Nitrosorbide tablets 10mg, No. 60

For oral administration: long-term treatment of coronary artery disease (prevention of angina attacks); secondary prevention of myocardial infarction and treatment for persistent angina pectoris (as part of combination therapy); long-term treatment of severe chronic heart failure (as part of combination therapy with cardiac glycosides, diuretics, ACE inhibitors).

For injection into the oral cavity: relief of angina attacks; prevention of angina attacks (including before physical or emotional stress); acute myocardial infarction; acute left ventricular failure.

For intravenous administration: angina pectoris (unstable and vasospastic); acute myocardial infarction; acute left ventricular failure.

The method of application and dosage regimen of a particular drug depends on its form of release and other factors. The optimal dosage regimen is determined by the doctor. It is necessary to strictly observe the compliance of the used dosage form of a particular drug with the indications for use and the dosage regimen.

Administered orally, intravenously, for injection into the oral cavity. Doses, method and scheme of application, duration of treatment are set individually, depending on the indications and clinical situation.

Isosorbide dinitrate - 10 mg

Hypersensitivity to isosorbide dinitrate, other nitrates; acute circulatory disorders (shock, collapse); cardiogenic shock (if no measures are taken to maintain end diastolic pressure); hypertrophic obstructive cardiomyopathy; constrictive pericarditis; cardiac tamponade; severe arterial hypotension (systolic blood pressure below 90 mm Hg); severe hypovolemia; severe anemia; severe aortic and subaortic stenosis, severe mitral stenosis; simultaneous administration of PDE5 inhibitors (including sildenafil, vardenafin, tadalafil); simultaneous reception with a soluble guanylate cyclase stimulant riociguat; age up to 18 years (effectiveness and safety have not been established); traumatic brain injury, cerebral hemorrhage; increased intraocular pressure, incl.angle-closure glaucoma (for intravenous injection).

Caution: Low left ventricular filling pressure, incl. with acute myocardial infarction, impaired left ventricular function (for example, with left ventricular failure); mild to moderate aortic and / or mitral stenosis; diseases accompanied by increased intracranial pressure; cerebral hemorrhage; increased intraocular pressure, incl. angle-closure glaucoma; tendency to orthostatic disorders of vascular regulation, severe renal and / or hepatic failure, hypothyroidism, malnutrition and malnutrition; pregnancy, breastfeeding period; old age (for injection into the oral cavity).

Clinical and pharmacological group: Peripheral vasodilator. Antianginal drug

Pharmaco-therapeutic group: Vasodilating agent, nitrate

pharmachologic effect

Peripheral vasodilator with a predominant effect on venous vessels. Antianginal remedy. The mechanism of action is associated with the release of the active substance nitric oxide in vascular smooth muscle. Nitric oxide activates guanylate cyclase and increases cGMP levels, which ultimately leads to relaxation of smooth muscles. Under the influence of isosorbide dinitrate, arterioles and precapillary sphincters relax to a lesser extent than large arteries and veins. This is partly due to reflex reactions, as well as less intense formation of nitric oxide from active substance molecules in the walls of arterioles.

The action of isosorbide dinitrate is mainly associated with a decrease in myocardial oxygen demand due to a decrease in preload (expansion of peripheral veins and a decrease in blood flow to the right atrium) and afterload (decrease in OPSS), as well as with a direct coronary dilating effect. Promotes redistribution of coronary blood flow in areas with reduced blood supply.

Increases exercise tolerance in patients with coronary artery disease, angina pectoris. In heart failure, it helps unload the myocardium by reducing preload. Reduces pressure in the pulmonary circulation.

Pharmacokinetics

When taken orally, after absorption from the gastrointestinal tract, isosorbide dinitrate undergoes a 'first pass' effect through the liver. Cmax in blood plasma is reached after 1 hour. With buccal administration, isosorbide dinitrate is rapidly absorbed, Cmax of the active substance in plasma is reached after 5-6 minutes.

It is metabolized to form an active metabolite of isosorbide-5-mononitrate, T1 / 2 of which is 5 hours, as well as isosorbide-2-mononitrate with T1 / 2 2.5 hours.

T1 / 2 of isosorbide dinitrate, depending on the dosage form used, varies from 20 minutes to 4 hours. It is excreted by the kidneys and through the intestines.

Indications

For oral administration: long-term treatment of coronary artery disease (prevention of angina attacks); secondary prevention of myocardial infarction and treatment for persistent angina pectoris (as part of combination therapy); long-term treatment of severe chronic heart failure (as part of combination therapy with cardiac glycosides, diuretics, ACE inhibitors).

For injection into the oral cavity: relief of angina attacks; prevention of angina attacks (including before physical or emotional stress); acute myocardial infarction; acute left ventricular failure.

For intravenous administration: angina pectoris (unstable and vasospastic); acute myocardial infarction; acute left ventricular failure.

Dosage regimen

The method of application and dosage regimen of a particular drug depends on its form of release and other factors. The optimal dosage regimen is determined by the doctor. It is necessary to strictly observe the compliance of the used dosage form of a particular drug with the indications for use and the dosage regimen.

Administered orally, intravenously, for injection into the oral cavity. Doses, method and scheme of application, duration of treatment are set individually, depending on the indications and clinical situation.

Side effect

From the nervous system: very often - headache; often - drowsiness, dizziness; when injected into the oral cavity - lethargy (especially at the beginning of treatment), cerebral ischemia.

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

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

On the part of the skin and subcutaneous tissues: infrequently - allergic skin reactions (including rash), hot flushes of blood to the skin of the face; very rarely - angioedema, Stevens-Johnson syndrome; frequency unknown - exfoliative dermatitis.

General disorders: often - asthenia, the development of tolerance (including cross-over to other nitrates). To prevent the development of tolerance, continuous use of high doses of isosorbide dinitrate should be avoided.

Long-term use of isosorbide dinitrate can cause transient hypoxemia due to a relative redistribution of blood flow to hypoventilated alveolar areas (in patients with coronary artery disease, it can lead to myocardial hypoxia).

Contraindications for use

Hypersensitivity to isosorbide dinitrate, other nitrates; acute circulatory disorders (shock, collapse); cardiogenic shock (if no measures are taken to maintain end diastolic pressure); hypertrophic obstructive cardiomyopathy; constrictive pericarditis; cardiac tamponade; severe arterial hypotension (systolic blood pressure below 90 mm Hg); severe hypovolemia; severe anemia; severe aortic and subaortic stenosis, severe mitral stenosis; simultaneous administration of PDE5 inhibitors (including sildenafil, vardenafin, tadalafil); simultaneous reception with a soluble guanylate cyclase stimulant riociguat; age up to 18 years (effectiveness and safety have not been established); traumatic brain injury, cerebral hemorrhage; increased intraocular pressure, incl.angle-closure glaucoma (for intravenous injection).

Caution: Low left ventricular filling pressure, incl. with acute myocardial infarction, impaired left ventricular function (for example, with left ventricular failure); mild to moderate aortic and / or mitral stenosis; diseases accompanied by increased intracranial pressure; cerebral hemorrhage; increased intraocular pressure, incl. angle-closure glaucoma; tendency to orthostatic disorders of vascular regulation, severe renal and / or hepatic failure, hypothyroidism, malnutrition and malnutrition; pregnancy, breastfeeding period; old age (for injection into the oral cavity).

Application during pregnancy and lactation

The use of isosorbide dinitrate during pregnancy and lactation (breastfeeding) is possible only if the intended benefit to the mother outweighs the potential risk to the fetus or child.

Application for violations of liver function

It should be used with caution in patients with severe hepatic impairment.

Application for impaired renal function

It should be used with caution in patients with severe renal impairment.

Application in children

Isosorbide dinitrate is contraindicated for use in children and adolescents under the age of 18 years.

Use in elderly patients

Use with caution in elderly patients.

special instructions

During therapy with isosorbide dinitrate, it is necessary to monitor the indicators of the cardiovascular system and other vital organs.

In acute myocardial infarction or acute heart failure, isosorbide dinitrate should be used only with careful clinical observation of the patient.

The intravenous administration of isosorbide dinitrate should be carried out only under stationary conditions under constant monitoring of the indicators of the cardiovascular system. Depending on the type and severity of the disease, in addition to the usual examination (symptoms, blood pressure, heart rate, diuresis), invasive procedures are performed to determine the hemodynamic parameters.

Avoid drinking alcohol during treatment.

Influence on the ability to drive vehicles and use mechanisms

During the period of treatment with isosorbide dinitrate, it is not recommended to drive vehicles and engage in other potentially hazardous activities.

Drug interactions

With simultaneous use with adsorbents, astringents and coating agents, the absorption of isosorbide dinitrate decreases.

With the simultaneous use of antihypertensive drugs, peripheral vasodilators, calcium channel blockers, beta-blockers, antipsychotics (neuroleptics), tricyclic antidepressants, PDE inhibitors, ethanol, an increase in the hypotensive effect is possible.

With simultaneous use with anticholinergics, memory and attention impairment in elderly patients is possible.

With simultaneous use with sympathomimetic agents, it is possible to reduce the antianginal effect of isosorbide dinitrate.

With simultaneous use with dihydroergotamine, it is possible to increase the concentration and enhance the effect of dihydroergotamine.

With simultaneous use with norepinephrine, the therapeutic effect of norepinephrine decreases.

With the simultaneous use of isosorbide dinitrate and phosphodiesterase-5 inhibitors (including sildenafil, tadalafil, vardenafil), there is a risk of severe arterial hypotension and myocardial infarction.

The simultaneous use of isosorbide dinitrate with the soluble guanylate cyclase stimulator riociguat can cause the development of arterial hypotension.