Vizarsin

Vizarsin is a medicine used in case of problems with erection; helps to restore a weakened erection by potentiating blood flow to the penis.

The principle of drug activity is based on the processes of release of nitrous oxide in the region of the corpora cavernosa in the presence of sexual stimulation. Free nitrous oxide stimulates the activation of the enzyme guanylate cyclase, increasing the cGMP values. The result of this is relaxation in the area of the smooth muscle fibers of the cavernous bodies, and in addition to this, the potentiation of blood flow. [1]

Indications Vizarsin

It is used in case of problems with erectile activity in a man (inability to obtain or maintain an erection of the penis , in which sexual contact can be successfully made).

Release form

The release of a medicinal product is realized in tablets - 1, 2 or 4 pieces inside a cell pack (1 similar pack inside a package), as well as 4 tablets inside a plate (2 or 3 plates inside a pack).

Pharmacodynamics

Sildenafil is a powerful selective agent that inhibits the activity of PDE-5 (the element has cGMP-specific properties). Helps to restore impaired erection by increasing blood flow to the penis area.

Physiological activity, which is the basis of penile erection, consists of the release of nitrous oxide in the area of the corpus cavernosum under the influence of a sexual stimulus. [2]

Sildenafil demonstrates a peripheral effect on erection. It does not have a direct relaxing effect affecting the isolated corpus cavernosum, but it potentiates the relaxing activity of NO.

The activation of the NO / cGMP ligament, which is realized during sexual arousal, and the inhibition of the PDE-5 element with the help of sildenafil, cause an increase in cGMP values in the area of the corpus cavernosum. Therefore, in order to obtain the medicinal effect of sildenafil, a sexual stimulus is needed.

In vitro testing revealed that the selectivity of the drug is manifested in relation to PDE-5, which is a participant in the processes of the appearance of an erection. The effect with respect to PDE-5 is more intense than with respect to other known PDE components. The effectiveness of the substance relative to PDE-6 (involved in the processes of retinal phototransmission) is ten times lower. When using the maximum allowable portions, it exhibits selectivity with respect to PDE-1, which is 80 times weaker, and with respect to PDE types within 2-4, as well as in the range 7-11, by 700 times.

The effect of sildenafil on PDE-5 is approximately 4000 times stronger than the effect on PDE-3 (this is a component with cAMP-specific activity, a participant in heart contractions).

Sildenafil leads to a temporary slight decrease in blood pressure, which often does not cause the appearance of clinical signs. The maximum decrease in the level of systolic blood pressure (on average) with a horizontal position, with oral administration of a dosage of drugs of 0.1 g, is equal to 8.4 mm Hg. In this case, the level of DBP changes by 5.5 mm Hg. Such a decrease in blood pressure values is associated with the vasodilating activity of sildenafil (possibly caused by an increase in cGMP indices inside the smooth muscle of vascular cells).

Single oral administration of a portion of sildenafil up to 0.1 g did not lead to clinically significant changes in ECG values in volunteers.

The medication does not change the parameters of cardiac output and blood circulation through stenotic arteries.

Pharmacokinetics

The pharmacokinetic parameters of sildenafil when using the recommended dosage are linear.

Absorption.

When administered orally, the substance is absorbed at a high rate. Average indicators of absolute bioavailability are approximately 40% (in the range of 25-63%). In vitro, sildenafil, with values of approximately 1.7 ng / ml, inhibits the effect of human PDE-5 by 50%.

With a single administration of a 0.1 g portion, the average level of intraplasmic Cmax of a free element is approximately 18 ng / ml. The values of Cmax with the introduction of drugs on an empty stomach are recorded on average after 1 hour (in the range of 0.5-2 hours).

Consumption with fatty foods reduces the absorption rate: Cmax decreases on average by 29%, and the Tmax value increases by 1 hour; while the degree of absorption remains the same (AUC falls by 11%).

Distribution processes.

The average Vss of the drug is 105 liters. The synthesis of sildenafil and the main N-demethyl metabolic element with intraplasmic blood proteins is approximately 96% and is not tied to the general parameters of sildenafil. Less than 0.0002% of the dosage of sildenafil (average level - 188 ng) is recorded 1.5 hours after the injection of the drug inside the sperm.

Exchange processes.

Sildenafil is involved in metabolism mainly within the liver under the influence of the CYP3A4 isoenzyme (main scheme) and the CYP2C9 isoenzyme (additional scheme). The main metabolic component with activity is formed during N-demethylation of drugs and then also participates in metabolic processes. The selectivity of this metabolite with respect to PDE is similar to that of sildenafil, and its effect relative to PDE-5 in vitro is approximately 50% of that of sildenafil.

The plasma level of the metabolite in the volunteers was approximately 40% of the values for sildenafil. The N-demethyl metabolic component involved in further metabolic processes has a half-life of up to 4 hours.

Excretion.

The general figures for the clearance of drugs are 41 l / h, and the final half-life reaches 3-5 hours.

When administered orally (or in / in an injection), sildenafil is excreted mainly through the intestines (approximately 80%; in this case, it has the form of metabolites); the smaller part is excreted through the kidneys (approximately 13% of the serving).

Dosing and administration

You need to take the medicine orally - the tablet is first dissolved in the mouth, after which this mixture is swallowed. For the drug effect to manifest itself, a sexual stimulus is required. Vizarsin should be consumed approximately 60 minutes before sexual intercourse.

For a single dose, 50 mg of the drug is usually administered (it is recommended to use it on an empty stomach). The size of the maximum 1-time serving is 0.1 g.

• Application for children

The medication is not prescribed in pediatrics (under the age of 18).

Use Vizarsin during pregnancy

Vizarsin is not used in women.

Contraindications

The main contraindications:

• the presence of an allergy associated with sildenafil;
• hypersensitivity caused by auxiliary elements of the drug;
• combined use with nitrous oxide donor substances (among them amyl nitrite) or nitrates;
• conditions in which it is impossible to have sex (angina pectoris of an unstable form or heart failure in a severe stage);
• loss of vision in one eye due to ischemic neuropathy affecting the optic nerve (anterior non-arterial form);
• severe forms of hepatic dysfunction;
• reduced blood pressure values (less than 90/50 mm Hg);
• a patient's recent myocardial infarction or stroke;
• retinal changes of a hereditary nature with a degenerative variety (for example, retinitis of the pigmentary type).

Side effects Vizarsin

Among the side symptoms:

• neurological disorders: migraine, paresthesias, headaches, neuralgia, flushing of the face and fainting, as well as ataxia, dizziness, hypesthesia, tremors, drowsiness / insomnia, depression and decreased reflexes;
• ophthalmic problems: conjunctivitis, pain or hemorrhage in the area of the eyeballs, visual disturbance (blurred vision, photophobia and changes in color perception), mydriasis, xerophthalmia and cataracts;
• otolaryngological lesions: ear ringing or deafness;
• respiratory disorders: pharyngitis, asthma, dyspnea and nasal congestion, as well as sinusitis, cough potentiation, laryngitis, increased sputum volume and bronchitis;
• cardiovascular problems: tachycardia, heart failure, changes in ECG readings, a decrease in blood pressure, palpitations and AV blockade, as well as orthostatic collapse, myocardial ischemia, cardiac arrest, angina pectoris, cerebral thrombosis and cardiomyopathy;
• hematological disorders: leukopenia or anemia;
• lesions of the gastrointestinal type: esophagitis, glossitis, nausea, gastroenteritis and stomatitis with dysphagia, and in addition, xerostomia, colitis, gingivitis, gastritis and rectal bleeding;
• metabolic problems: hypernatremia or -uricemia, hypo / hyperglycemia, thirst, labile diabetes and gout;
• urogenital disorders: nocturia, gynecomastia, cystitis, infection of the urethra, anorgasmia, urinary incontinence or increased frequency, swelling of the genitals and ejaculation disorder;
• lesions of the ODA function: arthritis, myasthenia gravis, rupture affecting the tendons, myalgia, synovitis, arthrosis, tendosynovitis and ossalgia;
• dermatological problems: common herpes, contact or exfoliative type dermatitis, itching, epidermal ulcers, photosensitivity, urticaria and rashes;
• others: hyperhidrosis, peripheral edema, shock, chills, pain and signs of allergies.

Overdose

Possible manifestations of intoxication include dizziness, visual disturbances, flushing, nasal congestion, dyspepsia, and headaches.

In the event of violations, standard supportive actions are taken.

Interactions with other drugs

The effect of other medications on the pharmacokinetic parameters of sildenafil.

In vitro tests.

The metabolic processes of sildenafil are mostly realized with the help of hemoprotein P450 (CYP) isoenzymes 3A4 (which is the main pathway), as well as 2C9 (which is an additional pathway), due to which substances that slow down the action of these isoenzymes are able to reduce the level of sildenafil clearance; and their inductors, respectively, increase the clearance values.

In vivo tests.

The introduction together with drugs that slow down the activity of the isoenzyme CYP3A4 (this includes erythromycin with ketoconazole and cimetidine), lowers the clearance rates of sildenafil.

Ritonavir increases the AUC level of sildenafil by 11 times, so the combination of these substances is prohibited.

The combination of Vizarsin (0.1 g once a day) with saquinavir (slows down the action of the CYP3A4 isoenzyme and HIV protease), when constant blood values of the latter (1.2 g 3 times a day) are obtained, leads to an increase in the Cmax level of sildenafil by 140%, and the AUC indicator - by 210%. At the same time, sildenafil does not alter the pharmacokinetic properties of saquinavir.

More potent drugs that slow down the activity of the isoenzyme CYP3A4 (among them itraconazole with ketoconazole) are likely to lead to more noticeable changes in the pharmacokinetic parameters of sildenafil.

With 1-time use of 0.1 g of sildenafil together with erythromycin, which specifically slows down the action of CYP3A4, when constant blood counts of erythromycin are obtained (use of 0.5 g 2 times a day for a period of 5 days), causes an increase of 182% sildenafil AUC values.

When volunteers used cimetidine (0.8 g), which nonspecifically slows down the activity of CYP3A4, and sildenafil (dosage 50 mg), the plasma parameters of the latter increased by 56%.

Slightly inhibiting the activity of CYP3A4, grapefruit juice is able to moderately increase the plasma levels of sildenafil.

Nicorandil is a compound containing nitrate and a K channel activator. Due to the presence of the nitrate element, it is able to create strong interactions with the substance sildenafil.

The effect of sildenafil in relation to other drugs.

In vivo testing.

Taking into account the established effect of sildenafil relative to NO / cGMP, it is able to potentiate the antihypertensive effect of nitrates, which is why it cannot be combined with NO donors or any form of nitrate.

The combination of a drug with α-blockers can provoke a symptomatic decrease in blood pressure values in people with hypersensitivity. A decrease in blood pressure usually occurs after 4 hours after using sildenafil.

During 3 special tests regarding drug interactions in persons with benign prostatic hyperplasia and a stable level of hemodynamics, the combination of doxazosin (4 and 8 mg each) and sildenafil (dosage 0.025, 0.05 or 0.1 g) was studied. All 3 tests showed an additional average decrease in blood pressure in the horizontal position by 7/7, 9/5, as well as 8/4 mm Hg, and in addition, an additional decrease in blood pressure in the vertical position by 6/6, 11/4, as well as 4/5 mm Hg.

Co-administration of the drug with doxazosin in people with stable hemodynamic parameters occasionally led to the appearance of symptomatic orthostatic collapse. With these disorders, dizziness or a feeling of lightness was observed, but without the development of fainting.

During special testing, 0.1 g of sildenafil was administered in combination with amlodipine in people with elevated blood pressure - this led to an additional decrease in systolic blood pressure (by 8 mm Hg on average) and DBP (by 7 mm Hg). In a horizontal position. A similar additional decrease in blood pressure values was observed when using only sildenafil in volunteers.

Storage conditions

Vizarsin must be stored at a temperature level not exceeding + 25 ° C.

Shelf life

Vizarsin can be used within a 5-year period from the date of sale of the therapeutic product.

Analogs

The analogs of the medicine are Maxigra, Vildegra and Viagra with Olmax Strong, and in addition to this Sildenafil, Vivaira and Ridgeamp with Viasan-LF, Silafil and Dynamiko with Viatail. Also on the list are Kamastil, Tornetis with Juvena, Revazio and Erexesil with Silden.