Zydena^® (Tablets) Instructions for Use

Marketing Authorization Holder

Valenta-Intellect, LLC (Russia)

Manufactured By

Dong-A ST Co., Ltd (Republic of Korea)

Packaging and Quality Control Release

VALENTA PHARM, JSC (Russia)

ATC Code

G04BE (Drugs for the treatment of erectile dysfunction)

Active Substance

Udenafil (Rec.INN registered by WHO)

Dosage Form

Zydena®

Film-coated tablets, 100 mg: 1, 2, or 4 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets light pink with a beige tint, oval, with the symbol “100” embossed on one side and symbols in the form of the letters “Z” and “Y” separated by a score on the other; on the break – white or almost white.

Excipients: lactose, corn starch, colloidal silicon dioxide, L-hydroxypropylcellulose, hydroxypropylcellulose-LF, talc, magnesium stearate.

Shell composition hydroxypropyl methylcellulose, talc, iron oxide red, iron oxide yellow, titanium dioxide.

1 pc. – contour cell packaging (1) – cardboard packs.
1 pc. – contour cell packaging (2) – cardboard packs.
2 pcs. – contour cell packaging (1) – cardboard packs.
2 pcs. – contour cell packaging (2) – cardboard packs.
4 pcs. – contour cell packaging (1) – cardboard packs.

Clinical-Pharmacological Group

Erectile dysfunction treatment drug. PDE5 inhibitor

Pharmacotherapeutic Group

Erectile dysfunction treatment agent – PDE5 inhibitor

Pharmacological Action

A drug for the treatment of erectile dysfunction, a reversible selective inhibitor of cGMP-specific PDE5.

Udenafil does not have a direct relaxing effect on the isolated corpus cavernosum, but during sexual stimulation it enhances the relaxing effect of nitric oxide by inhibiting PDE5, which is responsible for the breakdown of cGMP in the corpus cavernosum. The consequence of this is the relaxation of the smooth muscles of the arteries and blood flow to the tissues of the penis, which causes an erection. The drug has no effect in the absence of sexual stimulation.

In vitro studies have shown that Udenafil is a selective inhibitor of the PDE5 enzyme. PDE5 is present in the smooth muscles of the corpus cavernosum, 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 PDE5 than of PDE1, PDE2, PDE3, and PDE4, which are localized in the heart, brain, blood vessels, liver, and other organs.

Furthermore, Udenafil is 700 times more active against PDE5 than against PDE6, found in the retina and responsible for color perception. Udenafil does not inhibit PDE11, which explains the absence of cases of myalgia, low back pain, and manifestations of testicular toxicity.

Udenafil improves erection and the ability to successfully perform sexual intercourse. The effect of the drug has an optimal duration – up to 24 hours. The effect appears as early as 30 minutes after taking the drug in the presence of sexual arousal.

Udenafil in healthy individuals does not cause a significant change in systolic and diastolic blood pressure compared to placebo in the supine and standing positions (the average maximum decrease is 1.6/0.8 mm Hg and 0.2/4.6 mm Hg, respectively).

Udenafil does not cause changes in color recognition (blue/green), which is explained by its low affinity for PDE6. Udenafil does not affect visual acuity, electroretinogram, intraocular pressure, or pupil size.

When studying udenafil in men, no clinically significant effect of the drug on the quantity and concentration of semen, sperm motility and morphology was revealed.

Pharmacokinetics

After oral administration, Udenafil is rapidly absorbed. T_max is 30-90 minutes (average – 60 minutes). A high-fat meal does not affect the absorption of udenafil.

High binding of udenafil to plasma proteins (93.9%) prolongs its period of effectiveness to 24 hours after a single dose. Udenafil does not accumulate in the body. When healthy volunteers took udenafil at doses of 100 mg and 200 mg per day for 10 days, no significant changes in its pharmacokinetics were detected.

Udenafil is mainly metabolized with the participation of the CYP3A4 isoenzyme. T_1/2 is 12 hours. In healthy volunteers, the total clearance of udenafil is 755 ml/min. After oral administration, Udenafil is excreted as metabolites in the feces.

Indications

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

ICD codes

Dosage Regimen

Take Zydena^® orally as a single daily dose.

The recommended starting dose is 100 mg.

Administer the tablet approximately 30 to 60 minutes before anticipated sexual activity.

Increase the dose to a maximum of 200 mg only if the 100 mg dose provides insufficient effect and is well tolerated.

Do not exceed the maximum single dose of 200 mg.

Limit administration to once per 24-hour period.

The drug requires sexual stimulation for efficacy.

Dose adjustment is not required with food intake; the tablet can be taken with or without a meal.

For patients with severe hepatic impairment or severe renal impairment, use is not recommended due to lack of clinical data.

Avoid concomitant use with nitrates or nitric oxide donors due to the risk of a severe decrease in blood pressure.

Exercise caution with concurrent administration of potent CYP3A4 inhibitors (e.g., ketoconazole, ritonavir); consider a lower starting dose.

Do not use Zydena^® in combination with any other treatments for erectile dysfunction.

Adverse Reactions

From the cardiovascular system very often (>10%) – flushing of the face.

From the nervous system sometimes (0.1-1%) – dizziness, neck muscle stiffness, paresthesia.

From the organ of vision often (1-10%) – redness of the eyes; sometimes (0.1-1%) – blurred vision, eye pain, increased lacrimation.

Dermatological reactions sometimes (0.1-1%) – eyelid edema, facial edema, urticaria.

From the digestive system: often (1-10%) – dyspepsia, abdominal discomfort; sometimes (0.1-1%) – nausea, toothache, constipation, gastritis.

From the endocrine system : sometimes (0.1-1%) – thirst.

From the respiratory system often (1-10%) – nasal congestion; sometimes (0.1-1%) – shortness of breath, dry nose.

From the musculoskeletal system sometimes (0.1-1%) – periarthritis.

From the body as a whole: often (1-10%) – headache, chest discomfort, feeling of heat; sometimes (0.1-1%) – chest pain, abdominal pain, fatigue.

Contraindications

Simultaneous use of nitrates and other nitric oxide donors; hypersensitivity to udenafil.

Special Precautions

Udenafil should be used with caution in patients with uncontrolled arterial hypertension (BP >170/100 mm Hg), arterial hypotension (BP < 90/50 mm Hg); patients with hereditary degenerative retinal diseases (including retinitis pigmentosa, proliferative diabetic retinopathy); patients who have had a stroke, myocardial infarction, or coronary artery bypass grafting within the last 6 months; patients with severe hepatic or renal failure; in the presence of congenital long QT syndrome or QT interval prolongation due to medication; in patients with a predisposition to priapism, as well as in patients with anatomical deformation of the penis, in the presence of a penile implant.

The potential risk of complications during sexual activity in patients with such cardiovascular diseases as unstable angina or angina occurring during sexual intercourse; chronic heart failure of functional class II-IV (according to NYHA classification), developed within the last 6 months; uncontrolled cardiac arrhythmias should be taken into account.

With simultaneous use of udenafil and calcium channel blockers, alpha-blockers, or other antihypertensive agents, an additional decrease in systolic and diastolic BP by 7-8 mm Hg may be noted.

Sexual activity carries a potential risk for patients with cardiovascular diseases, therefore, treatment of erectile dysfunction, including with the use of udenafil, should not be carried out in men with heart diseases for which sexual activity is not recommended.

Patients with impaired outflow of blood from the left ventricle (aortic stenosis) may be more sensitive to the action of vasodilators, including PDE inhibitors. Despite the absence of cases of prolonged erection (more than 4 hours) and priapism (painful erection lasting more than 6 hours) during clinical studies, such phenomena are characteristic of this class of drugs. In case of an erection lasting more than 4 hours (regardless of the presence of pain), patients should immediately seek medical help. If priapism is not treated promptly, it can lead to irreversible damage to erectile tissue and erectile function.

Due to the lack of clinical data on the use of udenafil in patients over 71 years of age, use in these patients is not recommended.

It is not recommended to use Udenafil in combination with other types of treatment for erectile dysfunction.

Effect on the ability to drive vehicles and mechanisms

In patients whose activities are associated with driving vehicles and operating mechanisms, the individual reaction to taking udenafil should be determined.

Drug Interactions

Inhibitors of cytochrome CYP3A4 isoenzymes (ketoconazole, itraconazole, ritonavir, indinavir, cimetidine, erythromycin, grapefruit juice) can enhance the effect of udenafil.

Ketoconazole (at a dose of 400 mg) increases the bioavailability and C_max of udenafil (at a dose of 100 mg) by almost 2 times (212%) and 0.8 times (85%), respectively.

Ritonavir and indinavir significantly enhance the effect of udenafil.

Dexamethasone, rifampicin, and anticonvulsants (carbamazepine, phenytoin, and phenobarbital) may accelerate the metabolism of udenafil, so when used together, the effectiveness of udenafil is reduced.

In experimental studies with combined administration of udenafil (30 mg/kg orally) and nitroglycerin (2.5 mg/kg once intravenously), no effect on the pharmacokinetics of udenafil was observed, however, simultaneous clinical use of nitroglycerin and udenafil is not recommended due to a possible decrease in BP.

Udenafil and drugs from the group of alpha-blockers are vasodilators, therefore, if simultaneous use is necessary, both drugs should be used in minimal effective doses.

Storage Conditions

Store at 2°C (36°F) to 30°C (86°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.