Divalproex drug data and news

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Linear Relationship of Valproate Serum Concentration to Response ...  Feb 9, 2006
A post hoc analysis of pooled intent-to-treat data from three randomized, placebo-controlled studies of divalproex treatment for acute mania was performed to ... - Am J Psychiatry (subscription)

Neurocognitive Function in Unmedicated Manic and Medicated ...  Feb 8, 2006
...who were responders from a recently completed clinical trial that tested the efficacy of lithium plus risperidone (N=14) versus divalproex plus risperidone (N ... - Am J Psychiatry (subscription)

Myocarditis During Clozapine Treatment  Feb 14, 2006
This resulted in akathisia and confusion, and ziprasidone was subsequently cross-tapered to quetiapine, 800 mg/day, and divalproex sodium, 750 mg/day. ... - Am J Psychiatry (subscription)

Comorbidity in Bipolar Disorder Among the Elderly: Results From an ...  Feb 8, 2006
Medline]. Ponce H, Kunik ME, Molinari VA, Orengo C, Workman R, Reich L: Divalproex sodium treatment in elderly male bipolar patients. ... - Am J Psychiatry (subscription)

Teva Announces Tentative Approval of Divalproex Sodium Delayed ...  Jan 12, 2006
...(Nasdaq: TEVA) announced today that the US Food and Drug Administration has granted tentative approval for the Company's ANDA for Divalproex Sodium Delayed ... - Genetic Engineering News,

Abbott Reports Record Sales, Earnings and Cash Flow in 2005  Jan 25, 2006
In December, Abbott received FDA approval for Depakote ER(R) (divalproex sodium) to treat acute manic or mixed episodes associated with bipolar disorder. ... - MSN Money

US court approves Wyeth-Teva settlement on Effexor  Jan 15, 2006
Teva has also announced tentative FDA approval for its Divalproex Sodium Delayed-Release Tablets USP, 125 mg, 250 mg and 500 mg. ... - Globes,

Continuity of Antidepressant Treatment for Adults With Depression ...  Jan 24, 2006
Patients who reported use of mood stabilizer medications (lithium, carbamazepine, valproic acid, divalproex, gabapentin, and lamotrigine) during the study ... - Am J Psychiatry (subscription)

High-Cost Use of Second-Generation Antipsychotics Under ...  Jan 25, 2006
...attempted before other treatment options (9). Monotherapy with first-generation antipsychotics, clozapine monotherapy, or augmentation with divalproex are also ... - Psychiatric Services (subscription)

Brief Reports: Patterns of Psychotropic Medication Use by Race ...  Jan 25, 2006
...and benzodiazepines. Specifically, other mood stabilizers included divalproex, valproate, carbamazepine, and lamotrigine. First-generation ... - Psychiatric Services (subscription)

Teva gets tentative FDA OK for Depakote  Jan 12, 2006
The tentative approval covers 125 milligram, 250 milligram and 500 milligram tablets of delayed-release divalproex sodium, the active ingredient in Depakote ... - BusinessWeek

Depakote® ER Approved For Acute Manic Or Mixed Episodes ...  11 Dec 2005
Abbott announced that the US Food and Drug Administration (FDA) has approved a new indication for Depakote® ER (divalproex sodium extended-release tablets ... - Medical News Today (press release),

Suicidal Ideation and Pharmacotherapy Among STEP-BD Patients  Dec 10, 2005
OBJECTIVE: Little is known about the effects of lithium on suicidal ideation or about the possible antisuicidal effects of divalproex, second-generation ... - Psychiatric Services (subscription)

Abbott's Depakote ER (Divalproex Sodium Extended-Release Tablets) ...  Dec 7, 2005
December 6, 2005 -- Abbott announced that the US Food and Drug Administration (FDA) has approved a new indication for Depakote® ER (divalproex sodium extended ... - DG News

Abbott's Depakote(R) ER (Divalproex Sodium Extended-Release ...  Dec 7, 2005
Abbott (NYSE: ABT) announced that the US Food and Drug Administration (FDA) has approved a new indication for Depakote(R) ER (divalproex sodium extended ... - PR Newswire (press release),

Conclusions Inconsistent With Results With Amphetamines and ...  Nov 13, 2005
...hyperactivity disorder] can be safely and effectively treated with mixed amphetamine salts after their manic symptoms are stabilized with divalproex sodium" (p ... - Am J Psychiatry (subscription)

FDA Approvals: Angiomax, Depakote ER, Hylenex  Dec 8, 2005
...patients with or at risk of heparin-induced thrombocytopenia and thrombosis syndrome undergoing percutaneous coronary intervention; divalproex sodium extended ... - Medscape (subscription)

Dr. Scheffer and Colleagues Reply  Nov 13, 2005
2. We agree that higher doses of divalproex might have led to even greater benefits, although the doses and serum levels used were associated with a ... - Am J Psychiatry (subscription)

(PRN) - ONStor Wins 'Product of the Year' From Enterprise Systems ...  Dec 7, 2005
...(PRN) - Abbott's Depakote(R) ER (Divalproex Sodium Extended-Release Tablets) Approved for Acute Manic or Mixed Episodes Associated With Bipolar Disorder ... ... - Bolsamania.com,

Secondary Mania in Older Adults  Nov 13, 2005
Secondary Mania. Mr. B’s drug doses were titrated to 20 mg/day of olanzapine and 1500 mg bid of divalproex sodium. By the ninth ... - Am J Psychiatry (subscription)

Cadila gets USFDA nod for Divalproex  Sep 12, 2005
...has received tentative approval from the US Food and Drug Administration (FDA) for its abbreviated new drug application (ANDA) for Divalproex Sodium DR Tablets ... - Business Standard,

Zydus Cadila receives tentative approval for Divalproex Sodium DR ...  Sep 12, 2005
Cadila Healthcare Ltd has received tentative approval from the US FDA for its Abbreviated New Drug Application (ANDA) for Divalproex Sodium DR Tablets, 125 mg ... - Myiris.com,

Intravenous Valproate Use in Bipolar II Disorder After Gastric ...  Sep 24, 2005
...s bipolar II disorder had been well-controlled on an outpatient regimen of sustained-release buproprion 200 mg/day, paroxetine 40 mg QD, divalproex sodium 500 ... - Journal of Neuropsychiatry (subscription)

Ranbaxy gets tentative nod for anti-convulsion drug  Sep 15, 2005
America. Ranbaxy got the preliminary approval to sell extended release tablets of Divalproex sodium, the USFDA said on its Web site. ... - India Infoline.com,

Behavioral and Pharmacologic Treatment of Aggression in Children ...  Oct 3, 2005
Case reports and a retrospective review have reported on the use of lithium (Eskalith, Lithobid) or divalproex (Depakote) for aggressive behaviors in youth ... - Psychiatric Times,

Indian shares hit new peak, techs gain; Colombo up  Sep 12, 2005
...rose nearly 2 percent to 554.85 rupees, after it said on Monday it had received tentative approval from the US FDA for anti-convulsant Divalproex Sodium DR ... - Reuters India,

NIMH-Funded Study Examines the Use of Antipsychotic Medications ...  Sep 19, 2005
...for the treatment of acute manic episodes associated with bipolar I disorder, as either monotherapy or adjunct therapy with lithium or divalproex, and the ... - Finanzen.net,

Market rebounds after weak opening  Sep 12, 2005
Cadila has gained by 1.30% to Rs553 after the company received a tentative approval for Divalproex Sodium DR Tablets from US FDA. ... - India Infoline.com,

According to non-industry study, Zyprexa(R) is more effective in ...  Sep 21, 2005
The most common treatment-emergent adverse event associated with Zyprexa in combination with lithium or divalproex in 6-week combination bipolar mania trials ... - ArriveNet (press release),

Industry growth skids  Sep 12, 2005
12: Cadila Healthcare has received a tentative approval from the USFDA for its abbreviated new drug application for divalproex sodium dr tablets. - Calcutta Telegraph,

FDA-Approved Office Lithium Test Expected To Enhance Clinical Care  Aug 30, 2005
When lithium was compared to carbamazepine (Equetro, Tegretol) or divalproex (Depakote), it showed a differential effect in preventing suicides, Goodwin said. ... - Psychiatric Times,

Second-Generation Antipsychotics and the Risk of Insulin ...  Aug 15, 2005
Increases in triglycerides were correlated with weight gain, low baseline triglycerides, divalproex (Depakote) co-treatment, and Asian or African-American race ... - Psychiatric Times,

Extended-Release Divalproex Sodium for Patients With Side Effects ...  Jul 29, 2005
...with other axis I or axis II comorbidity) who exhibited side effects that limited their compliance or tolerability to delayed-release divalproex sodium were ... - Am J Psychiatry (subscription)

Clozapine-Induced Allergic Vasculitis  Jul 29, 2005
...upward. Besides haloperidol, his other medications included benztropine, divalproex sodium, lorazepam, trazodone, and levothyroxine. ... - Am J Psychiatry (subscription)

The "Kindling" Model  Jul 31, 2005
...bipolar disorder and substance abuse were much more likely to respond to treatment that included an anticonvulsant/mood stabilizer, divalproex (Depakote) or ... - bipolar.about.com

Easing The Pain  Jul 18, 2005
He suggested that she go to sleep earlier, and prescribed divalproex, a prophylactic medication frequently used in treating epilepsy, as a preventative against ... - New York Sun (subscription) <**results**>

Multi-Modal Integrated Treatment for Youth With Bipolar Disorder  Jun 20, 2005
The first treatment of choice continues to be a mood stabilizer such as lithium (Eskalith, Lithobid) or divalproex (Depakote), due to an established track ... - Psychiatric Times

Psychopharmacology of Autism Spectrum Disorders  Jun 20, 2005
...(2001) found a favorable response to divalproex (Depakote), with improvement in affective stability, impulsivity and aggression. ... - Psychiatric Times

A continuing headache  Jul 2, 2005
...occasional migraine. He suggested she go to sleep earlier, and prescribed divalproex at bedtime as a way to prevent the attacks. “It ... - Malaysia Star

Newly Published Study Investigates SEROQUEL(R) As Monotherapy ...  Jul 2, 2005
...for the treatment of acute manic episodes associated with bipolar I disorder, as either monotherapy or adjunct therapy with lithium or divalproex, and the ... - RedNova.com

Patients persevere against daily  Jun 28, 2005
Preventive medications include anti-seizure drugs, such as divalproex (brand name Depakote) and topiramate (Topamax), and antidepressants. ... - Waterbury Republican American

Most Migraine Sufferers Miss Out On Prevention  Jun 24, 2005
Appropriate preventive medications include Topamax (topiramate), Depakote (divalproex), certain beta blockers, calcium channel blockers, and anti-depressants ... - MedPage Today

Bipolar illness not just for adults  Jun 7, 2005
Researchers are measuring the impact of medicine - people with bipolar disorder typically take mood stabilizers such as lithium or divalproex - and intensive ... - Centre Daily Times,

Effects of Co-Administered Drugs on Valproate Clearance

Drugs that affect the level of expression of hepatic enzymes, particularly those that elevate levels of glucuronosyltransferases, may increase the clearance of valproate. For example, phenytoin, carbamazepine, and phenobarbital (or primidone) can double the clearance of valproate. Thus, patients on monotherapy will generally have longer half-lives and higher concentrations than patients receiving poly-therapy with antiepilepsy drugs.

In contrast,drugs that are inhibitors of cytochrome P450 isozymes, e.g., antidepressants, may be expected to have little effect on val-proate clearance because cytochrome P450 microsomal mediated oxidation is a relatively minor secondary metabolic pathway compared to glucuronidation and beta-oxidation.

Because of these changes in valproate clearance, monitoring of valproate and concomitant drug concentrations should be increased whenever enzyme inducing drugs are introduced or withdrawn.

The following list provides information about the potential for an influence of several commonly prescribed medications on valproate pharmacokinetics. The list is not exhaustive nor could it be, since new interactions are continuously being reported.

Drugs for which a potentially important interaction has been observed

Aspirin - A study involving the co-administration of aspirin at antipyretic doses (11 to 16 mg/kg) with valproate to pediatric patients (n=6) revealed a decrease in protein binding and an inhibition of metabolism of valproate. Valproate free fraction was increased 4-fold in the presence of aspirin compared to valproate alone. The ß-oxidation pathway consisting of 2-E-valproic acid, 3-OH-valproic acid, and 3-keto valproic acid was decreased from 25% of total metabolites excreted on valproate alone to 8.3% in the presence of aspirin. Caution should be observed if valproate and aspirin are to be co-administered.

Felbamate - A study involving the co-administration of 1200 mg/day of felbamate with valproate to patients with epilepsy (n=10) revealed an increase in mean valproate peak concentration by 35% (from 86 to 115 µg/mL) compared to valproate alone. Increasing the felbamate dose to 2400 mg/day increased the mean valproate peak concentration to 133 µg/mL (another 16% increase). A decrease in valproate dosage may be necessary when felbamate therapy is initiated.

Meropenem - Subtherapeutic valproic acid levels have been reported when meropenem was coadministered.

Rifampin - A study involving the administration of a single dose of valproate (7 mg/kg) 36 hours after 5 nights of daily dosing with rifampin (600 mg) revealed a 40% increase in the oral clearance of valproate. Valproate dosage adjustment may be necessary when it is co-administered with rifampin.

Drugs for which either no interaction or a likely clinically unimportant interaction has been observed

Antacids - A study involving the co-administration of valproate 500 mg with commonly administered antacids (Maalox, Trisogel, and Titralac - 160 mEq doses) did not reveal any effect on the extent of absorption of valproate.

Chlorpromazine - A study involving the administration of 100 to 300 mg/day of chlorpromazine to schizophrenic patients already receiving valproate (200 mg BID) revealed a 15% increase in trough plasma levels of valproate.

Haloperidol - A study involving the administration of 6 to 10 mg/day of haloperidol to schizophrenic patients already receiving val-proate (200 mg BID) revealed no significant changes in valproate trough plasma levels. Cimetidine and Ranitidine - Cimetidine and ranitidine do not affect the clearance of valproate.

Effects of Valproate on Other Drugs

Valproate has been found to be a weak inhibitor of some P450 isozymes, epoxide hydrase, and glucuronosyltransferases.

The following list provides information about the potential for an influence of valproate co-administration on the pharmacokinetics or pharmacodynamics of several commonly prescribed medications. The list is not exhaustive, since new interactions are continuously being reported.

Drugs for which a potentially important valproate interaction has been observed

Amitriptyline/Nortriptyline - Administration of a single oral 50 mg dose of amitriptyline to 15 normal volunteers (10 males and 5 females) who received valproate (500 mg BID) resulted in a 21% decrease in plasma clearance of amitriptyline and a 34% decrease in the net clearance of nortriptyline. Rare postmarketing reports of concurrent use of valproate and amitriptyline resulting in an increased amitriptyline level have been received. Concurrent use of valproate and amitriptyline has rarely been associated with toxicity. Monitoring of amitriptyline levels should be considered for patients taking valproate concomitantly with amitriptyline. Consideration should be given to lowering the dose of amitriptyline/nortriptyline in the presence of valproate.

Carbamazepine/carbamazepine-10,11-Epoxide - Serum levels of carbamazepine (CBZ) decreased 17% while that of carbamazepine-10,11-epoxide (CBZ-E) increased by 45% upon co-administration of valproate and CBZ to epileptic patients.

Clonazepam - The concomitant use of valproic acid and clonazepam may induce absence status in patients with a history of absence type seizures.

Diazepam - Valproate displaces diazepam from its plasma albumin binding sites and inhibits its metabolism. Co-administration of valproate (1500 mg daily) increased the free fraction of diazepam (10 mg) by 90% in healthy volunteers (n=6). Plasma clearance and volume of distribution for free diazepam were reduced by 25% and 20%, respectively, in the presence of valproate. The elimination half-life of diazepam remained unchanged upon addition of valproate.

Ethosuximide - Valproate inhibits the metabolism of ethosuximide. Administration of a single ethosuximide dose of 500 mg with valproate (800 to 1600 mg/day) to healthy volunteers (n=6) was accompanied by a 25% increase in elimination half-life of ethosux-imide and a 15% decrease in its total clearance as compared to ethosuximide alone. Patients receiving valproate and ethosuximide, espe-cially along with other anticonvulsants, should be monitored for alterations in serum concentrations of both drugs.

Lamotrigine - In a steady-state study involving 10 healthy volunteers, the elimination half-life of lamotrigine increased from 26 to 70 hours with valproate co-administration (a 165% increase). The dose of lamotrigine should be reduced when co-administered with valproate. Serious skin reactions (such as Stevens-Johnson Syndrome and toxic epidermal necrolysis) have been reported with concomitant lamotrigine and valproate administration. See lamotrigine package insert for details on lamotrigine dosing with concomitant valproate administration.

Phenobarbital - Valproate was found to inhibit the metabolism of phenobarbital. Co-administration of valproate (250 mg BID for 14 days) with phenobarbital to normal subjects (n=6) resulted in a 50% increase in half-life and a 30% decrease in plasma clearance of phenobarbital (60 mg single-dose). The fraction of phenobarbital dose excreted unchanged increased by 50% in presence of valproate.

There is evidence for severe CNS depression, with or without significant elevations of barbiturate or valproate serum concentrations. All patients receiving concomitant barbiturate therapy should be closely monitored for neurological toxicity. Serum barbiturate concentrations should be obtained, if possible, and the barbiturate dosage decreased, if appropriate.

Primidone, which is metabolized to a barbiturate, may be involved in a similar interaction with valproate.

Phenytoin - Valproate displaces phenytoin from its plasma albumin binding sites and inhibits its hepatic metabolism. Co-administration of valproate (400 mg TID) with phenytoin (250 mg) in normal volunteers (n=7) was associated with a 60% increase in the free fraction of phenytoin. Total plasma clearance and apparent volume of distribution of phenytoin increased 30% in the presence of val-proate. Both the clearance and apparent volume of distribution of free phenytoin were reduced by 25%.

In patients with epilepsy, there have been reports of breakthrough seizures occurring with the combination of valproate and phenytoin. The dosage of phenytoin should be adjusted as required by the clinical situation.

Tolbutamide - From in vitro experiments, the unbound fraction of tolbutamide was increased from 20% to 50% when added to plasma samples taken from patients treated with valproate. The clinical relevance of this displacement is unknown.

Warfarin - In an in vitro study, valproate increased the unbound fraction of warfarin by up to 32.6%. The therapeutic relevance of this is unknown; however, coagulation tests should be monitored if DEPAKOTE therapy is instituted in patients taking anticoagulants.

Zidovudine - In six patients who were seropositive for HIV, the clearance of zidovudine (100 mg q8h) was decreased by 38% after administration of valproate (250 or 500 mg q8h); the half-life of zidovudine was unaffected.

Drugs for which either no interaction or a likely clinically unimportant interaction has been observed:

Acetaminophen - Valproate had no effect on any of the pharmacokinetic parameters of acetaminophen when it was concurrently administered to three epileptic patients.

Clozapine - In psychotic patients (n=11), no interaction was observed when valproate was co-administered with clozapine.

Lithium - Co-administration of valproate (500 mg BID) and lithium carbonate (300 mg TID) to normal male volunteers (n=16) had no effect on the steady-state kinetics of lithium.

Lorazepam - Concomitant administration of valproate (500 mg BID) and lorazepam (1 mg BID) in normal male volunteers (n=9) was accompanied by a 17% decrease in the plasma clearance of lorazepam.

Oral Contraceptive Steroids - Administration of a single-dose of ethinyloestradiol (50 µg)/levonorgestrel (250 µg) to 6 women on valproate (200 mg BID) therapy for 2 months did not reveal any pharmacokinetic interaction.