Levocarnitine Injection

Name: Levocarnitine Injection

Indications

For the acute and chronic treatment of patients with an inborn error of metabolism which results in secondary carnitine deficiency.

For the prevention and treatment of carnitine deficiency in patients with end stage renal disease who are undergoing dialysis.

How supplied

CARNITOR® (levocarnitine) Injection is available in 1 g per 5 mL single dose vials packaged 5 vials per carton (NDC 54482-147-01).

Store vials at controlled room temperature (25°C). See USP. Discard unused portion of an opened vial, as the formulation does not contain a preservative.

Manufactured for Sigma-Tau Pharmaceuticals, Inc. by Sigma-Tau S.p.A., 00040 Pomezia (Rome), Italy.. Sigma-Tau Pharmaceuticals, Inc., Gaithersburg, MD 20878. Revised: Jun 2015.

Levocarnitine Injection - Clinical Pharmacology

Levocarnitine is a naturally occurring substance required in mammalian energy metabolism. It has been shown to facilitate long-chain fatty acid entry into cellular mitochondria, thereby delivering substrate for oxidation and subsequent energy production. Fatty acids are utilized as an energy substrate in all tissues except the brain. In skeletal and cardiac muscle, fatty acids are the main substrate for energy production.

Primary systemic carnitine deficiency is characterized by low concentrations of levocarnitine in plasma, RBC, and/or tissues. It has not been possible to determine which symptoms are due to carnitine deficiency and which are due to an underlying organic acidemia, as symptoms of both abnormalities may be expected to improve with levocarnitine. The literature reports that carnitine can promote the excretion of excess organic or fatty acids in patients with defects in fatty acid metabolism and/or specific organic acidopathies that bioaccumulate acylCoA esters.1-6

Secondary carnitine deficiency can be a consequence of inborn errors of metabolism. Levocarnitine may alleviate the metabolic abnormalities of patients with inborn errors that result in accumulation of toxic organic acids. Conditions for which this effect has been demonstrated are: glutaric aciduria II, methyl malonic aciduria, propionic acidemia, and medium chain fatty acylCoA dehydrogenase deficiency.7,8 Autointoxication occurs in these patients due to the accumulations of acylCoA compounds that disrupt intermediary metabolism. The subsequent hydrolysis of the acylCoA compound to its free acid results in acidosis which can be life-threatening. Levocarnitine clears the acylCoA compound by formation of acylcarnitine, which is quickly excreted. Carnitine deficiency is defined biochemically as abnormally low plasma concentrations of free carnitine, less than 20 μmol/L at one week post term and may be associated with low tissue and/or urine concentrations. Further, this condition may be associated with a plasma concentration ratio of acylcarnitine/levocarnitine greater than 0.4 or abnormally elevated concentrations of acylcarnitine in the urine. In premature infants and newborns, secondary deficiency is defined as plasma levocarnitine concentrations below age-related normal concentrations.

Metabolism and excretion

In a pharmacokinetic study where five normal adult male volunteers received an oral dose of [3H-methyl]-L-carnitine following 15 days of a high carnitine diet and additional carnitine supplement, 58% to 65% of the administered radioactive dose was recovered in the urine and feces in 5 to 11 days. Maximum concentration of [3H-methyl]-L-carnitine in serum occurred from 2.0 to 4.5 hr after drug administration. Major metabolites found were trimethlyamine N-oxide, primarily in urine (8% to 49% of the administered dose) and [3H]-γ-butyrobetaine, primarily in feces (0.44% to 45% of the administered dose). Urinary excretion of levocarnitine was about 4% to 8% of the dose. Fecal excretion of total carnitine was less than 1% of the administered dose.10

After attainment of steady state following 4 days of oral administration of levocarnitine tablets (1980 mg every 12 hours) or oral solution (2000 mg every 12 hours) to 15 healthy male volunteers, the mean urinary excretion of levocarnitine during a single dosing interval (12 hours) was about 9% of the orally administered dose (uncorrected for endogenous urinary excretion).

Contraindications

None known.

Precautions

Drug Interactions

 Reports of INR increase with the use of warfarin have been observed. It is recommended that INR levels be monitored in patients on warfarin therapy after the initiation of treatment with levocarnitine or after dose adjustments.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Mutagenicity tests performed in Salmonella typhimurium, Saccharomyces cerevisiae, and Schizosaccharomyces pombe indicate that levocarnitine is not mutagenic. No long-term animal studies have been performed to evaluate the carcinogenic potential of levocarnitine.

Pregnancy

Reproductive studies have been performed in rats and rabbits at doses up to 3.8 times the human dose on the basis of surface area and have revealed no evidence of impaired fertility or harm to the fetus due to levocarnitine. There are, however, no adequate and well controlled studies in pregnant women.

Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

Levocarnitine supplementation in nursing mothers has not been specifically studied.

Studies in dairy cows indicate that the concentration of levocarnitine in milk is increased following exogenous administration of levocarnitine. In nursing mothers receiving levocarnitine, any risks to the child of excess carnitine intake need to be weighed against the benefits of levocarnitine supplementation to the mother. Consideration may be given to discontinuation of nursing or of levocarnitine treatment.

Pediatric Use

See DOSAGE AND ADMINISTRATION.

How supplied

Levocarnitine Injection, USP

NDC 0517-1045-25      1 g/5 mL Single Dose Vial      packed in boxes of 25

Store at or below 25°C (77°F) (See USP). Do not freeze. Store vials in carton until their use to protect from light. Discard unused portion of an opened vial, as the formulation does not contain a preservative.

PRINCIPAL DISPLAY PANEL - 5 mL Carton

Levocarnitine Injection, USP

1 g/5 mL (200 mg/mL)

NDC 0517-1045-25

25 x 5 mL SINGLE DOSE VIALS

FOR INTRAVENOUS USE

Rx Only

Each mL contains: Levocarnitine 200 mg, Water for Injection q.s. pH (range 6.0-6.5) adjusted with Hydrochloric Acid.
WARNING: Protect from light. Retain in carton until time of use. Discard unused portion.
Contains no preservatives.
Store at or below 25°C (77°F) (See USP). Do not freeze.
Directions for Use: See Package Insert.

AMERICAN REGENT, INC.
SHIRLEY, NY 11967

Rev. 10/04

LEVOCARNITINE 
Levocarnitine Injection, solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0517-1045
Route of Administration INTRAVENOUS DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
LEVOCARNITINE (LEVOCARNITINE) LEVOCARNITINE 200 mg  in 1 mL
Inactive Ingredients
Ingredient Name Strength
WATER  
HYDROCHLORIC ACID  
Packaging
# Item Code Package Description
1 NDC:0517-1045-25 25 VIAL, SINGLE-DOSE in 1 TRAY
1 5 mL in 1 VIAL, SINGLE-DOSE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA075861 10/08/2001
Labeler - American Regent, Inc. (622781813)
Establishment
Name Address ID/FEI Operations
Luitpold Pharmaceuticals, Inc. 002033710 ANALYSIS(0517-1045), MANUFACTURE(0517-1045), STERILIZE(0517-1045)
Revised: 08/2016   American Regent, Inc.
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