Expiration date: 01/2025

Composition

Tablets, film-coated 1 tablet contains:

active substance:  

tadalafil 5 or 20 mg

excipients (core): lactose monohydrate (milk sugar) — 53,8/100,2 mg; lactose monohydrate (ektapress) (milk sugar) — 64/123 mg; MKC — 26/53 mg; croscarmellose sodium (Primerose) — 12,5/17 mg; crospovidone (Kollidon CL-M) — 4/5 mg, crospovidone (Kollidon CL) — 3/2 mg hyprolose extratone (hydroxypropyl cellulose) — 3/5 mg; hyprolose (hydroxypropyl cellulose) — 2/2 mg; sodium fumarate and 1.5/2 mg; sodium lauryl sulfate and 0.2/0.8 mg  

shell film (dosage 5 mg): 85F22048 Opadry II yellow (polyvinyl alcohol, partially hydrolyzed 2 mg titanium dioxide E171 — value of 1.0935 mg, macrogol (PEG 3350) — 1,01 mg, talc — 0,74 mg, aluminum lacquer dye quinoline yellow — 0,1505 mg, aluminum lacquer dye "sunset" yellow — 0,0035 mg, dye iron oxide (II), E172 yellow — 0.0015 mg, aluminum lacquer based Indigo dye is 0,0010 mg) — 5 mg  

film shell (for dosage 20 mg): Opadry II 85F240037 pink (polyvinyl alcohol, partially hydrolyzed-4 mg, titanium dioxide E171-2,236 mg, macrogol (PEG 3350) - 2,02 mg, talc-1,48 mg, iron dye oxide (II) yellow E172-0,143 mg, iron dye oxide (II) red E172-0,121 mg) - 10 mg  

Description of dosage form

Film coated tablets, 5 mg: yellow, round, biconvex, with risk on one side.

Film coated tablets, 20 mg: pinkish-orange, round, biconvex.

On the cross section - the core of the tablet is white or almost white.

Pharmacological action

Pharmacological action-stimulating erectile function.

Pharmacodynamics

Tadalafil is a reversible selective inhibitor of cGMP-specific PDE-5. When sexual arousal causes local release of nitric oxide, inhibition of PDE-5 by tadalafil leads to an increase in the concentration of cGMP in the cavernous body of the penis. The consequence of this is the relaxation of the smooth muscles of the arteries and the blood flow to the tissues of the penis, which causes an erection. Tadalafil has no effect in the absence of sexual arousal.

In vitro studies have shown that tadalafil is a selective PDE-5 inhibitor. PDE-5 is an enzyme found in the smooth muscles of the cavernous body, vessels of internal organs, skeletal muscles, platelets, kidneys, lungs and cerebellum. The effect of tadalafil on PDE-5 is more active than on other PDES. Tadalafil is 10,000 times more potent against PDE-5 than against PDE-1, PDE-2, PDE-4, and PDE-7, which are localized in the heart, brain, blood vessels, liver, leukocytes, skeletal muscles, and other tissues and organs. Tadalafil is 10,000 times more active in blocking PDE-5 than PDE — 3-an enzyme that is found in the heart and blood vessels. This selectivity for PDE-5 compared to PDE-3 is important because PDE-3 is an enzyme involved in heart muscle contraction. In addition, tadalafil is about 700 times more active against PDE-5 than against PDE-6, which is found in the retina and is responsible for photo transmission. Tadalafil is also showing the action in 9000 times more potent against PDE-5 compared with its effect on PDE-8, PDE-9, PDE-10 and 14 times more potent against PDE-5 compared to PDE-11. Tissue distribution and physiological effects of PDE-8 — PDE-11 inhibition have not been clarified to date.

Tadalafil improves erection and increases the possibility of full sexual intercourse.

Tadalafil in healthy individuals does not cause significant changes in SBP and DBP in comparison with placebo in the supine position (the average maximum reduction is 1.6/0.8 mm Hg.art respectively) and standing (mean maximum decrease of 0.2/4.6 mm Hg.art., respectively). Tadalafil does not cause a significant change in heart rate.

Tadalafil does not cause changes in color recognition (blue/green), due to its low affinity for PDE-6. In addition, there is no effect of tadalafil on visual acuity, electroretinogram, IOP and pupil size.

Several studies have been conducted to assess the effect of daily tadalafil on spermatogenesis. None of the studies showed an undesirable effect on the morphology of sperm and their mobility. One study found a decrease in the average concentration of sperm compared to placebo. The decrease in sperm concentration was associated with a higher ejaculation rate. In addition, there was no undesirable effect on the average concentration of sex hormones, including testosterone, LH and FSH when taking tadalafil compared to placebo.

There was an improvement in erection in patients with erectile dysfunction of all degrees of severity when taking tadalafil 1 time a day.

The mechanism of action in patients with benign prostatic hyperplasia (BPH). Inhibition of PDE-5 by tadalafil, leading to an increase in the concentration of cGMP in the cavernous body of the penis, is also observed in the smooth muscles of the prostate, bladder and vessels that supply them with blood. Relaxation of vascular smooth muscle leads to an increase in blood perfusion in these organs, and as a consequence, a decrease in the severity of symptoms of BPH. Relaxation of the smooth muscles of the prostate and bladder can further enhance vascular effects.

Pharmacokinetics

Suction. After oral tadalafil is rapidly absorbed. The average Cmax in plasma is reached after an average of 2 hours after ingestion. The rate and degree of absorption of tadalafil do not depend on food intake, so the drug Tadalafil can be used regardless of food intake. Time of admission (morning or evening) has no effect on the rate and extent of absorption. The pharmacokinetics of tadalafil in healthy individuals is linear in terms of time and dose. In the dose range from 2.5 to 20 mg AUC increases in proportion to the dose. Css in plasma are attained within 5 days while taking the drug 1 time per day. The pharmacokinetics of tadalafil in patients with erectile dysfunction is similar to the pharmacokinetics of the drug in patients without erectile dysfunction.

Distribution. The average Vd is about 63 liters, indicating that tadalafil is distributed in the tissues of the body. In therapeutic concentrations, 94% of tadalafil in plasma binds to proteins. Protein binding does not change with impaired renal function. In healthy volunteers less than 0.0005% of the administered dose was found in sperm.

Metabolism. Tadalafil is mainly metabolized with the participation of isoenzyme CYP3A4. The major circulating metabolite is methylethanolamine. This metabolite is at least 13,000 times less active against PDE-5 than tadalafil. Therefore, the concentration of this metabolite is not clinically significant.

Breeding. In healthy volunteers, the average clearance of tadalafil ingestion is 2.5 l/h, and the average T1/2 of 17.5 hours Tadalafil is excreted predominantly as inactive metabolites, mainly through the intestines (about 61% of the dose) and to a lesser extent by the kidneys (about 36% of the dose).

Special patient groups

Age older than 65 years. Healthy volunteers 65 years and older had a lower clearance of tadalafil when taken orally, which was expressed in an increase in AUC by 25% compared to healthy volunteers from 19 to 45 years. This difference is not clinically significant and does not require dose selection.

Renal failure. In patients with mild renal insufficiency (creatinine Cl 51 to 80 ml/min) and moderate severity (creatinine Cl 31 to 50 ml/min), as well as in patients with end-stage renal insufficiency who are on hemodialysis, the exposure of tadalafil (AUC) approximately doubled. In patients on hemodialysis, Cmax was 41% higher than in healthy volunteers. The excretion of tadalafil by haemodialysis is insignificant.

Liver failure. The pharmacokinetics of tadalafil in patients with mild to moderate hepatic insufficiency (class a and B according to the child-Pugh classification) is comparable to that in healthy volunteers. For patients with severe hepatic insufficiency (class C, child-Pugh classification), data are insufficient. When prescribing Tadalafil to patients with severe hepatic insufficiency, it is necessary to conduct a preliminary assessment of the risk and benefit of using the drug.

Diabetes. In patients with diabetes mellitus during the use of tadalafil AUC was less by about 19% compared to healthy volunteers. This difference does not require dose selection.

The testimony of the drug Tadalafil

• erectile dysfunction;
  
• lower urinary tract symptoms in patients with benign prostatic hyperplasia;
  
• erectile dysfunction in patients with lower urinary tract symptoms on the background of benign prostatic hyperplasia.
  

Contraindications

• hypersensitivity to tadalafil or any substance included in the preparation;
  
• taking drugs containing any organic nitrates;
  
• the presence of contraindications to sexual activity in patients with diseases of the cardiovascular system: myocardial infarction in the last 90 days, unstable angina, occurrence of angina attack during sexual intercourse, chronic heart failure of class II and higher classification NYHA in the last 6 months, uncontrolled arrhythmias, hypotension (blood PRESSURE <90/50 mm Hg.art.), uncontrolled hypertension, ischemic stroke during the last 6 months;
  
• vision loss due to non-arterial anterior ischemic optic neuropathy (NAPION) (regardless of the Association with PDE-5 inhibitors);
  
• the simultaneous use of doxazosin, other inhibitors of PDE-5, other means of therapy of erectile dysfunction, called guanylate cyclase stimulants such as riociguat;
  
• chronic renal failure (creatinine Cl <30 ml / min);
  
• lactase deficiency, lactose intolerance, glucose-galactose malabsorption;
  
• the age of 18.
  

With caution: severe hepatic insufficiency (class C according to child-Pugh classification) (there is no sufficient data for such patients); simultaneous administration of alpha1-adrenoblockers (simultaneous use of these drugs can lead to symptomatic arterial hypotension in some patients; when using a single dose of tadalafil, there is no symptomatic arterial hypotension while using tamsulosin, selective alpha1a-adrenoblocker (see "Interaction»); predisposition to priapism (sickle cell anemia, multiple myeloma or leukemia) or anatomical deformation of the penis (angular curvature, cavernous fibrosis or Peyronie's disease); simultaneous administration with CYP3A4 isoenzyme inhibitors (including ritonavir, saquinavir, ketoconazole, Itraconazole, clarithromycin, erythromycin, grapefruit juice), hypotensive agents, 5-alpha-reductase inhibitors.

Diagnosis of erectile dysfunction should include identification of the potential underlying cause, appropriate medical examination and determination of treatment tactics.

Use during pregnancy and breast-feeding

Tadalafil is not intended for use in women.

Side effect

The most common adverse events in patients with erectile dysfunction and BPH are headache and dyspepsia, as well as back pain, myalgia.

According to the who classification, all reactions are distributed by organ system and frequency of development: very often (?1/10); often (?1/100, <1/10); infrequently (?1/1000, <1/100); rarely (?110000, <11000); very rarely (<1/10000); the frequency is unknown (it is impossible to determine the frequency of reactions from the available data).

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

From the nervous system: often — headache; infrequently — dizziness, rarely — stroke (including acute cerebrovascular accident (CVA) hemorrhagic type), syncope, transient ischemic attacks, migraine, seizures epileptic transient amnesia.

On the part of the organ of vision: infrequently-blurred visual perception, pain in the eyeball; rarely-violation of visual fields, swelling of the eyelids, conjunctival hyperemia, NAPION1, occlusion of retinal vessels1.

On the part of the organ of hearing and labyrinth disorders: infrequent — tinnitus; rare — of sudden hearing loss.

From heart: rare — palpitations, tachycardia; rarely — myocardial infarction, ventricular disorders of rhythm, unstable angina.

From vessels: often — tides blood to a person; rare — reducing ADZ, increased blood pressure.

From the respiratory system, chest and mediastinal organs: often-nasal congestion; infrequently-shortness of breath, nasal bleeding.

By the blood: often — neuralgia; infrequently — pain in the abdomen, gastroesophageal reflux, diarrhea in patients older than 65 years of age, vomiting, nausea.

The skin and subcutaneous tissue: often — rash; rare — urticaria, syndrome Stevens-Johnson's, dermatitis exfoliative, hyperhidrosis (excessive sweating).

From the musculoskeletal system and connective tissue: often — back pain, myalgia, pain in the limbs.

The kidneys and urinary tract: rarely — hematuria.

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

General disorders: rare — pain in chest, peripheral edema, fatigue; rarely — face edema, sudden cardiac death.

Side reactions have been identified during post-marketing use, are not observed in a clinical placebo-controlled trials.

2 observed in patients who previously had cardiovascular risk factors. However, it is not possible to determine precisely whether these phenomena are directly related to these risk factors, tadalafil, sexual arousal or a combination of these or other factors.

Often was observed when tadalafil applied patients already receiving antihypertensives.

Interaction

Effect of other drugs on tadalafil

Tadalafil is mainly metabolized with the participation of isoenzyme CYP3A4. Selective inhibitor of CYP3A4 ketoconazole isoenzyme (400 mg/day) increases the exposure of a single dose of tadalafil (AUC) by 312% and Cmax by 22%, and ketoconazole (200 mg/day) increases the exposure of a single dose of tadalafil (AUC) by 107% and Cmax by 15% relative to AUC and Cmax values for only one tadalafil.

Ritonavir (200 mg 2 times a day), an inhibitor of CYP3A4, CYP2C9, CYP2C19 and CYP2D6 isoenzymes, increases the exposure of a single dose of tadalafil (AUC) by 124% without changing Cmax. Although specific interactions have not been studied, it can be assumed that other HIV protease inhibitors such as saquinavir, as well as CYP3A4 isoenzyme inhibitors such as erythromycin, clarithromycin, Itraconazole and grapefruit juice, may increase tadalafil plasma concentrations. The role of carriers (Including p-gp) in the distribution of tadalafil is unknown. There is a possibility of drug interaction mediated by inhibition of vectors.

Selective inducer of CYP3A4 isoenzyme, rifampicin (at a dose of 600 mg / day), reduces the exposure of a single dose of tadalafil (AUC) by 88% and Cmax by 46% relative to AUC and Cmax for only one tadalafil. It can be assumed that the simultaneous use of other inducers of CYP3A4 isoenzyme (such as phenobarbital, phenytoin or carbamazepine) should also reduce the concentration of tadalafil in blood plasma.

Simultaneous administration of antacid (magnesium hydroxide / aluminum hydroxide) and tadalafil reduces the rate of absorption of tadalafil without changing the AUC for tadalafil.

An increase in the pH of the stomach as a result of taking a blocker of H2-histamine receptors of nizatidine had no effect on the pharmacokinetics of tadalafil.

The safety and efficacy of the combination of tadalafil with other treatments for erectile dysfunction or other PDE-5 inhibitors has not been studied, so the use of such combinations is not recommended.

Effect of tadalafil on other drugs

It is known that tadalafil enhances the hypotensive effect of nitrates. This is due to the additive effect of nitrates and tadalafil on the metabolism of nitric oxide (II) and cGMP. Therefore, the use of tadalafil in patients receiving nitrates is contraindicated.

Tadalafil does not have a clinically significant effect on the clearance of drugs whose metabolism occurs with the participation of cytochrome P450.

Studies have confirmed that tadalafil does not inhibit or induce CYP1A2, CYP3A4, CYP2C9, CYP2C19, CYP2D6, CYP2E1 isoenzymes.

Tadalafil has no clinically significant effect on the AUC of S - or R-warfarin. Tadalafil does not affect the action of warfarin against PV.

Tadalafil does not potentiate an increase in the duration of bleeding caused by taking acetylsalicylic acid.

Tadalafil has systemic vasodilating properties and can enhance the action of antihypertensive drugs. In addition, patients who took several antihypertensive drugs, in which hypertension was poorly controlled, there was a slightly greater decrease in blood PRESSURE. In the vast majority of patients, this decrease was not associated with hypotensive symptoms. Patients receiving treatment with antihypertensive drugs and taking tadalafil should be given appropriate clinical recommendations.

Did not observed a significant decline in blood pressure while the use of healthy volunteers tadalafil and selective ?????1?-adrenoblocker tamsulosin.

Coadministration of tadalafil with doxazosin is contraindicated. When using tadalafil healthy volunteers who took doxazosin (4-8 mg/day), alfa1-adrenoblokator, there was an increase in the hypotensive effect of doxazosin. Some patients experienced symptoms associated with decreased blood PRESSURE, including fainting.

Simultaneous reception of riociguat with inhibitors of PDE-5, including tadalafil, are contraindicated since riociguat enhances the hypotensive effect of inhibitors of PDE-5.

Studies of the drug interaction of tadalafil and 5-alpha-reductase inhibitors have not been conducted, while taking them, caution should be exercised.

Tadalafil causes an increase in the bioavailability of ethinyl estradiol when taken orally. A similar increase in bioavailability can be expected when taking terbutaline, but the clinical consequences are not established.

Tadalafil did not affect the concentration of alcohol, nor did alcohol affect the concentration of tadalafil. At high doses of alcohol (0.7 g/kg), tadalafil did not cause a statistically significant decrease in the average blood PRESSURE. Some patients had postural dizziness 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 arose with the same frequency as when taking one alcohol.

Tadalafil has no clinically significant effect on the pharmacokinetics or pharmacodynamics of theophylline.

Dosage and administration

Inside.

Erectile dysfunction. For patients with frequent sexual activity (more than 2 times / week): the recommended frequency of reception — daily, 1 time a day, 5 mg, at the same time, regardless of food intake. The daily dose can be reduced to 2.5 mg (1/2 table. 5 mg) depending on individual sensitivity. For patients with infrequent sexual activity (less than 2 times/week): recommended drug Tadalafil at a dose of 20 mg, just before sexual activity according to the description. The maximum daily dose of Tadalafil is 20 mg.

BPH or erectile dysfunction/BPH. The recommended dose of Tadalafil when used once a day is 5 mg; the drug should be taken at about the same time of the day, regardless of the time of sexual activity. The duration of treatment is determined by the doctor individually.

Renal failure. In patients with renal insufficiency light (Cl creatinine from 51 to 80 ml/min) and moderate severity (Cl creatinine from 31 to 50 ml/min) dose adjustment is not required. In patients with severe renal insufficiency (creatinine Cl <30 ml/min and hemodialysis), the use of Tadalafil-CZ is contraindicated.

Overdose

Symptoms: with a single appointment to healthy volunteers tadalafil at a dose of up to 500 mg and patients with erectile dysfunction repeatedly, up to 100 mg/day, the undesirable effects were the same as with lower doses.

Treatment: symptomatic. In hemodialysis tadalafil practically displayed.

Special instruction

Sexual activity has a potential risk for patients with cardiovascular disease. Therefore, treatment of erectile dysfunction, including tadalafil, should not be carried out in men with such heart diseases, in which sexual activity is not recommended.

There are reports of priapism in the use of PDE-5 inhibitors, including tadalafil. Patients should be informed of the need for immediate medical attention in the event of an erection lasting 4 hours or more. Untimely treatment of priapism leads to damage to the tissues of the penis, resulting in irreversible impotence.

The safety and efficacy of the combination of Tadalafil with other PDE-5 inhibitors and erectile dysfunction treatments have not been studied. Therefore, the use of such combinations is not recommended.

Like other PDE - 5 inhibitors, tadalafil has systemic vasodilating properties, which can lead to a transient decrease in blood PRESSURE. Before prescribing Tadalafil, doctors should carefully consider whether patients with cardiovascular disease will not be exposed to undesirable effects due to such vasodilating effects.

NAPION is the cause of visual impairment, including complete loss of vision. There are rare post-marketing reports of cases of NAPION, time-related receiving PDE-5 inhibitors. Currently, it is impossible to determine whether there is a direct relationship between the development of NAPION and taking PDE-5 inhibitors or other factors. Doctors should recommend patients to stop taking tadalafil and seek medical help in case of sudden loss of vision. Doctors should also inform patients that people who have had NAPION have an increased risk of re-development of NAPION.

Patients with a suspected diagnosis of BPH should be screened to rule out prostate cancer.

The efficacy of Tadalafil in patients undergoing surgery on the pelvic organs or radical neuro-sparing prostatectomy is unknown.

Influence on the ability to drive vehicles, mechanisms. During treatment with Tadalafil, caution must be exercised when driving and engaging in other potentially dangerous activities that require increased concentration and speed of psychomotor reactions.

Form release

Film coated tablets, 5 mg, 20 mg. 10 or 14 table. (dosage 5 mg) or 4, 7, 8 or 10 tables. (dosage 20 mg) in a contour cell package. 20 table. in a polymeric-type BP of HDPE with LDPE lid or vial polymer of HDPE with LDPE lid. Each jar, bottle (dosage 5 and 20 mg), 2, 3, 6 contour cell packs of 10 tables. or 1, 2 contour cell packs of 14 pills. (dosage 5 mg), or 1 contour cell package of 4, 7, 8, 10 tables., or 2 contour cell packages of 10 tables. (dosage 20 mg) placed in a cardboard box.

Manufacturer

JSC "North star", Russia.

The legal address of the manufacturer: 111141, Moscow, Green Avenue 5/12, p.1.

Address of the manufacturer: 188663, Russia, Leningradskaya obl., Vsevolozhskiy R-n, Kuz'molovskoe urban settlement Kuzmolovsky settlement building, shop No. 188, korp. 2, 3.

Phone / Fax: (812) 309-21-77.

Name and address of the organization authorized to accept claims from the consumer: JSC "North star", Russia.

Storage conditions of tadalafil

In a dark place, at a temperature not exceeding 25 °C.

Keep out of reach of children.

Shelf life of Tadalafil

3 years.

Do not use after the expiration date specified on the package.