Sigma Tau Carnitene 1g L-carnitine 10 Chewable Tablets

NAME
CARNITENE

PHARMACOTHERAPEUTIC CATEGORY
Agonist of mitochondrial function.

ACTIVE PRINCIPLES
L-carnitine internal salt.

EXCIPIENTS
Solution for injection for intravenous use water for injections. Oral solution 1 g / 10 ml: malic acid, sodium benzoate, sodium saccharin, purified water. Oral solution 2 g / 10 ml: malic acid, sodium benzoate, sodium saccharin, pineapple powder flavor, purified water. Oral solution 1.5 g / 5 ml: sucrose, 70 percent sorbitol (not crystallizable), sodium methyl para-hydroxybenzoate, sodium propylpara-hydroxybenzoate, cherry flavor, black cherry flavor, purified water. Chewable tablets: mint flavor powder, licorice flavor powder, sucrose, magnesium stearate. Solution for infusion with sodium chloride sodium chloride, dilute hydrochloric acid, water pp for injections. Solution for infusion with glucose glucose monohydrate, injectable pp water.

INDICATIONS
Primary and secondary carnitine deficiencies.

CONTRAINDICATIONS / SECONDARY EFFECT
Hypersensitivity to the active substance or to any of the listed excipients; the solution for infusion with sodium chloride is contraindicated in patients with hypernatremia and in hydrosaline plethora; the solution for infusion with glucose is contraindicated in diabetic patients.

DOSAGE
>> Oral solution - chewable tablets. Primary deficiencies and secondary deficiencies to genetic diseases: the oral daily dose depends on age and weight; from 0 to 2 years 150 mg per kg of body weight are recommended, from 2 to 6 years 100 mg per kg, from 6 to 12 years 75 mg per kg; over 12 years and in adults 2 - 4 grams according to the severity of the disease and medical judgment. Secondary hemodialysis deficiencies: 2 - 4 grams per day. The oral solutions must be taken only after dilution, the one in the single-dose containers must be diluted in a glass of water. >> Solution for injection for intravenous use - Solution for infusion. Deficiencies secondary to hemodialysis: 2 grams at the end of the dialysis session administered slowly intravenously. The 2.5 g dosage can be indicated in dialysis patients over 1 year. 5 ml ampoules: intravenous administration should be performed slowly (2-3 minutes). 100 ml and 250 ml bags: administration by infusion should be 3 ml per minute, equal to approximately 30 minutes for 100 ml bags and 1 hour and 20 minutes for 250 ml bags. Patients with renal insufficiency: Patients with severe renal impairment should not be treated with chronic oral administration of high doses of levocarnitine because it can induce an accumulation of the potentially toxic metabolites trimethylamine (TMA) and trimethylamine-N-oxide. (TMAO). Elderly patients: No special precautions and changes in the dosage of the medicinal product are necessary in elderly patients. The safety profile observed in clinical trials is similar in elderly and young adults. Diabetic patients: the administration of L-carnitine in diabetic patients treated with insulin or with oral hypoglycemic agents, improving the utilization of glucose, could lead to hypoglycemia phenomena. Therefore, in these subjects the glycaemia must be checked regularly in order to promptly provide, if necessary, to the adjustment of the hypoglycemic therapy.

STORAGE
There are no special storage precautions to be observed. Solution for infusion with glucose: Do not store above 25 degrees C.

WARNINGS
The administration of L-carnitine in diabetic patients on insulin treatment or with oral hypoglycemic agents, improving the use of glucose, could cause hypoglycemia phenomena. Therefore, in these subjects the glycaemia must be kept under frequent control in order to promptly provide for the adjustment of hypoglycemic therapy. Intravenous administration should be performed slowly (2-3 minutes). The drug solution for infusion should be used with great caution in patients with congestive heart failure, severe renal insufficiency and in clinical states in which there is edema with saline retention, in patients receiving corticosteroid or corticotropin drugs. Continuous administration without the addition of potassium may cause hypokalaemia. Monitor fluid and electrolyte balance. In patients with a history of convulsive activity, administration of L-carnitine may increase the incidence and / or severity of seizures. In patients with predisposing conditions, treatment with L-carnitine could trigger seizures. The safety and efficacy of oral levocarnitine have not been demonstrated in patients with renal insufficiency. Chronic oral administration of high doses of levocarnitine in patients with severe renal impairment or end stage renal insufficiency (ESRD) and dialysis may induce an accumulation of the potentially toxic metabolites trimethylamine (TMA) etrimethylamine-N-oxide (TMAO), in how much these metabolites are normally excreted in the urine. This phenomenon does not occur with intravenous administration. Since L-carnitine is a physiological product, it does not present any risk of addiction or dependence. Very rare cases of increased INR have been reported in patients receiving coumarin drugs concomitantly. The INR - or other appropriate coagulation tests - should be checked weekly until the values stabilize and then monthly, in patients taking anticoagulants together with the drug. The oral solution 1.5 g / 5 ml and the chewable tablets 1 g contain sucrose. The oral solution 1.5 g / 5 ml contains, sorbitol and para-hydroxy-benzoates (methyl para-hydroxybenzoate and propyl para-hydroxybenzoate) as preservatives. The 1 g / 100 mL solution for infusion contains 15.2 mmol (or 350 mg) sodium per 100 mL bag and the 2.5 g / 250 mL solution for infusion contains 38 mmol (or 875 mg) sodium per bag of 250 ml. The 1 g / 100 ml glucose solution for infusion contains 5.5 g of glucose per dose (100 ml bag) and the 2.5 g / 250 ml glucose solution for infusion contains 13.75 g of glucose per dose ( 250 ml bag).

INTERACTIONS
An interaction between L-carnitine and coumarin drugs cannot be excluded. Very rare cases of increased INR have been reported in patients receiving coumarin drugs concomitantly. INR - or other suitable coagulation tests - should be checked weekly until the values stabilize and then monthly, in patients taking anticoagulants together with the drug. Concomitant administration of the drug with drugs that induce hypocarnitinemia due to increased loss of renal carnitine (valproic acid, prodrugs containing pivalic acid, cephalosporins, cisplatin, carboplatin and ifosfamide) can reduce the availability of L-carnitine.

SIDE EFFECTS
Adverse reactions from any source (clinical studies, literature and post-marketing) are listed in the table below by MedDRA system organ class. Furthermore, the corresponding frequency category for each adverse reaction is based on the following convention (CIOMS III): very common (> = 1/10), common (> = 1/100, <1/10), uncommon (> = 1 / 1,000, <1/100), rare (> = 1 / 10,000, <1 / 1,000) very rare (<1 / 10,000), not known. Nervous system disorders. Uncommon: headache; not known: convulsions, dizziness. Cardiac disorders: Not known: palpitations. Vascular pathologies. Uncommon: hypertension, hypotension. Respiratory, thoracic and mediastinal disorders. Not known: dyspnoea. Gastrointestinal disorders. Common: vomiting, nausea, diarrhea, abdominal pain; uncommon: dysgeusia, dyspepsia, dry mouth. Skin and subcutaneous tissue disorders. Uncommon: abnormal skin odor; not known: itching, rash. Musculoskeletal and connective tissue disorders. Uncommon: muscle spasms; not known: myasthenia, muscle tension. General disorders and administration site conditions. Uncommon: chest pain, feeling strange, pyrexia, injection site reaction. Diagnostic tests. Uncommon: increased blood pressure; very rare: increased INR. The reporting of suspected adverse reactions that occur after the authorization of the drug is important, as it allows continuous monitoring of the benefit / risk ratio of the drug.

PREGNANCY AND BREASTFEEDING
In clinical trials conducted in fertility, favorable effects have been identified and no safety concerns have been identified. Reproduction studies were conducted in rats and rabbits. There was no evidence of a teratogenic effect in either species. In rabbits, but not rats, there was a statistically insignificant higher number of post-implantation losses at the highest dose tested (600 mg / kg per day) than in the control group. The significance of these findings in humans is unknown. No adequate clinical studies have been performed in pregnant women. The drug should be given during pregnancy if the benefit to the mother outweighs the potential risks to the fetus. L-carnitine is a normal component of human milk. The use of L-carnitine supplementation in nursing mothers has not been studied. The drug should be used by the nursing mother if the benefit to the mother outweighs any potential risk to the baby from excessive exposure to carnitine.