Levocarnitine

Mechanism of Action

Quaternary ammonium compound found in all mammalian tissue (particularly striated muscle)

Important for lipid catabolism; essential for FFA transport from cytosol to mitochondria where they are oxidized

Pharmacokinetics

Bioavailability: 10-20%

Distribution half-life: 0.585 hr

Half-life elimination : 17.4 hr

Peak plasma time: (PO) 3.3 hr

Peak plasma concentration: (PO) 80 umol/L

Protein Bound: None

Total Body Clearance: 4 L/hr

Metabolism: Metabolized to trimethylamine-N-oxide and gamma-butyrobetaine

Excretion: Urine (76%); feces (<1%)

Levocarnitine may be found in some form under the following brand names:

• Carni Q-Gel Forte

• Carnitor

Take levocarnitine exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The Levocarnitine dose your doctor recommends will be based on the following (use any or all that apply):

• the condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication
• your weight
• your height
• your age
• your gender

Levocarnitine is available in the following doses:

• Levocarnitine 100 Mg/ml Oral Solution
• Levocarnitine 200 Mg/ml Injectable Solution
• Levocarnitine 250 Mg Oral Capsule
• Levocarnitine 330 Mg Oral Tablet

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• a seizure (convulsions).

Common side effects may include:

• stomach pain;

• nausea, vomiting; or

• diarrhea.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General

• Secondary Carnitine Deficiency Associated with an Inborn Error of Metabolism.

• Obtain plasma carnitine concentrations prior to initiation of parenteral therapy.1

• Perform weekly and monthly monitoring of blood chemistries, vital signs, plasma carnitine concentrations, and overall clinical condition of patient.1

• Plasma free carnitine concentrations should be 35–60 mcmol/L.1

• End-stage Renal Disease Patients undergoing Hemodialysis

• Obtain blood levocarnitine concentrations prior to therapy to establish levocarnitine deficiency.3

• Some experts recommend evaluating clinical response at 3-month intervals following initiation of drug, considering dosage adjustment to lowest effective dosage once desired outcome for specific manifestation has been attained, and discontinuing drug if clinical improvement has not occurred within 9–12 months.7

Administration

Administer orally (as a solution or tablets), by direct IV injection, or by IV infusion.1 2

Oral Administration

Solutions may be administered alone or dissolved in beverages or other liquid foods to reduce taste fatigue.2 Slowly administer solution in evenly spaced doses throughout the day (i.e., at least 3 or 4 hours apart), preferably during or following meals, to maximize tolerance; adverse GI reactions may result from rapid administration of solution.2

Periodically monitor blood chemistries, vital signs, plasma carnitine concentrations, and overall clinical condition of patient.2

Closely monitor tolerance to drug during first week of administration and following any dosage increases.2

IV Administration

For solution compatibility information, see Compatibility under Stability.

Vials are for single use only.1

Rate of Administration

Secondary carnitine deficiency associated with an inborn error of metabolism, direct IV injection: Slowly over 2–3 minutes.1

Carnitine deficiency in patients with end-stage renal disease undergoing dialysis, direct IV injection: Slowly over 2–3 minutes into the venous return line after each dialysis session.1

Dosage

Decreasing the dosage of oral levocarnitine may diminish or eliminate drug-related patient body odor or GI symptoms if present.2 11

Pediatric Patients

Primary Systemic Carnitine Deficiency Oral

Pediatric patients (≤18 years of age): Initially, 50 mg/kg daily, given in 2 or 3 divided doses (administer each dose at least 3 or 4 hours apart); slowly increase dosage while assessing tolerance and therapeutic response.2 3 (See General and also Administration, under Dosage and Administration.)

Usual recommended dosage range is 50–100 mg/kg daily, given in 2 or 3 divided doses (administer each dose at least 3 or 4 hours apart), up to a maximum total daily dosage of 3 g.2 3

Exact dosage based on clinical response.2 Administer increased dosages with caution and only when clinical and biochemical considerations make it seem likely that increased dosages will be of benefit.2

Secondary Carnitine Deficiency Associated with an Inborn Error of Metabolism Oral

Pediatric patients (≤18 years of age): Initially, 50 mg/kg daily, given in 2 or 3 divided doses (administer each dose at least 3 or 4 hours apart); slowly increase dosage while assessing tolerance and therapeutic response.2 3 (See General and also Administration, under Dosage and Administration.)

Usual recommended dosage range is 50–100 mg/kg daily, given in 2 or 3 divided doses (administer each dose at least 3 or 4 hours apart), up to a maximum total daily dosage of 3 g.2 3

Exact dosage depends on clinical response.2 Administer increased dosages with caution and only when clinical and biochemical considerations make it seem likely that increased dosages will be of benefit.2

IV

Pediatric patients (≤18 years of age): 50 mg/kg every 3 or 4 hours administered by slow, direct IV injection over 2–3 minutes or by IV infusion; do not administer less frequently than every 6 hours.1 3 Subsequent total daily dosage of approximately 50 mg/kg, adjusted as required and given in divided doses (i.e., every 3 or 4 hours), is recommended.1

In pediatric patients (≤18 years of age) with severe metabolic crisis, a loading dose has often been administered, followed by an equivalent dose over the following 24 hours.1 3 These patients underwent close supervision and monitoring of plasma levocarnitine concentrations, with subsequent dosage adjusted accordingly.3 In individual case reports, highest total daily dosage administered has been 300 mg/kg.1 3

Carnitine Deficiency in Patients with End-stage Renal Disease Undergoing Dialysis IV

Pediatric patients (≤18 years of age): Initially, 10–20 mg/kg (preferably 10 mg/kg) of dry body weight administered by slow, direct IV injection over 2–3 minutes into the venous return line after each dialysis session.1 3

Initiation of therapy may be prompted by trough (i.e., predialysis) plasma levocarnitine concentrations that are below normal (40–50 mcmol/L).1

Adjust dosage based on trough (i.e., predialysis) plasma levocarnitine concentrations; dosage reductions (e.g., to 5 mg/kg after dialysis) may be initiated as early as the third or fourth week of therapy.1 3

Adults

Primary Systemic Carnitine Deficiency Therapy with Levocarnitine Tablets Oral

990 mg 2 or 3 times daily, depending on clinical response.2

Therapy with Levocarnitine Oral Solution Oral

Initially, 1 g daily, given in 2 or 3 divided doses (administer each dose at least 3 or 4 hours apart); slowly increase dosage while assessing tolerance and therapeutic response.2 3 (See General and also Administration, under Dosage and Administration.)

Usual recommended dosage range for a 50-kg patient is 1–3 g daily, given in 2 or 3 divided doses (administer each dose at least 3 or 4 hours apart).2 3

Administer increased dosages with caution and only when clinical and biochemical considerations make it seem likely that increased dosages will be of benefit.2

Secondary Carnitine Deficiency Resulting from an Inborn Error of Metabolism Therapy with Levocarnitine Tablets Oral

990 mg 2 or 3 times daily, depending on clinical response.2

Therapy with Levocarnitine Oral Solution Oral

Initially, 1 g daily, given in 2 or 3 divided doses (administer each dose at least 3 or 4 hours apart); slowly increase dosage while assessing tolerance and therapeutic response.2 3 (See General and also Administration, under Dosage and Administration.)

Usual recommended dosage range for a 50-kg patient is 1–3 g daily, given in 2 or 3 divided doses (administer each dose at least 3 or 4 hours apart).2 3

Administer increased dosages with caution and only when clinical and biochemical considerations make it seem likely that increased dosages will be of benefit.2

IV

50 mg/kg every 3 or 4 hours administered by slow, direct IV injection over 2–3 minutes or by IV infusion; do not administer less frequently than every 6 hours.1 3 Subsequent total daily dosage of approximately 50 mg/kg, adjusted as required and given in divided doses (i.e., every 3 or 4 hours), is recommended.1 3

In patients with severe metabolic crisis, a loading dose often has been administered, followed by an equivalent dose during the following 24 hours.1 3 These patients underwent close supervision and monitoring of plasma levocarnitine concentrations, with subsequent dosage adjusted accordingly.3 In individual case reports, highest total daily dosage administered has been 300 mg/kg.1 3

Carnitine Deficiency in Patients with End-stage Renal Disease Undergoing Diaysis IV

Initially, 10–20 mg/kg of dry body weight administered by slow, direct IV injection over 2–3 minutes into the venous return line after each dialysis session.1

Initiation of therapy may be prompted by trough (i.e., predialysis) plasma levocarnitine concentrations that are below normal (40–50 mcmol/L).1

Adjust dosage based on trough (i.e., predialysis) plasma levocarnitine concentrations; dosage reductions (e.g., to 5 mg/kg after dialysis) may be initiated as early as the third or fourth week of therapy.1

Prescribing Limits

Pediatric Patients

Primary Carnitine Deficiency Oral

Pediatric patients (≤18 years of age): In individual case reports, maximum 3 g daily.2 3

Secondary Carnitine Deficiency Associated with an Inborn Error of Metabolism Oral

Pediatric patients (≤18 years of age): In individual case reports, maximum 3 g daily.2 3

IV

Pediatric patients (≤18 years of age): In individual case reports, total daily dosage of up to 300 mg/kg has been administered.1 3

Carnitine Deficiency in Patients with End-stage Renal Disease Undergoing Dialysis IV

Doses >20 mg/kg have not been shown to provide additional benefit.7 3

Adults

Secondary Carnitine Deficiency Associated with an Inborn Error of Metabolism IV

In individual case reports, total daily dosage of up to 300 mg/kg has been administered.1 3

Carnitine Deficiency in Patients with End-stage Renal Disease Undergoing Dialysis IV

Doses >20 mg/kg have not been shown to provide additional benefit.7

Special Populations

No special population dosage recommendations at this time.1 2 (See Renal Impairment under Cautions.)

Consult your pharmacist.

Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

Notes

No monograph available at this time.

Missed Dose

Consult your pharmacist.

Storage

Consult your pharmacist.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2016. Copyright(c) 2016 First Databank, Inc.

Applies to levocarnitine: capsule, powder, solution, tablet, wafer

Along with its needed effects, levocarnitine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor as soon as possible if any of the following side effects occur while taking levocarnitine:

More common

• High blood pressure

Less common

• Fast heartbeat
• fever

Rare

• Seizures

Some side effects of levocarnitine may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Abdominal or stomach cramps
• diarrhea
• headache
• nausea or vomiting

Less common

• Abdominal discomfort
• body odor
• depression
• dizziness
• impaired vision
• loss of appetite or weight
• swelling in hands, lower legs, and feet
• tingling sensation
• weakness