Levocarnitine

Approved Indications:

• Primary Systemic Carnitine Deficiency:
  Treatment of primary systemic carnitine deficiency caused by inherited defects in carnitine transport.
• Secondary Carnitine Deficiency:
  Management of secondary deficiency in:
• Patients with end-stage renal disease (ESRD) on hemodialysis
• Individuals with organic acidemias (e.g., propionic or methylmalonic acidemia)
• Valproate-induced hepatotoxicity or encephalopathy
• Certain inborn errors of metabolism causing impaired carnitine synthesis or transport

Clinically Accepted (Off-label) Uses:

• Male infertility (oligoasthenoteratozoospermia)
• Cardiomyopathy associated with metabolic disorders
• Chronic fatigue syndrome
• Hepatic encephalopathy (as adjunct)
• Supportive therapy in athletic performance and mitochondrial disorders

Routes: Oral (solution, tablet) and Intravenous (IV)

Oral Administration

Primary Carnitine Deficiency:

• Adults and Children: 50–100 mg/kg/day in 2–3 divided doses
• Maximum daily dose: Typically up to 3 g/day

Secondary Deficiency:

• 1–3 g/day in divided doses based on clinical response

Valproate-induced toxicity:

• 100 mg/kg/day orally (maximum 3 g/day), in divided doses

IV Administration

Hemodialysis Patients:

• 20 mg/kg IV after dialysis 2–3 times per week
• Or fixed dose: 1 g IV after dialysis session

Acute Metabolic Crises (e.g., organic acidemias):

• 50–100 mg/kg IV every 4–6 hours, or as a continuous infusion

Pediatric Use:

• Similar mg/kg dosing as in adults
• Neonates: typically start with 50 mg/kg/day IV or orally

Special Populations:

• Renal Impairment:
  IV is preferred in ESRD. Monitor for accumulation; adjust frequency accordingly.
• Hepatic Impairment:
  No dosage adjustment needed

Levocarnitine (L-carnitine) is an essential cofactor in mitochondrial energy production. It facilitates the transport of long-chain fatty acids across the inner mitochondrial membrane into the matrix, where they undergo β-oxidation to generate ATP. In carnitine-deficient states, fatty acid oxidation is impaired, leading to energy depletion and toxic metabolite accumulation. Supplementation restores normal mitochondrial function, clears toxic acyl groups, and enhances energy metabolism, especially in skeletal muscle, myocardium, and liver.

• Absorption (oral): ~10–20% bioavailability
• Peak Plasma Time: 3–6 hours after oral dosing
• Distribution: Widely distributed; highest concentrations in skeletal muscle, heart, and liver
• Plasma Protein Binding: Minimal
• Metabolism: Limited hepatic metabolism
• Half-life: ~17 hours (may increase in renal impairment)
• Excretion: Primarily via kidneys—urine as free and acylated carnitine
• Dialysis: Readily removed; supplemental dose required post-dialysis

• Pregnancy:
  Not formally classified by FDA. Animal studies do not show fetal harm. Use only if clearly indicated.
• Lactation:
  Levocarnitine is present in breast milk. No adverse effects reported in infants. Likely safe during breastfeeding.
• Recommendation:
  Use with caution during pregnancy and lactation; supplementation may benefit carnitine-deficient mothers or infants.

• Primary Class: Metabolic Agent / Nutritional Supplement
• Subclass: Fatty Acid Oxidation Cofactor
• Chemical Type: Quaternary ammonium compound (naturally occurring)

• Hypersensitivity to Levocarnitine or formulation excipients
• Oral use is contraindicated in patients with trimethylaminuria (due to risk of strong body odor)
• Anuric patients (without dialysis support) may develop accumulation with IV use

• Seizure Risk:
  May increase frequency or severity of seizures in predisposed patients
• Odor Development:
  Large oral doses may result in fishy body odor due to trimethylamine buildup
• ESRD Patients:
  Plasma levels do not always reflect tissue stores—assess symptoms clinically
• Metabolic Monitoring:
  Required during high-dose or emergency use in metabolic disorders

Common:

• Nausea
• Vomiting
• Diarrhea
• Abdominal cramps
• Body odor (fishy smell)

Less Common:

• Headache
• Restlessness
• Myasthenia or muscle weakness

Serious (Rare):

• Seizure exacerbation
• Hypersensitivity reactions (rash, urticaria, anaphylaxis)

Onset and Dose-Dependence:

• GI symptoms are typically dose-related and may decrease over time.
• CNS effects (e.g., seizures) may occur in susceptible individuals.

• Valproic Acid:
  Protective against valproate-induced hepatotoxicity and hyperammonemia; often co-administered
• Anticoagulants (e.g., Warfarin, Acenocoumarol):
  Possible enhancement of anticoagulant effect—monitor INR closely
• CYP450 Interaction:
  Not metabolized by CYP enzymes—minimal risk of pharmacokinetic drug interactions

• Pediatric Guidelines (2023–2024):
  Increased emphasis on Levocarnitine in treating organic acidemias and valproate toxicity
• Nephrology Guidelines:
  Support use in ESRD-related myopathy and fatigue management; post-dialysis dosing standard
• Metabolic Disease Management:
  Expanded recognition in rare inborn metabolic errors with FDA orphan drug considerations

• Oral Form (Tablet/Solution):
  Store at 20°C to 25°C (68°F to 77°F); excursions allowed from 15°C to 30°C
  Protect from moisture and light; do not freeze the oral solution
  Shake oral solution well before use
• IV Form:
  Store in original container at 20°C to 25°C
  Do not freeze
  Use reconstituted solution immediately or per manufacturer’s instruction
• Handling:
  Keep out of reach of children
  Discard any unused portion as per local regulations