Dosage / Administration
The optimal dose of levocarnitine (L-carnitine) for valproic acid toxicity (hyperammonemia or hepatotoxicity) has not been established, but dosages range from 50-100 mg/kg/day.

For acute valproic acid overdose without hepatic enzyme abnormalities or symptomatic hyperammonemia, an oral dose is preferred of 100 mg/kg/day divided every 8 hours up to 3 g/day.

For valproic acid overdose with hepatotoxicity and hyperammonemia, an intravenous (IV) dose is preferred of 100 mg/kg/day up to 3 g per dose over 30 minutes as a loading dose followed by 50 mg/kg every 8 hours over 10-30 minutes.

Therapy can continue until there is an improvement in clinical status and/or ammonia levels decrease.

L-carnitine has been given for up to 4 days.

The dosage in children is the same as in adults.

Indications
L-carnitine is a water-soluble amino acid vital for mitochondrial utilization of fatty acid.

L-carnitine administration is US Food and Drug Administration (FDA) approved for L-carnitine deficiency resulting from an inborn error of metabolism or hemodialysis-associated deficiency.

Off-label uses include valproic acid overdose and toxicity leading to hyperammonemia and encephalopathy and hepatotoxicity.

Side effects are usually mild and limited to nausea, vomiting, diarrhea, blurred vision, and fishy body odor.

Contraindications
No contraindications are known.

It is FDA Pregnancy Category B.

Monitoring
Levels of valproic acid do not corelate with hepatotoxicity; however, a level of 450 mg/dl or above is associated with encephalopathy and L-carnitine administration should be considered.

Adverse Effects
Adverse effects include transient nausea, diarrhea, blurry vision, and fishy body odor.

The patient may experience transient visual loss, headache, and lightheadedness following IV administration.

Toxicity
No cases of toxicity or overdose have been reported.

Mechanism of Action
Mitochondrial beta-oxidation of valproic acid depletes carnitine stores, especially in overdose.

L-carnitine replenishes the stores and increases the metabolism of valproic acid via enzyme carnitine translocase by beta oxidation inside the mitochondrial matrix, yielding several nontoxic metabolites.