Description
Pharmacological action of
Tadalafil is a reversible selective inhibitor of specific type 5 phosphodiesterase (PDE-5) cyclic guanosine monophosphate (cGMP). When sexual arousal causes local release of nitric oxide, inhibition of PDE-5 by tadalafil leads to an increase in the concentration of cGMP in the cavernous body 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.
In vitro studies have shown that tadalafil is a selective PDE-5 inhibitor. PDE-5 is an enzyme present in the smooth muscles of the cavernous body, blood vessels and internal organs, in skeletal muscles, platelets, kidneys, lungs and cerebellum. The effect of tadalafil on PDE-5 is more active than on other phosphodiesterases.
Tadalafil is 10,000 times more potent with respect to PDE-5 than with other types of phosphodiesterase (PDE-1, PDE-2, PDE-4 and PDE-7), which are localized in the heart, brain, blood vessels, liver, white blood cells and other organs. Tadalafil is 10,000 times more active in blocking PDE-5 than PDE-3, an enzyme that is found in the heart and blood vessels. This selectivity for PDE-5 compared to PDE-3 is important because PDE-3 is an enzyme involved in the contraction of the heart muscle.
In addition, tadalafil is approximately 700 times more active in relation to PDE-5 than PDE-6, which is found in the retina and is responsible for photo transmission. The action of tadalafil in relation to PDE-5 is 9000 times more pronounced than its effect on PDE-8, PDE-9 and PDE-10, and 14 times more pronounced than on PDE-11. The distribution in tissues and the physiological effects of the inhibition of PDE-8 – PDE-11 have not yet been clarified.
Tadalafil in healthy volunteers does not cause a significant change in systolic and diastolic blood pressure compared to placebo in the supine position (average maximum decrease is 1.6 and 0.8 mmHg, respectively) and in the standing position (average maximum decrease is 0 , 2 and 4.6 mmHg, respectively).
Tadalafil does not cause a significant change in heart rate.
Tadalafil does not cause color recognition changes (blue / green), due to its low affinity for PDE-6. In addition, there is no effect of tadalafil on visual acuity, electroretinogram, intraocular pressure and pupil size.
Several studies have been conducted to evaluate the effect of daily tadalafil on spermatogenesis. None of the studies showed an undesirable effect on sperm morphology and motility. One study found a decrease in mean sperm concentration compared to placebo.
A decrease in sperm concentration was associated with a higher frequency of ejaculation. Moreover, when comparing tadalafil with placebo, there was no undesirable effect on the average concentration of sex hormones (testosterone, luteinizing hormone and follicle-stimulating hormone).
Erectile Dysfunction (ED)
In our studies, tadalafil showed a statistically significant improvement in erectile function and the ability to have full sexual intercourse. Tadalafil has no effect in the absence of sexual arousal.
The efficacy and safety of tadalafil has been studied in clinical trials. An improvement in erection in patients with ED of all degrees of severity was observed when taking 5 mg of tadalafil once a day for 36 hours after administration, as well as maintaining an erection for 16 minutes after administration compared with placebo.
In studies of primary efficacy of 5 mg of tadalafil, 57% and 67% of attempts at sexual intercourse were successful compared with 31% and 37% with placebo. In studies of patients with secondary ED on the background of diabetes mellitus, 41% of attempts at sexual intercourse were successful compared to 28% with placebo.
Benign prostatic hyperplasia (BPH)
In patients with BPH, tadalafil, by inhibiting PDE-5, leads to an increase in the concentration of cGMP not only in the cavernous body of the penis, but also in the smooth muscles of the prostate, bladder and blood vessels that supply them. This in turn increases blood perfusion in these organs and, as a result, reduces the severity of symptoms of BPH.
Relaxation of the smooth muscles of the prostate and bladder and inhibition of the afferent innervation of the bladder can further enhance vascular effects.
Clinical studies have shown a decrease in symptoms of BPH within 1 week after taking 5 mg of tadalafil compared to placebo.
In studies involving patients with ED and symptoms of BPH with 5 mg of tadalafil, 71.9% of attempts at sexual intercourse were successful compared to 48.3% with placebo, and there was a significant improvement in erectile function and a decrease in symptoms of the prostate gland .
Indications
– Erectile dysfunction
– symptoms of the lower urinary tract in patients with BPH (for a dosage of 5 mg)
– erectile dysfunction in patients with symptoms of the urinary tract in patients with BPH (for a dosage of 5 mg).
Contraindications
– Hypersensitivity to tadalafil or to any substance that is part of the drug
– taking drugs, containing any organic nitrite
– children under 18 years of age
– contraindications to sexual activity in patients with diseases of the cardiovascular system: myocardial infarction in the last 90 days, unstable angina, the occurrence of angina attack during sexual intercourse, chronic heart failure II IV classes according to NYHA classification, uncontrolled arrhythmia, arterial hypotension (blood pressure <90/50 mm Hg), uncontrolled arterial hypertension, ischemic stroke during the last 6 months yatsev – loss of vision due nearterialnoy anterior ischemic optic neuropathy (regardless of the connection with the reception of PDE-5 inhibitors) – simultaneous reception doxazosin, other drugs for treating erectile dysfunction, guanylate cyclase stimulants (riotsiguat) – use in patients with severe renal failure (CC <30 ml / min). – lactase deficiency, lactose intolerance, glucose-galactose malabsorption. Caution: – Severe liver failure (Child-Pugh class C) due to insufficient data on the efficacy / safety of – simultaneous use of selective alpha-blockers, potent inhibitors of the isoenzyme CYP3A4 (ritonavir, saquinavir, itraconazole ), 5-alpha reductase inhibitors – predisposition to priapism (with sickle cell anemia, multiple myeloma or leukemia), anatomical deformation of the penis (angular curvature ny, cavernous fibrosis or Peyronie’s disease). Special instructions Diagnosis of ED and BPH should include identification of the underlying cause of the disease, appropriate medical examination, determination of treatment tactics and an individual assessment of the benefit / risk ratio. Sexual activity has a potential risk for patients with cardiovascular disease, therefore, treatment of ED should not be carried out in men with heart diseases in which sexual activity is not recommended. Like other PDE-5 inhibitors, tadalafil can have a systemic vasodilator effect, which can lead to a transient decrease in blood pressure and an increase in the hypotensive effect of nitrates, alpha-blockers. Before prescribing the drug, it is necessary to carefully assess the likelihood of such adverse reactions in patients with cardiovascular disease. Patients with a suspected diagnosis of BPH should be screened to rule out prostate cancer. Non-arterial anterior ischemic optic neuropathy (NAPION) is a cause of visual impairment, including complete loss of vision. There are rare post-marketing reports of cases of development of NAPION, in time associated with the intake of PDE-5 inhibitors. It s currently not possible to determine Is there a direct connection between the development of NAPION and the intake of PDE-5 inhibitors or other factors. Patients should be warned that in the event of a sudden loss of vision, stop taking tadalafil and seek medical help. Patients should also be informed that people who have undergone NAPION have an increased risk of re-developing NAPION. Priapism has been reported with PDE-5 inhibitors, including tadalafil. Patients should be informed about the need to immediately seek medical help in case of an erection lasting 4 hours or more. Untimely treatment of priapism leads to damage to the tissues of the penis, resulting in irreversible impotence. The effectiveness of the drug in patients undergoing surgery on the pelvic organs or radical nerve-sparing prostatectomy, is unknown. Impact on the ability to drive transp. Wed and fur .: Despite the fact that the incidence of dizziness against placebo and tadalafil is the same, during treatment, care must be taken when driving vehicles and engaging in other potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions. Patients should be aware of the possible development of drowsiness when taking the drug, especially at the beginning of therapy or in combination with alcohol. Composition Active ingredient: tadalafil – 5,000 mg. Excipients: lactose monohydrate (milk sugar) – 68.325 mg microcrystalline cellulose – 14.250 mg croscarmellose sodium – 6,000 mg hyprolose – 0.665 mg sodium lauryl sulfate – 0.285 mg magnesium srldkp 0.25 mg mg Shell composition: hypromellose – 1.450 mg macrogol-4000 – 0.425 mg titanium dioxide – 0.575 mg iron dye yellow oxide – 0.050 mg. Dosage and administration For oral administration. Use of the drug for ED For patients with frequent sexual activity (more than twice a week), the recommended frequency of administration: daily, 5 mg (1 tablet) once a day, at the same time, regardless of food intake. Dose should be periodically monitored and reviewed as necessary. 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), the recommended frequency of administration: 20 mg (1 tablet or 4 tablets in a dose of 5 mg) immediately before sexual activity according to the instructions for medical use. The maximum daily dose of the drug is 20 mg. Use of the drug for BPH or ED + BPH The recommended dose is 5 mg (1 tablet) once a day. The drug should be taken at approximately the same time of the day, regardless of food intake and time of sexual activity. The duration of treatment is set by the doctor individually. In patients with severe renal failure (CC <30 ml / min or hemodialysis), the use of the drug is contraindicated. In patients with mild renal insufficiency (CC 51 80 ml / min) and moderate severity (CC 31 50 ml / min) or mild and moderate hepatic insufficiency (Child-Pugh classification classes A and B), and also in elderly patients, dose adjustment is not required. Side effects According to the World Health Organization (WHO), adverse reactions are classified according to their frequency of development as follows: very often ( 1/10), often ( 1/100, <1/10), infrequently ( 1/1000, <1/100), rarely ( 1/10000, <1/1000) and very rarely (<1/10000) the frequency is unknown - according to the available data, it was not possible to establish the frequency of occurrence. Immune system disorders: infrequently – hypersensitivity reactions rarely – angioedema 3. Disorders of the nervous system: often – headache infrequently – dizziness rarely – stroke1 (including hemorrhagic), transient ischemic attacks1, fainting, migraine3, epileptic seizure, transient amnesia. Disorders of the organ of vision: infrequently – blurred visual perception, pain in the eyeball rarely – impaired visual fields, swelling of the eyelids, injection of scleral vessels, non-arterial anterior ischemic optic neuropathy 3, retinal vascular occlusion 3. Hearing disorders and labyrinth disorders: infrequently – tinnitus / ringing rarely – sudden hearing loss 2. Heart abnormalities1: infrequently – palpitations, tachycardia rarely – myocardial infarction, ventricular arrhythmias3, unstable angina3. Vascular disorders: often – flushing infrequently – lowering blood pressure (BP) (in patients taking antihypertensive drugs), increased blood pressure. Disorders of the respiratory system, chest and mediastinal organs: often – nasal congestion infrequently – shortness of breath, nose bleed. Disorders of the gastrointestinal tract: often – dyspepsia, gastroesophageal reflux infrequently – abdominal pain. Disorders of the skin and subcutaneous tissue: infrequently – rash, hyperhidrosis (excessive sweating) rarely – urticaria, Stevens-Johnson syndrome3, exfoliative dermatitis3. Violations of the musculoskeletal and connective tissue: often – back pain, pain in the limbs, myalgia. Disorders of the kidneys and urinary tract: often – hematuria. Disorders of the genitals and mammary gland: infrequently – bleeding from the penis, hemospermia rarely – prolonged erection, priapism 3. General disorders and disorders at the injection site: infrequently – chest pain1 rarely – swelling of the face3, sudden cardiac death1.3. 1 Observed in patients previously having cardiovascular risk factors. However, it is impossible to determine exactly whether these phenomena are directly related to these risk factors, to tadalafil, to sexual arousal, or to a combination of these or other factors. 2 Sudden hearing loss has been reported in a small number of cases during post-marketing and clinical trials using all PDE-5 inhibitors, including tadalafil. 3 Adverse reactions detected during post-marketing studies not observed in clinical placebo-controlled studies. Overdose of When prescribing tadalafil once in a dose of up to 500 mg to healthy individuals and repeatedly in a dose of up to 100 mg / day for patients with ED, undesirable reactions were comparable, as well as the use of lower doses. In case of overdose, symptomatic treatment is necessary. With hemodialysis, tadalafil is practically not excreted. Storage conditions At a temperature not exceeding 25 ° C. Keep out of the reach of children. Expiration 3 years. Do not use after expiration date. Deystvuyuschee substances tadalafil Terms and conditions prescription dosage form tablets
