INSTRUCTIONS FOR MEDICAL USE
REALIS® NEO
Trade name of the drug: REALIS® NEO
Active substance (INN): Tadalafil.
Dosage form: Coated tablets.
Contents:
1 coated tablet contains:
The active substance: Tadalafil – 20 mg.
Excipients: lactose, corn starch, sodium lauryl sulfate, povidone K-30, aerosil, talc, croscarmellose sodium, magnesium stearate.
Excipients in the shell: Hypromellose, titanium dioxide, polyethylene glycol 4000, tropeolin 0.
Description: Light yellow to brownish-yellow diamond-shaped, biconvex, coated tablets.
Pharmacotherapeutic group: Drugs for adjustment of potency.
ATX code: G04BE
Pharmacological properties
A drug for the treatment of erectile dysfunction. Tadalafil improves erection and the ability to have a successful intercourse. It is a reversible selective inhibitor of specific phosphodiesterase type 5 (FDE5) ts HMF. When sexual arousal causes local release of nitric oxide, inhibition of FDE5 by tadalafil leads to an increase in ts HMF levels in the corpora cavernosa of the penis. The consequence of this is relaxation of arterial smooth muscles and blood flow to the tissues of the penis, which causes an erection. Tadalafil has no effect in the absence of sexual stimulation. The drug works within 36 hours. The effect appears as early as 16 minutes after taking the drug in the presence of sexual arousal. Tadalafil in healthy subjects causes no significant changes in systolic and diastolic blood pressure compared to placebo when lying down (mean maximum decrease is 1.6/0.8 mm Hg, respectively) and when standing (mean maximum decrease is 0.2/4.6 mm Hg, respectively). Does not cause a significant change in heart rate (HR). Tadalafil has no effect on color recognition, visual acuity, electroretinogram, intraocular pressure, or pupil size. No clinically significant effect on semen characteristics has been observed in men taking the drug in daily doses for 6 months in placebo-controlled studies.
Pharmacokinetics
After oral administration, tadalafil is rapidly absorbed. The maximum concentration (Cmax) is reached on average in 2 hours. The speed and degree of absorption are not dependent on food intake. In the dose range from 2.5 mg to 20 mg, the area under the curve “concentration-time” (AUC) increases in proportion to the dose. The equilibrium plasma concentration (Css) is reached within 5 days if the drug is taken once daily. Tadalafil is distributed in body tissues. The volume of distribution (Vd) is about 63 l. At therapeutic concentrations, 94% of tadalafil is bound to plasma proteins. It is metabolized with participation of CYP3A4 isoenzyme. The main metabolite is methylcatecholglucuronide. In healthy individuals, the average oral clearance of tadalafil is 2.5 l/h and the average elimination half-life (T1/2) is 17.5 hours. It is excreted as inactive metabolites, mainly in the feces (about 61%) and to a lesser extent in the urine (about 36%).Pharmacokinetics in special clinical situations – in patients with mild renal failure (creatinine clearance (CK) of 51 to 80 ml/min) or medium severity (CK of 300 to 50 ml/min) AUC is greater than in healthy subjects. In patients with severe renal failure (CKD <30 ml/min), the use of the drug has not been studied. Pharmacokinetics of tadalafil in patients with mild to moderate hepatic dysfunction is similar to that in healthy subjects.
Indications for use
Erectile disorders characterized by the inability to achieve or maintain an erection of the penis sufficient for satisfactory intercourse.
Dosage and administration
Inside. It is recommended for middle-aged men to take the drug in a dose of 20 mg at least 16 min before the intended sexual activity, regardless of meals. Patients may attempt sexual intercourse at any time during 36 hours after taking the drug. The maximum recommended frequency of administration is 1 time/day.
There is no need for special dose adjustment for elderly men and patients with kidney function abnormalities (CK>30 ml/min) or liver disorders. Recommendations on the drug administration for middle-aged men are also applicable for elderly patients.
Side effects.
- Most common: headache (11%), dyspepsia (7%).
- Possible: back pain, myalgia, nasal congestion, flushes to the face.
- Rare: eyelid swelling, eye pain, conjunctival hyperemia, dizziness.
Contraindications
Hypersensitivity to tadalafil and other components of the drug;
concomitant use of drugs containing any organic nitrates;
Childhood and adolescence under 18 years of age;
Drug interactions
Effect of other drugs on tadalafil
The selective CYP3A4 inhibitor ketoconazole increases AUC by 107% and rifampicin decreases it by 88%. Although specific interactions have not been studied, it can be assumed that protease inhibitors such as ritonavir and saquinavir and CYP3A4 inhibitors such as erythromycin and itraconazole increase tadalafil activity.
Concomitant administration of antacid (magnesium hydroxide/aluminum hydroxide) and tadalafil decreases the rate of absorption of the latter without changing its AUC.
An increase in the pH of gastric juice as a result of taking the histamine H2-receptor blocker nizatidine has no effect on the pharmacokinetics of tadalafil. Effect of tadalafil on other drugs.
Tadalafil increases the hypotensive effect of nitrates. This is due to the additive effect of nitrates and tadalafil on nitric oxide and cGMP metabolism. Therefore, administration of the drug against the background of nitrates is contraindicated.
Tadalafil has no clinically significant effect on clearance of drugs whose metabolism involves cytochrome P450 isoenzymes.
It does not affect the effect of warfarin on prothrombin time and does not increase the duration of bleeding with acetylsalicylic acid.
Tadalafil shows no clinically significant interaction of antihypertensive drugs, including calcium channel blockers (amlodipine), angiotensin converting enzyme (ACE) inhibitors (enalapril), beta-adrenoblockers (metaprolol), alpha-adrenoblockers, thiazide diuretics (bendofluazide), angiotensin II receptor blockers. No differences in adverse events were found in patients taking the drug in combination with or without hypotensive drugs. No effect of a single drug administration on blood ethanol concentration, effect of ethanol on cognitive function and blood pressure (BP) was found. In addition, there were no changes in tadalafil blood concentrations in 3 hours after its administration in combination with ethanol. Tadalafil has no clinically significant effect on the pharmacokinetics and pharmacodynamics of theophylline.
Special indications
In patients with severe renal insufficiency (CK <30 ml/min) and severe hepatic failure, the drug should be used with extreme caution and only if absolutely necessary. During the preparation treatment in patients with moderate renal insufficiency (CKD from 31 to 50 ml/min), compared to patients with mild renal insufficiency (CKD from 51 to 80 ml/min) or healthy volunteers, back pain was more frequently observed. In patients with CKD <50 ml/min, the drug should be administered with caution.
Sexual activity has a potential risk for patients with cardiovascular disease. Therefore, treatment of erectile dysfunction, including with the drug, should not be performed in men with such heart diseases in which sexual activity is not recommended.
The potential risk of complications during sexual activity in patients with cardiovascular diseases should be taken into account:
- Myocardial infarction within the past 90 days;
- unstable angina or angina pectoris occurring during sexual activity;
- chronic heart failure (NYHA functional class II or higher) developed within the last 6 months;
- uncontrolled heart rhythm disorders;
- arterial hypotension (BP less than 90/50 mm Hg) or uncontrolled arterial hypertension;
- Stroke within the last 6 months.
Caution should be exercised when using the drug in patients with a predisposition to priapism (e.g., in sickle cell anemia, multiple myeloma or leukemia) or in patients with anatomical deformities of the penis (e.g., angulation, cavernous fibrosis or Peyronie’s disease). If an erection lasts for 4 hours or more, the patient should immediately consult a physician. Untimely treatment of priapism leads to penile tissue damage, which may result in long-term loss of potency.
The safety and efficacy of combining the drug with other treatments for erectile dysfunction have not been studied. Therefore, the use of such combinations is not recommended. Effect on the ability to drive motor transport and operate machinery – no special recommendations.
Overdose
When single use in healthy volunteers at a dose of 500 mg/day and in patients with erectile dysfunction – repeatedly up to 1000 mg/day, the adverse effects were the same as when using the drug at lower doses.
Treatment: standard symptomatic therapy.
Form of production
Coated tablets, 20 mg in a contoured cellular pack.
Storage conditions
Store in a dry, dark place at a temperature not exceeding 25°C. Keep out of the reach of children!
Shelf life
3 years. Do not use after the expiration date.
Conditions of dispensing from pharmacies
Released by a doctor’s prescription.