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Is your patient’s valproic acid dosage too low or high? Adjust it with this equation
 

Valproic acid (VPA) often is used to treat mania in bipolar disorder, and it has a therapeutic range of 50 to 125 µg/mL of total serum concentration.1 VPA binds highly to albumin, resulting in free drug concentrations (5 to 15 mg/L) that are responsible for its therapeutic effect.2 Monitoring total VPA levels in patients with hypoalbuminemia could reveal seemingly subtherapeutic VPA levels, which could lead to unnecessary dosage adjustments or drug toxicity. Hermida et al3 devised a correction equation to normalize total VPA serum concentrations <75 µg/mL in patients with hypoalbuminemia (Table 1, Box).

We present a case employing this equation in a patient

with reported results and validation.

Case

Ms. T, age 75, is admitted to the hospital with delusional, paranoid, assaultive, and combative behavior. By applying Ms. T’s baseline lab findings (Table 2) to the equation, a normalized total VPA level and estimated free VPA level of 70 µg/mL and 7 µg/mL, respectively, can be approximated. These estimates fall within the therapeutic range and are validated by the measured free VPA level of 9 µg/mL.

Her VPA dosage is increased from 250 mg, 3 times a day, to 375 mg, twice a day, with an additional mid-day dose of 250 mg. Ms. T’s behavioral symptoms improved 3 days following the increase to her VPA dosage, although she continued to show some confusion.
 

VPA serum levels should be assessed 2 to 4 days after initiation or dosage adjustments.1 Also, consider patient-specific goals and intended clinical effect when adjusting VPA dosage. In practice settings, where free VPA levels are not routinely monitored or are cost prohibitive, this equation can guide clinical decision-making.3

References

1. Depakote [divalproex sodium]. North Chicago, IL: AbbVie Inc; 2016.
2. DeVane CL. Pharmacokinetics, drug interactions, and tolerability of valproate. Psychopharmacol Bull. 2003;37(suppl 2):25-42.
3. Hermida J, Tutor JC. A theoretical method for normalizing total serum valproic acid concentration in hypoalbuminemic patients. J Pharmacol Sci. 2005;97(4):489-493.

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Dr. P. B. Vickery is Assistant Professor of Pharmacy Practice, Wingate University School of Pharmacy, and Internal Medicine and Psychiatric Pharmacist, Park Ridge Health, Hendersonville, North Carolina. Dr. S. B. Vickery is Clinical Staff Pharmacist, Mission Hospital, Asheville, North Carolina.

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The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

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Dr. P. B. Vickery is Assistant Professor of Pharmacy Practice, Wingate University School of Pharmacy, and Internal Medicine and Psychiatric Pharmacist, Park Ridge Health, Hendersonville, North Carolina. Dr. S. B. Vickery is Clinical Staff Pharmacist, Mission Hospital, Asheville, North Carolina.

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The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Author and Disclosure Information

Dr. P. B. Vickery is Assistant Professor of Pharmacy Practice, Wingate University School of Pharmacy, and Internal Medicine and Psychiatric Pharmacist, Park Ridge Health, Hendersonville, North Carolina. Dr. S. B. Vickery is Clinical Staff Pharmacist, Mission Hospital, Asheville, North Carolina.

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The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

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Valproic acid (VPA) often is used to treat mania in bipolar disorder, and it has a therapeutic range of 50 to 125 µg/mL of total serum concentration.1 VPA binds highly to albumin, resulting in free drug concentrations (5 to 15 mg/L) that are responsible for its therapeutic effect.2 Monitoring total VPA levels in patients with hypoalbuminemia could reveal seemingly subtherapeutic VPA levels, which could lead to unnecessary dosage adjustments or drug toxicity. Hermida et al3 devised a correction equation to normalize total VPA serum concentrations <75 µg/mL in patients with hypoalbuminemia (Table 1, Box).

We present a case employing this equation in a patient

with reported results and validation.

Case

Ms. T, age 75, is admitted to the hospital with delusional, paranoid, assaultive, and combative behavior. By applying Ms. T’s baseline lab findings (Table 2) to the equation, a normalized total VPA level and estimated free VPA level of 70 µg/mL and 7 µg/mL, respectively, can be approximated. These estimates fall within the therapeutic range and are validated by the measured free VPA level of 9 µg/mL.

Her VPA dosage is increased from 250 mg, 3 times a day, to 375 mg, twice a day, with an additional mid-day dose of 250 mg. Ms. T’s behavioral symptoms improved 3 days following the increase to her VPA dosage, although she continued to show some confusion.
 

VPA serum levels should be assessed 2 to 4 days after initiation or dosage adjustments.1 Also, consider patient-specific goals and intended clinical effect when adjusting VPA dosage. In practice settings, where free VPA levels are not routinely monitored or are cost prohibitive, this equation can guide clinical decision-making.3

 

Valproic acid (VPA) often is used to treat mania in bipolar disorder, and it has a therapeutic range of 50 to 125 µg/mL of total serum concentration.1 VPA binds highly to albumin, resulting in free drug concentrations (5 to 15 mg/L) that are responsible for its therapeutic effect.2 Monitoring total VPA levels in patients with hypoalbuminemia could reveal seemingly subtherapeutic VPA levels, which could lead to unnecessary dosage adjustments or drug toxicity. Hermida et al3 devised a correction equation to normalize total VPA serum concentrations <75 µg/mL in patients with hypoalbuminemia (Table 1, Box).

We present a case employing this equation in a patient

with reported results and validation.

Case

Ms. T, age 75, is admitted to the hospital with delusional, paranoid, assaultive, and combative behavior. By applying Ms. T’s baseline lab findings (Table 2) to the equation, a normalized total VPA level and estimated free VPA level of 70 µg/mL and 7 µg/mL, respectively, can be approximated. These estimates fall within the therapeutic range and are validated by the measured free VPA level of 9 µg/mL.

Her VPA dosage is increased from 250 mg, 3 times a day, to 375 mg, twice a day, with an additional mid-day dose of 250 mg. Ms. T’s behavioral symptoms improved 3 days following the increase to her VPA dosage, although she continued to show some confusion.
 

VPA serum levels should be assessed 2 to 4 days after initiation or dosage adjustments.1 Also, consider patient-specific goals and intended clinical effect when adjusting VPA dosage. In practice settings, where free VPA levels are not routinely monitored or are cost prohibitive, this equation can guide clinical decision-making.3

References

1. Depakote [divalproex sodium]. North Chicago, IL: AbbVie Inc; 2016.
2. DeVane CL. Pharmacokinetics, drug interactions, and tolerability of valproate. Psychopharmacol Bull. 2003;37(suppl 2):25-42.
3. Hermida J, Tutor JC. A theoretical method for normalizing total serum valproic acid concentration in hypoalbuminemic patients. J Pharmacol Sci. 2005;97(4):489-493.

References

1. Depakote [divalproex sodium]. North Chicago, IL: AbbVie Inc; 2016.
2. DeVane CL. Pharmacokinetics, drug interactions, and tolerability of valproate. Psychopharmacol Bull. 2003;37(suppl 2):25-42.
3. Hermida J, Tutor JC. A theoretical method for normalizing total serum valproic acid concentration in hypoalbuminemic patients. J Pharmacol Sci. 2005;97(4):489-493.

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Is your patient’s valproic acid dosage too low or high? Adjust it with this equation
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