Viatile^® (Tablets) Instructions for Use

Marketing Authorization Holder

Sun Pharmaceutical Industries, Ltd. (India)

ATC Code

G04BE03 (Sildenafil)

Active Substance

Sildenafil (USAN adopted for use in the USA)

Dosage Forms

	Viatile®	Film-coated tablets, 25 mg: 1, 2, 4, 8, 10 or 16 pcs.
		Film-coated tablets, 50 mg: 1, 2, 4, 8, 10 or 16 pcs.
		Film-coated tablets, 100 mg: 1, 2, 4, 8, 10 or 16 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets red in color, triangular in shape with rounded edges; with engraving “S21” on one side and smooth on the other.

Excipients: microcrystalline cellulose* – 84.38 mg, anhydrous calcium hydrogen phosphate – 25 mg, croscarmellose sodium – 3 mg, magnesium stearate – 2.5 mg, Opadry red (06B 55000) – 4.5 mg.

Composition of Opadry red (06B 55000) hypromellose 15 cP – 29.5%, hypromellose 6 cP – 29.5%, Ponceau 4R [Ponso 4R] dye (E124) – 19.712%, macrogol 400 – 11%, titanium dioxide – 8.846%, iron oxide red dye – 0.824%, indigo carmine – 0.618%.

1 pc. – blisters (1) – cardboard packs.
2 pcs. – blisters (1) – cardboard packs.
4 pcs. – blisters (1) – cardboard packs.
4 pcs. – blisters (2) – cardboard packs.
4 pcs. – blisters (4) – cardboard packs.
10 pcs. – blisters (1) – cardboard packs.

Film-coated tablets red in color, triangular in shape with rounded edges; with engraving “S22” on one side and smooth on the other.

Excipients: microcrystalline cellulose* – 168.76 mg, anhydrous calcium hydrogen phosphate – 50 mg, croscarmellose sodium – 6 mg, magnesium stearate – 5 mg, Opadry red (06B 55000) – 9 mg.

Composition of Opadry red (06B 55000) hypromellose 15 cP – 29.5%, hypromellose 6 cP – 29.5%, Ponceau 4R [Ponso 4R] dye (E124) – 19.712%, macrogol 400 – 11%, titanium dioxide – 8.846%, iron oxide red dye – 0.824%, indigo carmine – 0.618%.

1 pc. – blisters (1) – cardboard packs.
4 pcs. – blisters (1) – cardboard packs.
10 pcs. – blisters (1) – cardboard packs.

Film-coated tablets red in color, triangular in shape with rounded edges; with engraving “S23” on one side and smooth on the other.

Excipients: microcrystalline cellulose* – 337.52 mg, anhydrous calcium hydrogen phosphate – 100 mg, croscarmellose sodium – 12 mg, magnesium stearate – 10 mg, Opadry red (06B 55000) – 18 mg.

Composition of Opadry red (06B 55000) hypromellose 15 cP – 29.5%, hypromellose 6 cP – 29.5%, Ponceau 4R [Ponso 4R] dye (E124) – 19.712%, macrogol 400 – 11%, titanium dioxide – 8.846%, iron oxide red dye – 0.824%, indigo carmine – 0.618%.

1 pc. – blisters (1) – cardboard packs.
4 pcs. – blisters (1) – cardboard packs.

* the amount is adjusted according to the added amount of sildenafil citrate to maintain the average tablet weight.

Clinical-Pharmacological Group

Erectile dysfunction treatment drug. PDE5 inhibitor

Pharmacotherapeutic Group

Erectile dysfunction treatment agent – PDE5 inhibitor

Pharmacological Action

Sildenafil is a potent and selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5). The realization of the physiological mechanism of erection is associated with the release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. This, in turn, leads to an increase in cGMP levels, subsequent relaxation of the smooth muscle tissue of the corpus cavernosum, and increased blood flow. Sildenafil does not have a direct relaxing effect on the isolated human corpus cavernosum but enhances the effect of NO through PDE5, which is responsible for the breakdown of cGMP.

Sildenafil is selective for PDE5 in vitro, its activity against PDE5 exceeds its activity against 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 PDE3, which is of utmost importance since PDE3 is one of the key enzymes regulating myocardial contractility.

A prerequisite for the effectiveness of sildenafil is sexual stimulation.

The use of sildenafil in doses up to 100 mg did not lead to clinically significant changes in the electrocardiogram (ECG) in healthy volunteers. The maximum decrease in systolic blood pressure in the supine position after taking sildenafil at a dose of 100 mg was 8.3 mm Hg, and diastolic pressure – 5.3 mm Hg. A more pronounced, but also transient effect on blood pressure was noted in patients taking nitrates.

In a study of the hemodynamic effect of a single 100 mg dose of sildenafil in 14 patients with severe coronary artery disease (CAD) (more than 70% of patients had stenosis of at least one coronary artery), resting systolic and diastolic pressure decreased by 7% and 6%, respectively, and pulmonary artery systolic pressure decreased by 9%. Sildenafil did not affect cardiac output and did not impair blood flow in stenosed coronary arteries, and also led to an increase (approximately 13%) in adenosine-induced coronary flow in both stenosed and intact coronary arteries.

When taking sildenafil, exercise tolerance in patients with erectile dysfunction and stable angina taking antianginal drugs (except nitrates) is significantly higher.

Sildenafil improves erection in men with erectile dysfunction and arterial hypertension taking more than two antihypertensive drugs. The frequency of adverse effects is comparable to that in other patient groups, as well as in individuals taking more than three antihypertensive drugs.

In some patients, 1 hour after taking sildenafil at a dose of 100 mg, a mild and transient impairment of the ability to distinguish shades of color (blue/green) is detected using the Farnsworth-Munsell 100 test. These changes disappear 2 hours after taking the drug. It is believed that the color vision impairment is caused by inhibition of PDE6, which is involved in the process of light transmission in the retina. Sildenafil does not affect visual acuity, contrast perception, electroretinogram, intraocular pressure, or pupil diameter.

In patients with proven early age-related macular degeneration (n=9), Sildenafil in a single 100 mg dose was well tolerated, without significant vision changes.

The effectiveness of sildenafil is defined as the ability to achieve and maintain an erection sufficient for satisfactory sexual intercourse. A fixed dose improves erection in 62% (sildenafil dose 25 mg), 74% (sildenafil dose 50 mg), and 82% (sildenafil dose 100 mg) of cases. Analysis of the International Index of Erectile Function shows that in addition to improving erection, treatment with sildenafil also improves the quality of orgasm, achieves satisfaction from sexual intercourse and overall satisfaction.

According to summarized data, among patients who reported improvement in erection with sildenafil treatment were 59% of diabetics, 43% of patients who underwent radical prostatectomy, and 83% of patients with spinal cord injuries.

Pharmacokinetics

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

Absorption

After oral administration, Sildenafil is rapidly absorbed. The absolute bioavailability averages about 40% (from 25% to 63%). In vitro, Sildenafil at a concentration of about 1.7 ng/ml (3.5 nM) inhibits human PDE5 activity by 50%. After a single oral dose of sildenafil 100 mg, the mean maximum plasma concentration (C_max) of free sildenafil in men is about 18 ng/ml (38 nM). C_max after oral administration of sildenafil on an empty stomach is reached on average within 60 min (from 30 min to 120 min). When taken in combination with fatty food, the rate of absorption decreases: C_max decreases on average by 29%, and the time to reach maximum concentration (T_max) increases by 60 min, but the extent of absorption does not change significantly (area under the concentration-time pharmacokinetic curve (AUC) decreases by 11%).

Distribution

The V_d of sildenafil at steady state averages 105 L. The binding of sildenafil and its main circulating N-desmethyl metabolite to plasma proteins is about 96% and does not depend on the total concentration of the drug. Less than 0.0002% of the sildenafil dose (average 188 ng) was found in semen 90 minutes after taking the drug.

Metabolism

Sildenafil is metabolized mainly in the liver under the action of the cytochrome isoenzyme CYP3A4 (main pathway) and the cytochrome isoenzyme CYP2C9 (additional pathway). The main circulating active metabolite, formed as a result of N-demethylation of sildenafil, undergoes further metabolism. The selectivity of this metabolite for PDE is comparable to that of sildenafil, and its activity against PDE5 in vitro is about 50% of the activity of sildenafil. The plasma concentration of the metabolite in healthy volunteers is about 40% of the sildenafil concentration. The N-desmethyl metabolite undergoes further metabolism; its half-life (T_1/2) is about 4 hours.

Excretion

The total clearance of sildenafil is 41 L/h, and T_1/2 is 3-5 hours. After oral administration as well as after intravenous administration, Sildenafil is excreted as metabolites, mainly via the intestines (about 80% of the oral dose) and, to a lesser extent, via the kidneys (about 13% of the oral dose).

Pharmacokinetics in special patient groups

Elderly patients. In healthy elderly patients (over 65 years of age), the clearance of sildenafil is reduced, and the plasma concentration of free sildenafil is approximately 40% higher than in young patients (18-45 years). Age does not have a clinically significant effect on the frequency of adverse effects.

Renal impairment. In mild (creatinine clearance (CrCl) 50-80 ml/min) and moderate (CrCl 30-49 ml/min) renal failure, the pharmacokinetics of sildenafil after a single oral dose of 50 mg does not change. In severe renal failure (CrCl 30 ml/min), the clearance of sildenafil is reduced, leading to an approximately twofold increase in AUC (100%) and C_max (88%) compared to those with normal renal function in patients of the same age group.

Hepatic impairment. In patients with liver cirrhosis (Child-Pugh classes A and B), the clearance of sildenafil is reduced, leading to an increase in AUC (84%) and C_max (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 class C) has 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 with sexual stimulation.

ICD codes

Dosage Regimen

Orally.

The recommended dose for most adult patients is 50 mg approximately 1 hour before sexual activity. Depending on efficacy and tolerability, the dose can be increased to 100 mg or decreased to 25 mg. The maximum recommended dose is 100 mg. The maximum recommended frequency of administration is 1 time/day.

In mild and moderate renal impairment (CrCl 30-80 ml/min) no dose adjustment is required; in severe renal impairment (CrCl <30 ml/min) the dose of sildenafil should be reduced to 25 mg.

Since the elimination of sildenafil is impaired in patients with liver damage (in particular, cirrhosis), the dose of Viatile^® should be reduced to 25 mg.

For elderly patients the initial dose is 25 mg. If well tolerated, the dose can be increased to 50 mg or 100 mg.

Concomitant use with other medicines

When used concomitantly with ritonavir, the maximum single dose of Viatile^® should not exceed 25 mg, and the frequency of administration should be once every 48 hours.

When used concomitantly with cytochrome CYP3A4 isoenzyme inhibitors (erythromycin, saquinavir, ketoconazole, itraconazole), the initial dose of Viatile^® should be 25 mg.

To minimize the risk of postural hypotension in patients taking alpha-blockers, Viatile^® should be initiated only after hemodynamic stabilization has been achieved in these patients. The advisability of reducing the initial dose of sildenafil should also be considered.

Adverse Reactions

Usually, the side effects of Viatile^® are mild or moderate and transient. With fixed-dose use, the frequency of some adverse events increases with increasing dose. By frequency, side effects were divided according to WHO criteria into the following categories: very common (≥1/10); common (≥1/100 and <1/10); uncommon (≥1/1000 and <1/100); rare (≥1/10,000 and <1/1000); very rare (<1/10,000).

Immune system disorders rare – hypersensitivity.

Nervous system disorders very common – headache; common – dizziness; uncommon – drowsiness, hypoesthesia; rare – stroke, syncope; frequency unknown – transient ischemic attack, seizures, incl. recurrent.

Eye disorders common – vision changes (blurred vision, change in light sensitivity), chromatopsia (mild and transient, mainly change in perception of color shades); uncommon – eye disorders, incl. conjunctival disorders, lacrimation disorders; frequency unknown – anterior ischemic optic neuropathy, retinal vascular occlusion, visual field defects.

Ear and labyrinth disorders uncommon – vertigo, tinnitus; rare – deafness.

Cardiac and vascular disorders common – vasodilation (“flushing”); uncommon – palpitations, tachycardia, increased heart rate; rare – increased or decreased blood pressure, myocardial infarction, atrial fibrillation; frequency unknown – ventricular arrhythmias, unstable angina, sudden cardiac death.

Respiratory, thoracic and mediastinal disorders common – nasal congestion, rhinitis; rare – epistaxis.

Gastrointestinal disorders common – dyspepsia; uncommon – vomiting, nausea, dry mouth.

Allergic reactions uncommon – skin rash, frequency unknown – Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome).

Musculoskeletal and connective tissue disorders uncommon – myalgia.

Reproductive system and breast disorders uncommon – hematospermia and penile bleeding, frequency unknown – priapism, prolonged erection.

General disorders and administration site conditions uncommon – chest pain, fatigue.

Contraindications

• Hypersensitivity to sildenafil or to any other component of the drug;
• Use in patients receiving, continuously or intermittently, nitric oxide donors, organic nitrates or nitrites in any dosage forms, since Sildenafil enhances the hypotensive effect of nitrates;
• Concomitant use with ritonavir;
• Patients for whom sexual activity is undesirable, incl. those with severe cardiovascular diseases, such as unstable angina, severe heart failure, life-threatening arrhythmias;
• Unstable angina, myocardial infarction, stroke or life-threatening arrhythmias within the last 6 months, arterial hypertension (BP >170/100 mm Hg) or arterial hypotension (BP <90/50 mm Hg);
• Patients with vision loss in one eye due to non-arteritic anterior ischemic optic neuropathy (regardless of whether this occurred due to taking a PDE5 inhibitor or not);
• Hereditary degenerative retinal diseases, incl. retinitis pigmentosa (a small proportion of such patients have a genetic retinal PDE disorder);
• Severe hepatic insufficiency;
• Severe chronic renal failure.

Concomitant use with cytochrome CYP3A4 isoenzyme inhibitors is contraindicated.

There are no data on safety and efficacy when using sildenafil with other means of treating erectile dysfunction, so the use of such combinations is not recommended.

Not intended for use in children under 18 years of age.

Not intended for use in women.

With caution anatomical deformation of the penis (curvature of the penis, cavernous fibrosis or Peyronie’s disease); diseases predisposing to the development of priapism (sickle cell anemia, multiple myeloma, leukemia, thrombocythemia); diseases accompanied by bleeding; exacerbation of peptic ulcer; hereditary pigmentary retinitis; heart failure; history of episodes of anterior non-arteritic ischemic optic neuropathy; rarely encountered syndrome of multiple system atrophy, manifested by severe impairment of blood pressure regulation; obstruction of the left ventricular outflow tract, including aortic stenosis; simultaneous use of alpha-blockers.

Use in Pregnancy and Lactation

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

Use in Hepatic Impairment

The use of the drug is contraindicated in severe hepatic insufficiency.

Use in Renal Impairment

The use of the drug is contraindicated in severe chronic renal failure.

Pediatric Use

Not intended for use in children under 18 years of age.

Geriatric Use

For elderly patients, the initial dose is 25 mg. If well tolerated, the dose may be increased to 50 mg or 100 mg.

Special Precautions

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

Sexual activity poses a certain risk in the presence of heart disease, so before starting any therapy for erectile dysfunction, the physician should refer the patient for an examination of the cardiovascular system. Sexual activity is undesirable in patients with heart failure, unstable angina, myocardial infarction or stroke within the last 6 months, life-threatening arrhythmias, arterial hypertension (BP >170/100 mm Hg) or hypotension (BP <90/50 mm Hg). Clinical studies have shown no difference in the incidence of myocardial infarction (1.1 per 100 person-years) or mortality from cardiovascular diseases (0.3 per 100 person-years) in patients receiving Sildenafil compared with patients receiving placebo.

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

The drug Viatile^® 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. Nevertheless, before prescribing sildenafil, the physician should carefully assess the risk of possible adverse manifestations of the vasodilating effect in patients with relevant diseases, especially against the background of sexual activity. Increased susceptibility to vasodilators is observed in patients with obstruction of the left ventricular outflow tract (aortic stenosis, hypertrophic obstructive cardiomyopathy), as well as with the rarely encountered syndrome of multiple system atrophy, manifested by severe impairment of blood pressure regulation by the autonomic nervous system.

Rare cases of development of anterior ischemic optic neuropathy, not associated with arteritis, as a cause of deterioration or loss of vision against the background of the use of all PDE5 inhibitors, including Sildenafil, have been noted. Most of these patients had risk factors such as excavation of the optic nerve head, age over 50 years, diabetes mellitus, arterial hypertension, coronary heart disease (CHD), hyperlipidemia and smoking. No causal relationship between the use of PDE5 inhibitors and the development of anterior ischemic optic neuropathy, not associated with arteritis, has been identified. The physician should inform the patient about the increased risk of developing anterior ischemic optic neuropathy, not associated with arteritis, if this condition has been previously noted in him.

Since the combined use of sildenafil and alpha-blockers can lead to symptomatic hypotension in some sensitive patients, Sildenafil should be prescribed with caution to patients taking alpha-blockers. To minimize the risk of developing postural hypotension in patients taking alpha-blockers, sildenafil should be started only after hemodynamic stabilization has been achieved in these patients. The advisability of reducing the initial dose of sildenafil should also be considered. The physician should inform patients about what actions to take in case of symptoms of postural hypotension.

A small number of patients with hereditary pigmentary retinitis have genetically determined disorders of the functions of retinal phosphodiesterases. There is no information on the safety of sildenafil use in patients with pigmentary retinitis, so Sildenafil should be used with caution.

Sildenafil enhances the antiplatelet effect of sodium nitroprusside (a nitric oxide donor) on human platelets in vitro. There is no information on the safety of sildenafil use in patients with internal bleeding or active peptic ulcer of the stomach, so it should be used with caution.

Means for the treatment of erectile dysfunction should be used with caution in patients with anatomical deformation of the penis (curvature of the penis, cavernous fibrosis, Peyronie’s disease), or in patients with risk factors for the development of priapism (sickle cell anemia, multiple myeloma, leukemia).

Cases of priapism development with the use of sildenafil have been reported. If an erection persists for more than 4 hours, medical attention should be sought. If therapy for priapism is not performed in a timely manner, this can lead to damage to the tissues of the penis and irreversible loss of potency.

The safety and efficacy of sildenafil use in combination with other means of treating erectile dysfunction have not been studied, so the use of such combinations is not recommended.

In some post-marketing and clinical studies using all PDE5 inhibitors, including Sildenafil, sudden decrease or loss of hearing in patients has been reported. However, most of these patients had risk factors for the development of this pathology, and no correlation was found between the use of PDE5 inhibitors and sudden decrease or loss of hearing. In case of sudden decrease or loss of hearing, sildenafil therapy should be discontinued and a doctor should be consulted immediately.

Effect on the ability to drive vehicles and mechanisms

Since a decrease in blood pressure, development of chromatopsia, blurred vision and other side effects are possible when taking sildenafil, one should pay close attention to the individual effect of the drug in these situations, especially at the beginning of treatment and when changing the dosage regimen. In case of development of adverse reactions from the nervous system and sensory organs, patients are advised to refrain from driving a car and operating machinery, as well as to exercise caution when engaging in activities that require concentration and speed of psychomotor reactions.

Overdose

With a single dose of sildenafil at a dose of up to 800 mg, adverse events were comparable to those when taking the drug at lower doses, but occurred more often.

Treatment is symptomatic. Hemodialysis does not accelerate the clearance of sildenafil, because the latter is actively bound to plasma proteins and is not excreted by the kidneys.

Drug Interactions

Effect of other drugs on the pharmacokinetics of sildenafil

The metabolism of sildenafil occurs mainly under the action of cytochrome isoenzymes CYP3A4 (main pathway) and CYP2C9, therefore 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 has been noted with the simultaneous use of inhibitors of the cytochrome isoenzyme CYP3A4 (ketoconazole, erythromycin, cimetidine). Cimetidine (800 mg), a non-specific inhibitor of the cytochrome isoenzyme CYP3A4, when taken together with sildenafil (50 mg) causes an increase in the plasma concentration of sildenafil by 56%. A single dose of 100 mg of sildenafil together with erythromycin (250 mg twice a day for 5 days), a specific inhibitor of the cytochrome isoenzyme CYP3A4, against the background of achieving a constant concentration of erythromycin in the blood leads to an increase in the AUC of sildenafil by 182%. With the simultaneous use of sildenafil (single dose 100 mg) and saquinavir (400 mg/day 3 times a day), an inhibitor of HIV protease and the cytochrome isoenzyme CYP3A4, against the background of achieving a constant concentration of saquinavir in the blood, the C_max of sildenafil increased by 140%, and the AUC increased by 210%. Sildenafil does not affect the pharmacokinetics of saquinavir. Stronger inhibitors of the cytochrome isoenzyme CYP3A4, such as ketoconazole and itraconazole, may cause stronger changes in the pharmacokinetics of sildenafil.

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

If Sildenafil in recommended doses is taken by patients who are simultaneously receiving strong inhibitors of the cytochrome isoenzyme CYP3A4, then the C_max of free sildenafil does not exceed 200 nM, and the drug is well tolerated.

Inhibitors of the cytochrome isoenzyme CYP2C9 (tolbutamide, warfarin), the cytochrome isoenzyme CYP2D6 (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) does not affect the AUC, C_max, T_max, elimination rate constant and T_1/2 of sildenafil or its main circulating metabolite.

Simultaneous use of sildenafil and bosentan, an inducer of CYP3A4 and CYP2C9 isoenzymes, leads to a decrease in the AUC and C_max of sildenafil by 62.6% and 52.4%, respectively.

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

Effect of sildenafil on other drugs

Sildenafil is a weak inhibitor of cytochrome P450 isoenzymes – 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (IC₅₀ >150 µmol). When sildenafil is taken in recommended doses, its C_max is about 1 µmol, so it is unlikely that Sildenafil can affect the clearance of substrates of these isoenzymes. Sildenafil enhances the hypotensive effect of nitrates both with their long-term use and with their prescription for acute indications. In this regard, the use of sildenafil in combination with nitrates or nitric oxide donors is contraindicated.

With the simultaneous use of the alpha-blocker doxazosin (4 mg and 8 mg) and sildenafil (25 mg, 50 mg and 100 mg) in patients with benign prostatic hyperplasia with stable hemodynamics, the average additional decrease in systolic/diastolic blood pressure in the supine position was 7/7 mm Hg, 9/5 mm Hg and 8/4 mm Hg, respectively, and in the standing position – 6/6 mm Hg, 11/4 mm Hg and 4/5 mm Hg, respectively. Rare cases of the development of symptomatic postural hypotension in such patients, manifested as dizziness (without fainting), have been reported. In some sensitive patients receiving alpha-blockers, simultaneous use of sildenafil may lead to symptomatic hypotension.

Simultaneous use of sildenafil and bosentan leads to an increase in the AUC and C_max of bosentan by 49.8% and 42%, respectively. No signs of significant interaction with tolbutamide (250 mg) or warfarin (40 mg), which are metabolized by the cytochrome isoenzyme CYP2C9, were found. Sildenafil (100 mg) does not affect the pharmacokinetics of HIV protease inhibitors, saquinavir and ritonavir, which are substrates of the cytochrome isoenzyme CYP3A4, at their 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 at a maximum blood alcohol concentration of 0.08% on average (80 mg/dl).

In patients with arterial hypertension, no signs of interaction between sildenafil (100 mg) and amlodipine were found. The average additional decrease 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 the occurrence of additional side effects.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 30°C (86°F).

Shelf Life

Shelf life – 2 years. Do not use after the expiration date.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.