Ilomedin instructions for use of the drug

Release form, packaging and composition of the drug Clinical-pharmacological group Pharmaco-therapeutic group Pharmacological action Indications for use Method of administration and doses Side effects Contraindications for use Use in children Special instructions Drug interactions

Registration Certificate Holder:

BAYER PHARMA, AG (Germany)

ATX Code:

B01AC11

Active substance:

iloprost

Dosage form:

Ilomedin

Release form, packaging and composition of the drug Ilomedin

Concentrate for the preparation of solution for infusion

transparent, colorless or almost colorless.

Excipients

: trometamol, ethanol 96%, sodium chloride, hydrochloric acid 0.1M, water for injection.

1 ml - colorless glass ampoules with a capacity of 1 ml (1) - cardboard trays (1) - cardboard packs. 1 ml - colorless glass ampoules with a capacity of 1 ml (5) - cardboard trays (1) - cardboard packs. 1 ml - colorless glass ampoules with a capacity of 1 ml (5) - cardboard trays (4) - cardboard packs.

Concentrate for the preparation of solution for infusion

transparent, colorless or almost colorless.

Excipients

: trometamol, ethanol 96%, sodium chloride, hydrochloric acid 0.1M, water for injection.

2.5 ml - colorless glass ampoules with a capacity of 3 ml (1) - cardboard trays (1) - cardboard packs. 2.5 ml - colorless glass ampoules with a capacity of 3 ml (5) - cardboard trays (1) - cardboard packs. 2.5 ml - colorless glass ampoules with a capacity of 3 ml (5) - cardboard trays (4) - cardboard packs.

Ilomedin concentrate solution for infusion 20 mcg/ml ampoules of 1 ml 5 pcs.

Duration of treatment is up to 4 weeks. Ilomedin should only be used under closely monitored conditions in hospitals or outpatient settings with appropriate technical capabilities. Before starting treatment, women should exclude pregnancy. Ilomedin should be used only after dilution. The solution must be freshly prepared. The contents of the ampoule and the solvent must be thoroughly mixed. Breeding. The dilution method must be strictly followed depending on the method of administration of the solution. When using an infusion pump (infusion pump). The contents of an ampoule of 1 ml of concentrate for preparing a solution for infusion are diluted with a sterile 0.9% sodium chloride solution or 5% glucose (dextrose) solution for injection to a volume of 100 ml. The contents of an ampoule of 2.5 ml of concentrate for preparing a solution for infusion are diluted with a sterile 0.9% sodium chloride solution or 5% glucose (dextrose) solution for injection to a volume of 250 ml. When using an automatic syringe. The contents of an ampoule of 1 ml of concentrate for preparing a solution for infusion are diluted with a sterile 0.9% sodium chloride solution or 5% glucose (dextrose) solution for injection to a volume of 10 ml. The contents of an ampoule of 2.5 ml of concentrate for preparing a solution for infusion are diluted with a sterile 0.9% sodium chloride solution or 5% glucose (dextrose) solution for injection to a volume of 25 ml. After dilution, Ilomedin is administered daily as a 6-hour infusion into a peripheral vein or a catheter installed in a central vein. The rate of administration (dose) depends on individual tolerance and is 0.5-2.0 ng per 1 kg of body weight per minute. It is necessary to monitor blood pressure and heart rate at the beginning of the infusion and with each increase in the dose of the drug. During the first 2-3 days, individual tolerance to the drug is determined - treatment begins with an injection rate of 0.5 ng/kg/min for 30 minutes. After this, the dose is increased stepwise by 0.5 ng/kg/min approximately every 30 minutes. The exact infusion rate is calculated based on body weight at a maximum tolerated dose ranging from 0.5 to 2.0 ng/kg/min. (see below for infusion rate tables when using an infusion pump or an automatic syringe). Depending on the frequency of side effects such as headache, nausea or decreased blood pressure, the infusion rate should be reduced to the maximum tolerated. If severe side effects develop, the infusion must be interrupted. Treatment should be continued usually for 4 weeks, using doses that were well tolerated in the first 2-3 days of the previous course of treatment. It is not recommended to carry out continuous infusions over several days due to the possibility of developing tachyphylaxis, expressed in a weakening effect on platelets, and the possibility of “rebound syndrome”, manifested in an increased tendency to platelet aggregation upon completion of the course of therapy. However, there are no reports of any clinical complications associated with these phenomena. In renal failure requiring dialysis and liver cirrhosis, the excretion of iloprost is reduced. In these cases, it is necessary to reduce the recommended dose by 2 times.

pharmachologic effect

Iloprost is a synthetic analogue of prostacyclin, inhibits platelet aggregation, adhesion and platelet release reaction; dilates arterioles and venules; increases capillary density (restores impaired microcirculation by inducing vasodilation, inhibiting platelet activation, restoring and protecting the endothelium, activating endogenous fibrinolysis and correcting imbalances in the cytokine system) and reduces increased vascular permeability caused by mediators such as serotonin or histamine in the microcirculation system; activates endogenous fibrinolysis; exhibits an anti-inflammatory effect: suppresses the adhesion and migration of leukocytes after endothelial damage, as well as the accumulation of leukocytes in damaged tissue, reduces the production of tumor necrosis factor (TNFα).

Ilomedin instructions for use

Release form Concentrate for the preparation of solution for infusion

Compound

1 ml contains iloprost trometamol 27 mcg, which corresponds to the content of iloprost 20 mcg

Package

5 amp. 1 ml each

pharmachologic effect

Iloprost is a synthetic analogue of prostacyclin, inhibits platelet aggregation, adhesion and platelet release reaction; dilates arterioles and venules; increases capillary density (restores impaired microcirculation by inducing vasodation, inhibiting platelet activation, restoring and protecting the endothelium, activating endogenous fibrinolysis and correcting imbalances in the cytokine system) and reduces increased vascular permeability caused by mediators such as serotonin or histamine in the microcirculation system; activates endogenous fibrinolysis; exhibits an anti-inflammatory effect: suppresses the adhesion and migration of leukocytes after endothelial damage, as well as the accumulation of leukocytes in damaged tissue, reduces the production of tumor necrosis factor (TNF alpha).

Indications

— thromboangiitis obliterans (Buerger’s disease) in late stages with critical limb ischemia in cases where there are no indications for revascularization;

- severe forms of occlusive peripheral artery disease, especially in cases of risk of amputation and when vascular surgery or angioplasty is not possible;

- severe Raynaud's syndrome, leading to disability, not amenable to treatment with other drugs.

Contraindications

- pathological conditions in which the effect of iloprost on platelets may increase the risk of bleeding (for example, peptic ulcer of the stomach or duodenum in the acute stage, trauma, intracranial bleeding);

- severe coronary heart disease or unstable angina; myocardial infarction within the last 6 months; acute heart failure or chronic congestive heart failure stage II-IV (according to the New York Heart Association classification); severe heart rhythm disturbances;

— suspicion of congestion in the pulmonary circulation;

- lactation period;

- pregnancy;

- hypersensitivity to iloprost or other components of the drug

With caution: in patients with cerebrovascular accident in the last 3 months (for example, transient ischemic disorder, stroke). Such patients require a careful assessment of the benefit-risk ratio of treatment.

In renal failure requiring dialysis and liver cirrhosis, the excretion of iloprost is reduced.

It is necessary to take measures against a further decrease in blood pressure in patients with initially (before starting Ilomedin therapy) low blood pressure values; Patients with severe heart disease should be closely monitored.

The possibility of developing orthostatic hypotension should be taken into account when patients move from a horizontal to a vertical position after completing the administration of Ilomedin.

Directions for use and doses

IV, in the form of infusions, daily as a 6-hour infusion into a peripheral vein or a catheter installed in a central vein. The rate of administration (dose) depends on individual tolerance and is 0.5-2 ng/kg/min. During the first 2-3 days, individual tolerability of the drug is determined under the control of heart rate and blood pressure (should be determined at the beginning of the infusion and after each dose increase): treatment begins with an administration rate of 0.5 ng/kg/min for 30 minutes, then the dose is increased stepwise by 0.5 ng/kg/min every 30 min. The exact infusion rate is calculated based on body weight and the maximum tolerated dose, within the range of 0.5-2 ng/kg/min. Determination of the infusion rate (ml/h) when using an infusion pump (for example Infusomat): the contents of the ampoule are dissolved in a sterile 0.9% NaCl solution or 5% dextrose solution and the final volume of the solution is adjusted to the contents of the ampoule (2.5 ml) 50 mcg - to 250 ml, for an ampoule (1 ml) 20 mcg - up to 100 ml. A solution is obtained at a concentration of 0.2 μg/ml, the rate of its infusion is determined in accordance with the scheme depending on the dose and body weight (within 0.5-2 ng/kg/min): with a body weight of 40 kg and a dose of 0.5 ng/kg/min, the rate infusion - 6 ml/h, 1 ng/kg/min - 12 ml/h, 1.5 ng/ml/min - 18 ml/h, 2 ng/ml/min - 24 ml/h; with a body weight of 50 kg and a dose of about 5 ng/kg/min - 7.5 ml/h, 1 ng/kg/min - 15 ml/h, 1.5 ng/kg/min - 22.5 ml/h, 2 ng/kg/ min - 30 ml/h; with a body weight of 60 kg and a dose of 0.5 ng/kg/min - 9 ml/h, 1 ng/kg/min - 18 ml/h, 1.5 ng/kg/min - 27 ml/h, 2 ng/kg/min - 36 ml/h; with a body weight of 70 kg and a dose of 0.5 ng/kg/min - 10.5 ml/h, 1 ng/kg/min - 21 ml/h, 1.5 ng/kg/min - 31.5 ml/h, 2 ng/kg/min - 42 ml/h; with a body weight of 80 kg and a dose of 0.5 ng/kg/min - 12 ml/h, 1 ng/kg/min - 24 ml/h, 1.5 ng/kg/min - 36 ml/h, 2 ng/kg/min - 48 ml/h; with a body weight of 90 kg and a dose of 0.5 ng/kg/min - 13.5 ml/h, 1 ng/kg/min - 27 ml/h, 1.5 ng/kg/min - 40.5 ml/h, 2 ng/kg/min - 54 ml/h; with a body weight of 100 kg and a dose of 0.5 ng/kg/min - 16 ml/h, 1 ng/kg/min - 30 ml/h, 1.5 ng/kg/min 45 ml/h, 2 ng/kg/min - 60 ml/h; with a body weight of 110 kg and a dose of 0.5 ng/kg/min - 16.5 ml/h, 1 ng/kg/min - 33 ml/h, 1.5 ng/kg/min - 49.5 ml/h, 2 ng/kg/min - 66 ml/h. Determination of the infusion rate (ml/h) when using an automatic syringe (for example Perfusor): the contents of the ampoules are diluted in a sterile 0.9% NaCl solution or 5% dextrose solution and the final volume of the solution is adjusted for the contents of the ampoule (2.5 ml) 50 mcg - to 25 ml, for an ampoule (1 ml) 20 mcg - up to 10 ml. A solution is obtained at a concentration of 2 μg/ml, the rate of its infusion is determined in accordance with the scheme depending on the dose and body weight (within 0.5-2.0 ng/kg/min): with a body weight of 40 kg and a dose of 0.5 ng/kg/min, the rate infusion - 0.6 ml/h, 1 ng/kg/min - 1.2 ml/h, 1.5 ng/kg/min - 1.8 ml/h, 2 ng/kg/min - 2.4 ml/h; with a body weight of 50 kg and a dose of 0.5 ng/kg/min - 0.75 ml/h, 1.5 ng/kg/min - 1.5 ml/h, 1.5 ng/kg/min - 2.25 ml/h, 2 ng/kg/min - 3 ml/h; with a body weight of 60 kg and a dose of 0.5 ng/kg/min - 0.9 ml/h, 1 ng/kg/min - 1.8 ml/h, 1.5 ng/kg/min - 2.7 ml/h, 2 ng/kg/min - 3.6 ml/h; with a body weight of 70 kg and a dose of 0.5 ng/kg/min - 1.05 ml/min, 1 ng/kg/min - 2.1 ml/h, 1.5 ng/kg/min - 3.15 ml/h, 2 ng/kg/min - 4.2 ml/h; with a body weight of 80 kg and a dose of 0.5 ng/kg/min - 1.2 ml/h, 1 ng/kg/min - 2.4 ml/h, 1.5 ng/kg/min - 3.6 ml/h, 2 ng/kg/min - 4.8 ml/h; with a body weight of 90 kg and a dose of 0.5 ng/kg/min - 1.35 ml/h, 1 ng/kg/min - 2.7 ml/h, 1.5 ng/kg/min - 4.05 ml/h, 2 ng/kg/min - 5.4 ml/h; with a body weight of 100 kg and a dose of 0.5 ng/kg/min - 1.5 ml/h, 1 ng/kg/min - 3 ml/h, 1.5 ng/kg/min - 1.5 ml/h, 2 ng/kg/min - 6 ml/h; with a body weight of 110 kg and a dose of 0.5 ng/kg/min - 1.65 ml/h, 1 ng/kg/min - 3.3 ml/h, 1.5 ng/kg/min - 4.95 ml/h, 2 ng/kg/min - 6.6 ml/h. Duration of treatment - up to 4 weeks. In patients suffering from Raynaud's syndrome, shorter courses of treatment - 3-5 days - are often sufficient to achieve short-term remission (several weeks). If side effects such as headache, nausea or decreased blood pressure occur, the infusion rate should be reduced to the maximum tolerated. If severe side effects develop, the infusion must be interrupted. Treatment is usually resumed after 4 weeks in doses that the patient tolerated well in the first 2-3 days of the previous course of treatment. In case of renal failure requiring dialysis and liver cirrhosis, the recommended dose is reduced by 2 times.

Side effects

From the nervous system and sensory organs: often (more than 1%, but less than 10%) - dizziness, headache, paresthesia, hyperesthesia, tinnitus, anxiety, agitation, lethargy, apathy, drowsiness; less often (more than 0.1%, but less than 1%) - tremor, cerebrovascular disorders, depression, hallucinations, migraine, fainting, prolonged loss of consciousness, blurred vision, irritation and pain in the eyes; rarely (more than 0.01%, but less than 0.1%) - vestibular disorders; frequency unknown - confusion. From the cardiovascular system: often (more than 1%, but less than 10%) - decreased blood pressure, bradycardia, flushing of the skin and a feeling of heat; less often (more than 0.1%, but less than 1%) - arrhythmia (including extrasystole), myocardial ischemia, myocardial infarction, deep vein thrombosis, pulmonary embolism; frequency unknown - increased blood pressure, tachycardia; in isolated cases (in elderly patients with severe atherosclerosis) - pulmonary edema. From the respiratory system: less often (more than 0.1%, but less than 1%) - bronchial asthma; rarely (more than 0.01%, but less than 0.1%) - cough; in isolated cases (in elderly patients with severe atherosclerosis) - heart failure. From the digestive system: more often (more than 10%) - nausea, vomiting; often (more than 1%, but less than 10%) - anorexia, diarrhea, abdominal discomfort, abdominal pain; less often (more than 0.1%, but less than 1%) - dry mouth, change in taste, tenesmus, constipation, belching, dysphagia, diarrhea, melena, rectal bleeding, jaundice. From the musculoskeletal system: often (more than 1%, but less than 10%) - pain in the masticatory muscles, trismus, myalgia, arthralgia, muscle weakness; less often (more than 0.1%, but less than 1%) - tetany, convulsive muscle twitching, hypertonicity. From the urinary system: lower back pain, renal colic, changes in the cellular composition of urine, dysuria. Local reactions: often (more than 1%, but less than 10%) - skin hyperemia, pain, phlebitis at the injection site. Other: more often (more than 10%) - sweating; often (more than 1%, but less than 10%) - local pain, generalized pain, hyperthermia, itching, fatigue, thirst; frequency unknown - allergic reactions.

special instructions

In the hope of success of conservative therapy with iloprost, surgery should not be delayed in patients requiring emergency leg amputation (for example, with infected gas gangrene).

Patients should be strongly advised to quit smoking.

Accidental injection of undiluted Ilomedin solution into nearby tissues can lead to local changes at the injection site (redness, pain, itching, feeling of heat).

Avoid taking the drug orally and getting it on mucous membranes. If iloprost comes into contact with the skin, it can cause prolonged, although painless, erythema. Therefore, care must be taken to avoid contact of the drug with the skin. If iloprost gets on any part of the skin, it should be washed immediately with plenty of water or saline sodium chloride solution.

Directions for use and doses

Duration of treatment is up to 4 weeks.

Ilomedin should only be used under closely monitored conditions in hospitals or outpatient settings with appropriate technical capabilities.

Before starting treatment, women should exclude pregnancy.

Ilomedin should be used only after dilution. The solution must be freshly prepared.

The contents of the ampoule and the solvent must be thoroughly mixed.

Breeding

The dilution method must be strictly followed depending on the method of administration of the solution.

When using an infusion pump (infusion pump)

The contents of an ampoule of 1 ml of concentrate for preparing a solution for infusion are diluted with a sterile 0.9% sodium chloride solution or 5% glucose (dextrose) solution for injection to a volume of 100 ml.

The contents of an ampoule of 2.5 ml of concentrate for preparing a solution for infusion are diluted with a sterile 0.9% sodium chloride solution or 5% glucose (dextrose) solution for injection to a volume of 250 ml.

When using an automatic syringe

The contents of an ampoule of 1 ml of concentrate for preparing a solution for infusion are diluted with a sterile 0.9% sodium chloride solution or 5% glucose (dextrose) solution for injection to a volume of 10 ml.

The contents of an ampoule of 2.5 ml of concentrate for preparing a solution for infusion are diluted with a sterile 0.9% sodium chloride solution or 5% glucose (dextrose) solution for injection to a volume of 25 ml.

After dilution, Ilomedin is administered daily as a 6-hour infusion into a peripheral vein or a catheter installed in a central vein. The rate of administration (dose) depends on individual tolerance and is 0.5-2.0 ng/kg body weight/min.

It is necessary to monitor blood pressure and heart rate at the beginning of infusions and with each increase in the dose of the drug.

During the first 2-3 days, individual tolerability of the drug is determined - treatment begins with an injection rate of 0.5 ng/kg/min for 30 minutes. After this, the dose is increased stepwise by 0.5 ng/kg/min approximately every 30 minutes. The exact infusion rate is calculated based on body weight with a maximum tolerated dose ranging from 0.5 to 2.0 ng/kg/min.

Depending on the frequency of adverse reactions such as headache, nausea or decreased blood pressure, the infusion rate should be reduced to the maximum tolerated. If severe adverse reactions develop, the infusion must be interrupted. Treatment should be continued usually for 4 weeks, using doses that were well tolerated in the first 2-3 days of the previous course of treatment.

Infusion rate (ml/h) for administering different doses when using an infusion pump (infusion pump)

The following table can be used to calculate the infusion rate appropriate to the individual patient's body weight and the dose to be administered.

Infusion rate (ml/h) for different doses when using an auto-injector

The following table can be used to calculate the infusion rate appropriate to the individual patient's body weight and the dose to be administered.

In patients with systemic scleroderma and Raynaud's syndrome

, a shorter course of treatment (3-5 days) is often sufficient to achieve improvement lasting several weeks.

Continuous infusions over several days are not recommended due to the possibility of developing tachyphylaxis, expressed as a weakening effect on platelets, and the possibility of rebound syndrome, manifested by an increased tendency to platelet aggregation upon completion of the course of therapy. However, there are no reports of any clinical complications associated with these phenomena.

For renal failure requiring dialysis and cirrhosis of the liver

iloprost excretion is reduced. In these cases, it is necessary to reduce the recommended dose by 2 times.

Ilomedin, 20 mcg/ml, concentrate for solution for infusion, 1 ml, 5 pcs.

IV

, by infusion (using an infusion pump or an automatic syringe).

Ilomedin should only be used under conditions of close monitoring and control of the patient's condition in hospitals or outpatient facilities with appropriate technical capabilities.

Before starting treatment, women should exclude pregnancy.

Duration of treatment - up to 4 weeks.

Ilomedin should be used only after dilution. The solution must be freshly prepared. The contents of the ampoule and the solvent must be thoroughly mixed.

Breeding

The dilution method must be strictly followed depending on the method of administration of the solution.

1. Using an infusion pump (infusion pump)

The contents of the ampoule with 1 ml of concentrate for preparing a solution for infusion are diluted with a sterile 0.9% sodium chloride solution or 5% glucose (dextrose) solution for injection to a volume of 100 ml; the contents of the ampoule with 2.5 ml of concentrate for preparing a solution for infusion - up to a volume of 250 ml.

2. Using an automatic syringe

The contents of the ampoule with 1 ml of concentrate for preparing a solution for infusion are diluted with a sterile 0.9% sodium chloride solution or 5% glucose (dextrose) solution for injection to a volume of 10 ml; the contents of the ampoule with 2.5 ml of concentrate for preparing a solution for infusion - up to a volume of 25 ml.

After dilution, Ilomedin is administered daily as a 6-hour infusion into a peripheral vein or a catheter installed in the central vein. The rate of administration (dose) depends on individual tolerance and is 0.5–2 ng/kg/min.

It is necessary to monitor blood pressure and heart rate at the beginning of infusions and with each increase in the dose of the drug.

During the first 2–3 days, individual tolerability of the drug is determined - treatment begins with an administration rate of 0.5 ng/kg/min for 30 minutes. After this, the dose is increased stepwise by 0.5 ng/kg/min approximately every 30 minutes. The exact infusion rate is calculated based on body weight at the maximum tolerated dose, ranging from 0.5 to 2 ng/kg/min (see below tables for infusion rates when using an infusion pump or autosyringe).

Depending on the frequency of side effects such as headache, nausea or decreased blood pressure, the infusion rate should be reduced to the maximum tolerated. If severe side effects develop, the infusion must be interrupted. Treatment is usually continued for 4 weeks, using doses that were well tolerated in the first 2-3 days of the previous course of treatment.

Tables 1 and 2 can be used to calculate the infusion rate appropriate to the individual patient's body weight and dose to be administered.

Table 1

Infusion rate (ml/h) for administering different doses when using an infusion pump (infusion pump)

table 2

Infusion rate (ml/h) for different doses when using an auto-injector

In patients with systemic scleroderma who have Raynaud's phenomenon, a shorter course of treatment (3–5 days) is often sufficient to achieve improvement lasting several weeks.

Continuous infusions over several days are not recommended due to the possibility of developing tachyphylaxis, expressed as a weakening effect on platelets, and the possibility of rebound syndrome, manifested by an increased tendency to platelet aggregation upon completion of the course of therapy. However, there are no reports of any clinical complications associated with these phenomena.

In renal failure requiring dialysis and liver cirrhosis, the excretion of iloprost is reduced. In these cases, it is necessary to reduce the recommended dose by 2 times.

Side effect

The most commonly observed adverse reactions (≥10%) noted with the use of Ilomedin in clinical studies were headache, hot flashes, nausea, vomiting, and hyperhidrosis. Typically, these side effects occur at the beginning of treatment when selecting the maximum tolerated dose and quickly disappear with dose reduction.

The most serious adverse reactions observed with the use of Ilomedin were cerebrovascular events, myocardial infarction, pulmonary embolism, heart failure, convulsions, hypotension, tachycardia, bronchial asthma, angina pectoris, shortness of breath and pulmonary edema.

Another group of side effects is associated with reactions at the injection site. Thus, redness and pain may occur at the injection site, and dilatation of cutaneous vessels can sometimes lead to streak-like erythema over the infusion site.

Undesirable side effects noted with the use of Ilomedin during clinical trials are distributed according to the frequency of occurrence according to the following gradation: very common (≥1/10), common (≥1/100 and <1/10), uncommon (≥1/10). 1000 and <1/100, rare (≥1/10,000 and <1/1000), very rare (<1/10,000).

The safety profile of Ilomedin is assessed based on pooled clinical trial and post-marketing data.

Estimated incidence rates are based on a pooled database of 3,325 patients who received iloprost in both controlled and uncontrolled clinical trials or the compassionate use program. Data were obtained mainly from elderly patients and patients with multiple pathologies suffering from peripheral arterial occlusive disease in stages III and IV, as well as in patients with thromboangiitis obliterans.

*Life-threatening effects or death have been reported.

Iloprost can provoke angina, especially in patients with coronary artery disease. The use of iloprost in combination with platelet aggregation inhibitors, heparin or indirect anticoagulants (coumarin derivatives) increases the risk of bleeding.

Ilomedin 20 µg/ml 1 ml 5 pcs. concentrate for the preparation of solution for infusion

pharmachologic effect

Iloprost is a synthetic analogue of prostacyclin, inhibits platelet aggregation, adhesion and platelet release reaction; dilates arterioles and venules; increases capillary density (restores impaired microcirculation by inducing vasodilation, inhibiting platelet activation, restoring and protecting the endothelium, activating endogenous fibrinolysis and correcting imbalances in the cytokine system) and reduces increased vascular permeability caused by mediators such as serotonin or histamine in the microcirculation system; activates endogenous fibrinolysis; exhibits an anti-inflammatory effect: suppresses the adhesion and migration of leukocytes after endothelial damage, as well as the accumulation of leukocytes in damaged tissue, reduces the production of tumor necrosis factor (TNFα).

Composition and release form Ilomedin 20 µg/ml 1 ml 5 pcs. concentrate for the preparation of solution for infusion

Concentrate - 1 amp. (1 ml):

• Active substance: iloprost trometamol 27 mcg, which corresponds to the content of iloprost 20 mcg.
• Excipients: trometamol, ethanol 96%, sodium chloride, hydrochloric acid 0.1M, water for injection.

1 ml - colorless glass ampoules with a capacity of 1 ml (5) - cardboard trays (1) - cardboard packs.

Description of the dosage form

The concentrate for the preparation of solution for infusion is transparent, colorless or almost colorless.

Directions for use and doses

Duration of treatment is up to 4 weeks.

Ilomedin should only be used under closely monitored conditions in hospitals or outpatient settings with appropriate technical capabilities.

Before starting treatment, women should exclude pregnancy.

Ilomedin should be used only after dilution. The solution must be freshly prepared.

The contents of the ampoule and the solvent must be thoroughly mixed.

Breeding

The dilution method must be strictly followed depending on the method of administration of the solution.

When using an infusion pump (infusion pump)

The contents of an ampoule of 1 ml of concentrate for preparing a solution for infusion are diluted with a sterile 0.9% sodium chloride solution or 5% glucose (dextrose) solution for injection to a volume of 100 ml.

The contents of an ampoule of 2.5 ml of concentrate for preparing a solution for infusion are diluted with a sterile 0.9% sodium chloride solution or 5% glucose (dextrose) solution for injection to a volume of 250 ml.

When using an automatic syringe

The contents of an ampoule of 1 ml of concentrate for preparing a solution for infusion are diluted with a sterile 0.9% sodium chloride solution or 5% glucose (dextrose) solution for injection to a volume of 10 ml.

The contents of an ampoule of 2.5 ml of concentrate for preparing a solution for infusion are diluted with a sterile 0.9% sodium chloride solution or 5% glucose (dextrose) solution for injection to a volume of 25 ml.

After dilution, Ilomedin is administered daily as a 6-hour infusion into a peripheral vein or a catheter installed in a central vein. The rate of administration (dose) depends on individual tolerance and is 0.5-2.0 ng/kg body weight/min.

It is necessary to monitor blood pressure and heart rate at the beginning of infusions and with each increase in the dose of the drug.

During the first 2-3 days, individual tolerability of the drug is determined - treatment begins with an injection rate of 0.5 ng/kg/min for 30 minutes. After this, the dose is increased stepwise by 0.5 ng/kg/min approximately every 30 minutes. The exact infusion rate is calculated based on body weight with a maximum tolerated dose ranging from 0.5 to 2.0 ng/kg/min.

Depending on the frequency of adverse reactions such as headache, nausea or decreased blood pressure, the infusion rate should be reduced to the maximum tolerated. If severe adverse reactions develop, the infusion must be interrupted. Treatment should be continued usually for 4 weeks, using doses that were well tolerated in the first 2-3 days of the previous course of treatment.

Infusion rate (ml/h) for administering different doses when using an infusion pump (infusion pump)

The following table can be used to calculate the infusion rate appropriate to the individual patient's body weight and the dose to be administered.

Infusion rate (ml/h) for different doses when using an auto-injector

The following table can be used to calculate the infusion rate appropriate to the individual patient's body weight and the dose to be administered.

In patients with systemic scleroderma who have Raynaud's phenomenon, a shorter course of treatment (3-5 days) is often sufficient to achieve improvement lasting several weeks.

Continuous infusions over several days are not recommended due to the possibility of developing tachyphylaxis, expressed as a weakening effect on platelets, and the possibility of rebound syndrome, manifested by an increased tendency to platelet aggregation upon completion of the course of therapy. However, there are no reports of any clinical complications associated with these phenomena.

In renal failure requiring dialysis and liver cirrhosis, the excretion of iloprost is reduced. In these cases, it is necessary to reduce the recommended dose by 2 times.

Pharmacokinetics

Distribution

Equilibrium concentration in blood plasma is achieved very quickly, 10-20 minutes after the start of intravenous infusions. The time to achieve it depends linearly on the infusion rate; at an infusion rate of 3 ng/kg/min, a concentration is achieved approximately equal to 135 ± 24 pg/ml. After the end of the infusions, the concentration of iloprost in plasma decreases very quickly (this is due to the very high intensity of its metabolism). Metabolic clearance is approximately 20±5 ml/kg/min. T1/2 from blood plasma in the terminal phase of distribution is about 0.5 hours. 2 hours after cessation of infusions, the content of the drug substance is less than 10% of the equilibrium concentration. Binding to plasma albumin is 60%.

Metabolism

Iloprost is metabolized primarily by P-oxidation of the carboxyl side chain. The substance is not excreted from the body unchanged. The main metabolite, tetranoryloprost, is found in urine in free form and in four conjugated forms of diastereoisomers. Experiments on animals have shown that tetranoryloprost is pharmacologically inactive. The results of in vitro studies indicate a similar pattern of metabolism of iloprost in the lungs after intravenous administration or inhalation.

Removal

Elimination of iloprost after intravenous infusion in subjects with normal renal and hepatic function in most cases is characterized by a biphasic profile with average T1/2 durations of 3-5 minutes and 15-30 minutes, respectively. The total clearance of iloprost is approximately 20 ml/kg/min, indicating that iloprost metabolism occurs partially outside the liver.

A mass balance study was conducted using 3H-labeled iloprost in healthy subjects. After IV infusions, the excretion of total radioactivity was 81%, with 68% excreted in the urine and 12% in the feces. Elimination of metabolites from plasma and their excretion in urine have a two-phase character, with T1/2 from plasma in the first phase being about 2 hours, in the second - about 5 hours, and for urine - 2 and 18 hours, respectively.

Pharmacokinetics in special clinical situations

For renal failure

In a study using IV infusions of iloprost, patients with end-stage renal disease receiving intermittent dialysis showed significantly lower clearance (mean clearance = 5 ± 2 ml/min/kg) than in patients with renal failure. who are not receiving dialysis treatment (mean clearance = 18±2 ml/min/kg).

In case of liver dysfunction

Since iloprost is extensively metabolized in the liver, changes in hepatic function affect plasma concentrations of the drug. The results of the study with intravenous administration of the drug included data from 8 patients suffering from liver cirrhosis. The average clearance of iloprost was calculated to be 10 ml/min/kg.

Age and gender

The pharmacokinetics of iloprost does not depend on the age and gender of the patient.

Indications for use Ilomedin 20 µg/ml 1 ml 5 pcs. concentrate for the preparation of solution for infusion

• Thromboangiitis obliterans (Buerger's disease) in late stages with critical limb ischemia in cases where there are no indications for revascularization;
• severe forms of peripheral arterial occlusive disease, especially in cases of risk of amputation and when vascular surgery or angioplasty is not possible;
• severe Raynaud's syndrome, leading to disability, not amenable to treatment with other drugs.

Contraindications

• Pathological conditions in which the effect of iloprost on platelets may increase the risk of bleeding (for example, acute gastric or duodenal ulcer, trauma, intracranial bleeding);
• severe ischemic heart disease or unstable angina; myocardial infarction within the last 6 months; acute heart failure or chronic congestive heart failure stage II-IV (NYHA classification);
• severe heart rhythm disturbances;
• suspicion of congestion in the pulmonary circulation;
• lactation period;
• pregnancy;
• hypersensitivity to iloprost or other components of the drug.

With caution: in patients with cerebrovascular accident in the last 3 months (for example, transient ischemic disorder, stroke). Such patients require a careful assessment of the benefit-risk ratio of treatment.

In renal failure requiring dialysis and liver cirrhosis, the excretion of iloprost is reduced.

It is necessary to take measures against a further decrease in blood pressure in patients with initially (before starting Ilomedin therapy) low blood pressure values; Patients with severe heart disease should be closely monitored.

The possibility of developing orthostatic hypotension should be taken into account when patients move from a horizontal to a vertical position after completing the administration of Ilomedin.

Application Ilomedin 20 µg/ml 1 ml 5 pcs. concentrate for the preparation of a solution for infusion during pregnancy and lactation

Ilomedin should not be prescribed to women during pregnancy and lactation. There are no data on the use of iloprost in pregnant women.

Preclinical studies indicate that iloprost is toxic to the fetus in rats, but not in rabbits and monkeys.

Because The potential risk of therapeutic use of iloprost during pregnancy is unknown; when treating with iloprost, women of fertile age should use reliable contraception.

There is currently no evidence that iloprost is excreted into breast milk in humans, however, as there is evidence that iloprost can pass into milk in small amounts in rats, it should not be administered to nursing mothers.

Use in children

Currently, there are only isolated reports on the use of this drug in children and adolescents.

special instructions

In the hope of success of conservative therapy with iloprost, surgery should not be delayed in patients requiring emergency leg amputation (for example, with infected gas gangrene).

Patients should be strongly advised to quit smoking.

Accidental injection of undiluted Ilomedin solution into nearby tissues can lead to local changes at the injection site (redness, pain, itching, feeling of heat).

Avoid taking the drug orally and getting it on mucous membranes.

If iloprost comes into contact with the skin, it can cause prolonged, although painless, erythema. Therefore, care must be taken to avoid contact of the drug with the skin. If iloprost gets on any part of the skin, it should be washed immediately with plenty of water or saline sodium chloride solution.

Use in pediatrics

Currently, there are only isolated reports on the use of this drug in children and adolescents.

Overdose

Symptoms: possible decrease or increase in blood pressure, as well as headache, blood flow to the face, nausea, vomiting and diarrhea, bradycardia or tachycardia, pain in the legs or back.

Treatment: interruption of infusion, further monitoring of patients and symptomatic therapy are recommended. Specific antidotes are unknown.

Side effects Ilomedin 20 µg/ml 1 ml 5 pcs. concentrate for the preparation of solution for infusion

The most commonly observed adverse reactions (≥10%) noted with the use of Ilomedin in clinical studies were headache, hot flashes, nausea, vomiting, and hyperhidrosis. Typically, these side effects occur at the beginning of treatment when selecting the maximum tolerated dose and quickly disappear with dose reduction.

The most serious adverse reactions observed with the use of Ilomedin were cerebrovascular events, myocardial infarction, pulmonary embolism, heart failure, convulsions, hypotension, tachycardia, bronchial asthma, angina pectoris, shortness of breath and pulmonary edema.

Another group of side effects is associated with reactions at the injection site. Thus, redness and pain may occur at the injection site, and dilatation of cutaneous vessels can sometimes lead to streak-like erythema over the infusion site.

Undesirable side effects noted with the use of Ilomedin during clinical trials are distributed according to the frequency of occurrence according to the following gradation: very common (≥1/10), frequent (≥1/100 and

The safety profile of Ilomedin is assessed based on pooled clinical trial and post-marketing data.

Estimated incidence rates are based on a pooled database of 3,325 patients who received iloprost in both controlled and uncontrolled clinical trials or the compassionate use program. Data were obtained mainly from elderly patients and patients with multiple pathologies suffering from peripheral arterial occlusive disease in stages III and IV, as well as in patients with thromboangiitis obliterans.

*Life-threatening effects or death have been reported.

Iloprost can provoke angina, especially in patients with coronary artery disease. The use of iloprost in combination with platelet aggregation inhibitors, heparin or indirect anticoagulants (coumarin derivatives) increases the risk of bleeding.

Drug interactions

Due to possible interactions, Ilomedin should not be mixed in the same solution with other medications.

Iloprost enhances the antihypertensive effect of β-blockers, slow calcium channel blockers and all vasodilators, as well as ACE inhibitors. If significant arterial hypotension occurs, blood pressure can be adjusted by reducing the dose of iloprost.

Since iloprost suppresses platelet function, its use in combination with heparin or indirect anticoagulants (coumarin derivatives) or other platelet aggregation inhibitors (acetylsalicylic acid, NSAIDs, phosphodiesterase inhibitors and vasodilators from the nitrate group, for example, molsidomine) may increase the risk of bleeding. In such a case, Ilomedin infusion should be stopped.

The use of acetylsalicylic acid at a dose of up to 300 mg/day for a course of 8 days, preceding the use of Ilomedin, did not have any effect on the pharmacokinetics of iloprost.

In an animal study, it was found that iloprost may cause a decrease in the steady-state plasma concentrations of tissue plasminogen activator (tPA) drugs. Results from human studies indicate that iloprost infusions do not affect the pharmacokinetics of multiple oral doses of digoxin in patients, and that when administered concomitantly with tPA drugs, iloprost does not affect its pharmacokinetics.

In animal experiments, the vasodilatory effect of iloprost was weakened if the experimental animals had previously received GCS, but the inhibitory effect on platelet aggregation did not change. The significance of these data for the clinic has not yet been established.

Although no clinical studies have been conducted, in vitro studies examining the inhibitory potential of iloprost on the activity of cytochrome P450 enzymes have indicated that it is unlikely that iloprost will significantly inhibit drug metabolism by these enzymes.

Contraindications for use

• pathological conditions in which the effect of iloprost on platelets may increase the risk of bleeding (for example, acute gastric or duodenal ulcer, trauma, intracranial bleeding);
• severe ischemic heart disease or unstable angina; myocardial infarction within the last 6 months; acute heart failure or chronic congestive heart failure stage II-IV (NYHA classification);
• severe heart rhythm disturbances;
• suspicion of congestion in the pulmonary circulation;
• lactation period;
• pregnancy;
• hypersensitivity to iloprost or other components of the drug.

Carefully:

in patients with a cerebrovascular accident in the last 3 months (for example, transient ischemic disorder, stroke). Such patients require a careful assessment of the benefit-risk ratio of treatment.

In renal failure requiring dialysis and liver cirrhosis, the excretion of iloprost is reduced.

It is necessary to take measures against a further decrease in blood pressure in patients with initially (before starting Ilomedin therapy) low blood pressure values; Patients with severe heart disease should be closely monitored.

The possibility of developing orthostatic hypotension should be taken into account when patients move from a horizontal to a vertical position after completing the administration of Ilomedin.

Ilomedin

IV, in the form of infusions, daily as a 6-hour infusion into a peripheral vein or a catheter installed in a central vein. The rate of administration (dose) depends on individual tolerance and is 0.5-2 ng/kg/min.

During the first 2-3 days, individual tolerability of the drug is determined under the control of heart rate and blood pressure (should be determined at the beginning of the infusion and after each dose increase): treatment with the drug begins with an administration rate of 0.5 ng/kg/min for 30 minutes, then the dose is increased stepwise by 0.5 ng/kg/min every 30 minutes. The exact infusion rate is calculated based on body weight and the maximum tolerated dose, within the range of 0.5-2 ng/kg/min.

Determination of the infusion rate (ml/h) when using an infusion pump (for example Infusomat): the contents of the ampoule are dissolved in a sterile 0.9% NaCl solution or 5% dextrose solution and the final volume of the solution is adjusted to the contents of the ampoule (2.5 ml) 50 mcg - to 250 ml, for an ampoule (1 ml) 20 mcg - up to 100 ml. A solution is obtained at a concentration of 0.2 μg/ml, the rate of its infusion is determined in accordance with the scheme depending on the dose and body weight (within 0.5-2 ng/kg/min): with a body weight of 40 kg and a dose of 0.5 ng/kg/min, the rate infusion - 6 ml/h, 1 ng/kg/min - 12 ml/h, 1.5 ng/ml/min - 18 ml/h, 2 ng/ml/min - 24 ml/h; with a body weight of 50 kg and a dose of about 5 ng/kg/min - 7.5 ml/h, 1 ng/kg/min - 15 ml/h, 1.5 ng/kg/min - 22.5 ml/h, 2 ng/kg/ min - 30 ml/h; with a body weight of 60 kg and a dose of 0.5 ng/kg/min - 9 ml/h, 1 ng/kg/min - 18 ml/h, 1.5 ng/kg/min - 27 ml/h, 2 ng/kg/min - 36 ml/h; with a body weight of 70 kg and a dose of 0.5 ng/kg/min - 10.5 ml/h, 1 ng/kg/min - 21 ml/h, 1.5 ng/kg/min - 31.5 ml/h, 2 ng/kg/min - 42 ml/h; with a body weight of 80 kg and a dose of 0.5 ng/kg/min - 12 ml/h, 1 ng/kg/min - 24 ml/h, 1.5 ng/kg/min - 36 ml/h, 2 ng/kg/min - 48 ml/h; with a body weight of 90 kg and a dose of 0.5 ng/kg/min - 13.5 ml/h, 1 ng/kg/min - 27 ml/h, 1.5 ng/kg/min - 40.5 ml/h, 2 ng/kg/min - 54 ml/h; with a body weight of 100 kg and a dose of 0.5 ng/kg/min - 16 ml/h, 1 ng/kg/min - 30 ml/h, 1.5 ng/kg/min 45 ml/h, 2 ng/kg/min - 60 ml/h; with a body weight of 110 kg and a dose of 0.5 ng/kg/min - 16.5 ml/h, 1 ng/kg/min - 33 ml/h, 1.5 ng/kg/min - 49.5 ml/h, 2 ng/kg/min - 66 ml/h.

Determination of the infusion rate (ml/h) when using an automatic syringe (for example Perfusor): the contents of the ampoules are diluted in a sterile 0.9% NaCl solution or 5% dextrose solution and the final volume of the solution is adjusted for the contents of the ampoule (2.5 ml) 50 mcg - to 25 ml, for an ampoule (1 ml) 20 mcg - up to 10 ml. A solution is obtained at a concentration of 2 μg/ml, the rate of its infusion is determined in accordance with the scheme depending on the dose and body weight (within 0.5-2.0 ng/kg/min): with a body weight of 40 kg and a dose of 0.5 ng/kg/min, the rate infusion - 0.6 ml/h, 1 ng/kg/min - 1.2 ml/h, 1.5 ng/kg/min - 1.8 ml/h, 2 ng/kg/min - 2.4 ml/h; with a body weight of 50 kg and a dose of 0.5 ng/kg/min - 0.75 ml/h, 1.5 ng/kg/min - 1.5 ml/h, 1.5 ng/kg/min - 2.25 ml/h, 2 ng/kg/min - 3 ml/h; with a body weight of 60 kg and a dose of 0.5 ng/kg/min - 0.9 ml/h, 1 ng/kg/min - 1.8 ml/h, 1.5 ng/kg/min - 2.7 ml/h, 2 ng/kg/min - 3.6 ml/h; with a body weight of 70 kg and a dose of 0.5 ng/kg/min - 1.05 ml/min, 1 ng/kg/min - 2.1 ml/h, 1.5 ng/kg/min - 3.15 ml/h, 2 ng/kg/min - 4.2 ml/h; with a body weight of 80 kg and a dose of 0.5 ng/kg/min - 1.2 ml/h, 1 ng/kg/min - 2.4 ml/h, 1.5 ng/kg/min - 3.6 ml/h, 2 ng/kg/min - 4.8 ml/h; with a body weight of 90 kg and a dose of 0.5 ng/kg/min - 1.35 ml/h, 1 ng/kg/min - 2.7 ml/h, 1.5 ng/kg/min - 4.05 ml/h, 2 ng/kg/min - 5.4 ml/h; with a body weight of 100 kg and a dose of 0.5 ng/kg/min - 1.5 ml/h, 1 ng/kg/min - 3 ml/h, 1.5 ng/kg/min - 1.5 ml/h, 2 ng/kg/min - 6 ml/h; with a body weight of 110 kg and a dose of 0.5 ng/kg/min - 1.65 ml/h, 1 ng/kg/min - 3.3 ml/h, 1.5 ng/kg/min - 4.95 ml/h, 2 ng/kg/min - 6.6 ml/h.

Duration of treatment - up to 4 weeks. In patients suffering from Raynaud's syndrome, shorter courses of treatment - 3-5 days - are often sufficient to achieve short-term remission (several weeks).

If side effects such as headache, nausea or decreased blood pressure occur, the infusion rate should be reduced to the maximum tolerated. If severe side effects develop, the infusion must be interrupted. Treatment is usually resumed after 4 weeks in doses that the patient tolerated well in the first 2-3 days of the previous course of treatment.

In case of renal failure requiring dialysis and liver cirrhosis, the recommended dose of the drug is reduced by 2 times.

special instructions

In the hope of success of conservative therapy with iloprost, surgery should not be delayed in patients requiring emergency amputation of the leg (for example, with infected gas gangrene). Patients should be strongly advised to stop smoking. Accidental injection of undiluted Ilomedin solution into nearby tissues may lead to local changes in tissues at the injection site (redness, pain, itching, feeling of heat). Avoid taking the drug orally and getting it on the mucous membranes. If iloprost comes into contact with the skin, it can cause prolonged, although painless, erythema. Therefore, care must be taken to avoid contact of the drug with the skin. If iloprost gets on any part of the skin, it should be washed immediately with plenty of water or saline sodium chloride solution. Use in pediatrics

Currently, there are only isolated reports on the use of this drug in children and adolescents.

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** The Drug Directory is intended for informational purposes only. For more complete information, please refer to the manufacturer's instructions. Do not self-medicate; Before starting to use Ilomedin, you should consult a doctor. EUROLAB is not responsible for the consequences caused by the use of information posted on the portal. Any information on the site does not replace medical advice and cannot serve as a guarantee of the positive effect of the drug.

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Drug interactions

Due to possible interactions, Ilomedin should not be mixed in the same solution with other medications. Iloprost enhances the antihypertensive effect of β-blockers, slow calcium channel blockers and all vasodilators, as well as ACE inhibitors. If significant arterial hypotension occurs, blood pressure can be adjusted by reducing the dose of iloprost. Since iloprost suppresses platelet function, its use in combination with heparin or indirect anticoagulants (coumarin derivatives) or other inhibitors of platelet aggregation (acetylsalicylic acid, NSAIDs, phosphodiesterase inhibitors and vasodilators from the nitrate group, for example, molsidomine), may increase the risk of bleeding. In such a case, Ilomedin infusion should be stopped. The use of acetylsalicylic acid at a dose of up to 300 mg/day for a course of 8 days, preceding the use of Ilomedin, did not have any effect on the pharmacokinetics of iloprost. In an animal study, it was found that iloprost may cause a decrease in the steady-state plasma concentrations of tissue plasminogen activator (tPA) drugs. The results of human studies show that iloprost infusions do not affect the pharmacokinetics of multiple oral doses of digoxin in patients, and that when used concomitantly with tPA drugs, iloprost does not affect its pharmacokinetics. In animal experiments, the vasodilatory effect of iloprost was weakened if experimental animals had previously received GCS , however, the inhibitory effect on platelet aggregation did not change. The clinical significance of these data has not yet been established. Although clinical studies have not been conducted, in vitro studies examining the inhibitory potential of iloprost against the activity of cytochrome P450 enzymes have revealed that there is a significant suppression of drug metabolism by these enzymes as a result of exposure to iloprost unlikely.

Concentrate for the preparation of solution for infusion Ilomedin

Instructions for medical use of the drug

Description of pharmacological action

Iloprost is a synthetic analogue of prostacyclin, inhibits platelet aggregation, adhesion and platelet release reaction; dilates arterioles and venules; increases capillary density (restores impaired microcirculation by inducing vasodation, inhibiting platelet activation, restoring and protecting the endothelium, activating endogenous fibrinolysis and correcting imbalances in the cytokine system) and reduces increased vascular permeability caused by mediators such as serotonin or histamine in the microcirculation system; activates endogenous fibrinolysis; exhibits an anti-inflammatory effect: suppresses the adhesion and migration of leukocytes after endothelial damage, as well as the accumulation of leukocytes in damaged tissue, reduces the production of tumor necrosis factor (TNF alpha).

Indications for use

— thromboangiitis obliterans (Buerger’s disease) in late stages with critical limb ischemia in cases where there are no indications for revascularization; - severe forms of occlusive peripheral artery disease, especially in cases of risk of amputation and when vascular surgery or angioplasty is not possible; - severe Raynaud's syndrome, leading to disability, not amenable to treatment with other drugs.

Release form

concentrate for the preparation of solution for infusion 20 mcg/ml; ampoule 2.5 ml, strip packaging 5, cardboard pack 1; concentrate for the preparation of solution for infusion 20 mcg/ml; ampoule 1 ml, contour cell packaging 1, cardboard pack 1; concentrate for the preparation of solution for infusion 20 mcg/ml; ampoule 1 ml, contour cell packaging 5, cardboard pack 1; concentrate for the preparation of solution for infusion 20 mcg/ml; ampoule 1 ml, strip packaging 5, cardboard pack 4; concentrate for the preparation of solution for infusion 20 mcg/ml; ampoule 2.5 ml, contour cell packaging 1, cardboard pack 1; concentrate for the preparation of solution for infusion 20 mcg/ml; ampoule 2.5 ml, strip packaging 5, cardboard pack 4; Composition Concentrate for the preparation of solution for infusion 1 ml of iloprost trometamol 27 mcg (corresponding to 20 mcg of iloprost) excipients: trometamol; ethanol 96%; sodium chloride; hydrochloric acid solution 1M; water for injection in ampoules of 1 ml; in contour cell packaging 1, 5 or 20 ampoules; in a cardboard pack 1 package. Concentrate for the preparation of solution for infusion 2.5 ml iloprost trometamol 67 mcg (corresponding to 50 mcg iloprost) excipients: trometamol; ethanol 96%; sodium chloride; hydrochloric acid solution 1M; water for injection in ampoules of 2.5 ml; in contour cell packaging 1, 5 or 20 ampoules.

Pharmacodynamics

Iloprost is a synthetic analogue of prostacyclin, inhibits platelet aggregation, adhesion and platelet release reaction; dilates arterioles and venules; increases capillary density (restores impaired microcirculation by inducing vasodation, inhibiting platelet activation, restoring and protecting the endothelium, activating endogenous fibrinolysis and correcting imbalances in the cytokine system) and reduces increased vascular permeability caused by mediators such as serotonin or histamine in the microcirculation system; activates endogenous fibrinolysis; exhibits an anti-inflammatory effect: suppresses the adhesion and migration of leukocytes after endothelial damage, as well as the accumulation of leukocytes in damaged tissue, reduces the production of tumor necrosis factor (TNF alpha).

Pharmacokinetics

Distribution Equilibrium concentration in blood plasma is achieved very quickly, 10-20 minutes after the start of intravenous infusions. The time to achieve it depends linearly on the infusion rate; at an infusion rate of 3 ng/kg/min, a concentration is achieved approximately equal to 135 ± 24 pg/ml. After the end of the infusions, the concentration of iloprost in plasma decreases very quickly (this is due to the very high intensity of its metabolism). Metabolic clearance is approximately 20±5 ml/kg/min. T1/2 from blood plasma in the terminal phase of distribution is about 0.5 hours. 2 hours after cessation of infusions, the content of the drug substance is less than 10% of the equilibrium concentration. Binding to plasma albumin is 60%. Metabolism Iloprost is metabolized mainly by P-oxidation of the carboxyl side chain. The substance is not excreted from the body unchanged. The main metabolite, tetranoryloprost, is found in urine in free form and in four conjugated forms of diastereoisomers. Experiments on animals have shown that tetranoryloprost is pharmacologically inactive. The results of in vitro studies indicate a similar pattern of metabolism of iloprost in the lungs after intravenous administration or inhalation. Elimination The elimination of iloprost after intravenous infusion in subjects with normal renal and hepatic function is in most cases characterized by a biphasic profile with average T1/2 durations of 3-5 minutes and 15-30 minutes, respectively. The total clearance of iloprost is approximately 20 ml/kg/min, indicating that iloprost metabolism occurs partially outside the liver. A mass balance study was conducted using 3H-labeled iloprost in healthy subjects. After IV infusions, the excretion of total radioactivity was 81%, with 68% excreted in the urine and 12% in the feces. Elimination of metabolites from plasma and their excretion in urine have a two-phase character, with T1/2 from plasma in the first phase being about 2 hours, in the second - about 5 hours, and for urine - 2 and 18 hours, respectively. For renal failure In a study with Using IV infusions of iloprost, it has been shown that in patients with end-stage renal failure who are periodically treated with dialysis, clearance is significantly lower (mean clearance = 5±2 ml/min/kg) than in patients with renal failure who are not receiving treatment dialysis (average clearance = 18±2 ml/min/kg). For liver dysfunction Since iloprost is extensively metabolized in the liver, changes in liver function affect the concentration of the drug in the blood plasma. The results of the study with intravenous administration of the drug included data from 8 patients suffering from liver cirrhosis. The average clearance of iloprost was calculated to be 10 ml/min/kg. Age and gender The pharmacokinetics of iloprost does not depend on the age and gender of the patient.

Use during pregnancy

Ilomedin should not be prescribed to women during pregnancy and lactation. There are no data on the use of iloprost in pregnant women. Preclinical studies indicate that iloprost is toxic to the fetus in rats, but not in rabbits and monkeys. Since the potential risk of therapeutic use of iloprost during pregnancy is unknown, women of fertile age should use reliable contraception when treating iloprost. There is currently no evidence that iloprost is excreted into breast milk in humans, however, as there is evidence that iloprost can pass into milk in small amounts in rats, it should not be administered to nursing mothers.

Use for renal impairment

In renal failure requiring dialysis, the excretion of iloprost is reduced. In these cases, it is necessary to reduce the recommended dose by 2 times.

Other special occasions at reception

In liver cirrhosis, the excretion of iloprost is reduced. In these cases, it is necessary to reduce the recommended dose by 2 times.

Contraindications for use

- pathological conditions in which the effect of iloprost on platelets may increase the risk of bleeding (for example, peptic ulcer of the stomach or duodenum in the acute stage, trauma, intracranial bleeding); - severe coronary heart disease or unstable angina; myocardial infarction within the last 6 months; acute heart failure or chronic congestive heart failure stage II-IV (according to the New York Heart Association classification); severe heart rhythm disturbances; — suspicion of congestion in the pulmonary circulation; - lactation period; - pregnancy; - hypersensitivity to iloprost or other components of the drug. With caution: in patients with cerebrovascular accident in the last 3 months (for example, transient ischemic disorder, stroke). Such patients require a careful assessment of the benefit-risk ratio of treatment. In renal failure requiring dialysis and liver cirrhosis, the excretion of iloprost is reduced. It is necessary to take measures against a further decrease in blood pressure in patients with initially (before starting Ilomedin therapy) low blood pressure values; Patients with severe heart disease should be closely monitored. The possibility of developing orthostatic hypotension should be taken into account when patients move from a horizontal to a vertical position after completing the administration of Ilomedin.

Side effects

From the nervous system and sensory organs: often (more than 1%, but less than 10%) - dizziness, headache, paresthesia, hyperesthesia, tinnitus, anxiety, agitation, lethargy, apathy, drowsiness; less often (more than 0.1%, but less than 1%) - tremor, cerebrovascular disorders, depression, hallucinations, migraine, fainting, prolonged loss of consciousness, blurred vision, irritation and pain in the eyes; rarely (more than 0.01%, but less than 0.1%) - vestibular disorders; frequency unknown - confusion. From the cardiovascular system: often (more than 1%, but less than 10%) - decreased blood pressure, bradycardia, flushing of the skin and a feeling of heat; less often (more than 0.1%, but less than 1%) - arrhythmia (including extrasystole), myocardial ischemia, myocardial infarction, deep vein thrombosis, pulmonary embolism; frequency unknown - increased blood pressure, tachycardia; in isolated cases (in elderly patients with severe atherosclerosis) - pulmonary edema. From the respiratory system: less often (more than 0.1%, but less than 1%) - bronchial asthma; rarely (more than 0.01%, but less than 0.1%) - cough; in isolated cases (in elderly patients with severe atherosclerosis) - heart failure. From the digestive system: more often (more than 10%) - nausea, vomiting; often (more than 1%, but less than 10%) - anorexia, diarrhea, abdominal discomfort, abdominal pain; less often (more than 0.1%, but less than 1%) - dry mouth, change in taste, tenesmus, constipation, belching, dysphagia, diarrhea, melena, rectal bleeding, jaundice. From the musculoskeletal system: often (more than 1%, but less than 10%) - pain in the masticatory muscles, trismus, myalgia, arthralgia, muscle weakness; less often (more than 0.1%, but less than 1%) - tetany, convulsive muscle twitching, hypertonicity. From the urinary system: lower back pain, renal colic, changes in the cellular composition of urine, dysuria. Local reactions: often (more than 1%, but less than 10%) - skin hyperemia, pain, phlebitis at the injection site. Other: more often (more than 10%) - sweating; often (more than 1%, but less than 10%) - local pain, generalized pain, hyperthermia, itching, fatigue, thirst; frequency unknown - allergic reactions. Overdose. Symptoms: pronounced blood flow to the face and severe headache, pain in the legs and back, sudden pallor, heavy sweating, nausea, vomiting, spasmodic abdominal pain, diarrhea, decreased or increased blood pressure, bradycardia or tachycardia. Treatment: stopping the infusion, symptomatic therapy; a specific antidote is unknown.

Directions for use and doses

IV, in the form of infusions, daily as a 6-hour infusion into a peripheral vein or a catheter installed in a central vein. The rate of administration (dose) depends on individual tolerance and is 0.5-2 ng/kg/min. During the first 2-3 days, individual tolerability of the drug is determined under the control of heart rate and blood pressure (should be determined at the beginning of the infusion and after each dose increase): treatment begins with an administration rate of 0.5 ng/kg/min for 30 minutes, then the dose is increased stepwise by 0.5 ng/kg/min every 30 min. The exact infusion rate is calculated based on body weight and the maximum tolerated dose, within the range of 0.5-2 ng/kg/min. Determination of the infusion rate (ml/h) when using an infusion pump (for example Infusomat): the contents of the ampoule are dissolved in a sterile 0.9% NaCl solution or 5% dextrose solution and the final volume of the solution is adjusted to the contents of the ampoule (2.5 ml) 50 mcg - to 250 ml, for an ampoule (1 ml) 20 mcg - up to 100 ml. A solution is obtained at a concentration of 0.2 μg/ml, the rate of its infusion is determined in accordance with the scheme depending on the dose and body weight (within 0.5-2 ng/kg/min): with a body weight of 40 kg and a dose of 0.5 ng/kg/min, the rate infusion - 6 ml/h, 1 ng/kg/min - 12 ml/h, 1.5 ng/ml/min - 18 ml/h, 2 ng/ml/min - 24 ml/h; with a body weight of 50 kg and a dose of about 5 ng/kg/min - 7.5 ml/h, 1 ng/kg/min - 15 ml/h, 1.5 ng/kg/min - 22.5 ml/h, 2 ng/kg/ min - 30 ml/h; with a body weight of 60 kg and a dose of 0.5 ng/kg/min - 9 ml/h, 1 ng/kg/min - 18 ml/h, 1.5 ng/kg/min - 27 ml/h, 2 ng/kg/min - 36 ml/h; with a body weight of 70 kg and a dose of 0.5 ng/kg/min - 10.5 ml/h, 1 ng/kg/min - 21 ml/h, 1.5 ng/kg/min - 31.5 ml/h, 2 ng/kg/min - 42 ml/h; with a body weight of 80 kg and a dose of 0.5 ng/kg/min - 12 ml/h, 1 ng/kg/min - 24 ml/h, 1.5 ng/kg/min - 36 ml/h, 2 ng/kg/min - 48 ml/h; with a body weight of 90 kg and a dose of 0.5 ng/kg/min - 13.5 ml/h, 1 ng/kg/min - 27 ml/h, 1.5 ng/kg/min - 40.5 ml/h, 2 ng/kg/min - 54 ml/h; with a body weight of 100 kg and a dose of 0.5 ng/kg/min - 16 ml/h, 1 ng/kg/min - 30 ml/h, 1.5 ng/kg/min 45 ml/h, 2 ng/kg/min - 60 ml/h; with a body weight of 110 kg and a dose of 0.5 ng/kg/min - 16.5 ml/h, 1 ng/kg/min - 33 ml/h, 1.5 ng/kg/min - 49.5 ml/h, 2 ng/kg/min - 66 ml/h. Determination of the infusion rate (ml/h) when using an automatic syringe (for example Perfusor): the contents of the ampoules are diluted in a sterile 0.9% NaCl solution or 5% dextrose solution and the final volume of the solution is adjusted for the contents of the ampoule (2.5 ml) 50 mcg - to 25 ml, for an ampoule (1 ml) 20 mcg - up to 10 ml. A solution is obtained at a concentration of 2 μg/ml, the rate of its infusion is determined in accordance with the scheme depending on the dose and body weight (within 0.5-2.0 ng/kg/min): with a body weight of 40 kg and a dose of 0.5 ng/kg/min, the rate infusion - 0.6 ml/h, 1 ng/kg/min - 1.2 ml/h, 1.5 ng/kg/min - 1.8 ml/h, 2 ng/kg/min - 2.4 ml/h; with a body weight of 50 kg and a dose of 0.5 ng/kg/min - 0.75 ml/h, 1.5 ng/kg/min - 1.5 ml/h, 1.5 ng/kg/min - 2.25 ml/h, 2 ng/kg/min - 3 ml/h; with a body weight of 60 kg and a dose of 0.5 ng/kg/min - 0.9 ml/h, 1 ng/kg/min - 1.8 ml/h, 1.5 ng/kg/min - 2.7 ml/h, 2 ng/kg/min - 3.6 ml/h; with a body weight of 70 kg and a dose of 0.5 ng/kg/min - 1.05 ml/min, 1 ng/kg/min - 2.1 ml/h, 1.5 ng/kg/min - 3.15 ml/h, 2 ng/kg/min - 4.2 ml/h; with a body weight of 80 kg and a dose of 0.5 ng/kg/min - 1.2 ml/h, 1 ng/kg/min - 2.4 ml/h, 1.5 ng/kg/min - 3.6 ml/h, 2 ng/kg/min - 4.8 ml/h; with a body weight of 90 kg and a dose of 0.5 ng/kg/min - 1.35 ml/h, 1 ng/kg/min - 2.7 ml/h, 1.5 ng/kg/min - 4.05 ml/h, 2 ng/kg/min - 5.4 ml/h; with a body weight of 100 kg and a dose of 0.5 ng/kg/min - 1.5 ml/h, 1 ng/kg/min - 3 ml/h, 1.5 ng/kg/min - 1.5 ml/h, 2 ng/kg/min - 6 ml/h; with a body weight of 110 kg and a dose of 0.5 ng/kg/min - 1.65 ml/h, 1 ng/kg/min - 3.3 ml/h, 1.5 ng/kg/min - 4.95 ml/h, 2 ng/kg/min - 6.6 ml/h. Duration of treatment - up to 4 weeks. In patients suffering from Raynaud's syndrome, shorter courses of treatment - 3-5 days - are often sufficient to achieve short-term remission (several weeks). If side effects such as headache, nausea or decreased blood pressure occur, the infusion rate should be reduced to the maximum tolerated. If severe side effects develop, the infusion must be interrupted. Treatment is usually resumed after 4 weeks in doses that the patient tolerated well in the first 2-3 days of the previous course of treatment. In case of renal failure requiring dialysis and liver cirrhosis, the recommended dose is reduced by 2 times.

Overdose

Symptoms: possible decrease or increase in blood pressure, as well as headache, blood flow to the face, nausea, vomiting and diarrhea, bradycardia or tachycardia, pain in the legs or back. Treatment: interruption of infusion, further monitoring of patients and symptomatic therapy are recommended. Specific antidotes are unknown.

Interactions with other drugs

Due to possible interactions, Ilomedin should not be mixed in the same solution with other medications. Iloprost enhances the antihypertensive effect of β-blockers, slow calcium channel blockers and all vasodilators, as well as ACE inhibitors. If significant arterial hypotension occurs, blood pressure can be adjusted by reducing the dose of iloprost. Since iloprost suppresses platelet function, its use in combination with heparin or indirect anticoagulants (coumarin derivatives) or other platelet aggregation inhibitors (acetylsalicylic acid, NSAIDs, phosphodiesterase inhibitors and vasodilators from the nitrate group, for example, molsidomine) may increase the risk of bleeding. In such a case, Ilomedin infusion should be stopped. The use of acetylsalicylic acid at a dose of up to 300 mg/day for a course of 8 days, preceding the use of Ilomedin, did not have any effect on the pharmacokinetics of iloprost. In an animal study, it was found that iloprost may cause a decrease in the steady-state plasma concentrations of tissue plasminogen activator (tPA) drugs. Results from human studies indicate that iloprost infusions do not affect the pharmacokinetics of multiple oral doses of digoxin in patients, and that when administered concomitantly with tPA drugs, iloprost does not affect its pharmacokinetics. In animal experiments, the vasodilatory effect of iloprost was weakened if the experimental animals had previously received glucocorticosteroids, but the inhibitory effect on platelet aggregation did not change. The significance of these data for the clinic has not yet been established. Although no clinical studies have been conducted, in vitro studies examining the inhibitory potential of iloprost on the activity of cytochrome P450 enzymes have indicated that it is unlikely that iloprost will significantly inhibit drug metabolism by these enzymes.

Special instructions for use

In the hope of success of conservative therapy with iloprost, surgery should not be delayed in patients requiring emergency leg amputation (for example, with infected gas gangrene). Patients should be strongly advised to quit smoking. Accidental injection of undiluted Ilomedin solution into nearby tissues can lead to local changes at the injection site (redness, pain, itching, feeling of heat). Avoid taking the drug orally and getting it on mucous membranes. If iloprost comes into contact with the skin, it can cause prolonged, although painless, erythema. Therefore, care must be taken to avoid contact of the drug with the skin. If iloprost gets on any part of the skin, it should be washed immediately with plenty of water or saline sodium chloride solution.

Storage conditions

Under normal conditions.

Best before date

48 months

ATX classification:

B Hematopoiesis and blood

B01 Anticoagulants

B01A Anticoagulants

B01AC Platelet aggregation inhibitors (except heparin)

B01AC11 Iloprost