Vardenafil

A drug for the treatment of patients with erectile dysfunction, a selective PDE-5 inhibitor. Erection of the penis is a hemodynamic process, which is based on the relaxation of the smooth muscles of the cavernous bodies. During sexual stimulation, nitric oxide (NO) is released in the cavernous bodies, which activates the enzyme guanylate cyclase, which leads to an increase in the content of cGMP in the cavernous bodies. As a result, the smooth muscles of the cavernous bodies are relaxed, which contributes to an increase in blood flow to the penis. Vardenafil blocks PDE-5, under the influence of which the breakdown of cGMP occurs, as a result, the effect of endogenous NO in the cavernous bodies during sexual stimulation increases, which determines the ability of vardenafil to enhance the natural response to sexual stimulation. The clinical effect of vardenafil occurs approximately 15 minutes after administration and lasts 8–12 hours.

After oral administration, vardenafil is rapidly absorbed from the gastrointestinal tract. Absolute bioavailability is about 15%. C_max in blood plasma after oral administration at a dose of 20 mg is achieved after 30 minutes - 2 hours (on average, after 30 minutes). Simultaneous intake with fatty foods leads to a decrease in C_max in blood plasma by 18-50%. The mean volume of distribution of vardenafil at steady state is 208 liters. Metabolized in the liver. Approximately 95% of vardenafil and its major metabolite bind to plasma proteins. The total clearance of vardenafil is 56 l / h, the terminal half-life of vardenafil and its main metabolite is 4-5 hours. Excreted mainly with feces (91-95%), the rest (2-6%) is excreted with urine.

Erectile dysfunction.

At the beginning of treatment, the recommended dose is 10 mg, administered orally approximately 25-60 minutes before sexual contact, but it can be 4-5 hours before. The maximum recommended frequency of administration is 1 time / day. Vardenafil can be taken with or without food. Adequate level of sexual stimulation is essential for the treatment to be effective. Depending on the effectiveness and tolerability of treatment, the dose can be increased to 20 mg or reduced to 5 mg / day. The maximum recommended dose is 20 mg once daily. In the elderly, a change in dosing regimen is not required. In patients with moderate hepatic impairment, there is a decrease in the clearance of vardenafil, so the initial dose should be 5 mg / day. In the future, depending on the effectiveness and tolerability, the dose of vardenafil can be increased to 10 mg and then to 20 mg. In patients with mild hepatic impairment, no change in dosing regimen is required. In patients with minor, moderate and severe impaired renal function, changes in the dosing regimen are not required.

Dispersible tablets are not bioequivalent to film-coated tablets. The maximum recommended dose for dispersible tablets is 10 mg/day.

A dispersible tablet is placed in the oral cavity on the tongue, held until completely dissolved, then swallowed. The dispersible tablet should be taken immediately after removing it from the blister, without drinking liquid.

Hypersensitivity to vardenafil, concomitant use of organic nitrates or other NO donors, α-adrenergic blockers, severe liver failure, end-stage kidney disease requiring hemodialysis, arterial hypotension (systolic blood pressure at rest below 90 mm Hg . Art.), recent stroke or myocardial infarction (within the last 6 months), unstable angina pectoris, hereditary degenerative diseases of the retina (including retinitis pigmentosa), age up to 16 years.

Headache, dizziness, increased muscle tone, flushing of the skin of the face, increased or decreased blood pressure, dyspepsia, nausea, nasal congestion, photosensitivity, priapism.

with caution should be used in anatomical deformities of the penis (curvature, cavernous fibrosis or Peyronie's disease), diseases predisposing to the development of priapism (sickle cell anemia, multiple myeloma or leukemia), bleeding tendencies, peptic ulcer of the stomach and duodenum. Not intended for use in women and children.

Cytochrome P450 inhibitors (cimetidine, ketoconazole, itraconazole, indinavir, ritonavir) can reduce the clearance of vardenafil (when used simultaneously with these drugs, the dose of vardenafil 5 mg / day should not be exceeded). When used simultaneously with the CYP 3A4 inhibitor erythromycin, it is not recommended to exceed the dose of vardenafil 10 mg/day. Simultaneous use with α-adrenergic blockers can lead to a decrease in blood pressure, so vardenafil should be taken no earlier than 6 hours after taking these drugs. There were no significant pharmacokinetic interactions with the combined use of vardenafil with glibenclamide, nifedipine, warfarin and digoxin. With simultaneous use with warfarin, there was no change in prothrombin time and the level of blood coagulation factors. With simultaneous use with acetylsalicylic acid, antacids, ACE inhibitors, β-adrenergic blockers, diuretics, hypoglycemic drugs (sulfonylurea derivatives and metformin), ranitidine, the pharmacokinetics of vardenafil did not change. Since PDE inhibitors affect the NO/cGMP system, PDE-5 inhibitors may enhance the hypotensive effect of nitrates.

Vardenafil alone does not inhibit platelet aggregation induced by various platelet agonists. When using vardenafil at concentrations higher than therapeutic, there was a slight dose-dependent increase in the antiaggregation effect of sodium nitroprusside, which releases NO.