Isosorbide dinitrate: instructions for use, price and reviews

Pharmacodynamics and pharmacokinetics

The substance increases the level of NO2 ( nitric oxide ) in endothelium . The drug acts as a venous and arterial dilator . Reduces the need for oxygen in the heart muscle, reduces the overall tension of the walls of the ventricles of the heart. Isosorbide dinitrate reduces the load on the heart, dilates the coronary arteries, redistributes coronary blood flow to an area with insufficient oxygen supply, and reduces blood pressure on the walls of blood vessels in the pulmonary circulation.

The drug, as a rule, does not affect the heart rate; sometimes it slightly increases heart rate. Under the influence of the substance, cerebral vessels dilate and pulmonary vascular resistance changes.

After taking the tablets, the medicine is quickly and completely absorbed. The biological availability of the product is no more than 22%. When used sublingually, the bioavailability is 60%. The degree of binding to blood plasma proteins is no more than 30%.

The effect of taking sublingual tablets occurs after 3 minutes, from oral tablets - after 15-40 minutes. When sprayed onto the oral mucosa, the antianginal effect develops within 30 seconds and lasts up to 2 hours.

After injection of the drug, it is half eliminated from the body after 20 minutes; when administered sublingually, the half-life is one hour, when taking tablets - 4 hours. The substance is metabolized in the liver, forming active metabolites: isosorbide-5-mononitrate, isosorbide-2-mononitrate . Metabolites are eliminated by renal glomerular filtration.

Long-term use of the medicine may lead to the development of tolerance.

Publications in the media

Isosorbide dinitrate (Nitrosorbide, Isoket, Cardiket), extended-release capsules, concentrate for the preparation of solution for infusion, films for gluing to the gums, dosed sublingual spray, tablets, extended-release tablets, transdermal therapeutic system

Pharmaceutical group - vasodilating agent - nitrate.

Pharmaceutical action. Peripheral vasodilator with a predominant effect on venous vessels. Stimulates the formation of “first pass” nitric oxide (endothelial relaxing factor) in the vascular endothelium, which causes activation of intracellular guanylate cyclase, resulting in an increase in cGMP (a mediator of vasodilation). Reduces myocardial oxygen demand by reducing preload and afterload (reduces the end-diastolic volume of the LV and reduces the systolic tension of its walls). Has a coronary dilating effect. Reduces blood flow to the right atrium, helps reduce pressure in the “lesser” circulation and regression of symptoms of pulmonary edema. Promotes redistribution of coronary blood flow in areas with reduced blood circulation. Increases tolerance to physical activity in patients with coronary heart disease and angina pectoris. Dilates blood vessels in the brain, which may be accompanied by headaches. As with other nitrates, cross-tolerance develops. After cancellation (break in treatment), sensitivity to it is quickly restored. The onset of action after sublingual administration or chewing is 2-5 minutes, after oral administration of capsules and tablets - 15-40 minutes, prolonged forms - 30 minutes. The duration of action is 1-2 hours, 4-6 and 12 hours, respectively. After spraying onto the oral mucosa, the effect appears after 30 s and lasts 15-120 minutes.

Pharmacokinetics. Absorption for all dosage forms is high. Bioavailability when taken orally is 22% (the “first pass” effect through the liver), when administered sublingually - 60%. TCmax when taken orally - 1 hour. Plasma protein binding - 30%. T1/2 with intravenous administration - 20 minutes, with sublingual administration - 60 minutes, with oral administration - 4 hours. Metabolized in the liver to 2 active metabolites: isosorbide-5-mononitrate (75-85%) with T1/2 5 h and isosorbide-2-mononitrate (15-25%) with T1/2 - 2.5 h. Excreted by the kidneys (almost entirely in the form of metabolites).

Indications. Angina (relief and prevention, including unstable angina), acute myocardial infarction (including complicated by acute left ventricular failure), condition after myocardial infarction. Spasm of the coronary arteries (prevention and treatment when using a cardiac catheter). CHF, pulmonary edema, hypertension in the pulmonary circulation, cor pulmonale (as part of combination therapy). Spasm of peripheral arteries (obliterating endarteritis, angiospastic retinitis). Control of blood pressure when it increases before and during surgery (especially in cardiovascular surgery). Contraindications. Hypersensitivity. For intravenous administration (except in special circumstances) - hemorrhagic stroke, head injury (increases intracranial pressure), intracranial hypertension, cardiac tamponade, constrictive pericarditis, hypovolemia (must be corrected before using nitroglycerin - the risk of a pronounced decrease in blood pressure).

Carefully. For all forms (comparing risk and benefit) - hemorrhagic stroke, recent TBI, acute myocardial infarction (risk of decreased blood pressure and tachycardia, which can increase ischemia), glaucoma (risk of increased intraocular pressure), severe anemia, thyrotoxicosis, arterial hypotension with low systolic blood pressure (can aggravate the condition, causing paradoxical bradycardia and angina attacks), HOCM (possibly increased frequency of angina attacks), severe chronic renal failure, liver failure (risk of developing methemoglobinemia), pregnancy, lactation, childhood (safety of use has not been established). For oral dosage forms - increased gastrointestinal motility, malabsorption syndrome. Category of action on the fetus. C

Dosing. Sublingual, internally, parenterally, locally, externally. Sublingual. Spray: 1-3 doses (1.25-3.75 mg) are injected into the oral cavity at intervals of about 30 s while holding the breath. If after 5 minutes there is no improvement, inhalation is repeated (subject to constant monitoring of blood pressure and heart rate). To prevent coronary spasm in case of catheterization, 1-2 doses should be administered immediately before the procedure. Tablets: 2.5-5 mg, if necessary - every 2-3 hours. To relieve an attack of angina - sublingually (to speed up the action, it is advisable to chew the tablet). Inside. 10-20 mg 4-5 times a day 1 hour before or 2 hours after meals, without chewing, with a glass of water. If the effect is insufficient, from day 3-5 of treatment the dose is increased to 60-120 mg/day. The frequency of administration depends on the duration of action and is 3-4 times for tablets with an average duration of action (tablets containing 5, 10 and 20 mg); for retard tablets 20 mg - 2-3 times; for retard tablets 40 and 60 mg - 2 times; for retard tablets 120 mg - 1 time per day. As part of complex therapy for CHF, 10-20 mg is used 3-4 times a day. Parenterally. IV drip, 0.1 mg/ml at an initial rate of 3-4 drops/min or 0.2 mg/ml at a rate of 1-2 drops/min. The rate of administration can be increased every 5 minutes by 2-3 drops, depending on the patient’s response (subject to monitoring blood pressure, heart rate, ECG and diuresis). The maximum rate of administration is 33 drops/min (for a solution with a concentration of isosorbide dinitrate of 0.1 mg/ml) and 17 drops/min (for a solution with a concentration of 0.2 mg/ml). Transbuccally. Plates (20-40 mg) are glued to the mucous membrane of the gums on the front surface of the upper jaw at the level of the incisors or small molars, alternating sides each time, 1-3 times a day. TTS: the skin area is wiped with ethanol or water; The protective coating is removed from the system, the sticky side is applied to the skin and pressed to ensure contact of the entire surface with the skin. The selected area of skin should be hairless and not subject to intense mechanical stress (the inner surface of the forearm, the side or front surface of the chest, the skin of the back). The following system is glued to another (preferably symmetrical) area of the skin. The dose is proportional to the area and is 0.5-1 mg/sq.cm. To select an individual dose, the system can be cut into pieces of any size. The duration of a single application is 12-24 hours. The course of treatment is 2 weeks. Abrupt withdrawal should be avoided. Spray for skin application: spray 1-2 doses from a distance of 20 cm and rub it with your fingertips. After the spray has dried, the skin can be covered with clothing. After 20 minutes, the skin areas can be washed. Ointment: initial dose - 1 g of ointment 1-2 times a day; applied to the chest area, inner surface of the forearms or abdomen; The minimum application surface area is 20 sq.cm.

Side effect. From the cardiovascular system: headache, dizziness, flushing of the facial skin, feeling of heat, tachycardia, decreased blood pressure. In rare cases, a paradoxical increase in angina attacks and collapse. From the digestive system: nausea, vomiting, a slight burning sensation of the tongue, dry mouth. From the nervous system: stiffness, drowsiness, blurred vision, decreased ability for rapid mental and motor reactions (especially at the beginning of treatment). In rare cases, cerebral ischemia. Allergic reactions: skin rash. Local reactions: burning, itching, skin hyperemia at the site of application. Other: development of tolerance (including cross-tolerance to other nitrates), exfoliative dermatitis.

Overdose. Symptoms: collapse, fainting, headache, dizziness, palpitations, visual disturbances, hyperthermia, convulsions, skin flushing, increased sweating, nausea, vomiting, diarrhea, methemoglobinemia (cyanosis, anoxia), hyperpnea, dyspnea, bradycardia, increased intracranial pressure, paralysis , coma. Treatment: gastric lavage; remove ointment, TTC or buccal tablets (wipe the gums at the site of their application); for methemoglobinemia, depending on the severity, intravenous ascorbic acid in the form of sodium salt is prescribed (previously methylthioninium chloride (methylene blue) was used 0.1-0.15 ml/kg 1% solution up to 50 ml); oxygen therapy, hemodialysis, exchange transfusion. Symptomatic therapy: with a pronounced decrease in blood pressure - intravenous phenylephrine (epinephrine and related compounds are ineffective).

Interaction. Pharmacodynamic: under the influence of beta-adrenergic stimulants, alpha-adrenergic blockers (prazosin, dihydroergotamine, etc.), the severity of the antianginal effect of isosorbide dinitrate (tachycardia and excessive decrease in blood pressure) may be reduced. When combining amiodarone, propranolol, BMCA (verapamil, nifedipine, etc.), ASA and isosorbide dinitrate, the antianginal effect may be enhanced. When isosorbide dinitrate is used together with antihypertensive drugs, vasodilators, antipsychotic drugs (neuroleptics), tricyclic antidepressants, procainamide, ethanol, quinidine, beta-blockers, BMCC, ethanol, dihydroergotamine and sildenafil, the hypotensive effect may be enhanced. When combined with m-anticholinergic blockers (atropine, etc.), the likelihood of increased intraocular pressure increases. Pharmacokinetic: adsorbents, astringents and enveloping drugs reduce the absorption of isosorbide dinitrate in the gastrointestinal tract.

Special instructions. During treatment, especially in the case of a gradual increase in dose, monitoring of blood pressure and heart rate is necessary. To relieve attacks of angina, in acute myocardial infarction (including complicated by acute left ventricular failure), pulmonary edema, unstable angina, spasm of the coronary arteries (prevention and treatment when using a cardiac catheter), sublingual or intravenous routes of administration are used. If necessary, use against the background of arterial hypotension should simultaneously administer drugs that have a positive inotropic effect, or use circulatory support devices. Frequent administration and high doses may cause the development of tolerance; in this 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 isosorbide dinitrate with other antianginal agents during this time. While taking isosorbide dinitrate, you should avoid drinking ethanol. Pregnant and lactating women are prescribed the drug only according to strict indications, under the constant supervision of a doctor. Ineffective for heart failure caused by cardiac tamponade and toxic pulmonary edema. Abrupt withdrawal of the drug should be avoided and the dose should be reduced gradually. During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Indications for use

The medicine is prescribed orally, buccally and sublingually:

for relief and prevention of angina ;
during rehabilitation treatment after myocardial infarction ;
as part of complex treatment of chronic heart failure ;
for certain forms of pulmonary hypertension ;
as part of combination therapy for cor pulmonale.

The drug is used by inhalation:

for the relief and prevention of angina pectoris ;
in case of acute myocardial infarction , acute left ventricular failure ;
as a prophylaxis or to treat spasm of the coronary arteries if a cardiac catheter is used.

The medicine is administered intravenously:

in acute myocardial infarction ;
for unstable angina ;
patients with pulmonary edema .

It is also possible to use the substance cutaneously to prevent angina pectoris .

Use of the drug Isosorbide dinitrate

Adults - orally 30 minutes before meals, 5-10 mg 3-4 times a day. In some cases, according to indications, single doses are increased to 20–40 mg. In severe forms of heart failure, 20 mg is prescribed every 4–5 hours. Retard forms are prescribed orally at 40–80 mg every 8–12 hours. Sublingually to relieve angina attacks - 2.5–5 mg, if necessary - every 2 –3 hours. IV drip administration is usually started at a rate of 1–2 mg/hour; if necessary, the infusion rate is increased to 8–10 mg/h. Depending on the clinical picture, hemodynamic parameters and ECG, the infusion can be continued for up to 3 days or more. The solution is prepared ex tempore and administered in a diluted state through a long-term intravenous infusion using automatic perfusers under constant monitoring of the state of the cardiovascular system (blood pressure, heart rate, diuresis, ECG). To obtain a 0.01% solution (concentration 0.1 mg/ml), 50 ml of a 0.1% isosorbide dinitrate solution is diluted to obtain 500 ml of the finished solution; to obtain a 0.02% solution (concentration 0.2 mg/ml), 100 ml of a 0.1% isosorbide dinitrate solution is diluted to obtain 500 ml of the finished solution.

Contraindications

Isosorbide dinitrate preparations are not recommended for use:

with severe arterial hypotension ;
patients in shock;
during collapse ;
patients with constrictive pericarditis ;
with hypertrophic obstructive cardiomyopathy ;
patients with TBI , hemorrhagic stroke or simply increased intracranial pressure ;
in acute myocardial infarction with low blood pressure ;
with cardiac tamponade ;
patients with toxic pulmonary edema ;
for angle-closure glaucoma ;
if allergic to the active substance.

Special instructions for the use of the drug Isosorbide dinitrate

To prevent hypotension and “nitrate” headache, treatment should begin with the minimum recommended dose. To prevent nitrate tolerance, it is recommended that after 3–6 weeks of regular use of tablets or capsules, take a break for 3–5 days, replacing isosorbide dinitrate with other antianginal agents during this time. Use with caution in patients with acute myocardial infarction with low filling pressures. The use of infusion for myocardial infarction should be carried out with constant monitoring of blood pressure levels to prevent its excessive decrease (below 95 mm Hg). If an infusion is used against the background of arterial hypotension, cardiotonic agents should be administered simultaneously or auxiliary devices should be used to maintain blood circulation. During pregnancy and breastfeeding, use only according to strict indications.

Side effects

After taking the drug, the following may occur:

headache, facial flushing blood pressure ;
dizziness, tachycardia , hot flashes and fever;
paradoxical increase in angina ;
dryness of the oral mucosa, burning sensation on the tip of the tongue, nausea;
allergic skin rashes;
decreased visual acuity, weakness and drowsiness ;
collapse , cerebral ischemia (very rare).

Isosorbide Dinitrate, instructions for use (Method and dosage)

The substance is taken sublingually, orally, inhalation, buccally, cutaneously, or intravenous injections of the drug.

Orally, as a rule, 10 to 120 mg of the drug is prescribed, divided into 1-5 doses per day.

For buccal and sublingual use, up to 10 mg of the substance can be taken at a time. The medicine is taken at different frequencies depending on the indications.

Inhalation of the drug involves injecting 1-3 doses into the oral cavity. Between injections it is necessary to make a gap of 30 seconds, holding your breath.

To provide first aid for acute myocardial infarction or heart failure, use 1 to 3 doses. If after 5 minutes there is no improvement in the patient’s condition, then you can take the medicine again.

As a prophylactic agent during catheterization , to avoid coronary spasm, 1-2 doses of the substance are used before catheterization .

Intravenous injections are performed by medical personnel, the dosage varies, depending on the indications and condition of the patient.

The product is applied to the skin at night, 1 gram. In case of urgent need, the daily intake can be increased to 2 grams.

The course of treatment is determined by the attending physician on an individual basis.

Pharmacological properties of the drug Isosorbide dinitrate

Isosorbide dinitrate is one of the main antianginal agents from the group of organic nitrates. A peripheral vasodilator that affects primarily venous vessels. In addition to the direct coronary effect, it reduces heart function by reducing pre- and afterload, and reduces the myocardial oxygen demand. The use of isosorbide dinitrate improves coronary perfusion without developing the steal sign. Has an antihypertensive effect. It is also used as a peripheral vasodilator in severe forms of heart failure: due to a decrease in the tone of peripheral venous vessels, it reduces the load on the heart, pressure in the pulmonary vessels, shortness of breath, and suffocation. When taken orally in the form of tablets or capsules, the onset of action is noted after 15–40 minutes, the maximum effect develops after 1.5–2 hours, the total duration of action is 4–6 hours or more; when using long-acting dosage forms, the duration of action reaches 12 hours. Bioavailability is 59% after sublingual administration and 22% after oral administration. Metabolized in the liver and blood. The half-life of isosorbide dinitrate when taken orally in the form of capsules or tablets is 4 hours, when administered sublingually - 1 hour. It is excreted in the urine, almost entirely in the form of metabolites.

Overdose

In case of overdose, the following symptoms occur: anoxia , collapse , fainting and dizziness , cyanosis of nails and lips, headaches, general weakness, bradycardia , shortness of breath , increased body temperature, convulsions , diarrhea , blurred vision, decreased intracranial pressure , nausea .

As first aid, it is recommended to perform gastric lavage and use symptomatic therapy. With the development of methemoglobinemia, a solution of methylene blue 1-2 mg per kg of the victim’s weight is administered intravenously.

Overdose of the drug Isosorbide dinitrate, symptoms and treatment

The main symptoms are headache, dizziness, orthostatic hypotension, reflex tachycardia, hyperthermia, convulsions. When administered in high doses, methemoglobinemia may develop (cyanosis of the lips, nails and palms, a feeling of pressure in the head, general weakness, tachypnea). The infusion must be stopped; Place the patient in a horizontal position with raised lower limbs. If blood pressure does not return to normal, the blood volume is corrected; in severe cases, dopamine and sympathomimetics are administered. For methemoglobinemia, 1% methylene blue intravenously, oxygen therapy, mechanical ventilation are prescribed, and if necessary, an exchange transfusion is performed.

List of pharmacies where you can buy Isosorbide dinitrate:

Moscow
Saint Petersburg

Interaction

The substance enhances the effect and increases the plasma concentration of dihydroergotamine .

Anticholinergics lead to impairment of memory and attention, especially in older people.

When combining the drug with astringents, enveloping agents and adsorbents, the absorption capacity of isosorbide dinitrate decreases.

Simultaneous use of peripheral vasodilators, beta-blockers, antipsychotics, tricyclic antidepressants, antihypertensive drugs, calcium channel blockers, ethyl alcohol, PDE inhibitors enhances the hypotensive effect.

Sympathomimetics reduce the antianginal effect of the drug.

The medicine reduces the effect of norepinephrine .

When combined with sildenafil, myocardial infarction and a sharp decrease in blood pressure increases .

Drug interactions Isosorbide dinitrate

The hypotensive effect of isosorbide dinitrate is potentiated by other vasodilators, antihypertensive drugs, calcium ion antagonists, cyclic antidepressants, MAO inhibitors and alcohol. With the simultaneous administration of isosorbide dinitrate and dihydroergotamine, the concentration of the latter in the blood may increase, which leads to an increase in its hypotensive effect. Infusion systems made of polyvinyl chloride or polyurethane absorb isosorbide dinitrate, which requires an increase in its dose; Products made of polyethylene, polypropylene, polytetrafluoroethylene and glass do not interact with it. Isosorbide dinitrate solution is compatible with most infusion media: isotonic sodium chloride solution, 5–30% glucose solution, Ringer's solution, protein solutions.

special instructions

Particular care should be taken when treating patients with mitral or aortic stenosis , prone to low blood pressure , elderly people, and with cerebral circulatory disorders.

While undergoing therapy with the drug, you should not drive a car or perform tasks that require high reaction speed and concentration.

To avoid the development of tolerance, it is recommended to take 4 day breaks for every 3-6 weeks of using the substance.

With a gradual increase in the dosage of the drug, it is necessary to monitor blood pressure and heart rate.

Preparations containing (Isosorbide Dinitrate analogues)

Level 4 ATC code matches:
Nitrospray

Nitroglycerine

Efox

Monosan

Nitromint

Pectrol

Isoket

Erinite

Cardiket

Sustak Forte

Nitrosorbide

Trade names of Isosorbide Dinitrate: Aerosonit, Isacardin, Iso Mak spray, Isolong, Cardiket, Nitrosorbide, Nitrosorbide tablets, Dinisorb, Iso Mak retard, Isoket, Isosorbide dinitrate, Cardix, Nitrosorbide-Rusfar, TD-spray Iso Mak .