Carnitine deficiency, treatment: Limited data available: Note: Variability in gene-specific mutations and clinical presentations exist; dosage should be individualized based upon patient response and serum carnitine concentrations with consultation with a metabolic specialist.
Primary deficiency: Preterm and term neonates: Oral: Initial: 50 to 100 mg/kg/day in divided doses; reported frequency varies from 2 to 4 times daily up to every 3 to 4 hours; titrate slowly as needed based on serum carnitine concentrations; reported range: 100 to 400 mg/kg/day in divided doses (Almannai 2019; BIMDG 2016a; BIMDG 2020; Longo 2006; Longo 2016; Magoulas 2012; Rasania 2021; Stanley 2020; manufacturer's labeling).
Secondary deficiency (other inborn errors of metabolism):
Preterm and term neonates:
Oral: Initial: 50 to 100 mg/kg/day in divided doses; reported frequency varies from 2 to 4 times daily up to every 3 to 4 hours; titrate slowly as needed based on patient response to usual reported dose: 100 to 200 mg/kg/day in divided doses; some conditions may require higher daily doses (eg, 300 mg/kg/day) (BIMDG 2016b; BIMDG 2020; Boy 2017; Burton 2021; Sutton 2012; Wojcik 2022; manufacturer's labeling).
IV: 50 to 100 mg/kg as a single dose; titrate based on patient response. In patients with severe metabolic crisis, administer a loading dose followed by an equivalent dose given over the next 24 hours as a continuous infusion or divided every 3 to 6 hours; some conditions may require higher daily doses (eg, 300 mg/kg/day) (BIMDG 2016b; Boy 2017; Sutton 2012; manufacturer's labeling).
Parenteral nutrition, supplement: Limited data available: Preterm and term neonates: Note: Neonates weighing <5 kg are generally carnitine deficient and require supplementation: IV: Initial: 2 to 5 mg/kg/day in parenteral nutrition solution; higher doses up to 10 to 20 mg/kg/day may be necessary in patients with elevated triglyceride levels or receiving parenteral nutrition longer than 7 days; free and total plasma carnitine concentrations should be monitored and doses adjusted accordingly (ASPEN [Corkins 2015]; ASPEN [Vanek 2012]).
Carnitine deficiency, treatment:
Note: Variability in gene-specific mutations and clinical presentations exist; dosage should be individualized based upon patient response and serum carnitine concentrations with consultation with a metabolic specialist.
Primary deficiency: Infants, Children, and Adolescents: Oral: Initial: 50 to 100 mg/kg/day in divided doses; reported frequency varies from 2 to 4 times daily up to every 3 to 4 hours; may titrate slowly as needed based on serum carnitine concentrations; reported range: 100 to 400 mg/kg/day; maximum daily dose: 3,000 mg/day (Almannai 2019; BIMDG 2016a; BIMDG 2020; Longo 2006; Longo 2016; Magoulas 2012; Stanley 2020; manufacturer's labeling).
Secondary deficiency:
Infants, Children, and Adolescents:
Oral: Initial: 50 to 100 mg/kg/day in divided doses; reported frequency varies from 2 to 4 times daily up to every 3 to 4 hours; may titrate slowly as needed based on patient response; usual dose: 100 to 200 mg/kg/day; some patients may require higher doses (eg, 300 mg/kg/day); maximum daily dose: 3,000 mg/day (BIMDG 2016b; BIMDG 2020; Boy 2017; Shchelochkov 2020; Sutton 2012; manufacturer's labeling).
IV: 50 to 100 mg/kg as a single dose; titrate based on patient response. In patients with severe metabolic crisis, administer a loading dose based on patient's usual therapy, followed by an equivalent dose given over the next 24 hours as a continuous infusion or divided every 3 to 6 hours; some conditions may require higher daily doses (eg, 300 mg/kg/day) (BIMDG 2016b; BIMDG 2020; Boy 2017; Shchelochkov 2020; Sutton 2012; manufacturer's labeling).
Carnitine deficiency in patients with end-stage renal disease (ESRD) requiring dialysis: Limited data available:
Note: Although described in manufacturer labeling, current guidelines do not support the use of levocarnitine in patients on dialysis (KDOQI 2009; KDIGO 2012).
Children and Adolescents: IV: 10 to 20 mg/kg dry body weight after each dialysis session; titrate dose based on serum concentrations; lower doses may be sufficient (manufacturer's labeling).
Cyclic vomiting syndrome, supplemental/adjunctive therapy: Limited data available:
Children and Adolescents: Oral: Initial: 50 to 100 mg/kg/day in divided doses 2 or 3 times daily; usual maximum dose: 1,000 mg/dose twice daily; higher doses (eg, up to a daily dose of 4,000 mg/day) have been used if needed based on laboratory testing of blood carnitine levels; however, this should be done with caution and careful monitoring of adverse events (eg, diarrhea) (Boles 2011; Kovacic 2018; Li 2018; Maqbool 2020; NASPGHAN [Li 2008]; Raucci 2020).
Valproic acid toxicity, acute: Limited data available:
Children and Adolescents: Dosing based on level of hepatic involvement and should be adjusted based on clinical response or serum level of valproic acid:
No hepatotoxicity: IV: 100 mg/kg/day divided every 6 hours until serum ammonia and valproic acid concentrations begin to decrease and clinical improvement is evident; maximum daily dose: 3,000 mg/day (Russell 2007).
Symptomatic hyperammonemia or hepatotoxicity: Reported dosing regimens variable: IV: Loading dose: 100 mg/kg; maximum loading dose: 6 g; followed by 15 mg/kg/dose every 4 to 6 hours; continue treatment until serum ammonia concentrations begin to decrease and clinical improvement is evident; patients may require several days of therapy. Doses of 50 mg/kg/dose (up to 3,000 mg/dose) every 8 hours have also been described (EASL 2019; Howland 2019; Perrott 2010; Russell 2007).
Oral: There are no dosage adjustments provided in the manufacturer's labeling; safety and efficacy of oral carnitine have not been evaluated in patients with renal insufficiency. Chronic administration of high oral doses to patients with severely compromised renal function or with end-stage renal disease on dialysis may result in accumulation of potentially toxic metabolites.
IV: There are no dosage adjustments provided in the manufacturer's labeling; dosage adjustments should be determined based on levocarnitine levels and clinical response.
Oral, IV: There are no dosage adjustments provided in the manufacturer's labeling.
(For additional information see "Carnitine supplements (Levocarnitine): Drug information")
Carnitine deficiency:
Primary or secondary: Oral:
Oral solution: Initial: 1,000 mg/day in divided doses (every 3 to 4 hours throughout the day); titrate slowly as needed to 1,000 to 3,000 mg/day in divided doses based on tolerance and therapeutic response; higher doses may be needed in some patients (administer only with caution).
Tablet: 990 mg 2 to 3 times a day, depending on clinical response.
Secondary: IV: 50 mg/kg/day in divided doses (every 3 to 6 hours); subsequent doses in the range of 50 mg/kg/day or higher if clinically indicated (maximum reported dose: 300 mg/kg/day). In patients with severe metabolic crisis, a 50 mg/kg loading dose followed by an additional 50 mg/kg in divided doses over the next 24 hours may be required.
Carnitine deficiency in patients with ESRD requiring dialysis: IV: 10 to 20 mg/kg (dry body weight) after each dialysis session; guide dosage adjustments by trough (predialysis) levocarnitine concentrations. Evaluate clinical response at 3-month intervals and titrate to the lowest effective dose; therapy should be discontinued if no improvement is seen after 9 to 12 months of therapy (Eknoyan 2003). Note: Current guidelines do not support the routine use of levocarnitine in dialysis patients (K/DOQI guidelines 2000); however, the National Kidney Foundation indicates levocarnitine therapy in patients with hyporesponsiveness to erythropoietin-based products, symptomatic intradialytic hypotension, NYHA functional class III-IV or ACC/AHA stage C-D heart failure or symptomatic cardiomyopathy, or muscle weakness and fatigability affecting quality of life which are unresponsive to standard medical therapy (Eknoyan 2003).
Dietary supplement (OTC use): Oral: Refer to individual product labeling.
Valproic acid toxicity, acute (off-label use): IV: Initial: 100 mg/kg as an IV bolus followed by 50 mg/kg (maximum: 3,000 mg) as an IV bolus or intermittent infusion (over 15 to 30 minutes) every 8 hours; continue until ammonia levels are decreasing and clinical improvement is evident; patients may require several days of therapy (Perrott 2010). Some experts recommend a higher maximum loading dose (eg, 100 mg/kg [maximum: 6,000 mg]) and smaller, more frequent maintenance doses (eg, 15 mg/kg every 4 to 6 hours) in symptomatic patients (EASL 2019; Howland 2019; Russell 2007).
Oral: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied). However, safety and efficacy of oral carnitine have not been evaluated in patients with renal insufficiency. Chronic administration of high oral doses to patients with severely compromised renal function or ESRD patients on dialysis may result in accumulation of potentially toxic metabolites.
IV: There are no dosage adjustments provided in the manufacturer’s labeling; dosage adjustments should be determined by levocarnitine levels and clinical response. Note: Current guidelines do not support the routine use of levocarnitine in dialysis patients (K/DOQI guidelines 2000); however, the National Kidney Foundation indicates levocarnitine therapy in patients with hyporesponsiveness to erythropoietin-based products, symptomatic intradialytic hypotension, NYHA functional class III-IV or ACC/AHA stage C-D heart failure or symptomatic cardiomyopathy, or muscle weakness and fatigability affecting quality of life which are unresponsive to standard medical therapy (Eknoyan 2003).
Oral, IV: There are no dosage adjustments provided in the manufacturer’s labeling.
The following adverse drug reactions are derived from product labeling unless otherwise specified. Adverse reactions include intravenous use in hemodialysis patients.
Frequency not defined:
Cardiovascular: Atrial fibrillation, chest pain, ECG abnormality, hypertension, palpitations, peripheral edema, tachycardia, vascular disease
Dermatologic: Body odor, skin rash, urticaria
Endocrine & metabolic: Hypercalcemia, parathyroid disorder, weight gain, weight loss
Gastrointestinal: Abdominal cramps, abdominal pain, anorexia, diarrhea, dysgeusia, gastritis, melena, nausea, vomiting
Hematologic & oncologic: Anemia, hemorrhage
Hypersensitivity: Facial edema, hypersensitivity reaction (including anaphylaxis, bronchospasm, and laryngeal edema)
Infection: Infection
Nervous system: Asthenia, depression, dizziness, headache, myasthenia (uremic patients), paresthesia, seizure, vertigo
Ophthalmic: Amblyopia, eye disease
Renal: Renal failure syndrome
Respiratory: Bronchitis, cough, rhinitis
Miscellaneous: Fever
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to levocarnitine or any component of the formulation.
Concerns related to adverse effects:
• Gastrointestinal effects: GI reactions may result from too rapid consumption of oral carnitine; consume oral solution slowly and space doses evenly throughout the day to maximize tolerance.
• Hypersensitivity reactions: Serious hypersensitivity reactions have been reported after oral (eg, rash, urticaria, facial edema) and intravenous (eg, anaphylaxis, laryngeal edema, and bronchospasm) administration. Reactions from IV use have typically occurred in patients with end stage renal disease on dialysis and may occur within minutes after use. Discontinue immediately and institute appropriate medical therapy if an acute reaction occurs; consider risks and benefits of reinitiating therapy, and monitor patient for recurrence of severe hypersensitivity reaction if therapy is reinstated.
Disease-related concerns:
• Carnitine deficiency: Risk factors include: Age (infants and young children are deficient in the enzyme that activates carnitine), chronic valproic acid administration, concomitant neurologic disorders, congenital metabolic disorders, hepatic cirrhosis, renal failure, critical care patients (burns, sepsis, trauma, organ failure), use of multiple antiseizure drugs and other drugs (chemotherapy agents, antinucleoside analogues) (Katiyar 2007).
• Renal impairment: Safety and efficacy of oral carnitine have not been evaluated in patients with renal insufficiency. Chronic administration of high oral doses to patients with severely compromised renal function or ESRD patients on dialysis may result in accumulation of potentially toxic metabolites.
• Seizure disorder: Use with caution in patients with seizure disorders or in those at risk of seizures; both new-onset seizure activity as well as an increased frequency and/or severity of seizures has been observed.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Carnitor: 200 mg/mL (5 mL)
Generic: 200 mg/mL (5 mL)
Solution, Intravenous [preservative free]:
Generic: 200 mg/mL (20 mL)
Solution, Oral:
Carnitor: 1 g/10 mL (118 mL) [contains methylparaben, propylparaben; cherry flavor]
Carnitor SF: 1 g/10 mL (118 mL) [sugar free; contains methylparaben, propylparaben, saccharin sodium; cherry flavor]
G-levOCARNitine S/F: 1 g/10 mL (474 mL) [sugar free; contains methylparaben, propylene glycol, propylparaben]
Generic: 1 g/10 mL (5 mL, 10 mL, 118 mL)
Tablet, Oral:
Carnitor: 330 mg
Generic: 330 mg
Yes
Solution (Acticarnitine SF Oral)
1 g/10 mL (per mL): $0.05
Solution (Carnitor Intravenous)
200 mg/mL (per mL): $9.11
Solution (Carnitor Oral)
1 g/10 mL (per mL): $0.42
Solution (Carnitor SF Oral)
1 g/10 mL (per mL): $0.50
Solution (levOCARNitine (Dietary) Oral)
1 g/10 mL (per mL): $0.03
Solution (levOCARNitine Intravenous)
200 mg/mL (per mL): $8.56
Solution (levOCARNitine Oral)
1 g/10 mL (per mL): $0.39
Tablets (Carnitor Oral)
330 mg (per each): $1.47
Tablets (levOCARNitine (Dietary) Oral)
330 mg (per each): $0.34
Tablets (levOCARNitine L-Tartrate Oral)
330 mg (per each): $0.20
Tablets (levOCARNitine Oral)
330 mg (per each): $1.10
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Carnitor: 200 mg/mL (5 mL)
Solution, Oral:
Carnitor: 10% (118 mL) [contains methylparaben, propylparaben]
Generic: 10% (118 mL)
Tablet, Oral:
Carnitor: 330 mg
Oral: Oral solution: Administer undiluted or diluted in either beverages or liquid food; consume slowly; doses should be spaced evenly throughout the day, preferably during or following meals to improve tolerance.
Parenteral:
Carnitine deficiency: May be administered undiluted (200 mg/mL) as IV push over 2 to 3 minutes or further diluted and administered as intermittent IV infusion over 30 minutes or as continuous infusion (BIMDG 2016a).
End-stage renal disease on hemodialysis: May be administered undiluted (200 mg/mL) as IV push over 2 to 3 minutes into the venous return line.
Valproic acid toxicity: May be administered undiluted (200 mg/mL) as IV push over 2 to 3 minutes or further diluted and administered as IV infusion over 10 to 30 minutes (Howland 2019; Perrott 2010; Russell 2007).
Oral solution: Solution is for oral use only (not for parenteral use); may be consumed alone or dissolved in either a drink or liquid food, and should be consumed slowly. Space doses every 3 to 4 hours evenly throughout the day, preferably during or following meals, to maximize tolerance.
IV:
Carnitine deficiency: Administer as a bolus dose over 2 to 3 minutes or by infusion. Doses should be administered every 3 to 4 hours, but never less than every 6 hours (eg, 4 doses/day).
Hemodialysis patients: Administer as a bolus dose over 2 to 3 minutes into the venous return line after each dialysis session.
Oral: Store at 20°C to 25°C (68°F to 77°F). Protect oral solution from freezing and excessive heat.
IV: IV solution is stable for up to 24 hours when mixed in NS or LR in PVC bags and stored at 25°C (77°F).
Pharmacy supply of emergency antidotes: Guidelines suggest that at least 9 to 15 g of levocarnitine be stocked. Suggested amount is stated to be a sufficient quantity to treat 1 patient weighing 100 kg for an initial 8- to 24-hour period (Dart 2018); actual amount to be stocked should take into account site-specific and population-specific needs.
Oral: Solution, tablets: Treatment of primary or secondary carnitine deficiency (FDA approved in infants, children, and adults); dietary supplement of carnitine (dietary supplement indicated for use in adults); has also been used as a supplemental therapy in cyclic vomiting syndrome. Note: Approved ages and uses for dietary supplements may vary; consult product-specific labeling for details.
Parenteral: Treatment of secondary carnitine deficiency and prevention and treatment of carnitine deficiency in patients undergoing dialysis for end-stage renal disease (ESRD) (FDA approved in pediatric patients [age not specified] and adults); has also been used for treatment of valproic acid toxicity. Note: Although described in manufacturer labeling, current guidelines do not support the use of levocarnitine in patients on dialysis (KDIGO 2012; KDOQI 2009).
LevOCARNitine may be confused with levETIRAcetam, levocabastine
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Vitamin K Antagonists (eg, warfarin): LevOCARNitine may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Teratogenic effects were not observed in animal studies. Carnitine is a naturally occurring substance in mammalian metabolism.
Carnitine serum concentrations should be obtained at baseline and subsequently monitored weekly to monthly. Monitor for diarrhea.
Metabolic disorders (primary or secondary carnitine deficiency): Blood chemistry, vital signs, and plasma carnitine concentration.
Valproic acid toxicity: Serum valproic acid concentrations (every 4 to 6 hours until a downward trend is observed), electrolytes, blood gases, mental status, hepatic function, serum ammonia concentration, serum lactate, and platelets.
Normal plasma free carnitine level: Neonates PNA ≥1 week, Infants, Children, and Adolescents: ≥20 micromoles/L; target plasma free carnitine level during therapy: 35 to 60 micromoles/L; to evaluate for carnitine deficiency, determine the plasma acylcarnitine/free carnitine ratio (A/F ratio).
A/F ratio = [plasma total carnitine - free carnitine] divided by free carnitine
Normal plasma A/F ratio = 0.25; in carnitine deficiency A/F ratio >0.4
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 acyl CoA esters and disruption of intermediary metabolism.
In patients with valproic acid toxicity, the administration of exogenous carnitine shifts the metabolism of valproic acid toward beta-oxidation and away from omega-oxidation and potentially hepatotoxic metabolite production (Baddour 2018; Eyer 2005).
Protein binding: None
Metabolism: Hepatic; Major metabolites: Trimethylamine (TMA) and trimethylamine N-oxide (TMAO)
Bioavailability: Oral solution: 15.9% ± 4.9%; Tablet: 15.1% ± 5.3%
Half-life elimination: 17.4 hours
Time to peak: Oral: 3.3 hours
Excretion: Urine (76%, 4% to 8% as unchanged drug); feces (<1%)
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