Tadalafil-SZ pills 5mg, 28pcs

Composition

1 film-coated tablet contains:

dosage 5 mg:

Active ingredient:  

tadalafil-5 mg

excipients (core):  

Lactose monohydrate (milk sugar) – 53,8 mg; lactose monohydrate (lectores) (milk sugar) – 64,0 mg; cellulose microcrystalline – 26.0 mg; croscarmellose sodium (Primerose) – 12.5 mg; crospovidone (Kollidon CL-M) – 4,0 mg crospovidone (Kollidon CL) and 3.0 mg hyprolose extra fine (hydroxypropylcellulose over) – 3.0 mg; of hyprolose (hydroxypropyl cellulose) – 2.0 mg; sodium fumarate – 1.5 mg; sodium lauryl sulfate 0.2 mg;

auxiliary substances (shell):  

Opadray II 85F22048 yellow-5 mg (polyvinyl alcohol, partially hydrolyzed-2.0 mg; titanium dioxide E 171-1.0935 mg; macrogol (polyethylene glycol 3350) – 1.01 mg; talc – 0.74 mg; aluminum varnish based on quinoline yellow dye-0.1505 mg; aluminum varnish based on sunny sunset yellow dye-0.0035 mg; iron oxide (I) yellow dye E 172-0.0015 mg; aluminum varnish based on indigocarmin dye-0.0010 mg); Pharmacological

action

Pharmacodynamics

Tadalafil is a reversible selective inhibitor of specific phosphodiesterase type 5 (PDE-5) cyclic guanosine monophosphate (cGMP). When sexual arousal causes a local release of nitric oxide, inhibition of PDE5 by tadalafil leads to an increase in the concentration of cGMP in the penile cavernosa. The result is a relaxation of the smooth muscles of the arteries and 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 inhibitor of PDE-5. PDE-5 is an enzyme found in cavernous smooth muscle, vascular smooth muscle of internal organs, skeletal muscle, platelets, kidney, lung, and cerebellum.

The effect of tadalafil on PDE-5 is more active than on other phosphodiesterases. 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, white blood cells, skeletal muscle and other organs.

Tadalafil is 10,000 times more active in blocking PDE-5 than PDE-3, an enzyme found in the heart and blood vessels. This selectivity for PDE-5 over PDE-3 is important because PDE-3 is an enzyme involved in heart muscle contraction. In addition, tadalafil is approximately 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 9,000 times more potent against PDE-5 compared to its effects on PDE-8, PDE-9, and PDE-10, and 14 times more potent against PDE-5 compared to PDE-11. The distribution in tissues and physiological effects of PDE-8 – PDE-11 inhibition have not yet been elucidated. Tadalafil improves erection and increases the possibility of a full-fledged sexual intercourse.

Tadalafil in healthy subjects does not cause significant changes in systolic and diastolic blood pressure compared to placebo in the supine position (the average maximum decrease is 1.6/0.8 mm Hg, respectively) and in the standing position (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 explained by its low affinity for PDE-6. In addition, tadalafil does not affect visual acuity, electroretinogram, intraocular pressure and pupil size.

Several studies have been conducted to evaluate the effect of daily tadalafil on spermatogenesis. No adverse effects on sperm morphology and motility were observed in any of the studies.

One study found a decrease in the average sperm count compared to placebo. A 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, testosterone, luteinizing hormone and follicle-stimulating hormone when taking tadalafil compared to placebo.

There was an improvement in erectile function in patients with erectile dysfunction of all degrees of severity when taking tadalafil once a day. Mechanism of action in patients with benign prostatic hyperplasia (BPH)

Inhibition of PDE-5 by tadalafil, which leads to an increase in the concentration of cGMP in the penile cavernosa, is also observed in the smooth muscles of the prostate, bladder, and blood vessels that supply them.

Relaxation of vascular smooth muscles leads to an increase in blood perfusion in these organs, and, as a result, to a decrease in the severity of BPH symptoms. Relaxation of the smooth muscles of the prostate and bladder can further enhance vascular effects.

Pharmacokinetics

Suction

After oral use, tadalafil is rapidly absorbed. The average maximum concentration (Ctax) in plasma is reached on average 2 hours after oral use.

The rate and degree of absorption of tadalafil do not depend on food intake, so the drug Tadalafil-SZ can be used regardless of food intake. The time of use (morning or evening) does not affect the rate and degree of absorption.

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 area under the concentration-time curve (AUC) increases in proportion to the dose. Steady-state plasma concentrations are reached within 5 days when the drug is taken once a day.

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

Distribution

The average volume of distribution is about 63 liters, which indicates that tadalafil is distributed in the body’s tissues. At 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 semen.

Metabolism

Tadalafil is mainly metabolized by the cytochrome P450 isoenzyme CYP3A4. The main circulating metabolite is methylcatecholglucuronide. This metabolite is at least 13,000 times less active against PDE5 than tadalafil. Therefore, the concentration of this metabolite is not clinically significant.

Deduction

In healthy volunteers, the average oral clearance of tadalafil is 2.5 l / h, and the average elimination half-life is 17.5 hours. Tadalafil is mainly excreted as inactive metabolites, mainly through the intestine (about 61% of the dose) and, to a lesser extent, by the kidneys (about 36% of the dose).

Special patient groups over 65 years

of age Healthy volunteers aged 65 years and older had a lower oral clearance of tadalafil, which was expressed in a 25% increase in the area under the concentration-time curve compared to healthy volunteers aged 19 to 45 years. This difference is not clinically significant and does not require dose adjustment.

Kidney failure

In patients with mild renal insufficiency (creatinine clearance from 51 to 80 ml/min) and moderate renal insufficiency (creatinine clearance from 31 to 50 ml/min), as well as in patients with end-stage renal insufficiency on hemodialysis, tadalafil exposure (AUC) approximately doubled.

In patients undergoing hemodialysis, Ctax was 41% higher compared to healthy volunteers. Elimination of tadalafil by hemodialysis is negligible.

Hepatic insufficiency

The pharmacokinetics of tadalafil in patients with mild to moderate hepatic insufficiency (Child-Pugh class A and B) are comparable to those in healthy volunteers. Data are insufficient for patients with severe hepatic insufficiency (Child-Pugh class C). When prescribing Tadalafil-SZ to patients with severe hepatic insufficiency, it is necessary to conduct a preliminary assessment of the risk and benefit of using the drug.

Patients with diabetes mellitus

In diabetic patients treated with tadalafil, the area under the concentration-time curve was reduced by approximately 19% compared to healthy volunteers. This difference does not require dose adjustment.

Indications

• Erectile dysfunction;
• lower urinary tract symptoms in patients with benign prostatic hyperplasia (for a dosage of 5 mg);
• erectile dysfunction in patients with lower urinary tract symptoms on the background of benign prostatic hyperplasia (for a dosage of 5 mg).

Use during pregnancy and lactation

Tadalafil-SZ is not intended for use in women.

Contraindications

• Hypersensitivity to tadalafil or any substance that is part of the drug;
• taking drugs containing any organic nitrates;
• the presence of contraindications to sexual activity in patients with diseases of the cardiovascular system: myocardial infarction within the last 90 days, unstable angina, occurrence of angina during sexual intercourse, chronic heart failure class II and higher NYHA classification in the last 6 months, uncontrolled arrhythmias, hypotension (BP <90/50 mm Hg. St. ), uncontrolled hypertension, ischemic stroke within the last 6 months;
• loss of vision due to partiranno anterior ischemic optic neuropathy (NATION)
• concomitant use with doxazosin, other PDE-5 inhibitors, other therapies for erectile dysfunction, and guanylate cyclase stimulants such as riociguat;
• chronic renal failure (creatinine clearance <30 ml/min);lactase
• deficiency, lactose intolerance, glucose-galactose malabsorption;
• age up to 18 years.

With caution: severe hepatic insufficiency (Child-Pugh class C) (there are insufficient data for such patients); concomitant use of alpha-1-blockers (concomitant use of these drugs may lead to symptomatic hypotension in some patients; when using a single dose of tadalafil, there is no symptomatic hypotension when used simultaneously with tamsulosin, a selective alpha-1A-blocker (see “Interaction”); predisposition to priapism (when using a single dose of tadalafil). sickle cell anemia, multiple myeloma or leukemia) or anatomical deformity of the penis (angular curvature, cavernous fibrosis or Peyronie’s disease); concomitant use with CYP3A4 isoenzyme inhibitors (including ritonavir, saquinavir, ketoconazole, itraconazole, clarithromycin, erythromycin, grapefruit juice), antihypertensive agents,5-alpha reductase inhibitors. Diagnosis of erectile dysfunction should include identification of the potential underlying cause, appropriate medical examination, and determination of treatment options.

Side effects

The most common adverse events in patients with erectile dysfunction and BPH are headache and dyspepsia, as well as back pain and myalgia. According to the classification WHO all reactions are distributed by organ system and frequency of development: very often (> 1/10); often (>> 1/100, >>< 1/10); infrequently (> 1/1000, < 1/10); infrequently (>< 1/100); rarely (> 1U0000, < 1/100); rarely (>< 11000); very rarely (

Immune system disorders:

Infrequently: hypersensitivity reactions. Rarely: angioedema. Nervous system disorders:

Often: headache. Infrequently: dizziness. Rarely: stroke’ (including acute hemorrhagic cerebrovascular accident), syncope, transient ischemic attacks, migraines, epileptic seizures, and transient amnesia.

Visual disturbances:Infrequently: blurred vision, pain in the eyeball. Rarely: visual field disorders, eyelid swelling, conjunctival hyperemia, non-arterial anterior ischemic optic neuropathy, retinal vascular occlusion.

Hearing disorders and labyrinth disorders:

Infrequently: ringing in the ears. Rarely: sudden hearing loss.

Cardiac disorders:Infrequently: palpitation, tachycardia. Rarely: myocardial infarction, ventricular arrhythmias, unstable angina.

Vascular disorders: Common: “flushes” of blood to the face.

Infrequently: lowering blood pressure, increasing blood pressure. Respiratory, thoracic and mediastinal disorders:

Often: nasal congestion. Infrequently: shortness of breath, nosebleeds. Disorders of the gastrointestinal tract:

Often: dyspepsia. Infrequently: abdominal pain, gastroesophageal reflux, diarrhea in patients over 65 years of age, vomiting, nausea.

Skin and subcutaneous tissue disorders:Infrequently: a rash. Rarely: urticaria, Stevens-Johnson syndrome, exfoliative dermatitis, hyperhidrosis (excessive sweating).

Musculoskeletal and connective tissue disorders:

Often: back pain, myalgia, pain in the extremities. Renal and urinary tract disorders: Infrequent: hematuria.

Genital and breast disorders: Infrequent: prolonged erection. Rarely: priapism, hematospermia, penile bleeding.

Common disorders:Infrequently: chest pain, peripheral edema, fatigue. Rarely: facial edema, sudden cardiac death.

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

Adverse reactions identified with post-marketing use that were not observed in clinical placebo-controlled studies.

More often observed when tadalafil was used in patients already taking antihypertensive agents.

Interaction

Effect of other drugs on tadalafil

Tadalafil is mainly metabolized by the CYP3A4 isoenzyme. A selective inhibitor of the CYP3A4 isoenzyme ketoconazole (400 mg per day) increases the exposure of a single dose of tadalafil (AUC) by 312% and Ctax by 22%, and ketoconazole (200 mg per day) increases the exposure of a single dose of tadalafil (AUC) by 107% and Ctax by 15% relative to the AUC and Ctax values for tadalafil alone.

Ritonavir (200 mg twice daily), an inhibitor of the CYP3A4,2C9,2C19 and 2D6 isoenzymes, increases the exposure to a single dose of tadalafil (AUC) by 124% without changing the Ctax.

Although specific interactions have not been studied, it can be assumed that other HIV protease inhibitors, such as saquinavir, as well as inhibitors of the CYP3A4 isoenzyme, such as erythromycin, clarithromycin, and itraconazole and grapefruit juice, can increase tadalafil concentrations in blood plasma. The role of transporters (e. g., P-glycoprotein) in the distribution of tadalafil is unknown.

There is a possibility of drug interaction mediated by vector inhibition. A selective inducer of the CYP3A4 isoenzyme, rifampicin (at a dose of 600 mg per day), reduces the exposure of a single dose of tadalafil (AUC) by 88% and Ctax by 46%, relative to the AUC and Ctax values for tadalafil alone.

It can be assumed that the simultaneous use of other inducers of the CYP3A4 isoenzyme (such as phenobarbital, phenytoin or carbamazepine) should also reduce the concentration of tadalafil in blood plasma..

Concomitant use of an antacid (magnesium hydroxide/aluminum hydroxide) and tadalafil reduces the rate of absorption of tadalafil without changing the AUC for tadalafil.

An increase in gastric pH as a result of taking the H2-histamine receptor blocker nizatidine did not affect the pharmacokinetics of tadalafil.

The safety and efficacy of combining tadalafil with other treatments for erectile dysfunction or other PDE5 inhibitors have not been studied, so the use of such combinations is not recommended.

Effect of tadalafil on other medications

Tadalafil 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 nitric oxide II (N0) and cGMP. Therefore, the use of tadalafil against the background of taking nitrates is contraindicated.

Tadalafil does not have a clinically significant effect on the clearance of drugs that are metabolized with the participation of cytochrome P450. Studies have confirmed that tadalafil does not inhibit or induce the isoenzymes CYP1A2, CYP3A4, CYP2C9, CYP2C19, CYP2D6, or CYP2E1. Tadalafil has no clinically significant effect on the AUC of S-warfarin or R-warfarin. Tadalafil does not affect the effect of warfarin on prothrombin time.

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

Tadalafil has systemic vasodilating properties and may enhance the effect of antihypertensive drugs aimed at lowering blood pressure. Additionally, patients who took multiple antihypertensive medications and whose hypertension was poorly controlled experienced a slightly greater reduction in blood pressure.

In the vast majority of patients, this decrease was not associated with hypotensive symptoms. Patients receiving antihypertensive medications and taking tadalafil should be given appropriate clinical recommendations. No significant reduction in blood pressure was observed with the simultaneous use of tadalafil and the selective alpha-1 A-blocker tamsulosin in healthy volunteers.

Concomitant use of tadalafil with doxazosin is contraindicated. When using tadalafil in healthy volunteers taking doxazosin (4-8 mg per day), an alpha-beta blocker, an increase in the hypotensive effect of doxazosin was observed. Some patients experienced symptoms associated with lower blood pressure, including fainting.

Concomitant use of riociguat with PDE-5 inhibitors, including tadalafil, is contraindicated, as riociguat increases the hypotensive effect of PDE-5 inhibitors. Drug interaction studies of tadalafil and 5-alpha reductase inhibitors have not been conducted, and caution should be exercised when taking them simultaneously.

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

Tadalafil did not affect the alcohol concentration, nor did alcohol affect the tadalafil concentration. At high doses of alcohol (0.7 g/kg), taking tadalafil did not cause a statistically significant decrease in the average blood pressure. Some patients experienced postural vertigo and orthostatic hypotension.

When taking tadalafil in combination with lower doses of alcohol (0.6 g/kg), no reduction in blood pressure was observed, and dizziness occurred with the same frequency as when taking alcohol alone.

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

How to take, course of use and dosage

For oral use. Use of Tadalafil-SZ for indications of erectile dysfunction (ED)For patients with frequent sexual activity (more than twice a week): the recommended frequency of use is 5 mg daily, once a day, at the same time, regardless of food intake. The daily dose can be reduced to 2.5 mg (1/2 tablet 5 mg) depending on individual sensitivity. For patients with infrequent sexual activity (less than twice a week): it is recommended to prescribe Tadalafil-SZ at a dose of 20 mg, immediately before sexual activity, according to the instructions for medical use of the drug. The maximum daily dose of Tadalafil-SZ is 20 mg. Use of Tadalafil-SZ as indicated by BPH or ED/BPH. The recommended dose of Tadalafil-SZ when used once a day is 5 mg; the drug should be taken at approximately the same time of day, regardless of the time of sexual activity. The duration of treatment is determined by the doctor individually. In patients with mild renal insufficiency (creatinine clearance from 51 to 80 ml/min) and moderate renal insufficiency (creatinine clearance from 31 to 50 ml/min), no dose adjustment is required. In patients with severe renal insufficiency (creatinine clearance: the use of Tadalafil-SZ is contraindicated.

Overdose

When tadalafil was administered once to healthy volunteers 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: in case of overdose, standard symptomatic treatment should be performed. During hemodialysis, tadalafil is practically not excreted.

Special instructions

Sexual activity has a potential risk for patients with cardiovascular diseases. Therefore, treatment of erectile dysfunction, including with the drug Tadalafil-SZ, should not be carried out in men with heart diseases in which sexual activity is not recommended.

Priapism has been reported with PDE5 inhibitors, including tadalafil. Patients should be informed about the need to seek 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, which can lead to irreversible impotence.

The safety and efficacy of the combination of Tadalafil-SZ with other PDE5 inhibitors and treatments for erectile dysfunction have not been studied. Therefore, the use of such combinations is not recommended. Like other PDE5 inhibitors, tadalafil has systemic vasodilating properties, which can lead to a transient decrease in blood pressure.

Before prescribing the drug Tadalafil-SZ, doctors should carefully consider whether patients with cardiovascular disease will be exposed to undesirable effects due to such vasodilating effects. Non-arterial anterior ischemic optic neuropathy (NAPION) is a cause of visual impairment, including complete loss of vision.

There are rare post-marketing reports of cases of NAPION development that are associated with the use of PDE-5 inhibitors.

Currently, it is not possible to determine whether there is a direct relationship between the development of NAPION and the use of PDE5 inhibitors or other factors. Doctors should recommend that patients with sudden vision loss stop taking tadalafil and seek medical attention.

Doctors should also inform patients that people who have had NAPION have an increased risk of developing NAPION again. Patients with a suspected BPH diagnosis should be screened to rule out prostate cancer.

The efficacy of Tadalafil-SZ in patients undergoing pelvic surgery or radical neuroprotective prostatectomy is unknown.

During treatment with Tadalafil-SZ, care should be taken when driving vehicles and engaging in other potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.

Storage conditions

Keep out of the reach of children in a dark place, at a temperature not exceeding 25 °C.

Shelf

life is 3 years.

Active ingredient

Tadalafil

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For men, For adults as prescribed by a doctor

Indications

Erectile Dysfunction