Isacardin, 1.25 mg/dose 300 doses 15 ml

Peripheral vasodilator with predominant effect on venous vessels. It stimulates the formation of nitric oxide (endothelial relaxing factor) in the vascular endothelium, causing activation of intracellular guanylate cyclase, the consequence of which is an increase of cyclic guanosine monophosphate (cGMP), mediator of vasodilation.

Limits myocardial oxygen demand by reducing preload (decreases left ventricular end-diastolic volume (EDV) and reduces systolic wall tension). It has coronary dilator effect. It acts on peripheral arteries and veins. Relaxation of the veins leads to a decrease in venous return to the heart (preload), which reduces the filling pressure of the left ventricle. There is also (although to a lesser extent) dilation of arterial vessels, which is accompanied by a decrease in BP, a decrease in PPS (post-load).

The decrease in pre- and post-load leads to a decrease in myocardial oxygen consumption. By improving oxygen delivery to ischemic areas, it reduces the area of myocardial damage. Reduces blood flow to the right atrium, reduces pressure in the small circle of circulation and regresses the symptoms of pulmonary edema. It promotes redistribution of coronary blood flow in favor of subendocardial zones, especially in atherosclerosis of coronary arteries (mainly large ones). Vasodilatation of collateral arteries may improve the blood supply to the myocardium. Increases exercise tolerance in patients with CHD, angina pectoris.

Limiting myocardial oxygen consumption and improving oxygen delivery to ischemic areas, reduces the area of myocardial damage, also relaxes the smooth muscles of the bronchi, gastrointestinal tract, biliary and urinary tract.

Dilates cerebral vessels, dura mater, which may be accompanied by headache. As with other nitrates, cross-tolerance develops.

After withdrawal (interruption of treatment), sensitivity to it is quickly restored. After spraying on the oral mucosa, the effect is evident in 30 seconds and lasts 15-120 minutes.

Pharmacokinetics

The absorption is high. Bioavailability through the oral mucosa is 60%. Blood plasma protein binding – 30%. T_1/2 is 60 min. It is metabolized in the liver to two active metabolites – isosorbide-5-monononitrate, which is 75-85%, T_1/2 is 5 h and isosorbide-2-monononitrate, which is 15-25% with T_1/2 2.5 h.

The drug is excreted by the kidneys (almost completely as metabolites).

Indications

relief and prevention of angina attacks, incl. before physical activity;
acute myocardial infarction (including complicated by acute left ventricular failure);
condition after myocardial infarction.

Pharmacological effect

Peripheral vasodilator with a predominant effect on venous vessels. Stimulates the formation of nitric oxide (endothelial relaxing factor) in the vascular endothelium, which causes activation of intracellular guanylate cyclase, resulting in an increase in cyclic guanosine monophosphate (cGMP), a mediator of vasodilation.

Reduces myocardial oxygen demand by reducing preload (reduces end-diastolic volume (EDV) of the left ventricle and reduces the systolic tension of its walls). Has a coronary dilating effect. Acts on peripheral arteries and veins. Relaxation of the veins results in decreased venous return to the heart (preload), which reduces left ventricular filling pressure. Also, (albeit to a lesser extent) dilation of arterial vessels occurs, which is accompanied by a decrease in blood pressure and a decrease in peripheral vascular resistance (afterload).

Reduced pre- and afterload leads to a decrease in myocardial oxygen consumption. By improving oxygen delivery to ischemic areas, it reduces the area of ​​myocardial damage. Reduces blood flow to the right atrium, helps reduce pressure in the pulmonary circulation and regression of symptoms of pulmonary edema. Promotes the redistribution of coronary blood flow in favor of subendocardial zones, especially with atherosclerosis of the coronary arteries (mainly large ones). Vasodilation of collateral arteries may improve myocardial blood supply. Increases exercise tolerance in patients with coronary artery disease and angina pectoris.

By reducing myocardial oxygen consumption and improving oxygen delivery to ischemic areas, it reduces the area of ​​myocardial damage and also relaxes the smooth muscles of the bronchi, gastrointestinal tract, biliary and urinary tracts.

Dilates blood vessels in the brain and dura mater, which may be accompanied by headaches. As with other nitrates, cross-tolerance develops.

After cancellation (break in treatment), sensitivity to it is quickly restored. After spraying onto the oral mucosa, the effect appears within 30 seconds and lasts 15–120 minutes.

Pharmacokinetics

Absorption is high. Bioavailability through the oral mucosa is 60%. Connection with blood plasma proteins – 30%. T1/2 is 60 min. Metabolized in the liver to two active metabolites – isosorbide-5-mononitrate, whose share is 75–85%, T1/2 – 5 hours and isosorbide-2-mononitrate, which is 15-25% with T1/2 2.5 hours.

The drug is excreted by the kidneys (almost entirely in the form of metabolites).

Special instructions

During therapy, monitoring of blood pressure and heart rate is necessary. Abrupt withdrawal of the drug should be avoided and the dose should be reduced gradually. Frequent administration and high doses may cause the development of tolerance, in which case it is recommended to discontinue it for 24–48 hours, or after 3–6 weeks of regular use, take a break for 3–5 days, replacing at this time the drug Izacardin®, a sublingual spray dosed with other antianginal agents. Particularly careful medical supervision is necessary in acute myocardial infarction with reduced ventricular filling pressure. The solution contains about 85% ethanol. During treatment with Isacardin® dosed sublingual spray, the consumption of ethanol (alcohol) should be avoided.

Impact on the ability to drive vehicles and other mechanisms. When using the drug Izacardin®, dosed sublingual spray, you must be careful when driving vehicles and machinery (risk of dizziness).

Active ingredient

Isosorbide dinitrate

Composition

1 bottle (300 doses):

Active substance:

isosorbide dinitrate aqueous (in terms of 100% isosorbide dinitrate) – 0.375 g,

(1 dose contains 1.25 mg isosorbide dinitrate):

Excipients: macrogol 400 (polyethylene oxide 400) – 1.8 g; ethanol 96% – up to 15 ml.

Pregnancy

The use of Isacardin® sublingual dosage spray during pregnancy is possible only in cases where the expected benefit outweighs the potential risk to the fetus and child, and should be carried out under the supervision of a physician. If it is necessary to use isosorbide dinitrate during breastfeeding, it is recommended to stop breastfeeding, because There is information about the penetration of nitrates into breast milk. If it is necessary to urgently use the drug Isacardin® dosed sublingual spray, for example, to relieve an attack of angina, it is necessary to monitor the child for the development of possible side effects.

Contraindications

– acute circulatory disorder (shock, collapse);

– severe arterial hypotension (systolic blood pressure below 90 mm Hg, diastolic blood pressure below 60 mm Hg);

– severe hypovolemia;

– cardiogenic shock, if it is impossible to correct the end-diastolic pressure of the left ventricle using intra-aortic counterpulsation or drugs with a positive inotropic effect; – hypertrophic obstructive cardiomyopathy, constrictive pericarditis, cardiac tamponade;

– severe aortic, subaortic and mitral stenosis;

– cerebral hemorrhage;

– severe anemia;

– simultaneous use of PDE5 inhibitors (including sildenafil, vardenafil, tadalafil) – the risk of a pronounced decrease in blood pressure;

– age under 18 years (efficacy and safety have not been established);

– hypersensitivity to nitrates or other components of the drug.

With caution:

– with low filling pressure of the left ventricle, incl. in acute myocardial infarction;

– with aortic or mitral stenosis;

– with a tendency to orthostatic reactions (a sharp decrease in blood pressure when changing body position);

– for diseases accompanied by increased intracranial pressure (including hemorrhagic stroke, traumatic brain injury);

– in case of severe renal failure;

– with liver failure (risk of developing methemoglobinemia);

– with hyperthyroidism;

– with angle-closure glaucoma;

– in old age;

– with insufficient and malnutrition;

– toxic pulmonary edema.

Side Effects

Possible side effects are listed below by body system and frequency of occurrence: very often (more than 1/10); often (more than 1/100 and less than 1/10); uncommon (more than 1/1000 and less than 1/100), rare (more than 1/10000 and less than 1/1000); very rare (less than 1/10000), frequency unknown (it is not possible to determine the frequency of development based on available data).

From the side of the central nervous system: very often – headache; often – dizziness, drowsiness, blurred vision.

From the cardiovascular system: often – orthostatic hypotension, reflex tachycardia; infrequently – paradoxical intensification of angina attacks, collapse (accompanied by bradyarrhythmia and fainting), transient hypoxemia due to the relative redistribution of blood flow to hypoventilated alveolar areas (in patients with coronary artery disease can lead to myocardial hypoxia).

From the digestive system: often – burning of the tongue; infrequently – nausea, vomiting; very rarely – heartburn.

From the skin: infrequently – allergic skin reactions (including skin rash), flushes of blood to the skin of the face; very rarely – angioedema, Stevens-Johnson syndrome; frequency unknown – exfoliative dermatitis.

Other: often – asthenia. It is possible to develop tolerance, incl. cross to other nitrates.

Interaction

It is possible to enhance the hypotensive effect of the drug Isacardin® sublingual spray when taken simultaneously with other vasodilators (vasodilators), antihypertensive drugs, beta-blockers, CCBs, antipsychotics (neuroleptics) and tricyclic antidepressants, in combination with ethanol, as well as when using PDE-5 inhibitors (including sildenafil, vardenafil, tadalafil).

When used simultaneously with procainamide and quinidine, the hypotensive effect may also be enhanced.

When combined with amiodarone, propranolol, CCBs (verapamil, nifedipine, etc.), the antianginal effect may be enhanced.

The simultaneous use of isosorbide dinitrate with dihydroergotamine may lead to an increase in the plasma concentration of the latter and thus enhance its hypertensive effect.

When used simultaneously with m-anticholinergics (atropine), the likelihood of increasing IOP increases.

Nitro compounds may reduce the therapeutic effect of norepinephrine (norepinephrine).

Barbiturates accelerate metabolism and reduce the concentration of nitro compounds in the blood plasma.

Overdose

Symptoms: marked decrease in blood pressure (less than 90 mm Hg), pallor, increased sweating, thready pulse, tachycardia, dizziness, headache, weakness, fainting, nausea, vomiting, diarrhea, methemoglobinemia (accompanied by tachypnea, anxiety, loss of consciousness, cardiac arrest). The use of high doses of the drug may cause an increase ICP,

Treatment: in mild cases – transfer the patient to a lying position with raised legs or lowered head end of the bed; in more serious cases, with a pronounced decrease in blood pressure, replenishment of blood volume, administration of norepinephrine or vasoconstrictors (vasoconstrictors), for example phenylephrine, dopamine (the use of epinephrine is not recommended); for methemoglobinemia – ascorbic acid – 1 g orally or in the form of sodium salt – IV 0.1–0.15 ml/kg of 1% solution (up to 50 ml), oxygen therapy, mechanical ventilation, hemodialysis.

Storage conditions

The drug should be stored out of the reach of children, at a temperature not exceeding 30°C, away from fire.

Shelf life

4 years.

Manufacturer

Farmamed LLC, Russia