Dosage: 1 ml per 25kg body weight / day
Chemical Name: Cyanocobalamin
Quantity: 100ml vial
Levocarnitine (L-3-hydroxy-4-N-trimethylaminobutyrate) is synthesized in the liver from the amino acids methionine and lysine. This naturally occurring substance is found in all mammalian tissues, especially striated muscle, and is required in energy metabolism, such as the oxidation of fatty acids, facilitating the aerobic metabolism of carbohydrates, and enhancing the excretion of certain organic acids. While only the L isomer is present in the biologic system, commercial synthesis of carnitine produces a D,L racemic mixture, from which the L-isomer is obtained. The D-isomer has pharmacologic effects but does not participate in lipid metabolism. Commercially, carnitine is available as both a prescription and non-prescription product. The prescription version is levocarnitine, while most dietary supplements contain D,L-carnitine which is commonly sold in health food stores.
Levocarnitine has been used in the treatment of primary and secondary carnitine deficiency in adults and neonates, Alzheimer's disease, dilated cardiomyopathy in adults and children, valproic acid-induced hepatotoxicity in children, and hyperlipoproteinemia. Its use in alcohol induced fatty liver, Down's syndrome, and chronic fatigue syndrome has shown varying results. Some athletes use carnitine supplements to increase exercise performance, however, the concept of carnitine loading does not appear to be very effective.1 Further, D,L-carnitine competitively inhibits levocarnitine. This inhibition may lead to a deficiency. Prescription forms of levocarnitine were approved by the FDA in 1985 (tablets), 1986 (oral solution), and 1992 (injection).If oxygen tension is limited, carnitine serves to maintain a ratio of free to esterified CoA within mitochondria that is optimal for oxidative phosphorylation and for the consumption of acetyl CoA.
Pharmacokinetics
Levocarnitine can be administered orally or intravenously. Levocarnitine is not bound to plasma proteins including albumin.
If plasma carnitine concentrations exceed the renal reabsorption maximum (roughly 60—100 µmol/L), excess carnitine is eliminated in the urine. Carnitine supplementation appears to have little, if any, affect on muscle carnitine content in humans. Carnitine in the central compartment does distribute into tissue, however, muscle is particularly refractory to acute supplementation because of its slower net turnover.1 After administration of large doses of carnitine, most of the dose is rapidly recovered in the urine. Levocarnitine is hepatically metabolized, with the major metabolite, trimethylamine N-oxide, excreted primarily in the urine (8—49%). Urinary excretion of carnitine is 4—8% of the total administered dose. Fecal excretion of total carnitine is < 1% of total carnitine excretion.
Special Populations:
Renal Impairment: Pharmacokinetic and clinical studies have shown that administration of levocarnitine to patients with end-stage renal disease (ESRD) on hemodialysis results in increased plasma levocarnitine concentrations. The safety and efficacy of oral levocarnitine has not been evaluated in patients with renal insufficiency. Chronic administration of high doses of oral levocarnitine in patients with severe renal impairment or in ESRD patients on dialysis may result in accumulation of the potentially toxic metabolites, trimethylamine (TMA) and trimethylamine-N-oxide (TMAO), since these metabolites are normally excreted in the urine. The accumulation of these metabolites does not occur to the same extent following intravenous administration (manufacturer information).
Indications/Dosage
For the treatment of primary systemic carnitine deficiency or for acute and chronic treatment of patients with an inborn error of metabolism that results in secondary carnitine deficiency:
NOTE: Levocarnitine is designated an an orphan drug by the FDA for this indication.
Intravenous dosage: Adults, Adolescents and Children: The recommended dose is 50 mg/kg IV given as a slow 2 to 3 minute bolus injection or by infusion. Often a loading dose is given to those with severe metabolic crisis, followed by an equivalent dose over the following 24 hours. Per the manufacturer literature, it should be administered every 3 to 4 hours, and never less than every 6 hours. All subsequent daily doses are recommended to be in the range of 50 mg/kg/day IV or as therapy may require. The highest dose administered has been 300 mg/kg. Monitoring should include blood chemistries, plasma carnitine (the plasma free carnitine concentration should be between 35 to 60 micromol/L) and overall clinical condition.
For the prevention and treatment of carnitine deficiency in patients with end stage renal impairment who are undergoing dialysis:
NOTE: Levocarnitine is designated an an orphan drug by the FDA for this indication.
Intravenous dosage: Adults: The recommended starting dose is 10 to 20 mg/kg dry body weight IV as a slow 2 to 3 minute bolus injection into the venous return line after each dialysis session. Initiation of therapy may be prompted by trough (pre-dialysis) plasma levocarnitine concentrations that are below normal (40 to 50 micromol/L). Dose adjustment should be guided by trough (pre-dialysis) levocarnitine levels, and downward dose adjustments (e.g., to 5 mg/kg after dialysis) may be made as early as the third or fourth week of therapy. NOTE: Do NOT use oral formulations for this indication.
Patients with Renal Impairment Dosing:
The IV formulation of this drug is acceptable for use in patients with end-stage renal disease (ESRD) on dialysis; no dosage adjustments are needed (see specific indication above). NOTE: Do NOT use oral (PO) levocarnitine to treat patients with severe renal impairment or ESRD. Major metabolites formed during oral administration following chronic high oral dosage may accumulate (manufacturer information, see Precautions).
Administration Information:
Intravenous (IV) Injection: Levocarnitine should be given as a slow 2—3 minute bolus injection or by continuous infusion. Parenteral admixtures of levocarnitine in sodium chloride 0.9% or Lactated Ringers solution, with concentrations ranging from 0.5—8 mg/ml, are stable for 24 hours at room temperature in PVC plastic bags.
Side Effects
Gastrointestinal (GI) adverse effects are possible with oral and intravenous (IV) levocarnitine therapy. These GI symptoms include abdominal pain, dyspepsia, diarrhea, gastritis, nausea, and vomiting.
