Isoket - instructions for use, doses, side effects, contraindications

Active substanceIsosorbide dinitrateIsosorbide dinitrate

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Dosage form: & nbspconcentrate for solution for infusion

Composition:

1 ml of concentrate for solution for infusion contains:

active substance: isosorbide dinitrate 1.0 mg (in the form of isosorbide dinitrate-sodium chloride 10/90).

Excipients: sodium chloride 9.0 mg, water for injection 994.9 mg (up to 1.00 ml).

Description:Clear, colorless, odorless solution.

Pharmacotherapeutic group:vasodilator - nitrate

ATX: & nbsp

C.05.A.E.02 Isosorbide dinitrate

C.01.D.A.08 Isosorbide dinitrate

Pharmacodynamics:

Isosorbide dinitrate is a peripheral vasodilator with a predominant effect on venous vessels. Has an antianginal effect, causes a marked decrease in blood pressure. The mechanism of action is associated with the release of nitric oxide (an endothelial relaxing factor) in the vascular endothelium,which causes activation of intracellular guanylate cyclase, resulting in an increase in the level of cyclic guanosine monophosphate (cGMP) (mediator of vasodilation). The latter stimulates cGMP-dependent protein kinase, which disrupts the phosphorylation of some smooth muscle cell proteins, including the light chain of myosin, which ultimately reduces contractility and subsequently leads to relaxation of smooth muscle vessels.

It acts on the peripheral arteries and veins. Relaxation of veins leads to a decrease in venous return to the heart (preload), which reduces the filling pressure of the left ventricle. There is also an increase (albeit to a lesser extent) of arterial vessels, which is accompanied by a decrease in blood pressure (BP), a decrease in the total peripheral resistance of the vessels (postload).

Decrease in pre- and postnagruzki leads to a decrease in oxygen consumption by the myocardium.

Promotes redistribution of coronary blood flow in favor of subendocardial zones, especially in coronary artery atherosclerosis (mostly large). Vasodilation of the collateral arteries can improve the blood supply of the myocardium.

Reducing myocardial oxygen consumption and improving oxygen delivery to ischemic areas, reduces the area of myocardial damage.

Improves hemodynamics in patients with chronic heart failure, both at rest and during physical exertion.

Reduces the flow of blood to the right atrium, helps reduce pressure in a small circle of circulation and regression of symptoms with pulmonary edema. It dilates the vessels of the brain, the dura mater, which can be accompanied by a headache.

It also relaxes the smooth muscles of the bronchi, gastrointestinal tract, bile and urinary tract.

Like other nitrates, cross tolerance is developing. After cancellation (interruption in treatment) sensitivity to it is quickly restored.

Pharmacokinetics:Since 0.1% concentrate for the preparation of solution for infusion Isoket is administered intravenously, there is no effect of "primary passage" through the liver. Isosorbide dinitrate metabolized by the participation of the enzyme system glutathione-8-transferase. The active metabolites formed during the cleavage of the nitro group, isosorbide-2-nitrate and isosorbide-5-nitrate have half-lives of 1.5 to 2 hours or 4 to 6 hours, respectively.The half-life of isosorbide dinitrate, administered intravenously, is 10 minutes.

Indications:

- Angina pectoris (unstable and vasospastic).

- Acute myocardial infarction.

- Acute left ventricular failure.

Contraindications:

- Hypersensitivity to isosorbide dinitrate, other nitro compounds or other components of the drug.

- Acute circulatory disturbance (shock, vascular collapse).

- Cardiogenic shock (with the exception of the cases when, with the help of appropriate measures, sufficient enough diastolic pressure is maintained).

- 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 phosphodiesterase-5 inhibitors (such as sildenafil, varnenafil or tadalafil), as they potentiate the hypotensive effect of nitrates.

- Age to 18 years (efficacy and safety of use not established).

- Craniocerebral injury, cerebral hemorrhage, increased intraocular pressure, incl. angle-closure glaucoma.

Carefully:

- With reduced pressure, the filling of the left ventricle, including acute myocardial infarction, left ventricular dysfunction (eg, left ventricular failure);

- With aortic and / or mitral stenosis of mild to moderate;

- In diseases accompanied by increased intracranial pressure (until now, increased intracranial pressure was observed only after intravenous injection of nitroglycerin in high doses);

- With a tendency to arterial hypotension (orthostatic disorders of blood circulation regulation);

- With severe renal failure.

- In severe hepatic insufficiency (risk of development of methemoglobinemia).

- Inadequate and malnutrition.

- Hypothyroidism.

- Pregnancy.

Pregnancy and lactation:For safety reasons, Isoket® can be used with pregnancy and lactation only strictly according to the doctor's prescription, after a thorough evaluation of the benefits to the mother and the possible risk to the fetus, as there is currently insufficient data on the effects of its use in pregnant and lactating mothers.If Isoket ® is used during breastfeeding, it is recommended that breastfeeding be interrupted for the period of treatment.

Dosing and Administration:

The dosage regimen is set individually according to the patient's clinical condition and hemodynamic parameters.

Intravenously

The recommended initial dose of Isoket® is 1-2 mg / hour. The maximum dose of the drug is 8-10 mg / hour. For patients with heart failure, usually higher doses are required - up to 10 mg / h, in some cases up to 50 mg / h. The average dose is approximately 7.5 mg / hour.

Patients who used to take organic nitrates (for example, isosorbide dinitrate, isosorbide-5-mononitrate and nitroglycerine), a higher dose can be administered to achieve the desired hemodynamic effect.

Isoket® should be administered in diluted form intravenously with the help of automatic infusion systems or in an undiluted form using a syringe infusion pump under stationary conditions under constant monitoring of cardiovascular system parameters. 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.

Isoket® is compatible with such infusion solutions used in the hospital as 0.9% solution of sodium chloride, 5-30% dextrose (glucose) solution, Ringer's solution, solutions containing albumin. When combined with other infusion solutions, attention should be paid to the information of the relevant manufacturers about their solutions, as well as compatibility, contraindications, side effects.

Application of a diluted solution for infusions

- Concentration 100 μg / ml (0.01%): 50 ml of 0.1% Isoketo concentrate (5 ampoules of 10 ml) are needed to prepare 500 ml of the ready-made infusion solution.

- Concentration of 200 μg / ml (0.02%): 100 ml of 0.1% Isocet concentrate (10 ampoules of 10 ml) are required to prepare 500 ml of the ready-made infusion solution.

Dose calculation table for diluted solution for infusions

100 μg / ml		Isoket®	200 μg / ml
5 ampoules of 10 ml of concentrate		Dosage	10 ampoules of 10 ml of concentrate
dilute to 500 ml of solution for			dilute to 500 ml of solution for
infusions			infusions
Speed	infusion		Speed	infusion
ml / hour	drops / min	mg / hour	ml / hour	drops / min
10	3-4	1	5	1-2
20	7	2	10	3
30	10	3	15	5
40	13	4	20	7
50	17	5	25	8
60	20	6	30	10
70	23	7	35	12
80	27	8	40	13
90	30	9	45	15
100	33	10	50	17

1 ml corresponds to 20 drops.

Depending on the clinical picture, parameters of hemodynamics and ECG treatment can be continued up to 3 or more days.

Information on the need for dosage adjustment in elderly patients is lacking.

Side effects:

Possible side effects are given below for body systems and frequency of occurrence: very often (more than 1/10), often (more than 1/100 and less than 1/10), infrequently (more than 1/1000 and less than 1/100), rarely more than 1/10000 and less than 1/1000), very rarely (less than 1/10000), the frequency is unknown (the frequency can not be estimated from available data).

From the central nervous system

Very often: headache.

Often: drowsiness, slight dizziness.

From the side of the cardiovascular system

Often: tachycardia, orthostatic hypotension.

Infrequently: the "paradoxical" intensification of angina attacks, collapse (sometimes accompanied by bradyarrhythmia and syncope).

Very rarely: arterial hypotension (lowering blood pressure).

From the gastrointestinal tract

Infrequent: nausea, vomiting. Very rarely: heartburn.

Disturbances from the skin and subcutaneous tissues

Infrequent: skin allergic reactions (including rash), "hot flashes" of blood to the skin of the face.

Very rarely: angioedema, Stevens-Johnson syndrome.

The frequency is unknown: exfoliative dermatitis.

General violations and violations at the site of introduction

Often: asthenia.

Other: development of tolerance (including cross-over to other nitrates). To prevent the development of tolerance, continuous intake of high doses of the drug should be avoided.

For organic nitrates, there have been cases of development of severe hypotension accompanied by nausea, vomiting, anxiety, pallor and increased sweating.

Prolonged use of the drug may cause transient hypoxemia due to the relative redistribution of blood flow to hypoventilation alveolar sites (in patients with coronary heart disease - may lead to myocardial hypoxia).

Overdose:

Symptoms: a marked decrease in blood pressure with symptoms of orthostatic vasodilation, reflex tachycardia and headache. There may appear pallor, increased sweating, "threadlike" pulse, weakness, dizziness, incl. postural, skin hyperemia, nausea, vomiting, diarrhea.In high doses (more than 20 mg / kg body weight), the appearance of methemoglobinemia, cyanosis, tachypnea, dyspnoea due to the formation of nitrite ions due to the metabolism of isosorbide mononitrate, it is also possible the appearance of anxiety, loss of consciousness and cardiac arrest. It is possible that these symptoms can be caused by an overdose of isosorbide dinitrate.

At very high doses of the drug, intracranial pressure may increase, which can lead to cerebral symptoms (headache, dizziness, drowsiness). In chronic overdose, an increase in methemoglobin is detected.

Treatment: when symptoms of an overdose appear, the drug should be discontinued.

If there is a pronounced decrease in blood pressure and / or a shock condition, give the patient a horizontal position with raised legs and take measures to replenish the volume of circulating blood (BCC); in exceptional cases, to improve blood circulation, it is possible to carry out infusions of norepinephrine (noradrenaline) and / or dopamine.

The introduction of epinephrine (adrenaline) and related compounds is contraindicated!

With methemoglobinemia:

1. Ascorbic acid - 1 g inside or in the form of sodium salt intravenously - 0.1 - 0.15 ml / kg 1% solution up to 50 ml.

2. Oxygenotherapy, hemodialysis, exchange blood transfusion.

Interaction:

The use of isosorbide dinitrate with antihypertensive agents (eg, beta-blockers, diuretics, slow calcium channel blockers, angiotensin converting enzyme inhibitors), neuroleptics, tricyclic antidepressants, ethanol and ethanol-containing agents can lead to a marked decrease in blood pressure.

Simultaneous use of Isoket® and phosphodiesterase-5 inhibitors (including sildenafil, tadalafil, vardenafil) is contraindicated in view of the possibility of a marked decrease in blood pressure.

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

When combined with amiodarone, propranolol, blockers of "slow" calcium channels (verapamil, nifedipine, etc.), the antianginal effect may increase.

When intravenously reduces the anticoagulant effect of heparin Saprotherin cofactor of nitric oxide synthase.It is advisable to use caution while using sapropterine-containing medications with all vasodilating agents whose action is associated with nitric oxide (N0), including classical donors N0 (for example, nitroglycerine, isosorbide dinitrate, isosorbide mononitrate) and others.

Special instructions:

Immediate treatment with Isoket® should not be used in patients who immediately before did take phosphodiesterase-5 inhibitors (for example, sildenafil, tadalafil, vardenafil).

During therapy with the drug, it is necessary to monitor the parameters of the cardiovascular system and other vital organs.

Isoket Concentrate is sterile, does not contain preservatives, it is not designed for reusable use. Concentrate should be used immediately after opening the ampoules in aseptic conditions.

For intravenous infusion of Izoket® infusion, systems for transfusion of blood from polyethylene, polypropylene or polytetrafluoroethylene are used. Infusion materials made of polyvinyl chloride or polyurethane reduce the effectiveness of the drug as a result of adsorption, which must be compensated for by increasing the dose.If PVC and / or polyurethane materials are used, the concentration of isosorbide dinitrate should be monitored and dosage adjusted if necessary.

Patients who follow a sodium-restricted diet should note that Isoket® contains 0.15 mmol (3.54 mg) of sodium in 1 ml.

Since Isoket® concentrate is a supersaturated solution, when it is used undiluted, crystallization of the substance can be observed. Despite the fact that under normal conditions this does not affect the activity, in the case of crystallization, concentrate in ampoules is not recommended.

Solution for infusion should be used within 24 hours after breeding!

Effect on the ability to drive transp. cf. and fur:It is recommended to be careful.

Form release / dosage:

Concentrate for the preparation of a solution for infusions 1 mg / ml.

Packaging:For 10 ml of the solution in ampoules of colorless transparent glass with one coding color ring and a notch on the neck of the ampoule, the place of which is indicated by a colored dot on top. For 10 ampoules installed in the cells along with instructions for use in a cardboard bundle.

Storage conditions:At a temperature of no higher than 25 ° C.Keep out of the reach of children.

Shelf life:

5 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N012496 / 01

Date of registration:16.09.2011

The owner of the registration certificate:YUSB Farma SpAYUSB Farma SpA Italy

Manufacturer: & nbsp

EVER Pharma Jena, GmbH Germany

Representation: & nbspYUSB FARMA LLC YUSB FARMA LLC Russia

Information update date: & nbsp18.06.2014

Illustrated instructions

Instructions

Isoket® (Isoket®)