What is the recommended dosage and usage of Levocarnitine (L-carnitine) for treating primary and secondary carnitine deficiency?

Levocarnitine Dosing and Usage for Carnitine Deficiency

For primary carnitine deficiency, administer oral levocarnitine 50-100 mg/kg/day in divided doses (maximum 3 g/day) for children, and 990 mg two to three times daily (1.98-2.97 g/day total) for adults, with doses spaced every 3-4 hours during or after meals. 1

Primary Carnitine Deficiency

Primary carnitine deficiency is a genetic disorder of the cellular carnitine-transporter system that typically manifests by age 5 with cardiomyopathy, skeletal muscle weakness, and hypoglycemia. 2

Dosing Strategy for Primary Deficiency

• Start at 50 mg/kg/day and increase slowly while monitoring tolerance and therapeutic response 1
• Children and infants: 50-100 mg/kg/day divided into multiple doses, maximum 3 g/day 1
• Adults: 990 mg two or three times daily (using 330 mg tablets), or 1-3 g/day of oral solution 1
• Divide doses evenly throughout the day (every 3-4 hours), preferably during or following meals, consumed slowly to maximize tolerance 1

Baseline Assessment Required

Before initiating treatment, obtain: 3

• Echocardiogram and electrocardiogram
• Creatine kinase (CK) concentration
• Liver transaminases (AST, ALT)
• Pre-prandial blood glucose levels
• Plasma carnitine concentration (diagnostic if <5 μM; normal 25-50 μM) 3

Monitoring Parameters

• Periodic blood chemistries and vital signs 1
• Plasma carnitine concentrations to ensure adequate replacement 1
• Annual echocardiogram and electrocardiogram for cardiac surveillance 3
• CK and liver transaminases during acute illness 3

Secondary Carnitine Deficiency

Secondary carnitine deficiencies occur in chronic renal failure, prolonged parenteral nutrition, continuous renal replacement therapy, and with certain medications or inborn errors of metabolism. 2

Dosing for Secondary Deficiency

• Patients on prolonged PN or continuous renal replacement therapy: 0.5-1 g/day for prevention or treatment 2
• Hemodialysis patients: 1 mg/kg to 2 g IV at the end of each dialysis session (thrice weekly), or 10 mg/kg/day to 3 g/day orally in divided doses 2
• Pharmacologic supplementation when deficiency is profound: 50-100 mg/kg/day, with adults often receiving 3 g/day 2

Clinical Context for Secondary Deficiency

Biologic effects of low carnitine levels may not be clinically significant until they reach less than 10-20% of normal. 2 Profound deficiency causes: 2

• Hypoketotic hypoglycemia due to impaired fatty acid oxidation
• Muscle weakness and rhabdomyolysis
• Cardiomyopathy and arrhythmias
• Increased plasma triglycerides and lactate
• Rapid loss of lean body mass with amyotrophy
• Hepatomegaly with fatty liver changes

Diagnostic Confirmation

Measure acyl-to-free carnitine ratio: normal ≤0.25; deficiency >0.4. 2 When investigating suspected deficiency, simultaneously measure: 2

• Blood triglycerides
• Liver function tests (AST, ALT)
• Glucose, lactate, ammonium
• Urine ketones

Safety and Adverse Effects

At doses of approximately 3 g/day, expect gastrointestinal side effects including nausea, vomiting, abdominal cramps, diarrhea, and "fishy" body odor. 2

Rare but Serious Side Effects

• Muscle weakness in uremic patients 2
• Seizures in patients with pre-existing seizure disorders 2, 4
• Impaired fat oxidation with acute high-dose infusion (100 mg over 4 hours increased protein oxidation and reduced fat oxidation) 2

Critical Clinical Caveats

Higher doses should be administered only with caution and only where clinical and biochemical considerations make it likely that higher doses will be beneficial. 1

• Do not use levocarnitine as primary treatment for seizure management - it can paradoxically worsen seizures in susceptible patients 4
• Carnitine is not routinely indicated for all dialysis patients - reserve for those with specific symptoms not responding to standard therapies (erythropoietin-resistant anemia, intradialytic symptoms, post-dialytic malaise, general weakness) 2, 5
• Oral bioavailability is dose-dependent: 5-18% for pharmacologic doses (1-6 g) versus up to 75% for dietary amounts 6
• Pregnant women with primary carnitine deficiency should consult a metabolic specialist before conception, as carnitine levels typically decrease during pregnancy 3

Route-Specific Considerations

Oral solution may be consumed alone or dissolved in liquid food, with doses spaced evenly and consumed slowly. 1 The FDA-approved formulations include: 1

• CARNITOR® tablets (330 mg)
• CARNITOR® oral solution
• CARNITOR® SF sugar-free oral solution

Intravenous administration is reserved for hemodialysis patients or those unable to tolerate oral therapy, with initial distribution volume of 0.2-0.3 L/kg corresponding to extracellular fluid volume. 6