV phenytoin, do not use in the prevention of posttraumatic seizures in patients with acute head injuries.
Abrupt discontinuation may precipitate status epilepticus with attendant life-threatening hypoxia in patients receiving valproic acid to prevent major seizures.
Thrombocytopenia, inhibition of secondary phase of platelet aggregation and abnormal coagulation parameters (eg, low fibrinogen) may occur. Risk of bleeding may be increased.
Reactions usually occur within first 6 mo of therapy and are preceded by symptoms such as lost seizure control, malaise, weakness, lethargy, facial edema, anorexia, jaundice, and vomiting. Use drug with caution in patients with prior history of liver disease. Monitor results of LFTs frequently.
May occur with or without lethargy and coma and contribute to hepatotoxicity.
Clinical data from long-term studies (more than 3 wk) are not available.
Life-threatening pancreatitis has been reported.
Suicidal ideation may be a manifestation of certain psychiatric disorders and may persist until significant remission of symptoms occurs.
Motor restlessness, somnolence, heart block, visual hallucinations, asterixis, deep coma, death.
calproic acid and derivatives, balproic acid and derivatives, galproic acid and derivatives, falproic acid and derivatives, vzlproic acid and derivatives, vslproic acid and derivatives, vwlproic acid and derivatives, vqlproic acid and derivatives, vakproic acid and derivatives, vapproic acid and derivatives, vaoproic acid and derivatives, valoroic acid and derivatives, vallroic acid and derivatives, val-roic acid and derivatives, val0roic acid and derivatives, valpeoic acid and derivatives, valpdoic acid and derivatives, valpfoic acid and derivatives, valptoic acid and derivatives, valp5oic acid and derivatives, valp4oic acid and derivatives, valpriic acid and derivatives, valprkic acid and derivatives, valprlic acid and derivatives, valprpic acid and derivatives, valpr0ic acid and derivatives, valpr9ic acid and derivatives, valprouc acid and derivatives, valprojc acid and derivatives, valprokc acid and derivatives, valprooc acid and derivatives, valpro9c acid and derivatives, valpro8c acid and derivatives, valproix acid and derivatives, valproiv acid and derivatives, valproif acid and derivatives, valproid acid and derivatives, valproic zcid and derivatives, valproic scid and derivatives, valproic wcid and derivatives, valproic qcid and derivatives, valproic axid and derivatives, valproic avid and derivatives, valproic afid and derivatives, valproic adid and derivatives, valproic acud and derivatives, valproic acjd and derivatives, valproic ackd and derivatives, valproic acod and derivatives, valproic ac9d and derivatives, valproic ac8d and derivatives, valproic acis and derivatives, valproic acix and derivatives, valproic acic and derivatives, valproic acif and derivatives, valproic acir and derivatives, valproic acie and derivatives, valproic acid znd derivatives, valproic acid snd derivatives, valproic acid wnd derivatives, valproic acid qnd derivatives, valproic acid abd derivatives, valproic acid amd derivatives, valproic acid ajd derivatives, valproic acid ahd derivatives, valproic acid ans derivatives, valproic acid anx derivatives, valproic acid anc derivatives, valproic acid anf derivatives, valproic acid anr derivatives, valproic acid ane derivatives, valproic acid and serivatives, valproic acid and xerivatives, valproic acid and cerivatives, valproic acid and ferivatives, valproic acid and rerivatives, valproic acid and eerivatives, valproic acid and dwrivatives, valproic acid and dsrivatives, valproic acid and ddrivatives, valproic acid and drrivatives, valproic acid and d4rivatives, valproic acid and d3rivatives, valproic acid and deeivatives, valproic acid and dedivatives, valproic acid and defivatives, valproic acid and detivatives, valproic acid and de5ivatives, valproic acid and de4ivatives, valproic acid and deruvatives, valproic acid and derjvatives, valproic acid and derkvatives, valproic acid and derovatives, valproic acid and der9vatives, valproic acid and der8vatives, valproic acid and dericatives, valproic acid and deribatives, valproic acid and derigatives, valproic acid and derifatives, valproic acid and derivztives, valproic acid and derivstives, valproic acid and derivwtives, valproic acid and derivqtives, valproic acid and derivarives, valproic acid and derivafives, valproic acid and derivagives, valproic acid and derivayives, valproic acid and deriva6ives, valproic acid and deriva5ives, valproic acid and derivatuves, valproic acid and derivatjves, valproic acid and derivatkves, valproic acid and derivatoves, valproic acid and derivat9ves, valproic acid and derivat8ves, valproic acid and derivatices, valproic acid and derivatibes, valproic acid and derivatiges, valproic acid and derivatifes, valproic acid and derivativws, valproic acid and derivativss, valproic acid and derivativds, valproic acid and derivativrs, valproic acid and derivativ4s, valproic acid and derivativ3s, valproic acid and derivativea, valproic acid and derivativez, valproic acid and derivativex, valproic acid and derivatived, valproic acid and derivativee, valproic acid and derivativew, alproic acid and derivatives, vlproic acid and derivatives, vaproic acid and derivatives, valroic acid and derivatives, valpoic acid and derivatives, valpric acid and derivatives, valproc acid and derivatives, valproi acid and derivatives, valproicacid and derivatives, valproic cid and derivatives, valproic aid and derivatives, valproic acd and derivatives, valproic aci and derivatives, valproic acidand derivatives, valproic acid nd derivatives, valproic acid ad derivatives, valproic acid an derivatives, valproic acid andderivatives, valproic acid and erivatives, valproic acid and drivatives, valproic acid and deivatives, valproic acid and dervatives, valproic acid and deriatives, valproic acid and derivtives, valproic acid and derivaives, valproic acid and derivatves, valproic acid and derivaties, valproic acid and derivativs, valproic acid and derivative, avlproic acid and derivatives, vlaproic acid and derivatives, vaplroic acid and derivatives, valrpoic acid and derivatives, valporic acid and derivatives, valprioc acid and derivatives, valproci acid and derivatives, valproi cacid and derivatives, valproica cid and derivatives, valproic caid and derivatives, valproic aicd and derivatives, valproic acdi and derivatives, valproic aci dand derivatives, valproic acida nd derivatives, valproic acid nad derivatives, valproic acid adn derivatives, valproic acid an dderivatives, valproic acid andd erivatives, valproic acid and edrivatives, valproic acid and dreivatives, valproic acid and deirvatives, valproic acid and derviatives, valproic acid and deriavtives, valproic acid and derivtaives, valproic acid and derivaitves, valproic acid and derivatvies, valproic acid and derivatievs, valproic acid and derivativse, vvalproic acid and derivatives, vaalproic acid and derivatives, vallproic acid and derivatives, valpproic acid and derivatives, valprroic acid and derivatives, valprooic acid and derivatives, valproiic acid and derivatives, valproicc acid and derivatives, valproic acid and derivatives, valproic aacid and derivatives, valproic accid and derivatives, valproic aciid and derivatives, valproic acidd and derivatives, valproic acid and derivatives, valproic acid aand derivatives, valproic acid annd derivatives, valproic acid andd derivatives, valproic acid and derivatives, valproic acid and dderivatives, valproic acid and deerivatives, valproic acid and derrivatives, valproic acid and deriivatives, valproic acid and derivvatives, valproic acid and derivaatives, valproic acid and derivattives, valproic acid and derivatiives, valproic acid and derivativves, valproic acid and derivativees, valproic acid and derivativess, etc.