Carnitor 1 g Chewable Tablets

L-Carnitine inner salt 1 g

For a full list of excipients, see section 6.1.

White, round, standard convex tablets, approximately 22.3 mm diameter.

Indicated for the treatment of primary and secondary carnitine deficiency in adults and children over 12 years of age.

For oral administration only.

Adults and children over 12 years of age

The tablets should be given in divided doses.

It is advisable to monitor therapy by measuring free and acyl carnitine levels in both plasma and urine.

The management of inborn errors of metabolism

The dosage required depends upon the specific inborn error of metabolism concerned and the severity of presentation at the time of treatment. However, the following can be considered as a general guide.

An oral dosage of up to 200mg/kg/day in divided doses (2 to 4) is recommended for chronic use in some disorders, with lower doses sufficing in other conditions. If clinical and biochemical symptoms do not improve, the dose may be increased on a short-term basis. Higher doses of up to 400mg/kg/day may be necessary in acute metabolic decompensation or the i.v. route may be required.

Haemodialysis - maintenance therapy

If significant clinical benefit has been gained by a first course of intravenous Carnitor then maintenance therapy can be considered using 1 g per day of Carnitor orally. On the day of the dialysis oral Carnitor has to be administered at the end of the session.

Hypersensitivity to any constituent of the product.

There is limited experience of use in patients with primary and secondary systemic carnitine deficiency suffering from renal failure.

The chewable tablets contain sucrose. This must be considered when treating diabetics or patients who are following diets to reduce calorie intake.

There are no known interactions.

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.

None known.

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.

There have been no reports of toxicity from levocarnitine overdosage. Overdosage should be treated with supportive care.

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 and ketone bodies but also that of glucose and some amino acids.

The absorbed L-carnitine is transported to various organ systems via the blood. The presence of membrane-bound proteins in several tissues including red blood cells that bind carnitine, suggest that a transport system in the blood and a cellular system for the collective uptake is present in several tissues. Tissue and serum carnitine concentration depend on several metabolic processes, carnitine bio-synthesis and dietary contributions, transport into and out of tissues, degradation and excretion may all affect tissue carnitine concentrations.

Absorption

L-carnitine is absorbed by the mucosal cells of the small intestine and enters the blood stream relatively slowly; the absorption is probably associated with an active transluminal mechanism.

The apparent systemic availability after oral administration is limited (<10%) and variable.

Distribution

Absorbed L-carnitine is transported to various organ systems via the blood; it is thought that a transport system in the blood and a cellular system for selective uptake is involved.

Excretion

L-carnitine is excreted mainly in the urine and is variable. The excretion is directly proportional to the blood levels.

Metabolism

L-carnitine is metabolised to a very limited extent.

L-Carnitine is a naturally occurring body substance in human beings, plants and animals. Carnitor products are used to bring the level of L-carnitine in the body up to those found naturally. Appropriate pre-clinical studies have been undertaken and show no signs of toxicity at normal therapeutic levels.

Compressible sugar (DIPAC)

Magnesium stearate (E572)

Mint flavour atomised 1 x 2000

Liquorice flavour 1 x 2000.

None known.

5 years.

Store below 25°C.

Strip packaging consisting of aluminium (30 microns) and low density polyethylene (30 microns). Strip size 2 tablets.

Pack size 10, 30, 50 and 100 tablets.

None

Sigma-Tau Industrie Farmaceutiche Riunite SpA,

Viale Shakespeare 47-00144,

Rome, Italy.

PL 08381/0001

25 August 1994

February 2009