Ventavis

Ventavis has a vasodilating and antiaggregatory effect on the pulmonary arterial bed.

Indications Ventavisa

It is used for therapy in the pulmonary form of hypertension, which has a moderate or severe form:

• Aersa's disease, as well as the family form of LH;
• increased values of blood pressure, caused by the development of the disease in the field of connective tissues, or the influence of medication or toxins;
• increased blood pressure as a result of the development of chronic thrombosis or PE, in cases where it is impossible to perform a surgical procedure.

Release form

The release of the substance is realized as an inhalation liquid, inside the ampoules with a volume of 2 ml. The blister contains 30 such ampoules, inside the box there are 3 such blisters.

Pharmacodynamics

Iloprost is an artificial analogue of prostacyclin; it is an active element of the drug. The drug slows down the processes of platelet aggregation and adhesion, as well as the release of soluble adhesion molecules. In addition, it leads to dilatation of venules with arterioles, strengthens capillary as well as vascular strength in cases when their permeability increases under the influence of mediators such as histamine or serotonin (this occurs inside the microcirculatory bed).

Also, the drug stimulates the internal fibrinolytic effect and has an anti-inflammatory effect - slows the leukocyte adhesion in endothelium damage, as well as leukocyte infiltration inside the damaged tissue. In addition, it prevents the release of the factor of necrosis of α-neoplasm.

After the inhalation procedure, the development of a direct vasodilator effect on the arteries of the pulmonary bed is noted, which leads to a significant improvement in such parameters as the values of blood pressure, LSS, cardiac output, and at the same time saturation of mixed blood inside the veins with oxygen. The effect on blood pressure and overall vascular resistance is minimal.

Pharmacokinetics

Suction.

For inhalations of iloprost persons with increased values of blood pressure (the dosage size of the medicament injected through the mouthpiece is 5 μg, and the duration of the procedure is within 4.6-10.6 minutes), the serum Cmax level is recorded at the end of the procedure and is 100-200 pg / ml.

The values of the drug substance decrease as it is excreted (half-life is about 5-25 minutes). In the interval 0.5-1 hour after the end of inhalation, the medication is no longer noted inside the central chamber (the limit of the permissible sensitivity of the method is 25 pg / ml).

Distribution processes.

After intravenous infusion, the apparent Vss for volunteers was 0.6-0.8 l / kg. With a spectrum of 30-3000 pg / ml, the total synthesis of iloprost with plasma protein is not related to concentration and is approximately 60%, about 75% of which is albumin synthesis.

Exchange processes.

In vitro tests show similarity in the metabolic processes of iloprost inside the lungs with intravenous administration and inhalation. Most of the intravenous element is involved in metabolic processes, mainly in the β-oxidation of the side chain carboxyl chain.

Excretion of the unmodified drug component does not occur. The main product of decomposition is tetranoriloprost; it is noted in a free state and conjugated form inside the urine. Experimental tests performed on animals demonstrated that tetranoriloprost does not have therapeutic activity.

The data obtained after in vitro tests show that the hemoprotein P450 takes a minimal part in the exchange processes of iloprost.

Excretion.

Excretion of the substance with intravenous infusions in individuals with healthy renal / hepatic activity often occurs in 2 stages, the average T1 / 2 values at which are 3-5 minutes, and also 15-30 minutes.

The total values of clearance of iloprost are approximately 20 ml / kg / minute, from which it can be concluded that the active element undergoes additional extrahepatic metabolic processes.

Previously, a test was carried out regarding the weight balance in volunteers, while 3-H-labeled iloprost was used. After the completion of intravenous infusion, the excretion rate of total radioactivity was 81%. With urine, 68% of the substance was excreted, and another 12% - with feces. Elimination of the decay products is carried out in 2 stages, the calculated half-lives for which are approximately 2 and 5 hours (with plasma) and approximately 2 and 18 hours (with urine).

Problems with renal activity.

Tests for intravenous administration of iloprost have demonstrated that in people with terminal kidney failure who undergo periodic dialysis procedures, the level of drug clearance (mean 5 ± 2 ml / minute / kg) is significantly lower than in people with kidney failure who do not are subjected to such procedures (mean value is 18 ± 2 ml / minute / kg).

Problems with hepatic function.

Due to the fact that most of iloprost is exposed to hepatic metabolism, various problems in the functioning of the liver affect the plasma parameters of drugs. In the tests for intravenous use of the drug involved 8 people with hepatic cirrhosis. Their data showed that the average clearance level of iloprost according to calculations was equal to 10 ml / minute / kg.

Dosing and administration

The ready medicamental solution is administered to the patient in the form of inhalation - through the nebulizer.

The treatment regimen should be selected, taking into account the individual characteristics of the patient. Therapy is carried out by a long cycle.

The dimensions of the recommended dosage portions.

For the first inhalation, 2.5 μg iloprost is required, which is administered to the patient through a special inhaler. If the use of drugs does not cause the patient any complications, the size of the portion is increased to 5 μg, and then maintain this dosage with new inhalation procedures. If the use of the solution causes complications, it is necessary to stop at a dosage of 2.5 μg.

Inhalation procedures are performed within 6-9 times / day (taking into account the individual characteristics of the patient and the tolerability of drugs).

Taking into account the necessary dosage of medication, administered through an inhaler or nebulizer, the duration of the procedure is 4-10 minutes.

People with disorders of hepatic activity.

People with liver problems have decreased iloprost elimination. To avoid excessive accumulation of drugs throughout the day, the determination of the initial portion in such patients should be done with caution. It is required to perform a thorough titration of the initial portion, with intervals between inhalations of 3-4 hours.

The size of the initial dosage is 2.5 μg, and the interval between the procedures is 3-4 hours (thus, no more than 6 inhalations are taken per day). Next, you can carefully reduce the length of intervals between procedures, given how the patient tolerates the drug.

If necessary in the further increase of the dose to 5 mcg, the intervals between inhalations should first last 3-4 hours, and then they can be reduced depending on the tolerance. The subsequent cumulation of the medication after a few days of treatment is rather unlikely, because it does not need to be used at night.

Scheme of use.

For each new inhalation, a new ampoule with a solution is required. Her contents are poured into the nebulizer before the procedure begins. It is required to follow exactly the instructions regarding the cleaning and hygiene of the medicinal product.

If after the procedure a certain amount of solution remains, it should be poured.

Use Ventavisa during pregnancy

Women with a pulmonary form of hypertension should avoid conception, because this can cause a life-threatening exacerbation of the pathology. At present, there is very little information on the use of VENTAVIS in pregnant women. Prescribe a drug in pregnancy is allowed only in situations where the benefit from it is more expected than the development of complications in the fetus.

Since there is no information as to whether iloprost is excreted with its breakdown products into breast milk, if it is needed, it should be refrained from breastfeeding for the duration of therapy.

Contraindications

The main contraindications:

• presence of strong sensitivity towards iloprost or other elements of the drug;
• painful conditions, during which the influence of Wentawis relative to platelets may increase the likelihood of bleeding (among them, exacerbated gastric or intestinal ulcers, hemorrhage within the skull, or trauma);
• an unstable form of angina pectoris, as well as severe coronary heart disease;
• occurred during the previous 6 months of myocardial infarction;
• heart failure, having a decompensated form, with lack of adequate medical supervision;
• arrhythmias in severe degree;
• the presence of suspicion of a stagnation of blood inside the lungs;
• complications of cerebrovascular nature (stroke and temporary ischemic attack among them) observed in the patient during the 3 previous months;
• induced pulmonary form of hypertension;
• defects of the heart valves (can have acquired or congenital nature), against which there are clinically significant disorders in the work of the myocardium, and which develop independently of LH.

Caution is required for such violations:

• a disorder in the liver, as well as kidney failure in people who require dialysis sessions;
• decreased values of blood pressure;
• HABL;
• BA in severe degree.

Side effects Ventavisa

The use of Vantavis can cause such negative signs:

• disorders of the function of lymph or blood: bleeding often occurs. Possible development of thrombocytopenia;
• immune manifestations: possible development of symptoms of intolerance;
• problems with the work of the National Assembly: often there are headaches, a little less often - dizziness;
• violations of the CAS: often there is an expansion of the vessels, a little less often there are syncope or a decrease in pressure;
• disorders affecting cardiac function: often there is an increase in heart rate or tachycardia;
• problems affecting the mediastinum, sternum and respiratory organs: often there is a cough or pain in the sternum, a little less often there are pharyngolaryngeal pains, dyspnoea and irritation in the throat. Perhaps the development of nasal congestion, wheezing, or spasm of the bronchi;
• disorders of the gastrointestinal tract: often there is nausea, more rarely - irritation in the area of the tongue and oral mucosa (also painful sensations), vomiting and diarrhea. Disturbance of taste perception is possible;
• lesions in the subcutaneous layer and epidermis: often there are rashes;
• disorders in the area of connective tissue, musculature and skeleton: often jaw trism or pain in the jaw area. Often, also there are pain in the back;
• systemic manifestations and lesions at the site of injection: peripheral puffiness often develops.

There are reports of the development of intracranial or cerebral hemorrhage, which led to death.

[1]

Overdose

In case of substance intoxication, the substance can have an antihypertensive effect, and besides this, blood tides, headaches, vomiting, diarrhea and nausea. In addition, overdose can cause an increase in blood pressure, tachycardia or a bradycardia, and along with this pain in the back or limbs.

To eliminate violations, you should stop the introduction of drugs, and then perform symptomatic procedures and monitor the patient's condition. The medicine does not have an antidote.

Interactions with other drugs

Since tests regarding the compatibility of the drug with other drugs have not been carried out, it is prohibited to mix with other medications with inhalations.

Iloprost is able to potentiate the hypotensive effect of vasodilator drugs and other antihypertensive drugs. Therefore, it is necessary to combine these medicines with Ventavis with caution, because with therapy it may be necessary to adjust the dosages of these drugs.

Since iloprost inhibits platelet activity, its use together with anticoagulants (such as coumarin derivatives and heparin) or other antiplatelet agents (among them NSAIDs, aspirin, vasodilator drugs from the nitrate category and PDE inhibitors) may increase the likelihood of bleeding.

People who are treated with anticoagulants or other platelet aggregation inhibitors should be under the constant supervision of a physician who monitors coagulation rates. Previous use of aspirin in a dose of up to 0.3 g / day for 8 days does not affect the pharmacokinetic characteristics of iloprost.

Animal tests have shown that the use of the drug can cause a decrease in the plasma Css values within the TAP. Data from studies conducted in humans show no effect from iloprost infusions on the pharmacokinetics of oral digoxin. Also, iloprost does not affect the pharmacokinetic properties of the TAP assigned with it.

In experiments conducted on animals, the vasodilating effect of drugs decreased with prior application of GCS, but the depressing effect on platelet aggregation remained the same. It is not known what significance this information can have for the human body.

Although no clinical tests were performed, during in vitro studies performed to assess the likely delayed effect of iloprost on the activity of isoenzymes of the hemoprotein P450, it was found that the strong inhibition of metabolic processes mediated by these isoenzymes under the influence of Wentawis is unlikely.

[2], [3]

Storage conditions

Ventasis is required to be kept in a place that is not accessible to young children. The temperature should not exceed 30 ° C.

[4]

Shelf life

Ventavis may be used within 24 months of the release of the therapeutic agent.

Application for children

Due to the limited amount of data on the use of drugs in persons under the age of 18, it is forbidden to assign it to pediatrics.

Analogues

Analogues of the drug are Ilomedin with Iloprost.

Reviews

Ventavis receives good feedback from people who use this medicine. Many doctors and patients believe that it has high drug efficacy. Of the minuses allocate a sufficiently high cost of the drug.