Dosage valproate

Six months later, an attempt was made to reduce the dosage cf valproate. On a twice-daily dose of 300 mg (600 mg/d total), mean serum levels dropped to 34 mg/E There was a prompt recurrence of seizures, but they declined again when valproate dosage was returned to 2400 mg/d. A follow-up study 8 months later demonstrated a continuing favorable response. 

In 7 children the serum levels of primidone 10 to 18 mg/kg daily rose two to threefold when valproate (dosage not stated) was also given. After 1 to 3 months of continued therapy the serum primidone levels fell in 3 of the patients but persisted in one. Follow-up primidone levels were not taken in the other 3 patients, and no patient had phenobarbital levels measured. ... 

A study investigating allopurinol in refractory epilepsy found that allopu-ri nol (150 mg daily in those less than 20 kg, and 300 mg daily for other patients for 4 months) had no effect on valproate levels in 28 patients taking antiepileptics including valproate. In another similar study, allopurinol 10 mg/kg increased to 15 mg/kg daily for 12 weeks had no effect on serum valproate levels in 6 patients taking antiepileptics including valproate. Therefore valproate dosage alterations are unlikely to be required if allopurinol is used. 

Although there is only an isolated report of an interaction between valproate and imipenem, there are now several reports of the interaction between valproate and meropenem or panipenem. Seizures or increased seizure frequeney have been reported. It would therefore seem prudent to monitor the valproate levels in any patient also given carbapenems, being alert for the need to increase the valproate dosage, or to use another antibacterial, or an alternative to valproate. Carbamazepine and phenytoin did not interact in the above reports. The manufacturers of ertapenem have no reports of an interaction on their files, but prudently warn about a possible interaction with valproate because of the interactions seen with other carbapenems. 

In one study sodium valproate was reported to have no marked effeet on clobazam, but a study in children found that clobazam caused an 11% increase in the serum levels of valproate, despite a reduction of at least 10% in the valproate dosage. ... 

Conversion from adjunctive therapy with valproate to monotherapy with lamotrigine Achieve a dosage of 200 mg/day of lamotrigine according the guidelines. While... 

Valproate should then be discontinued completely and lamothgine increased by 100 mg/day every week until the recommended monotherapy dosage of 500 mg/day is reached. 

Dosage regimen for bipolar disorder The target dose of lamotrigine is 200 mg/day (100 mg/day in combination with valproate and 400 mg/day in combination with carbamazepine or other enzyme-inducing drugs). Doses above 200 mg/day are not recommended. 

Pharmacology This group includes valproic acid, sodium valproate (the sodium salt), and divalproex sodium (a compound containing equal proportions of valproic acid and sodium valproate). Regardless of form, dosage is expressed as valproic acid equivalents. 

Elderly In elderly patients, increase dosage more slowly and with regular monitoring for fluid and nutritional intake, dehydration, somnolence, and other adverse events. Consider dose reductions or discontinuation of valproate in patients with decreased food or fluid intake and in patients with excessive somnolence. A reduced starting dose is recommended (see Administration and Dosage). 

In a report of 122 elderly patients on risperidone, hypotension was noted in 28.7% and symptomatic orthostatic hypotension was noted in 9.8%. Significant decreases in blood pressure occurred with risperidone treatment (p = 0.0001) and were common in patients with cardiovascular disease and those taking an SSRI or valproate (p = 0.03) (502). Hence, like other antipsychotics, risperidone should be prescribed cautiously for elderly patients and those with preexisting cardiac disease. Its hypotensive versus its orthostatic hypotensive effects may be an age-related pharmacodynamic response. Blood pressure, including orthostatic blood pressure, should be monitored routinely until the risperidone dosage is stabilized. Furthermore, when risperidone therapy is initiated in the elderly, dosage should be titrated from 0.25 to 0.5 mg two times a day with increments of 0.25 to 0.5 mg weekly (92). 

The sodium salt of valproate is marketed in Europe as a tablet and is quite hygroscopic. In Central and South America, the magnesium salt is available, which is considerably less hygroscopic. The free acid of valproate was first marketed in the USA in a capsule containing corn oil the sodium salt is also available in syrup, primarily for pediatric use. An enteric-coated tablet of divalproex sodium is also marketed in the USA. This improved product, a 1 1 coordination compound of valproic acid and sodium valproate, is as bioavailable as the capsule but is absorbed much more slowly and is preferred by many patients. Peak concentrations following administration of the enteric-coated tablets are seen in 3-4 hours. Various extended-release preparations are available not all are bioequivalent and may require dosage adjustment. 

Dosages of 25-30 mg/kg/d may be adequate in some patients, but others may require 60 mg/kg/d or even more. Therapeutic levels of valproate range from 50 to 100 mcg/mL. 

Q12 Yes, valproate increases the risk of giving birth to a baby with spina bifida or anencephaly since valproate antagonizes the effects of folic acid and causes these neural tube defects. Thus women who suffer from epilepsy and who are taking valproate should receive a much higher dosage of folic acid (5 mg daily) compared to healthy women, who are advised to take 400 J.g daily. 

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