CARNITOR PRODUCT MONOGRAPH - NATALIA

Question 1

What are the indications for oral Carnitor?

Answer 1

1. Treatment of primary systemic carnitine deficiency; 2. Treatment of secondary carnitine deficiency due to inborn error of metabolism

Question 2

What are the indications for IV Carnitor?

Answer 2

1. Treatment of primary systemic carnitine deficiency; 2. Treatment of secondary carnitine deficiency due to inborn error of metabolism; 3. Prevention/treatment of deficiency in patients with ESRD on dialysis

Question 3

What are the most common adverse reactions of oral Carnitor?

Answer 3

N/V/D/abdo cramps – dose/concentration dependent; Mild myasthenia in uremic patients; Fishy body-odor – dose dependent; Headache

Question 4

What are the most common adverse reactions of IV Carnitor?

Answer 4

N/V/gastritis, body odor – rare

Question 5

Drug/food/herb Interactions

Answer 5

Use with Vitamin K antagonists (warfarin) may increase INR. Information based on multiple reported cases but no apparent mechanism identified and no confirmatory studies exist. Levocarnitine has been shown to modulate platelet activation and aggregation (UpToDate).

Question 6

Use in pregnancy

Answer 6

No harm to fetus in animal studies when given 3.8x the human dose; no human studies, so use only if necessary.

Question 7

How is Carnitor supplied (product strength/formulation)

Answer 7

Oral tabs: 330 mg; Oral solution: 1g/100mL (100mg/mL), sucrose-free available; IV: 1g/5mL (200mg/mL), single use vial

Question 8

Dosing for oral tabs

Answer 8

Adults: 990mg BID-TID ; Peds: 50-100mg/kg/day (max 3g/day) divided BID-TID

Question 9

Dosing for oral liquid

Answer 9

1-3g/day (=10-30mL/day) for 50kg person, start at 1g/day and increase as needed

Question 10

Dosing of IV in metabolic disorders

Answer 10

50mg/kg bolus loading dose, repeat in 24 hours, then q3-4h

Question 11

Dosing of IV in ESRD patients on hemodialysis

Answer 11

20mg/kg of dry weight as 2-3min bolus after dialysis (some centers give 1g dose, not in monograph); After ~2 months (or once plasma levels normalize), maintain at 5mg/kg after each dialysis session

Question 12

When should IV Carnitor be started for HD patients

Answer 12

Start after patient has been on dialysis for 6 months

Question 13

Preparation/stability of IV Carnitor

Answer 13

Mix in NS 0.9% or RL at concentration between 250mg/500mL (0.5mg/mL) and 4,000mg/500mL (0.8mg/mL); Store at room temperature (25C) up to 24 hrs in PVC bag; Vial is single use only

Question 14

Mechanism of Action/Function of L-carnitine

Answer 14

Carnitine is a naturally occurring substance required for energy metabolism. It facilitates long-chain fatty acids entry into mitochondria for oxidation and energy production. Fatty acids are the main substrate for energy in skeletal and cardiac muscle.

Question 15

Monitoring (when to draw level, when to recheck level) in metabolic disorders, ESRD on hemodialysis

Answer 15

Metabolic disorders: check plasma carnitine level prior to starting IV therapy, then monitor weekly-monthly; target 35-60mmol/L trough. ESRD (not in monograph, National Kidney Foundation guidelines): base treatment of clinical signs and symptoms, evaluate response at 3-month intervals and discontinue if no clinical improvement noted within 9-12 months (Eknoyan 2003).