Zydena® [Udenafil]

Pharmacological properties

Udenafil is a selective reversible inhibitor of cyclic guanosine monophosphate (cGMP), a specific type 5 phosphodiesterase (PDE-5).

Udenafil does not have a direct relaxing effect on an isolated cavernous body, but with sexual stimulation enhances the relaxing effect of nitric oxide by inhibiting PDE-5, which is responsible for the breakdown of cGMP in the cavernous body. The consequence of this is relaxation of the smooth muscles of the arteries and blood flow to the tissues of the penis, which causes an erection. The drug is ineffective in the absence of sexual arousal.

Udenafil is a selective inhibitor of the enzyme PDE-5. PDE-5 is found in the smooth muscles of the corpora cavernosa, in the smooth muscles of the vessels of internal organs, in skeletal muscles, platelets, kidneys, lungs and cerebellum. Udenafil is 10,000 times more potent an inhibitor of PDE-5 than PDE-1, PDE-2, PDE-3 and PDE-4, which are localized in the heart, brain, blood vessels, liver and other organs.

In addition, udenafil is 700 times more active in relation to PDE-5 than to PDE-6, detected in the retina, responsible for color perception. Udenafil is not inhibited by PDE-11, which explains the absence of cases of myalgia, lower back pain and manifestations of testicular toxicity.

The optimal duration of action of the drug is up to 24 hours. The effect manifests itself already 30 minutes after taking the drug in the presence of sexual arousal.

Udenafil in healthy volunteers does not cause a significant change in systolic and diastolic pressure compared with placebo in the supine and standing position (average maximum decrease is 1.6 / 0.8 and 0.2 / 4.6 mm Hg, respectively). Udenafil does not change color recognition (blue / green), due to its low affinity for PDE-6. Udenafil does not affect visual acuity, electroretinogram, intraocular pressure and pupil size.

No clinically significant effect of the drug on sperm count and concentration, sperm motility and morphology was revealed.

Pharmacokinetics

Suction. After oral administration, udenafil is rapidly absorbed. Time to reach C_max in blood plasma is 30–90 min (on average - 60 min). T_½ is 12 hours, the high binding of udenafil to plasma proteins (93.9%) prolongs the period of its effectiveness up to 24 hours after taking just one dose.

Eating high fat foods does not affect the absorption of Udenafil. Concomitant administration of 112 ml of alcohol (in terms of 40% ethyl alcohol) with oral administration of udenafil at a dose of 200 mg does not affect the pharmacokinetic profile of udenafil.

Metabolism. Udenafil is mainly metabolized by the CYP 3A4 cytochrome P450 enzyme.

In healthy volunteers, the total clearance of Udenafil is 755 ml / min. After oral administration, Udenafil is excreted in the form of metabolites with feces.

Udenafil does not accumulate in the body. With daily intake by healthy volunteers of Udenafil at a dose of 100 and 200 mg / day for 10 days, there were no significant changes in its pharmacokinetics.

Indications

Treatment of erectile dysfunction, characterized by the inability to achieve or maintain an erection of the penis, necessary for successful sexual intercourse.

For effective action, Ziden requires sexual arousal.

Application

Apply to adult men inside, regardless of food intake. apply one tablet 100 mg per day inside about 30 minutes –12 hours before the alleged sexual activity. the dose can be increased with caution to 200 mg after a careful assessment of all adverse events that occurred after taking 100 mg of the drug. maximum recommended number of applications - 1 time per day.

For elderly men (over 65), dose adjustment is not required.

Men with mild renal failure do not require dose adjustment.

Patients with mild hepatic impairment do not require dose adjustment (Child-Pugh class A).

Children. Do not use.

Contraindications

Hypersensitivity to any of the components of the drug; regular or periodic use of nitrates and other nitric oxide donors; uncontrolled ag (hell 170/100 mmHg), arterial hypotension (hell 90/50 mmHg) uncontrolled arrhythmia; hereditary degenerative diseases of the retina (including retinitis pigmentosa); severe hepatic or renal failure; the presence of a congenital syndrome of prolongation of the q – t interval or an increase in the q – t interval due to the use of drugs; unstable angina or severe heart failure; a stroke, myocardial infarction, or coronary artery bypass grafting during the last 6 months; the use of potent cytochrome p450 inhibitors (a protease inhibitor of HIV indinavir or ritonavir), the simultaneous administration of ziden with other drugs for the treatment of erectile dysfunction.

Loss of vision in one eye due to non-arterial ischemic neuropathy.

The drug contains lactose, so it should not be taken by patients with hereditary diseases such as galactose intolerance, lactase deficiency or impaired glucose-galactose absorption.

Age to 18 years.

Side effects

Adverse reactions indicated in the table arose during clinical trials with the use of Ziden 100 or 200 mg at the request of patients before sexual activity. in general, adverse reactions were transient and had mild or moderate severity. the most common adverse reactions include headache and facial flushing.

The following adverse reactions were not noted during pre-registration studies of the drug, however, they were recorded during additional clinical studies, therefore, their cause-effect relationships cannot be ruled out: heaviness in the head, feeling of cold, drowsiness, palpitations, orthostatic dizziness, lethargy, numbness of the auricle , eye discomfort, rash, erythema, vomiting, diarrhea, shortness of breath during exercise, coughing, nosebleeds, increased erection and hypotension.

In patients taking a dose of up to 200 mg / day, an increase in the frequency and number of adverse reactions was noted compared with the use of a dose of 100 mg.

During the post-registration observation, a temporary appearance of anterior non-arteritic ischemic optic nerve neuropathy (NAINSN) was rarely observed, although no clinical data were obtained on this in clinical studies of Ziden, as well as on decreased vision due to the use of PDE-5 inhibitors, including Ziden drug. Most of these patients, but not all, had concomitant anatomical or vascular risk factors for NAINSN, including, but not limited to: low ratios of excavation and optic disc (congestive disc), age 50, diabetes, hypertension, coronary heart disease, hyperlipidemia, and smoking.It is not possible to establish precisely whether these adverse events are directly related to the use of PDE-5 inhibitors, to the associated vascular risk factors or anatomical disorders of the patient, or to a combination of these factors or other causes.

During post-registration observation in patients taking PDE-5 inhibitors, including Ziden, there were no cases of sudden decrease or loss of hearing. At the same time, it was reported that sometimes the state of health and other factors can affect the appearance of adverse events from the side of the hearing organ. Often in such cases, information about further medical follow-up is limited. It is not possible to determine exactly whether these unwanted