Viagra, 50 mg 12 pcs

Sildenafil is a potent selective inhibitor of 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 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 corpora cavernosa and an increase in blood flow.

Sildenafil has no direct relaxant effect on the isolated human cavernous body, but it enhances the effect of NO by inhibiting FDE5, which is responsible for the breakdown of cGMP.

Sildenafil is selective against FDE5 in vitro, its activity against FDE5 is superior to 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 FDE3, which is of critical importance because FDE3 is one of the key enzymes regulating myocardial contractility.

The prerequisite for the effectiveness of sildenafil is sexual stimulation.

Indications

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

Sildenafil is effective only in the presence of sexual stimulation.

Active ingredient

Composition

Active ingredient:

sildenafil (in the form of citrate) 50 mg.

Associates:

Cellulose microcrystalline,

calcium hydrophosphate,

croscarmellose sodium,

magnesium stearate.

Composition of the film coating:

Opadry blue OY-LS-20921 (hypromellose, lactose, triacetin, titanium dioxide (E171), indigo carmine-based aluminum varnish (E132)) and Opadry clear YS-2-19114-A (hypromellose, triacetin).

How to take, the dosage

The drug is taken orally.

In most patients, the recommended dose is 50 mg approximately 1 hour before sexual activity. Depending on efficacy and tolerability, the dose may be increased to 100 mg or decreased to 25 mg.

The maximum recommended dose is 100 mg. The maximum recommended frequency of use is once daily.

In mild to moderate renal failure

In mild to moderate renal failure (CKR 30-80 ml/min), no dose adjustment is required.

In severe renal failure (CKD

In impaired liver function

In impaired liver function, the dose of the drug can be reduced to 25 mg.

In co-administration with ritonavir

In co-administration with ritonavir, the maximum single dose of Viagra should be 25 mg and the frequency of use should be once every 48 hours.

In co-administration with CYP3A4 isoenzyme inhibitors

In co-administration with CYP3A4 isoenzyme inhibitors (erythromycin, saquinavir, ketoconazole, itraconazole), the starting dose of Viagra should be 25 mg.

In patients taking alpha-adrenoblockers

In order to minimize the risk of postural hypotension in patients taking alpha-adrenoblockers, sildenafil should be started only after hemodynamic stabilization has been achieved in these patients. A reduction in the initial dose of Viagra should be considered.

Interaction

The effect of other drugs on sildenafil metabolism

The metabolism of sildenafil occurs mainly in the liver under the action of CYP3A4 isoenzymes (main pathway) and CYP2C9, therefore inhibitors of these isoenzymes may decrease sildenafil clearance, and inducers, respectively, increase sildenafil clearance.

Concomitant use of CYP3A4 inhibitors (such as ketoconazole, erythromycin, cimetidine) has been shown to decrease sildenafil clearance.

Cimetidine (800 mg), which is a non-specific CYP3A4 inhibitor, when taken simultaneously with sildenafil (50 mg) causes an increase in plasma concentration of sildenafil by 56%.

Single administration of sildenafil at a dose of 100 mg concomitantly with erythromycin, a specific CYP3A4 inhibitor (when taking erythromycin 2 times/day at 500 mg for 5 days), while achieving constant levels of erythromycin in the blood results in an increase in sildenafil AUC by 182%.

Concomitant use of sildenafil (once in a dose of 100 mg) and saquinavir, which is both an HIV protease inhibitor and a CYP3A4 inhibitor (when taking saquinavir 3 times/day in a dose of 1200 mg), against reaching constant levels of saquinavir in blood, C max sildenafil in blood was increased by 140% and AUC was increased by 210%. Sildenafil had no effect on the pharmacokinetic parameters of saquinavir.

The stronger CYP3A4 isoenzyme inhibitors, such as ketoconazole or itraconazole, may cause more pronounced changes in the pharmacokinetics of sildenafil.

Concomitant use of sildenafil (single dose of 100 mg) and ritonavir, which is an HIV protease inhibitor and a strong inhibitor of cytochrome P450 system isoenzymes (while taking ritonavir at 500 mg twice daily), against reaching constant levels of ritonavir in blood, C max sildenafil increased by 300% (4 times) and AUC by 1000% (11 times). After 24 h the plasma concentration of sildenafil was approximately 200 ng/ml (5 ng/ml with a single sildenafil administration).

If sildenafil is taken in recommended doses in patients receiving concomitant strong CYP3A4 inhibitors, the C max of free sildenafil does not exceed 200 nM and the drug is well tolerated.

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

The CYP2C9 inhibitors (such as tolbutamide, warfarin), CYP2D6 inhibitors (such as selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazides and thiazide-like diuretics, ACE inhibitors and calcium antagonists do not influence sildenafil pharmacokinetic parameters.

Concomitant administration of azithromycin (500 mg/day for 3 days) has no effect on AUC, C max , T max , elimination rate constant and T 1/2 of sildenafil or its main circulating metabolite.

The effect of sildenafil on other drugs

Sildenafil is a weak inhibitor of the cytochrome P450 system isoenzymes 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (IR 50 >150 μmol). It is unlikely that sildenafil can affect the clearance of substrates of these isoenzymes.

Sildenafil enhances the hypotensive effects of nitrates both with long-term use and when used for acute indications. Therefore, the use of sildenafil in combination with nitrates or nitric oxide donors is contraindicated.

The concomitant use of the alpha-adrenoblocker doxazosin (4 mg and 8 mg) and sildenafil (25 mg, 50 mg, and 100 mg) in patients with benign prostatic hyperplasia with stable hemodynamics had an average additional decrease of systolic/diastolic BP in the supine position of 7/7 mm Hg, 9/5 mmHg and 8/4 mmHg, respectively, and in the standing position were 6/6 mmHg, 11/4 mmHg, and 4/5 mmHg, respectively. Rare cases of symptomatic postural hypotension, manifested as Dizziness (without syncope), have been reported in these patients. In certain sensitive patients receiving alpha-adrenoblockers, concomitant use of sildenafil may result in symptomatic hypotension.

There is no evidence of significant interaction of sildenafil with tolbutamide (250 mg) or warfarin (40 mg), which are metabolized by CYP2C9.

Sildenafil at a dose of 100 mg has no effect on the pharmacokinetic parameters of HIV protease inhibitors at their constant blood concentrations, such as saquinavir and ritonavir, which are simultaneously CYP3A4 substrates.

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

Sildenafil (50 mg) does not increase the hypotensive effect of ethanol in healthy volunteers at a maximum blood ethanol level of 80 mg/dL on average.

In patients with arterial hypertension, there is no evidence of interaction between sildenafil (100 mg) and amlodipine. The mean additional decrease of BP in the supine position is: systolic – by 8 mmHg, diastolic – by 7 mmHg.

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

Special Instructions

The diagnosis of erectile dysfunction, the determination of its possible causes, and the choice of appropriate treatment require a complete medical history and a thorough physical examination.

Sexual activity poses some risk for heart disease; therefore, a cardiovascular exam may be considered necessary before any therapy for erectile dysfunction. 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.Hg) or hypotension (BP

The drugs intended to treat erectile dysfunction should not be prescribed for men for whom sexual activity is undesirable.

Viagra has a systemic vasodilatory effect that leads to a transient decrease in BP. This effect is not clinically significant and has no effect in most patients. However, before prescribing Viagra, the physician should carefully consider the risk of adverse vasodilatory effects in patients with certain comorbidities, especially during sexual activity. Increased susceptibility to vasodilators is seen in patients with left ventricular outflow tract obstruction (e.g., aortic stenosis, hypertrophic obstructive cardiomyopathy), and with the rare multiple systemic atrophy syndrome manifesting severe autonomic nervous system BP dysregulation.

Impact on the ability to drive and operate machinery

There have been no adverse effects on the ability to drive a vehicle or other technical devices while taking Viagra. However, since the drug may cause decreased blood pressure, chromatopsia, and blurred vision, careful consideration should be given to the individual action of the drug in the above situations, especially at the beginning of treatment and when changing the dosing regimen.

Contraindications

With caution: In anatomical deformation of the penis, angulation, cavernous fibrosis, Peyronie’s disease, in diseases predisposing to the development of priapism, sickle cell anemia, multiple myeloma, leukemia, thrombocytopenia, in diseases accompanied by bleeding, In acute gastric and duodenal ulcer disease, in hereditary retinitis pigmentosa, in heart failure, unstable angina, myocardial infarction within last 6 months, stroke, severe life-threatening arrhythmias, arterial hypertension (BP over 170/100 mm Hg), hypotension, hypertension in patients with diabetes.Hg), with hypotension (BP less than 90/50 mm Hg).

Side effects

The side effects are usually transient and mild to moderate.

The incidence of adverse events increases with increasing dose.

Nervous system: dizziness – sildenafil (%) – 2.9, placebo (%) – 1.0. Most common (>1/10): headache – sildenafil (%) – 10.8, placebo (%) – 2.8.

Cardiovascular system: increased heart rate – sildenafil (%) – 1.0, placebo (%) – 0.2. Frequent (>1/100 and <1/10) – vasodilation (flushes to the face) – sildenafil (%) – 10.9, placebo (%) – 1.4.

Visual organ: changes in vision (blurred vision, changes in sensitivity to light) – sildenafil (%) – 2.5, placebo (%) – 0.4. Chromatopsia (mild and transient, mainly change in perception of color shades) – sildenafil (%) – 1.1, placebo (%) – 0.03.

Respiratory system: rhinitis (nasal congestion) – sildenafil (%) – 2.1, placebo (%) – 0.3.

Digestive system: dyspepsia – sildenafil (%) – 3.0 , placebo (%) – 0.4.

When the drug was used in doses higher than recommended, the side effects were similar to those noted above, but tended to be more frequent.

Allergic reactions: hypersensitivity reactions (including skin rash).

CNS disorders: seizures.

Cardiovascular system: tachycardia, decreased BP, syncope Nasal bleeding.

Digestive system: vomiting.

Visual system: pain in the eyes, red eyes/injections of the sclerae.

Perior genital system: prolonged erection and/or priapism.

Overdose

Symptoms: with a single dose of up to 800 mg, adverse events were comparable to those with sildenafil at lower doses, but were more frequent.

Treatment: if necessary, symptomatic therapy is indicated.
Hemodialysis does not increase sildenafil clearance because sildenafil actively binds to plasma proteins and is not excreted in the urine.

Similarities