Isolong (Capsules) Instructions for Use

ATC Code

C01DA08 (Isosorbide dinitrate)

Active Substance

Isosorbide dinitrate (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Peripheral vasodilator. Anti-anginal drug

Pharmacotherapeutic Group

Vasodilating agent – nitrate

Pharmacological Action

A peripheral vasodilator with a predominant effect on venous vessels. An anti-anginal agent. The mechanism of action is associated with the release of the active substance nitric oxide in the vascular smooth muscle. Nitric oxide causes activation of guanylate cyclase and increases the level of cGMP, 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 the molecules of the active substance 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 (dilation of peripheral veins and a decrease in blood flow to the right atrium) and afterload (decrease in total peripheral vascular resistance), as well as a direct coronary dilating effect. It promotes the redistribution of coronary blood flow to areas with reduced blood supply.

It increases exercise tolerance in patients with coronary artery disease and angina pectoris. In heart failure, it promotes myocardial unloading by reducing preload. It 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. The C_max in blood plasma is reached after 1 hour. With buccal application, isosorbide dinitrate is rapidly absorbed; the C_max of the active substance in plasma is reached in 5-6 minutes.

It is metabolized to form the active metabolite isosorbide-5-mononitrate, whose T_1/2 is 5 hours, and isosorbide-2-mononitrate with a T_1/2 of 2.5 hours.

The T_1/2 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 (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 spraying 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 (unstable and vasospastic); acute myocardial infarction; acute left ventricular failure.

ICD codes

Dosage Regimen

Determine the dose, route of administration, and treatment duration individually based on the clinical situation and indication.

For long-term treatment of coronary artery disease and chronic heart failure, administer capsules orally. Initiate therapy with a low dose and titrate upwards to the effective dose.

Take capsules with a sufficient amount of water. For prophylactic use, administer two to three times daily. Maintain a dosing interval of at least 6-8 hours to prevent the development of tolerance.

For the relief of an acute angina attack, use the oral spray formulation. Spray one to three doses onto or under the tongue. Do not inhale. Repeat after 5 minutes if pain persists. If pain continues after three sprays, seek immediate medical attention.

For intravenous administration, administer only in a hospital setting under continuous hemodynamic monitoring. Prepare the infusion solution according to manufacturer instructions. Adjust the infusion rate based on clinical response and blood pressure.

In patients with severe hepatic or renal impairment, use a lower starting dose and titrate cautiously. Monitor for signs of excessive vasodilation.

In elderly patients, initiate therapy at the lower end of the dosing range due to potential increased sensitivity.

Avoid abrupt discontinuation of therapy; taper the dose gradually to prevent withdrawal reactions.

Adverse Reactions

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

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

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

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

General disorders: often – asthenia, development of tolerance (including cross-tolerance 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 relative redistribution of blood flow to hypoventilated alveolar areas (in patients with coronary artery disease – can lead to myocardial hypoxia).

Contraindications

Hypersensitivity to isosorbide dinitrate, other nitrates; acute circulatory disorders (shock, collapse); cardiogenic shock (if measures to maintain end-diastolic pressure are not taken); 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 use of PDE5 inhibitors (including sildenafil, vardenafil, tadalafil); simultaneous use with the soluble guanylate cyclase stimulator riociguat; age under 18 years (efficacy and safety not established); traumatic brain injury, cerebral hemorrhage; increased intraocular pressure, including closed-angle glaucoma (for intravenous administration).

With caution low left ventricular filling pressure, including in acute myocardial infarction, left ventricular dysfunction (for example, in left ventricular failure); mild and moderate aortic and/or mitral stenosis; diseases accompanied by increased intracranial pressure; cerebral hemorrhage; increased intraocular pressure, including closed-angle glaucoma; tendency to orthostatic disorders of vascular regulation, severe renal and/or hepatic insufficiency, hypothyroidism, inadequate and malnutrition; pregnancy, breastfeeding period; old age (for spraying into the oral cavity).

Use in 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.

Use in Hepatic Impairment

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

Use in Renal Impairment

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

Pediatric Use

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

Geriatric Use

It is used with caution in elderly patients.

Special Precautions

During therapy with isosorbide dinitrate, monitoring of the cardiovascular system and other vital organs is necessary.

In acute myocardial infarction or acute heart failure, Isosorbide dinitrate should be used only under conditions of careful clinical monitoring of the patient.

Intravenous administration of isosorbide dinitrate should be carried out only in a hospital setting under constant monitoring 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 hemodynamic parameters.

Avoid alcohol consumption during treatment.

Influence on the ability to drive vehicles and mechanisms

During 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 is reduced.

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

With simultaneous use with anticholinergic agents, memory and attention disorders are possible in elderly patients.

With simultaneous use with sympathomimetic agents, a decrease in the antianginal effect of isosorbide dinitrate is possible.

With simultaneous use with dihydroergotamine, an increase in the concentration and enhancement of the action of dihydroergotamine is possible.

With simultaneous use with norepinephrine, the therapeutic effect of norepinephrine is reduced.

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

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

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.