Key points
- We recommend to consult your poison centre with the use of this antidote
- When the serum concentration of valproic acid is equal or greater to 6250 mcmol/L, hemodialysis must be considered.
- The administration of levocarnitine should be considered in consultation with your poison centre.
+ Synonyms and other terms
- Carnitine
- Carnitor™
- L-carnitine
+ Indications
- Its use should be considered as an adjuvant in cases of acute valproic acid poisoning in symptomatic patients (encephalopathy or hepatotoxicity), not hemodialized with hyperammonemia (serum ammonia level greater than the highest reference lab value based on age).
- The threshold for levocarnitine administration may be lower in pediatric patients, consult your poison centre.
+ Dosage
+ Pediatric Dose
- Loading Dose: 100 mg/kg by direct IV (max 6 g).
- Maintenance dose: 15 mg/kg by direct IV every 4 h.
- Maximum: 12 g/24 h.
+ Adult Dose
- Loading Dose: 100 mg/kg by direct IV (max 6 g).
- Maintenance dose: 15 mg/kg by direct IV every 4 h.
- Maximum: 12 g/24 h.
+ Renal Impairment
Possibility of potentially toxic buildup of metabolites (trimethylamine and trimethylamine-N-oxide) in the case of renal impairment, but no data suggests that the dose should be modified for short-term use
+ Hepatic Impairment
No data suggests that the dose should be modified for short-term use.
+ Hemodialysis Patient
- No data suggests that the dose should be modified for short-term use.
- Levocarnitine is dialysable.
- When hemodialysis is indicated for poisoning management, the role of levocarnitine is less pertinent.
+ Pregnancy
- Its safety has not been demonstrated.
- Do not hesitate to use carnitine during pregnancy if the anticipated toxic effects pose a significant risk of morbidity or mortality.
- No data suggests that the dose should be modified for short-term use.
+ Obese or Overweight Patient
No data suggests that the dose should be modified for short-term use.
+ Adverse effects
- At high doses: fishy smell from skin, diarrhea, nausea, vomiting.
+ Monitoring
- Gastrointestinal symptoms
- State of consciousness
- Serum valproic acid levels
- Conversion factor for valproic acid: 1 mcmol/l = 0.144217 mcg/ml (or mg/L); 1 mcg/ml (or mg/L) = 6.934 mcmol/L.
- Serum ammonia level
+ End of treatment
- Normal state of consciousness.
- Normal serum ammonia level.
- Serum levels of valproic acid dropping (lower than 693 mcmol/L) and significant clinical improvement.
+ Special Notes on Administration
Intravenous Route (IV)
- Direct IV: Administer the solution for injection concentrated at 200 mg/ml by IV direct over 2 to 3 min.
- IV infusion over 10 - 30 min: Dose of levocarnitine can be diluted in NS or LR in order to obtain a final concentration of 0.5 to 8 mg/ml to be administered over 10 to 30 minutes using a volumetric pump.
Subcutaneous Route (SC)
- No data available.
Intramuscular Route (IM)
- No data available.
Intraosseous Route (IO)
- No data available.
Enteral Route (PO or NG Tube)
- Use commercialized oral formulations.
- Consult your poison centre for dosage information.
- Intravenous route is the preferred route.
Compatibility
Partial list only. Consult the pharmacist on duty at your health care facility.
- Compatible solutions: NS, LR.
- Y-site compatibility: No data available.
- Y-site incompatibility: No data available.
Stability
- Does not contain any preservatives. The product is supplied as a single-use vial. Discard any unused portion after opening.
- Store vials at room temperature (15°C to 30°C). Protect from light and extreme temperatures.
- Compatible and stable when mixed with a parenteral solution of 0.9% NaCl or lactated Ringer’s concentrations ranging from 0.5 to 8.0 mg/ml and stored at room temperature (25°C) for a maximum of 24 hours in PVC plastic containers.
+ Available products
- Carnitor, 200 mg/ml, Inj. Sol., 5 ml per vial, PPC/Sigma-tau Pharmaceuticals, DIN 02144344,
+ Amount required to treat a person weighting 70kg during 24 hours
- At least 12,000 mg.
+ References
Chopra, Amit, Bhanu Prakash Kolla, Meghna P. Mansukhani, Pamela Netzel, and Mark A. Frye. 2012. “Valproate-Induced Hyperammonemic Encephalopathy: An Update on Risk Factors, Clinical Correlates and Management.” General Hospital Psychiatry 34 (3):290–98.
Ghannoum, Marc, Martin Laliberté, Thomas D. Nolin, Robert MacTier, Valery Lavergne, Robert S. Hoffman, Sophie Gosselin, and EXTRIP Workgroup. 2015. “Extracorporeal Treatment for Valproic Acid Poisoning: Systematic Review and Recommendations from the EXTRIP Workgroup.” Clinical Toxicology 53 (5):454–65.
Lheureux, Philippe E. R., and Philippe Hantson. 2009. “Carnitine in the Treatment of Valproic Acid-Induced Toxicity.” Clinical Toxicology 47 (2):101–11.
Lheureux, Philippe E. R., Andrea Penaloza, Soheil Zahir, and Mireille Gris. 2005. “Science Review: Carnitine in the Treatment of Valproic Acid-Induced Toxicity - What Is the Evidence?” Critical Care / the Society of Critical Care Medicine 9 (5):431–40.
Mock, Christie M., and Kristen H. Schwetschenau. 2012. “Levocarnitine for Valproic-Acid-Induced Hyperammonemic Encephalopathy.” American Journal of Health-System Pharmacy: AJHP: Official Journal of the American Society of Health-System Pharmacists 69 (1):35–39.
Perrott, Jerrold, Nancy G. Murphy, and Peter J. Zed. 2010. “L-Carnitine for Acute Valproic Acid Overdose: A Systematic Review of Published Cases.” The Annals of Pharmacotherapy 44 (7-8):1287–93.
Russell, Scott. 2007. “Carnitine as an Antidote for Acute Valproate Toxicity in Children.” Current Opinion in Pediatrics 19 (2):206–10.
