Sealex Sildenafil, 50 mg

Sildenafil is a powerful selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5).

Mechanism of action.

The realization of the physiological mechanism of erection is associated with the release of nitric oxide (NO) in the cavernous body during sexual stimulation. This, in turn, leads to an increase in cGMP levels, a subsequent relaxation of the smooth muscle tissue of the cavernous body, and an increase in blood flow.

Sildenafil has no direct relaxant effect on the isolated human cavernous body, but it enhances the effect of nitric oxide (NO) through

Inhibition of FDE5, which is responsible for the breakdown of cGMP.

Sildenafil is selective against FDE5 shuigo, its activity against FDE5 is greater than that against other known phosphodiesterase isoenzymes: FDE6, 10 times; FDE1, more than 80 times; FDE2, FDE4, FDE7-FDE11, more than 700 times. Sildenafil is 4,000 times more selective against FDE5 compared to FDEZ, which is of critical importance because FDEZ is one of the key enzymes

Regulation of myocardial contractility.

The mandatory condition for the effectiveness of sildenafil is sexual stimulation. Pharmacokinetics

The pharmacokinetics of sildenafil in the recommended dose range is linear. Absorption

After oral administration, sildenafil is rapidly absorbed. Absolute bioavailability averages about 40 % (25 % to 63 %). sildenafil at a concentration of about 1.7 ng/ml (3.5 nM) inhibits human FDE5 activity by 50 %. After a single dose of sildenafil at a dose of 100 mg, the average maximum plasma concentration of free sildenafil (Stah) in men is about 18 ng/ml (38 nM). The average absorption rate when sildenafil is taken orally on an empty stomach is reached within 90 minutes:

The rate of absorption decreases by 29% and the time to reach the maximum concentration (Ttach) increases by 60 min, but the degree of absorption does not change significantly (the area under the pharmacokinetic curve of concentration-time (ATC) decreases by 11%).

Metabolism

Sildenafil is metabolized primarily in the liver by the cytochrome isoenzyme SURSA4 (major pathway) and the cytochrome isoenzyme SUR2C9 (minor pathway). The main circulating active metabolite formed as a result of

Ms-demethylation of sildenafil undergoes further – metabolism.

The selectivity of this metabolite against FDE is comparable with that of sildenafil, and its activity against FDE5 {t uigo is about 50% of the activity of sildenafil. Concentration of the metabolite in plasma of healthy volunteers was about 40% of sildenafil concentration. M-demethyl metabolite undergoes further metabolism; its half-life (T1/2) is about 4 hours.

Elevation

The total clearance of sildenafil is 41 L/hour, and the final T!/? – 3 to 5 hours. After oral administration as well as after intravenous administration sildenafil is excreted as metabolites mainly by the intestine (about 80% of the oral dose) and, to a lesser extent, by the kidneys (about 13% of the oral dose).

Pharmacokinetics in special groups of patients:

Elderly patients

In the elderly (65 years and older), sildenafil clearance is decreased and free sildenafil plasma concentrations are about 40% higher than in younger patients (18-45 years). Age has no clinically significant effect on the incidence of side effects. Renal dysfunction

In mild (creatinine clearance 50-80 ml/min) and moderate (creatinine clearance 30-49 ml/min) renal impairment, the pharmacokinetics of sildenafil after

Single oral administration of 50 mg does not change. In severe renal impairment

The area under the pharmacokinetic, concentration-time curve (APS by 100%) and Csache (88%) is approximately doubled compared to that of normal renal function in patients of the same age group.

Liver function disorders

In patients with cirrhosis (Child-Pugh stages A and B), sildenafil clearance is reduced, resulting in increased APS (84%) and Csache (47%) compared

with those of normal hepatic function in patients of the same age group. The pharmacokinetics of sildenafil in patients with severe hepatic impairment (Child-Pugh stage C) have not been studied.

Indications

The treatment of erectile dysfunction characterized by the inability to achieve or maintain a penile erection sufficient for satisfactory intercourse.

Sildenafil is effective only in the presence of sexual stimulation.

Active ingredient

Composition

Tablets 50 mg

Active ingredient:

sildenafil citrate — 70.2 mg (in terms of sildenafil – 50.0 mg).

Auxiliary substances:

Corn starch – 156.0 mg,

Cellulose

.p> Microcrystalline — 74.0 mg,

magnesium stearate – 5.0 mg,

/p>

talc — 5.0 mg,

silicon dioxide

Colloidal – 3.0 mg,

sodium carboxymethyl starch – 10.0 mg.

The film coating of Tyasoa! pink – 10.0 mg:

Titanium dioxide – 1.1 mg,

Red iron oxide dye – 1.6 mg,

How to take, the dosage

Ingestion.

The recommended dose for most adult patients is 50 mg approximately | hour before sexual activity. Depending on efficacy and tolerability, the dose may be increased to 100 mg. The maximum recommended dose is 100 mg. The maximum recommended frequency of use is once daily.

Elderly patients

There is no need to adjust the sildenafil dose.

Synopsis

Packeted film-coated tablets are pink, biconvex, diamond-shaped with cut and rounded edges, with “50” engraved on one side.

On the cross section of the tablet core is white or almost white.

Contraindications

1. Hypersensitivity to sildenafil or any other component of the drug. Use in patients receiving nitric oxide donators, organic nitrates or nitrites in any form continuously or intermittently, because sildenafil enhances the hypotensive effect of nitrates (see section “Interaction with other medicinal products”).

2. use in patients for whom sexual activity is undesirable (e.g., with severe cardiovascular disease, such as severe heart failure, unstable angina).

3. Arterial hypotension (blood pressure less than 90/50 mm Hg).

4. Severe chronic renal failure.

5. 5. Have had a cerebral circulation disorder or myocardial infarction within the past 6 months.

6. Severe liver dysfunction.

7. Hereditary degenerative retinal diseases, including retinitis pigmentosa. Concurrent use of ritonavir.

The safety and effectiveness of sildenafil when used in combination with other erectile dysfunction treatments have not been studied, so these combinations are not recommended (see section “Special Precautions”).

For the registered indication, sildenafil is not indicated for use in children

under 18 years of age. For the registered indication, sildenafil is not indicated for use in women.

With caution

1. Arterial hypertension (BP > 170/100 mm Hg).

2. Heart failure.

3. Life-threatening arrhythmias.

4. Anatomical deformity of the penis (angulation, cavernous fibrosis or Peyronie’s disease) (see section “Special Precautions”).

5. diseases predisposing to the development of priapism (sickle cell anemia, multiple myeloma, leukemia, thrombocythemia) (see section “Special Precautions”). Patients with a history of episodes of anterior nonarteritic ischemic optic neuropathy.

6. diseases accompanied by bleeding.

7. Exacerbation of gastric and duodenal ulcers.

8. Simultaneous use of alpha-adrenoblockers.

The use in pregnancy and during breastfeeding

The drug is not intended for use in women according to the registered indication.

Side effects

In general, sildenafil side effects are mild to moderate

In fixed-dose studies, the incidence of some

adverse events has been shown to increase with increasing dose.

General condition disorders: chest pain, general weakness, irritability,

feeling of fever, feeling of fatigue. Allergic reactions: hypersensitivity reactions (including skin rash), Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome). Central and peripheral nervous system disorders: somnolence, stroke, syncope, hypoesthesia, transient ischemic attack, convulsions including recurrent ones.

Cardiovascular system disorders: tachycardia, increased or decreased BP, myocardial infarction, atrial fibrillation, ventricular arrhythmia, unstable angina, “hot flashes” and palpitation, sudden death. Respiratory disorders: nasal bleeding, sinus congestion, feeling of tightness in the throat, dry nasal mucosa, nasal mucosa edema.

Digestive system disorders: vomiting, nausea, dry oral mucosa, dyspepsia, abdominal pain, gastroesophageal reflux disease, oral mucosa hypoesthesia.

Visual disorders: Eye pain, eye redness/sclera injections, conjunctival lesions, tear production disorders, anterior ischemic optical neuropathy, retinal vascular occlusion, visual field defects, photophobia, photopsia, diplopia, glaucoma, decreased visual acuity, Myopia, asthenopia, retinal edema, retinal vascular disease, eye discomfort, mydriasis, blurred vision, visual disturbances, retinal hemorrhage, atherosclerotic retinopathy, eye irritation, eyelid edema, sclera discoloration.

Hearing disorders: vertigo, tinnitus, deafness, tinnitus. Musculoskeletal disorders: myalgia, pain in the extremities.

Reproductive system disorders: prolonged erection and/or priapism, hematospermia and bleeding from the penis.

Urogenital system disorders: hematuria.

Overdose

Single doses of up to 800 mg had similar adverse events to those of lower doses, but were more frequent.

Similarities