Ventavis

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

Indications Ventavisa

It is used for the treatment of pulmonary hypertension, which is moderate or severe:

• Ayerza disease, as well as the familial form of PH;
• an increase in blood pressure values caused by the development of a disease in the area of connective tissue or the influence of medications or toxins;
• an increase in blood pressure as a result of the development of chronic thrombosis or pulmonary embolism, in cases where a surgical procedure cannot be performed.

Release form

The substance is released in the form of an inhalation liquid, inside ampoules with a volume of 2 ml. The blister contains 30 such ampoules, inside the box - 3 such blisters.

Pharmacodynamics

Iloprost is an artificial analogue of the substance prostacyclin; it is the 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 dilation of venules with arterioles, increases capillary and vascular strength in cases where their permeability increases under the influence of such mediators as histamine or serotonin (this occurs within the microcirculatory bed).

The drug also stimulates internal fibrinolytic action and has an anti-inflammatory effect - it slows down leukocyte adhesion in case of endothelial damage, as well as leukocyte infiltration inside damaged tissues. In addition, it prevents the release of the α-neoplasm necrosis factor.

After the inhalation procedure, a direct vasodilatory effect is observed in relation to the pulmonary arteries, which subsequently results in a significant improvement in such parameters as blood pressure, pulmonary vascular resistance, cardiac output, and, along with this, the saturation of mixed blood inside the veins with oxygen. The effect on blood pressure and total vascular resistance is minimal.

Pharmacokinetics

Suction.

When inhaling iloprost in individuals with elevated blood pressure (the dosage of the drug administered through the mouthpiece is 5 mcg, and the duration of the procedure is within 4.6-10.6 minutes), the serum Cmax level is recorded by the time the procedure is completed and is 100-200 pg/ml.

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

Distribution processes.

Following intravenous infusion, apparent Vss values in volunteers were in the range of 0.6-0.8 L/kg. With a range of values 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 synthesis with albumin.

Exchange processes.

In vitro test data demonstrate similarities in the metabolic processes of iloprost inside the lungs after intravenous administration and inhalation. Most of the intravenously administered element is involved in metabolic processes, mainly in the β-oxidation of the side-type carboxyl chain.

There is no excretion of unchanged drug component. The main degradation product is tetranoriloprost; it is found in free and conjugated form in urine. Experimental tests conducted on animals have shown that tetranoriloprost has no therapeutic activity.

Data obtained from in vitro tests indicate that hemoprotein P450 plays a minimal role in the metabolism of iloprost.

Excretion.

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

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

Previously, weight balance testing was performed in volunteers using 3H-labeled iloprost. Following intravenous infusion, the excretion rate of total radioactivity was 81%. 68% of the substance was excreted in the urine and another 12% in the feces. The elimination of decay products occurs in 2 stages, with estimated half-lives of approximately 2 and 5 hours (in plasma) and approximately 2 and 18 hours (in urine).

Problems with kidney function.

Tests of intravenous iloprost have shown that in individuals with end-stage renal failure who periodically undergo dialysis procedures, the drug clearance rate (mean value – 5±2 ml/minute/kg) is significantly lower than in individuals with renal failure who do not undergo such procedures (mean value – 18±2 ml/minute/kg).

Problems with liver function.

Because most iloprost is metabolized in the liver, various liver problems affect plasma levels of the drug. Intravenous drug tests were performed on 8 people with liver cirrhosis. Their data showed that the mean clearance rate of iloprost was calculated to be 10 ml/minute/kg.

Dosing and administration

The prepared medicinal solution is administered to the patient by inhalation – through a nebulizer.

The treatment regimen must be selected taking into account the individual characteristics of the patient. The therapy is carried out in a long cycle.

Recommended serving sizes.

The first inhalation requires 2.5 mcg of iloprost, which are administered to the patient through a special inhaler. If the use of the drug does not cause any complications in the patient, the portion size is increased to 5 mcg, and then this dosage is maintained during new inhalation procedures. If the use of the solution causes complications, it is necessary to stop at a dosage of 2.5 mcg.

Inhalation procedures are performed 6-9 times a day (taking into account the individual characteristics of the patient and tolerance of the drug).

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

People with liver dysfunction.

In people with liver problems, there is a decrease in the elimination of iloprost. In order to avoid excessive accumulation of the drug during the day, the initial dose in such patients should be determined with caution. It is necessary to carry out careful titration of the initial dose, with intervals between inhalations of 3-4 hours.

The initial dosage is 2.5 mcg, and the interval between procedures is 3-4 hours (thus, no more than 6 inhalations are performed per day). Then, the duration of the intervals between procedures can be carefully reduced, taking into account how the patient tolerates the drug.

If it is necessary to further increase the dose to 5 mcg, the intervals between inhalations should first last 3-4 hours, and then they can be reduced depending on tolerance. Subsequent accumulation of the drug after several days of treatment is quite unlikely, because Ventavis should not be used at night.

Usage diagram.

For each new inhalation, a new ampoule with the solution must be used. Its contents are poured into the nebulizer just before the procedure. It is necessary to strictly follow the instructions regarding cleaning and hygiene of the medicinal device.

If any solution remains after the procedure, it should be poured out.

Use Ventavisa during pregnancy

Women with pulmonary hypertension should avoid conception, as this can cause a life-threatening exacerbation of the pathology. Currently, there is very little information regarding the use of Ventavis in pregnant women. Prescribing the drug during 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 on whether iloprost is excreted with its breakdown products into breast milk, if its use is necessary, breastfeeding should be discontinued during therapy.

Contraindications

Main contraindications:

• the presence of severe sensitivity to iloprost or other components of the medication;
• painful conditions during which the effect of Ventavis on platelets may increase the likelihood of bleeding (including an aggravated gastric or intestinal ulcer, intracranial hemorrhage or trauma);
• unstable angina, as well as severe coronary heart disease;
• myocardial infarction that occurred within the previous 6 months;
• heart failure in a decompensated form, with no adequate medical supervision;
• severe arrhythmia;
• there is a suspicion of blood stagnation occurring inside the lungs;
• complications of a cerebrovascular nature (including stroke and temporary ischemic attack) observed in the patient during the previous 3 months;
• pulmonary hypertension caused by pulmonary hypertension;
• heart valve defects (may be acquired or congenital), against the background of which clinically significant disorders in the functioning of the myocardium are observed, and which develop independently of pulmonary hypertension.

Caution is required in the following cases:

• liver dysfunction, as well as kidney failure in people who require dialysis sessions;
• decreased blood pressure values;
• COPD;
• Severe asthma.

Side effects Ventavisa

The use of Ventavis may cause the following negative symptoms:

• disorders of lymph or blood function: bleeding often occurs. Thrombocytopenia may develop;
• immune manifestations: development of intolerance symptoms is possible;
• problems with the functioning of the nervous system: headaches often appear, a little less often – dizziness;
• disturbances in the functioning of the cardiovascular system: vasodilation often occurs, fainting or decreased blood pressure are observed somewhat less frequently;
• disorders affecting cardiac function: often there is increased heart rate or tachycardia;
• problems affecting the mediastinum, sternum and respiratory organs: cough or pain in the sternum area often appears, pharyngolaryngeal pain, dyspnea and irritation in the throat area occur a little less often. Nasal congestion, wheezing or bronchial spasm may develop;
• Gastrointestinal disorders: nausea often occurs, less frequently – irritation in the tongue and oral mucosa (also painful sensations), vomiting and diarrhea. Taste perception may be impaired;
• lesions in the subcutaneous layer and epidermis: rashes are often observed;
• disorders in the connective tissue, muscles and skeleton: jaw trismus or pain in the jaw area often occurs. Pain in the back also often appears;
• systemic manifestations and lesions at the injection site: peripheral edema often develops.

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

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Overdose

In case of intoxication with the substance, an antihypertensive effect may be observed, as well as hot flashes, headaches, vomiting, diarrhea and nausea. In addition, an overdose may cause an increase in blood pressure, tachycardia or bradycardia, and along with this, pain in the back or limbs.

To eliminate the violations, it is necessary to stop the administration of the drug, and then perform symptomatic procedures and monitor the patient's condition. The drug has no antidote.

Interactions with other drugs

Since tests regarding the compatibility of the drug with other drugs have not been conducted, it is prohibited to mix it with other drugs during inhalation.

Iloprost can potentiate the hypotensive effect of vasodilators and other hypotensive agents. Therefore, such drugs should be combined with Ventavis with caution, because during therapy, dosage adjustments of these drugs may be required.

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

People who are treated with anticoagulants or other inhibitors of platelet aggregation should be under continuous medical supervision, who monitors coagulation parameters. 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 plasma Css values within tPA. Data from studies conducted in humans demonstrate that iloprost infusions do not affect the pharmacokinetics of oral digoxin. Iloprost also does not affect the pharmacokinetic properties of co-administered tPA.

In animal experiments, the vasodilating effect of the drug was reduced by prior use of GCS, but the inhibitory effect on platelet aggregation remained the same. It is not known what significance this information may have for the human body.

Although clinical tests have not been performed, in vitro studies performed to evaluate the potential inhibitory effect of iloprost on the activity of hemoprotein P450 isoenzymes have shown that strong inhibition of drug metabolism mediated by these isoenzymes under the influence of Ventavis is unlikely.

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Storage conditions

Ventavis should be kept in a place out of reach of small children. Temperature values should not exceed 30°C.

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Shelf life

Ventavis can be used within 24 months from the date of release of the therapeutic agent.

Application for children

Due to limited data regarding the use of the drug in individuals under 18 years of age, it is prohibited to prescribe it in pediatrics.

Analogues

Analogues of the drug are Ilomedin and Iloprost.

Reviews

Ventavis gets good reviews from people who have used this medicine. Many doctors and patients believe that it has high medicinal effectiveness. The disadvantages include the rather high cost of the drug.