Cialis pills 20mg, 1pc

Composition

1 film-coated tablet contains:

Active ingredient:

tadalafil 20 mg;

excipients:

lactose monohydrate;

lactose monohydrate (spray dried);

giprolose;

giprolose (extra thin);

sodium lauryl sulfate;

microcrystalline cellulose”;

MCC;

croscarmellose sodium;

magnesium stearate (vegetable);

film shell:

Opadry Yellow (Y-30-12863-A) (lactose monohydrate, hypromellose, titanium dioxide, triacetin, iron oxide yellow dye)

Pharmacological action

Tadalafil 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 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 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, 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 sBP and dBP in comparison with 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, LH and FSH when taking tadalafil compared to placebo.

The efficacy and safety of Cialis (in doses of 2.5 mg and 5 mg) was studied in clinical trials. There was an improvement in erections in patients with erectile dysfunction of all degrees of severity when taking tadalafil once a day. In studies of the primary efficacy of tadalafil 5 mg,62% and 69% of sexual intercourse attempts were successful, compared to 34% and 39% of patients taking placebo. Taking tadalafil at a dose of 5 mg significantly improved erectile function within 24 hours between doses.

The mechanism of action of tadalafil in patients with BPH is inhibition of PDE-5 by tadalafil, which leads to an increase in the concentration of cGMP in the penile cavernosa, 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 plasma Cmax is reached on average 2 hours after oral use. The rate and degree of absorption of tadalafil do not depend on food intake, so Cialis can be used regardless of food intake. The time of use (morning or evening) had no clinically significant effect on 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 AUC increases proportionally to the dose.

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

Distribution. Css in plasma is achieved within 5 days when taking the drug 1 time a day.

The average Vd 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.

In healthy individuals, 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.

Output. In healthy individuals, the average oral clearance of tadalafil is 2.5 l / h, and the average T1 / 2 is 17.5 h. Tadalafil is mainly excreted as inactive metabolites, mainly in the faeces (about 61% of the dose) and to a lesser extent in the urine (about 36% of the dose).

Special population groups

Elderly patients. Healthy elderly patients (65 years and older) had a lower oral clearance of tadalafil, which resulted in a 25% increase in AUC compared to healthy individuals aged 19 to 45 years. This difference is not clinically significant and does not require dose adjustment.

Patients with renal insufficiency. No dose adjustment is required in patients with mild to moderate renal insufficiency. Due to the increased exposure of tadalafil (AUC), patients with severe renal insufficiency are not recommended to use Cialis.

Patients with hepatic insufficiency. The pharmacokinetics of tadalafil in patients with mild to moderate hepatic insufficiency are comparable to those in healthy individuals. No data are available for patients with severe hepatic insufficiency (Child-Pugh class C). When prescribing Cialis 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 patients with diabetes mellitus treated with tadalafil, the AUC was approximately 19% lower than in healthy individuals. This difference does not require dose adjustment.

Indications

• erectile dysfunction (ED);
• lower urinary tract symptoms in patients with benign prostatic hyperplasia;
• erectile dysfunction in patients with lower urinary tract symptoms associated with benign prostatic hyperplasia.

Use during pregnancy and lactation

Cialis is not intended for use in women.

Contraindications

• hypersensitivity to tadalafil or any substance included in the composition of the drug Cialis;
• medicines containing any organic nitrates;
• used by persons under 18 years of age;
• the presence of contraindications to sexual activity in patients with diseases of the SSS (myocardial infarction within the last 90 days, unstable angina, occurrence of angina during sexual intercourse, chronic heart failure II–IV class NYHA classification, uncontrolled arrhythmias, hypotension (BP less than 90/50 mm Hg. St. ), uncontrolled hypertension, ischemic stroke within the last 6 months);
• vision loss due to partiranno of the anterior ischemic optic neuropathies (regardless of the context of inhibitors PDE-5);
• simultaneous reception of doxazosin, as well as drugs for the treatment of erectile dysfunction;
• frequent (more than 2 times per week) use in patients with chronic renal insufficiency (Cl creatinine
• lactase deficiency, lactose intolerance, glucose-galactose malabsorption.

Caution: Since there are no data available for patients with severe hepatic insufficiency (Child-Pugh Class C), caution should be exercised when prescribing Cialis to this group of patients.

Caution should be exercised when prescribing Cialispatients taking alpha-1-blockers, since simultaneous use may lead to symptomatic hypotension in some patients.In a clinical pharmacology study,18 healthy volunteers who received a single dose of tadalafil did not experience symptomatic hypotension with simultaneous use of tamsulosin alpha-1 A-blocker (see “Interaction”).

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

Cialis should be used with caution in patients with a predisposition to priapism (sickle cell anemia, multiple myeloma, or leukemia) or with an anatomical deformity of the penis (angular curvature, cavernous fibrosis, or Peyronie’s disease). Caution should also be exercised when taking concomitantly with powerful inhibitors of the CYP3A4 isoenzyme (ritonavir, saquinavir, ketoconazole, itraconazole, erythromycin), antihypertensive agents.

Side effects

The most common adverse events in patients with ED are headache and dyspepsia, as well as back pain, myalgia, flushes of blood to the face, and nasal congestion.

The most common adverse events in patients with ED/BPH are headache and dyspepsia, pain in the extremities, gastroesophageal reflux, and myalgia.

From the immune system:infrequently (≥0.1%,

Nervous system disorders: very common (≥10%) – headache; often (≥1%,1, transient ischemic attacks 1, migraine 3, epileptic seizure, transient amnesia.

From the side of the visual organs: infrequently (≥0.1%,3, retinal vascular occlusion).

Hearing disorders and labyrinth disorders: rare (≥0.01%,2.

From the cardiovascular system: infrequently (≥0.1%,3, unstable angina).

Respiratory system disorders:infrequently (≥0.1%,

From the gastrointestinal tract:frequently (≥1%,

Skin and subcutaneous tissue disorders: infrequently (≥0.1%,3, exfoliative dermatitis).

Musculoskeletal and connective tissue disorders:frequently (≥1%,

Genital and breast disorders: rare (≥0.01%,3.

Common disorders: Infrequently (≥0.1%,1; rarely (≥0.01%,3, sudden cardiac death

).1 Observed in patients with previous 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.

2 Sudden hearing loss has been reported in a small number of cases from post-marketing and clinical studies with all PDE-5 inhibitors, including tadalafil.

3 Adverse reactions detected in post-marketing studies that were not observed in clinical placebo-controlled studies.

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/day) increases the AUC of tadalafil in a single dose by 312% and Cmax by 22%, and ketoconazole (200 mg/day) increases the AUC of tadalafil in a single dose by 107% and Cmax by 15% relative to the AUC and Cmax values for tadalafil alone. Ritonavir (200 mg twice daily), an inhibitor of the CYP3A4,2C9,2C19 and 2D6 isoenzymes, increases the AUC of tadalafil in a single dose 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 inhibitors of the CYP3A4 isoenzyme, such as erythromycin and itraconazole, increase the activity of tadalafil.

A selective inducer of the CYP3A4 isoenzyme, rifampicin (600 mg/day), reduces the exposure of a single dose of tadalafil (AUC) by 88% and Cmax by 46% relative to the AUC and Cmax values for tadalafil alone. It can be assumed that the simultaneous use of other inducers of the CYP3A4 isoenzyme should also reduce the concentration of tadalafil in plasma.

Concomitant use of an antacid (magnesium hydroxide/aluminum hydroxide) and tadalafil reduces the rate of absorption of tadalafil without changing the area under the pharmacokinetic curve 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 have not been studied, so the use of such combinations is not recommended.

Tadalafil does not potentiate the increase in bleeding time caused by taking acetylsalicylic acid.

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 (NO) 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 pharmacokinetics of S-warfarin or R-warfarin. Tadalafil does not affect the effect of warfarin on PV.

Tadalafil does not increase the duration of bleeding caused by acetylsalicylic acid.

Tadalafil has systemic vasodilating properties and may enhance the effect of antihypertensive drugs aimed at lowering blood pressure.

Additionally, patients who took several antihypertensive agents and whose arterial 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 symptoms. Patients receiving antihypertensive medications and taking tadalafil should be given appropriate clinical recommendations.

There was no significant reduction in blood pressure when using tadalafil in healthy individuals taking the selective alpha-1 A-blocker tamsulosin based on the results of two clinical studies.

Concomitant use of tadalafil with doxazosin is contraindicated. When using tadalafil in healthy volunteers taking doxazosin (4-8 mg/day), an alpha-1-blocker, an increase in the hypotensive effect of doxazosin was observed. Some patients experienced symptoms associated with a decrease in blood pressure, including fainting.

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), a decrease in blood pressure was not 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

Use of Cialis as indicated by ED. For patients with frequent sexual activity (more than 2 times 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 depending on individual sensitivity.

For patients with infrequent sexual activity (less than 2 times a week): it is recommended to prescribe Cialis 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 Cialis is 20 mg.

Use of Cialis for BPH or ED / BPH indications. The recommended dose of Cialis once daily 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 (Cl creatinine), the use of Cialis 1 time per day is not recommended.

Overdose

When tadalafil was administered once to healthy individuals at a dose of up to 500 mg and in patients with ED — repeatedly up to 100 mg/day, the undesirable effects were the same as when using 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 ED, including Cialis, should not be performed 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 Cialis with other PDE5 inhibitors and ED treatments 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 Cialis, doctors should carefully consider whether patients with cardiovascular disease will be exposed to undesirable effects due to such vasodilating effects.

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 Cialis in patients undergoing pelvic surgery or radical neuroprotective prostatectomy is unknown.

Influence on the ability to drive a car and perform work that requires an increased rate of psychomotor reactions. Despite the fact that the frequency of dizziness with placebo and tadalafil is the same, during treatment, caution should be exercised when driving vehicles and engaging in other potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.

Form of production

Film-coated tablets

Storage conditions

At a temperature not exceeding 30 °C

Shelf life

3 years

Active ingredient

Tadalafil

Conditions of release from pharmacies

By prescription

Dosage form

Tablets