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Levocarnitine

(lee voe kar' ni teen)

Molecule Info

 
Content & Description

Tablet: Each tablet contains Levocarnitine USP 330 mg.
Solution: Each 5 ml solution contains Levocarnitine USP 500 mg.

Injection levocarnitine 1gm/5ml.

Levocarnitine is a carrier molecule in the transport of long-chain fatty acids across the inner mitochondrial membrane and thereby delivering substrate for oxidation and subsequent energy production in the form of Adenosine Tri phosphate or ATP. Fatty acids are utilized as an energy substrate in all tissues except the brain. In skeletal and cardiac muscle, fatty acids are the main substrate for energy production. 

Levocarnitine Injection USP is a sterile aqueous solution containing 1 g of levocarnitine per 5 mL vial. The pH is adjusted to 6.0 to 6.5 with hydrochloric acid. Chemically, levocarnitine is (R)-(3-Carboxy-2-hydroxypropyl)trimethyl-ammonium hydroxide, inner salt. It is a white powder with a melting point of 196° to 197°C and is readily soluble in water, hot alcohol, and insoluble in acetone. The pH of a solution (1 in 20) is between 6 to 8 and its pKa value is 3.8. 
Molecular Formula: C7H15NO3                     Molecular Weight: 161.20

Indications

For the acute and chronic treatment of patients with an inborn error of metabolism that results in secondary carnitine deficiency.

Supplemental Levocarnitine may be used in the management of cardiac ischemia and peripheral arterial disease. It is generally indicated for cardio protection. It lowers triglyceride levels and increases levels of HDL-cholesterol. It is used with benefits in those with primary and secondary carnitine deficiency syndromes. There is also evidence of its use in liver, kidney and immune disorders or in diabetes and Alzheimer's disease. There is little evidence that supplemental Levocarnitine boosts energy, increases athletic performance or inhibits obesity. Overall indications may be summarized as follows:

  • Heart Diseases
  • Congestive Heart Failure
  • Kidney Disease
  • Chronic Fatigue Syndrome
  • High Cholesterol
  • Intermittent Claudication
  • Dementia and memory impairment
  • Down Syndrome
  • Male infertility
  • Hyperthyroidism
Dosage

Tablet
Adults: 330 mg two or three times a day depending on clinical response.
Infants and children: Between 50 and 100 mg/kg/day in divided doses, with a maximum of 3 g/day. Dosage should begin at 50 mg/kg/day. The exact dosage will depend on
clinical response.
Solution
Adults: 10 to 30 ml/day. Dosage should start at 10 ml/day in divided doses, and be increased slowly while assessing tolerance and therapeutic response.

Infants and children: 50 to 100 mg/kg/day which is equivalent to 0.5 ml/kg/day. Dosage should start at 50 mg/kg/day, and be increased slowly to a maximum of 3 g/day (30
ml/day) while assessing tolerance and therapeutic response. Solution may be consumed alone or dissolved in drink or other liquid food. Doses should be spaced evenly
throughout the day (every three or four hours) preferably during or following meals and should be consumed slowly in order to maximize tolerance.

Injection

Levocarnitine Injection is administered intravenously. The recommended dose is 50 mg/kg given as a slow 2 to 3 minute bolus injection or by infusion. Often a loading dose is given in patients with severe metabolic crisis followed by an equivalent dose over the following 24 hours. It should be administered q3h or q4h, and never less than q6h either by infusion or by intravenous injection. All subsequent daily doses are recommended to be in the range of 50 mg/kg or as therapy may require. The highest dose administered has been 300 mg/kg.

It is recommended that a plasma carnitine level be obtained prior to beginning this parenteral therapy. Weekly and monthly monitoring is recommended as well. This monitoring should include blood chemistries, vital signs, plasma carnitine concentrations (the plasma free carnitine level should be between 35 and 60 micromoles/liter) and overall clinical condition.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Compatibility and Stability
Levocarnitine Injection USP is compatible and stable when mixed in parenteral solutions of Sodium Chloride 0.9% or Lactated Ringer's in concentrations ranging from 250 mg/500 mL (0.5 mg/mL) to 4200 mg/500 mL (8.0 mg/mL) and stored at room temperature (25°C) for up to 24 hours in PVC plastic bags.

Overdosage There have been no reports of toxicity from levocarnitine overdosage.

Metabolic Disorders
Levocarnitine is easily removed from plasma by dialysis. The intravenous LD50 of levocarnitine in rats is 5.4 g/kg and the oral LD50 of levocarnitine in mice is 19.2 g/kg. Large doses of levocarnitine may cause diarrhea.
Contraindications None known.
Warnings None.
Special Precautions Carcinogenesis, Mutagenesis, Impairment of Fertility
Mutagenicity tests performed in Salmonella typhimurium, Saccharomyces cerevisiae, and Schizosaccharomyces pombe indicate that levocarnitine is not mutagenic. No long-term animal studies have been performed to evaluate the carcinogenic potential of levocarnitine.

Pregnancy
Teratogenic Effects - Pregnancy Category B
Reproductive studies have been performed in rats and rabbits at doses up to 3.8 times the human dose on the basis of surface area and have revealed no evidence of impaired fertility or harm to the fetus due to levocarnitine. There are, however, no adequate and well controlled studies in pregnant women.

Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers
Levocarnitine supplementation in nursing mothers has not been specifically studied.

Studies in dairy cows indicate that the concentration of levocarnitine in milk is increased following exogenous administration of levocarnitine. In nursing mothers receiving levocarnitine, any risks to the child of excess carnitine intake need to be weighed against the benefits of levocarnitine supplementation to the mother. Consideration may be given to discontinuation of nursing or of levocarnitine treatment.
Adverse Drug Reactions Transient nausea and vomiting have been observed. Less frequent adverse reactions are body odor, nausea, and gastritis. An incidence for these reactions is difficult to estimate due to the confounding effects of the underlying pathology.

Seizures have been reported to occur in patients with or without pre-existing seizure activity receiving either oral or intravenous levocarnitine. In patients with pre-existing seizure activity, an increase in seizure frequency and/or severity has been reported.
Pharmacology CLINICAL PHARMACOLOGY
Levocarnitine is a naturally occurring substance required in mammalian energy metabolism. It has been shown to facilitate long-chain fatty acid entry into cellular mitochondria, thereby delivering substrate for oxidation and subsequent energy production. Fatty acids are utilized as an energy substrate in all tissues except the brain. In skeletal and cardiac muscle, fatty acids are the main substrate for energy production.

Primary systemic carnitine deficiency is characterized by low concentrations of levocarnitine in plasma, RBC, and/or tissues. It has not been possible to determine which symptoms are due to carnitine deficiency and which are due to the underlying organic acidemia, as symptoms of both abnormalities may be expected to improve with carnitine. The literature reports that carnitine can promote the excretion of excess organic or fatty acids in patients with defects in fatty acid metabolism and/or specific organic acidopathies that bioaccumulate acyl CoA esters.1-6

Secondary levocarnitine deficiency can be a consequence of inborn errors of metabolism. Levocarnitine may alleviate the metabolic abnormalities of patients with inborn errors that result in accumulation of toxic organic acids. Conditions for which this effect was demonstrated are: glutaric aciduria II, methyl malonic aciduria, propionic acidemia, and medium chain fatty acyl CoA dehydrogenase deficiency.7,8 Autointoxication occurs in these patients due to the accumulations of acyl CoA compounds that disrupt intermediary metabolism. The subsequent hydrolysis of the acyl CoA compound to its free acid results in acidosis that can be life-threatening. Levocarnitine clears the acyl CoA compound by formation of acyl carnitine which is quickly excreted. Levocarnitine deficiency is defined biochemically as abnormally low plasma levels of free carnitine, less than 20 micromole/L at one week post term and may be associated with low tissue and/or urine concentrations. Further, this condition may be associated with a plasma concentration ratio of acylcarnitine/levocarnitine greater than 0.4 or abnormally elevated concentrations of acylcarnitine in the urine. In premature infants and newborns, secondary deficiency is defined as plasma free levocarnitine levels below age-related normal levels.

Pharmacokinetics
In a relative bioavailability study in 15 healthy adult male volunteers Levocarnitine Tablets were found to be bio-equivalent to Levocarnitine Oral Solution. Following 4 days of dosing with 6 tablets of levocarnitine 330 mg bid or 2 g of levocarnitine oral solution bid, the maximum plasma concentration (Cmax) was about 80 micromole/L and the time to maximum plasma concentration (Tmax) occurred at 3.3 hours.

The plasma concentration profiles of levocarnitine after a slow 3 minute intravenous bolus dose of 20 mg/kg of levocarnitine were described by a two-compartment model. Following a single IV administration, approximately 76% of the levocarnitine dose was excreted in urine during the 0 to 24h interval. Using plasma concentrations uncorrected for endogenous levocarnitine, the mean distribution half-life was 0.585 hours and the mean apparent terminal elimination half-life was 17.4 hours.

The absolute bioavailability of levocarnitine from the two oral formulations of levocarnitine, calculated after correction for circulating endogenous plasma concentrations of levocarnitine, was 15.1 ± 5.3% for levocarnitine tablets and 15.9 ± 4.9% for levocarnitine oral solution.

Total body clearance of levocarnitine (Dose/AUC including endogenous baseline concentrations) was a mean of 4.00 L/h.

Levocarnitine was not bound to plasma protein or albumin when tested at any concentration or with any species including the human.9

Metabolism and Excretion
In a pharmacokinetic study where five normal adult male volunteers received an oral dose of [3H-methyl]-L-carnitine following 15 days of a high carnitine diet and additional carnitine supplement, 58 to 65% of the administered radioactive dose was recovered in the urine and feces in 5 to 11 days. Maximum concentration of [3H-methyl]-L-carnitine in serum occurred from 2 to 4.5 hr after drug administration. Major metabolites found were trimethylamine N-oxide, primarily in urine (8% to 49% of the administered dose) and [3H]-y-butyrobetaine, primarily in feces (0.44% to 45% of the administered dose). Urinary excretion of levocarnitine was about 4 to 8% of the dose. Fecal excretion of total carnitine was less than 1% of the administered dose.10

After attainment of steady state following 4 days of oral administration of levocarnitine tablets (1980 mg q 12h) or oral solution (2000 mg q 12h) to 15 healthy male volunteers, the mean urinary excretion of levocarnitine during a single dose interval (12h) was about 9% of the orally administered dose (uncorrected for endogenous urinary excretion).

 

Brand/Product Info


Total Products : 5     
Brand Name Manufacturer/Marketer Composition Dosage Form Pack Size & Price
CARNITAB Beximco Pharmaceuticals Ltd Levocarnitine USP 330mg Tablet 30's: 150.60 MRP
LEVOCAR 330 Square Pharmaceuticals Ltd. Levocarnitine 330mg Tablet 5x6's: 150.90 MRP
LEVOCAR SOLN Square Pharmaceuticals Ltd. Levocarnitine 500mg/5 ml Solution 100 ml: 100.68 MRP
Ocarnix Incepta Pharmaceuticals Limited Levocarnitine USP 330mg Tablet 4x5's :MRP 100 Tk
Ocarnix Solution Incepta Pharmaceuticals Limited Levocarnitine USP 500mg/5ml Solution 100ml :MRP 100 Tk

Gen. MedInfo

Why is this medication prescribed?

Levocarnitine is an amino acid derivative. Levocarnitine is used to treat l-carnitine deficiency when dietary intake is inadequate. This medication is sometimes prescribed for other uses; ask your doctor for more information.

Your health care provider (e.g. doctor) may measure the effectiveness and side effects of your treatment using laboratory tests and physical examinations. It is important to keep all appointments with your doctor and the laboratory. The length of treatment depends on how your symptoms respond to the medication.

Precautions

Before administering levocarnitine,

  • tell your doctor if you are allergic to any drugs.
  • tell your doctor what prescription and nonprescription medications you are taking, including vitamins.
  • tell your doctor if you have or have ever had kidney disease or diabetes.
  • tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking levocarnitine, call your doctor.

Administering your medication

Before you administer levocarnitine injection, look at the solution closely. It should be clear and free of floating material. Gently squeeze the bag or observe the solution container to make sure there are no leaks. Do not use the solution if it is discolored, if it contains particles, or if the bag or container leaks. Use a new solution, but show the damaged one to your health care provider.

It is important that you use your medication exactly as directed. Do not stop your therapy on your own for any reason. Do not change your dosing schedule without talking to your health care provider. Your health care provider may tell you to stop your infusion if you have a mechanical problem (such as a blockage in the tubing, needle, or catheter); if you have to stop an infusion, call your health care provider immediately so your therapy can continue.

Side effects

Levocarnitine may cause side effects. Tell your health care provider if any of these symptoms are severe or do not go away:

  • upset stomach

  • vomiting

  • stomach cramps

  • diarrhea

  • drug-related body odor

Storing your medication

  • Your health care provider will probably give you a several-day supply of levocarnitine at a time. You will be told to store it in the refrigerator.

  • Take your next dose from the refrigerator 1 hour before using it; place it in a clean, dry area to allow it to warm to room temperature.

Store your medication only as directed. Make sure you understand what you need to store your medication properly.

Keep your supplies in a clean, dry place when you are not using them, and keep all medications and supplies out of reach of children. Your health care provider will tell you how to throw away used needles, syringes, tubing, and containers to avoid accidental injury.

In case of emergency/overdose

In case of overdose, consult your doctor. If the victim has collapsed or is not breathing, consult local medical emergency services.

Signs of infection

If you are receiving levocarnitine injection in your vein or under your skin, you need to know the symptoms of a catheter-related infection (an infection where the needle enters your vein or skin). If you experience any of these effects near your intravenous catheter, tell your health care provider as soon as possible:

  • tenderness

  • warmth

  • irritation

  • drai nage

  • redness

  • swelling

  • pain

What other information should I know?

Keep all appointments with your doctor and the laboratory. Your doctor will order certain lab tests to check your response to this medicine.

Do not let anyone else use your medication. If you still have symptoms and need further treatment, consult your doctor.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

Ref:  U.S. National Library of Medicine.


This information is provided for reference only and not a replacement for and should only be used in conjunction with full consultation with a registered medical practitioner. It may not contain all the available information you require and cannot substitute professional medical care, nor does it take into account all individual circumstances. Although great effort has been made to ensure content accuracy, mph-bd shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise.

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