Levocarnitine (L-carnitine)is an endogenous carboxylic acid that is involved in transport oflong-chain fatty acids into cellular mitochondria for energy metabolism(Krebs cycle). L-carnitine is ubiquitous in diets richin meats and dairy products and is also synthesized in the body fromthe amino acids lysine and methionine. Although dietary deficienciesare rare, hypocarnitinemia can result from certain medical conditionsand inborn errors of metabolism and in patients receiving multipleanticonvulsant medications. It is hypothesized that valproic acid (VPA;see Valproic Acid) induces carnitine deficiency, thereby disruptingmitochondrial function and resulting in ammonia accumulation.Carnitine-deficient states may result in production of hepatotoxic VPAmetabolites via microsomal oxidation. L-carnitinesupplementation has been shown to be beneficial in both the preventionand the treatment of hyperammonemia associated with VPA therapy, andcarnitine may improve the outcome in cases of VPA–inducedhepatotoxicity and coma. However, there is no consensus on the optimaldose or route of administration (oral vs. parenteral) of L-carnitine.

L-carnitineis also sold as a dietary supplement with a wide range of unprovenclaims ranging from improved sperm motility to prevention ofAlzheimer’s disease. It is postulated that carnitine supplementationenhances fat utilization during exercise, thereby improving enduranceand promoting weight loss. However, published studies have failed toshow that supraphysiologic doses of L-carnitine have any benefit in well-nourished individuals. Because the FDA does not regulate dietary supplements, the safety of L-carnitine supplements cannot be guaranteed (see Herbal and Alternative Products).

Drug Indications ::

Indications

Hyperammonemia, encephalopathy, and hepatotoxicity related to VPA therapy.

Lowplasma free carnitine concentrations (reference range 19–60 mcmol/L) ortotal carnitine (reference range 30–73 mcmol/L) in patients takingvalproic acid.

Acute VPA overdose (see Valproic Acid) or supratherapeutic plasma VPA concentrations.

Primary or secondary carnitine deficiency.

E. Infants and children < 2 years of age receiving VPA as part of a multianticonvulsant drug regimen.

Drug Contra-Indications ::

III. Contraindications. None known.

Drug Adverse Effects ::

IV. Adverse effects

Dose-related nausea, vomiting, diarrhea, and fishy body odor.

Seizures have been reported in patients receiving oral and IV L-carnitine.

Use in pregnancy. CategoryB (see Table III–1). No adequate studies have been conducted inpregnant women. It is not known if this drug is secreted in humanbreast milk.

Drug Lab Interactions ::

Drug or laboratory interactions. None known.

Drug Dose Management ::

Dosage and method of administration

Severe valproate-induced hepatotoxicity, hyperammonemia, coma, or acute valproic acid overdose. Early intervention with IV (rather than oral) L-carnitine has been associated with better outcomes. Administer L-carnitineintravenously in a dose of 100 mg/kg by infusion or slow bolusinjection over 2–3 minutes. An equivalent dose may be given every 8hours to severely ill patients.

Drug-induced carnitine deficiency and asymptomatic hyperammonemia. Give orally 50–100 mg/kg/day in two to three divided doses, with a maximum of 3 g per day.

Drug Chemical Formulations ::

Formulations

Oral. Levocarnitine (Carnitor, L-carnitine); 330- and 500-mg tablets; 250-mg capsules; and oral solution (1 g/10 mL) in 118-mL multiple-use containers.

Parenteral. Levocarnitine (Carnitor, others); injection of single-dose (5 mL) vials and amps containing 1 g L-carnitine per vial or amp.

C. The suggested minimum stocking level to treat a severely ill 70-kg adult for the first 24 hours is 7 g (seven vials).

Disclaimer ::

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