Dynamico Long pills 5mg, 28pcs

Composition

1 tablet contains: Active ingredient: tadalafil 5,00 mg; excipients: lactose monohydrate (spray dried) 88.25 mgg, sodium lauryl sulfate 0.75 mg, povidone-K 12 12.50 m, crospovidone 12.50 mg, sodium stearyl fumarate 1.00 mg; film coated: Opadray II 85F32782 yellow 4.00 mg (partially hydrolyzed polyvinyl alcohol 1,600 mg, macrogol-3350 0.808 mg, titanium dioxide (E 171) 0.688 mg, talc 0.592 mg, iron oxide yellow dye (E 172) 0.312 mg

Pharmacological action

The drug for the treatment of erectile dysfunction, is a reversible selective inhibitor of specific PDE5 cGMP. When sexual arousal causes a local release of nitric oxide, inhibition of PDE5 by tadalafil leads to an increase in cGMP levels in the penile cavernous body. The result is relaxation of the smooth muscles of the arteries and blood flow to the tissues of the penis, which causes an erection. Tadalafil is ineffective in the absence of sexual stimulation.

In vitro studies have shown that tadalafil is a selective inhibitor of PDE5. PDE5 is an enzyme found in the smooth muscles of the cavernous body, in the smooth muscles of the vessels of internal organs, in skeletal muscles, platelets, kidneys, lungs, and cerebellum.

The effect of tadalafil on PDE5 is more active than on other phosphodiesterases. Tadalafil is 10,000 times more active against PDE5 than against PDE1, PDE2, and PDE4, which are localized in the heart, brain, blood vessels, liver, and other organs. Tadalafil is 10,000 times more active in blocking PDE5 than PDE3, an enzyme found in the heart and blood vessels. This selectivity for PDE5, compared to PDE3, is important because PDE3 is an enzyme involved in heart muscle contraction. In addition, tadalafil is approximately 700 times more active against PDE5 than against PDE6, which is found in the retina and is responsible for photo transmission. Tadalafil is also 10,000 times more active against PDE5, compared to its effect on PDE7-PDE10.

It works for 36 hours. The effect is manifested as early as 16 minutes after ingestion in the presence of sexual arousal.

Tadalafil in healthy subjects does not cause significant changes in systolic and diastolic blood pressure, compared with placebo in the supine position (the average maximum decrease is 1.6/0.8 mm Hg, respectively) and standing (the average maximum decrease is 0.2/4.6 mm Hg, respectively). Tadalafil does not cause a significant change in heart rate.

Tadalafil does not cause changes in color recognition (blue/green), which is due to its low affinity for PDE6. In addition, tadalafil does not affect visual acuity, electroretinogram, intraocular pressure and pupil size.

There was no clinically significant effect on semen characteristics in men who took tadalafil in daily doses for 6 months.

Pharmacokinetics

After oral use, tadalafil is rapidly absorbed. _{Cmax is} reached in an average of 2 hours. The rate and degree of absorption do not depend on food intake. The pharmacokinetics of tadalafil in healthy individuals are linear with respect to time and dose. In the dose range from 2.5 to 20 mg, the AUC increases proportionally to the dose. C_ss in plasma is reached within 5 days when taking the drug 1 time/day.

The pharmacokinetics of tadalafil in patients with erectile dysfunction are similar to the pharmacokinetics of the drug in individuals without erectile dysfunction.

_The vd is about 63 liters, which indicates that tadalafil is distributed in the body’s tissues. At therapeutic concentrations,94% of tadalafil binds to plasma proteins. In healthy individuals, less than 0.0005% of the administered dose was detected in semen.

It is metabolized with the participation of the CYP3A4 isoenzyme. The main circulating metabolite is methylcatecholglucuronide, which is 13,000 times less active against PDE5 than tadalafil, so it is unlikely that this metabolite is clinically significant.

In healthy individuals, the average oral clearance of tadalafil is 2.5 l/h, and the average T_1/2 is 17.5 h. Tadalafil is mainly excreted as inactive metabolites, mainly in the faeces (about 61%) and to a lesser extent in the urine (about 36%).

In patients with mild (creatinine clearance 51 to 80 ml/min) or moderate (creatinine clearance 31 to 50 ml/min) renal insufficiency, AUC is higher than in healthy individuals.

Indications

Erectile dysfunction.

Contraindications

• Hypersensitivity to tadalafil or any other component of the drug.
• Concomitant use of tadalafil, nitrates, and nitrate-like medications, as tadalafil enhances the hypotensive effect of nitrates due to the NO/cGMP interaction.
• Contraindications to sexual activity in patients with cardiovascular diseases:

* myocardial infarction within the last 90 days;

* unstable angina or the occurrence of an angina attack during sexual intercourse;

* chronic heart failure of NYHA classes II-IV;

* uncontrolled arrhythmias, hypotension (blood pressure less than 90/50 mm Hg), uncontrolled arterial hypertension;

* ischemic stroke in the last 6 months.

• Loss of vision due to non-arterial anterior ischemic optic neuropathy (regardless of its association with PDE5 inhibitors).
• Simultaneous use of doxazosin, as well as medications for the treatment of erectile dysfunction.
• Daily (more than 2 times a week) use in patients with severe renal insufficiency (creatinine clearance less than 30 ml / min).
• Lactase deficiency, lactose intolerance, and glucose-galactose malabsorption.
• Children under 18 years of age.

With caution

In patients with severe renal insufficiency (creatinine clearance less than 30 ml/min), severe hepatic insufficiency (Child-Pugh class C), concomitant use with alpha-blockers, in patients with a predisposition to priapism (sickle cell anemia, multiple myeloma or leukemia) or with anatomical deformity of the penis (angular curvature, cavernous fibrosis or Peyronie’s disease); when used simultaneously with powerful anti-inflammatory drugs. inhibitors of the CYP3A4 isoenzyme (ritonavir, saquinavir, ketoconazole, itraconazole, erythromycin), antihypertensive agents.

Side effects

The most common adverse reactions in patients with erectile dysfunction treated with tadalafil are headache, dyspepsia, myalgia, back pain, most often they were intermittent and mostly mild or moderate. The most frequent reports of headache were reported in patients who used tadalafil daily for 10-30 days from the start of taking the drug.

Adverse reactions are classified with the following frequency: very common (≥1/10); common – (≥1/100 to

From the immune system: infrequently-hypersensitivity reactions; rarely-angioedema 2.

From the nervous system: often-headache; infrequently-dizziness; rarely-stroke 1 (including hemorrhagic), syncope, transient ischemic attack 1, migraine 2, cluster seizures, transient amnesia.

From the side of the visual organs: infrequently-blurred vision, pain in the eyes; rarely-visual field defects, edema of the eyelids, conjunctival hyperemia, ischemic neuropathy of the optic nerve 2, retinal vascular occlusion 2.

From the heart 1: infrequently-tachycardia, strong palpitations; rarely-myocardial infarction, unstable angina 2, ventricular arrhythmia 2.

From the side of blood vessels: often – “flushes” of blood to the face; infrequently-hypotension 3, hypertension.

From the respiratory system: often-nasal congestion; infrequently-shortness of breath, nosebleeds.

From the gastrointestinal tract: often-dyspepsia, gastroesophageal reflux; infrequently-abdominal pain.

From the skin and subcutaneous tissues: infrequently-skin rash, hyperhidrosis (sweating); rarely-urticaria, Stevens-Johnson syndrome 2, exfoliative dermatitis 2.

Musculoskeletal and connective tissue disorders: often-back pain, myalgia, pain in the extremities.

From the side of the kidneys and urinary tract: infrequently-hematuria.

From the genitals: infrequently-bleeding from the penis, hematospermia; rarely-prolonged erection, priapism 2.

Other: infrequently-chest pain; rarely-facial edema 2, sudden death 1,2.

(1) Most patients had previous cardiovascular risk factors.

(2) Side effects have been reported in the post-marketing period.

(3) Reports of adverse reactions in patients taking tadalafil concomitantly with antihypertensive drugs.

Description of individual adverse reactions

Electrocardiogram changes (sinus bradycardia) have been reported in patients treated with tadalafil daily. These changes were not associated with adverse reactions.

Interaction

Cytochrome P 450 inhibitors

Tadalafil is mainly metabolized with the participation of the CYP3A4 isoenzyme. A selective inhibitor of the CYP3A4 isoenzyme ketoconazole (200 mg/day) increases the AUC of tadalafil (10 mg once) by 2 times and Cmax by 15%, and ketoconazole (400 mg/day) increases the AUC of tadalafil (20 mg once) by 4 times and Cmax by 22% compared to taking tadalafil alone tadalafil in the same dose.

Ritonavir (200 mg twice daily), which is an inhibitor of the isoenzymes CYP3A4, CYP2C9, CYP2C19 and CYP2D6, increased the AUC of tadalafil (20 mg) twice without changing the Cmax. Despite the fact that specific interactions have not been studied, it can be assumed that

other protease inhibitors, such as saquinavir and other inhibitors of the CYP3A4 isoenzyme, such as erythromycin, clarithromycin, itraconazole and grapefruit juice, may increase the concentration of tadalafil in the blood plasma, as well as increase the likelihood of adverse reactions, so caution should be used simultaneously with tadalafil.

The selective inducer of the CYP3A4 isoenzyme rifampicin, when co-administered with tadalafil, reduces the AUC of tadalafil (10 mg once) by 88%. This may reduce the effect of tadalafil and reduce its effectiveness. The degree of reduced efficiency is unknown. It can be assumed that other inducers of the CYP3A4 isoenzyme, such as carbamazepine, phenytoin, and phenobarbital, can also reduce the concentration of tadalafil in blood plasma.

Other medicinal products

Tadalafil (5 mg,10 mg and 20 mg) is known to enhance the hypotensive effect of nitrates. This occurs as a result of the additive action of nitrates and tadalafil on the metabolism of NO and cGMP. Therefore, the use of tadalafil against the background of the use of nitrates is contraindicated. However, if necessary, nitrates can be used at least 48 hours after the last dose of tadalafil. In this situation, the intake of nitrates should be carried out only under the supervision of a doctor and accompanied by monitoring of hemodynamic parameters.

Antihypertensive drugs, including slow calcium channel blockers

Concomitant use of doxazosin (4 mg and 8 mg daily) with tadalafil (5 mg daily and 20 mg once) significantly increases the antihypertensive effect of alpha-blockers. This effect lasts for at least 12 hours and may be accompanied by appropriate symptoms, including syncope, and therefore the simultaneous use of these drugs is not recommended. These reactions have not been reported with the concomitant use of alfuzosin or tamsulosin with tadalafil, but tadalafil should be used with caution in patients treated with alpha-blockers, especially in elderly patients. Treatment should start with a minimum dose and then adjust the dose.

Tadalafil has a systemic vasodilator property and can enhance the antihypertensive effect of antihypertensive drugs, including such groups of antihypertensive drugs as slow calcium channel blockers (amlodipine), angiotensin-converting enzyme inhibitors (enalapril), beta-blockers (metoprolol), thiazide diuretics (bendrofluazide) and angiotensin II receptor antagonists (various types and doses, alone or in combination with thiazide diuretics, calcium channel blockers, beta-blockers and/or alpha-blockers).

Additionally, patients who took several antihypertensive drugs and whose hypertension was poorly controlled showed a slightly greater decrease in blood pressure. In the vast majority of patients, this decrease was not associated with hypotensive syndrome. Patients receiving concomitant treatment with antihypertensive drugs with tadalafil should be given appropriate clinical recommendations.

5-alpha reductase inhibitor

No additional adverse reactions were reported when tadalafil (5 mg) was co-administered with finasteride (5 mg) to relieve the symptoms of benign prostatic hyperplasia. However, the interaction of these drugs is not fully understood and they should be used with caution at the same time.

Substrate of the CYP1A2 isoenzyme (for example, theophylline)

No adverse reactions were reported with concomitant use of tadalafil (10 mg) and theophylline (a non-selective phosphodiesterase inhibitor), but there was a slight change in pharmacodynamic properties: an increase in heart rate by 3.5 beats per minute. This effect is considered insignificant and has no clinical significance, but it should be taken into account when using these drugs simultaneously.

Ethinyl Estradiol and terbutaline

An increase in oral bioavailability of ethinyl estradiol has been reported when co-administered with tadalafil; a similar increase can be expected with oral terbutaline, although the clinical significance of this effect is insignificant.

Alcohol

Tadalafil did not affect the concentration of alcohol, just as alcohol did not affect the concentration of tadalafil. Tadalafil (20 mg) did not increase the reduction in blood pressure caused by alcohol (0.7 g/kg). Some patients experienced postural vertigo and orthostatic hypotension. When taking tadalafil in combination with lower doses of alcohol (0.6 g/kg), a decrease in blood pressure was not observed, and dizziness occurred with the same frequency as when taking alcohol without tadalafil. The effect of alcohol on cognitive functions does not change when used simultaneously with tadalafil.

Drugs metabolized by the cytochrome P450 system

Tadalafil does not have a clinically significant effect on the clearance of drugs metabolized with the participation of the CYP450 isoenzyme. Studies have confirmed that tadalafil does not inhibit or induce the isoenzymes CYP3A4, CYP1A2, CYP2D6, CYP2E1, CYP2C9 and CYP2C19.

Substrate of the CYP2C19 isoenzyme (for example, R-warfarin)

Tadalafil at a dose of 10 mg and 20 mg does not have a clinically noticeable effect on the AUC of S-warfarin or R-warfarin. Tadalafil also does not affect the effect of warfarin on prothrombin time.

Acetylsalicylic Acid

Tadalafil in doses of 10 mg and 20 mg does not increase the duration of bleeding caused by acetylsalicylic acid.

Antidiabetic medications

Specific interaction studies with antidiabetic drugs have not been conducted.

How to take, course of use and dosage

Inside, regardless of food intake.

Erectile dysfunction

The recommended dose is 10 mg before the intended sexual intercourse.

In patients in whom the drug DYNAMICO LONG at a dose of 10 mg is not effective, a dose of 20 mg is used. DYNAMICO LONG should be taken at least 30 minutes before sexual activity.

The maximum frequency of taking the drug DYNAMICO LONG is 1 time per day.

Doses of 10 mg and 20 mg are used immediately before sexual activity and are not recommended for daily use. For patients with frequent sexual activity (more than twice a week), it is recommended to use DYNAMICO LONG at a dose of 5 mg daily,1 time a day at the same time. The daily dose can be reduced to 2.5 mg depending on individual sensitivity. For patients with infrequent sexual activity (less than 2 times a week), the use of DYNAMICO LONG in a dose of 20 mg immediately before sexual activity is recommended. The maximum daily dose is 20 mg.

Special patient group

No dose adjustment is required in elderly patients.

No dose adjustment is required in patients with mild or moderate renal insufficiency. The maximum dose in patients with severe renal insufficiency is 10 mg. Daily use (more than 2 times a week) of DYNAMICO LONG in patients with severe renal insufficiency is not recommended.

In patients with mild to moderate hepatic insufficiency, the recommended dose of DYNAMICO LONG is 10 mg. The use of a dose greater than 10 mg in patients with impaired liver function has not been evaluated. There are insufficient data on the use of DYNAMICO LONG in patients with severe hepatic insufficiency (Child-Pugh class C). Caution should be exercised when using DYNAMICO LONG in this group of patients.

Patients with diabetes mellitus

When used in patients with diabetes mellitus, no dose adjustment is required.

Overdose

When tadalafil was administered once in healthy volunteers at a dose of 500 mg and in patients with erectile dysfunction (repeatedly up to 100 mg/day), the undesirable effects were the same as when using lower doses.

In case of overdose, standard symptomatic treatment should be performed. During hemodialysis, tadalafil is practically not excreted.

Special instructions

Before using tadalafil

Before using DYNAMICO LONG, it is necessary to diagnose erectile dysfunction, determine possible causes and choose adequate treatment methods, evaluate the medical history and conduct a physical examination.

Before starting treatment of erectile dysfunction with DYNAMICO LONG, the doctor should study the state of the patient’s cardiovascular system, since there is a certain degree of risk of developing disorders associated with sexual activity. The drug DYNAMIKO LONG has vasodilating properties, as a result of which a moderate and periodic decrease in blood pressure can be observed, which can increase the hypotensive effect of nitrates.

The efficacy of tadalafil in patients undergoing pelvic surgery, pelvic organs, or nerve-sparing radical prostatectomy is not known.

Cardiovascular complications

Serious adverse reactions from the cardiovascular system, such as: myocardial infarction, sudden death, angina pectoris, ventricular arrhythmia, stroke, transient ischemic attacks, chest pain, palpitations and tachycardia, were reported both in the post-marketing period and during clinical trials. Most of the patients who experienced these reactions previously had cardiovascular risk factors. However, it is not possible to determine the association of these reactions with tadalafil use, cardiovascular risk factors, sexual activity, or a combination of these or other factors.

In patients receiving combined therapy with antihypertensive drugs and DYNAMICO LONG, the latter may cause a decrease in blood pressure. With daily use of the drug DYNAMIKO LONG, it may be necessary to adjust the dose of antihypertensive

In some patients, concomitant use of alpha-blockers with DYNAMICO LONG may cause a decrease in blood pressure. Concomitant use of these drugs is not recommended.

Visual disturbances

Visual impairment and ischemic optic neuropathy have been reported in association with the use of tadalafil and other PDE5 inhibitors. It is necessary to stop using the drug DYNAMIKO LONG if there are signs of visual impairment and immediately consult a doctor.

Renal and hepatic insufficiency

Due to the increased AUC of tadalafil, limited clinical experience with its use, and the limited effectiveness of hemodialysis in reducing the clearance of tadalafil, daily use of DYNAMICO LONG is not recommended in patients with severe renal insufficiency.

There are no data on the daily use of DYNAMICO LONG in patients with severe hepatic insufficiency (Child-Pugh class C). Tadalafil should be used with caution in these patients.

Priapism and anatomical deformities of the penis

Patients who have an erection lasting more than 4 hours should immediately consult a doctor. Untimely treatment of priapism can lead to penile tissue damage and loss of potency.

DYNAMICO LONG should be used with caution in patients with anatomical deformity of the penis (angulation, cavernous fibrosis, Peyronie’s disease), or in patients with risk factors for priapism (sickle cell anemia, multiple myeloma, leukemia).

Use with CYP3A4 isoenzyme inhibitors

Caution should be exercised when using DYNAMICO LONG concomitantly with potent inhibitors of the CYP3A4 isoenzyme (ritonavir, saquinavir, ketoconazole, itraconazole, and erythromycin), due to a possible increase in the AUC of tadalafil.

Use simultaneously with other treatments for erectile dysfunction

Concomitant use of DYNAMICO LONG with other medications used for the treatment of erectile dysfunction is not recommended, as the efficacy and safety of combined treatment has not been studied.

Influence on the ability to drive vehicles and mechanisms

Caution should be exercised when using the drug DYNAMICO LONG due to the fact that dizziness may develop, which may affect the ability to drive vehicles and work with potentially dangerous mechanisms.

Form of production

Film-coated tablets,2.5 mg,5 mg,10 mg,20 mg

.2,5 mg,5 mg. 7 tablets in a blister 1.2 or 4 blisters together with the instructions for use in a cardboard pack.

10 tablets in a blister 1.1 blister together with the instructions for use in a cardboard pack.

10 mg. 4 tablets in a blister 1.1 or 2 blisters together with the instructions for use in a cardboard pack.

10 tablets in a blister 1.1 blister together with the instructions for use in a cardboard pack.

20 mg. 1 or 2, or 10 tablets in a blister 1.1 blister together with the instructions for use in a cardboard pack.

4 tablets in a blister 1.1 or 2 blisters together with the instructions for use in a cardboard pack.

1-PVC/AKLAR/PVC blister//aluminum foil (or made of aluminum (OPA/alum. /PVC) foils, or PVC/ACLAR/PVDC/PVC KPMAX / / aluminum foil).

Storage conditions

Store at a temperature not exceeding 25 °C.

Keep out of the reach of children.

Shelf

life is 2 years.

Active ingredient

Tadalafil

Conditions of release from pharmacies

By prescription

Dosage form

Tablets