Isacardine sublingual spray 1.25mg/dose 300 doses, 15ml

Composition

1 bottle (300 doses): Active ingredient: isosorbide dinitrate water (in terms of 100% isosorbide dinitrate) – 0.375 g, (1 dose contains 1.25 mg of isosorbide dinitrate): Auxiliary substances:  macrogol 400 (polyethylene oxide 400) — 1,8 g; ethanol 96% – up to 15 ml

Pharmacological action

Peripheral vasodilator with a predominant effect on venous vessels. It stimulates the formation of nitric oxide (an 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 the oxygen demand of the myocardium by reducing preload (reduces the end-diastolic volume of the left ventricle and reduces the systolic tension of its walls). It has a corona-expanding 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. Arterial vasodilation also occurs (although to a lesser extent), which is accompanied by a decrease in blood pressure, a decrease in OPSS (afterload).

A decrease in 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 to reduce pressure in the small circle of blood circulation and regression of symptoms in pulmonary edema. Promotes the redistribution of coronary blood flow in favor of subendocardial zones, especially in atherosclerosis of the coronary arteries (mainly large). Vasodilation of the collateral arteries can improve blood supply to the myocardium. Increases exercise tolerance in patients with coronary artery disease, angina pectoris.

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

Dilates the blood vessels of the brain, dura mater, which can be accompanied by a headache. As with other nitrates, cross-tolerance develops.

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

Pharmacokinetics

Absorption is high. Bioavailability through the oral mucosa is 60%. Binding to plasma proteins is 30%. T_1/2 is 60 min. It is metabolized in the liver to two active metabolites-isosorbide-5-mononitrate, the proportion of which is 75-85%, T_1/2-5 hours and isosorbide-2-mononitrate, which is 15-25% with T_1/2-2.5 hours.

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

Indications

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

Use during pregnancy and lactation

Use of Izacardin®during pregnancy sublingual dosed spray is possible only in cases where the expected benefit exceeds the potential risk to the fetus and child, and should be carried out under the supervision of a doctor. If it is necessary to use isosorbide dinitrate during breastfeeding, it is recommended to stop breastfeeding, since there are reports of nitrate penetration into breast milk. If necessary, emergency use of the drug Izacardin® hypoglossal dosed spray, for example, to stop an attack of angina pectoris, it is necessary to monitor the child for the development of possible side effects.

Contraindications

— acute circulatory failure (shock, collapse);

— severe hypotension (systolic blood pressure below 90 mm Hg. St., diastolic blood pressure below 60 mm Hg. St. )

— severe hypovolemia;

— cardiogenic shock, if not possible correction of end-diastolic pressure of the left ventricle using the intra-aortic pump therapy or drugs with positive inotropic effect; — hypertrophic obstructive cardiomyopathy, constrictive pericarditis, cardiac tamponade;

— severe aortic valve, subaortic stenosis and mitral;

— brain hemorrhage;

severe anemia;

— concomitant use of PDE 5 inhibitors (including sildenafil, vardenafil, tadalafil) is a risk decrease in blood pressure;

— age under 18 years (effectiveness and safety not established);

— hypersensitivity to nitrates or other components of the drug.

With caution:

— at a low filling pressure of the left ventricle, including in acute myocardial infarction;

— if aortalni or mitral stenosis;

— a tendency to orthostatic reactions (a sharp decrease in blood pressure when changing position of the body);

— at diseases characterized by increased intracranial pressure (including hemorrhagic stroke, traumatic brain injury);

— severe renal failure;

— liver failure (risk of methemohlobinemia);

— hyperthyroidism;

— in angle-closure glaucoma;

in old age;

— when there is insufficient and inferior food;

— toxic pulmonary edema.

Side effects

Possible side effects are listed below for body systems and frequency of occurrence: very common (more than 1/10); common (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), the frequency is unknown (according to available data, it is not possible to determine the frequency of development).

From the central nervous system:  very often — headache; often-dizziness, drowsiness, blurred vision.

From the CCC side:  often-orthostatic hypotension, reflex tachycardia; infrequently-paradoxical increase in angina attacks, collapse (accompanied by bradyarrhythmia and syncope), transient hypoxemia due to relative redistribution of blood flow to hypoventilated alveolar areas (in patients with CHD can lead to myocardial hypoxia).

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

From the side of 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 services:  often-asthenia. It is possible to develop tolerance, including cross-tolerance to other nitrates.

Interaction

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

When used concomitantly with procainamide, quinidine, it is also possible to increase the hypotensive effect.

When combined with amiodarone, propranolol, BCC (verapamil, nifedipine, etc. ), it is possible to increase the antianginal effect.

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

Concomitant use with m-holinoblokatorami (atropine) increases the likelihood of increased IOP.

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

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

How to take, course of use and dosage

Izacardin®preparation sublingual metered spray is used for spraying on the oral mucosa, under the tongue. The solution should not be inhaled. Hold the spray close to your mouth and press the spray gun to inject the solution into your mouth:

– take a deep breath;

– hold your breath;

– inject the solution into your mouth (this may cause a slight burning sensation of the tongue);

– close your mouth and breathe through your nose for about 30 seconds.

One dose of the drug contains 1.25 mg of isosorbide dinitrate.

To stop an angina attack or before physical or emotional stress that can cause an attack, you need to inject the spray into your mouth 1-3 times with an interval of 30 seconds between injections while holding your breath. A single dose of 3 injections to stop an attack can be increased only on the recommendation of a doctor.

In acute myocardial infarction and acute heart failure, therapy is carried out under the control of blood pressure, heart rate and doctor’s supervision, start with 1-3 sprays, with a 30-second interval between sprays; in the absence of an effect,1 spray can be repeated after 5 minutes; if no improvement occurs, then repeat 1 spray again after 10 minutes. When using Izacardin®for the first time spray or break in use for more than a day, you should press the spray several times before the first drops of the solution appear. When applying, the spray bottle should be held vertically with the spray bottle facing up. Avoid contact with eyes.

Overdose

Symptoms:  marked decrease in blood pressure (less than 90 mm Hg).paleness, 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 in ICP,

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

Special instructions

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

Influence on the ability to drive vehicles and other mechanisms. When using the drug Izacardin®, sublingual dosed spray, care should be taken when driving vehicles and mechanisms (risk of dizziness).

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 is 4 years.

Active ingredient

Isosorbide dinitrate

Conditions of release from pharmacies

By prescription

Dosage Form

spray sublingual