Carnimet

INTERNATIONAL NONPROPRIETARY NAME: Levocarnitine / Levocarnitine

DRUG FORM: solution for intravenous administration of 200 mg/ml.

COMPOSITION:

1 ml contains:

Active substance: levocarnitine – 200.00 mg;

Excipients: 1M hydrochloric acid solution, water for injection.

PHARMACOTHERAPEUTIC GROUP

Aminoacids and their derivatives

ATC Code: A16AA01

PHARMACOLOGICAL PROPERTIES

PHARMACODYNAMICS

Levocarnitine is a derivative of 3-hydroxy-4-trimethylaminobutanoic acid involved into normal energy metabolism. Participates in transport of long chain fatty acids through the inner membrane into mitochondria where they undergo β-oxidation process with a large amount of metabolic energy formation in a form of ATP.

Primary levocarnitine deficiency occurs due to a congenital genetic disorder in levocarnitine biosynthesis or its transport and absorption mechanisms.

Systemic levocarnitine deficiency is characterized by a low concentration of levocarnitine in the blood, red blood cells and/or tissues.

Secondary levocarnitine deficiency is registered in hemodialysis patients as well as in case of parenteral nutrition. Levocarnitine deficiency can occur in newborns, especially in premature infants.

Carnitine deficiency results in triglycerides and free fatty acids plasma level increase, ketogenesis and a decrease in accumulation of fat in the liver and muscles. Chronic carnitine deficiency (mainly in primary deficiency) can result in hypoglycemia, myasthenia gravis, hypotension, lethargy, liver enlargement, hepatic encephalopathy, hepatic coma, cardiomegaly, congestive heart failure, cardiac arrest, neurological disorders, children’ growth and development disorders.

Indications for use:

Primary and secondary carnitine deficiency in adults and children including newborns and infants.

Secondary carnitine deficiency in hemodialysis patients.

Suspicion of secondary carnitine deficiency in patients with long-term hemodialysis occurred in the following cases:

- severe persistent muscle cramps and/or hypotensive episodes in dialysis;

- energy deficiency resulted in a significant negative impact on life quality;

- muscle weakness and/or myopathy;

- cardiopathy;

- anemia or uremia, not responded to treatment with erythropoietin or required high doses of erythropoietin;

- loss of muscle mass.

DOSAGE AND ADMINISTRATION:

The drug should be administered slowly, intravenously within 2-3 minutes.

Drug administration in congenital metabolic disorders

During the therapy it is recommended to control carnitine and acyl-carnitine level in plasma and urine.

The required dose depends on congenital metabolic disorder specificity and severity of disease manifestations.

In case of acute decompensation the recommended dose can be up to 100 mg/kg per day given in 3-4 injections. If necessary, higher doses can also be prescribed although side effects, in particular diarrhea, may increase.

Secondary carnitine deficiency in hemodialysis patients

Before the therapy it is advisable to check the plasma carnitine level.

Secondary carnitine deficiency is diagnosed in case when the ratio of acyl-carnitine to free carnitine in plasma is higher than 0.4 and/or free carnitine concentration is less than 20 μmol/L.

The dose of 20 mg/kg should be administered intravenously (bolus) at the end of each dialysis session. The overall response should be determined by monitoring acyl-carnitine and free carnitine plasma levels and patient’s condition assessment. Carnitine content normalization in muscle tissue and cardiomyocytes occurs approximately in 3 months with a normal carnitine plasma concentration establishment. When carnitine administration is stopped, its level will certainly begin to decline again.

The necessity for a repeated intensive course of treatment should be evaluated by quantitative determination of plasma carnitine at regular intervals and by monitoring of the patient condition.

Hemodialysis – supportive therapy

After an intensive course of drug therapy the maintenance oral dose of levocarnitine 1000 mg once a day. On dialysis day i/v dose of 1000 mg should be injected immediately after the next session completion.

Children

The drug is used in children from the day of birth, including premature babies.

SIDE EFFECT

Adverse reactions in treatment with levocarnitine have not been observed when prescribed by the doctor.

Adverse reactions are classified based on the degree of incidence: rarely (≥1/10,000, <1/1000), very rare (<1/10 000) and frequency of incidence is unknown (cannot be determined according to the data available).

Blood and lymphatic system: the frequency is unknown – increased platelet aggregation (at high doses of levocarnitine) in dialysis.

Metabolism and nutrition: the frequency is unknown – an increase in triglycerides plasma concentration in dialysis.

Nervous system: very rare - headache, dizziness and visual disturbances after i/v administration of the drug at high doses and high flow rate.

Rare:

- nausea, vomiting, abdominal pain, diarrhea (dose reduction results in side effects elimination);

- muscle weakness in patients with uremia;

- cramps;

- allergic reactions;

- at high i/v flow rate pain may occur along the vein, disappearing with a decrease in i/v flow rate.

CONTRAINDICATIONS

Hypersensitivity to the drug components

Overdose

There is no data on levocarnitine toxicity in case of overdose. In case of overdose general strategy should be applied.

The drug is administered intravenously, slowly (within 2-3 minutes).

In case of increased glucose utilization levocarnitine therapy in diabetic patients on insulin or oral hypoglycemic therapy may increase hypoglycemia.

It is necessary to monitor the glucose plasma level for immediate hypoglycemic therapy regulation (if needed).

Levocarnitine therapy PO safety and efficacy cannot be evaluated in patients with renal failure. Long-term therapy with high doses of levocarnitine PO in patients with various renal function disorders or at last stage of kidney diseases during hemodialysis can lead to accumulation of toxic metabolites, trimethylamine and trimethylamine N-oxide as these metabolites are excreted in the urine. This situation is not observed with intravenous levocarnitine administration.

Use in pregnancy and lactation.

Experimental reproduction studies have shown any teratogenic effect. There is no data on levocarnitine therapy in pregnant women with a primary deficiency of levocarnitine. When canceling Carnimet therapy it is necessary to take into account prevalence of risk for the mother over the theoretical risk to the fetus. Levocarnitine is a normal component of the breast milk. There is no data on levocarnitine administration in nursing mothers.

Effect on ability to drive and operate machinery

Carnimet does not affect the ability to drive and operate machinery.

INTERACTION WITH OTHER DRUGS

Carnimet administration in patients with diabetes on insulin or oral hypoglycemic drugs therapy can cause hypoglycemia due to increased glucose uptake. Therefore for this category of patients during levocarnitine therapy plasma glucose levels should be constantly monitored to correct hypoglycemic therapy regimen.

Glucocorticosteroids contribute in drug accumulation in the tissues (except for the liver). Lipoic acid, anabolic steroids enhance the effect of levocarnitine.

STORAGE CONDITIONS:

Store in a place protected from moisture at a temperature not above 25°C.

Keep out of reach of children!

SHELF LIFE:

Shelf life is 4 years. Should not be uses after the expiration date indicated on the label.

PRESCRIPTION STATUS

By prescription

PACKAGING

5 ml ampoules made of dark glass of class I. Ampules with a white colour break ring.

Manufacturer Information

Foreign production and trade unitary enterprise “Reb-Pharma”, 223216, Republic of Belarus, Minsk region, Chervensky district, Smilovichi, Sadovaya st., 1, tel./fax: (+375) 17 240 26 35,