Erexesil, 100 mg 4 pcs.

Erexesil is a remedy for the treatment of erectile dysfunction. It restores impaired erectile function and provides a natural response to sexual arousal.

Sildenafil is a potent and selective inhibitor of cGMP-specific phosphodiesterase type 5 (PDE5), which is responsible for the breakdown of cGMP in the corpora cavernosa. Sildenafil has no direct relaxing effect on the cavernous body, but it actively enhances the relaxing effect of nitric oxide on this tissue. During sexual excitement, local release of NO under the influence of sildenafil leads to inhibition of FDE5 and increase of cGMP level in the cavernous body, as a result of this there is relaxation of smooth muscles and increase of blood flow in the cavernous body.

Sildenafil can cause mild and transient color (blue/green) impairment. The inhibition of FDE6, which is involved in the transmission of light in the retina, is thought to be the presumed mechanism of color vision impairment. In vitro studies have shown that the effect of sildenafil on FDE6 is 10 times inferior to its activity against FDE5.

In vitro studies show that the activity of sildenafil against FDEP5 is 10-10000 times greater than its activity against other phosphodiesterase isoforms (FDEP 1, 2, 3, 4 and 6). In particular, sildenafil activity against FDE5 is 4,000 times greater than its activity against FDE3 – cAMP-specific phosphodiesterase involved in heart contraction.

Pharmacokinetics

After oral administration sildenafil is rapidly absorbed. Absolute bioavailability averages 40% (25-63%). After a single oral dose of 100 mg, Cmax is 18 ng/mL and is reached when taken on an empty stomach within 30-120 minutes. When sildenafil is taken in combination with fatty foods, the rate of absorption is reduced; Tmax is increased by 60 min and Cmax is reduced by an average of 29%. The Vd of sildenafil in equilibrium is on average 105 L. Sildenafil and its main circulating N-desmethyl metabolite are approximately 96% bound to plasma proteins. Protein binding is independent of the total concentration of sildenafil. Less than 0.0002% of the dose (188 ng on average) was detected in semen 90 min after sildenafil administration.

Sildenafil is metabolized primarily by the microsomal liver isoenzymes CYP3A4 (main pathway) and CYP2C9.

The main circulating metabolite, which is formed by N-desmethylation of sildenafil, undergoes further metabolism. In terms of selectivity of action on FDE, the metabolite is comparable with sildenafil, and its activity against FDE5 in vitro is approximately 50% of the activity of sildenafil itself. Plasma concentration of the metabolite is about 40% of that of sildenafil. N-desmethylmetabolite undergoes further metabolism; its terminal T1/2 is about 4 hours.

The total clearance of sildenafil from the body is 41 l/h, and the T1/2 during the terminal phase is 3-5 hours. After oral administration sildenafil is excreted as metabolites mainly in the feces (about 80% of the dose) and, to a lesser extent, in the urine (about 13% of the dose).

In elderly patients (65 years and older) sildenafil clearance is decreased, and plasma concentrations of free active substance are about 40% higher than its concentration in young (18-45 years) patients.

In mild (KC 50-80 ml/min) and moderate (KC 30-49 ml/min) renal impairment, the pharmacokinetic parameters of sildenafil are unchanged after oral administration once (50 mg). In severe renal failure (CK≤30 ml/min), sildenafil clearance is decreased, resulting in approximately two-fold increase of AUC (100%) and Cmax (88%) compared to these parameters in normal renal function in patients of the same age group.

In patients with cirrhosis (Child-Pugh class A and B), sildenafil clearance is decreased, resulting in increased AUC (84%) and Cmax (47%) compared to those in normal liver function in patients in the same age group.

Indications

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

Pulmonary hypertension.

Active ingredient

Composition

1 film-coated tablet contains:

the active ingredient:

sildenafil citrate 140.48 mg (corresponds to sildenafil – 100 mg),

excipients:

MC – 324.52 mg;

calcium hydrophosphate – 90 mg;

Croscarmellose sodium – 36 mg;

Magnesium stearate – 9 mg

coat film:

Opadry II 85F20464 blue – 12 mg (polyvinyl alcohol – 4.8 mg; macrogol 3350 – 2.424 mg; titanium dioxide, 2.16 mg; talc, 1.776 mg; indigo carmine aluminum varnish, 0.84 mg)

How to take, the dosage

Treatment of erectile dysfunction: taken orally about 1 h before planned sexual activity. A single dose is 50 mg. Taking into account efficacy and tolerability, the dose can be increased to 100 mg or decreased to 25 mg. The maximum single dose is 100 mg. Maximum frequency of use is 1 time per day. For elderly patients aged over 65 years and in concomitant renal or hepatic dysfunction, the dose is 25 mg.

Pulmonary hypertension: orally, 20 mg 3 times/day at intervals of about 6-8 hours regardless of meals. The maximum daily dose is 60 mg. In patients with impaired renal function the dose adjustment is not required; however, in case of poor tolerance the dose is reduced to 20 mg 2 times per day.

Interaction

Concomitant use of CYP3A4 inhibitors (erythromycin, cimetidine) decreases sildenafil clearance and increases sildenafil plasma concentration.

Concomitant use of indinavir, saquinavir, ritonavir increases plasma Cmax and AUC of sildenafil due to inhibition of CYP3A4 isoenzyme by indinavir, saquinavir, ritonavir.

The stronger CYP3A4 isoenzyme inhibitors, such as ketoconazole or itraconazole, can be expected to increase the plasma concentration of sildenafil

The hypotensive effect of nitrates is increased when used concomitantly with nitrates.

A case of development of rhabdomyolysis symptoms after a single dose of sildenafil in a patient receiving simvastatin has been described.

Special Instructions

An examination of the cardiovascular system should be performed before starting sildenafil for the treatment of erectile dysfunction.

With caution should be used in patients with anatomical deformities of the penis (e.g., angulation, cavernous fibrosis, or Peyronie’s disease) and people with conditions that predispose to the development of priapism (such as sickle cell anemia, multiple myeloma, or leukemia).

Do not use in patients for whom sexual activity is undesirable.

With caution, use in patients with a tendency to bleeding, in the acute phase of gastric and duodenal ulcer, in hereditary retinitis pigmentosa.

Sildenafil is not used in patients under 18 years of age.

Impact on the ability to drive and operate machinery

Sildenafil has no effect on the ability to drive and operate machinery.

Contraindications

Simultaneous use of nitric oxide donors or nitrates in any form, hypersensitivity to sildenafil.

Side effects

CNS disorders: headache, hot flashes, dizziness, insomnia are possible.

Digestive system disorders: dyspepsia, asthenia, diarrhea, abdominal pain, nausea are possible.

Muscular system disorders: arthralgia, myalgia, increased muscle tone.

Respiratory system disorders: nasal congestion, pharyngitis, rhinitis, sinusitis, respiratory tract infections, respiratory disorders.

A visual organ: changes in vision (mild and transient; mainly changes in the color of objects, as well as increased perception of light and impaired visual clarity), conjunctivitis.

Others: flu-like syndrome, development of infectious diseases, symptoms of vasodilation, back pain, rash, urinary tract infections, prostate disorders; in single cases – priapism.

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