Vecta

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

Indications Vektas

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

For the drug to take effect, the patient must be sexually aroused.

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Release form

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

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Pharmacodynamics

Vecta helps restore a man's ability to achieve an erection by providing the necessary natural response of the body to the sensation of sexual arousal. Physiologically, an erection is achieved by releasing the element N2O inside the cavernous body during sexual stimulation. NO stimulates the activity of the enzyme guanylate cyclase, resulting in an increase in the cGMP index, relaxation of the smooth muscles in the cavernous body and an increase in the blood circulation process inside the penis.

Sildenafil is a strong selective inhibitor of the cGMP-specific element of PDE-5, which helps the process of cGMP component breakdown 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 able to potentiate the relaxing effect of NO inside the cavernous body tissues. In the process of activation of the 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 indicators inside the cavernous body. Because of this, the drug requires adequate sexual arousal to implement the desired medicinal effect.

A single oral administration of up to 100 mg of the drug by a volunteer did not cause significant changes in ECG values. The maximum decrease in systolic blood pressure when the patient was in a supine position (taking 100 mg of the drug) averaged 8.4 mm Hg. The decrease in diastolic blood pressure in a similar position was 5.5 mm Hg. The decrease in blood pressure is associated with the vasodilating properties of sildenafil (probably due to an increase in cGMP levels within the smooth vascular muscles).

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Pharmacokinetics

The drug is rapidly absorbed after oral administration. When taken on an empty stomach, the peak plasma level is observed after 30-120 minutes (average - 60 minutes). The absolute level of bioavailability after oral use in standard doses has linear indicators. In case of taking the drug 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 indicator itself decreases by an average of 29%.

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

The substance is metabolized mainly by CYP3A4 (its main pathway) and CYP2C9 (a minor pathway), which are microsomal liver isoenzymes. The main circulating decay product is formed during N-desmethylation of the active substance. The decay product is comparable in selectivity of its effect on PDE to 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 that of sildenafil. The N-desmethyl metabolite undergoes further metabolism, and its terminal half-life is approximately 4 hours. The total clearance of the active ingredient is 41 l/hour, while the terminal half-life is about 3-5 hours.

After oral administration of the drug, excretion of the substance in the form of decay products occurs mainly with feces (approximately 80% of the consumed dose), and the remainder is excreted with urine (13% of the substance).

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Dosing and administration

The medicine should be taken orally.

The dosage of the drug for adult men is 50 mg. The tablet should be taken approximately 1 hour before sexual intercourse. Taking into account the effectiveness and tolerability of the drug, its dose can be increased to 100 mg or decreased to 25 mg. The maximum that can be taken per day without the risk of intoxication is 100 mg. If the drug is taken with food, its effect may begin later than if taken on an empty stomach.

Since people with severe liver or kidney failure (CC level <30 ml/min) have a reduced sildenafil clearance rate, it is necessary to consider the option of using the drug at a dosage of 25 mg. Then, taking into account the tolerability and effectiveness of Vecta, it is possible to gradually increase the dose to 50 or 100 mg.

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Contraindications

Among the existing contraindications:

• the presence of intolerance to sildenafil or other additional components of the drug;
• combined use with NO donors (amyl nitrite among them) or with any form of nitrates. Such a combination is prohibited, because there is evidence that sildenafil affects the NO/cGMP metabolic pathways, and in addition enhances the antihypertensive properties of nitrates;
• in conditions in which sexual activity is not recommended (for example, in the case of severe disorders of the cardiovascular system – severe heart failure or unstable angina);
• loss of visual function in one eye due to non-arteritic PIN (regardless of the presence/absence of a connection between this disease and the previous use of PDE-5 inhibitors);
• in the following pathologies: severe form of functional liver disorder, low blood pressure (indicator less than 90/50 mm Hg), recent myocardial infarction or stroke, as well as known degenerative retinal diseases of hereditary origin (including pigment retinitis; a small number of such patients have PDE disorders inside the retina of a genetic type), because the safety of using the drug in such subgroups of patients has not been tested.

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Side effects Vektas

The use of tablets may provoke the following side effects:

• invasions or infections: development of a runny nose;
• immune manifestations: development of hypersensitivity;
• reactions of the nervous system: a feeling of drowsiness, dizziness with headaches, the development of a stroke, hypoesthesia or microstroke, the appearance of fainting and convulsions (or their relapses);
• visual impairment: color vision impairment (such as cyanopsia with chloropsy, and also xanthopsia and chromatopsia with erythropsy), vision problems and the occurrence of opacities, the development of lacrimation (intensification of the process, disorder of the lacrimation function and dryness of the ocular mucosa), eye pain, photopsia and photosensitivity, as well as conjunctivitis and ocular hyperemia. In addition, visual brightness, non-arteritic PIN, retinal hemorrhage, retinal vascular occlusion, arteriosclerotic retinopathy, retinal disorders, diplopia with glaucoma and visual impairment occur. Visual field defects, asthenopia with myopia, mydriasis, PPST, iris problems, visual field halo, eye swelling, edema and disorder may occur. Eye irritation, eyelid swelling, conjunctival hyperemia and white discoloration are also observed;
• reactions of the vestibular apparatus and auditory organs: tinnitus, as well as the appearance of dizziness or the development of deafness;
• cardiac disorders: increased heart rate, development of myocardial infarction, tachycardia, ventricular or atrial fibrillation, as well as unstable angina, and also sudden death due to the heart;
• vascular disorders: flushing of the face, hypo- or hypertension and the appearance of hot flashes;
• reactions of the respiratory system and mediastinum with the sternum: nosebleeds, nasal (or sinus) congestion, swelling of the nasal mucosa (or its dryness), as well as a feeling of constriction in the throat;
• manifestations in the gastrointestinal tract: dyspeptic symptoms, vomiting, dry mouth, nausea, GERD, hypoesthesia in the oral cavity and pain in the upper abdomen;
• disorders of the subcutaneous layer and skin: rash, as well as Lyell's or Stevens-Johnson syndromes;
• disorders in the area of connective tissue and musculoskeletal system: pain in the limbs, as well as myalgia;
• manifestations from the urinary system: development of hematuria;
• diseases of the mammary glands and reproductive organs: the occurrence of bleeding from the penis, the development of an excessively long erection, priapism, and hemospermia;
• systemic disorders: pain in the sternum, increased fatigue, feeling of heat and feeling of irritation;
• test results: increased heart rate.

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Overdose

In tests involving volunteers after a single dose of up to 800 mg of the drug, reactions were similar to similar manifestations developing in the case of using lower doses, but they were observed more often. The effectiveness of the effect at a dose of up to 200 mg did not change, but it should be noted that the frequency of negative manifestations increased (including hot flashes, dyspeptic phenomena, headaches, vision problems, and nasal congestion).

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

Interactions with other drugs

Sildenafil metabolism processes are mainly carried out by isoform 3A4 (is the main route), and also isoform 2C9 (used as a secondary route) of hemoprotein P450 (CYP). As a result, inhibitors of these isoenzymes are able to reduce the clearance rate of the substance, while their inducers, on the contrary, increase it.

A decrease in sildenafil clearance values occurred as a result of a combination with inhibitors of the CYP3A4 element (including cimetidine with ketoconazole, as well as erythromycin). Although an increase in the development of negative symptoms in such patients was not observed, it is recommended to consider the option of taking Vecta at an initial dosage of 25 mg with such a combination.

When using the drug in combination (single use of 100 mg) with the component ritonavir - an HIV protease inhibitor (this is an extremely strong inhibitor of the P450 element), which is used in a steady state (single use of 500 mg per day), there is an increase in the peak level of sildenafil (fourfold - by 300%), as well as the plasma value of AUC of the substance (11 times - by 1000%). After 24 hours, the plasma values of the component still remained at a level of approximately 200 ng / ml compared to a figure of about 5 ng / ml, which is usually observed in the case of using only sildenafil. This corresponds to a significant effect of ritonavir on a wide range of P450 substrates. The active component of Vecta does not affect the pharmacokinetic parameters of ritonavir. Due to all of the above, it can be concluded that the combination of these drugs is prohibited. In any case, if it is necessary to use such a combination, sildenafil should not be taken in a dosage exceeding 25 mg within 48 hours.

Taking the drug (100 mg once) in combination with saquinavir (HIV protease and CYP3A4 inhibitor), in a dosage that allows to provide equilibrium values of the substance (1200 mg - three times a day), causes an increase in the peak level of the active component of Vecta by 140%, as well as AUC values (by 210%). Sildenafil does not affect various pharmacokinetic parameters of the saquinavir component. There are suggestions that stronger drugs-inhibitors of the CYP3A4 element (among them itraconazole or ketoconazole) will have more pronounced properties.

The use of a single dose (100 mg) of sildenafil with a moderate CYP3A4 inhibitor, erythromycin (equilibrium administration - 500 mg 2 times a day for 5 days), led to an increase in the AUC level of the active component of the drug by 182%.

In male volunteers, administration of 500 mg azithromycin for 3 days had no effect on the AUC, peak level, time to peak level, elimination rate constant or subsequent half-life of the active component of Vecta or its major circulating breakdown product.

Taking 800 mg of cimetidine (an inhibitor of hemoprotein P450, and also a non-specific drug-inhibitor of the CYP3A4 element) together with 50 mg of the active substance Vecta caused an increase in the latter's levels in the plasma of the volunteers who used them by 56%.

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

Although no specific interaction tests have been performed with all drugs, data from population pharmacokinetic studies have shown that the properties of sildenafil are not altered when combined with drugs from the category of CYP2C9 inhibitors (such as warfarin with tolbutamide and phenytoin). In addition, no changes are observed when combined with drugs from the category of CYP2D6 inhibitors (including selective serotonin reuptake inhibitors and tricyclics), as well as with the category of thiazides, as well as thiazide-like diuretics, calcium antagonists, ACE inhibitors, as well as beta-adrenergic antagonists or drugs that induce the metabolism of the CYP450 element (including barbiturates with rifampicin).

Combination with strong inducers of the CYP3A4 component (with the substance rifampicin) can cause a more significant decrease in the plasma level of sildenafil.

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

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

The combined use of drugs with α-adrenergic receptor blockers can cause symptomatic hypotension in individual patients (with a predisposition). Such manifestations often appeared within 4 hours after using Vecta.

The combination of the drug with doxazosin in people who had stabilized their condition using doxazosin occasionally resulted in symptomatic orthostatic collapse. Dizziness and light-headedness (but not syncope) were reported.

In subjects taking sildenafil, no changes in the side effect profile (compared to placebo) occurred when combined with the following groups of antihypertensive drugs: ACE inhibitors, diuretics, β-adrenergic receptor blockers, antihypertensive drugs with central and vasodilatory effect, angiotensin type 2 antagonists, and in addition with Ca channel blockers, adrenergic neurons, and α-adrenergic receptors.

In a special test of the combined use of sildenafil (100 mg) with amlodipine in individuals with elevated blood pressure, an additional decrease (by 8 mm Hg) in systolic blood pressure was observed in the supine position. The decrease in diastolic blood pressure was equal to 7 mm Hg.

In male volunteers, taking the drug at steady state (three times a day, 80 mg) increased the AUC and peak levels of bosentan (two times a day, 125 mg) by 49.8% and 42%, respectively.

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Storage conditions

Vecta should be kept out of reach of small children. Temperature indicators – no more than 25°C.

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Shelf life

Vecta can be used for a period of 3 years from the date of release of the drug.

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