Carnitene 1 g/10 ml 10 single dose oral solution

In ottemperanza all'articolo 118 “autorizzazione della pubblicità presso il pubblico” del decreto legislativo 24 aprile 2006, numero 219

INDICATIONS

Primary and secondary carnitine deficiencies.

ACTIVE INGREDIENTS

CARNITENE 1 g/5 ml solution for injection for intravenous use One vial contains: Active ingredient: L-carnitine internal salt 1.00 g CARNITENE 2 g/5 ml solution for injection for intravenous use One vial contains: Active ingredient: L-carnitine internal salt 2.00 g CARNITENE 1 g/10 ml oral solution A single-dose container contains: Active ingredient: L-carnitine internal salt 1.00 g CARNITENE 2 g/10 ml oral solution A single-dose container contains: Active ingredient: L-carnitine internal salt 2.00 g CARNITENE 1.5 g/ 5 ml oral solution 100 ml of solution contains: Active ingredient: L-carnitine internal salt 30 g Excipients with known effects: sucrose, sorbitol (E420), sodium methyl para-hydroxybenzoate (E219), sodium propyl para-hydroxybenzoate (E217). CARNITENE 1 g chewable tablets One chewable tablet contains: Active ingredient: L-carnitine internal salt 1.00 g Excipient with known effects: sucrose. CARNITENE 1 g/100 ml solution for infusion with sodium chloride One bag contains: active component: L-carnitine internal salt 1.00 g. Excipient with known effects: sodium chloride. CARNITENE 2.5 g/250 ml solution for infusion with sodium chloride One bag contains: active component: L-carnitine internal salt 2.50 g. Excipient with known effects: sodium chloride. CARNITENE 1 g/100 ml solution for infusion with glucoseOne bag contains: active component: L-carnitine internal salt 1.00 g. Excipient with known effects: glucose CARNITENE 2.5 g/250 ml solution for infusion with glucose One bag contains: active component: L-carnitine internal salt 2.50 g. Excipient with known effects: glucose For the complete list of excipients see section 6.1.

EXCIPIENTS

Injectable solution for intravenous use water for injections. 1 g/10 ml oral solution: d–l malic acid, sodium benzoate, sodium saccharin, purified water. 2 g/10 ml oral solution: d–l malic acid, sodium benzoate, sodium saccharin, pineapple flavoring powder, purified water. 1.5 g/5 ml oral solution: sucrose, sorbitol 70 percent (non-crystallizable), sodium methyl para-hydroxybenzoate, sodium propyl para-hydroxybenzoate, cherry flavouring, black cherry flavouring, purified water. Chewable tablets mint flavor powder, liquorice flavor powder, sucrose, magnesium stearate. Solution for infusion with sodium chloride sodium chloride, diluted hydrochloric acid, water p.p. injectable.Solution for infusion with glucose glucose monohydrate, water p.p. injectable.

CONTRAINDICATIONS AND SIDE EFFECTS

Hypersensitivity to the active substance or to any of the excipients listed in paragraph 6.1. Sodium chloride infusion solution is contraindicated in patients with hypernatremia and in hydrosaline plethora. Glucose infusion solution 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 pathology and the doctor's judgment.Deficiencies secondary to hemodialysis 2 – 4 grams per day. Oral solutions must be taken only after dilution, the one in single-dose containers must be diluted in a glass of water. Injectable solution 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 may be indicated in patients with dialysis age greater than 1 year. 5 ml vials Intravenous administration should be performed slowly (2–3 minutes). 100 ml and 250 ml bags Administration by infusion must be 3 ml per minute, equal to approximately 30 minutes for 100 ml bags and 1 hour and 20 minutes for 250 ml bags. Special populations Patients with renal failure Patients with severely impaired renal function should not be treated with chronic oral administration of high doses of levocarnitine because it may induce an accumulation of the potentially toxic metabolites trimethylamine (TMA) and trimethylamine-N-oxide (TMAO), see section 4.4. Elderly patients No particular precautions and dosage changes of CARNITENE 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 oral hypoglycaemics, improving the use of glucose, could cause hypoglycaemic phenomena. Therefore, in these subjects, blood sugar levels must be checked regularly in order to promptly adjust the hypoglycaemic therapy if necessary (see section 4.4).

CONSERVATION

There are no special precautions to be observed for storage. CARNITENE solution for infusion with glucose: Do not store above 25°C.

WARNINGS

The administration of L-carnitine in diabetic patients treated with insulin or oral hypoglycaemics, improving the use of glucose, could cause hypoglycaemic phenomena. Therefore, in these subjects, blood sugar levels must be kept under frequent control in order to promptly adjust the hypoglycemic therapy. Intravenous administration should be performed slowly (2–3 minutes). CARNITENE solution for infusion should be used with great caution in patients with congestive heart failure, severe renal insufficiency and in clinical states in which edema with salt retention exists, in patients being treated with corticosteroids or corticotropin drugs. Continuous administration without addition of potassium may cause hypokalemia. Monitor fluid balance and electrolytes. In patients with a history of convulsive activity, the administration of L-carnitine may increase the incidence and/or severity of convulsive seizures. In patients with predisposing conditions, treatment with L-carnitine could trigger convulsive 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 severely impaired renal function or end-stage renal disease (ESRD) and on dialysis may induce an accumulation of the potentially toxic metabolites trimethylamine (TMA) and trimethylamine-N-oxide (TMAO), as these metabolites are normally excreted in the urine. This phenomenon does not occur with intravenous administration (see paragraph 5.2). Since L-carnitine is a physiological product, it does not present any risk of habituation or dependence. Very rare cases of increased INR (International Normalized Ratio) have been reported in patients undergoing concomitant therapy with coumarin drugs (see sections 4.8 and 4.5). The INR - or other appropriate coagulation tests - should be monitored weekly until values ​​stabilize and subsequently monthly, in patients taking anticoagulants together with CARNITENE. CARNITENE 1.5 g/5 ml oral solution and CARNITENE 1 g chewable tablets contain sucrose: patients suffering from rare hereditary problems of fructose intolerance, glucose-galactose malabsorption, or sucrase isomaltase insufficiency should not take this medicine. It can be harmful to your teeth. Furthermore, this should be taken into account in diabetic patients and in those undergoing low-calorie diets. CARNITENE 1.5 g/5 ml oral solution contains sorbitol. Patients suffering from rare hereditary problems of fructose intolerance should not take this medicine. CARNITENE 1.5 g/5 ml oral solution contains para-hydroxy-benzoates (methyl para-hydroxybenzoate and propyl para-hydroxybenzoate) as preservatives: these may cause allergic reactions (even delayed). CARNITENE 1 g/100 ml solution for infusion contains 15.2 mmol (or 350 mg) sodium per 100 ml bag and CARNITENE 2.5 g/250 ml solution for infusion contains 38 mmol (or 875 mg) sodium per 250 ml bag. To be taken into consideration in people with reduced kidney function or who follow a low sodium diet. CARNITENE 1 g/100 ml solution for infusion with glucose contains 5.5 g of glucose per dose (100 ml bag) and CARNITENE 2.5 g/250 ml solution for infusion with glucose contains 13.75 g of glucose per dose (250 ml bag): patients suffering from rare hereditary problems of glucose-galactose malabsorption should not take this medicine. To be taken into consideration in people suffering from diabetes mellitus.

INTERACTIONS

An interaction between L-carnitine and coumarin drugs cannot be excluded. Very rare cases of increased INR (International Normalized Ratio) have been reported in patients undergoing concomitant therapy with coumarin drugs (see sections 4.8 and 4.4). The INR - or other appropriate coagulation tests - should be monitored weekly until the values ​​stabilize and subsequently monthly, in patients taking anticoagulants together with CARNITENE (see section 4.4). Concomitant administration of CARNITENE with drugs that induce hypocarnitinemia due to increased loss of renal carnitine (valproic acid, prodrugs containing pivalic acid, cephalosporins, cisplatin, carboplatin and ifosfamide) may reduce the availability of L-carnitine.

SIDE EFFECTS

Adverse reactions from all sources (clinical studies, literature and post-marketing) are listed in the table below by MedDRA system organ class. Within each class, adverse reactions are classified according to frequency. Within each frequency class, adverse reactions are classified in order of decreasing severity. 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 (the frequency is not can be defined on the basis of available data)

Nervous system disorders.

Uncommon: Headache.

Not known: Convulsions *, Dizziness.

Cardiac diseases.

Not known: Palpitations.

Vascular pathologies.

Uncommon: Hypertension, Hypotension.

Respiratory, thoracic and mediastinal disorders.

Not known: Dyspnoea.

Gastrointestinal disorders.

Common: Vomiting, Nausea, Diarrhoea, Abdominal pain.

Uncommon: Dysgeusia, Dyspepsia, Dry mouth.

Pathologies of the skin and subcutaneous tissue.

Uncommon: Abnormal skin odor **.

Not known: Itching, Rash.

Pathologies of the musculoskeletal system and connective tissue.

Uncommon: Muscle spasms.

Not known: Myasthenia***, Muscle tension.

Systemic pathologies and conditions relating to the administration site.

Uncommon: Chest pain, Feeling strange, Pyrexia, Injection site reaction****.

Diagnostic tests.

Uncommon: Blood pressure increased.

Very rare: Increased INR*****.

* Cases of seizures have been reported in patients, with or without a history of seizure activity, who have received oral or intravenous L-carnitine. The administration of L-carnitine can increase the incidence and/or severity of convulsive attacks. In patients with predisposing conditions, treatment with L-carnitine could trigger convulsive seizures. ** In subjects with severely compromised renal function or on dialysis, chronic oral administration of L-carnitine can give rise to accumulation of TMA and TMAO in the blood resulting in trimethylaminuria, a pathological condition characterized by a strong "fishy smell" present in the patient's urine, breath and sweat (see paragraph 5.2) *** Mild myasthenic symptoms have been reported in uremic patients **** Reactions at the injection site have been reported only in i.v. administration. ***** Very rare cases of increased INR (International Normalized Ratio) have been reported in patients undergoing concomitant therapy with coumarin drugs (see sections 4.4 and 4.5). Reporting of suspected adverse reactions Reporting suspected adverse reactions that occur after authorization of the medicine is important, as it allows continuous monitoring of the benefit/risk balance of the medicine. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system at www.agenziafarmaco.gov.it/it/responsabili.

OVERDOSE

Overdose and long-term administration of L-carnitine have been associated with diarrhea. L-carnitine is easily removed from the blood by dialysis.

PREGNANCY AND BREASTFEEDING

Fertility In clinical studies conducted in fertility, favorable effects were identified and no safety concerns were identified. Pregnancy Reproduction studies were conducted 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 non-significant greater number of post-implantation losses, at the maximum dose tested (600 mg/kg per day), compared to the control group. The significance of these findings in humans is unknown. Adequate clinical studies have not been carried out in pregnant women. CARNITENE should be administered during pregnancy if the benefit to the mother outweighs the potential risk to the fetus. Breastfeeding L-carnitine is a normal component of human milk. The use of L-carnitine supplementation in breastfeeding mothers has not been studied. CARNITENE should be used by the breastfeeding mother if the benefit to the mother outweighs any potential risk to the baby due to excessive exposure to carnitine.

EFFECTS ON DRIVING ABILITY

CARNITENE does not alter the ability to drive or use machines.