Vizarsin

Vizarsin is a medication used in cases of erectile dysfunction; it helps restore weakened erection by increasing blood flow to the penis.

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

Indications Vizarsin

It is used in cases of problems with erectile function in men (inability to achieve or maintain an erection of the penis that can successfully perform sexual intercourse).

Release form

The medicinal product is released in tablets - 1, 2 or 4 pieces inside a cell pack (1 such pack inside the package), as well as 4 tablets inside a plate (2 or 3 plates inside the pack).

Pharmacodynamics

Sildenafil is a powerful selective agent that slows down the activity of PDE-5 (the element has cGMP-specific properties). It helps restore erectile dysfunction by increasing blood flow to the penis.

The physiological activity that is the basis of penile erection consists of the release of nitrous oxide in the corpora cavernosa region under the influence of sexual stimulus. [ 2 ]

Sildenafil exhibits a peripheral effect on erection. It has no direct relaxing effect on the isolated human corpus cavernosum, but it potentiates the relaxing activity of NO.

Activation of the NO/cGMP linkage, which occurs during sexual arousal, and inhibition of the PDE5 element by sildenafil cause an increase in cGMP levels in the cavernous body. Therefore, to obtain the medicinal effect of sildenafil, a sexual stimulus is needed.

In vitro testing has shown that the drug's selectivity is manifested in relation to PDE-5, which is a participant in the processes of erection. The effect in relation to PDE-5 is more intense than in relation to other known PDE components. The effectiveness of the substance in relation to PDE-6 (participates in the processes of retinal phototransmission) is ten times lower. When using the maximum permissible doses, it exhibits selectivity in relation to PDE-1, which is weaker by 80 times, and in relation to PDE types within 2-4, as well as in the range of 7-11 - by 700 times.

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

Sildenafil causes a temporary, slight decrease in blood pressure, which often does not cause clinical signs. The maximum decrease in systolic blood pressure (on average) in a horizontal position, with oral administration of a 0.1 g dose of the drug, is 8.4 mm Hg. In this case, the level of diastolic blood pressure changes by 5.5 mm Hg. Such a decrease in blood pressure is associated with the vasodilating activity of sildenafil (possibly caused by an increase in cGMP levels inside the smooth muscles of vascular cells).

Single oral doses of sildenafil up to 0.1 g did not result in clinically significant changes in ECG values in volunteers.

The drug does not change cardiac output indices or blood circulation processes through stenotic arteries.

Pharmacokinetics

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

Absorption.

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

With a single administration of a 0.1 g portion, the average level of intraplasmic Cmax of the free element is approximately 18 ng/ml. The Cmax values when administering the drug 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 rate of absorption: Cmax decreases by an average of 29%, and the Tmax value increases by 1 hour; however, the degree of absorption remains the same (AUC decreases by 11%).

Distribution processes.

Average values of Vss of the drug are 105 l. Synthesis of sildenafil and the main N-demethyl metabolic element with intraplasmic blood proteins is approximately 96% and is not tied to the general indicators of sildenafil. Less than 0.0002% of the dosage of sildenafil (average level - 188 ng) is recorded after 1.5 hours from the moment of administration of the drug inside the sperm.

Exchange processes.

Sildenafil is metabolized primarily in the liver by the CYP3A4 isoenzyme (primary pathway) and the CYP2C9 isoenzyme (secondary pathway). The main metabolic component with activity is formed during N-demethylation of the drug and then also participates in metabolic processes. The selectivity of this metabolite's activity for PDE is similar to that of sildenafil, and its effect on PDE-5 in vitro is approximately 50% of sildenafil's activity.

Plasma levels of the metabolite in volunteers were approximately 40% of those of sildenafil. The N-demethyl metabolic component involved in further metabolic processes has a half-life of up to 4 hours.

Excretion.

The overall drug clearance figures are 41 l/hour, and the final half-life reaches 3-5 hours.

When administered orally (or intravenously), sildenafil is excreted primarily through the feces (approximately 80%; in the form of metabolites); a smaller portion is excreted through the kidneys (approximately 13% of the dose).

Dosing and administration

The medicine must be taken orally - the tablet is first dissolved in the mouth, after which the mixture is swallowed. For the medicinal effect to manifest itself, a sexual stimulus is required. Vizarsin should be taken approximately 60 minutes before sexual intercourse.

Usually 50 mg of the drug is administered per single dose (it is recommended to use it on an empty stomach). The maximum single dose is 0.1 g.

• Application for children

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

Use Vizarsin during pregnancy

Vizarsin is not used in women.

Contraindications

Main contraindications:

• presence of allergy associated with sildenafil;
• hypersensitivity caused by excipients of the drug;
• combined use with nitrous oxide donor substances (amyl nitrite among them) or nitrates;
• conditions in which sexual activity is prohibited (unstable angina or severe heart failure);
• loss of vision in one eye due to ischemic neuropathy affecting the optic nerve (anterior non-arteritic form);
• severe forms of liver dysfunction;
• decreased blood pressure values (less than 90/50 mmHg);
• the patient has recently suffered a myocardial infarction or stroke;
• having a degenerative variety of retinal changes of a hereditary nature (for example, retinitis pigmentosa).

Side effects Vizarsin

Side effects include:

• neurological disorders: migraine, paresthesia, headaches, neuralgia, flushing of the face and fainting, as well as ataxia, dizziness, hypoesthesia, tremor, drowsiness/insomnia, depression and decreased reflexes;
• ophthalmological problems: conjunctivitis, pain or hemorrhage in the eyeball area, visual disturbances (blurred vision, photophobia and changes in color perception), mydriasis, xerophthalmia and cataracts;
• otolaryngological lesions: tinnitus or deafness;
• respiratory disorders: pharyngitis, bronchial asthma, dyspnea and nasal congestion, as well as sinusitis, increased cough, laryngitis, increased sputum volume and bronchitis;
• cardiovascular problems: tachycardia, heart failure, changes in ECG readings, decreased blood pressure, palpitations and AV block, as well as orthostatic collapse, myocardial ischemia, cardiac arrest, angina pectoris, cerebral vascular thrombosis and cardiomyopathy;
• hematological disorders: leukopenia or anemia;
• gastrointestinal lesions: esophagitis, glossitis, nausea, gastroenteritis and stomatitis with dysphagia, as well as xerostomia, colitis, gingivitis, gastritis and rectal bleeding;
• metabolic problems: hypernatremia or -uricemia, hypo-/hyperglycemia, thirst, labile diabetes and gout;
• urogenital disorders: nocturia, gynecomastia, cystitis, urinary tract infections, anorgasmia, incontinence or increased urination, genital swelling and ejaculation disorder;
• lesions of the musculoskeletal system: arthritis, myasthenia, rupture affecting tendons, myalgia, synovitis, arthrosis, tendosynovitis and ossalgia;
• dermatological problems: common herpes, contact or exfoliative dermatitis, itching, ulcers on the epidermis, photosensitivity, urticaria and rashes;
• others: hyperhidrosis, peripheral edema, shock, chills, pain and signs of allergy.

Overdose

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

In case of violations, standard supportive actions are carried out.

Interactions with other drugs

Effects of other drugs on the pharmacokinetic parameters of sildenafil.

In vitro tests.

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

In vivo tests.

Administration together with drugs that inhibit the activity of the CYP3A4 isoenzyme (this includes erythromycin with ketoconazole and cimetidine) reduces the clearance rates of sildenafil.

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

Combining Vizarsin (0.1 g once a day) with saquinavir (slows down the action of the CYP3A4 isoenzyme and HIV protease), with constant blood values of the latter (1.2 g 3 times a day), 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 change the pharmacokinetic properties of saquinavir.

More potent CYP3A4 inhibitors (including itraconazole and ketoconazole) are likely to result in greater changes in the pharmacokinetic parameters of sildenafil.

With a single use of 0.1 g of sildenafil together with erythromycin, which specifically slows down the action of CYP3A4, when obtaining constant blood levels of erythromycin (use of 0.5 g 2 times a day for 5 days), it causes an increase of 182% in the AUC values of sildenafil.

When volunteers used cimetidine (0.8 g), which non-specifically inhibits CYP3A4 activity, and sildenafil (50 mg dosage), there was an increase in plasma levels of the latter by 56%.

Grapefruit juice, a weak inhibitor of CYP3A4 activity, can moderately increase plasma levels of sildenafil.

Nicorandil is a compound that includes a nitrate and a K channel activator. Due to the presence of the nitrate element, it is capable of creating strong interactions with the substance sildenafil.

The effect of sildenafil on other drugs.

In vivo testing.

Given the established effect of sildenafil on NO/cGMP, it is capable of potentiating the antihypertensive effect of nitrates, which is why it cannot be combined with NO donors or any forms of nitrates.

Combination of the drug with α-blockers may provoke a symptomatic decrease in blood pressure in people with hypersensitivity. A decrease in blood pressure usually occurs after 4 hours from the moment of using sildenafil.

In three separate drug-drug interaction studies in patients with benign prostatic hyperplasia and stable hemodynamics, a combination of doxazosin (4 and 8 mg) and sildenafil (0.025, 0.05, or 0.1 g) was studied. All three studies showed an additional mean reduction in supine BP of 7/7, 9/5, and 8/4 mmHg, and an additional mean reduction in upright BP of 6/6, 11/4, and 4/5 mmHg.

Co-administration of the drug with doxazosin in hemodynamically stable individuals has occasionally resulted in symptomatic orthostatic collapse. These events included dizziness or a feeling of lightheadedness, but without syncope.

In a special test, 0.1 g of sildenafil was administered in combination with amlodipine in people with elevated blood pressure values - this led to an additional decrease in systolic blood pressure (by 8 mmHg on average) and diastolic blood pressure (by 7 mmHg) in a horizontal position. A similar additional decrease in blood pressure values was also observed when sildenafil was used alone in volunteers.

Storage conditions

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

Shelf life

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

Analogues

Analogues of the drug are Maxigra, Wildegra and Viagra with Olmax Strong, and in addition to this, Sildenafil, Vivaira and Ridjamp with Viasan-LF, Silafil and Dinamico with Viatail. Also on the list are Kamastil, Tornetis with Juvena, Revatio and Erexezil with Silden.