Yes

Dietary Supplement

Oral: Primary systemic carnitine deficiency; acute and chronic treatment of patients with an inborn error of metabolism which results in secondary carnitine deficiency

I.V. Acute and chronic treatment of patients with an inborn error of metabolism which results in secondary carnitine deficiency; prevention and treatment of carnitine deficiency in patients with end stage renal disease who are undergoing hemodialysis.

B

No adequate or well controlled studies in pregnant women. However, carnitine is a naturally occurring substance in mammalian metabolism. In breast-feeding women, use must be weighed against the potential exposure of the infant to increased carnitine intake. Use caution in breast-feeding women.

Caution in patients with seizure disorders or in those at risk of seizures (CNS mass or medications which may lower seizure threshold). Both new-onset seizure activity as well as an increased frequency of seizures has been observed.

I.V. therapy in HD patients: >5%:

Cardiovascular: Hypertension (18% to 21%), peripheral edema (3% to 6%)

Endocrine & metabolic: Hypercalcemia (6% to 15%)

Gastrointestinal: Diarrhea (9% to 35%), abdominal pain (5% to 21%), vomiting (9% to 21%), nausea (5% to 12%)

Neuromuscular & skeletal: Weakness (9% to 12%)

Miscellaneous: Allergic reaction (2% to 6%)

No reports of overdose; easily removed by dialysis

Valproic acid, sodium benzoate

Intravenous solution: Intact ampuls should be stored at controlled room temperature (25°C) and protected from light. Further dilutions in 0.9% sodium chloride or lactated Ringers at a concentration ranging from 0.5-8 mg/mL are stable up to 24 hours in PVC at room temperature.

Carnitine is a naturally occurring metabolic compound which functions as a carrier molecule for long-chain fatty acids within the mitochondria, facilitating energy production. Carnitine deficiency is associated with accumulation of excess acylCoA esters and disruption of intermediary metabolism. Carnitine supplementation increases carnitine plasma concentrations. The effects on specific metabolic alterations have not been evaluated. ESRD patients on maintenance HD may have low plasma carnitine levels because of reduced intake of meat and dairy products, reduced renal synthesis, and dialytic losses. Certain clinical conditions (malaise, muscle weakness, cardiomyopathy and arrhythmias) in HD patients may be related to carnitine deficiency.

Bioavailability: 15% to 16% (oral tablets, solution)

Half-life: 17.4 hours

Time to peak: 3.3 hours (oral tablets, solution)

Elimination: Unchanged, in urine: 76%

Oral:

Infants/Children: Initial: 50 mg/kg/day; titrate to 50-100 mg/kg/day in divided doses with a maximum dose of 3 g/day

Adults: 990 mg (oral tablets) 2-3 times/day or 1-3 g/day (oral solution)

I.V.:

Metabolic disorders: 50 mg/kg as a slow 2- to 3-minute I.V. bolus or by I.V. infusion

Severe metabolic crisis:

A loading dose of 50 mg/kg followed by an equivalent dose over the following 24 hours administered as every 3 hours or every 4 hours (never less than every 6 hours either by infusion or by intravenous injection)

All subsequent daily doses are recommended to be in the range of 50 mg/kg or as therapy may require

The highest dose administered has been 300 mg/kg

It is recommended that a plasma carnitine concentration be obtained prior to beginning parenteral therapy accompanied by weekly and monthly monitoring

ESRD patients on hemodialysis:

Predialyis levocarnitine concentrations below normal (40-50 mmol/L): 10-20 mg/kg dry body weight as a slow 2- to 3-minute bolus after each dialysis session

Dosage adjustments should be guided by predialysis trough levocarnitine concentrations and downward dose adjustments (to 5 mg/kg after dialysis) may be made as early as every 3rd or 4th week of therapy

Oral: Solution may be dissolved in either drink or liquid food. Doses should be spaced every 3 to 4 hours throughout the day, preferably during or following meals.

I.V.: Hemodialysis patients: Injection should be given over 2-3 minutes into the venous return line after each dialysis session.

Plasma concentrations should be obtained prior to beginning parenteral therapy, and should be monitored weekly to monthly. In metabolic disorders: monitor blood chemistry, vital signs, and plasma carnitine levels (maintain between 35-60 mmol/L). In ESRD patients on dialysis: Plasma levels below the normal range should prompt initiation of therapy. Monitor predialysis (trough) plasma carnitine levels.

Normal carnitine levels are 40-50 mmol/L; levels should be maintained on therapy between 35-60 mmol/L

None reported

None reported

No information available to require special precautions

No effects or complications reported

The oral solution should be consumed slowly and spaced evenly throughout the day to improve tolerance

Parenteral: May be administered by direct I.V. infusion over 2-3 minutes or as continuous infusion

Monitor serum triglycerides, fatty acids, and carnitine levels

Injection: Ampul: 200 mg/mL (2.5 mL, 5 mL)

Solution, oral: 100 mg/mL (118 mL)

Tablet: 330 mg

Although supplemental carnitine has been shown to increase carnitine concentrations, effects on the signs and symptoms of carnitine deficiency have not been determined