Vivaira chewable tablets 100mg, No. 1

• Treatment of erectile dysfunction, characterized by an inability to achieve or maintain an erection of the penis sufficient for satisfactory intercourse.

• Pulmonary hypertension.

Treatment of erectile dysfunction: taken orally about 1 hour before the planned sexual activity. A single dose is 50 mg. Taking into account the effectiveness and tolerability, the dose can be increased to 100 mg or reduced to 25 mg. The maximum single dose is 100 mg. The maximum frequency of use is 1 time / day. For elderly patients over the age of 65 and with concomitant renal or hepatic impairment, the dose is 25 mg.

Pulmonary hypertension: inside, 20 mg 3 times / day with an interval of about 6-8 hours, regardless of food intake. The maximum daily dose is 60 mg. Patients with impaired renal function do not require dose adjustment, however, with poor tolerance, the dose is reduced to 20 mg 2 times / day.

Chewable tablets, white, triangular, biconvex

sildenafi 100mg; 50mg; 25mg.

Excipients: potassium polacrilin, magnesium stearate, colloidal silicon dioxide, aspartame, croscarmellose sodium, mint flavor (maltodextrin - 71%, modified E1450 starch (waxy corn) - 2.5%, peppermint leaf oil - 26.5%, lactose monohydrate30 , potassium hydroxide or hydrochloric acid - q.

• Simultaneous intake of nitric oxide or nitrate donors in any form,

• hypersensitivity to sildenafil.

pharmachologic effect

Selective inhibitor of cycloguanosine monophosphate (cGMP) -specific PDE5. PDE5, responsible for the breakdown of cGMP, is contained not only in the cavernous body of the penis, but also in the vessels of the lungs. Restores impaired erectile function and provides a natural response to sexual arousal. Sildenafil does not have a direct relaxing effect on the corpora cavernosa, but actively enhances the relaxing effect of nitric oxide on this tissue. With sexual arousal, the local release of NO under the influence of sildenafil leads to inhibition of PDE5 and an increase in the level of cGMP in the corpus cavernosum, resulting in relaxation of smooth muscles and increased blood flow in the corpus cavernosum. As a PDE5 inhibitor, sildenafil increases the content of cGMP in the smooth muscle cells of the pulmonary vessels and causes them to relax.In patients with pulmonary hypertension, taking sildenafil leads to vasodilation of the lungs and, to a lesser extent, other vessels. Sildenafil is selective for PDE5 in vitro. Its activity in relation to PDE5 exceeds the activity in relation to other known PDE isozymes: PDE6, which is involved in the transmission of a light signal in the retina of the eye - 10 times; PDE1 - 80 times; PDE2, PDE4, PDE7-PDE11 - more than 700 times. The activity of sildenafil against PDE5 is more than 4000 times higher than its activity against PDE3, a cAMP-specific PDE involved in cardiac contraction. Sildenafil can cause mild and transient color discrimination (blue / green). The putative mechanism of color vision impairment is the inhibition of PDE6, which is involved in the process of light transmission in the retina. In vitro studies have shownthat the effect of sildenafil on PDE6 is 10 times inferior to its activity against PDE5.

Pharmacokinetics

After oral administration, sildenafil is rapidly absorbed. Absolute bioavailability averages 40% (25-63%). After a single oral dose of 100 mg, Cmax is 18 ng / ml and is achieved when taken on an empty stomach for 30-120 minutes. When taking sildenafil in combination with fatty foods, the rate of absorption is reduced; “max increases by 60 minutes, and Cmax decreases by an average of 29%. The Vd of sildenafil in an equilibrium state averages 105 liters. Sildenafil and its main circulating N-desmethyl metabolite are approximately 96% bound to plasma proteins. Protein binding is independent of the total concentration of sildenafil. Less than 0.0002% of the dose (average 188 ng) was found in semen 90 minutes after taking sildenafil. Sildenafil is metabolized mainly by the action of microsomal liver isoenzymes CYP3A4 (main pathway) and CYP2C9.The main circulating metabolite, which is formed as a result of the N-desmethylation of sildenafil, undergoes further metabolism. In terms of selectivity of action on PDE, the metabolite is comparable to sildenafil, and its activity against PDE5 in vitro is approximately 50% of the activity of sildenafil itself. The plasma concentration of the metabolite is approximately 40% of that of sildenafil. N-desmethylmetabolite undergoes further metabolism; its terminal T1 / 2 is about 4 hours.The total clearance of sildenafil from the body is 41 l / h, and T1 / 2 in the terminal phase is 3-5 hours.After oral administration, sildenafil is excreted as metabolites mainly in the feces (about 80% dose) and to a lesser extent - with urine (approximately 13% of the dose). In elderly patients (65 years and older), the clearance of sildenafil is reduced,and the concentration of the free active substance in plasma is about 40% higher than its concentration in young (18-45 years old) patients. In renal failure mild (CC 50-80 ml / min) and moderate (CC 30-49 ml / min) severity, the pharmacokinetic parameters of sildenafil after oral administration of a single dose (50 mg) do not change. In severe renal failure (CC ? 30 ml / min), the clearance of sildenafil decreases, which leads to an approximately two-fold increase in AUC (100%) and Cmax (88%) compared with those with normal renal function in patients of the same age group. In patients with cirrhosis of the liver (class A and B on the Child-Pugh scale), the clearance of sildenafil decreases, which leads to an increase in AUC (84%) and Cmax (47%) compared with those with normal liver function in patients of the same age group ...In renal failure mild (CC 50-80 ml / min) and moderate (CC 30-49 ml / min) severity, the pharmacokinetic parameters of sildenafil after oral administration of a single dose (50 mg) do not change. In severe renal failure (CC ? 30 ml / min), the clearance of sildenafil decreases, which leads to an approximately twofold increase in AUC (100%) and Cmax (88%) compared with those in patients with normal renal function in patients of the same age group. In patients with cirrhosis of the liver (class A and B on the Child-Pugh scale), the clearance of sildenafil decreases, which leads to an increase in AUC (84%) and Cmax (47%) compared with those with normal liver function in patients of the same age group ...In renal failure mild (CC 50-80 ml / min) and moderate (CC 30-49 ml / min) severity, the pharmacokinetic parameters of sildenafil after oral administration of a single dose (50 mg) do not change. In severe renal failure (CC ? 30 ml / min), the clearance of sildenafil decreases, which leads to an approximately twofold increase in AUC (100%) and Cmax (88%) compared with those in patients with normal renal function in patients of the same age group. In patients with cirrhosis of the liver (class A and B on the Child-Pugh scale), the clearance of sildenafil decreases, which leads to an increase in AUC (84%) and Cmax (47%) compared with those with normal liver function in patients of the same age group ...which leads to an approximately twofold increase in AUC (100%) and Cmax (88%) compared with those with normal renal function in patients of the same age group. In patients with cirrhosis of the liver (class A and B on the Child-Pugh scale), the clearance of sildenafil decreases, which leads to an increase in AUC (84%) and Cmax (47%) compared with those with normal liver function in patients of the same age group ...which leads to an approximately twofold increase in AUC (100%) and Cmax (88%) compared with those with normal renal function in patients of the same age group. In patients with cirrhosis of the liver (class A and B on the Child-Pugh scale), the clearance of sildenafil decreases, which leads to an increase in AUC (84%) and Cmax (47%) compared with those with normal liver function in patients of the same age group ...

Side effect

From the side of the central nervous system: headache, hot flashes, dizziness, insomnia are possible. From the digestive system: possible dyspepsia, asthenia, diarrhea, abdominal pain, nausea. From the musculoskeletal system: arthralgia, myalgia, increased muscle tone. Respiratory system: nasal congestion, pharyngitis, rhinitis, sinusitis, respiratory tract infections, respiratory failure. From the side of the organ of vision: changes in vision (mild and transient; mainly a change in the color of objects, as well as increased perception of light and impaired clarity of vision), conjunctivitis. Others: possible flu-like syndrome, development of infectious diseases, symptoms of vasodilation, back pain, rash, urinary tract infections, dysfunction of the prostate gland; in isolated cases - priapism.

Application for violations of liver function

For violations of liver function, the dose is 25 mg.

Application for impaired renal function

For impaired renal function, the dose is 25 mg.

Application in children

Sildenafil is not used in patients under the age of 18 years.

Use in elderly patients

For elderly patients over the age of 65, the dose is 25 mg.

special instructions

Before taking sildenafil for the treatment of erectile dysfunction, a cardiovascular examination should be performed. It should be used with caution in patients with anatomical deformity of the penis (for example, angulation, cavernous fibrosis or Peyronie's disease) and people with diseases that predispose to the development of priapism (such as sickle cell anemia, multiple myeloma or leukemia). Should not be used in patients for whom sexual activity is undesirable. Use with caution in patients with a tendency to bleeding, with gastric ulcer and duodenal ulcer in the acute phase, with hereditary retinitis pigmentosa. Sildenafil is not used in patients under the age of 18.Effect on the ability to drive vehicles and use mechanisms Sildenafil does not affect the ability to drive vehicles and use mechanisms.

Drug interactions

With the simultaneous use of CYP3A4 inhibitors (erythromycin, cimetidine), the clearance of sildenafil decreases, the concentration of sildenafil in the blood plasma increases. With the simultaneous use of indinavir, saquinavir, ritonavir, the Cmax in the blood plasma and the AUC of sildenafil increase, which is due to the inhibition of the CYP3A4 isoenzyme under the influence of indinavir, saquinavir, ritonavir. It can be expected that stronger inhibitors of the isoenzyme CYP3A4, such as ketoconazole or itraconazole, will increase the concentration of sildenafil in blood plasma. When used simultaneously with nitrates, the hypotensive effect of nitrates is enhanced. A case of the development of symptoms of rhabdomyolysis after a single dose of sildenafil in a patient receiving simvastatin is described.