Cialis
Active material: Tadalafil
When ATH: G04BE08
CCF: Drug for the treatment of erectile dysfunction. PDE-5 inhibitor
ICD-10 codes (testimony): F52.2, N48.4
When CSF: 28.08.01.01.01
Manufacturer: ELI LILLY Vostok S.A.. (Switzerland)
Pharmaceutical form, composition and packaging
Pills, Film-coated yellow color, Almond -shaped, with an inscription “With 20” on one side.
| 1 tab. | |
| tadalafil | 20 mg |
Excipients: lactose monohydrate, giproloza (hydroksypropyltsellyuloza), Croscarmellose sodium, microcrystalline cellulose, magnesium stearate, sodium lauryl.
The composition of the coating film: Opadry II yellow – lactose monohydrate, gipromelloza, Titanium dioxide, triacetine, dye iron oxide yellow.
1 PC. – blisters (1) – packs cardboard.
2 PC. – blisters (1) – packs cardboard.
2 PC. – blisters (2) – packs cardboard.
2 PC. – blisters (4) – packs cardboard.
Pharmacological action
Medication for the treatment of erectile dysfunction. Is a reversible selective inhibitor of specific phosphodesturas of type 5 (PDE5) cGMP. When sexual excitement causes local release of nitrogen oxide, Inhibiting FDE5 Tadalafil leads to an increase in the level of the CGMF in the cavernous body of the 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 FDE5 inhibitor. PDE5 – enzyme, cavernous body, in smooth muscles receptacles internal organs, in skeletal muscle, platelets, kidney, light, cerebellum.
Tadalafil on FDE5 is more active, than on other phosphodesterases. Tadalafil in 10 000 Once more active in relation to FDE5, than with respect to FDE1, FDE2, PDE4, FD7, which are located in the heart of, brain, blood vessels, liver, leukocytes, skeletal muscles and other organs. Tadalafil in 10 000 once more actively blocks FDE5, than FDE3 – enzyme, which is found in the heart and blood vessels. This selectivity in relation to FDE5 compared to FDE3 is important, Since FDE3 is an enzyme, participating in the contraction of the heart muscle. Besides, Tadalafil approximately in 700 Once more active in relation to FDE5, than with FDE6, discovered in the retina and which is responsible for the photo transmission.
Tadalafil also manifests itself in 9000 once more powerful in relation to FDE5, Compared to his influence on FDE8, in 9 and 10 and in 14 once more powerful in relation to FDE5, Compared to FDE11. Distribution in tissues and physiological effects of inhibition of FDE8-FDE11 to date have not yet been clarified.
Tadalafil improves an erection and the possibility of successful sexual intercourse.
The drug acts during 36 no. The effect is already in 16 minutes after taking the drug in the presence of sexual stimulation.
Tadalafil in healthy individuals does not cause a significant change in systolic and diastolic blood pressure, compared to placebo, in the supine position (The average maximum decrease in blood pressure is 1.6/0.8 mmHg. respectively) And standing (The average maximum decrease in blood pressure is 0.2/4.6 mmHg. respectively). Tadalafil does not cause a reliable change in heart rate.
Tadalafil does not cause changes in color recognition (Blue/Green), What is explained by his low affinity to FDE6. Besides, There is no influence of Tadalafil on visual acuity, jelektroretinogrammu, intraocular pressure and pupil size.
In order to assess the influence of tadalphil, several studies were conducted with a daily admission on spermatogenesis. None of the studies have an undesirable effect on the morphology of sperm and their mobility. One of the studies revealed a decrease in the average concentration of sperm compared to placebo. A decrease in sperm concentration was associated with a higher ejaculation frequency. Besides, Tadalafil did not cause undesirable changes in testosterone content, LH and FSH in blood plasma, compared to placebo.
Pharmacokinetics
Absorption
After taking the tadalafil is quickly absorbed. Cmax reached on average through 2 no. The speed and degree of absorption do not depend on eating. The time of taking the drug (morning or evening) does not have a clinically significant effect on the speed and degree of absorption.
Pharmacokinetics of Tadalafil in healthy persons of linear with respect to time and dose. The dose range 2.5 to 20 MG AUC increases in proportion to the dose. Css in plasma achieved within 5 days when taking the drug 1 time / day.
Pharmacokinetics of Tadalafil in patients with impaired erection function is similar to the pharmacokinetics of the drug in people without impaired erection function.
Distribution
Average Vd is about 63 l, which indicates, that tadalafil is distributed in the tissues of the body. In therapeutic concentrations 94% Tadalafila is associated with plasma proteins. Healthy individuals have less 0.0005% Dose introduced in sperm.
Metabolism
Metabolized mainly with the participation of the CYP3A4 isoenzyme. The main circulating metabolite is metilcatecholglyukuronide. He is in 13 000 once less active in relation to FDE5, than Tadalafil. Hence, This metabolite is hardly clinically significant.
Deduction
In healthy individuals, the average clearance of tadalafil when oral administration is 2.5 l /, And the average t1/2 – 17.5 no. Tadalafil is excreted mainly in the form of inactive metabolites, mainly in the faeces (about 61%) And to a lesser extent with urine (about 36%).
Pharmacokinetics in special clinical situations
In healthy people of the elderly (65 years or more) The lower clearance of tadalafil is determined, which is expressed in an increase in AUC on 25% Compared to healthy people from the age of 19 to 45 years. This difference is not clinically significant and does not require dose selection.
In patients with renal insufficiency, including patients, hemodialysis, AUC is more, than in healthy individuals. Binding with proteins does not change when impaired renal function.
Pharmacokinetics of Tadalafil in patients with mild or moderate liver failure is comparable to that in healthy individuals. In relation to patients with severe liver failure (class C on the scale of Child-Pugh) There is no data.
In patients with diabetes, against the background of the use of tadalafil AUC, it was less approximately on 19%, than in healthy individuals. This difference is not required to change the dose.
Testimony
- erectile dysfunction.
Dosage regimen
The drug is taken orally, regardless of the meal.
Recommended maximum dose of Sialis® is 20 mg. Maximum recommended reception frequency – 1 time / day.
Cialis® take at least for 16 min to alleged sexual activity.
Patients may attempted sexual intercourse at any time during 36 h after taking the drug for that, to set the optimal response time to the drug.
Side effect
Frequently: headache (11%), dyspepsia (7%).
Side effects are usually insignificant or medium in terms of severity, transient and decrease when continuing to take the drug.
Maybe: backache, myalgia, dizziness, nasal congestion, flushing.
Rarely: swelling of the eyelids, sore eyes, conjunctival hyperemia.
Rarely: hypersensitivity reactions (including rashes, Cocking and facial swelling, Stevens-Johnson syndrome and exfoliative dermatitis); hypotension (patients, which have already taken antihypertensive drugs), hypertension and sycopop; abdominal pain and gastroesophageal reflux; hyperhidrosis (increased sweating); Priapism and delay of erection; blurred vision, non -arterial anterior ischemic neuropathy of the optic nerve, Occlusion of the veins of the retina, violation of the visual fields, migraine, nose bleed.
In patients with cardiovascular risk factors: myocardial infarction, Sudden cardiogenic death, stroke, chest pain, palpitations, tachycardia. However, it is impossible to accurately determine if these phenomena are directly related to these risk factors, tadalafiloma, With sexual excitement, or with a combination of these or other factors.
Contraindications
- Concomitant use of drugs, containing any organic nitrates;
- Application in people aged to 18 years;
- Hypersensitivity to the drug.
Pregnancy and lactation
The drug is not intended for use in women.
Cautions
With caution, the drug should be prescribed to patients with severe liver failure (class C on the scale of Child-Pugh), Since the data of controlled clinical studies on the safety and efficiency of the use of the drug Cialis® This category of patients does not have.
Caution is necessary when prescribing Sialis® patients, receiving α1-adrenoblokatorы, eg, doksazozin, since the simultaneous use in some cases can lead to symptomatic arterial hypotension. When studying clinical pharmacology in 18 Healthy volunteers, taking tadalafil in a single dose, Symptomatic arterial hypotension was not observed with the simultaneous administration of α1-Tamsulosin's adrenobler.
Sexual activity is a potential risk for patients with cardiovascular disease. Therefore, treatment of erectile dysfunction, incl. using the drug Cialis®, should not be carried out in men with such diseases of the heart, in which sexual activity is not recommended.
The potential risk of complications in sexual activity in patients with diseases of the cardiovascular system should be taken into account: myocardial infarction during the last 90 days; unstable angina or angina, occurring during sexual intercourse; congestive heart failure (II functional class and higher according to NYHA classification), evolved in the past 6 months; uncontrolled cardiac arrhythmia; hypotension (BP less 90/50 mmHg.) or uncontrolled hypertension; stroke, transferred over the last 6 months.
Caulis should be used with caution® in patients with severe renal insufficiency (CC less than 30 ml / min), in renal failure of moderate severity (KK from 31 to 50 ml / min), In patients with a predisposition to priapism (eg, with sickle cell anemia, multiple myeloma or leukemia) or in patients with anatomical deformation of the penis (eg, during angulation, cavernous fibrosis or Peyronie's disease).
There are reports about the occurrence of priapism when using FDE5 inhibitors, Including Tadalphil. The patient must be informed about the need for immediate seeing a doctor in case of an erection, ongoing 4 h or more. Untimely treatment of jokes leads to damage to penis tissues, As a result of this, long -term loss of potency may occur.
Safety and effectiveness of the combination of the drug Cialis® with other types of treatment of erectile dysfunction were not studied. Therefore, the use of such combinations is not recommended.
Like other FDE5 inhibitors, Tadalafil has systemic vasodilating properties, what can lead to a transient decrease in blood pressure. Before prescribing the drug Cialis® Doctors must carefully consider the issue – Would patients with their cardiovascular disease be of an undesirable effect due to such vasodilating effects.
Non -arterial anterior ischemic optical neuropathy (Nipo) is the cause of visual impairment, Including full vision loss. There are rare post -marketing messages about cases of PIONE development, by time related to the reception of FDE5 inhibitors. It is currently impossible to determine, Is there a direct connection between the development of Pion and the use of FDE5 inhibitors or other factors. Doctors should recommend to patients in case of sudden loss of vision to stop taking tadalphil and seek medical help. Patients should be warned about, that people, Transferred puppes, Increased risk of re -development of this state.
Effects on ability to drive vehicles and management mechanisms
Despite, that the frequency of dizziness against the background of placebo and tadalphil is the same, During the treatment period, patients must be careful when driving vehicles and classes of other potentially dangerous activities, require high concentration and speed of psychomotor reactions.
Overdose
With a single appointment of healthy volunteers at the dose 500 mg/day and patients with erectile dysfunction – repeatedly 100 mg / day, Unwanted effects were the same, As with the use of the drug in lower doses.
Treatment: Conducting standard symptomatic therapy. With hemodialysis, tadalafil is practically not excreted.
Drug Interactions
The influence of other drugs on tadalafil
Tadalafil is mainly metabolized with the participation of the CYP3A4 enzyme. Selective inhibitor CYP3A4 ketoconazole in the dose 400 mg/day increases the AUC Tadalafil in a single dose on 312%, a Cmax – on 22%, and ketoconazole in the dose 200 mg/day increases the effects of tadalafil, in a single dose 107% and Cmax – on 25%, regarding AUC and values Cmax only for one tadalafil.
Ritonavir (200 mg 2 times / day), CYP3A4 inhibitor, 2C9, 2A19 and 2D6, increases AUC Tadalphila in a single dose on 524% without changing Cmax. Despite, that specific interactions were not studied, We can assume, that other HIV-prosthesis inhibitors, eg, saquinavir, as well as CYP3A4 inhibitors, such as erythromycin and itraconazole, Increase the activity of tadalafil.
Selective inductor CYP3A4 Rifampin (rifampicin, 600/mg / day), reduces AUC Tadalafil in a single dose by 88% and Cmax on 46%, regarding AUC and values Cmax only for one tadalafil. Expected, that the simultaneous introduction of other CYP3A4 inducers should also reduce the concentration of tadalafil in plasma.
With the simultaneous use of antacid (magnesium hydroxide / aluminum hydroxide) and tadalafila decreases the speed of absorption of the latter without changing its aUC.
An increase in the pH of gastric juice as a result of taking a histamine block2-Nizatidine receptors does not affect the pharmacokinetics of tadalafil.
The effect of Tadalafil on other drugs
Tadalafil enhances the hypotensive effect of nitrates. This happens as a result of the additive action of nitrates and tadalafil on the metabolism of nitrogen oxide and the CGMF. Therefore, the appointment of Cialis® against the background of the use of nitrates is contraindicated.
Tadalafil does not have a clinically significant effect on the clearance of drugs, The metabolism of which occurs with the participation of cytochrome p450 isoenzymes. Studies have confirmed, that Tadalafil does not inhibit and does not induce cyp3a4 isoenzymes, CYP1А2, CYP2D6, CYP2E1, CYP2C9, CYP2C19.
Tadalafil does not have a clinically significant effect on the pharmacokinetics S-R-R-Warfarin. Tadalafil does not affect the action of warfarin in relation to prothrombin time.
Tadalafil does not increase the duration of bleeding against the background of acetylsalicylic acid.
Tadalafil has systemic vasodilating properties and can enhance the effect of antihypertensive drugs, aimed at reducing blood pressure. Additionally, patients, taking several antihypertensive agents, in which hypertension was poorly controlled, There were somewhat greater decrease in blood pressure. In the vast majority of patients, these reducations were not associated with hypotensive symptoms. Patients, receiving treatment with anthropethensum drugs and taking tadalafil, relevant clinical recommendations must be given.
There was no significant decrease in blood pressure with the use of tadalafil simultaneously with selective alpha1A-Adren blocker Tamsulosin.
When using tadalafil healthy volunteers, accepting alpha1-Doxazososin adrenobler (8 mg / day), There was an increase in the hypotensive effect of doxasosine. Some patients experienced dizziness. There were no cases of syncope. The lower doses of doxasosine did not study.
Tadalafil did not affect the concentration of ethanol, As well as ethanol did not affect the concentration of tadalafil. At high doses of ethanol (0.7 g / kg) Tadalafil's intake did not cause a statistically significant decrease in the average blood pressure. In some patients, postural dizziness and orthostatic hypotension were observed. With the introduction of tadalafil in combination with lower doses of ethanol (0.6 g / kg) arterial hypotension was not observed, and dizziness arose with the same frequency, what to take alcohol alone.
Tadalafil does not have a clinically significant effect on the pharmacokinetics and pharmacodynamics of Theophylline.
Conditions of supply of pharmacies
The drug is released under the prescription.
Conditions and terms
The drug should be stored out of reach of children, In the original packaging at temperatures below 30 ° C. Shelf life – 3 year.
