nal insufficiency. Chronic administration of high doses of oral L-carnitine in patients with severely compromised renal function or in end stage renal disease (ESRD) patients on dialysis may result in an accumulation of the potentially toxic metabolites, trimethylamine (TMA) and trimethylamine-N-oxide (TMAO), since these metabolites are usually excreted in the urine. This situation has not been observed following intravenous administration of L-carnitine.
4.5 Interaction with other medicinal products and other forms of interaction
There are no known interactions.
4.6 Pregnancy and lactation
Reproductive studies were performed in rats and rabbits. There was no evidence of a teratogenic effect in either species. In the rabbit but not in the rat there was a statistically insignificant greater number of post implantation losses at the highest dose tested (600mg/kg daily) as compared with control animals. The significance of these findings in man is unknown. There is no experience of use in pregnant patients with primary systemic carnitine deficiency.
Taking into account the serious consequences in a pregnant woman who has primary systemic carnitine deficiency stopping treatment, the risk to the mother of discontinuing treatment seems greater than the theoretical risk to the foetus if treatment is continued.
Levocarnitine is a normal component of human milk. Use of levocarnitine supplementation in nursing mothers has not been studied.
4.7 Effects on ability to drive and use machines
None known.
4.8 Undesirable effects
Various mild gastro-intestinal complaints have been reported during the long term administration of oral levocarnitine, these include transient nausea and vomiting, abdominal cramps and diarrhoea.
Decreasing the dosage often diminishes or eliminates drug related patient body odour or gastro-intestinal symptoms when present. Tolerance should be monitored very closely during the first week of administration and after any dosage increase.
4.9 Overdose
There have been no reports of toxicity from levocarnitine overdosage. Overdosage should be treated with supportive care.
5. Pharmacological properties
5.1 Pharmacodynamic properties
ATC Code: A16AA01 (Amino acids and derivatives)
L-Carnitine is present as a natural constituent in animal tissues, micro-organisms and plants. In man the physiological metabolic requirements are met both by the consumption of food containing carnitine and the endogenous synthesis in the liver and kidneys from lysine with methionine serving as the methyl donor. Only the L-isomer is biologically active, playing an essential role in lipid metabolism as well as in the metabolism of ketone bodies as branched chain-amino-acids. L-Carnitine as a factor is necessary in the transport of long-chain fatty acids into the mitochondria - facilitating the oxidation of fatty acids rather than their incorporation into triglycerides. By releasing CoA from its thioesters, through the action of CoA; carnitine acetyl transferase, L-carnitine also enhances the metabolic flux in the Kreb's cycle; with the same mechanism it stimulates the activity of pyruvate dehydrogenase and in skeletal muscle, the oxidation of branched-chain amino acids. L-Carnitine is thus involved, directly or indirectly in several pathways so that its availability should be an important factor controlling not only the oxidative utilisation of fatty acids an
