Carnitor

Amino Acids and Derivatives Supplements
Metabolic Agents, Carnitine Deficiency
Supplemental Dietary Agents

Tablets: Levocarnitine tablets should be administered 2 or 3 times daily, depending on clinical response.

Oral Solution: Levocarnitine doses should be spaced evenly throughout the day (every 3 or 4 hours) preferably during or following meals. Levocarnitine oral solution may be consumed alone or dissolved in a drink or other liquid food. Levocarnitine solution should be consumed slowly (over a period of several minutes) in order to maximize tolerance.

Levocarnitine injection is administered intravenously.
 
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.

hyperkalemia / Delayed / 6.0-6.0
atrial fibrillation / Early / 2.0-6.0
seizures / Delayed / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
laryngeal edema / Rapid / Incidence not known
bronchospasm / Rapid / Incidence not known

hypertension / Early / 18.0-21.0
hypotension / Rapid / 3.0-19.0
hypercalcemia / Delayed / 6.0-15.0
chest pain (unspecified) / Early / 6.0-15.0
anemia / Delayed / 3.0-12.0
hypervolemia / Delayed / 3.0-12.0
dyspnea / Early / 3.0-11.0
sinus tachycardia / Rapid / 5.0-9.0
bleeding / Early / 2.0-9.0
palpitations / Early / 3.0-8.0
melena / Delayed / 2.0-6.0
depression / Delayed / 5.0-6.0
amblyopia / Delayed / 3.0-6.0
peripheral edema / Delayed / 3.0-6.0
constipation / Delayed / 3.0-3.0
hypertonia / Delayed / 1.0-3.0
gastritis / Delayed / Incidence not known
edema / Delayed / Incidence not known

injection site reaction / Rapid / 27.0-38.0
headache / Early / 3.0-37.0
diarrhea / Early / 9.0-35.0
pharyngitis / Delayed / 15.0-27.0
infection / Delayed / 10.0-24.0
abdominal pain / Early / 5.0-21.0
vomiting / Early / 9.0-21.0
dizziness / Early / 10.0-18.0
cough / Delayed / 9.0-18.0
nausea / Early / 5.0-12.0
paresthesias / Delayed / 3.0-12.0
asthenia / Delayed / 8.0-12.0
fever / Early / 5.0-12.0
rhinitis / Early / 6.0-11.0
dyspepsia / Early / 5.0-9.0
dysgeusia / Early / 2.0-9.0
back pain / Delayed / 6.0-9.0
weight loss / Delayed / 3.0-8.0
pruritus / Rapid / 3.0-8.0
anorexia / Delayed / 3.0-6.0
vertigo / Early / 2.0-6.0
insomnia / Early / 3.0-6.0
rash / Early / 3.0-5.0
weight gain / Delayed / 2.0-3.0
sinusitis / Delayed / 2.0-3.0
anxiety / Delayed / 1.0-2.0
drug-induced body odor / Delayed / Incidence not known
weakness / Early / Incidence not known
urticaria / Rapid / Incidence not known

ACTICARNITINE, CarniteX, Carnitor

Rx, OTC

Natural substance; found in all mammalian tissues; required in aerobic metabolism
Prescription-only forms used in the treatment of primary and secondary carnitine deficiency in adults and pediatric patients
Dietary supplement (D, L carnitine) formulations available; little evidence to support promoted off-label health claims as dietary supplements

Initially, 990 mg PO 2 to 3 times per day with food, depending on clinical response.

Initially, 50 mg/kg/day PO in 2 to 3 divided doses. May increase to 100 mg/kg/day PO based on clinical response. Max: 3 g/day.

Initially, 1 g PO once daily with food. May increase slowly as tolerated to a maximum of 1 g PO 3 times per day with food.

Initially, 50 mg/kg/day PO in divided doses (every 3 to 4 hours, preferably during or after meals). May increase slowly as tolerated to a maximum of 100 mg/kg/day PO based on clinical response. Max: 3 g/day.

Initially, 50 mg/kg/day PO in divided doses (every 3 to 4 hours, preferably during or after feedings). May increase slowly as tolerated to a maximum of 100 mg/kg/day PO based on clinical response.

Initially, 50 mg/kg/dose 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 FDA-approved labeling, 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.

Initially, 50 mg/kg/dose 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 FDA-approved labeling, 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.

Initially, 50 mg/kg/dose 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 FDA-approved labeling, 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.

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 concentrations, 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. Do NOT use oral formulations for this indication.

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 concentrations, 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. Do NOT use oral formulations for this indication.

Valproic acid induced hepatoxicity is related directly or indirectly to carnitine deficiency; hence, a 1996 consensus conference of pediatric neurologists recommended levocarnitine treatment for valproic acid induced hepatotoxicity. The panel's recommended dose was 150 to 500 mg/kg/day PO.

2 to 5 mg/kg/day IV is recommended by guidelines for all neonates receiving PN. Higher doses (10 to 20 mg/kg/day IV) have also been used.

†Indicates off-label use

Specific dosage information is not available.

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.
Do not use oral levocarnitine to treat patients with severe renal impairment or ESRD. Major metabolites formed during oral administration following chronic high oral dosage may accumulate.

Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with levocarnitine is necessary. Concomitant use has resulted in increased INR levels in case reports. The mechanism of this interaction has not been identified.

ACTICARNITINE/Carnitor/L-Carnitine Oral Sol: 1g, 10mL
CarniteX/L-Carnitine Oral Cap: 340mg
Carnitor/L-Carnitine Intravenous Inj Sol: 1mL, 200mg
Carnitor/L-Carnitine Oral Tab: 330mg

3 grams/day PO is FDA-approved maximum; 50 mg/kg/day IV is the usual maximum dosage; doses up to 300 mg/kg/day IV have been used.

3 grams/day PO is FDA-approved maximum; 50 mg/kg/day IV is the usual maximum dosage; doses up to 300 mg/kg/day IV have been used.

3 grams/day PO; 50 mg/kg/day IV is usual maximum dosage; however, doses up to 300 mg/kg/day IV have been used.

100 mg/kg/day PO (Max: 3 grams/day); 50 mg/kg/day IV is usual maximum dosage; however, doses up to 300 mg/kg/day IV have been used.

100 mg/kg/day PO; 50 mg/kg/day IV is usual maximum dosage.

100 mg/kg/day PO; 50 mg/kg/day IV is usual maximum dosage.

Levocarnitine facilitates long-chain fatty acid transport from the cytosol to the mitochondria, providing substrates for oxidation and subsequent cellular energy production. Levocarnitine can promote the excretion of excess organic or fatty acids in patients with defects in fatty acid metabolism or specific organic acidopathies that bioaccumulate acyl CoA esters. Levocarnitine clears the acyl CoA esters by formation of acylcarnitine which is rapidly excreted.
 
Carnitine acetyltransferases (CATs) catalyze the interconversion of fatty acid esters of coenzyme A and carnitine, which are located in the cytosol and mitochondrial membranes. Translocases, which exist in mitochondrial membranes, rapidly transport both free carnitine and its esters in and out of cells. Fatty acid esters of CoA, formed in the cytosol, inhibit enzymes of the Krebs cycle, and are involved in oxidative phosphorylation. Hence, the oxidation of fatty acids requires the formation of acylcarnitines and their translocation into mitochondria where the CoA esters are reformed and metabolized. 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.

 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. 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.

Bioavailability of oral levocarnitine (tablet or solution) is approximately 15—16%, with a time to peak concentration of 3.3 hours. Levocarnitine tablets and oral solution are considered bioequivalent. There are no differences in the AUC and urinary excretion between levocarnitine tablets and oral solution.

Levocarnitine should be used during pregnancy only if clearly needed. No adequate, well controlled studies exist in pregnant women. Reproductive studies performed in rats and rabbits at doses up to 3.8 times the human dose have reported no evidence of impaired fertility or harm to the fetus.

Supplementation with levocarnitine in women who are breast-feeding has not been specifically studied; however, levocarnitine is a normal component of human milk which is required for fat metabolism. Consumption of levocarnitine within the normal range of dietary intake leads to excretion into the breast-milk, which is relatively constant. Women with carnitine deficiency and preterm infants may require prescription levocarnitine supplementation under the supervision of a healthcare professional. It is unlikely that maternal levocarnitine supplements during nursing would be harmful to the infant, but it is probably best to avoid over-the-counter supplementation until more data is available. Levocarnitine has been studied in dairy cows; data 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.