Anticonvulsant levels and reloading

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Background

  • IV load can be performed with phenobarbital, phenytoin, valproate, levetiracetam
  • Oral loading can be spread over day or more to avoid GI upset

Dose

Dose (mg) = ideal body weight (kg) X Vd X [desired level - current level (mcg/mL)]

Volume of Distribution

Agent
Volume of Distribution
Phenytoin (dilantin) 0.8
Carbamazepine (tegretol) 0.8
Phenobarbital 0.6
Valproate (depakote) 0.2

Desired Level

  • Pt's optimal level = desired level
    • If optimal level unknown target upper end of therapeutic range:
      • Phenytoin = 20 mcg/mL
      • Valproate = 100 mcg/mL
      • Phenobarbital = 40 mcg/mL

Loading

Phenytoin

Zero Level of Initial Load

  • IV: 18mg/kg at max rate of 25mg/min[1]
    • PO: 18mg/kg as single dose or divided into 3 doses q2hr[2]

Subtherapeautic level >0

Concentration adjusted = (concentration desired - concentration measured) x (0.8 x adjusted body weight)

Sheiner-Tozer Equation

  • may be needed to correct level in patients with low albumin or abnormal creatinine[3]
  • Corrected level = measured level/[(adjustment x albumin) + 0.1]
  • adjustment is 0.2 unless patient has Creatinine clearance <20 then it is 0.1

Fosphenytoin

  • IV: 18mg PE/kg at 100-150mg/min

Dapakote

Subtherapeutic level > 0

  • (100-level) .25 x wt
  • give over 1 hr

See Also

Source

  1. Osborn HH, Zisfein J, Sparano R. Single-dose oral phenytoin loading. Ann Emerg Med. 1987;16(4):407-12
  2. Ratanakorn D, Kaojarern S, Phuapradit P, Mokkhavesa C. Single oral loading dose of phenytoin: a pharmacokinetics study. J Neurol Sci. 1997;147(1):89-92
  3. Martin E, Tozer TN, Sheiner LB, Riegelman S. The clinical pharmacokinetics of phenytoin. J Pharmacokinet Biopharm. 1977 Dec;5(6):579-96.