Tadalafil-SZ is a Russian generic of the drug Cialis , intended to improve erectile function. Produced (hence the abbreviation “SZ”). "Tadalafil-SZ" belongs to the group of PDE-5 isoenzyme inhibitors. When its activity is blocked, the vessels of the penis relax as much as possible and fill with blood. “Tadalafil-SZ is an analogue of Viagra (find out about other generics of Viagra), it acts on the same principle, but the active substance is not sildenafil, but tadalafil.
Compound
1 tab.
- tadalafil 20 mg. Excipients: lactose monohydrate - 100.2 mg, lactose monohydrate (lactopress) - 123 mg, microcrystalline cellulose - 53 mg, croscarmellose sodium - 17 mg, crospovidone M (Kollidon CL-M) - 5 mg, crospovidone (Kollidon CL) - 2 mg , extra thin hyprolose - 5 mg, hyprolose - 2 mg, sodium stearyl fumarate - 2 g, sodium lauryl sulfate - 0.8 mg.
Film shell composition: opadry II 85F22037 pink - 10 mg (polyvinyl alcohol, partially hydrolyzed - 4 mg, titanium dioxide E171 - 2.236 mg, macrogol (polyethylene glycol 3350) - 2.02 mg, talc - 1.48 mg, iron dye oxide (II) yellow E172 - 0.143 mg, dye iron oxide (II) red E172 - 0.121 mg).
Reviews from men
Stanislav, 39 years old: “I tried Sildenafil-SZ for the first time (2 tablets of 25 mg at once). After 20 minutes, my nose was stuffy, my face was red, my head was hurting, my hands were shaking - I was scared, I had no time for sex, I could barely get over it. Then I bought Tadalafil-SZ and took only one tablet (5 mg) about half an hour before sex. There were no side effects before or after. It acts gently, safely, no shocks.”
Alexey, 42 years old: “I suffer from diabetes, so I have erection problems, but I was afraid to take stimulants. Tadalafil-SZ was prescribed by a doctor. First at the minimum dosage, then increased to 20 mg (one-time). I haven’t noticed any deterioration in my health, but there is definitely an effect in terms of enhancing intimate life.”
Review of the drug "Tadalafil-C3" from the North Star concern
Directions for use and doses
Inside.
Erectile disfunction. For patients with frequent sexual activity (more than 2 times/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 (1/2 tablet 5 mg) depending on individual sensitivity. For patients with infrequent sexual activity (less than 2 times/week): it is recommended to prescribe Tadalafil-SZ at a dose of 20 mg, immediately before sexual activity as described. The maximum daily dose of Tadalafil-SZ is 20 mg.
BPH or erectile dysfunction/BPH. The recommended dose of Tadalafil-SZ when used once a day is 5 mg; the drug should be taken at approximately the same time of day, regardless of the time of sexual activity. The duration of treatment is determined by the doctor individually.
Kidney failure. In patients with mild (creatinine clearance from 51 to 80 ml/min) and moderate renal failure (creatinine clearance from 31 to 50 ml/min) no dose adjustment is required. In patients with severe renal failure, creatinine Cl.
Reviews from doctors
Doctors prescribe Tadalafil-SZ much more often than Cialis. The domestic drug is not inferior in effectiveness, but is much more affordable. The latter is especially important during long-term course treatment of prostate hyperplasia and serious erectile dysfunction (the course can last 1-2 years, and some take the drug constantly).
Experts consider Tadalafil-SZ a safe remedy, including for men over 65 years of age. First, the minimum dosage is prescribed to check the body's response.
Contraindications
Hypersensitivity to tadalafil or any substance included in the drug; taking medications containing any organic nitrates; the presence of contraindications to sexual activity in patients with 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 class II or higher according to the NYHA classification within the last 6 months, uncontrolled arrhythmias, arterial hypotension (BP loss of vision due to non-arterial anterior ischemic optic neuropathy (NAPION) (regardless of the connection with taking PDE-5 inhibitors); simultaneous use with doxazosin, other PDE-5 inhibitors, other drugs for the treatment of erectile dysfunction, with guanylate cyclase stimulators such as riociguat; chronic renal failure (Cl creatinine, lactase deficiency, lactose intolerance, glucose-galactose malabsorption; age up to 18 years.
With caution: severe liver failure (class C according to the Child-Pugh classification) (there is insufficient data for such patients); simultaneous use of alpha1-blockers (simultaneous use of these drugs can lead to symptomatic arterial hypotension in some patients; when using a single dose of tadalafil, symptomatic hypotension is not observed when used simultaneously with tamsulosin, a selective alpha1A-blocker (see “Interactions”); predisposition to priapism (with sickle cell anemia, multiple myeloma or leukemia) or anatomical deformation of the penis (angular curvature, cavernous fibrosis or Peyronie's disease); concomitant use with inhibitors of the CYP3A4 isoenzyme (including ritonavir, saquinavir, ketoconazole, itraconazole, clarithromycin , erythromycin, grapefruit juice), antihypertensive drugs, 5-alpha reductase inhibitors.
Diagnosis of erectile dysfunction should include identifying the potential underlying cause, appropriate medical examination, and determining treatment options.
special instructions
Sexual activity has potential risks for patients with cardiovascular disease. Therefore, treatment of erectile dysfunction, incl. Tadalafil-SZ should not be used 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 of the need to seek immediate medical attention if an erection occurs that lasts 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 Tadalafil-SZ with other PDE5 inhibitors and treatments for erectile dysfunction 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 Tadalafil-SZ, physicians should carefully consider whether patients with cardiovascular disease would be adversely affected by these vasodilatory effects.
NAPION causes visual impairment, including complete loss. 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.
Patients suspected of having BPH should undergo testing to rule out prostate cancer.
The effectiveness of Tadalafil-SZ in patients undergoing pelvic surgery or radical neurosparing prostatectomy is unknown.
Influence on the ability to drive vehicles and machinery. During treatment with Tadalafil-SZ, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.
Analogs
Some men are afraid to buy Tadalafil-SZ, preferring Cialis. Both drugs have the same active ingredient, so the only difference between them is the price. On thematic forums, many claim that only the original works well, but doctors claim that this is just a placebo effect and they work the same way.
Some people experienced stronger side effects after taking Tadalafil-SZ than after taking Cialis. This can be explained by the purchase of a counterfeit drug, the characteristics of the current condition, or inappropriate dosage.
Severnaya Zvezda also produces Sildenafil-SZ, a generic drug of Viagra (one active ingredient), an analogue of Talalafil-SZ. It cannot be combined with fatty foods and alcohol - the first will slow down absorption, the second will increase side effects. The drug begins to act within an hour. Compared to tadalafil, sildenafil works more sharply. After taking it, the maximum level of erection is achieved, in some men even to the point of pain in the penis. "Sildenafil-SZ" is suitable for those who want to surprise their woman, cope with psychological stress, as well as those suffering from serious erectile dysfunction.
Comparison of popular generics for enhancing erections (click on the image to enlarge)
"Tadalafil-SZ" is a drug for married couples in long-term relationships who want to enhance and diversify sensations. It acts softly and naturally, the maximum effect is manifested during friction.
Side effects are more pronounced with Sildenafil-SZ, since the active substance acts less selectively and inhibits various types of PDE isoenzymes, not only PDE-5. For this reason, many men have a headache, a red face, and a stuffy nose after taking it. After Tadalafil-SZ, such symptoms occur much less frequently, but the joints and lower back may hurt (especially if you have kidney problems).
Have you ever taken erectile dysfunction pills?
The price of Sildenafil-SZ is cheaper than Tadalafil-SZ: 20 tablets of 25 mg (standard dosage) cost 365 rubles. The original Viagra and Cialis will cost 528 rubles. per tablet of 100 mg and 830 rubles. per tablet of 20 mg, respectively.
Analogues of Tadalafil-SZ are also the drugs Levitra (considered the safest), Avanafil, Zidena. A similar principle of action is used for Impaza tablets (400 rubles per pack), the active substance of which is antibodies with enzymatic activity. "Impaza" also helps to dilate the blood vessels of the penis, but this effect is cumulative. Suitable for combined use with tadalafil (allows you to reduce its dosage).
A drug for the treatment of erectile dysfunction, it increases libido (sex drive) and satisfaction with sexual intercourse. The price of the drug is from 449 rubles.
Cialis has many relatively cheap Indian generics (Tadarise, Tadacip, Vidalista), but many men are dissatisfied with the effect they provide. The reason may be the dishonesty of the manufacturer or the falsification of the drug.
All PDE5 inhibitors have one more thing in common - they will not work without sexual arousal. This explains the dissatisfaction of some men: there are side effects after taking the pill, but the penis does not react.
Side effects
The most common adverse events in patients with erectile dysfunction and BPH are headache and dyspepsia, as well as back pain and myalgia.
In accordance with the WHO classification, all reactions are distributed according to organ system and frequency of development: very often (≥1/10); often (≥1/100,
From the immune system: infrequently - hypersensitivity reactions; rarely - angioedema.
From the nervous system: often - headache; infrequently - dizziness; rarely - stroke (including acute cerebrovascular accident (ACVA) of the hemorrhagic type), fainting, transient ischemic attacks, migraine, epileptic seizures, transient amnesia.
From the organ of vision: infrequently - blurred visual perception, pain in the eyeball; rarely - impaired visual fields, swelling of the eyelids, conjunctival hyperemia, NAPION, occlusion of retinal vessels.
From the organ of hearing and labyrinthine disorders: infrequently - ringing in the ears; rarely - sudden hearing loss.
From the side of the heart: infrequently - palpitations, tachycardia; rarely - myocardial infarction, ventricular arrhythmias, unstable angina.
From the side of blood vessels: often - flushing of blood to the face; infrequently - decreased blood pressure, increased blood pressure.
From the respiratory system, chest and mediastinal organs: often - nasal congestion; infrequently - shortness of breath, nosebleeds.
From the gastrointestinal tract: often - dyspepsia; uncommon - abdominal pain, gastroesophageal reflux, diarrhea in patients over 65 years of age, vomiting, nausea.
From the skin and subcutaneous tissues: infrequently - rash; rarely - urticaria, Stevens-Johnson syndrome, exfoliative dermatitis, hyperhidrosis (excessive sweating).
From the musculoskeletal system and connective tissue: often - back pain, myalgia, pain in the extremities.
From the kidneys and urinary tract: infrequently - hematuria.
From the genital organs and mammary gland: infrequently - prolonged erection; rarely - priapism, hematospermia, bleeding from the penis.
General disorders: uncommon - chest pain, peripheral edema, fatigue; rarely - facial swelling, sudden cardiac death.
Tadalafil-SZ tab.p.p.o.20mg No. 4 259846
Description
Pharmacological action Drug for the treatment of erectile dysfunction - PDE-5 inhibitor Indications erectile dysfunction; lower urinary tract symptoms in patients with benign prostatic hyperplasia (for a dosage of 5 mg); erectile dysfunction in patients with lower urinary tract symptoms due to benign prostatic hyperplasia (for a dosage of 5 mg). Contraindications: hypersensitivity to tadalafil or any substance included in the drug; taking medications containing any organic nitrates; the presence of contraindications to sexual activity in patients with 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 class II or higher according to the NYHA classification within the last 6 months, uncontrolled arrhythmias, arterial hypotension (BP <90/50 mmHg), uncontrolled arterial hypertension, ischemic stroke within the last 6 months; loss of vision due to non-arterial anterior ischemic optic neuropathy (NAPION) (regardless of the connection with taking PDE-5 inhibitors); simultaneous use with doxazosin, other PDE-5 inhibitors, other drugs for the treatment of erectile dysfunction, with guanylate cyclase stimulators, such as riociguat; chronic renal failure (Cl creatinine <30 ml/min); lactase deficiency, lactose intolerance, glucose-galactose malabsorption; age up to 18 years. With caution: severe liver failure (class C according to the Child-Pugh classification) (there is insufficient data for such patients); simultaneous use of alpha1-blockers (simultaneous use of these drugs can lead to symptomatic arterial hypotension in some patients; when using a single dose of tadalafil, symptomatic hypotension is not observed when used simultaneously with tamsulosin, a selective alpha1A-blocker (see “Interactions”); predisposition to priapism (with sickle cell anemia, multiple myeloma or leukemia) or anatomical deformation of the penis (angular curvature, cavernous fibrosis or Peyronie's disease); concomitant use with inhibitors of the CYP3A4 isoenzyme (including ritonavir, saquinavir, ketoconazole, itraconazole, clarithromycin , erythromycin, grapefruit juice), antihypertensive drugs, 5-alpha reductase inhibitors. Diagnosis of erectile dysfunction should include identification of the potential underlying cause, appropriate medical examination and determination of treatment tactics. Use during pregnancy and lactation Tadalafil-SZ is not intended for use in women. Special instructions Sexual activity has a potential risk for patients with cardiovascular diseases. Therefore, treatment of erectile dysfunction, incl. Tadalafil-SZ should not be used 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 of the need to seek immediate medical attention if an erection occurs that lasts 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 Tadalafil-SZ with other PDE5 inhibitors and treatments for erectile dysfunction 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 Tadalafil-SZ, physicians should carefully consider whether patients with cardiovascular disease would be adversely affected by these vasodilatory effects. NAPION causes visual impairment, including complete loss. 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. Patients suspected of having BPH should undergo testing to rule out prostate cancer. The effectiveness of Tadalafil-SZ in patients undergoing pelvic surgery or radical neurosparing prostatectomy is unknown. Influence on the ability to drive vehicles and machinery. During treatment with Tadalafil-SZ, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions. Side effects The most common adverse events in patients with erectile dysfunction and BPH are headache and dyspepsia, and also back pain, myalgia. In accordance with the WHO classification, all reactions are distributed according to organ system and frequency of development: very often (≥1/10); often (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rarely (≥1\10000, <1\1000); very rare (<1/10000); frequency unknown (it is impossible to determine the frequency of occurrence of reactions from the available data). From the immune system: infrequently - hypersensitivity reactions; rarely - angioedema. From the nervous system: often - headache; infrequently - dizziness; rarely - stroke (including acute cerebrovascular accident (ACVA) of the hemorrhagic type), fainting, transient ischemic attacks, migraine, epileptic seizures, transient amnesia. From the organ of vision: infrequently - blurred visual perception, pain in the eyeball; rarely - impaired visual fields, swelling of the eyelids, conjunctival hyperemia, NAPION, occlusion of retinal vessels. From the organ of hearing and labyrinthine disorders: infrequently - ringing in the ears; rarely - sudden hearing loss. From the side of the heart: infrequently - palpitations, tachycardia; rarely - myocardial infarction, ventricular arrhythmias, unstable angina. From the side of blood vessels: often - flushing of blood to the face; infrequently - decreased blood pressure, increased blood pressure. From the respiratory system, chest and mediastinal organs: often - nasal congestion; infrequently - shortness of breath, nosebleeds. From the gastrointestinal tract: often - dyspepsia; uncommon - abdominal pain, gastroesophageal reflux, diarrhea in patients over 65 years of age, vomiting, nausea. From the skin and subcutaneous tissues: infrequently - rash; rarely - urticaria, Stevens-Johnson syndrome, exfoliative dermatitis, hyperhidrosis (excessive sweating). From the musculoskeletal system and connective tissue: often - back pain, myalgia, pain in the extremities. From the kidneys and urinary tract: infrequently - hematuria. From the genital organs and mammary gland: infrequently - prolonged erection; rarely - priapism, hematospermia, bleeding from the penis. General disorders: uncommon - chest pain, peripheral edema, fatigue; rarely - facial swelling, sudden cardiac death. Drug interactions Tadalafil is mainly metabolized with the participation of the CYP3A4 isoenzyme. A selective inhibitor of the CYP3A4 isoenzyme ketoconazole (400 mg/day) increases the exposure of a single dose of tadalafil (AUC) by 312% and Cmax by 22%, and ketoconazole (200 mg/day) increases the exposure of a single dose of tadalafil (AUC) by 107% and Cmax by 107% and Cmax by 22%. 15% relative to AUC and Cmax values for tadalafil alone. Ritonavir (200 mg twice daily), an inhibitor of CYP3A4, CYP2C9, CYP2C19 and CYP2D6, increases single-dose tadalafil exposure (AUC) by 124% without changing Cmax. Although specific interactions have not been studied, it can be assumed that other inhibitors
Compound
1 tab. — tadalafil 20 mg. Excipients: lactose monohydrate - 100.2 mg, lactose monohydrate (lactopress) - 123 mg, microcrystalline cellulose - 53 mg, croscarmellose sodium - 17 mg, crospovidone M (Kollidon CL-M) - 5 mg, crospovidone (Kollidon CL) - 2 mg , extra thin hyprolose - 5 mg, hyprolose - 2 mg, sodium stearyl fumarate - 2 g, sodium lauryl sulfate - 0.8 mg. Film shell composition: opadry II 85F22037 pink - 10 mg (polyvinyl alcohol, partially hydrolyzed - 4 mg, titanium dioxide E171 - 2.236 mg, macrogol (polyethylene glycol 3350) - 2.02 mg, talc - 1.48 mg, iron dye oxide (II) yellow E172 - 0.143 mg, dye iron oxide (II) red E172 - 0.121 mg).
Application
Inside. Erectile disfunction. For patients with frequent sexual activity (more than 2 times/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 (1/2 tablet 5 mg) depending on individual sensitivity. For patients with infrequent sexual activity (less than 2 times/week): it is recommended to prescribe Tadalafil-SZ at a dose of 20 mg, immediately before sexual activity as described. The maximum daily dose of Tadalafil-SZ is 20 mg. BPH or erectile dysfunction/BPH. The recommended dose of Tadalafil-SZ when used once a day is 5 mg; the drug should be taken at approximately the same time of day, regardless of the time of sexual activity. The duration of treatment is determined by the doctor individually. Kidney failure. In patients with mild (creatinine clearance from 51 to 80 ml/min) and moderate renal failure (creatinine clearance from 31 to 50 ml/min) no dose adjustment is required. In patients with severe renal failure (creatinine clearance <30 ml/min and on hemodialysis), the use of Tadalafil-SZ is contraindicated.
Drug interactions
Tadalafil is mainly metabolized with the participation of the CYP3A4 isoenzyme. A selective inhibitor of the CYP3A4 isoenzyme ketoconazole (400 mg/day) increases the exposure of a single dose of tadalafil (AUC) by 312% and Cmax by 22%, and ketoconazole (200 mg/day) increases the exposure of a single dose of tadalafil (AUC) by 107% and Cmax by 107% and Cmax by 22%. 15% relative to AUC and Cmax values for tadalafil alone.
Ritonavir (200 mg twice daily), an inhibitor of CYP3A4, CYP2C9, CYP2C19 and CYP2D6, 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, clarithromycin, itraconazole and grapefruit juice, may increase tadalafil plasma concentrations. The role of transporters (including P-gp) in the distribution of tadalafil is unknown. The potential for drug interactions mediated by transporter inhibition exists.
A selective inducer of the CYP3A4 isoenzyme, rifampicin (at a dose of 600 mg/day), reduces single-dose tadalafil exposure (AUC) by 88% and Cmax by 46% relative to AUC and Cmax for tadalafil alone. It can be assumed that the simultaneous use of other inducers of the CYP3A4 isoenzyme (such as phenobarbital, phenytoin or carbamazepine) 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 AUC of tadalafil.
An increase in gastric pH as a result of taking the H2-histamine receptor blocker nizatidine had no effect on the pharmacokinetics of tadalafil.
The safety and effectiveness of combining tadalafil with other treatments for erectile dysfunction or other PDE5 inhibitors has not been studied and the use of such combinations is not recommended.
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) 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 AUC of S- or R-warfarin. Tadalafil does not affect the effect of warfarin on PT.
Tadalafil does not potentiate the increase in the duration of bleeding caused by taking acetylsalicylic acid.
Tadalafil has systemic vasodilatory properties and may enhance the effect of antihypertensive drugs. 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 healthy volunteers co-administered tadalafil and the selective alpha1A-blocker tamsulosin.
Concomitant use of tadalafil with doxazosin is contraindicated. When tadalafil was administered to healthy volunteers taking doxazosin (4–8 mg/day), an alpha1-blocker, an increase in the hypotensive effect of doxazosin was observed. Some patients experienced symptoms associated with decreased blood pressure, including syncope.
Concomitant use of riociguat with PDE5 inhibitors, including tadalafil, is contraindicated because Riociguat enhances the hypotensive effect of PDE-5 inhibitors.
Drug interaction studies have not been conducted with tadalafil and 5-alpha reductase inhibitors; caution should be exercised when taking them simultaneously.
Tadalafil causes an increase in the bioavailability of ethinyl estradiol when taken orally. A similar increase in bioavailability can be expected with terbutaline, but the clinical implications have not been established.
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.
Pharmacodynamics and pharmacokinetics
The drug promotes the release of nitric oxide from nerve endings located in the endothelium of the cavernous bodies. The oxide, in turn, stimulates the synthesis of cyclic guanosine monophosphate in smooth muscle fiber cells. CGMP accumulates in muscle tissue and causes it to relax, increasing blood flow to the carvenous bodies. Thus, the process of inhibition of phosphodiesterase 5 is accompanied by increased erection and an increase in cGMP . The main condition for the occurrence of the chain of reactions listed above is sexual stimulation. In the absence of this kind of activity, the active substance is ineffective.
The drug affects PDE 5 in the smooth muscles of the carvenous bodies, skeletal muscles, smooth muscles of internal organs and blood vessels, platelets , lungs, pancreas, kidneys and cerebellum.
The drug affects all phosphodiesterases in the human body (PDE 2, PDE 7, PDE 1, PDE 4, PDE 3 ), located in the brain, liver, middle, blood vessels, skeletal muscles and leukocytes , however, PDE 5 almost exclusively 700-1000 times stronger. Tadalafil also has a minor effect on PDE11A1, PDE 8, PDE 10 and PDE 9 . The drug also has the ability to inhibit the activity of recombinant PDE11A1 in standard, therapeutic concentrations.
After oral administration, the drug is quickly and completely absorbed in the gastrointestinal tract; pharmacokinetic parameters do not change with parallel food intake. After a single dose of the recommended therapeutic dosage, the maximum concentration of the substance is observed after 30 minutes - 6 hours. When using therapeutic doses, the degree of binding to plasma proteins is 94%.
When conducting studies on healthy patients, after taking a tablet, less than one ten-thousandth of the substance taken was found in the sperm (the drug had no effect on sperm motility, their morphology and quantity).
Daily administration of the drug leads to the establishment of an equilibrium concentration within 5 days after the start of treatment. In this case, AUC increases approximately 1.6 times compared to a single use of the drug.
During metabolism, Tadalafil is converted to catechol using the CYP3A4 isoenzyme . Catechol then undergoes glucuronidation and methylation, forming methylcatechol and its glucuronide conjugant . The resulting metabolites are pharmacologically inactive.
In healthy patients, the half-life is approximately 17.5 hours. The drug is excreted in the form of inactive metabolites in feces and urine.
In elderly individuals, a decrease in drug clearance and an increase in AUC are observed.
In persons suffering from liver disease, when taking 10 mg of the drug, no clinically significant changes in pharmacokinetics were observed. In patients with renal impairment, plasma concentrations and AUC increased.
Clinical studies have shown that no dosage adjustment is required for patients with diabetes .
The drug does not exhibit carcinogenic, mutagenic or clastogenic activity.
Animal tests did not reveal any effect of the drug on fertility , morphology of the reproductive organs or reproductive behavior. The substance and its metabolites penetrate the placenta of animals and are excreted in milk.
The medicine begins to act 16 minutes after oral administration and continues for 36 hours.
The drug has no effect on blood pressure and heart rate, but enhances the hypotensive effect after parallel administration of nitrates .
During research on the substance, a Farnsworth-Munsell 100 , which demonstrated a transient, dose-dependent distortion of the patient's color perception. However, the medicine had no effect on pupil size, visual acuity or intraocular pressure .
In general, this substance has been well researched and tested on various groups of patients.
