Vecta

Vekta is a medicine used to treat impotence. The active ingredient is sildenafil.

Indications of the vectors

It is used in men with impotence (it is defined as the inability to achieve or support the erection necessary for successful sexual intercourse).

In order for the medicine to act, the patient must be sexually aroused.

[1], [2], [3], [4], [5], [6]

Release form

Release in tablets, 1 or 4 pieces inside a blister pack. Inside a separate pack - 1 blister.

[7]

Pharmacodynamics

Vekta helps restore the ability of a man to achieve an erection, providing the necessary natural reaction of the body to a sense of sexual arousal. Physiologically, an erection is achieved by releasing the N2O element inside the cavernous body during sexual stimulation. NO stimulates the activity of the enzyme guanylate cyclase, as a result of which the cGMP index increases, the smooth muscle in the cavernous body relaxes, and the circulatory process inside the penis increases.

Sildenafil is a strong selective inhibitor of the cGMP-specific element of PDE-5, which helps the process of decomposition of the cGMP component inside the cavernous body. The substance has an erectile effect of the peripheral type. Sildenafil does not have a direct relaxing effect on the isolated cavernous body, but it is capable of potentiating the relaxing effect of NO exposure inside the tissues of the cavernous body. In the process of activation of NO / cGMP pathway, which occurs in the case of sexual arousal, the suppression of the PDE-5 element with the participation of sildenafil causes an increase in cGMP indices within the cavernous body. Because of this, the drug also requires adequate sexual arousal for the required medication.

As a result of a single oral intake of a drug by a volunteer at a dose of up to 100 mg, it does not cause significant changes in ECG values. The maximum reduction in systolic blood pressure in the case of a patient lying in a supine position (taking drugs at a rate of 100 mg) averaged 8.4 mm Hg. The decrease in the level of the diastolic AD in a similar position was 5.5 mm Hg. The decrease in the values of AD is associated with the vasodilating properties of sildenafil (probably due to an increase in the cGMP indices inside the smooth vascular musculature).

[8], [9], [10], [11], [12]

Pharmacokinetics

The drug passes rapid absorption after oral administration. In the case of fasting, the peak plasma level is observed after 30-120 minutes (mean - 60 minutes). The absolute level of bioavailability after oral use in standard doses is linear. In the case of drugs in combination with fatty foods, the absorption rate decreases, the time to reach the peak value is extended by 1 hour, and the maximum plasma index on average decreases by 29%.

The equilibrium distribution volume of the substance is on the average 105 liters / kg. The sildenafil component with its main circulating M-desmethyl decay product is synthesized with a plasma protein by approximately 96% (this value does not depend on the concentration of the drug). In volunteers who took the drug once in a dose of 100 mg, less than 0.0002% (the average level of 188 mg) of the accepted dosage was observed inside the sperm - 1.5 hours after ingestion. A single oral dose of such a dose did not cause changes in the morphological characteristics or motility of spermatozoa.

Metabolism of the substance is carried out mainly with the help of components CYP3A4 (this is its main path), as well as CYP2C9 (is a non-essential pathway), which are microsomal hepatic isoenzymes. The main circulating decomposition product is formed during the N-desmethylation of the active substance. The decay product is selectively comparable to the PDE with the substance sildenafil, and the active effect on PDE-5 is about 50% of the total activity of the drug. The plasma level of the decay product is approximately 40% of the same value of sildenafil. The process of further metabolism passes through the element N-desmethyl metabolite, and the terminal term of its half-life is approximately 4 hours. The total clearance of the active ingredient is 41 liters / hour, while the terminal half-life is about 3-5 hours.

After oral administration of the drug, excretion of the substance under the guise of degradation products is mainly carried out with feces (approximately 80% of the dose used), and the remainder with urine (13% of the substance).

[13], [14], [15],

Dosing and administration

The medicine should be taken orally.

The dosage of drugs for adult men is 50 mg. The tablet should be taken about 1 hour before sexual intercourse. Taking into account the effectiveness, as well as the tolerability of the drug, its dose can be raised to 100 mg or reduced to 25 mg. The maximum that can be taken for a day without the risk of intoxication is 100 mg. In the case of taking drugs along with food, its effect can begin later than in the case of fasting.

Because in people with liver failure or kidneys in severe form (CC level <30 ml / minute) there is a decreased rate of clearance of sildenafil, it is required to consider the option with the use of drugs at a dosage of 25 mg. Further, taking into account the tolerability and effectiveness of Vekta, it is possible to gradually increase the dose to 50 or 100 mg.

[25], [26], [27], [28], [29], [30], [31],

Contraindications

Among the existing contraindications:

• the presence of intolerance against sildenafil or other additional components of the drug;
• combined reception with NO donors (among them amyl nitrite) or with any form of nitrates. This combination is prohibited, because there is evidence that sildenafil affects the metabolic pathways of NO / cGMP, and in addition increases the antihypertensive properties of nitrates;
• at conditions in which sexual activity is not recommended (for example, in case of severe violations of the CCC - heart failure in severe form or unstable angina);
• loss of one eye of visual function due to IDU non-arterial type (regardless of the presence / absence of communication of the disease with the previous use of inhibitors of the element PDE-5);
• with the following pathologies: severe form of functional disorder of the liver, reduced blood pressure (less than 90/50 mm Hg), a recent myocardial infarction or stroke, as well as known diseases of the retina of the degenerate type, with hereditary origin (among them retinitis pigmentosa; in a small number of such patients there are violations of PDE inside the retina of the genetic type), because the safety of the use of drugs in such subgroups of patients being treated has not been tested.

[16], [17], [18], [19]

Side effects of the vectors

The use of tablets can trigger the appearance of the following side effects:

• invasion or infection: development of the common cold;
• immune manifestations: development of hypersensitivity;
• reactions of NS: sensation of drowsiness, dizziness with headaches, development of a stroke, hypoesthesia or a micro stroke, the appearance of fainting and convulsions (or their relapses);
• disturbances in the function of the visual organs: disorders of color perception (such as cyanopsy with chloropsy, as well as xanthopsy and chromatopsy with erythropsy), vision problems and the appearance of turbidity, development of lacrimation (exacerbation of the process, lacrimation and dry eye mucosa), eye pains , photopsy and photosensitivity, as well as conjunctivitis and ocular hyperemia. In addition, visual brightness, non-arterial-type PIN, retinal haemorrhage, retinal vascular occlusion, arteriosclerotic-type retinopathy, retinal disorders, diplopia with glaucoma and visual impairment appear. There may be defects in the visual field, asthenopia with myopia, mydriasis, PPTS, problems in the iris, the appearance of a halo in the field of the visual field, eye swelling, swelling and frustration. Also, there is irritation in the eye area, eyelid edema, hyperemia in the conjunctiva and discoloration of the eye protein;
• reactions of the vestibular apparatus and auditory organs: ear ringing, as well as the appearance of dizziness or the development of deafness;
• cardiac disorders: increased rhythm of the heartbeat, the development of myocardial infarction, tachycardia, ventricular or atrial fibrillation, as well as unstable angina, and in addition sudden death due to the heart;
• cardiovascular disorders: a rush of blood in the face, hypo- or hypertension and the appearance of hot flashes;
• reaction of the respiratory system and mediastinum with the sternum: bleeding from the nose, nasal (or nasal sinuses), congestion, swelling of the nasal mucosa (or its dryness), and a feeling of compression in the throat;
• manifestations in the gastrointestinal tract: dyspepsia, vomiting, dry oral mucosa, nausea, GERD, hypoesthesia in the oral cavity and pain in the upper abdomen;
• disorders of the subcutaneous layer and skin: rash, and in addition Lyell's syndrome or Stevens-Johnson;
• disorders in the field of connective tissue and ODA: pain in the limbs, as well as myalgia;
• manifestations of the system of urination: the development of hematuria;
• diseases of the mammary glands and reproductive organs: the appearance of bleeding from the penis, the development of excessively long erections, priapism, and hemospermia;
• systemic disorders: pain in the sternum, increased fatigue, a feeling of heat and a feeling of irritation;
• test results: increased heart rate.

[20], [21], [22], [23], [24],

Overdose

In tests involving volunteers after a single dose of up to 800 mg of LS, the reactions were similar to those occurring in the case of lower doses, but they were more frequent. The effectiveness of the effect at a dosage of up to 200 mg did not change, but it should be noted that the frequency of negative manifestations increased (among them, hot flashes, dyspepsia, headaches, vision problems, and with it nasal congestion).

In case of an overdose, symptomatic therapy is performed. The use of dialysis does not increase the level of clearance of the active substance, because it is actively synthesized with the plasma protein and not excreted in the urine.

Interactions with other drugs

The processes of sildenafil metabolism are mainly carried out with the isoform of ZA4 (is the main route), and in addition the 2S9 isoform (used as a secondary pathway) of the hemoprotein P450 (CYP). As a result, inhibitors of these isoenzymes are able to reduce the clearance of the substance, while their inductors, on the contrary, increase it.

Reduction in the values of clearance of sildenafil arose as a result of a combination with inhibitors of the element CYP3A4 (among them cimetidine with ketoconazole, as well as erythromycin). Although there was no increase in the development of negative symptoms in such treated patients, it is recommended to consider the variant with Vekta intake in the initial dosage of 25 mg with a similar combination.

When combined use of drugs (a single use of 100 mg) with a component of ritonavir, an HIV protease inhibitor (this is an extremely potent inhibitor of the P450 element), which is used in equilibrium (a single dose of 500 mg per day), an increase in the peak level of sildenafil (quadruple 300%), and in addition the plasma value of AUC substance (11 times - by 1000%). After 24 hours, the plasma values of the component still remained at approximately 200 ng / ml, compared to a figure of about 5 ng / ml, which is usually observed when only sildenafil is used. This corresponds to a significant effect of ritonavir substance on a large range of substrates such as P450. The active component of Vecta does not affect the pharmacokinetic parameters of ritonavir. Due to all the above, it can be concluded that the combination of these drugs is prohibited. In any case, if you used this combination, you still should not take sildenafil in a period of 48 hours in a dosage that exceeds the value of 25 mg.

Drug administration (once 100 mg) in combination with saquinavir (HIV protease inhibitor and CYP3A4 element), in a dosage that allows to achieve equilibrium values of the substance (1200 mg - three times per day), causes an increase in the peak level of the active component of the Vecta by 140%, and also AUC values (by 210%). Sildenafil has no effect on the various pharmacokinetic parameters of the saquinavir component. There are suggestions that stronger inhibitor drugs of the element CYP3A4 (among them itraconazole or ketoconazole) will have more pronounced properties.

The use of a single dose (100 mg) of sildenafil with an inhibitory agent of a moderate-type CYP3A4 element, erythromycin (equilibrium use of 500 mg twice daily for a period of 5 days), led to a 182% increase in the AUC level of the active drug component.

In male volunteers, when 500 mg of azithromycin was taken, during 3 days, the effect on the AUC, the peak level, the time of its attainment, and also the rate constant of the elimination process and the further half-life of the active component of Vecta or its main circulating decay product were not determined.

The administration of 800 mg of cimetidine (an inhibitor of the hemoprotein P450, and also a non-specific inhibitory drug of the CYP3A4 element) together with 50 mg of the active substance Vekta caused a 56% increase in the indices of the volunteers using the volunteers.

Grapefruit juice can slow down the action of the element CYP3A4 inside the intestinal walls (with a weak effect), and also increase the plasma values of sildenafil (moderately).

Although no tests have been performed to identify specific interactions with all drugs, the results of population pharmacokinetic studies have shown that the properties of sildenafil are not changed in the case of combined use with drugs from the category of inhibitors of the CYP2C9 element (such as warfarin with tolbutamide and phenytoin). In addition, there is no change when combined with drugs from the category of inhibitors of the CYP2D6 component (including selective drugs for inhibiting reverse serotonin uptake and tricyclics), as well as with the category of thiazide, and with it thiazide-like diuretics, calcium antagonists, ACE inhibitors, and in addition to these β-adrenoreceptor antagonist drugs or agents inducing the metabolism of the CYP450 element (among them barbiturates with rifampicin).

The combination with strong inducers of CYP3A4 component (with rifampicin substance) can cause a greater decrease in the plasma level of sildenafil.

The drug nicorandil is a hybrid agent containing nitrates and promoting the activation of Ca channels. Nitrate element suggests the possibility of developing close interaction with the substance sildenafil.

Since there is information that Vekta can affect the metabolism of NO / cGMP, it has been found that sildenafil can enhance the antihypertensive properties of nitrates. As a consequence, it is forbidden to combine the drug with nitrates of any type or with NO donors.

Combined use of drugs with α-adrenoreceptor blocking agents can cause symptomatic type hypotension in individual patients (having a predisposition). Such manifestations often appeared in the period of 4 hours after the use of Vekta.

Combination of a drug with doxazosin in people who achieved stabilization of their condition, using doxazosin, occasionally led to the appearance of an orthostatic collapse of a symptomatic type. At the same time, there were reports of dizziness and development of a pre-fainting condition (but without fainting).

In patients taking sildenafil, there were no changes in the profile of side effects (in comparison with placebo) in the case of combination with the following groups of antihypertensive drugs: ACE inhibitors, diuretics, β-adrenergic blocker drugs, antihypertensive agents with central and vasodilating effect, angiotensin type antagonists 2, and in addition to blockers of Ca channels, adrenergic type neurons, and α-adrenergic receptors.

In special testing of the combined use of sildenafil (100 mg) with amlodipine, an additional reduction (by 8 mm Hg) of the systolic blood pressure level was observed in persons with elevated blood pressure when lying down. The decrease in the diastolic blood pressure was 7 mm Hg.

In male volunteers, taking medications at the equilibrium concentration (three times per day 80 mg) increased the AUC and the peak level of the substance bosentan (twice daily 125 mg per day) by 49.8% and 42%, respectively.

[32], [33], [34], [35], [36], [37], [38], [39]

Storage conditions

The vector must be kept out of reach of small children. Temperature indices - not more than 25 ° С.

[40], [41]

Shelf life

Vekta can be used in the period of 3 years from the date of release of the drug.

[42], [43], [44]