Pharmacological properties of the drug Cialis
Tadalafil is a reversible, selective inhibitor of cyclic guanosine monophosphate (cGMP) specific phosphodiesterase type 5 (PDE5). When sexual arousal causes local release of nitric oxide, inhibition of PDE5 by tadalafil results in increased levels of cGMP in the corpus cavernosum of the penis. The consequence of this is 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 stimulation. In vitro studies have shown that tadalafil is a selective PDE5 inhibitor. PDE-5 is an enzyme identified in the smooth muscles of the corpus cavernosum and vessels of internal organs, in skeletal muscles, platelets, kidneys, lungs and cerebellum. The effect of tadalafil on PDE-5 is 10,000 times greater than its effect on other types of phosphodiesterase (PDE-1, PDE-2, PDE-4 and PDE-7). Tadalafil is 10,000 times more active in blocking PDE-5 than PDE-3, an enzyme that is detected in the heart and blood vessels. This selectivity for PDE-5 over PDE-3 is important because PDE-3 is an enzyme involved in cardiac muscle contraction. In addition, tadalafil is approximately 700 times more active against PDE5 than against PDE6, an enzyme found in the retina that is responsible for phototransduction. Tadalafil is also 9000 times more potent against PDE5 than it is against PDE8, PDE9 and PDE10, and 14 times more potent than PDE11. The tissue distribution and physiological effects of PDE-8 and PDE-11 have not been determined. Tadalafil does not affect color perception (blue/green), which is explained by its low affinity for PDE-6 compared to PDE-5. In addition, there was no effect of tadalafil on visual acuity, electroretinogram, intraocular pressure and pupil size. Tadalafil in healthy individuals does not cause significant changes in systolic and diastolic blood pressure compared to placebo in the supine position (average maximum decrease is 1.6/0.8 mm Hg) and in the standing position (average maximum decrease is 0.2/ 4.6 mmHg). Tadalafil does not cause a significant change in heart rate. A placebo-controlled study of the effect of taking tadalafil on spermatogenesis for 6 months did not reveal a clinically significant effect of the drug on sperm characteristics (number, motility and structure of sperm). Taking tadalafil had no effect on the levels of testosterone, LH and FSH in the blood. The drug is effective for 36 hours. The effect appears within 16 minutes after taking the drug in the presence of sexual arousal. Pharmacokinetics. Suction . After oral administration, tadalafil is rapidly absorbed. The average maximum concentration in blood plasma is achieved on average 2 hours after oral administration. The rate and extent of absorption of tadalafil do not depend on food intake, so the drug can be taken regardless of food. Time of administration (morning or evening) does not have a significant effect on the rate and extent of absorption. Distribution . The average volume of distribution is approximately 63 l. At therapeutic concentrations, 94% of tadalafil binds to plasma proteins. In healthy individuals, less than 0.0005% of the administered dose is detected in semen. Metabolism . Tadalafil is mainly metabolized with the participation of the CYP3A4 isoenzyme of cytochrome P450. The main circulating metabolite is methylcatechol glucuronide. This metabolite is 13,000 times less active against PDE-5 than tadalafil. Therefore, it can be assumed that this metabolite is not clinically significant at detectable concentrations. Removal . In healthy individuals, the average half-life is 17.5 hours. Tadalafil is excreted primarily in the form of inactive metabolites, mainly in feces (about 61% of the dose) and to a lesser extent in urine (about 36% of the dose). Selected groups of patients . In healthy elderly individuals (65 years and older), a lower clearance of tadalafil was observed when taking the drug orally, which was reflected in an increase in AUC by 25% compared with that in healthy individuals aged 19–45 years. This difference is not clinically significant and does not require dose adjustment. Kidney failure . In individuals with renal impairment (including patients on hemodialysis), tadalafil exposure (based on AUC value) was greater than in healthy individuals. Liver failure . The exposure of tadalafil (based on AUC value) in patients with mild to moderate hepatic impairment is comparable to that in healthy individuals. There are no data on the pharmacokinetics of tadalafil in severe hepatic impairment. In patients with diabetes mellitus , while using tadalafil, its exposure (AUC) was approximately 19% less than the AUC value in healthy individuals. This difference in exposure does not require dose adjustment.
The drug Cialis 5 mg in modern urological practice. Satellite Symposium
Topic of the debate: “Cialis 5 mg in modern urological practice” The debate was opened by Associate Professor of the Department of Urology at Moscow State Medical University, Ph.D. P.I. Rasner. P.I. Rasner spoke about the epidemiology of erectile dysfunction (ED), based on data from various studies. One of them, conducted in 2011 in the United States, was a large-scale 45-minute survey of 123,163 adult respondents, of whom 75,000 completed it. This survey showed that ED was present in 24.6% of men surveyed (average age: 60 years), and ED with lower urinary tract symptoms (LUTS) was identified in 4.9% of respondents (average age: 68 years). Interestingly, 66% of respondents told doctors about their problems, which, according to P.I. Rasner, is still an unattainable figure for Russia, and 23% received drugs for the treatment of ED. As a result of the European study MSAM-7, which involved more than 14,000 men aged 50–80 years in 7 countries (Russia was not included in this study), it was revealed that men of this age also need effective treatment for ED. Thus, the average number of sexual intercourses among men 70–80 years old is 3 times a month. The speaker pointed out that these figures are of great interest: “Sexual intercourse almost once a week for an 80-year-old man is somewhat unexpected data.” At the same time, sexual activity was absolutely clearly associated with the severity of LUTS: the more severe the symptoms were, the lower the activity. Even more intriguing data came from a large Asian study that was divided by country. It turned out that on average, people in Asia are slightly less sexually active than in Europe, but not all countries have the same sexual activity in their respective age categories. In Japan, for example, 44% of men are sexually active and over the age of 80, which cannot be said about other countries. Another interesting fact for urology specialists was mentioned: many studies have shown that men who initially involved their sexual partners in treatment were much more motivated. And they were absolutely satisfied that they shared this problem with their partner. Chief urologist of the Ministry of Health of the Russian Federation, professor, head. Department of Urology, Moscow State Medical University, Doctor of Medical Sciences D.Yu. Pushkar summarized and summarized the data presented in the studies. He said that, despite the lack of Russian research in this area, by and large, all patients - in France, Japan, Italy and Russia - are no different. And, in principle, all this research can be transferred to our country. The professor asked his colleagues to pay attention to how quickly a urologist’s patient is changing in the modern world: “What is called erectile dysfunction today was not considered such 10–20 years ago. Today the evolution of patients is happening very quickly. Yesterday this patient would have undergone transurethral resection, the day before yesterday he would have undergone extensive surgery, today he is being observed and is ready to be observed. Moreover, he chooses observation, and I do not have the right to offer him surgery for indications for which it would have been done yesterday. And today the indications are different, and patients are more literate - they listen to their urination in a completely different way. But therapy is also changing: not so long ago there was no magic pill that we are talking about today. Also, there was no this unique dosage – 5 mg, which is the only one for daily use among phosphodiesterase type 5 inhibitors (PDE-5 inhibitors), but at the same time shows high efficiency compared to the use of PDE-5 inhibitors on demand.” In his speech prof. D.Yu. Pushkar raised another important point that no one has ever studied the quality of urination in men who take enough fluids. It is known that to prevent urolithiasis, osteoarticular disorders, and cardiovascular pathology, it is necessary to drink 11 glasses of water daily. Most men, incl. participants in the studies do not receive as much fluid. What data can be obtained from studies conducted taking this factor into account? After all, many urinary disorders may not be detected until there are conditions for their detection. Next, the issue of risk factors for early termination of sexual life in Russian men was raised. Data from a domestic study were presented, which showed that the age of cessation of sexual activity among men in Russia is on average 45–60 years. 37% of men surveyed stopped having sex before the age of 60, and this was done on the initiative of the men themselves in 70% of cases. The risk factors are obvious: 63% drink alcohol, 50% smoke, the majority have an increased body mass index. D.Yu. Pushkar pointed out that today's symposium is discussing a rare case where doctors can meet the expectations of patients. A small dosage of Cialis 5 mg with the possibility of daily use - as the speaker said - has revolutionized the ideas of urologists about the formula for treating ED.
Professor of the Department of Urology of the First Moscow State Medical University named after I.M. Sechenova Doctor of Medical Sciences A.Z. Vinarov provided data on various representatives of the PDE-5 inhibitor group: in addition to tadalafil, there are other, and more studied, drugs. The most studied drug used in the treatment of ED is sildenafil; It is followed by tadalafil in terms of the number of studies. According to the European Association of Urology (EAU) guidelines, there is currently no evidence to suggest that patients prefer sildenafil, tadalafil or vardenafil. Today, the choice of drug depends on the frequency of sexual intercourse and the patient’s own experience. Therefore, the patient should be aware that there are short- and long-acting drugs and should know their disadvantages and advantages.
Associate Professor, Department of Urology, First Moscow State Medical University named after I.M. Sechenova Doctor of Medical Sciences N.D. Akhvlediani contrasted the data of Prof. A.Z. Vinarov the following facts: “If we compare Cialis 5 mg and Cialis 20 mg,” he began, “then we can definitely say that these are different drugs with different philosophies of use. If we try to use Cialis 20 mg in a sexually active patient, then, based on the instructions, we can prescribe it only every other day. It is known to be effective for 36 hours. Thus, there is an 8-hour window when the patient will not have the effect of the PDE5 inhibitor, and he may get into the unpleasant situation of forgetting about it, hoping for the effect of the drug. This is excluded when using Cialis 5 mg, because the concentration of this drug does not constantly change due to daily use, and the effectiveness does not decrease. We must admit that there is objective research data: by using inhibitors more often, for example, daily, like Cialis 5 mg, we have better results in terms of the frequency of spontaneous night or morning erections. We are talking about a comparison with Cialis 20 mg and sildenafil. The pattern is this: the more often the patient takes the inhibitor, the better the effect. In addition, we must admit, based on data from long-term serious studies, that with daily use, almost 60% of men experienced complete normalization of erectile function, i.e. they show no signs of illness and feel healthy. Interestingly, after 2 years of use this figure remains virtually unchanged. This suggests that there is no tachyphylaxis. The psychological status of patients taking tadalafil 5 mg, Cialis 20 mg and sildenafil is different. Data from a large-scale study are such that patients who take a PDE-5 inhibitor - Cialis 5 mg - daily are less concerned about the duration of action of the drug, the speed of onset of the effect, and the spontaneity of sexual activity. The patient does not think about whether the pill he takes will work. This cannot be said about the action of the on-demand PDE-5 inhibitor sildenafil. Why is tadalafil 5 mg daily more effective than on-demand PDE5 inhibitors? Firstly, in these patients morning erections are restored and they occur more often. And the man feels healthy again. Secondly, this drug is easier to use. After all, many patients take PDE-5 inhibitors incorrectly. Because you may forget how long before sexual intercourse you should take the medicine, because some of these medicines are titrated, i.e. it is necessary to select a dosage. Thirdly, there is no concern about the duration of action of the drug and the speed of onset of the effect. And the most convincing data (this work has not yet been published) is a comparison of the effectiveness of tadalafil 5 mg, tadalafil 20 mg and placebo in the most severe patients with radical prostatectomy, naturally nerve-sparing. Over a long follow-up period of 13.5 months, the most effective results were shown by long-acting PDE-5 inhibitors compared to placebo, but the best result was with Cialis 5 mg: the only reliable indicator of the relative probability of restoration of erection.”
Professor A.Z. Vinarov: “You know that PDE-5 inhibitors are now included in the EAU recommendations as drugs that can be used in patients with urinary disorders. Moreover, it has long been known that sildenafil improves symptoms of impaired urination. In 2013, recommendations appeared in the journal "European Urology", which indicated that PDE-5 inhibitors reduce the severity of moderate and severe storage and excretory symptoms of impaired urination in men with or without ED disorders. But only tadalafil 5 mg is registered for the treatment of men with urinary symptoms in Europe.”
Associate Professor N.D. Akhvlediani: “We understand that the treatment of urinary disorders requires continuous exposure, long-term inhibition of phosphodiesterase-5. In Europe and other countries, PDE-5 inhibitors are registered for both the treatment of ED and urinary symptoms. Tadalafil is a leader in this sense. 111 publications mentioning tadalafil used in the treatment of symptoms of impaired urination. Second place, oddly enough, was taken by the short-acting drug sildenafil. But this is the first drug from the PDE-5 inhibitor group, and these studies began with it. But should it be used in the treatment of patients?
Professor A. Z. Vinarov summed up: “PDE-5 inhibitors and, in particular, tadalafil, can be equally effective in patients with ED and urinary disorders, and in patients with urinary disorders, but without erectile dysfunction.”
Associate Professor, Department of Urology, Moscow State Medical University, Ph.D. A.V. Govorov raised another important topic - the daily use of PDE-5 inhibitors for the treatment of benign prostatic hyperplasia (BPH). “What do we know about standard treatment for BPH? We know that α-blockers are the standard of care for BPH because they act quickly, they are effective, and they have low incidence and severity of side effects. We know that they reduce patients' I-PSS on treatment by about 30 to 40% and increase peak urinary flow rate by about 25%. They can be prescribed to a patient with BPH at any age. Lately we have been saying that the selectivity of these drugs is important to us. On the one hand, we understand that the higher the selectivity, the better it would seem. At the same time, more selective drugs are characterized by the presence of such a criterion as retrograde ejaculation. When we talk about this with patients, we explain to them upfront that modern selective drugs can cause this condition. Patients seem to agree to such conditions. But quite often, using this therapy, they return to us with complaints about exactly what they were warned about. Now let's talk about the group of drugs that we know well: PDE-5 inhibitors. They are the only group of medications that prevent BPH symptoms while also effectively reducing I-PSS, effectively reducing prostate volume by approximately 18-25% when used for 2-4 years. We remember that the larger the patient's prostate volume, the more pronounced the effect of PDE-5 inhibitor treatment. These drugs are needed and important in modern combinations. Now there are drugs that combine α-blockers with PDE-5 inhibitors. We are talking about the fact that today other patients come to see us and, thanks to the Internet, have an idea of what kind of treatment they want to receive. There are more and more such patients. These are the patients with whom we can discuss new treatment options for BPH.”
Professor of the Department of Urology and Surgical Andrology of the Russian Medical Academy of Postgraduate Education, Doctor of Medical Sciences. E.I. Veliyev spoke about a study that compared the effectiveness of tadalafil 5 mg with placebo: “Half of the patients had successful sexual intercourse from the 2nd day of therapy. Then the number of such attempts increased. Tadalafil 5 mg was studied with long-term use - over 12 months. The conclusions are: the dose is small, it acts quickly and it works well.” Further E.I. Veliyev briefly discussed the effect of tadalafil on LUTS: “When we talk about the effects of Cialis 5 mg with constant use, we mean the effects associated with both LUTS and the severity of ED. Data from a study in which patients were divided into 3 groups - with mild ED, with moderate and severe ED - show that tadalafil 5 mg with chronic use showed an improvement in I-PSS scale scores. Today we know several methods for treating BPH and LUTS. We are accustomed to dividing our patients into several groups: these are patients who can use monotherapy and those who are indicated for combination therapy. We say, as a rule, that those patients for whom combination therapy is recommended have progressive BPH. Regardless of the progression of BPH, Cialis 5 mg is effective. Where ED is associated with LUTS, tadalafil 5 mg demonstrates effectiveness everywhere, regardless of the severity of its manifestation. Tadalafil 5 mg improves LUTS, with any degree of ED in the patient.” Prof. E.I. Veliyev, summing up the debate, said that two problems can really have one solution in the group of patients discussed today: ED and urinary disorders with BPH. And this number of patients can be more than 70%.
Side effects of Cialis
The most common symptom is headache (≥10% of cases). Other common side effects (with an incidence of ≥1% but ≤10%) are back pain, dyspepsia, dizziness, flushing, myalgia, nasal congestion. In isolated cases (with a frequency of ≥0.1%, but ≤1%), swelling of the eyelids, painful sensations in the eyes, and conjunctival hyperemia were noted. In post-marketing studies, the following side effects were very rarely identified: General reactions: hypersensitivity reactions - skin rash, urticaria and facial swelling, Stevens-Johnson syndrome, exfoliative dermatitis; from the cardiovascular system: cases of such severe reactions from the cardiovascular system as myocardial infarction, sudden cardiac death, stroke, angina pectoris, tachycardia have been described, however, most patients had a history of risk factors from the cardiovascular system . However, it is impossible to establish a reliable connection between the development of the above reactions and cardiac risk factors, taking tadalafil, sexual activity, or a combination of all of these factors. The development of arterial hypotension (usually in the case of simultaneous use of tadalafil with antihypertensive drugs), hypertension (arterial hypertension), fainting has also been reported; from the gastrointestinal tract : abdominal pain, gastroesophageal reflux; from the skin : hyperhidrosis; from the organ of vision: blurred vision, non-arterial anterior optical ischemic neuropathy, retinal vein occlusion, visual field impairment; from the genitourinary system: prolonged erection, priapism. from the central nervous system : migraine from the respiratory system : nosebleeds. Side effects reported that were not encountered during clinical trials and therefore their frequency is unknown: seizures, temporary memory loss, some disorders affecting ocular circulation, arrhythmia, skin rash, and sudden decrease or loss of hearing. Sometimes men experienced a decrease in sperm concentration.
Special instructions for the use of Cialis
Special security measures. Sexual activity has potential risks for patients with cardiovascular disease. Therefore, treatment of erectile dysfunction, including the use of Cialis, should not be carried out in men with heart diseases for which sexual activity is not recommended. The potential risk of complications during sexual activity should be taken into account in patients with cardiovascular diseases such as: - myocardial infarction within the last 90 days, - unstable angina or angina that occurs during sexual intercourse, - heart failure II class II above NYHA, developed in during the last 6 months, - uncontrolled heart rhythm disturbances, arterial hypotension (BP ≤90/50 mm Hg) or hypertension (arterial hypertension), - stroke suffered during the last 6 months. An assessment of erectile dysfunction includes determining its underlying cause and the advisability of a course of treatment. Before initiating any treatment for erectile dysfunction, the physician must evaluate the patient's cardiovascular condition, since there is a certain degree of risk associated with sexual activity. Non-arterial anterior ischemic optic neuropathy (NAION) can cause vision impairment, including vision loss. NAPION has been rarely reported with PDE5 inhibitors in post-marketing studies. It is unknown whether NAPI is associated with the use of PDE5 inhibitors or other factors. The patient should be informed that in case of sudden loss of vision, it is necessary to stop using tadalafil and consult a doctor. It is also necessary to warn the patient about a significant increase in the risk of NAPION if he has a history of NAPION. The safety and effectiveness of the combination of Cialis with other types of treatment for erectile dysfunction have not been studied, so the use of such combinations is not recommended. There have been reports of priapism occurring with the use of PDE5 inhibitors, including tadalafil. Patients should be warned to seek immediate medical attention if an erection occurs that persists for 4 hours or more. Untimely treatment of priapism leads to damage to the tissues of the penis with the onset of long-term impotence. Cialis should be used with caution in patients with a predisposition to priapism (eg, sickle cell disease, multiple myeloma, or leukemia) or in those with penile deformity (eg, angular curvature, cavernous fibrosis, or Peyronie's disease). Given the lack of data on the use of Cialis in patients with severe liver dysfunction (Child-Pugh class C), Cialis is prescribed to patients in this group with caution. Caution should be exercised when prescribing Cialis to patients taking α-1 adrenergic blockers (doxazosin), as in some cases, simultaneous use of these drugs can lead to symptomatic hypotension. Like other PDE5 inhibitors, tadalafil can have a systemic vasodilatory effect, which can lead to a transient decrease in blood pressure. Therefore, before starting treatment, the doctor should assess the likelihood of a similar effect in patients with diseases of the cardiovascular system. Use during pregnancy or breastfeeding. Cialis is not indicated for use in women, so studies on the use of the drug during this period have not been conducted. Children. The use of the drug is not recommended for persons under 18 years of age. The ability to influence reaction speed when driving vehicles or other mechanisms. Cialis does not have or has an insignificant effect on the ability to drive vehicles and operate machinery.
Cialis 5mg n14 film-coated tablets
Latin name
Cialis
Release form
Film-coated tablets.
Package
Pack of 14 pcs.
pharmachologic effect
Cialis is a treatment for erectile dysfunction (impotence, erectile dysfunction) in men and is part of a group of drugs called PDE5 inhibitors (phosphodiesterase type 5). The drug dilates the blood vessels of the penis during sexual arousal. As a result, blood circulation in the penis increases, and this, in turn, contributes to the onset of a stable erection.
Indications
Erectile disfunction.
Lower urinary tract symptoms in patients with benign prostatic hyperplasia.
Erectile dysfunction in patients with lower urinary tract symptoms secondary to benign prostatic hyperplasia.
Contraindications
- Hypersensitivity to tadalafil or to any substance included in the drug.
— In case of taking medications containing any organic nitrates.
— Age up to 18 years.
— Diseases of the cardiovascular system: myocardial infarction within the last 90 days, unstable angina, the occurrence of an attack of angina during sexual intercourse, chronic heart failure of classes II-IV according to the NYHA classification, uncontrolled arrhythmias, arterial hypotension (BP less than 90/50 mm Hg .st.), uncontrolled arterial hypertension, ischemic stroke within the last 6 months.
Loss of vision due to non-arterial anterior ischemic optic neuropathy (regardless of the connection with taking PDE-5 inhibitors).
— Simultaneous 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).
— Lactase deficiency, lactose intolerance, glucose-galactose malabsorption.
Carefully:
— Severe liver failure (class C according to the Child-Pugh classification).
— Patients taking alpha 1-blockers.
- Predisposition to priapism (with sickle cell anemia, multiple myeloma or leukemia).
— Anatomical deformation of the penis (angular curvature, cavernous fibrosis or Peyronie’s disease).
- Simultaneous use with powerful inhibitors of the CYP3A4 isoenzyme (ritonavir, saquinavir, ketoconazole, itraconazole, erythromycin), antihypertensive drugs.
special instructions
Caution should be exercised when prescribing Cialis to patients taking alpha1-blockers, as concomitant use may lead to symptomatic hypotension in some patients. In a clinical pharmacology study in 18 healthy volunteers receiving a single dose of tadalafil, no symptomatic hypotension was observed during concomitant administration of tamsulosin, an alpha-1 blocker. Diagnosis of erectile dysfunction should include identifying the potential underlying cause, appropriate medical examination, and determining treatment options. Sexual activity has potential risks for patients with cardiovascular disease. Therefore, treatment of erectile dysfunction, including with Cialis, should not be carried out in men with heart diseases for which sexual activity is not recommended. There are reports of priapism with the use of PDE5 inhibitors, including tadalafil. Patients should be informed to seek immediate medical attention if they experience an erection lasting 4 hours or more. Untimely treatment of priapism leads to damage to the tissue of the penis, which may result in irreversible impotence. The safety and effectiveness of the combination of Cialis with other types of treatment for disorders have not been studied. Therefore, the use of such combinations is not recommended. Like other PDE-5 inhibitors, tadalafil has systemic vasodilatory properties, which may lead to a transient decrease in blood pressure. Before prescribing Cialis, physicians should carefully consider whether patients with cardiovascular disease would be adversely affected by these vasodilatory effects. Non-arterial anterior ischemic optic neuropathy (NAION) causes visual impairment, including complete loss of vision. There are rare post-marketing reports of cases of the development of NAPION, temporally associated with the use of PDE-5 inhibitors. It is currently impossible to determine whether there is a direct relationship between the development of NAPION and the use of PDE5 inhibitors or other factors. Doctors should advise patients to stop taking tadalafil and seek medical help if sudden vision loss occurs. Doctors should also tell patients that people who have had NAPION have an increased risk of developing NAPION again. The effectiveness of Cialis in patients who have undergone pelvic surgery or radical neurosparing prostatectomy is unknown.
Use in hepatic impairment: Since there are no data in patients with severe hepatic impairment (Child-Pugh class C), caution should be exercised when prescribing the drug to this group of patients.
Effect on the ability to drive vehicles and operate machinery: despite the fact that the incidence of dizziness with placebo and tadalafil is the same, during the treatment period it is necessary to be careful when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions .
Compound
1 film-coated tablet contains: tadalafil 5 mg.
Excipients: lactose monohydrate 109.65 mg, lactose monohydrate (spray dried) 17.50 mg, hyprolose 1.22 mg, hyprolose (extra fine) 2.80 mg, sodium lauryl sulfate 0.49 mg, microcrystalline cellulose 26.25 mg , croscarmellose sodium 11.20 mg, magnesium stearate (vegetable) 0.88 mg.
Shell composition: opadry yellow (Y-30-12863-A) 8.75 mg (lactose monohydrate 3.72 mg, hypromellose 2.59 mg, titanium dioxide 1.54 mg, triacetin 0.74 mg, iron dye yellow oxide 0 ,16).
Directions for use and doses
For oral administration.
For patients with frequent sexual activity (more than twice a week), the recommended dosage frequency is daily, once a day, 5 mg, 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 the drug at a dose of 20 mg, immediately before sexual activity, according to the instructions for medical use of the drug. The maximum daily dose is 20 mg.
Side effects
Adverse events associated with taking tadalafil are usually minor or moderate in severity, transient and decreased with continued use of the drug.
The most common (>=1%, headache, dyspepsia, back pain, myalgia, flushing, nasal congestion.
Cardiovascular system disorders:
uncommon - palpitations*, tachycardia*, decreased blood pressure (in patients who were already taking antihypertensive drugs), increased blood pressure; rarely - myocardial infarction*; unknown - unstable angina*.
Nervous system disorders:
very often - headache; often - dizziness; rarely - fainting, migraine, transient ischemic attacks, stroke.
Visual disorders:
infrequently - blurred visual perception; rarely - visual field impairment; unknown - non-arterial anterior ischemic optic neuropathy of the optic nerve, retinal vein occlusion.
Respiratory system disorders:
infrequently - nosebleeds.
Digestive system disorders:
often - abdominal pain; infrequently - gastroesophageal reflux.
Skin and subcutaneous tissue disorders:
uncommon - rash, urticaria, hyperhidrosis (excessive sweating); unknown - Stevens-Johnson syndrome and exfoliative dermatitis.
General violations:
uncommon - chest pain*; rarely - swelling of the face; unknown - sudden cardiac death*.
Immune system disorders:
infrequently - hypersensitivity reactions.
Reproductive system disorders:
rarely - prolonged erection; unknown - priapism.
* Observed in patients with previous cardiovascular risk factors. However, it is not possible to determine with certainty whether these events are directly related to these risk factors, to tadalafil, to sexual arousal, or to a combination of these or other factors.
Drug interactions
Effect of other drugs on tadalafil
Tadalafil is mainly metabolized with the participation of the CYP3A4 isoenzyme. A selective inhibitor of the CYP3A4 isoenzyme ketoconazole (400 mg per day) increases the exposure of a single dose of tadalafil (AUC) by 312% and Cmax by 22%, and ketoconazole (200 mg per day) increases the exposure of a single dose of tadalafil (AUC) by 107% and Cmax max by 15% relative to AUC and C max values for tadalafil alone.
Ritonavir (200 mg twice daily), an inhibitor of CYP3A4, 2C9, 2C19 and 2D6, increases single-dose tadalafil exposure (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 CYP3A4 inhibitors, such as erythromycin and intraconazole, increase the activity of tadalafil.
A selective inducer of the CYP3A4 isoenzyme, rifampicin (600 mg per 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 tadalafil plasma concentrations.
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 effectiveness of the combination of tadalafil with other types of treatment 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 drugs
Tadalafil is known to enhance the hypotensive effect of nitrates. This occurs as a result of the additive effect of nitrates and tadalafil on the metabolism of nitric oxide II (NO) and cGMP. Therefore, the use of tadalafil while taking nitrates is contraindicated.
Tadalafil does not have a clinically significant effect on the clearance of drugs whose metabolism occurs with the participation of cytochrome P450. Studies have confirmed that tadalafil does not inhibit or induce the isoenzymes CYP1A2, CYP3A4, CYP2C9, CYP2C19, CYP2D6, CYP2E1.
Tadalafil does not have a 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 vasodilatory properties and may enhance the effect of antihypertensive drugs aimed at lowering blood pressure. Additionally, patients taking multiple antihypertensive agents 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 treated with antihypertensive drugs and taking tadalafil should be given appropriate clinical advice.
There was no significant reduction in blood pressure when using tadalafil in individuals taking the selective alpha 1A blocker tamsulosin.
Concomitant use of tadalafil with doxazosin is contraindicated. When tadalafil was administered to healthy volunteers taking doxazosin (4-8 mg per day), an alpha1-blocker, an increase in the hypotensive effect of doxazosin was observed. Some patients experienced dizziness. No fainting was observed. Doxazosin has not been studied at lower doses.
Tadalafil did not affect the concentration of alcohol, nor did alcohol affect the concentration of tadalafil. At high doses of alcohol (0.7 g/kg), taking tadalafil did not cause a statistically significant decrease in mean blood pressure. Postural dizziness and orthostatic hypotension have been observed in some patients. When taking tadalafil in combination with lower doses of alcohol (0.6 g/kg), no decrease in blood pressure was observed, and dizziness occurred with the same frequency as when taking alcohol alone.
Tadalafil does not have a clinically significant effect on the pharmacokinetics or pharmacodynamics of theophylline.
Overdose
Symptoms:
with a single dose of up to 500 mg to healthy volunteers and multiple doses of up to 100 mg/day to patients with erectile dysfunction, the undesirable effects were the same as when using the drug in lower doses.
Treatment:
carrying out standard symptomatic therapy. During hemodialysis, tadalafil is practically not excreted.
Storage conditions
Store at a temperature not exceeding 30°C.
Best before date
3 years.
Conditions for dispensing from pharmacies
On prescription
Cialis drug interactions
Cialis does not have a clinically significant effect on the clearance of drugs whose metabolism occurs with the participation of the cytochrome P450 isoenzyme. The results of the study confirmed that tadalafil does not inhibit or induce the isoenzymes CYP 3A4, CYP 1A2, CYP 2D6, CYP 2C19, CYP 2E1 and CYP 2C9. Tadalafil is mainly metabolized by the CYP3A4 enzyme. The selective CYP3A4 inhibitor ketoconazole, when taken at a dose of 400 mg/day, increases the AUC of tadalafil after a single dose by 312%, increases the maximum concentration in blood plasma by 22%, and at a dose of 200 mg/day - by 107 and 15%, respectively. Ritonavir (inhibitor of CYP 3A4, 2C9, 2C19 and 2D6) at a dose of 200 mg 2 times a day increases the AUC of tadalafil after a single dose by 124%, without changing the maximum concentration in the blood. Although specific interactions have not been studied, it can be assumed that protease inhibitors such as saquinavir, as well as CYP3A4 inhibitors such as erythromycin and intraconazole, increase the plasma levels of tadalafil. The selective inducer of CYP 3A4 rifampicin at a dose of 600 mg/day reduces the AUC of tadalafil after a single dose by 88%, and increases its maximum plasma concentration by 46%. It can be expected that the simultaneous use of other CYP3A4 inducers will also reduce the concentration of tadalafil in the blood plasma. Antihypertensive drugs . Tadalafil has a systemic vasodilating effect, which may potentiate the hypotensive effect of antihypertensive drugs. In addition, patients with poorly controlled hypertension taking multiple antihypertensive drugs simultaneously may experience greater reductions in blood pressure. In the vast majority of patients, a decrease in blood pressure is not accompanied by symptoms of hypotension. Patients treated with antihypertensive drugs and taking tadalafil should be given appropriate clinical advice. α-adrenergic receptor blockers . There was no significant reduction in blood pressure in patients taking tadalafil and the selective α1-adrenergic receptor blocker tamsulosin simultaneously. When tadalafil was prescribed to healthy volunteers taking the α1-adrenergic receptor blocker doxazosin at a dose of 4–8 mg/day, an increase in the hypotensive effect was noted. Some patients experienced dizziness. Alcohol . Tadalafil had no effect on ethanol concentrations, and ethanol had no effect on tadalafil concentrations. When taking ethanol in high doses (0.7 g/kg), simultaneous administration of tadalafil did not lead to a statistically significant decrease in blood pressure. Some patients experienced postural dizziness and orthostatic hypotension. Taking tadalafil with lower doses of ethanol (0.6 g/kg) did not cause the development of arterial hypotension, and dizziness was detected with the same frequency as when taking alcohol alone. H2 antagonists . An increase in gastric pH as a result of taking the H2 receptor blocker nizatidine did not affect the pharmacokinetics of tadalafil. Antacids (magnesium hydroxide/aluminum hydroxide) . Concomitant use of antacids (magnesium hydroxide/aluminum hydroxide) with tadalafil reduces the rate of its absorption without changing the AUC exposure of tadalafil. Acetylsalicylic acid . Tadalafil does not increase the duration of bleeding while taking acetylsalicylic acid. Warfarin . Tadalafil has no clinically significant effect on the pharmacokinetics of S-warfarin or R-warfarin and does not affect the prothrombin time induced by warfarin. Theophylline . Tadalafil does not have a clinically significant effect on the pharmacokinetics or pharmacodynamics of theophylline.
