- Pharmacological properties
- Indications for Cialis
- Use of Cialis
- Side Effects
- Special Instructions
- Storage Conditions
- Current information
- Recommended equivalents
- Trade names
The active substance of the drug Cialis - tadalafil - is a reversible selective inhibitor of specific PDE type 5 (PDE-5) cGMP. When sexual stimulation causes local release of nitric oxide, PDE-5 inhibition by tadalafil results in an increase in cGMP levels in the corpus cavernosum of the penis. The consequence of this is the relaxation of the smooth muscles of the arteries and the flow of blood to the tissues of the penis, which causes an erection. Tadalafil has no effect in the absence of sexual stimulation.
In in vitro studies, it has been established that tadalafil is a selective PDE-5 inhibitor. PDE-5 is an enzyme found in the smooth muscles of the cavernous body 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 PDE (PDE-1, PDE-2, PDE-4 and PDE-7). Tadalafil is 10,000 times more active at 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 cardiac muscle contraction. In addition, tadalafil is about 700 times more active against PDE-5 than against PDE-6, an enzyme found in the retina and responsible for phototransduction. Tadalafil is also 9000 times more potent against PDE-5 compared to its effect on PDE-8, PDE-9 and PDE-10, and 14 times more potent than PDE-11.
The distribution in tissues and the physiological effects of PDE-8 and PDE-11 have not been determined.
Tadalafil does not affect the perception of colors (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.
For 2.5 mg, 5 mg tablets: rare (<0.1%) reported in all studies about the change in color perception.
Three clinical studies were conducted with the participation of 1504 patients in order to determine the period of onset of the effect of Cialis, which demonstrated a statistically confirmed improvement in erectile function. Cialis acts for 36 hours. The effect appears already 16 minutes after taking the dose in the presence of sexual arousal.
Tadalafil in healthy individuals does not cause a significant change in systolic and diastolic blood pressure compared with placebo in the supine position (mean maximum the decrease is 1.6/0.8 mm Hg) and in the standing position (the average maximum decrease is 0.2/4.6 mm Hg). Tadalafil does not cause a significant change in heart rate. Significant changes were observed in patients who also took nitrates.
A placebo-controlled study of the effect on spermatogenesis of taking tadalafil for 6 months did not reveal a clinically significant effect of the drug on sperm characteristics (quantity, motility and structure of spermatozoa). For 2.5 mg, 5 mg tablets: Tadalafil had no effect on blood levels of testosterone, LH, and FSH.
Tadalafil 2.5 mg and 5 mg once daily have been evaluated in 3 clinical studies including 853 patients of different age (from 21 to 82 years old) and ethnic group, with erectile dysfunction of different severity (mild, moderate, severe) and different etiologies. Most patients have previously taken PDE-5 inhibitors as needed. In the 2 primary efficacy studies, the success rates were 57% and 67% for Cialis 5mg, 50% for Cialis 2.5mg compared to 31% and 37% for placebo. In studies in patients with secondary erectile dysfunction in relation to diabetes, the success rate was 41 and 46% for Cialis 5 mg and 2.5 mg, respectively, compared with 28% for placebo.
Pharmacokinetics. Absorption. After oral administration, tadalafil is rapidly absorbed. The average Cmax in blood plasma is achieved on average 2 hours after ingestion.
The rate and degree of absorption of tadalafil do not depend on food intake, so the drug can be taken regardless of food. The time of administration (morning or evening) does not significantly affect the rate and extent of absorption.
Distribution. The average volume of distribution is about 63 liters. At therapeutic concentrations, 94% of tadalafil binds to plasma proteins.
In healthy individuals, <0.0005% of the administered dose is detected in semen.
Metabolism. Tadalafil is mainly metabolized with the participation of the CYP 3A4 isoenzyme of cytochrome P450. The main circulating metabolite is methylcatecholglucuronide. This metabolite is 13,000 times less active against PDE-5 than tadalafil. Therefore, it can be assumed that this metabolite is not clinically relevant at detectable concentrations.
Excretion. In healthy individuals, the average T½ is 17.5 hours. Tadalafil is excreted mainly in the form of inactive metabolites, mainly with feces (about 61% of the dose) and to a lesser extent in the urine (about 36% of the dose) .
2.5 mg and 5 mg tablets
Oral clearance of tadalafil is 2.5 l/h.
The pharmacokinetics of tadalafil in healthy subjects is linearly proportional to time and dose. Increasing the dose from 2.5 mg to 20 mg, exposure (AUC) increases in proportion to the dose. A constant plasma concentration is achieved within 5 days after a single dose.
The pharmacokinetics of the drug is the same in patients with and without erectile dysfunction.
Separate groups of patients
In healthy elderly people (≥65 years), a lower clearance of tadalafil was noted when taking the drug orally, which was expressed in an increase in AUC by 25% compared with healthy individuals aged 19–45 years. This difference is not clinically significant and does not require dose adjustment.
Renal failure. For 2.5 mg and 5 mg tablets: In studies using a single dose of tadalafil (5-20 mg), tadalafil AUC exposure almost doubled in subjects with mild (creatinine clearance - from 51 to 80 ml / min) or moderate (creatinine clearance - 31 to 50 ml/min) in renal insufficiency, also in subjects with end-stage renal disease on dialysis.
For 20 mg tablets: in subjects with renal insufficiency, including patients on hemodialysis, exposure The AUC of tadalafil was higher than in healthy subjects.
Liver failure. The exposure of tadalafil (according to the AUC value) in patients with mild to moderate hepatic insufficiency is comparable to that in healthy individuals. There are no data on the pharmacokinetics of tadalafil in severe liver failure.
In patients with diabetes mellitus, while using tadalafil, its exposure (AUC) was approximately 19% less than the AUC value in healthy people persons. This difference in exposure does not require dose adjustment.
treatment for erectile dysfunction. The drug is effective in the presence of sexual stimulation.
Adults (men) should be taken by mouth, regardless of food intake.
2.5 mg and 5 mg tablets
The drug should be taken at least 30 minutes before the intended sexual activity.
The effectiveness of tadalafil can be maintained for 36 hours after taking the drug.
Adult men: The usual recommended dose is 10 mg. In patients in whom tadalafil at a dose of 10 mg does not give an adequate effect, it is advisable to use 20 mg. The maximum recommended frequency of administration is 1 time per day.
Tadalafil at a dose of 10 mg and 20 mg is prescribed for use before anticipated sexual activity and is not recommended for continuous daily use.
In patients those planning frequent use of Cialis (at least 2 times a week), it may be appropriate to take the drug daily at a low dose, based on the choice of the patient and the decision of the doctor.
For daily use, the recommended dose is 5 mg / day in approximately the same time. The dose may be reduced to 2.5 mg 1 time per day, depending on individual tolerance.
The feasibility of long-term daily use should be periodically reassessed.
Elderly patients. Dosage adjustment is not required.
Patients with impaired renal function. Patients with mild or moderate renal impairment do not require dosage adjustment. For patients with severe renal insufficiency, the maximum recommended dose is 10 mg, daily use is not recommended.
Patients with impaired liver function. The recommended dose of Cialis is 10 mg, which should be used before intended sexual activity regardless of food intake. Clinical data on the safety of Cialis in patients with severe hepatic insufficiency (Child-Pugh class C) are limited, so the physician must carefully and individually evaluate the benefits / risks of therapy. There are no data on the use of tadalafil at a dose higher than 10 mg in patients with liver damage. Once daily single dose administration has not been evaluated in patients with hepatic impairment, therefore the physician should carefully and individually assess the benefits/risks of this therapy.
Patients with diabetes mellitus: no dosage adjustment required.
20 mg tablets
The recommended dose is 20 mg before anticipated sexual activity. The drug can be taken 16 minutes before sexual activity. The effectiveness of tadalafil may be maintained for up to 36 hours after a dose.
The maximum recommended frequency of administration is 1 time per day.
Elderly patients. Dosage adjustment not required.
Patients with impaired renal function. Dosage adjustment is not required in patients with mild or moderate renal impairment. For patients with severe renal insufficiency, the maximum recommended dose is 10 mg, daily use is not recommended.
Patients with impaired liver function. The recommended dose of Cialis is 10 mg, which should be used before intended sexual activity regardless of food intake. Clinical data on the safety of Cialis in patients with severe hepatic insufficiency (Child-Pugh class C) are limited, so the physician must carefully and individually assess the benefits / risks of therapy. No data are available on the use of tadalafil at doses above 10 mg in patients with hepatic impairment.
hypersensitivity to tadalafil or other components of the drug; simultaneous use of organic nitrates in any dosage form.
The drug is not used in men with heart disease, for whom sexual activity is contraindicated. Physicians should be aware of the potential cardiac risk of sexual activity for patients with cardiovascular disease.
The following groups of patients with cardiovascular disease have not been included in clinical trials and therefore tadalafil is contraindicated in them:
- patients with myocardial infarction within the last 90 days;
- patients with unstable angina or angina that occurs during sexual intercourse;
- patients with heart failure that meets II NYHA class or higher in the last 6 months;
- patients with uncontrolled arrhythmias, arterial hypotension (<90/50 mm Hg) or uncontrolled hypertension;
- patients after a stroke that occurred within the last 6 months.
The drug is contraindicated in patients with loss of vision in one eye as a result of non-arterial anterior ischemic optic neuropathy (NAPION), regardless of whether this was due to previous exposure to PDE-5 inhibitors.20mg tablets: Do not use Cialis in patients under the age of 18.
2.5 and 5 mg tablets
Undesirable effects, o reported most frequently were headache and dyspepsia. Adverse reactions were short-term, from mild to moderate.
Data on adverse reactions in patients over the age of 75 years are limited.
The following are data on adverse reactions recorded during clinical studies among patients who used tadalafil when needed and daily, as well as data obtained as a result of post-marketing surveillance among patients who used Cialis when necessary.
(≥1/ 100 to >1/10)
(≥1/1000 to 1/100)
|On the part of the immune system|
|From the CNS|
Temporary memory loss
|From the side of the organ of vision|
|  ;||Blurred vision
Sensations described as pain in the eyes
Swelling of the eyelids
Retinal vein occlusion
|On the side of the ear|
|Sudden hearing loss|
|Palpitation||Tachycardia||Myocardial infarction||Unstable angina
|Redness of the face||Arterial hypotension (more often in patients who used tadalafil along with antihypertensive drugs)
|Respiratory, thoracic and mediastinal systems|
|Skin and subcutaneous tissue|
|On the part of the musculoskeletal system and connective tissue|
|On the part of the reproductive system and mammary gland|
|General disorders and condition of the insertion zone|
|Chest pain||Facial swelling||Sudden cardiac death|
A slightly higher prevalence of ECG abnormalities, primarily sinus bradycardia, has been reported in patients treated with tadalafil 1 once daily compared to placebo. Most of these ECG abnormalities were not associated with adverse reactions.
20 mg tablets
Reported adverse effects the most common are headache and dyspepsia (≥10%).
Below is a table that contains data on adverse reactions that were obtained during placebo-controlled clinical trials and post-marketing observations.
|Very common (≥10%)||Often (≥1%, <10%)||Rarely (≥0.01%, <0.1%)|
|Immune System Disorders|
|Nervous system disorders|
|Headache||Dizziness||Impaired cerebral circulation1 (including hemorrhagic phenomena), loss consciousness, transient ischemic attack1, migraine3 , convulsions, transient anemia|
|Blurred vision, sensations described as pain in eyes||Visual field defects, eyelid edema, conjunctival hyperemia, non-arterial anterior optic ischemic neuropathy3, retinal vein occlusion3|
|Hearing and balance disorders|
|  ;||Sudden hearing loss2|
|Tachycardia, palpitations||Myocardial infarction, unstable angina3, ventricular arrhythmia3|
|Flushing||Hypotension (more often when patients used tadalafil together with antihypertensive drugs), hypertension|
|Respiratory System Disorders|
|Abdominal pain and gastroesophageal reflux|
|Skin and subcutaneous tissue disorders|
|Rash, hyperhidrosis||Urticaria, Stevens-Johnson syndrome3 and exfoliative dermatitis|
|Disorders of the musculoskeletal system, connective and musculoskeletal tissue|
|Reproductive System Disorders|
|Prolonged erections, priapism3|
|Abdominal pain1||Swelling persons3, sudden cardiac death1.3|
1Most of the patients who reported these side effects had previous cardiovascular risk factors.
2About the sudden decline or hearing loss have been reported in a small number of cases, all associated with the use of PDE-5 inhibitors, including tadalafil.
3 Adverse reactions from post-marketing studies that were not detected in placebo controlled clinical trials.
Description of selected adverse reactions. A slightly higher incidence of ECG abnormalities, primarily sinus bradycardia, has been reported in patients treated with once-daily tadalafil compared with placebo. Most of these ECG abnormalities were not associated with adverse reactions.
2.5 mg and 5 mg tablets
Erectile dysfunction assessment should include identification of potential underlying causes and identification of an appropriate course of treatment following appropriate medical definitions.
Before starting any treatment for erectile dysfunction, physicians should consider the cardiovascular status of patients, as there is a degree of cardiac risk associated with sexual activity. Tadalafil has an effect on vasodilatation, which can lead to a slight and transient decrease in blood pressure and thus enhance the hypotensive effect of nitrates.
In patients who simultaneously use antihypertensive drugs, tadalafil may cause a decrease in blood pressure. In the case of the start of daily use of tadalafil, measures should be taken regarding the possible correction of the dose of antihypertensive therapy.
Serious cardiovascular events including myocardial infarction, sudden cardiac death, unstable angina, ventricular arrhythmia, stroke, transient ischemic attacks, chest pain, irregular heartbeat, and tachycardia have been reported in post-marketing and/or clinical trials. research. The majority of patients with reported similar cases had previously noted cardiovascular risk factors. However, it is not possible to definitively determine whether these cases are directly related to risk factors, the use of Cialis, sexual activity, or a combination of those and other factors.
Visual defects and cases of NAPION have been associated with the use of tadalafil and other PDE-5 inhibitors. The doctor should warn the patient about the need to stop using tadalafil and seek medical attention in case of sudden loss of vision.
Due to increased tadalafil exposure (AUC), limited clinical experience, and lack of ability to influence dialysis clearance, daily use of tadalafil is not recommended in patients with severe renal impairment.
Given the lack data on the use of tadalafil in patients with severe hepatic impairment (Child-Pugh class C) in this group, tadalafil is prescribed with caution. The use of the drug daily has not been carefully studied in patients with hepatic insufficiency. Before prescribing Cialis, the physician should carefully assess the benefits/risks of this therapy individually.
Patients who experience erections lasting 4 hours or more should be advised to seek medical attention. If priapism is not treated immediately, this can lead to damage to the tissues of the penis and a prolonged loss of potency.
Tadalafil should be used with caution in patients with conditions that may cause a tendency to priapism (such as sickle cell anemia). , multiple myeloma, or leukemia), or patients with anatomical deformities of the penis (such as angular distortion, cavernous fibrosis, or Peyronie's disease).
Evaluation of erectile dysfunction should include identification of underlying potential causes and determination of appropriate therapy after appropriate medical evaluation . It is not known whether Cialis is effective in patients who have undergone pelvic surgery or radical nerve-sparing prostatectomy.
In some patients, the simultaneous use of tadalafil and α1-adrenergic blockers can lead to symptomatic arterial hypotension. The combination of tadalafil and doxazosin is not recommended.
Tadalafil should be used with caution in patients using CYP 3A4 inhibitors (ritonavir, saquinavir, ketoconazole, itraconazole, erythromycin), since an increase in the AUC of tadalafil was noted with the simultaneous use of these drugs.
The safety and efficacy of the combination of tadalafil and other drugs for the treatment of erectile dysfunction have not been studied. Therefore, the use of this combination is not recommended.
The product contains lactose monohydrate, therefore patients with rare hereditary forms of galactose intolerance, lactase deficiency or glucose-galactase malabsorption syndrome should not use the drug.
Assessing erectile dysfunction includes determining its underlying cause and the appropriateness of a course of treatment. Before starting any treatment for erectile dysfunction, the doctor should assess the patient's cardiovascular system, as there is a certain degree of risk associated with sexual activity.
It is not known whether Cialis is effective in patients who have undergone pelvic surgery or radical surgery. prostatectomy without nerve sparing.
There have been reports of visual impairment and NAPION during the use of Cialis and other PDE-5 inhibitors. The physician should warn the patient about the need to stop using tadalafil and seek medical help in case of sudden loss of vision.
The patient should also be warned about a significant increase in the risk of developing NAPION if he had a history of NAPION.< /p>
Patients who experience erections lasting 4 hours or more should be advised to seek immediate medical attention. Untimely treatment of priapism leads to damage to the tissues of the penis with the onset of prolonged impotence.
Cialis should be used with caution in patients with a predisposition to priapism (for example, sickle cell anemia, multiple myeloma or leukemia) or in individuals with deformity of the penis (for example, with angular curvature, cavernous fibrosis or Peyronie's disease).
Data on the safety of using a single dose of Cialis in patients with severe hepatic insufficiency (Child-Pugh class C) are limited. When prescribing Cialis to such patients, a thorough clinical assessment is required.
Caution should be exercised when prescribing Cialis to patients taking α1-adrenergic receptor blockers, since in some cases, the simultaneous use of these drugs can lead to symptomatic hypotension. It is not recommended to combine the use with doxazosin.
Calis should be used with caution in patients receiving treatment with strong inhibitors of CYP 3A4 (ritonavir, saquinavir, ketoconazole, itraconazole, erythromycin), since an increase in the concentration of tadalafil AUC was noted with the simultaneous use of these drugs .
The safety and efficacy of the combination of Cialis and other PDE-5 inhibitors or other drugs for the treatment of erectile dysfunction have not been studied. Therefore, it is necessary to inform patients that Cialis should not be taken in such combinations. Like other PDE-5 inhibitors, tadalafil is able to exert a systemic vasodilating effect, which can lead to a transient decrease in blood pressure. Therefore, before starting treatment, the doctor should assess the degree of the patient's tendency to adverse vasodilatory effects.
The drug should not be prescribed to patients with rare hereditary forms of galactose intolerance, glucose-galactase malabsorption syndrome and Lapp lactase deficiency due to the content of lactose monohydrate.
Use in pregnancy and breastfeeding
Cialis not indicated for use in women. Data from studies on the use of tadalafil in pregnant women are limited.
Children. The use of the drug is not recommended for persons under the age of 18.
Ability to influence reaction speed when driving a vehicle or operating other mechanisms
Tablets of 2.5 and 5 mg. No studies have been conducted on the ability of Cialis to influence the reaction rate when driving vehicles or working with other mechanisms.
Tablets of 20 mg. No studies have been conducted on the ability of Cialis to influence the reaction rate when driving vehicles or working with other mechanisms. Despite the fact that the incidence of dizziness during clinical studies with placebo and during clinical studies with tadalafil was similar, patients should know how tadalafil affects them before driving vehicles or working with other mechanisms.
tadalafil is not expected to have a clinically significant inhibition or induction of drug clearance , the metabolism of which occurs with the participation of the cytochrome P450 isoenzyme. The results of the study confirmed that tadalafil does not inhibit or induce CYP 3A4, CYP 1A2, CYP 2D6, CYP 2C19, CYP 2E1 and CYP 2C9 isoenzymes.
Influence of other substances on tadalafil
Tadalafil is mainly metabolized by the CYP 3A4 enzyme. The selective CYP3A4 inhibitor ketoconazole at a dose of 400 mg/day increases the AUC of tadalafil (20 mg) by 312%, increases plasma Cmax by 22%, and ketoconazole (200 mg daily) increases the AUC one dose of tadalafil (10 mg) by 107% and Cmax by 15% relative to the AUC and Cmax values of one tadalafil.
For 2.5 and 5 mg tablets: CYP 3A4, 2C9, 2C19 and 2D6 inhibitor at a dose of 200 mg 2 times a day increases the AUC of tadalafil after a single dose intake by 124% without changing Cmax in the blood. Although specific interactions have not been studied, it can be assumed that other HIV protease inhibitors, such as saquinavir and others, as well as CYP 3A4 inhibitors, such as erythromycin and itraconazole, increase the level of tadalafil in blood plasma.
For tablets of 20 mg: an 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 Cmax in the blood. Although specific interactions have not been studied, protease inhibitors such as saquinavir and CYP3A4 inhibitors such as erythromycin, clarithromycin, itraconazole, and grapefruit juice may be expected to increase plasma levels of tadalafil.
For 2.5 and 5 mg tablets: reduced exposure to tadalafil is expected when co-administered with rifampicin, which reduces the effectiveness of a daily dose of tadalafil, the magnitude of the reduction is unknown. It is possible that the combined use of tadalafil with other CYP 3A4 inducers will also cause a decrease in the concentration of tadalafil in the blood plasma.
For 20 mg tablets: the selective CYP 3A4 inducer rifampicin (600 mg/day) reduces AUC with a single dose of tadalafil by 88% and Cmax by 46% compared with AUC and Cmax values for only one tadalafil (10 mg). It can be expected that such a decrease in concentration will lead to a decrease in the effectiveness of tadalafil.
It can be expected that the simultaneous use of other CYP 3A4 inducers, such as phenobarbital, phenytoin, carbamazepine, will also contribute to a decrease in the concentration of tadalafil in blood plasma.
Influence of tadalafil on other medicinal products
For tablets of 2.5 and 5 mg: tadalafil has a systemic vasodilatory effect, which may potentiate the hypotensive effect of antihypertensive drugs. In addition, in patients with poorly controlled hypertension, taking several antihypertensive drugs at the same time, a more significant decrease in blood pressure is possible. In most patients, a decrease in blood pressure is not accompanied by symptoms of hypotension. Appropriate clinical advice should be given to persons treated with antihypertensive drugs and taking tadalafil.
For 20 mg tablets: tadalafil has a systemic vasodilatory effect, which may potentiate the hypotensive effect of antihypertensive drugs (calcium channel blockers, ACE inhibitors , beta-adrenergic blockers, thiazide diuretics and angiotensin II receptor blockers, alone and in combination with thiazide diuretics, calcium channel blockers, beta-adrenergic blockers and / or alpha-adrenergic blockers.In addition, in patients with poorly controlled hypertension, taking simultaneously several antihypertensive drugs (up to 4), more significant reduction in blood pressure is possible.In most patients, a decrease in blood pressure is not accompanied by symptoms of hypotension.Appropriate clinical recommendations should be given to persons receiving treatment with antihypertensive drugs and taking tadalafil.
For 2.5 and 5 mg tablets: no significant decrease in blood pressure was found in patients taking tadalafil and a selective α1-adrenergic receptors tamsulosin.
A significant increase in hypotensive action. The effect lasts up to 12 hours and may be symptomatic, including loss of consciousness. The use of this combination is not recommended.
The number of patients with a potentially clinically significant decrease in blood pressure was higher when taking a combination of drugs. Dizziness has been noted in some patients.
For 20 mg tablets: no significant decrease in blood pressure was found in patients taking tadalafil and the selective α1-adrenergic receptor blocker tamsulosin simultaneously.
Alcohol. Tadalafil did not affect the concentration of ethanol, and ethanol did not affect the concentration of tadalafil. Against the background of taking ethanol in high doses (0.7 g/kg of body weight), the simultaneous administration of tadalafil did not lead to a statistically significant decrease in blood pressure. Some patients reported postural dizziness and orthostatic hypotension. The use of tadalafil against the background of ethanol at lower doses (0.6 g / kg) did not cause the development of arterial hypotension, and dizziness was detected with the same frequency as with the use of alcohol alone.
Н 2-antagonists. An increase in gastric pH as a result of the use of the H2-receptor blocker nizatidine had no effect on the pharmacokinetics of tadalafil.< /p>
Antacids (magnesium hydroxide/aluminum hydroxide). Co-administration of antacids (magnesium hydroxide/aluminum hydroxide) with tadalafil reduces its rate of absorption without altering tadalafil AUC exposure.
Acetylsalicylic acid. Tadalafil does not increase the duration of bleeding while taking acetylsalicylic acid.
Warfarin. Tadalafil does not have a clinically significant effect on the pharmacokinetics of S-warfarin or R-warfarin and does not affect warfarin-induced prothrombin time.
For tablets of 2.5 and 5 mg: tadalafil has no clinically significant effect on the pharmacokinetics or pharmacodynamics of theophylline.
For 20 mg tablets: when taking tadalafil (10 mg) with theophylline, no pharmacokinetic interaction was detected. The only minor pharmacodynamic effect was an increase in heart rate. It is necessary to take into account the occurrence of this effect with the simultaneous use of tadalafil with theophylline, despite the fact that this effect has no clinical significance.
For tablets of 20 mg: ethinyl estradiol. Tadalafil increased the bioavailability of oral dosage forms with ethinyl estradiol. A similar increase in bioavailability can be expected when combined with terbutaline, although the clinical consequences of the use of this combination are unknown.
For 20 mg tablets: specific studies of the interaction of tadalafil with antidiabetic drugs have not been conducted.
Incompatibility. Tadalafil is contraindicated in patients using any form of organic nitrate.
symptoms: with a single use in healthy individuals of tadalafil at a dose of up to 500 mg and in patients with erectile dysfunction - repeatedly up to 100 mg / day - side effects were the same as at lower doses. Treatment: in case of overdose, standard symptomatic treatment should be carried out. With hemodialysis, tadalafil is slightly eliminated.
tablets by 2.5 and 5 mg: in the original packaging at a temperature not exceeding 30 °C.
20 mg tablets: in the original packaging at a temperature below 30 °C.
Cialis is relatively new drug for the treatment of erectile dysfunction - the first publications that relate to the experience of its clinical use appeared only in 2001 (Padma-Nathan H., 2001). In recent years, active research has been carried out on its effectiveness, side effects, advantages and disadvantages, as well as other possibilities of its use are being analyzed.
Mechanism of action Cialis
В The action of Cialis is based on the therapeutic effects of tadalafil, a specific reversible inhibitor of phosphodiesterase type 5 (PDE-5). Phosphodiesterases are a superfamily of enzymes that inactivate cAMP and cGPM. These two substances are secondary transmitters in reactions with prostacyclin or nitric oxide. The rationale for its clinical use is the property of PDE-5 inhibitors to express the oxide pathway through inhibition of cGMP hydrolysis. An increase in the concentration of the latter has vasodilating, antiproliferative and proapoptotic effects. The ability of the drug to directly improve the contractile function of the right ventricle has also been proven (Beltrán-Gámez M.E., 2015).
The mechanism of its main effect can be described as follows. As a result of sexual stimulation, a large amount of nitric oxide is locally released in the tissues of the external genital organs of a man (latent phase). In parallel with this, due to the inhibition of PDE-5 by tadalafil, the level of c-GMP increases in the cavernous body of the penis. This contributes to the relaxation of smooth muscle structures and blood flow to the tissues, due to which an erection (tumescence phase) occurs sufficient for sexual intercourse (instruction of the Ministry of Health of Ukraine).
Indications and method of application
Of course , the main and most widely known indication for the use of Cialis is erectile dysfunction. For one-time episodes of sexual activity, it is optimal to take the drug “on demand” (Bansal U.K., 2018). In this case, the patient is recommended a single dose of 10 mg, which is taken at least 30 minutes before sexual activity (although the initial therapeutic effect begins already 16 minutes after oral administration). If the effect of the specified dose is insufficient, then a single dose can be doubled. The drug is taken 1 r / day, with repeated sexual intercourse during the day, a second dose of the drug is not required.
If a man is expected to use Cialis frequently (with interval of no more than 2-3 days), then it would be more rational to systematically take the drug daily at a dose of 5 mg (Peng Z., 2017). If the indicated dose contributes to the development of a pronounced therapeutic effect, then the daily dose can be individually reduced to 2.5 mg (Brock G., 2016).
First of all Cialis relevant for the treatment of erectile dysfunction of vascular origin. However, it also has a positive therapeutic effect in psychogenic erectile dysfunction (Li G., 2017), as well as in neurogenic pathology - the consequences of spinal cord injury (García-Perdomo H.A., 2017).
PDE-5 inhibitors are effective for the treatment of erectile dysfunction, even if it develops as a result of radical or extended prostatectomy. These surgeries are performed for prostate cancer and the technique usually requires the transection of the pudendal nerve, which provides the somatic innervation of the penis. Quality of life studies show that erectile function is better restored with the systematic use of the drug than with its use on demand (Qui Sh., 2016). A similar effect is observed after radiotherapy - Cialis effectively helps with erectile dysfunction, which has arisen as a result of one or more courses of brachytherapy (a treatment method in which a radiation source in a capsule is injected directly into the tissue of the affected organ) (Incrocci L., 2007).
When choosing a drug for the treatment of erectile dysfunction, it must be clearly understood that taking Cialis cannot be equated with receiving stable erection without additional stimulation. It only improves a man's response to sexual stimulation. The drug does not affect sexual desire, therefore, it cannot be recommended for use in women (instruction of the Ministry of Health of Ukraine), however, today studies are underway on the possibility of using tadalafil to improve the quality of sexual life in menopausal women (Borghi C., 2017). If the drug does not bring the expected effect to the man, it is necessary to carefully collect anamnesis - he may have previously used stimulating dietary supplements, in which tadalafil or other PDE-5 inhibitors are added uncontrollably (Park H.N., 2017), sometimes even in doses that significantly exceed the content of the active substance in the original preparation.
Regular or one-time use of Cialis does not require insulin dose adjustment in patients with diabetes, and also does not affect alcohol tolerance.
Other Clinical Uses for Cialis
In 2015, the Canadian Medicines Review Committee published a recommendation to use tadalafil for initial therapy in functional class II or III pulmonary arterial hypertension. A post-marketing study in Japan (Yamazaki H., 2017) demonstrated the safety of long-term use of the drug (2 years or more) for the treatment of this pathology. The use of PDE-5 inhibitors has a relatively short history. The FDA recommendation for the use of the first representative of this group - sildenafil - for the treatment of pulmonary hypertension appeared relatively recently, only in 2005, while tadalafil was approved four years later - in 2009 (Beltrán-Gámez M.E., 2015).
There is also information about the possibility of using the drug to eliminate pulmonary edema in mountain sickness (Leshem E., 2012). This is a specific disease of climbers, which occurs due to a significant pressure drop and oxygen level in the air for a short period of time. Altitude sickness is an extremely severe acute pathological process and can even lead to death if a person is not evacuated to a lower altitude. Therefore, it is important to understand that Cialis is not a remedy for the treatment of pulmonary edema in this situation, and even more so does not allow you to continue climbing. But it can be successfully used as a first aid.
In our time, the possibility of using tadalafil-containing drugs for the treatment of complications of hypertension is being studied. Tadalafil has a positive effect on the rigidity of the arterial bed in the absence of pronounced atherosclerotic changes, as well as on the diastolic function of the left ventricle (Özdabakoğlu O., 2016).
There is a large amount of information about the treatment of benign prostatic hyperplasia with drugs containing tadalafil. It is noted that the maximum therapeutic effect is achieved when PDE-5 inhibitors are combined with tamsulosin (Pattanaik S., 2019). The drug not only improves the oxygenation of the glandular tissue, but also helps to relax the smooth muscles of the bladder neck near the prostate gland, reduces the severity of inflammation, improves pelvic blood flow and afferent transmission of nerve impulses (Fukumoto K., 2016). Thus, tadalafil significantly alleviates the symptoms of chronic pelvic pain in men (Nishino Y., 2017).
It has also been proven (Tan P., 2017) that long-term use of PDE-5 inhibitors contributes to a moderate increase in sperm motility and improvement of their morphological characteristics in men with infertility. However, the official instructions indicate that Cialis helps to reduce the concentration of sperm in the ejaculate (possibly due to liquefaction of the mucous fraction).
It can also be considered promising the use of tadalafil for the prevention of osteoporosis in women who, for one reason or another, underwent bilateral oophorectomy (Hamit H.A., 2017), that is, underwent surgical castration. In such a situation, hormonal changes do not occur smoothly, as with menopause, but at the same time, and therefore they are much more difficult to tolerate.
The literature describes the experience of using tadalafil for the treatment of intrauterine growth retardation (Kubo M., 2016). The drug reduces the severity of fetal distress syndrome and modulates the processes of intrauterine development. However, in the official Cialis instructions, pregnancy is considered a contraindication to the use of this drug.
In an experiment on rats, the nephroprotective properties of tadalafil have been proven - it is able to protect the kidney tissue and reduce the level of pro-inflammatory cytokines in case of short-term renal ischemia followed by its reperfusion (Medeiros V.F., 2017). The nephroprotective properties of tadalafil can be used for the treatment of contrast-induced nephropathy - a kind of damage to the renal parenchyma by drugs for radiopaque or MR contrast studies (Abassi Z., 2015).
In addition, a positive effect of the use of tadalafil in patients with simulated syndrome of multiple organ failure (Oliveira G.G., 2017). It significantly reduces the severity of damage to internal organs both during ischemia and during reperfusion. However, to date, these properties have not found clinical application. This can be explained by the fact that tadalafil, both in the original and in generic drugs, is presented exclusively in tablet form, which cannot be used in intensive care - due to the peculiarities of the clinical situation, parenteral routes of administration are preferred. From the experiments described, the only practical recommendation at the moment can be made - Cialis can be used in the complex of preoperative preparation for extensive interventions in which significant surgical trauma is expected.
< h3>Peculiarities of use and side effects
The available literature reports the possibility of partial loss of vision after the use of Cialis (Bella A.J., 2006). This phenomenon has been associated with a specific condition called non-arterial ischemic optic neuropathy. To date, it has not been proven that the drug is the direct cause of impaired blood supply to the optic nerve, however, its uncontrolled use can become a trigger for the development of such pathological processes.
There are also separate reports of reversible hearing loss associated with taking Cialis (Wester J.L., 2018). Symptoms of hearing loss (preceding tinnitus) indicate a neurological genesis of the pathology. In this case, the pathogenesis of the disease is presumably similar to the optic nerve neuropathy described above.
Regular use of tadalafil can lead to spontaneous migration of stones from the distal urinary tract (Bai Y., 2017), which will be accompanied by unpleasant sensations of varying severity , similar to the symptoms of renal colic.
Patients who use high doses of PDE-5 inhibitors at a single time often note a specific side effect - an imperative urge to defecate. This phenomenon is not considered medically significant, however, for those who are taking the drug for the first time, it is necessary to take into account such phenomena.
Priapism is a rare side effect of Cialis, since an erection does not occur spontaneously, but only after sexual stimulation. However, if the patient has penile deformities (congenital or traumatic origin) or Peyronie's disease (fibrous degeneration of the tissue of the cavernous bodies), then a stable painful erection may develop even after sexual contact.
The adverse reactions mentioned above cause some discomfort when using Cialis, so the need for a comparative analysis of PDE-5 inhibitors. As a result of the meta-analysis (Gong B., 2017), it was found that tadalafil is similar to sildenafil in terms of the speed of onset of the therapeutic effect, its severity and duration. However, sildenafil is significantly inferior to tadalafil when taking into account the frequency of side effects.