Isoketum

Isoketum – anti-anginal drug, a peripheral vazodilatator.

Form of release and structure

Dosage forms:

• Concentrate for preparation of solution for infusions (on 10 ml in ampoules, in cardboard packs on 10 ampoules);
• The spray dosed: colourless transparent liquid, has an alcohol smell (on 15 ml, or 300 doses, in glass bottles of dark color with the portioning device, in a cardboard pack 1 bottle).

Active agent – isosorbide dinitrate:

• 1 ml of a concentrate – 1 mg;
• 1 dose (1 injection) of spray – 1,25 mg.

Auxiliary components:

• Concentrate: sodium chloride, chlorohydrogen acid 1M (to рН 5.0-7.0), hydroxide sodium solution 2M, water for injections;
• Spray: ethanol of 100%, macrogoal 400.

Indications to use

Use of Isoketum is shown:

• Concentrate for preparation of solution for infusions: at heart failure of various etiology, an acute myocardial infarction with a left ventricular failure, unstable stenocardia, an acute left ventricular failure;
• Spray: for prevention and stopping of attacks of stenocardia, at an acute myocardial infarction (including, complicated by an acute left ventricular failure), during rehabilitation after the postponed myocardial infarction.

Contraindications

• Acute vascular insufficiency (vascular collapse);
• The expressed arterial hypotension (the systolic arterial pressure (AP) below 90 mm of a mercury column (hg), diastolic the ABP is lower than 60 mm hg);
• Cardiogenic shock;
• Hypersensitivity to drug components.

With care, under control of the attending physician it is necessary to apply Isoketum: at an acute myocardial infarction with the reduced filling pressure of ventricles, a mitral and/or aortal stenosis (it is impossible to allow decrease in the systolic ABP lower than 90 mm hg), tendency to orthostatic reactions; at the diseases which are followed by increase in intracranial pressure including a hemorrhagic stroke and a craniocereberal injury.

During pregnancy and breastfeeding drug is appointed only in urgent cases if the expected therapeutic effect for mother considerably exceeds potential risk for a fruit or the child.

Besides, a contraindication to use of a concentrate is:

• Hypertrophic subaortic stenosis;
• Cardiac tamponade;
• Chronic cardial compression;
• Primary pulmonary diseases (risk of emergence of an anoxemia);
• Coronary heart disease;
• The craniocereberal injury, hemorrhagic stroke and other states proceeding with increase in intracranial pressure;
• Toxic fluid lungs.

Additional contraindications to use of Isoketum in the form of spray:

• Closed-angle glaucoma;
• Deficit glyukozo-6-fosfatdegidrogenazy;
• Hyperthyroidism;
• Concomitant use with phosphodiesterase inhibitors (strengthening of hypotensive effect of drug is possible);
• Age up to 18 years.

With care the severe form of a renal failure should appoint spray at a cardiac tamponade, chronic cardial compression, a hypertrophic subaortic stenosis, a liver failure (the risk of a methemoglobinemia increases), to patients of advanced age.

Route of administration and dosage

• Concentrate for preparation of solution for infusions: it is intended for in/in infusional a vvdeniye by means of automatic systems. Systems for in/in administrations of drug should be applied from polyethylene, polypropylene and polytetrafluoroethylene, systems from other materials cause loss of active ingredient. The procedure is carried out in stationary conditions, under continuous monitoring of indicators of cardiovascular system. On the basis of clinical testimonies and a condition of the patient the doctor makes purpose of drug, since a low dose and gradually increasing, brings it to therapeutic effective. Ampoules with a concentrate should be opened just before use, meeting asepsis conditions. For infusions use solution in concentration of 100 mkg/ml (neobkhodimo50 to part ml of drug of 0,1% to 500 ml) or in 200 mkg/ml (it is necessary to part 100 ml of drug of 0,1% to 500 ml). The initial dose makes 2-7 mg an hour, if necessary increase up to 10 mg an hour is allowed. To patients with heart failure, usually, appoint the raised doses, to 50 mg an hour. Speed of infusion depends on concentration of solution and is determined by the special table of calculation that 20 drops correspond to 1 ml of solution. Taking into account a clinical picture, indicators of the electrocardiogram (ECG) and a hemodynamics the course of treatment can last 3 and more days;
• Spray: the bottle should be held vertically. Before the first use and in case from the last use there passed more than 1 days the first stream of spray it is necessary to send to air. Use of spray is made by its injection in an oral cavity, for this purpose it is necessary to bring the sprayer to a mouth, to make a deep breath and, having held the breath (the aerosol cannot be inhaled), to press the portioning device. After injection of companies it is necessary to close, the feeling of easy burning of language is allowed and to breathe 30 seconds through a nose, then to repeat the procedure. A single dose – 3 injections. Dosing is appointed by the doctor on the basis of clinical testimonies of the patient. Use at an acute heart failure and an acute myocardial infarction is made under control of the ABP and heart rate. Treatment is begun with 1 dose, if necessary with an interval of 5-10 minutes the patient can accept two more doses of spray under control of the attending physician. For stopping and prevention of attacks of stenocardia 1-3 injections are recommended. For stopping of attacks only the doctor can increase a single dose (3 injections).

Side effects

• From cardiovascular system: perhaps – orthostatic hypotension and/or decrease in the ABP (at the first use or increase in a dose of drug), the state can be followed by block, reflex increase in pulse rate, feeling of weakness, dizziness; at the beginning of therapy there can be a headache which is temporary and passes during the first days of use; seldom – strengthening of symptoms of stenocardia against the background of the expressed decrease in the ABP; very seldom – a kollaptoidny state, sometimes with a syncope and bradycardia;
• From the alimentary system: seldom – nausea and vomiting;
• Others: allergic reactions of a dermatological etiology, erubescence of the person; very seldom – exfoliative dermatitis.

Besides, use of spray can cause side effects:

• From the alimentary system: perhaps – dryness in a mouth, feeling of easy burning of language;
• From a nervous system: drowsiness, constraint, a vision disorder (illegibility), decrease in psychomotor reactions (is more often in an initiation of treatment); seldom – brain ischemia.

Special instructions

At in introduction it is necessary to control pulse, the ABP (systolic not lower than 100 mm hg), the volume of the emitted urine (bladder catheterization), to carry out monitoring of an ECG.

It is not recommended to use a concentrate in case of its crystallization.

Use of spray needs to be accompanied with control of the ABP and pulse.

Drug withdrawal is recommended to be carried out gradually.

At frequent appointment and use of high doses for the patient tolerance to drug can develop, in case of decrease in action Isoketum should be cancelled for 24–48 hours. It is recommended to alternate regular reception within 3–6 weeks to a 3-5-day break, temporarily accepting other anti-anginal means.

As a part of spray there are about 85% of ethanol. During treatment alcohol intake should be excluded.

Not to allow hit of drug in eyes.

Spray does not contain freon therefore it is safe for the environment.

During drug use, especially in an initiation of treatment, during the changing of drug or increase in a dose, it is necessary to refrain or observe temporarily extra care at control of vehicles and mechanisms.

Medicinal interaction

Strengthening of hypotensive activity of drug at a combination to other peripheral vazodilatator, beta adrenoblockers, anti-hypertensive means, phosphodiesterase inhibitors, blockers of calcium channels, tricyclic antidepressants, neuroleptics is possible, novokainamidy, ethanol, quinidine.

Increase of anti-anginal effect of drug can happen at a concomitant use of blockers of slow calcium channels (verapamil, nifedipine), Amiodaronum, propranolol.

Decrease in expressiveness of anti-anginal action is possible at a combination with alpha adrenoblockers (dihydroergotamine), sympathomimetics.

At simultaneous use of Isoketum about m-holinoblokatorami (atropine) the risk of increase in intracranial pressure increases.

Terms and storage conditions

To store at a temperature up to 25 °C. To protect from children.

Period of validity – 5 years.