Sealex Sildenafil pills 100mg, 1pc

Composition

Active ingredient:

sildenafil citrate – 140.5 mg (in terms of sildenafil-100.0 MG).

Auxiliary substances:

corn starch — 223.0 mg,

microcrystalline cellulose-110.0 mg,

magnesium stearate-8.0 mg,

talc-5.0 mg,

colloidal silicon dioxide-3.0 mg,

sodium carboxymethyl starch-10.0 mg.

Film coating blue-12.0 mg:

titanium dioxide-1.3 mg, Diamond blue dye-1.9 mg,

hypromellose-3.8 mg,

macrogol-4.5 mg,

talc-0.5 mg

Pharmacological action

Pharmacodynamics

Sildenafil is a potent 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, subsequent relaxation of the smooth muscle tissue of the cavernous body, and increased blood flow.

Sildenafil does not have a direct relaxing effect on the isolated human cavernous body, but it enhances the effect of nitric oxide (NO) by inhibiting PDE5, which is responsible for the breakdown of cGMP. Sildenafil is selective for PDE5 in vitro, its activity against PDE5 exceeds that of other known phosphodiesterase isoenzymes: PDE6-by 10 times; PDE1-by more than 80 times; PDE2, PDE4, PDE7-PDE11 – by more than 700 times.

Sildenafil is 4000 times more selective for PDE5 compared to PDE5, which is of crucial importance, since PDE5 is one of the key enzymes in the regulation of myocardial contractility.

A prerequisite for the effectiveness of sildenafil is sexual stimulation.

Pharmacokinetics

The pharmacokinetics of sildenafil in the recommended dose range are linear.

Suction

After oral use, sildenafil is rapidly absorbed. Absolute bioavailability averages about 40% (from 25% to 63%). In vitro, sildenafil at a concentration of about 1.7 ng/ml (3.5 nM) suppresses human PDE5 activity by 50%.

After a single 100 mg dose of sildenafil, the average maximum concentration of free sildenafil in the blood plasma (Cmax) of men is about 18 ng / ml (38 nM). Cmax when taking sildenafil orally on an empty stomach is reached on average within 90 minutes.

When taken in combination with fatty foods, the absorption rate decreases: Cmax decreases by an average of 29%, and the time to reach the maximum concentration (Tmax) increases by 60 minutes, but the degree of absorption does not change significantly (the area under the pharmacokinetic curve concentration-time (AUC) decreases by 11%).

Distribution

The volume of distribution of sildenafil at steady state averages 105 liters. The plasma protein binding of sildenafil and its main circulating N-demethyl metabolite is approximately 96% and does not depend on the total concentration of the drug. Less than 0.0002% of the dose (average 188 ng) was detected in semen 90 minutes after taking sildenafil.

Metabolism

Sildenafil is mainly metabolized in the liver by the cytochrome CYP3A4 isoenzyme (major pathway) and the cytochrome CYP2C9 isoenzyme (minor pathway). The main circulating active metabolite formed as a result of N-demethylation of sildenafil undergoes further metabolism.

The selectivity of this metabolite against PDE is comparable to that of sildenafil, and its activity against PDE5 in vitro is about 50% of that of sildenafil. The concentration of the metabolite in the blood plasma of healthy volunteers was about 40% of the concentration of sildenafil. The N-demethyl metabolite undergoes further metabolism; its half-life (T 1/2) is about 4 hours.

Deduction

The total clearance of sildenafil is 41 l / h, and the final T 1/2 is 3-5 hours. After oral use, as well as after intravenous use, sildenafil is excreted as metabolites, mainly by the intestines (about 80% of the oral dose) and, to a lesser extent, by the kidneys (about 13% of the oral dose).

Pharmacokinetics in special patient groups:

Elderly patients

In the elderly (65 years and older), the clearance of sildenafil is reduced, and the concentration of free sildenafil in plasma is approximately 40% higher than in young people (18-45 years). Age does not have a clinically significant effect on the incidence of side effects.

Impaired renal function

In mild (creatinine clearance 50-80 ml/min) and moderate (creatinine clearance 30-49 ml/min) renal insufficiency, the pharmacokinetics of sildenafil after a single oral dose of 50 mg do not change. In severe renal insufficiency (creatinine clearance < 30 ml/min), sildenafil clearance decreases, resulting in approximately a twofold increase in the area under the concentration-time pharmacokinetic curve (AUC per 100%) and Cmax (88%) compared to those with normal renal function in patients of the same age group.

Liver function disorders

In patients with cirrhosis of the liver (stages A and B according to the Child-Pugh classification), the clearance of sildenafil decreases, which leads to an increase in AUC (84%) and Cmax (47%) compared to those with normal liver 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

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

Sildenafil is effective only in the presence of sexual stimulation.

Contraindications

1. Hypersensitivity to sildenafil or any other component of the drug. Use in patients receiving continuous or intermittent nitric oxide donors, organic nitrates or nitrites in any form, as sildenafil increases the hypotensive effect of nitrates (see the section “Interaction with other drugs”).

2. Use in patients for whom sexual activity is undesirable (for example, with severe cardiovascular diseases, such as severe heart failure, unstable angina).

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

4. Severe chronic renal failure.

5. A brain circulatory disorder or myocardial infarction that has occurred in the last six months.

6. Severe liver function disorders.

7. Hereditary degenerative diseases of the retina, including retinitis pigmentosa. Simultaneous use of ritonavir.

The safety and efficacy of sildenafil when co-administered with other treatments for erectile dysfunction have not been studied, so the use of such

combinations is not recommended (see section “Special instructions”).

According to the registered indication, sildenafil is not intended for use in children

under 18 years of age. According to the registered indication, sildenafil is not intended 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 the section “Special instructions”).

5. Diseases predisposing to the development of priapism (sickle cell anemia, multiple myeloma, leukemia, thrombocythemia) (see the section “Special instructions”). Patients with a history of anterior non-arteritic ischemic optic neuropathy.

6. Diseases accompanied by bleeding.

7. Exacerbation of peptic ulcer of the stomach and duodenum.

8. Simultaneous use of alpha-blockers.

Use during pregnancy and lactation

According to the registered indication, the drug is not intended for use in women.

Side effects

Usually, the side effects of sildenafil are mild to moderate

Fixed-dose studies have shown that the frequency of some adverse events increases with increasing dose.

Disorders of the general condition: chest pain, general weakness, irritability, feeling hot, feeling tired.

Allergic reactions: hypersensitivity reactions (including skin rash), Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome).

Central and peripheral nervous system disorders: drowsiness, stroke, syncope, hypesthesia, transient ischemic attack, convulsions, including recurrent ones.

Cardiovascular disorders: tachycardia, increased or decreased blood pressure, myocardial infarction, atrial fibrillation, ventricular arrhythmia, unstable angina, hot flashes and palpitations, sudden death.

Respiratory disorders: nasal bleeding, sinus congestion, tightness in the throat, dryness of the nasal mucosa, swelling of the nasal mucosa.

Disorders of the digestive system: vomiting, nausea, dryness of the oral mucosa, dyspepsia, abdominal pain, gastroesophageal reflux disease, hypesthesia of the oral mucosa.

Visual disorders: eye pain, redness of the eyes/sclera injections, conjunctival damage, lacrimation disorders, anterior ischemic optic 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 impairment, retinal hemorrhage, atherosclerotic retinopathy, eye irritation, edema of the eyelids, discoloration of the sclera.

Hearing disorders: vertigo, tinnitus, deafness, ringing in the ears.

Musculoskeletal disorders: myalgia, pain in the extremities.

Reproductive system disorders: prolonged erections and / or priapism, hematospermia, and penile bleeding.

Disorders of the genitourinary system: hematuria.

Interaction

Effect of other drugs on the pharmacokinetics of sildenafil

The metabolism of sildenafil occurs mainly under the action of cytochrome CYP3A4 (main pathway) and CYP2C9 isoenzymes, so inhibitors of these isoenzymes can reduce the clearance of sildenafil, and inducers, respectively, increase the clearance of sildenafil.

A decrease in the clearance of sildenafil was observed with the simultaneous use of inhibitors of the cytochrome CYP3A4 isoenzyme (ketoconazole, erythromycin, cimetidine). Cimetidine (800 mg), a non-specific inhibitor of the cytochrome CYP3A4 isoenzyme, when co-administered with sildenafil (50 mg) causes an increase in the concentration of sildenafil in plasma by 56%.

A single dose of 100 mg of sildenafil together with erythromycin (500 mg / day 2 times a day for 5 days), a specific inhibitor of the cytochrome CYP3A4 isoenzyme, against the background of achieving a constant concentration of erythromycin in the blood, leads to an increase in the AUC of sildenafil by 182%.

When co-administered with sildenafil (100 mg once) and saquinavir (1200 mg / day 3 times a day), an HIV protease inhibitor and cytochrome CYP3A4 isoenzyme, while achieving a constant concentration of saquinavir in the blood, the Cmax of sildenafil increased by 140%, and the AUC increased by 210%.

Sildenafil does not affect the pharmacokinetics of saquinavir. Stronger inhibitors of the cytochrome CYP3A4 isoenzyme, such as ketoconazole and itraconazole, can also cause stronger changes in the pharmacokinetics of sildenafil.

Simultaneous use of sildenafil (100 mg once) and ritonavir (500 mg twice daily), an HIV protease inhibitor and a strong cytochrome P450 inhibitor, while achieving a constant concentration of ritonavir in the blood leads to an increase in the Cmax of sildenafil by 300% (4 times), and AUC by 1000% (11 times). After 24 hours, the concentration of sildenafil in the blood plasma is about 200 ng / ml (after a single application of sildenafil alone-5 ng/ml).

If sildenafil is taken at the recommended doses in patients receiving simultaneously strong inhibitors of the cytochrome CYP3A4 isoenzyme, the Cmax of free sildenafil does not exceed 200 nM, and the drug is well tolerated.

A single antacid dose (magnesium hydroxide/aluminum hydroxide) does not affect the bioavailability of sildenafil.

Inhibitors of the cytochrome CYP2C9 isoenzyme (tolbutamide, warfarin), cytochrome CYP2D6 isoenzyme (selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazide and thiazide-like diuretics, ACE inhibitors and calcium antagonists do not affect the pharmacokinetics of sildenafil.

Azithromycin (500 mg / day for 3 days) has no effect on the AUC, Cmax, Tmax, elimination rate constant and T 1/2 of sildenafil or its main circulating metabolite.

Effect of sildenafil on other medications

Sildenafil is a weak inhibitor of cytochrome P450 isoenzymes-1A2,2C9,2C19,2D6,2E1 and 3A4 (IR 5O >150 mmol). When taking sildenafil at the recommended doses, its Cmax is about 1 micromol, so it is unlikely that sildenafil can affect the clearance of substrates of these isoenzymes.

Sildenafil enhances the hypotensive effect of nitrates both with prolonged use of the latter, and when they are prescribed for acute indications. In this regard, the use of sildenafil in combination with nitrates or nitric oxide donors is contraindicated.

When the alpha-blocker doxazosin (4 mg and 8 mg) and sildenafil (25 mg,50 mg and 100 mg) were co – administered in patients with benign prostatic hyperplasia with stable hemodynamics, the average additional reduction in systolic/diastolic blood pressure in the supine position was 7/7 mmHg,9/5 mmHg and 8/4 mmHg, respectively, and in the standing position-6/6 mmHg,11/4 mmHg and 4/5 mmHg, respectively. mercury, respectively.

Rare cases of symptomatic postural hypotension, which manifested itself in the form of dizziness (without fainting), have been reported in such patients. In some sensitive patients receiving alpha-blockers, concomitant use of sildenafil may lead to symptomatic hypotension.

There were no signs of significant interaction with tolbutamide (250 mg) or warfarin (40 mg), which are metabolized by the cytochrome CYP2C9 isoenzyme. Sildenafil (100 mg) does not affect the pharmacokinetics of HIV protease inhibitors, saquinavir and ritonavir, which are substrates of the cytochrome CYP3A4 isoenzyme, at constant blood levels.

Sildenafil (50 mg) does not cause an additional increase in bleeding time when taking acetylsalicylic acid (150 mg).

Sildenafil (50 mg) does not enhance the hypotensive effect of alcohol in healthy volunteers with a maximum blood alcohol concentration of 0.08% (80 mg/dl) on average.

In patients with arterial hypertension, there were no signs of interaction between sildenafil (100 mg) and amlodipine. The average additional reduction in blood pressure in the supine position is 8 mm Hg (systolic) and 7 mm Hg (diastolic).

The use of sildenafil in combination with antihypertensive agents does not lead to additional side effects.

When sildenafil was co-administered with bosentan (an inducer of CYP3A4 and CYP2C9 isoenzymes), the AUC and Cmax of sildenafil decreased by 62.6% and 52.4%, respectively. Sildenafil increased the AUC and Cmax of bosentan by 49.8% and 42%, respectively.

How to take, course of use and dosage

Inside.

The recommended dose for most adult patients is 50 mg approximately 1 hour before sexual activity. Depending on the effectiveness and tolerability, the dose can be increased to 100 mg. The maximum recommended dose is 100 mg. The maximum recommended frequency of use is once a day.

Elderly patients

No dose adjustment of sildenafil is required.

Overdose

With a single dose of the drug up to 800 mg, adverse events were

comparable to those with lower doses of the drug, but were more common.

Description

Tablets covered with a film-coated blue color, biconvex, diamond-shaped with cut and rounded edges, with the inscription ” 1005 SAO one.

On a cross-section, the tablet core is white or almost white in color.

Pharmacotherapeutic group: treatment for erectile dysfunction-PDE5 inhibitor.

Special instructions

To diagnose erectile dysfunction, determine their possible causes, and choose appropriate treatment, it is necessary to collect a complete medical history and conduct a thorough physical examination.

Treatment of erectile dysfunction should be used with caution in patients with anatomical deformity of the penis (angulation, cavernous fibrosis, Peyronie’s disease), or in patients with risk factors for priapism (sickle cell anemia, multiple myeloma, leukemia) (see the section “With caution”).

Drugs intended for the treatment of erectile dysfunction should not be prescribed to men for whom sexual activity is undesirable.

If your erection persists for more than 4 hours, you should seek medical attention. If priapism therapy is not carried out in a timely manner, it can lead to damage to penile tissues and irreversible loss of potency.

Sexual activity poses a certain risk in the presence of heart disease, so before starting any therapy for erectile dysfunction, the doctor should refer the patient for a cardiovascular examination.

Sexual activity is undesirable in patients with heart failure, unstable angina, a history of myocardial infarction or stroke in the last 6 months, life-threatening arrhythmias, arterial hypertension (BP >170/100 mm Hg) or hypotension (BP > 

Clinical studies have shown no differences in the incidence of myocardial infarction (1.1 per 100 people per year) or the incidence of cardiovascular mortality (0.3 per 100 people per year) in patients treated with sildenafil compared to patients treated with placebo.

Cardiovascular complications

Adverse events such as serious cardiovascular events (including myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmia, hemorrhagic stroke, transient ischemic attack, hypertension, and hypotension) that were temporarily associated with the use of sildenafil have been reported during post-marketing use of sildenafil for the treatment of erectile dysfunction.

Most of these patients, but not all of them, had risk factors for cardiovascular complications. Many of these adverse events were observed shortly after sexual activity, and some of them were observed after taking sildenafil without subsequent sexual activity. It is not possible to establish a direct link between the observed adverse events and these or other factors.

Hypotension

Sildenafil has a systemic vasodilating effect, leading to a transient decrease in blood pressure, which is not a clinically significant phenomenon and does not lead to any consequences in most patients. However, before prescribing sildenafil, the doctor should carefully assess the risk of possible undesirable manifestations of vasodilating effects in patients with the corresponding diseases, especially against the background of sexual activity.

Increased susceptibility to vasodilators is observed in patients with obstruction of the left ventricular exit tract (aortic stenosis, hypertrophic obstructive cardiomyopathy), as well as with a rare syndrome of multiple systemic atrophy, manifested by a severe violation of blood pressure regulation by the autonomic nervous system.

Since the combined use of sildenafil and alpha-blockers can lead to symptomatic hypotension in some sensitive patients, the drug should be prescribed with caution to patients taking alpha-blockers (see the section “Interaction with other drugs”).

To minimize the risk of postural hypotension in patients taking alpha-blockers, sildenafil should be started only after the hemodynamic parameters have stabilized in these patients. Consideration should also be given to reducing the initial dose of sildenafil (see section “Dosage and use”). The doctor should inform patients about what actions should be taken in case of symptoms of postural hypotension.

Visual impairments

Rare cases of anterior non-arteritic ischemic optic neuropathy have been reported as a cause of visual impairment or loss with all PDE5 inhibitors, including sildenafil.

Most of these patients had risk factors such as an excavated optic disc, age over 50 years, diabetes mellitus, hypertension, coronary heart disease, hyperlipidemia, and smoking. A small number of patients with hereditary retinitis pigmentosa have genetically determined disorders of retinal phosphodiesterase functions.

There is no information on the safety of sildenafil in patients with retinitis pigmentosa.

Hearing disorders

Some post-marketing and clinical studies have reported cases of sudden hearing impairment or loss associated with the use of all PDE5 inhibitors, including sildenafil. Most of these patients had risk factors for sudden deterioration or loss of hearing.

No causal relationship has been established between the use of PDE5 inhibitors and sudden hearing impairment or hearing loss. In case of sudden hearing loss or loss of hearing while taking sildenafil, you should immediately consult your doctor.

Bleeding issues

Sildenafil enhances the antiplatelet effect of sodium nitroprusside, a nitric oxide donor, on human platelets in vitro.

There are no data on the safety of using sildenafil in patients with a tendency to bleeding or exacerbation of gastric and duodenal ulcers, so sildenafil should be used with caution in these patients (see the section “With caution”).

The incidence of nosebleeds in patients with PH associated with diffuse connective tissue diseases was higher (sildenafil 12.9%, placebo 0%) than in patients with primary pulmonary hypertension (sildenafil 3.0%, placebo 2.4%). In patients treated with sildenafil in combination with a vitamin K antagonist, the incidence of nosebleeds was higher (8.8%) than in patients who did not take a vitamin K antagonist (1.7%). Use in conjunction with other means of treating erectile dysfunction.

The safety and efficacy of sildenafil in combination with other treatments for erectile dysfunction have not been studied, so the use of such combinations is not recommended (see section “Contraindications”).

Influence on the ability to drive a car and manage mechanisms

Since taking sildenafil may reduce blood pressure, develop chromatopsia, blurred vision, you should carefully consider the individual effect of the drug, especially at the beginning of treatment and when changing the dosage regimen, and be careful when driving vehicles and engaging in potentially dangerous activities that require increased concentration and speed of psychomotor reactions.

Storage conditions

At a temperature not exceeding 25 °C.

Keep out of reach of children.

Expiration date

Shelf life is 3 years.

Do not use after the expiration date.

Active ingredient

Sildenafil

Conditions of release from pharmacies

By prescription

Dosage form

Tablets