Usage
- Medical Conditions: Levo-carnitine is prescribed for the treatment of primary and secondary carnitine deficiency. Primary carnitine deficiency is a genetic disorder affecting the body’s ability to utilize carnitine for fatty acid metabolism. Secondary carnitine deficiency can arise from various factors like inherited metabolic disorders, liver or kidney disease, certain medications (e.g., valproic acid), and hemodialysis. It may also be used in specific clinical situations such as during valproic acid overdose or in cases of zidovudine-induced mitochondrial myopathy.
- Pharmacological Classification: Nutritional supplement, metabolic agent.
- Mechanism of Action: Levo-carnitine facilitates the transport of long-chain fatty acids into the mitochondria, the cellular powerhouses, where they are oxidized to produce energy. It acts as a carrier molecule, shuttling fatty acids across the inner mitochondrial membrane. This process is crucial for energy production, particularly in tissues like skeletal and cardiac muscle that rely heavily on fatty acid oxidation.
Alternate Names
- L-carnitine
- Vitamin BT (Note: this form contains D,L-carnitine, which can inhibit levo-carnitine and cause deficiency)
- Brand Names: Carnitor
How It Works
- Pharmacodynamics: Levo-carnitine enhances energy production by increasing fatty acid transport into the mitochondria. It may also have antioxidant properties and protect against cellular damage. In patients with carnitine deficiency, supplementation helps restore normal fatty acid metabolism and alleviate symptoms.
- Pharmacokinetics:
- Absorption: Orally administered levo-carnitine has limited bioavailability (around 14-18%). Absorption occurs primarily in the small intestine via a carrier-mediated process.
- Metabolism: Levo-carnitine is not extensively metabolized. A small portion is converted to trimethylamine (TMA) and trimethylamine-N-oxide (TMAO) by intestinal bacteria.
- Elimination: Primarily renal excretion, both as unchanged drug and metabolites. Small amounts are also excreted in feces. The elimination half-life varies depending on the route of administration (oral vs. intravenous).
- Mode of Action: Levo-carnitine binds to long-chain fatty acids, forming acylcarnitine esters. These esters are transported across the inner mitochondrial membrane by carnitine-acylcarnitine translocase. Inside the mitochondria, the fatty acids are released and undergo beta-oxidation, generating energy.
- Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Levo-carnitine is not known to bind to specific receptors or directly inhibit enzymes or modulate neurotransmitters.
Dosage
Standard Dosage
Adults:
- Oral: 1-3 grams/day divided into 2-3 doses, preferably with meals. The starting dose is typically 1 gram/day, increased as needed based on clinical response and tolerance.
- Intravenous: 50 mg/kg/day, as a slow intravenous bolus or infusion. In acute metabolic crisis, a loading dose may be given, followed by the same dose over the next 24 hours.
Children:
- Oral: 50-100 mg/kg/day divided into 2-3 doses, preferably with meals. The maximum dose is generally 3 grams/day.
- Intravenous: 50 mg/kg/day as a slow intravenous bolus or infusion.
Special Cases:
- Elderly Patients: No specific dose adjustments are routinely recommended. Monitor for potential side effects.
- Patients with Renal Impairment: Chronic oral levo-carnitine is not recommended for patients with severely compromised renal function or those on dialysis due to accumulation of TMA and TMAO metabolites. Intravenous administration is preferred in hemodialysis patients. Dose adjustments may be necessary based on carnitine levels and clinical condition.
- Patients with Hepatic Dysfunction: No specific dose adjustments are routinely recommended. Monitor for potential side effects.
- Patients with Comorbid Conditions: Use with caution in patients with diabetes, cardiovascular disease, or a history of seizures. Monitor closely.
Clinical Use Cases
- Intubation/Surgical Procedures/Mechanical Ventilation/ICU Use/Emergency Situations: Dosing is determined based on patient-specific factors, the underlying condition, and the severity of the carnitine deficiency. In acute settings, intravenous administration is often preferred.
Dosage Adjustments:
Dose adjustments may be needed based on patient-specific factors such as renal or hepatic impairment, metabolic disorders, concomitant medications, and clinical response. Therapeutic drug monitoring of plasma carnitine levels can guide dose optimization.
Side Effects
Common Side Effects:
- Nausea
- Vomiting
- Abdominal cramps
- Diarrhea
- Headache
- Body odor (“fishy” smell)
- Muscle pain or weakness
- Tingling sensation
Rare but Serious Side Effects:
- Seizures
- Allergic reactions (e.g., hives, difficulty breathing, swelling of the face, lips, tongue, or throat)
Long-Term Effects:
- Potential for elevated TMAO levels with chronic high-dose oral supplementation, possibly increasing the risk of atherosclerosis.
Adverse Drug Reactions (ADR):
- Severe allergic reactions (anaphylaxis) with intravenous administration, especially in patients with end-stage renal disease undergoing dialysis.
- Worsening of seizure control in some patients.
Contraindications
- Hypersensitivity to levo-carnitine.
Drug Interactions
- Warfarin: Levo-carnitine may enhance the anticoagulant effects of warfarin. Monitor INR closely.
- Valproic Acid: Levo-carnitine may be beneficial in valproic acid-induced hyperammonemia.
- Anticonvulsants: Several anticonvulsants may decrease levo-carnitine levels.
- Other: Interactions may occur with other medications metabolized by the kidneys or liver.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: B (animal studies have not shown fetal harm, but adequate human studies are lacking). Use only if clearly needed.
- Breastfeeding: Levo-carnitine is present in human milk. Supplementation in nursing mothers has not been extensively studied. Use with caution if the benefits outweigh the potential risks to the infant from excess carnitine exposure.
Drug Profile Summary
- Mechanism of Action: Facilitates long-chain fatty acid transport into the mitochondria for energy production.
- Side Effects: Nausea, vomiting, diarrhea, body odor, seizures (rare).
- Contraindications: Hypersensitivity.
- Drug Interactions: Warfarin, anticonvulsants.
- Pregnancy & Breastfeeding: Use with caution if benefits outweigh risks.
- Dosage: Adults: 1-3 g/day orally, 50 mg/kg/day IV; Children: 50-100 mg/kg/day orally, 50 mg/kg/day IV.
- Monitoring Parameters: Plasma carnitine levels, renal function, liver function, INR (if on warfarin), seizure frequency.
Popular Combinations
- Lactulose (in valproic acid-induced hyperammonemia).
Precautions
- General Precautions: Monitor patients with renal or hepatic impairment, history of seizures, diabetes, and cardiovascular disease closely.
- Pregnant Women: Assess risks and benefits carefully. Monitor carnitine levels.
- Breastfeeding Mothers: Monitor for potential neonatal side effects.
- Children & Elderly: Monitor for side effects and adjust dose accordingly.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Levo-carnitine?
A: Adults: 1-3 grams/day orally, 50 mg/kg/day IV. Children: 50-100 mg/kg/day orally, 50 mg/kg/day IV. Dose adjustments are necessary for specific conditions and patient populations.
Q2: What are the common side effects of Levo-carnitine?
A: Common side effects include gastrointestinal disturbances (nausea, vomiting, diarrhea, abdominal cramps), body odor (“fishy” smell), and headache.
Q3: Is Levo-carnitine safe during pregnancy?
A: Pregnancy Safety Category B. Animal studies suggest no fetal harm, but human data are limited. Use only if clearly needed and under medical supervision.
Q4: Can Levo-carnitine be used in patients with kidney disease?
A: Chronic oral use is not recommended for patients with severe renal impairment or on dialysis due to accumulation of metabolites. Intravenous administration is preferred for hemodialysis patients.
Q5: Does Levo-carnitine interact with any medications?
A: Yes. It can interact with warfarin, increasing its anticoagulant effects. It may also interact with certain anticonvulsants.
Q6: How should Levo-carnitine be administered?
A: Levo-carnitine is available in oral (tablets, solution) and intravenous formulations. Oral forms are usually taken with meals. Intravenous administration should be slow, either as a bolus or infusion.
Q7: What is the role of Levo-carnitine in valproic acid toxicity?
A: Levo-carnitine can be used to treat valproic acid-induced hyperammonemia by facilitating ammonia detoxification.
Q8: Are there any long-term effects of Levo-carnitine use?
A: Chronic high-dose oral use may increase TMAO levels, potentially increasing the risk of atherosclerosis.
Q9: How is Levo-carnitine different from D-carnitine?
A: D-carnitine is the inactive isomer of carnitine and can inhibit the effects of Levo-carnitine. It is important to avoid using D-carnitine or DL-carnitine when supplementing with Levo-carnitine.
Q10: Can Levo-carnitine be used in pediatric patients?
A: Yes, but the dosage needs to be adjusted based on the child’s weight and the specific condition.
