Universal reference book for medicines
Product name: ILOMEDIN (ILOMEDIN ® )

Active substance: iloprost

Type: Antiaggregant.
Synthetic analog prostacyclin
Manufacturer: BAYER PHARMA (Germany) manufactured by BERLIMED (Spain)
Composition, form of production and packaging
Concentrate for the preparation of a solution for infusions is
transparent, colorless or almost colorless.

1 amp.
(1 ml)
iloprosta trometamol 27 mcg,

which corresponds to the content of iloprost 20 μg

Excipients: trometamol, ethanol 96%, sodium chloride, hydrochloric acid 0.1 M, water d / u.

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

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

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

Concentrate for the preparation of a solution for infusions is transparent, colorless or almost colorless.

1 amp.
(2.5 ml)
iloprosta trometamol 67 mcg,

which corresponds to the content of iloprost 50 μg

Excipients: trometamol, ethanol 96%, sodium chloride, hydrochloric acid 0.1 M, water d / u.

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

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

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

INSTRUCTION FOR THE SPECIALIST.

Description of the drug approved by the manufacturer for the printed edition of 2015.

PHARMACHOLOGIC EFFECT

Iloprost is a synthetic analog of prostacyclin, inhibits aggregation, adhesion and platelet release;
expands arterioles and venules; increases the density of capillaries (restores disturbed microcirculation by induction of vasodilation, inhibition of platelet activation, restoration and protection of endothelium, activation of endogenous fibrinolysis, and correction of imbalance in the cytokine system) and reduces the increased vascular permeability caused by mediators such as serotonin or histamine in the microcirculation system; activates endogenous fibrinolysis; has anti-inflammatory effect: suppresses adhesion and migration of leukocytes after endothelial damage, as well as accumulation of leukocytes in damaged tissue, reduces the production of tumor necrosis factor (TNF?).
PHARMACOKINETICS

Distribution

The equilibrium concentration in blood plasma is reached very quickly, 10-20 minutes after the onset of IV infusions.
The time of its achievement depends linearly on the infusion rate, at a infusion rate of 3 ng / kg / min, a concentration approximately equal to 135 ± 24 pg / ml is achieved. After the end of the infusion, the concentration of iloprost in the plasma decreases very rapidly (this is due to the very high intensity of its metabolism). The metabolic clearance is approximately 20 ± 5 ml / kg / min. T 1/2 from blood plasma in the terminal phase of distribution is about 0.5 h. 2 hours after the termination 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.
In the unmodified form, the substance is not excreted from the body. The main metabolite, tetranoriloprost, is found in the urine in free form and in four conjugated forms of diastereoisomers. As experiments on animals have shown, tetranoriloprost is pharmacologically inactive. The results of in vitro studies indicate a similar pattern of iloprost metabolism in the lungs after intravenous injection or inhalation.
Excretion

Elimination of iloprost after IV infusions in subjects with normal renal and hepatic function in most cases is characterized by a two-phase profile with mean T 1/2duration, respectively, 3-5 min and 15-30 min.
The total clearance of iloprost is approximately 20 ml / kg / min, indicating that the metabolism of iloprost occurs partly outside the liver.
A mass balance study using iloprost, labeled with 3 N, was performed in healthy subjects.
After intravenous infusions, excretion of the total radioactivity was 81%, with 68% being excreted in the urine and 12% with feces. Elimination of metabolites from the plasma and excretion in the urine have a two-phase character, with T 1/2from the plasma in the first phase about 2 hours, the second - about 5 hours, and for urine - 2 and 18 hours, respectively.
Pharmacokinetics in special clinical cases

With renal insufficiency

In a study using intravenous infusions of iloprost, it was shown that in patients with terminal stage of renal failure periodically receiving dialysis treatment, clearance is significantly lower (mean clearance = 5 ± 2 ml / min / kg) than in patients with renal insufficiency, who do not receive dialysis treatment (mean clearance = 18 ± 2 ml / min / kg).

When a violation of liver function

Since iloprost is extensively metabolized in the liver, changes in hepatic 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 cirrhosis of the liver. The average clearance of iloprost was calculated as 10 ml / min / kg.
Age and gender

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

INDICATIONS

- obliterating thromboangiitis (Buerger's disease) at late stages with critical limb ischemia in cases of absence of indications for revascularization;

- severe forms of occlusive disease of peripheral arteries, especially in cases of risk of amputation and with the impossibility of surgical operation on vessels or angioplasty;

- Severe Raynaud's syndrome, leading to disability, not amenable to therapy with other drugs.

DOSING MODE

Duration of treatment - up to 4 weeks.

Ilomedin should be used only in conditions of careful monitoring monitoring in hospitals or outpatient facilities that have the appropriate technical capabilities.

Before starting treatment, women should be excluded from 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

It is necessary to strictly follow the dilution method, depending on the method of administration of the solution.

When using an infusion pump (infusion pump)

Contents of the ampoule 1 ml of concentrate for the preparation of the solution for infusion is diluted with sterile 0.9% sodium chloride solution or 5% glucose solution (dextrose) for injection to a volume of 100 ml.

Ampoule contents 2.5 ml concentrate for solution for infusion dilute with sterile 0.9% sodium chloride solution or 5% glucose solution (dextrose) for injection up to a volume of 250 ml.

When using an automatic syringe

Contents of the ampoule 1 ml of concentrate for the preparation of the solution for infusion is diluted with sterile 0.9% sodium chloride solution or 5% glucose solution (dextrose) for injection up to a volume of 10 ml.

Ampoule contents 2.5 ml concentrate for solution for infusion dilute with sterile 0.9% sodium chloride solution or 5% glucose solution (dextrose) for injection up to a volume of 25 ml.

After breeding, Ilomedin is administered daily as a 6-hour infusion into the peripheral vein or a catheter installed in the central vein.
The rate of administration (dose) depends on the individual tolerability 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, the individual tolerability of the drug is determined - treatment is started at a rate of 0.5 ng / kg / min for 30 minutes.
After that, the dose is incremented stepwise by 0.5 ng / kg / min approximately every 30 minutes. The exact infusion rate is calculated based on the body weight at the maximum tolerated dose ranging from 0.5 to 2.0 ng / kg / min.
Depending on the frequency of such adverse reactions as headache, nausea, or lowering blood pressure, the infusion rate should be reduced to the maximum tolerable.With the development of severe adverse reactions, infusion should be interrupted.
Treatment should be continued usually within 4 weeks, applying doses that were well tolerated in the first 2-3 days of the previous course of treatment.
The infusion rate (mL / h) for the administration of various doses when using an infusomat (infusion pump)

The following table can be used to calculate the infusion rate corresponding to the body weight of a particular patient and the dose to be administered.

Body weight (kg) Dose (ng / kg / min)

0.5 1.0 1.5 2.0

Infusion rate (ml / h)

40 6.0 12 18.0 24

50 7.5 15 22.5 30

60 9.0 18 27.0 36

70 10.5 21 31.5 42

80 12.0 24 36.0 48

90 13.5 27 40.5 54

100 15.0 30 45.0 60

110 16.5 33 49.5 66

Infusion rate (mL / h) for administration of various doses using an automatic syringe

The following table can be used to calculate the infusion rate corresponding to the body weight of a particular patient and the dose to be administered.

Body weight, (kg) Dose (ng / kg / min)

0.5 1.0 1.5 2.0

Infusion rate (ml / h)

40 0.60 1.2 1.80 2.4

50 0.75 1.5 2.25 3.0

60 0.90 1.8 2.70 3.6

70 1.05 2.1 3.15 4.2

80 1.20 2.4 3.60 4.8

90 1.35 2.7 4.05 5.4

100 1.50 3.0 4.50 6.0

ON 1.65 3.3 4.95 6.6

In patients with systemic scleroderma suffering from Raynaud's syndrome , a shortened course of treatment (3-5 days) is often sufficient to achieve improvement lasting several weeks.

It is not recommended to perform continuous infusions for several days because of the possibility of developing tachyphylaxis, which is manifested in a weakened effect on platelets, and the possibility of a rebound syndrome, manifested in an increase in the propensity to aggregate platelets at the conclusion of the course of therapy.
At the same time, there are no reports of any clinical complications related to these phenomena.
With renal failure requiring dialysis, and with liver cirrhosis, the removal of iloprost is reduced.
In these cases, it is necessary to reduce the recommended dose by 2 times.
SIDE EFFECT

The most frequently observed undesirable 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 choosing the maximum tolerated dose and quickly disappear with a decrease in dose.
The most serious adverse reactions noted with the use of Ilomedin were cerebrovascular disorders, 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 site of administration.
Thus, redness and pain may occur at the site of administration, and dilatation of the cutaneous vessels can sometimes lead to erythema in the form of a strip above the infusion site.
The undesirable side effects noted with the use of Ilomedin during clinical trials are distributed according to the frequency of occurrence in accordance with the following gradation: very frequent (? 1/10), frequent (? 1/100 and <1/10), infrequent (? 1 / 1000 and <1/100, rare (? 1/10 000 and <1/1000), very rare (<1/10 000).

The safety profile of Ilomedin is assessed on the basis of pooled data from clinical trials and post-marketing use.

Approximate frequency scores are based on a cumulative database of 3325 patients who received iloprost in both controlled and uncontrolled clinical trials, or as part of a charitable-test use program.
Data were obtained mainly in elderly patients, and patients with multiple pathologies suffering from occlusive disease of peripheral arteries in the III and IV stages, as well as in patients with obliterative thromboangiitis.
Very Frequent Frequent Infrequent Rare

Metabolic and nutritional disorders

loss of appetite

Nervous system

headache apathy, confusion, dizziness / vertigo, paresthesia / increased skin sensitivity, hyperesthesia / burning sensation, anxiety / agitation, retardation, drowsiness convulsions *, fainting, tremor, anxiety, depression, hallucinations, migraine

From the side of the organ of vision

impaired vision, irritation of the mucous membrane of the eyes, pain in the eyes

From the side of the hearing organ

vestibular disorders

From the cardiovascular system

tidal hypotension *, tachycardia, bradycardia, stenocardia *, increased blood pressure myocardial infarction *, heart failure *, arrhythmia / extrasystole, cerebrovascular disorders * / cerebrovascular ischemia, deep vein thrombosis, pulmonary embolism *

On the part of the hematopoiesis system

thrombocytopenia

From the respiratory system:

shortness of breath * bronchial asthma *, pulmonary edema * cough

From the gastrointestinal tract

nausea, vomiting diarrhea, abdominal discomfort / pain, diarrhea with blood, rectal bleeding, dyspepsia, rectal tenesmus, constipation, belching, dysphagia, dry mouth / taste change proctitis

From the liver and biliary tract

jaundice

From the skin and subcutaneous tissues

hyperhidrosis itching

From the musculoskeletal system

pain in the chewing muscles / trismus, myalgia, arthralgia tetany, muscle spasms, hypertonia

From the urinary system

pain in the kidney, vesic tenesmus, changes in urine, dysuria, impaired urinary tract

General pathology and local reactions

pain, hyperthermia, fever, sensation of heat, general weakness / malaise, chills, fatigue / fatigue, thirst, local reactions (erythema, pain, phlebitis) hypersensitivity reactions

* There were reports of life-threatening consequences or death.

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

- pathological conditions in which the action of iloprost on platelets may increase the risk of bleeding (eg peptic ulcer of the stomach or duodenum in the acute stage, 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 II-IV stage (according to the NYHA classification);
- severe violations of the rhythm of heartbeats;

- Suspicion of congestion in a small circle of blood circulation;

- lactation period;

- Pregnancy;

- hypersensitivity to iloprost or other components of the drug.

With caution: in patients with impaired cerebral circulation for the past 3 months (eg, transient ischemic disorder, stroke).
Such patients need a thorough assessment of the relationship between the benefits and risks of treatment.
With renal failure requiring dialysis, and with liver cirrhosis, the removal of iloprost is reduced.

It is necessary to take measures against a further reduction in blood pressure in patients with initially low blood pressure (before starting therapy with Ilomedin);patients with severe heart disease should be under close monitoring control.

One should consider the possibility of developing orthostatic hypotension when patients move from horizontal to vertical position after completion of Ilomedin administration.

PREGNANCY AND LACTATION

Ilomedin should not be given to women during pregnancy and lactation.
There are no data on the use of iloprost in pregnant women.
According to preclinical studies, iloprost has a toxic effect on the fetus in rats, but not in rabbits and monkeys.

Because
the potential risk of therapeutic use of iloprost in pregnancy is not known, when treating iloprost women of fertile age should use reliable contraception.
At present, there is no information on the penetration of iloprost into human breast milk, however, since there is evidence that iloprost can penetrate into milk in rats in small amounts, it should not be administered to nursing mothers.

APPLICATION FOR FUNCTIONS OF THE LIVER

With renal failure requiring dialysis, the elimination of iloprost is reduced.
In these cases, it is necessary to reduce the recommended dose by 2 times.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS

With cirrhosis, the elimination of iloprost is reduced.
In these cases, it is necessary to reduce the recommended dose by 2 times.
APPLICATION FOR CHILDREN

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

SPECIAL INSTRUCTIONS

In the hope of success of conservative therapy with iloprost, surgical surgery should not be postponed to patients who need emergency amputation of the leg (for example, with an infected gas gangrene).

Patients should be strongly advised to quit smoking.

Accidental administration of undiluted Ilosidine solution into nearby tissues can lead to their local change at the injection site (redness, pain, itching, a feeling of heat).

Avoid taking the drug inside and its contact with mucous membranes.

Getting on the skin, iloprost can lead to a long, albeit painless, erythema.
Therefore, you must be careful and avoid contact with the skin. If you get iloprost on any part of the skin, you should immediately wash it with plenty of water or with a physiological solution of sodium chloride.
Use in Pediatrics

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

OVERDOSE

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

Treatment: it is recommended to interrupt infusion, further monitoring of patients and symptomatic therapy.
Specific antidotes are unknown.
DRUG INTERACTION

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

Iloprost enhances the antihypertensive effect? Adrenoblokatorov, calcium channel blockers slow and all vasodilators and ACE inhibitors. If there is significant hypotension, BP will be able to adjust by reducing the dose of iloprost.
Since iloprost inhibits 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 group consisting of nitrates, e.g., molsidomine) may increase the risk of bleeding. In this case, the infusion should be discontinued Ilomedina.
Use of acetylsalicylic acid in a dose of 300 mg / day course of 8 days prior to use Ilomedina, had no effect on the pharmacokinetics of iloprost.
In animal studies, it was found that iloprost may cause a reduction of equilibrium concentration of drug tissue plasminogen activator (tPA) in plasma. Results of studies in humans show that iloprost infusions do not affect the pharmacokinetics of digoxin multiple oral doses in patients and that while the use of drugs iloprost tPA has no influence on its pharmacokinetics.
In animal experiments vasodilator action iloprost weakened if the experimental animals were pretreated with corticosteroids, but the inhibitory effect on platelet aggregation is not changed. The significance of these data for the clinic until set.
Although clinical studies have been conducted, studies in vitro, in which was studied the inhibitory potential of iloprost against enzyme activity of cytochrome P450, revealed that significant suppression of drug metabolism by these enzymes result in exposure to iloprost unlikely.
TERMS OF RELEASE FROM PHARMACY

The drug is released by prescription.

TERMS AND CONDITIONS OF STORAGE

The drug should be stored out of reach of children at a temperature of no higher than 30 ° C.
Shelf life - 4 years.
Alphabetical index of medicines:
A  B  V  G  D  E  J
Z  I  Y  K  L  M  N
O  P  R  S  T  U  F
H  C  CH  SH  E  U  Y
Rambler's Top100
Privacy policy:
Copyright 2009 - 2017. Universal reference book of medicines. All rights reserved.
When using site materials, an active hyperlink is required!