Isacardin, 1 piece, 15 ml, 1.25 mg/dose, sublingual dosed spray

Isacardin, 1 piece, 15 ml, 1.25 mg/dose, sublingual dosed spray

Concentrate for the preparation of solution for infusion

IV,

slowly.

The dosage regimen is set individually in accordance with the patient’s clinical condition and hemodynamic parameters. The recommended initial dose is 1–2 mg/hour depending on the patient’s response (subject to monitoring blood pressure, heart rate, ECG and diuresis). The maximum dose of the drug is 8–10 mg/hour. For patients with heart failure, higher doses are usually required - in some cases up to 50 mg/hour. The average dose is approximately 7.5 mg/hour. In patients who have previously taken organic nitrates (eg, isosorbide dinitrate, isosorbide-5-mononitrate), higher doses of Izacardin® can be administered to achieve the desired hemodynamic effect.

Isacardin® concentrate 1 mg/ml should be administered in dissolved form intravenously using automatic infusion systems (or, in extreme cases, as a drip infusion) in a hospital setting under constant monitoring of cardiovascular parameters.

To prepare a solution with a concentration of 100 mcg/ml (0.01%) - 50 ml of Isacardin® concentrate 1 mg/ml (5 ampoules of 10 ml each) must be diluted in 450 ml of 0.9% sodium chloride solution; to prepare a solution with a concentration of 200 mcg/ml (0.02%) - 100 ml of Isacardin® concentrate 1 mg/ml (10 ampoules of 10 ml each) must be diluted in 400 ml of 0.9% sodium chloride solution.

Sublingual dosed spray

The drug Isacardin® sublingual dosed spray is used for spraying onto the oral mucosa, under the tongue. The solution should not be inhaled. Bring the spray close to your mouth and, pressing the spray nozzle, inject the solution into the oral cavity:

- take a deep breath;

- hold the breath;

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

In case of acute myocardial infarction and acute heart failure, therapy is carried out under the control of blood pressure, heart rate and medical supervision, starting with 1-3 injections, with a 30-second interval between injections; if there is no effect after 5 minutes, you can repeat 1 injection; If there is no improvement, then repeat 1 injection after 10 minutes. When using Isacardin® spray for the first time or after a break in use for more than a day, you should press the sprayer several times until the first drops of the solution appear. When using, the spray bottle should be held vertically with the spray nozzle facing upward. Avoid getting the spray in your eyes.

Isacardin 1.25 mg/dose 15ml sublingual dosed spray

pharmachologic 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, a mediator of vasodilation. Reduces myocardial oxygen demand by reducing preload (reduces the end-diastolic volume 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.

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 after 30 seconds and lasts 15-120 minutes.

Composition and release form Isacardin 1.25 mg/dose 15 ml sublingual dosed spray

Spray - 1 dose:

• Active substance: isosorbide dinitrate - 1.25 mg;
• Excipients: macrogol-400 (polyethylene oxide-400) - 6 mg, ethanol 96% - up to 0.05 ml.

Sublingual spray in a dark glass bottle with a mechanical dosing pump and sprayer in a cardboard package - 15 ml.

Description of the dosage form

Sublingual dosed spray is transparent, colorless or yellowish, with an alcoholic odor.

Directions for use and doses

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

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

In case of acute myocardial infarction and acute left ventricular failure, therapy is carried out under the control of blood pressure, heart rate and medical supervision, starting with 1-3 injections, with a 30-second interval between injections; if there is no effect after 5 minutes, you can repeat 1 injection; if there is no improvement, then after 10 minutes repeat 1 injection.

Pharmacokinetics

Absorption and distribution.

Absorption is high. Bioavailability through the oral mucosa is 60%. Binding to blood plasma proteins is 30%.

Metabolism and excretion.

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 (constituting 15-25% with T1/2 2.5 hours). The drug is excreted by the kidneys (almost entirely in the form of metabolites).

Indications for use Isacardin 1.25 mg/dose 15 ml sublingual dosed spray

• Relief of angina attacks;
• prevention of angina attacks (including before physical or emotional stress);
• acute myocardial infarction;
• acute left ventricular failure.

Contraindications

• Acute vascular insufficiency (vascular 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, udenafil), because they potentiate the hypotensive effect of nitrates; simultaneous use with a soluble guanylate cyclase stimulator (riociguat);
• age under 18 years (efficacy and safety have not been established);
• hypersensitivity to the active substance, other organic nitrates or auxiliary components of the drug.

Carefully:

• With low filling pressure of the left ventricle, incl. with acute myocardial infarction, dysfunction of the left ventricle (for example, with left ventricular failure). It is necessary to avoid reducing systolic blood pressure to less than 90 mm Hg;
• with aortic or mitral stenosis of mild to moderate degree;
• with a tendency to orthostatic disorders of vascular regulation;
• for diseases accompanied by increased intracranial pressure (including hemorrhagic stroke, traumatic brain injury);
• with severe renal failure;
• with severe liver failure (risk of developing methemoglobinemia);
• with hypothyroidism;
• with angle-closure glaucoma (risk of increased intraocular pressure);
• in old age;
• with insufficient and malnutrition.

Effect on the body

Reduces blood flow to the right atrium, helps reduce pressure in the pulmonary circulation and regression of symptoms of pulmonary edema. Promotes redistribution of coronary blood flow in areas with reduced blood circulation. Increases exercise tolerance in patients with coronary artery disease and angina pectoris.

Dilates blood vessels in the brain and dura mater, which may be accompanied by headaches.

Application of Isacardin 1.25 mg/dose 15 ml sublingual spray dosed during pregnancy and breastfeeding

There are no data on the effect of the drug on human fertility. There are no adequate and well-controlled safety studies of isosorbide dinitrate. Reproduction studies conducted in rats and rabbits at doses reaching levels of maternal toxicity showed no evidence of harmful effects of isosorbide dinitrate on the fetus. Since animal studies are not always able to reproduce the effect of the drug on humans, the use of Izacardin 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 lactation, breastfeeding should be stopped, because There is information about the penetration of nitrates into breast milk. If emergency use of the drug Isacardin spray is necessary, for example, to relieve an attack of angina, it is necessary to monitor the child for the development of possible side effects.

There is information about the penetration of nitrates into breast milk, but the exact content of isosorbide dinitrate in breast milk has not been determined. A possible risk of developing methemoglobinemia in infants has also been reported; therefore, if administration of the drug is necessary, breastfeeding should be discontinued.

The use of the drug is contraindicated in people under 18 years of age (efficacy and safety have not been established).

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 Izacardin spray with other antianginal agents during this time.

Particularly careful medical supervision is necessary in acute myocardial infarction with reduced ventricular filling pressure.

Treatment with Isacardin spray should not be used in patients who immediately previously took phosphodiesterase-5 inhibitors (including sildenafil, vardenafil, tadalafil, udenafil).

The solution contains about 85% ethanol. During treatment with Isacardin spray, the use of ethanol (alcohol) should be avoided.

Influence on the ability to drive vehicles and operate machinery.

During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities due to the fact that taking the drug can lead to a decrease in the speed of motor and mental reactions (risk of dizziness).

Overdose

Symptoms: severe arterial hypotension (less than 90 mm Hg), pallor, increased sweating, thready pulse, tachycardia, postural dizziness, throbbing headache, weakness, fainting, nausea, vomiting, diarrhea, methemoglobinemia (accompanied by tachypnea, anxiety, loss of consciousness, cardiac arrest). When used in high doses, intracranial pressure may increase.

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

Side effects Isacardin 1.25 mg/dose 15 ml sublingual dosed spray

The frequency of side effects is given according to the WHO classification: very often (>1/10), often (>1/100 and 1/1000 and 1/10,000 and

From the side of the central nervous system: very often - headaches (“nitrate” headaches) at the beginning of treatment, which, as a rule, disappear with further use of the drug; often - slight dizziness, drowsiness, blurred vision; frequency unknown - lethargy (especially at the beginning of treatment), cerebral ischemia.

From the cardiovascular system: often - orthostatic hypotension, reflex tachycardia; infrequently - “paradoxical” intensification of angina attacks, collapse (sometimes accompanied by bradyarrhythmia and fainting); frequency unknown - marked decrease in blood pressure.

From the digestive system: often - burning of the tongue; infrequently - nausea, vomiting; very rarely - heartburn; frequency unknown - dryness of the oral mucosa.

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.

Long-term use of the drug can cause transient hypoxemia due to the relative redistribution of blood flow into hypoventilated alveolar areas (in patients with coronary artery disease, this can lead to myocardial hypoxia).

It is possible to develop tolerance, incl. cross to other nitrates.

If any of the side effects indicated in the instructions are aggravated or any other side effects not specified in the instructions are noted, the patient should inform the doctor.

Drug interactions

It is possible to enhance the hypotensive effect of Isacardin spray when taken simultaneously with other vasodilators (vasodilators), antihypertensive drugs (beta-blockers, diuretics, slow calcium channel blockers, ACE inhibitors), antipsychotics (neuroleptics) and tricyclic antidepressants, in combination with ethanol and ethanol-containing drugs, as well as PDE5 inhibitors (including sildenafil, vardenafil, tadalafil, udenafil).

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

With the simultaneous use of sapropterin and isosorbide dinitrate, there is an increased risk of arterial hypotension (since sapropterin, being a coenzyme of nitric oxide synthetase, potentiates the synthesis of additional amounts of nitric oxide).

When combined with amiodorone, propranolol, slow calcium channel blockers (verapamil, nifedipine and others), the antianginal effect may be enhanced.

Under the influence of sympathomimetics, alpha-blockers (dihydroergotamine and others), it is possible to reduce the severity of the antianginal effect (excessive decrease in blood pressure, and, as a consequence, coronary perfusion).

When used simultaneously with m-anticholinergic blockers (atropine and others), the likelihood of increased intraocular pressure 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.

When used simultaneously with the soluble guanylate cyclase stimulator riociguat, there is a risk of developing arterial hypotension.

Isacardin, 1 mg/ml, concentrate for solution for infusion, 10 ml, 10 pcs.

Concentrate for the preparation of solution for infusion

IV,

slowly.

The dosage regimen is set individually in accordance with the patient’s clinical condition and hemodynamic parameters. The recommended initial dose is 1–2 mg/hour depending on the patient’s response (subject to monitoring blood pressure, heart rate, ECG and diuresis). The maximum dose of the drug is 8–10 mg/hour. For patients with heart failure, higher doses are usually required - in some cases up to 50 mg/hour. The average dose is approximately 7.5 mg/hour. In patients who have previously taken organic nitrates (eg, isosorbide dinitrate, isosorbide-5-mononitrate), higher doses of Izacardin® can be administered to achieve the desired hemodynamic effect.

Isacardin® concentrate 1 mg/ml should be administered in dissolved form intravenously using automatic infusion systems (or, in extreme cases, as a drip infusion) in a hospital setting under constant monitoring of cardiovascular parameters.

To prepare a solution with a concentration of 100 mcg/ml (0.01%) - 50 ml of Isacardin® concentrate 1 mg/ml (5 ampoules of 10 ml each) must be diluted in 450 ml of 0.9% sodium chloride solution; to prepare a solution with a concentration of 200 mcg/ml (0.02%) - 100 ml of Isacardin® concentrate 1 mg/ml (10 ampoules of 10 ml each) must be diluted in 400 ml of 0.9% sodium chloride solution.

Sublingual dosed spray

The drug Isacardin® sublingual dosed spray is used for spraying onto the oral mucosa, under the tongue. The solution should not be inhaled. Bring the spray close to your mouth and, pressing the spray nozzle, inject the solution into the oral cavity:

- take a deep breath;

- hold the breath;

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

In case of acute myocardial infarction and acute heart failure, therapy is carried out under the control of blood pressure, heart rate and medical supervision, starting with 1-3 injections, with a 30-second interval between injections; if there is no effect after 5 minutes, you can repeat 1 injection; If there is no improvement, then repeat 1 injection after 10 minutes. When using Isacardin® spray for the first time or after a break in use for more than a day, you should press the sprayer several times until the first drops of the solution appear. When using, the spray bottle should be held vertically with the spray nozzle facing upward. Avoid getting the spray in your eyes.