Cialis pills 20mg, 4pcs

Composition

1 film-coated tablet contains:  

Tadalafil 20 mg.

Auxiliary substances:  

Lactose monohydrate

Hyprolose (hydroxypropylcellulose)

Croscarmellose Sodium

Microcrystalline cellulose

Magnesium Stearate

Sodium Lauryl Sulfate

Shell composition:

opadry II yellow – lactose monohydrate, hypromellose, titanium dioxide, triacetin, iron oxide yellow dye.

Pharmacological action

Pharmacodynamics

Tadalafil is a reversible selective inhibitor of cyclic guanosine monophosphate (cGMP) specific phosphodiesterase type 5 (PDE-5).

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, electrorstinogram, 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.

Reduced 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.

The efficacy and safety of Cialis® (in doses of 2.5 mg,5.0 mg) has been 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 5 mg tadalafil,62% and 69% of sexual intercourse attempts were successful, compared to 34% and 39% of patients taking placebo. Taking 5 mg of tadalafil significantly improved erectile function within 24 hours between doses.

Pharmacokinetics

Suction

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

The rate and degree of absorption of tadalafil does not depend on the intake of pish, so Cialis® can be used regardless of the intake of pish.

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 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 individuals 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 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.

Deduction

In healthy individuals, 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 in the faeces (about 61% of the dose) and, to a lesser extent, in the urine (about 36% of the dose).

Indications

Erectile dysfunction.

Use during pregnancy and lactation

Cialis® is not intended for use in women.

Contraindications

• Hypersensitivity to tadalafil or to any substance that is part of the drug;
• In the case of taking drugs containing any organic nitrates;wbr>Use in persons under 18 years of age;
• 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 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;
• Loss of vision due to non-arterial anterior ischemic neuropathy of the optic nerve (regardless of the connection with the use of PDE-5 inhibitors);
• Concomitant use of doxazosin, as well as medications for the treatment of erectile dysfunction;
• Frequent (more than 2 times a week) use in patients with chronic renal failure (creatinine clearance less than 30 ml / min);
• lactose deficiency, lactose intolerance, glucose-galactose malabsorption.
• With 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 Cialis® to patients. patients taking alpha-1 blockers, as concomitant 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, an alpha-1A-blocker (see “Interaction with other drugs”).

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 in patients with 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

Side effects are usually minor or moderate in severity, transient and decrease with continued use of the drug.

Most often:  

headache (11%)

• dyspepsia (7%)

• Possible:  

back pain

• myalgia

• nasal

• congestion hot flashes to the face

• Rarely:  

swelling of the eyelids

• pain in the eyes

• conjunctival hyperemia

• dizziness

• Very rare:  

• hypersensitivity reactions (including rash, urticaria and facial edema, Stevens-Johnson syndrome and exfoliative dermatitis)

• arterial hypotension (in patients who have already taken antihypertensive drugs)

• hypertension and syncope

• abdominal pain and gastroesophageal reflux

• hyperhidrosis (excessive sweating)

• priapism and delayed erection, blurry vision

• non-arterial anterior ischemic neuropathy of the optic nerve

• retinal vein occlusion

• visual field impairment

From the cardiovascular system: 

• in patients with cardiovascular risk factors – myocardial infarction

• sudden cardiogenic death

• stroke, chest pain

• palpitations and tachycardia

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.

Interaction

Effect of other drugs on tadalafil

Tadalafil is mainly metabolized by the CYP3A4 isoenzyme. The selective CYP3A4 isoenzyme inhibitor ketoconazole (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 the AUC and Cmax values for tadalafil alone.

Ritonavir (200 mg twice daily), an inhibitor of the nsoenzymes CYP3A4,2C9,2C19 and 2D6, increases the exposure to 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 inhibitors of the CYP3A4 isoenzyme, such as erythromycin and intraconazole, 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 nizatidine H2-histamine receptor blockers 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 II (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 prothrombin time.

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 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 use of tadalafil by individuals taking the selective alpha-1A-blocker tamsulosin.

Concomitant use of tadalafil with doxazosin is contraindicated. When using tadalafil in healthy volunteers taking doxazosin (4-8 mg per day), an alpha-1-blocker, an increase in the hypotensive effect of doxazosin was observed. Some patients experienced dizziness. No fainting spells were observed. The use of doxazosin in lower doses has not been studied.

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 hyperthyroidism. 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.

• 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 depending on individual sensitivity.
• For patients with infrequent sexual activity (less than twice 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.

Maximum daily dose of Cialis® it is 20 mg.

Overdose

When tadalafil was administered once to healthy individuals 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. 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 Cuavtc9, 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 treatments for disorders 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®, physicians 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.

Despite the fact that the frequency of dizziness with placebo and tadalafil is the same, caution should be exercised during treatment when driving vehicles and engaging in other potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.

The efficacy of Cialis® in patients undergoing pelvic surgery or radical neuroprotective prostatectomy is unknown.

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