Cialis – drug for treatment of erectile dysfunction (erection disorders). Causes relaxation of penile arteries and increases blood flow to the tissues of the penis, resulting in and an erection.

Latin name:
Cialis / Cialis.

The composition and the form of:
Cialis tablets, coated tablets, for 1, 2, 4 or 8 pieces. in the package.
1 tablet contains 20 mg of Cialis tadalafil.

Active-active substance:
Tadalafil / Tadalafil.

Properties / Action:
Cialis (tadalafil) is an effective, reversible, selective inhibitor of specific phosphodiesterase type 5 (PDE5), cyclic guanosine monophosphate (cGMP). When sexual stimulation causes local release of nitric oxide, inhibition of PDE5 tadalafil leads to higher levels of cGMP in the cavernous body of penis. The result is relaxation of smooth muscles of arteries and blood flow to the tissues of the penis that causes erections. Tadalafil has no effect in the absence of sexual stimulation.
Studies in vitro have shown that tadalafil is a selective inhibitor of PDE5. PDE5 is an enzyme found in corpus cavernosum smooth muscle, in vascular smooth muscle internal organs, skeletal muscle, platelets, kidney, lung and cerebellum. Effects of tadalafil for PDE5 is more active than other phosphodiesterase. Tadalafil is 10 000 times more potent for PDE5 than for FDE1, FDE2 and FDE4, which are located in the heart, brain, blood vessels, liver and other organs. Tadalafil 10 000 times more active blocks PDE5 than FDE3 – an enzyme that is found in the heart and blood vessels. This selectivity for PDE5 compared with FDEZ is important, because FDEZ an enzyme involved in reduction of the heart muscle. In addition, tadalafil about 700 times more active against PDE5 than against FDE6 discovered in the retina and is responsible for fotoperedachu. Tadalafil also shows the action of 10 000 times more potent for PDE5 compared to its effect on FDE7 – FDE10.
Tadalafil improves erection and the possibility of successful sexual intercourse. The drug acts within 36 hours. The effect is manifested even after 16 minutes after taking the drug in the presence of sexual arousal.
Tadalafil in healthy individuals does not cause reliable changes in systolic and diastolic blood pressure compared with placebo in the prone position (mean maximum decrease of 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 reliable changes in heart rate.
Tadalafil does not cause changes in recognition colors (blue / green), due to its low affinity to FDEb. In addition, no observed effect on visual acuity tadalafil, elektroretinogrammu, intraocular pressure and pupil size.
In the study of tadalafil in men in a daily dose of 10 mg found no clinically significant effect on the drug quantity and concentration of sperm motility and morphology of spermatozoa.

Pharmacokinetics:
After taking Cialis tadalafil is rapidly absorbed into. Average maximum concentration (Smax) in plasma is reached after an average of 2 hours after ingestion.
The speed and extent of absorption of tadalafil is not dependent on food intake, therefore, Cialis can be taken without regard to meals. Hours (morning or evening) had no clinically significant 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 of 2, 5 to 20 mg of the area under the curve concentration-time “(AUC) increased in proportion to dose. Equilibrium plasma concentrations are reached within 5 days while taking the drug once a day.
The pharmacokinetics of tadalafil in patients with erectile dysfunction is similar pharmacokinetics in patients without erectile dysfunction.
The average volume of distribution is about 63 liters, which points to the fact that Tadalafil is distributed in the tissues of the body. In therapeutic concentrations, 94% of tadalafil in plasma is associated with protein-mi. Protein binding is not altered by impaired renal function.
In healthy persons less than 0, 0005% of the administered dose found in semen.
Tadalafil is mainly metabolized with isoenzyme (CYP) 3A4 cytochrome P450. The main circulating metabolite is metilkateholglyukuronid. This metabolite of at least 13000 times less active against PDE5 than Tadalafil. Hence, one can hardly assume that this metabolite in the observed concentrations is clinically significant.
In healthy individuals the average clearance of tadalafil ingestion of 2, 5 liters / hour, and the average half-life – 17, 5 hours. Tadalafil appears mainly as inactive metabolites, mainly in the faeces (about 61% of the dose) and, to a lesser extent, with urine (about 36% of the dose).
Healthy elderly (65 years and over) had a lower clearance of tadalafil when taken orally, which was reflected in the increase in area under the curve concentration-time “by 25% compared with healthy people aged 19 to 45 years. This distinction is not clinically significant and does not require selection of the dose.
In subjects with mild (creatinine clearance 51 – 80 ml / min) or moderate (kreatinina31-clearance 50 ml / min) renal insufficiency area under the curve concentration-time was greater than in healthy individuals. In subjects with severe renal insufficiency (creatinine clearance 30 ml / min) Tadalafil has not been studied (see “Special warnings and precautions for use”).
The pharmacokinetics of tadalafil in patients with low and moderate hepatic insufficiency comparable to that in healthy individuals. In these patients, titration is not required.
Patients with diabetes against the background of tadalafil area under the curve “concentration-time was less than about 19% than in healthy individuals. This distinction does not require the selection of the dose.

Indications:
Cialis is indicated for erectile dysfunction.

Dosage and administration:
Cialis are inside.
Application Cialis middle-aged men
The recommended dose of Cialis is 20 mg. Cialis taken before anticipated sexual activity, regardless of the meal. Cialis should be taken at least 16 minutes prior to the alleged sexual activity.
Patients may attempt to carry out a sexual act at any time within 36 hours after taking Cialis in order to establish the optimal response time to receive the drug.
The maximum recommended frequency of admission – once a day.
Application of Cialis in older men
For elderly patients a special dosage is not required. Recommendations for acceptance specified in the section “Use of middle-aged men” apply to elderly patients.
Application of Cialis in men with impaired renal function and liver
For patients with impaired renal function (creatinine clearance 30 ml / min) and liver of a special selection of dose is not required (see “Special warnings and special precautions for use”).
Application Cialis children
Cialis does not apply for persons under 18 years.

Overdose:
With the appointment of a single healthy person tadalafil at a dose of 500 mg and patients with erectile dysfunction – many times up to 100 mg / day., Adverse effects were the same as the use of lower doses. In case of overdose is necessary to standard symptomatic treatment.

Contraindications:
# Set hypersensitivity to tadalafil or to any substances in the composition of Cialis;
# In case of taking the drugs containing any organic nitrates;
# Use by persons under 18 years.

Use during pregnancy and lactation:
Cialis is not intended for use in women.

Side effects:
The most frequently reported adverse events were headache and dyspepsia (11 and 7% of cases, respectively). Adverse events associated with taking tadalafil were generally small or medium degree of severity, transient and diminish with continued use of the drug.
Other common adverse effects include back pain, myalgia, nasal congestion and “tides” of blood to the face.
Seldom – swelling of the eyelids, eye pain, hyperemia of the conjunctiva and dizziness.

Precautions and special instructions:
Since there is no evidence of controlled clinical studies on safety and efficacy of Cialis in the following groups of patients:
# Patients with severe renal insufficiency (creatinine clearance 30 ml / min)
# Patients with severe hepatic insufficiency, such patients the drug should be prescribed with caution.
Sexual activity is a potential risk for patients with cardiovascular diseases. Therefore, treatment of erectile dysfunction, including those using Cialis, you should not hold for men with heart disease, in which sexual activity is not recommended.
Keep in mind the potential risk of complications in sexual activity in patients with cardiovascular diseases:
# Myocardial infarction in the last 90 days;
# Unstable angina or angina occurring during sexual intercourse;
# Heart failure class 2 and higher NYHA, evolved in the past 6 months;
# Uncontrolled cardiac arrhythmia, hypotension (blood pressure of <90/50 mm Hg. St.) Or uncontrolled hypertension;
# Stroke brought forward during the last 6 months.
Cialis should be used with caution in patients with predisposition to priapism (eg sickle-cell anemia, multiple myeloma or leukemia), or in patients with anatomical deformation of the penis (eg, angular distortion, cavernous fibrosis or Peyronie’s disease).
There are reports of occurrence of priapism using another PDE5 inhibitor – sildenafil, although while taking Cialis are not reported cases of priapism. Patients should be informed of the need for immediate access to medical care in the event of an erection that lasted 4 hours and more. Delays in treatment of priapism leads to tissue damage of the penis, resulting in a loss may occur long-term potency.
Safety and efficacy of a combination of Cialis with other treatments violations erectile function was not studied. Therefore, the use of such combinations is not recommended.
Against the background of treatment of Cialis in patients with renal insufficiency moderately (creatinine clearance 31 -50 mL / min) is more frequent adverse event, as back pain, compared with patients with poor renal impairment (creatinine clearance 51-80 ml / min) or healthy individuals. In patients with severe renal impairment (creatinine clearance 30 ml / min) Tadalafil has not been studied. Cialis should be used with caution in patients with creatinine clearance 50 ml / min.

Drug Interactions:
Influence of other drugs on Cialis (tadalafil):
Tadalafil is mainly metabolized with the participation of the enzyme CYP3A4. Selective inhibitor of CYP3A4, ketoconazole, increases the area under the curve concentration-time “at 107%, and rifampicin, it reduces by 88%.
Despite the fact that the specific interactions have not been studied, one can assume that protease inhibitors such as ritonavir and saquinavir, as well as inhibitors of CYP3A4, such as erythromycin and itraconazole increases the activity of tadalafil.
Simultaneous treatment with an antacid (magnesium and aluminum hydroxide) and tadalafil reduce the rate of absorption of tadalafil without altering the area under the pharmacokinetic curve for tadalafil.
Increasing the pH of the stomach as a result of receiving H2-antagonist nizatidina, had no influence on the pharmacokinetics of tadalafil.
Effect of Cialis (tadalafil) on other drugs:
Know that Tadalafil increases the hypotensive effect of nitrates (nitroglycerin, isosorbide dinitrate, isosorbide mononitrate). This is a result of the additive action of nitrates and tadalafil on the metabolism of nitric oxide and cGMP. Therefore, the use of Cialis on a background of nitrates is contraindicated.
Cialis no clinically significant effect on clearance of drug metabolism that takes place with the participation of cytochrome P450 isoenzyme. Studies have confirmed that Tadalafil does not inhibit or induce isozymes CYP3A4, CYP1A2, CYP2D6, CYP2E1 and CYP2C9.
Tadalafil has no clinically significant effect on the pharmacokinetics of S-warfarin or R-warfarin. Tadalafil does not affect the action of warfarin on prothrombin time.
Tadalafil does not increase the duration of bleeding caused by acetylsalicylic acid.
Tadalafil does not show a clinically significant interaction with the major classes of antihypertensive agents, including calcium channel blockers (amlodipine), angiotensin converting enzyme inhibitors (enalapril), beta-blockers adrenergic receptors (metoprolol), alpha-blockers, thiazide diuretics (bendoflyuazid) and angiotensin II receptor blockers used in different doses as monotherapy or in combination. Revealed no differences in adverse events in patients taking Tadalafil in combination with antihypertensive drugs or without them.
There is no evidence the influence of single dose of tadalafil on the concentration of alcohol in the blood, the influence of alcohol on cognitive function and blood pressure. In addition, there was no changes in the level of concentration of tadalafil in the blood 3 hours after his admission, in combination with alcohol.
Tadalafil has no clinically significant effect on the pharmacokinetics or pharmacodynamics of theophylline.

Effect on ability to drive a car and work with the arrangements:
No special requirements.

Storage:
Store at temperatures below 30 ° C in the original packaging.
Keep out of reach of children.
Shelf life 2 years. Do not use later than the date specified on the package.
Conditions of supply of pharmacies – a doctor’s prescription.
Cialis – Information for patients:

What is Cialis?
Cialis – drug for treatment of erectile dysfunction. Cialis belongs to a class of inhibitors of the enzyme phosphodiesterase-5. Its action is based on a selective and effective blockade of phosphodiesterase-5, which promotes relaxation of smooth muscle cells and increase blood flow to the penis. Cialis treats erectile dysfunction by increasing blood flow to the penis, with the appropriate sexual arousal.
Cialis is used for treating erectile dysfunction of any degree of severity. It is recommended to apply orally at a dose of 20 mg prior to anticipated sexual activity, regardless of concomitant food intake or alcohol.
Currently Cialis – the only inhibitor of phosphodiesterase-5, the effect of which persists more than a day – up to 36 hours. It is important to note that an erection occurs only when sexual initiation. This will allow couples do not plan their sexual relations and not to abandon the habitual rhythm of life. Taking the drug in the morning, take advantage of its effect can be in the evening.
Cialis is already well established in Europe, Australia and New Zealand. The first countries where the drug appeared, were Britain, Denmark, Finland, Sweden and Germany.
To date, over 4000 men have participated in more than 60 clinical studies have proven efficacy and safety of the drug. Cialis improved erectile function in 81% of men and showed good tolerability.
Cialis has a positive effect on the following manifestations and consequences of erectile dysfunction:

* Erection in general;
* Ability to achieve an erection sufficient for sexual intercourse;
* Ability to maintain an erection during sexual intercourse;
* Getting satisfaction from sexual intercourse;
* Positive emotions;
* Satisfaction of a good erection;
* Confidence in the ability to achieve and maintain an erection;
* Addressing the partner of a sexual act;
* Because Cialis has a prolonged effect, men can now not to think constantly about taking it.

Why Cialis?
Cialis has a high efficiency, which not only improves the erection but also helps the patient regain the naturalness of sexual relations. Cialis is reliable, efficient, convenient to use and safe, it restores the normal sexual life for patients suffering from erectile dysfunction, freeing them from the constant thoughts about treatment.
For a certain number of patients the clinical effect starts within 16 min. after taking Cialis and lasts 36 hours.
Cialis, which is taken as needed, up to once a day, improves erectile function in most men suffering from erectile dysfunction of any degree.

What are the treatments for erectile dysfunction are most common?
There are various methods. Oral medications penialnye injections, vacuum erector and implants can help with erectile dysfunction. The sexual or psychological counseling may be useful in erectile dysfunction of psychogenic type.