Composition
Active ingredient: Tadalafil.
Each tablette of Cialis preparation contains 20 mg of tadalafil
Auxiliary substances: lactoses monohydrate, sodium croscarmellose, hydroxypropyl cellulose, microcrystalline cellulose, sodium lauryl sulfate, magnesium stearate, a mix of Opadri dyer II, talc.
Description
Yellow tablets, film-covered. The tablets are almond-shaped and bear on one side the inscription “C 20”.
Pharmacological properties
Pharmacodymanics
Tadalafil is effective, reversible selective inhibitor of specific phosphodiesterase type 5 (PDE5) of cyclic guanosine monophosphate (cGMP). When sexual excitation causes local extricating of nitrogen oxydes, inhibition of PDE5 by tadalafil leads to increase of cGMP levels in cavernous body of a sexual member. A consequence of that is relaxation of smooth muscles of arteries and blood inflow to tissues of a sexual member, which causes erection. Tadalafil does not render an effect in absence of sexual stimulation.
Researches in vitro have shown that Tadalafil is a selective inhibitor of PDE5. PDE5 is the enzyme which has been found out in smooth muscles of a cavernous body, in smooth muscles of vasculars of internal organs, in skeletal muscles, thrombocytes, kidneys, lungs and a cerebellum. Action of Tadalafil on PDE5 is more active, than on others of phosphodiesterase. Tadalafil acts 10 000 times more powerfully on PDE5 over PDE1, PDE2 and PDE4 which are localized in heart, brain, blood vasculars, liver and in other organs. Tadalafil 10 000 times more actively blocks PDE5 over PDE3 - enzyme which is found out in heart and blood vasculars. This selectivity concerning PDE5 in comparison with PDE3 has a great value as PDE3 is the enzyme which is taking part in cardiac muscle contracting. Besides, Tadalafil 700 times is more active concerning PDE5 over PDE6, found out in a retina and being responsible for phototransfer. Tadalaphyl also acts 10 000 times more powerfully on PDE5 in comparison with its influence on PDE7 – PDE10..
Tadalafil improves erection and possibility to sexually intercourse successfully. The preparation acts within 36 hours. The effect is shown in 16 minutes after adhibiting of the preparation at presence of sexual excitation.
Tadalafil at healthy persons does not cause authentic fluctuation systolic and diastolic pressure in comparison with placebo in a prone position (average maximum decrease makes 1 6/0, 8 mm hg, accordingly) and in an upright position (average maximum decrease makes 0 2/4, 6 mm hg, accordingly). Tadalafil does not cause authentic fluctuation of frequency of heart contractings. Tadalafil does not cause fluctuations of colour recognition (blue/green) that reveals its low affinity to PDE6. Besides, Tadalafil does not influence on vision acuteness, electroretinogram, intraocular pressure and pupil size.
Tadalafil researches at men in a daily dose of 10 mg did not revealed a clinically significant influence of a preparation on quantity and concentration of sperm, mobility and morphology of spermatozoa
Pharmacokinetics
Resorbtion
After intake Tadalafil is quickly soaked up. Average maximum concentration (Ñmax) in plasma is reached on the average in 2 hours after intake. Speed and degree of resorbtion of Tadalafil do not depend on food intake, therefore preparation CIALYS can be adhibited independently from food intake. Time of intaking (in the morning or in the evening) had no clinically significant effect on the speed and degree of resorbtion. The pharmacokinetics of Tadalafil at healthy persons is linear concerning time and a dose. In the range of doses from 2, 5 to 20 mg the area under a curve "concentration-time" (AUC) is increased proportionally to a dose. Equilibrium of concentration in plasma is reached within 5 days at preparation intake once a day. The pharmacokinetics of Tadalafil at patients with erection dysfunction is similar to pharmacokinetics of the preparation at persons without erection dysfunction.
Tissue distribution
An average volume of tissue distribution makes about 63 of liters, the fact specifying that Tadalafhil is distributed into organism fabrics. In therapeutic concentration as much as 94 % of Tadalafil in plasma are linked with albumens. Linking with albumens is not changed at dysfunction of kidneys.
At healthy persons less than 0, 0005 % of the given dose are revealed in sperm.
Metabolism
Tadalafil is basically metabolized with isoenzyme participation (CYP) 3A4 cytochrome Ð450. The principal circulating metabolyte is metilkateholglyukuronid. This metabolite is at least 13000 times less active against PDE5, than Tadalafil. Hence, it is hardly possible to assume that this metabolyte is clinically significant at observable concentrations.
Clearance
At healthy persons the average clearance of Tadalafil at intake makes 2, 5 l/hour, and the average period of semiclearance - 17, 5 hours. Tadalafil is mainly egested in the form of inactive metabolytes, basically, with feces (about 61 % of a dose) and, to a lesser degree, with urine (about 36 % of a dose).
Special groups of the population
Healthy persons oà elderly age (65 years and over) had lower clearance of Tadalafil at intake which was shown in the area increase under a curve "concentration-time" to 25 % in comparison with healthy persons aged from 19 up to 45 years old. This distinction is not clinically significant and does not require dose selection.
Patients with nephritic insufficiency
At persons with mild (creatinine clearance is 51 - 80 ml/min) or medium severe (clearance of kreatinine 31-50 ml/min) nephritic insufficiency the area under a curve "concentration-time" was wider than that at healthy persons. At persons with severe nephritic insufficiency (clearance of creatinine30 ml/min) Tadalafil was not studied (the section "Special warnings and precautions at application").
Patients with hepatic insufficiency
The pharmacokinetics of Tadalafil at persons with mild and medium severe hepatic insufficiency is comparable with that at healthy persons. Dose selection is not required for such patients.
Patients with a diabetes
At patients with diabetes against application of Tadalafil the area under a curve ""concentration-time" was less approximately to 19 %, than at healthy persons. This difference does not require a dose selection.
Indications to use
Dysfunction of erection
Contra indications
• An established hypersensibility to Tadalafil or to any substance which is a part of a preparation;
• In case of intake of the preparations containing any organic nitrates;
• Application for persons under 18 years.
Safety measures:
As there is no data of clinical researches under control on safety and efficiency of the preparation CIALIS in the following groups of patients:
• patients with severe nephritic insufficiency (clearance of creatinine is 30 ml/min)
• patients with heavy hepatic insufficiency, for such patient the preparation should be prescribed with care.
Way of application and dose
Orally
Application for middle aged men
A recommended dose of the preparation Cialis makes 20 mg. Cialis is adhibited before prospective sexual activity irrespective of food intake. The preparation should be administered at least 16 minutes prior to prospective sexual activity. Patients can have a sexual intercourse attempt any time within 36 hours after preparation intake to establish an optimum time of the reaction for the preparation intake. The maximum recommended frequency of adhibiting - once a day.
Application for elderly men
For elderly patients special selection of a dose is not required. Recommendations on the adhibiting, specified in section "Application for men of middle age" are applicable for elderly patients also.
Application for men with dysfunction of kidneys and liver
For patients with dysfunction of kidneys (creatinine clearance - 30 ml/min) and liver a special matching of a dose is not required (see the section "Special warnings and special precautions at application”).
Application for children
Cialis is not applied at persons under 18 years.
Collateral action
The most often marked undesirable events are a headache and dyspepsia (11 and 7 % of cases, accordingly). The undesirable events connected with Taladafil intake, were as usual insignificant or average on expressiveness degree, full-transistorized and decreased at continuation of the preparation intake. Other routine undesirable effects were pain in the back, myalgia, stufinnes in nose and blood "inflow" to the person. Seldom – baggy eyelids, pain in eyes, conjunctiva hyperemia and dizziness.
Overdose
At unitary prescription to healthy persons of Tadalafil dosed up to 500 mg and to patients with erectile dysfunction - repeatedly up to 100 mg/day, undesirable effects were the same, as at use of lower doses. In case of overdose it is necessary to carry out a standard symptomatic treatment.
Interaction with other medical products
Influence of other preparations on Tadalafil
Tadalafil basically is metabolized with participation of enzyme CYP3A4. Selective inhibitor CYP3A4, ketoconazole, increases the area under a curve "concentration-time" to 107 %, and rifampicin reduces it to 88 %. In spite of the fact that specific interactions were not studied, it is possible to assume that such inhibitors of proteolytic enzymes such as ritonavir and sacvinavir, and also inhibitors CYP3A4, such as erythromycin and intraconasole enhance activity of Tadalanafil. Simultaneous intake of antacid (magnesium hydroxide \aluminium hydroxide) and Tadanafil reduces the speed of resorbtion of Tadanafil without area fluctuation under pharmacokinetik curve for Tadalanafil.. The ðÍ- increase of a stomach as a result of intake of Í2-antagonist nizatidine, did not influence Tadalanafil pharmacokinetics
Influence of Tadalafhil on other preparations
It is known that Tadalafil strengthens action of nitrates. It results from additive action of nitrates and Tadalafil on the metabolism of nitrogen oxides and cGMP. Therefore, use of the preparation Cialis against application of nitrates is counter-indicative.
Cialis does not render clinically significant action on clearance of the medicines the metabolism of which proceeds with participation of isoenzyme cytochrome Ð450. Researches have confirmed that Tadalafhil does not inhibit and does not induce isoenzymes CYP3A4, CYP1À2, CYP2D6, CYP2E1 and CYP2C9.
Tadalafil does not render clinically appreciable influence on pharmacokinetics of S-varfarine or R-varfarine. Tadalafil does not influence varfarine towards prothrombin time..
Tadalafil does not prolongate the bleeding caused by acetylsalicylic acid.
Òadalafhyl does not show clinically significant interaction with the basic classes of antihypertensive means, including calcium channel blockers (amlodipine), angiotensin converting enzyme (enalapril), blockersof beta-adrenergicheskih receptors (metoprolol), an alpha-blockers, thiazide diuretics (bendoflyuazid) and blockers of receptors of angiotensin II which were used in various doses as monotherapy or in combinations. There are no distinctions revealed at undesirable events at the patients accepting Tadalafhil in a combination with antihypertensive preparations or without them.
It is not established an influence of unitary intake of Tadalafil on concentration of alcohol in blood, alcohol influence on cognitive function and arterial pressure. Besides, there were no observations of fluctuations of concentration level of Tadalafil in blood after 3 hours after acceptance in combination with alcohol.
Tadalafil does not render clinically significant effect on pharmacokinetics or pharmakodynamics of theophyllin.
Special instructions
Precautions
Sexual activity is potentially risky for patients with cardiovascular diseases. Therefore, treatment of erectile dysfunction, including that with use of the preparation Cialis, must not be carried out for patients with such heart diseases at which sexual activity is not recommended
A potential risk of complications at sexual activity should be taken into account with patients having cardio-vascular diseases:
• myocardial infarction within previous 90 days
• an unstable stenocardia or a stenocardia, arising during sexual intercourse
• heart insufficiency of class 2 and above by NYHA, developed within last 6 months
• uncontrollable infringements of a heart rhythm, hypotonia (with the AP <90/50 mm of mercury) or an uncontrollable arterial hypertensia
• an insult had within last 6 months
CIALIS must be applied with care at patients with predisposition to priapism (for example, at sickle cell anemia,multiple myeloma or leukaemia), or at patients with anatomic deformation of a sexual member (for example, at an angulation, cavernous fibrosis or illnesses of Pejroni).
There are reports on occurrence of priapism at use of another inhibitor of PDE5 – sildenafil, although against intake of the preparation Cialis cases of priapism were not reported. Patients should be informed about necessity to immediately seek for medical advise in case of occurrence of erection , lasting 4 hours and more. Untimely treatment of priapism can result in damage of tissues of a sexual member which can cause a long-term impotence.
Safety and efficiency of combination of the preparation Cialis with other kinds of treatment of erection dysfunction were not studied. Therefore application of similar combinations is not recommended.
Against treatment by Cialis patients with nephritic insufficiency of moderate severity level ( creatinine clearance 31-50 ml/min) had such undesirable phenomenon, as dorsodynia more often than patients having slight nephritic insufficiency (clearance of creatinine is 51-80 ml/min) or healthy persons. At patients with severe kidneys dysfunction (clearance of creatinine 30 ml/min) Tadalafil was not studied. The preparation Cialis should be prescribed with care to patients with creatinine clearance 50 ml/min.
Influence on capability of driving and work with mechanism
No special prescribing.
Application during pregnancy and lactation
The preparation Cialis is not intended for application for women.
Storage conditions
Store at temperature below 30 degrees in original package. Keep away from children
Expiration period
2 years. Do not use after the date specified on package.
