Carlonas

General characteristics. Structure:

Active ingredient: 5 mg or 10 mg of enalapril of a maleate.

Excipients: lactose anhydrous, starch corn, cellulose microcrystallic PH 102, aerosil, Natrii hydrocarbonas, magnesium stearate.

Anti-hypertensive drug.

Pharmacological properties:

Pharmacodynamics. Carlonas is AKF inhibitor of long action which is applied to treatment of arterial hypertension and chronic heart failure. The active metabolite of enalapril – enalaprilat, prevents transformation of inactive angiotensin I into angiotensin II and eliminates its vasoconstrictive action. Decrease in concentration of plasma and fabric angiotensin II results. Owing to inhibition of AKF arterial pressure at the expense of a vazodilatation of arteries and veins decreases.

It has no significant effect on cordial emission and on a stroke output. Reduces the general peripheric resistance of vessels (GPRV), reduces an afterload and preloading, reduces pressure in the right auricle and a small circle of blood circulation. Drug reduces a hypertrophy of a left ventricle. At use of drug the tone of the taking-out arterioles of balls of kidneys decreases, the intraglomerular hemodynamics thereby improves that interferes with development of a diabetic nephropathy.

Pharmacokinetics. At oral administration about 70% of enalapril are soaked up in digestive tract. Enalapril is metabolized in a liver in an active form - enalaprilat. The peak of concentration of enalaprilat in serum is observed in 3 – 4 hours.

Enalapril is distributed in fabrics and fluid mediums. Gets through a placental barrier, it is allocated with breast milk. 50–60% of enalapril contact proteins of plasma. The elimination half-life of enalapril makes 11 hours. At a chronic renal failure this period is extended. 60-70% of enalapril of a maleate at a single dose of 10 mg are removed with urine, 30% - with excrements in 24-48 hours in the form of enalapril and enalaprilat.

The anti-hypertensive effect proceeds within 24 hours. However the maximum therapeutic effect is reached after several weeks of use.

Indications to use:

- arterial hypertension, including renovascular;

- prevention of symptomatic heart failure at patients with asymptomatic dysfunction of a left ventricle;

- chronic heart failure (as a part of complex therapy).

Route of administration and doses:

Drug is appointed orally. Meal does not influence absorption of drug from digestive tract.

Treatment of arterial hypertension. An initial dose - 5 mg once a day. Usually appointed maintenance dose of enalapril of a maleate makes 10-20 mg a day once or having divided into two receptions. At arterial hypertension of heavy degree the dose can be increased to 40 mg a day (the maximum daily dose).

It is recommended to stop reception of diuretics in 2-3 days prior to drug use. If cancellation of diuretics is impossible, then the initial dosage of drug of Carlonas makes 2,5 mg a day. Control of renal function and level of potassium in serum is recommended.

Renal failure    

Renal function	Clearance of creatinine of ml/min.	Initial dose of mg/day
Normal function of kidneys	> 80 ml/min.	5 mg
Easy degree of MONDAY	£80> 30 ml/min.	5 mg
MONDAY of average and heavy degree	£30 ml/min.	2,5 mg
Dialysis therapy		2,5 mg in days of carrying out dialysis

At a hemodialysis. 2,5 mg of enalapril in days of carrying out dialysis are recommended to the patients who are on dialysis therapy, and in days between dialysis drug should be accepted under control of arterial pressure.

Chronic heart failure. Carlonas it can be used as a part of complex therapy. An initial dose - 2,5 mg once a day.

Usually the dose of Carlonas at chronic heart failure makes 2,5-20 mg twice a day. The maximum daily dose makes 40 mg.

At chronic a cordial nedostatochnochta the noticeable clinical effect is observed at prolonged treatment – 6 months and more.

Asymptomatic dysfunction of the left ventricle / Heart failure. An initial dose - 2,5 mg twice a day.

The maintenance dose can be increased to the standard 20 mg a day once or, depending on portability, divide into two receptions. It is necessary to establish a drug dosage on the basis of the ABP level and under control of the attending physician. It is recommended to carry out such selection of a dose within 2-4 weeks.

The recommended mode of selection of a dose: 1 week: from 1 to 3 day – 2,5 mg a day once (to observe special precautionary measures in case of patients with a renal failure or being on treatment by diuretics), from 4 to 7 day – 5 mg a day in two steps; The 2nd week – 10 mg once or in two steps; The 3rd week – 20 mg in a single dose or for two receptions.

Till the beginning of therapy it is necessary to carry out by drug careful control of arterial pressure and renal function.

Prolonged treatment. Duration of treatment depends on efficiency of therapy.

Features of use:

As a result of inhibition a renin – angiotensin – aldosteronovy system, at some patients changes of function of kidneys can be observed. At patients with heart failure whose renal function can influence activity a renin – angiotensin – aldosteronovy system, treatment by AKF inhibitors, including Carlonas, can lead to an oliguria, the progressing azotemia and, in rare instances, to an acute renal failure and a possible lethal outcome.

At some patients with arterial hypertension and heart diseases, without visible renovascular disturbances, increase in level of urea and creatinine in blood, usually insignificant and fast-passing, especially can be observed if Carlonas it is applied with diuretics. It is especially often observed at patients with earlier existing renal failure. In these cases it is necessary to cancel drug or to lower a dose of diuretics and/or Carlonas.

Increase in level of potassium (more than 5,7 meq/l) is observed in 1% of cases at patients with arterial hypertension. In most cases it were separate indicators which changed during treatment. At 0.28% of patients the hyperpotassemia was caused by drug withdrawal. During clinical tests at 3.8% of patients with heart failure the hyperpotassemia was observed, but it did not serve as the drug withdrawal reason.

Risk factors of development of a hyperpotassemia include: a renal failure, a diabetes mellitus and combined use of the drugs containing potassium salts which have to be used carefully with drug of Carlonas.

Level of plasma potassium usually within norm, however hyperpotassemia cases are observed.

Carlonas can increase potassium level in blood at patients with a renal failure. In addition drugs of potassium are not recommended, to patients with a renal failure as it can lead to increase in potassium in blood. However, at inevitability of sharing of these substances, care and конроль potassium level in blood is necessary.

Liver failure. At treatment by APF inhibitors cholestatic jaundice occasionally can be observed up to a fulminant hepatic necrosis (sometimes with a lethal outcome). The pathogeny is not clear. At emergence of simtom of a liver failure (jaundice or clear increase in level of liver enzymes) it is necessary to cancel APF inhibitors and to carry out the corresponding treatment.

The patients who are on treatment by a hemodialysis method. When using membranes of high-flukh (for example, "AN 69") when carrying out dialysis and simultaneous use of APF inhibitors it was reported about anaphylactoid reactions. In such cases it is necessary to use other type of membranes for dialysis or to appoint anti-hypertensive drug of other class.

Presumably, because of suppression of destruction of endogenous bradikinin, at use of AKF inhibitors, long dry cough which always passes after cancellation of drugs is observed. The cough connected using AKF inhibitors should be considered at differential diagnosis of cough.

Features of influence of medicine on ability to manage the vehicle or potentially dangerous mechanisms

With care appoint drug to the patients who are engaged in potentially dangerous types of activity requiring special attention.

Side effects:

Very often (≥ 1/10):

- a vision disorder, in the form of a sight illegibility;

- cough;

- dizziness;

- nausea;

- adynamy.

Often (≥ 1/100-<1/10):

- hypotonia (including orthostatic hypotonia), a faint, thorax pain, disturbances of a cordial rhythm, stenocardia, tachycardia;

- headache, depression;

- fatigue;

- asthma;

- diarrhea, abdominal pains, change of flavoring perception;

- skin rash, Quincke's disease of the person, extremities, lips, language, glottis and/or throat;

- hyperpotassemia, increase in level of creatinine.

Sometimes (≥ 1/1 000 - <1/100):

- orthostatic hypotonia, heartbeat, a myocardial infarction or a cerebral stroke, presumably as a result of excessive falling of arterial pressure at patients with existence of high risk factors;

- confusion of consciousness, drowsiness, sleeplessness, nervousness, dizziness, paresthesias;

- heartbeat;

- intestinal impassability, pancreatitis, vomiting, dyspepsia, a lock, lack of appetite, the phenomenon of irritation of a stomach, dryness in a mouth, a round ulcer;

- anemia (including aplastic and hemolitic anemia);

- rhinorrhea, pharyngalgia and osiplost, bronchospasm/asthma;

- perspiration, itch, urticaria, alopecia;

- renal failure, renal failure, proteinuria;

- impotence;

- muscular spasms, inflows, sonitus, indisposition, fever;

- increase in level of urea, hyponatremia, hypoglycemia.

Seldom (≥ 1/10 000 - <1/1000):

- liver failure, hepatitis, cholestasia, jaundice, increase in activity of "hepatic" transaminases, hyperbilirubinemia;

- neutropenia, decrease in hemoglobin and hematocrit, thrombocytopenia, agranulocytosis, oppression of marrow, pancytopenia, increase in lymph nodes, autoimmune diseases;

- change of character of dreams, sleep disorders;

- Reynaud's syndrome;

- pulmonary infiltrates, rhinitis, allergic alveolitis / eosinophilic pneumonia;

- stomatitis / aphthous sores, glossitis;

- a liver failure, hepatitis – hepatocellular or cholestatic, including a hepatic necrosis, a cholestasia (including jaundice);

- multiformny erythema, Stephens-Johnson's syndrome, exfoliative dermatitis, toxic epidermal necrolysis, pemphigus, erythrosis;

- oliguria;

- gynecomastia;

- increase in level of liver enzymes, increase in indicators of bilirubin of serum.

Very seldom (<1/10 000):

- Quincke's disease of intestines.

Frequency is unknown:

- Parkhon's syndrome (syndrome of inadequate secretion of antidiuretic hormone).

It was reported about a symptom complex which can be followed by some or all from the following side effects: fever, serositis, vasculitis, миалгией / miositis, arthralgia/arthritis, increase in a caption of anti-nuclear antibodies (ANA), increase by SOE, eosinophilia and leukocytosis. Skin rash, a photosensitization or other skin manifestations can take place.

Interaction with other medicines:

At simultaneous use of CARLONAS 5 and CARLONAS 10 with:

- other anti-hypertensive substances, such as a beta blockers, Methyldopa, antagonists of calcium and diuretics, anti-hypertensive effect of drug amplifies;

- adrenoblockers, the patient has to be under careful observation of the doctor;

- propranolol, bioavailability Carlona can decrease, but it has no clinical value;

- lithium drugs, slow down its removal and concentration of lithium in blood can increase;

- non-steroidal anti-inflammatory drugs, leads to weakening of hypotensive action;

- the vazodilatator containing nitrates, or anesthetics can exponentiate hypotensive effect;

- diuretics, the probability of development of a hyperpotassemia decreases;

- tricyclic antidepressants, neuroleptics, means for the general anesthesia strengthen arterial hypotension;

- sympathomimetics, leads to easing of hypotensive effect;

- antidiabetic medicines hypoglycemic action amplifies;

- alcohol the hypotensive effect amplifies.

Contraindications:

- hypersensitivity to enalapril and other components of drug, or to other APF inhibitors;

- the hereditary or Quincke's disease arising after use of inhibitors of an angiotensin-converting enzyme in the anamnesis;

- bilateral stenosis of renal arteries or renal artery stenosis of the only kidney;

- hyperpotassemia;

- porphyria;

- primary hyper aldosteronism;

- pregnancy and period of a lactation;

- children's and teenage age up to 18 years.

Overdose:

Symptoms - the expressed arterial hypotension

Treatment - intravenous administration of isotonic solution of sodium of chloride. Symptomatic therapy. Carlonas it can be brought out of the general blood-groove by a hemodialysis.

Storage conditions:

To store at a temperature not above 25 °C, in the dry, protected from light place. To store in the place, unavailable to children! Period of storage 2 years. Not to apply after a period of storage.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets place in a blister strip packaging from a white film of PVH/PE/PVDH and printing aluminum foil.

On the 2nd blister strip packagings together with the instruction on a medical use in the state and Russian languages place in a pack from a cardboard with the hologram of manufacturing firm.