Simdax

Simdax is a non-glycosidic type of cardiotonic drug.

In people with heart failure, the positive inotropic and vasodilatory properties of levosimendan cause an increase in myocardial contractility and a decrease in post- and preload without adversely affecting diastolic activity. [1]

Levosimendan helps to activate the affected myocardium in individuals who have undergone thrombolysis or coronary angioplasty. [2]

Indications Simdax

It is used for short-term therapy in the active stage of severe decompensated CHF (when standard treatment is ineffective, and when an inotropic effect is required).

Release form

The release of the therapeutic substance is made in the form of a concentrate for the infusion liquid - inside 5 ml vials; in a pack - 1 such bottle.

Pharmacodynamics

Levosimendan potentiates the sensitivity exhibited by contractile proteins to calcium by synthesizing with cardiotroponin C using a calcium-dependent method. The substance potentiates contractile force without disturbing ventricular relaxation. At the same time, the drug opens ATP-sensitive potassium channels inside the smooth muscles of the vessels, which stimulates the expansion of the vessels of the common and coronary arteries, as well as common veins. Levosimendan selectively inhibits PDE-3 in vitro.

Pharmacodynamic properties were studied in volunteers and patients with unstable and stable heart failure. At the same time, it turned out that the effectiveness of the drug depends on the size of the portion administered by the intravenous method at a saturation dosage (within 3-24 μg / kg), as well as through continuous infusion (in a portion of 0.05-0.2 μg / kg). [3]

In comparison with placebo, Simdax increases cardiac output with stroke volume, heart rate and ejection fraction, and in addition reduces diastolic and systolic blood pressure, pressure inside the terminal pulmonary capillaries and right atrium, as well as peripheral vascular resistance.

Infusion of the medication increases coronary circulation in people recovering from coronary operations, and also improves myocardial perfusion in people with heart failure. With the development of these advantages, the oxygen consumption of the myocardium does not increase. Therapy with the use of drugs significantly reduces the indicators of circulating endothelin-1 in persons with CHF. This avoids an increase in plasma catecholamines when the infusion is administered at the recommended rate.

Pharmacokinetics

Levosimendan has linear pharmacokinetic parameters within the dosage range of 0.05-0.2 μg / kg / minute.

Distribution processes.

The drug distribution volume is approximately 0.2 l / kg. The active substance is 97-98% involved in protein synthesis (mainly with albumin). In OR-1855 with OR-1896, the level of the degree of synthesis of the metabolic element and protein is 39% and 42%, respectively.

Exchange processes.

Metabolic processes of levosimendan are carried out by conjugation with cyclic or N-acetylated conjugates (cysteine and cysteinylglycine). About 5% is involved in intraintestinal metabolism through reduction to the substance aminophenylpyridazinone (OR-1855), which then (after the reabsorption process) is involved in metabolism using N-acetyltransferase to the active metabolic component OR-1896.

The metabolic product OR-1896 is slightly higher in people with genetically higher rates of acetylation. But with the introduction of the recommended portions, this does not affect the clinical hemodynamic effect.

Excretion.

The clearance level of levosimendan is approximately 3 ml / minute / kg, and the half-life is approximately 1 hour.

With urine, 54% of the dosage is excreted, and with feces - 44%. Over 95% of the portion is excreted over a period of 7 days. Small amounts of unchanged levosimendan (<0.05% of the dosage) are excreted in the urine. Circulating metabolic products OR-1855 with OR-1896 are formed and excreted at a low rate.

Plasma indicator Cmax of metabolic components is noted after 2 days from the end of the Simdax infusion. The term for the half-life of metabolic elements is 75-80 hours. Components OR-1855 with OR-1896 are involved in conjugation or intrarenal filtration and are excreted mainly in the urine.

Dosing and administration

Simdax is used exclusively in a hospital setting - when there is equipment within walking distance to monitor and assess the patient's condition; healthcare providers should also be experienced in the use of inotropic substances.

The medicinal concentrate is diluted before infusion. The drug should be administered intravenously (peripheral and central veins).

Like any other parenteral substance, the dissolved fluid is carefully examined before administration to exclude the presence of solids or a change in shade.

The portion size and duration of the course are selected individually, taking into account the response to therapy and the clinical condition of the patient.

Therapy begins with a saturation portion of 6-12 μg / kg, which is administered over a period of at least 10 minutes, followed by continuous infusion at a rate of 0.1 μg / kg per minute. A decrease in the dosage of saturation to 6 μg / kg is prescribed to persons who are simultaneously treated with intravenous treatment with the introduction of inotropic or vasodilating drugs.

The largest portions of saturation cause a powerful hemodynamic response (possibly due to a short-term increase in the number of side effects). The clinically noticeable response of the patient to therapy is assessed during the introduction of a portion of saturation or in the period of 0.5-1 hour from the moment the dosage is changed.

In case of an excessive patient's response to the infusion (development of tachycardia or a decrease in blood pressure), the rate of fluid administration can be reduced to 0.05 μg / kg per minute (or the infusion is stopped). With good tolerance of the initial dosage, it is required to potentiate the hemodynamic effect - the infusion rate is increased to 0.2 μg / kg per minute.

The duration of the infusion in the severe stage of decompensated CHF is usually 24 hours. After the completion of the procedure, there were no symptoms of addiction or the phenomenon of reverse action. The hemodynamic effect lasts at least 24 hours and is observed up to 9 days after the completion of the 24-hour procedure.

Persons with impaired renal function.

It is required to use the medicine very carefully in mild to moderate stages of the disorder. Persons with severe renal dysfunction (CC values <30 ml / minute) should not be used.

People with liver failure.

In mild to moderate form of the disorder, Simdax is used very carefully. With severe dysfunction, it is not prescribed.

• Application for children

It is forbidden to prescribe a medication in pediatrics (under the age of 18), because there is only limited information regarding its use at this age.

Use Simdax during pregnancy

There is no experience with the use of levosimendan during pregnancy. The medication is prescribed only in situations where the likely benefits are more expected than the risks to the development of the fetus.

Due to the fact that there is no information regarding whether Simdax is excreted with breast milk, when the drug is administered, HS should be abandoned.

Contraindications

The main contraindications:

• severe intolerance to levosimendan or additional components of drugs;
• a strong decrease in blood pressure and tachycardia;
• significant obstacles of a mechanical type that affect the blood filling of the heart ventricles or impede blood outflow from them;
• renal dysfunction of severe type (CC level is <30 ml / minute);
• severe forms of hepatic dysfunction;
• a history of torsades de Pointes.

Side effects Simdax

Among the side signs:

• metabolic disorders: hypokalemia often develops;
• mental disorders: insomnia often appears;
• problems with the function of the NA: headaches most often occur. Dizziness is also common;
• symptoms associated with the work of the CVS: most often, ventricular tachycardia develops or the blood pressure indicator decreases. Tachycardia, HF, atrial fibrillation, extrasystoles, myocardial ischemia and ventricular extrasystoles also often occur;
• disorders of the gastrointestinal tract: diarrhea, nausea, constipation or vomiting often develop;
• systemic manifestations and signs in the area of the injection: symptoms of intolerance;
• laboratory test results: a decrease in hemoglobin values is often noted.

Ventricular fibrillation has been reported with post-marketing use.

Overdose

Poisoning with levosimendan can cause tachycardia and a decrease in blood pressure. In clinical tests, the decrease in blood pressure values associated with levosimendan was corrected using vasoconstrictors (for example, dopamine (in people with CHF) or adrenaline (in people after surgery in the heart)). Due to an excessive decrease in the filling pressure of the heart ventricles, there may be a limitation of the clinical response to the medication - this disorder can be removed with the help of parenteral fluid administration. Large doses of drugs during an infusion lasting more than 24 hours increase the heart rate, and sometimes cause prolongation of the QT-interval.

In case of an overdose with levosimendan, continuous monitoring of ECG readings, repeated monitoring of serum electrolytes, and invasive hemodynamic monitoring are performed. Intoxication can increase the plasma parameters of the active metabolic element, which can lead to a stronger and more prolonged effect relative to the pulse rate - in this regard, it is necessary to extend the observation period.

Interactions with other drugs

Levosimendan is very carefully prescribed together with other vasoactive substances for intravenous injection - as this increases the likelihood of lowering blood pressure.

The medication without loss of medicinal efficacy is used in combination with digoxin and β-blockers.

The combination of the drug with isosorbide mononitrate in volunteers caused a significant increase in orthostatic collapse.

Storage conditions

Simdax should be kept out of the reach of small children. The temperature level is within the 2-8 ° С mark. Do not freeze the medicinal liquid.

Shelf life

Simdax can be applied within a 24-month term from the date of manufacture of the pharmaceutical product.

Analogs

Drugs analogs are Dopamine, Dobutamine with Levosimendan, Dopamine and Kudesan.

Reviews

Simdax receives generally conflicting reviews. It is quite effective in the treatment of CHF of the decompensated type, but at the same time it has a fairly large number of side symptoms (mainly vomiting, dizziness, a strong decrease in blood pressure and cardiac arrhythmias). In addition, of the minuses, the rather high cost of the medication is noted.