Dynamico Long, 14 pcs., 5 mg, film-coated tablets
The drug for the treatment of erectile dysfunction is a reversible selective inhibitor of the specific PDE5 cGMP. When sexual arousal causes local release of nitric oxide, inhibition of PDE5 by tadalafil results in increased cGMP levels 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 is ineffective in the absence of sexual stimulation.
In vitro studies have shown that tadalafil is a selective PDE5 inhibitor. PDE5 is an enzyme found in the smooth muscles of the corpus cavernosum, in the smooth muscles of the vessels of internal organs, in skeletal muscles, platelets, kidneys, lungs, and cerebellum.
The effect of tadalafil on PDE5 is more active than on other phosphodiesterases. Tadalafil is 10,000 times more active against PDE5 than against PDE1, PDE2, PDE4, which are localized in the heart, brain, blood vessels, liver and other organs. Tadalafil is 10,000 times more potent at blocking PDE5 than PDE3, an enzyme found in the heart and blood vessels. This selectivity for PDE5 over PDE3 is important because PDE3 is an enzyme involved in cardiac muscle contraction. In addition, tadalafil is approximately 700 times more active against PDE5 than against PDE6, which is found in the retina and is responsible for phototransmission. Tadalafil is also 10,000 times more active against PDE5 compared to its effect on PDE7-PDE10.
Effective for 36 hours. The effect appears within 16 minutes after ingestion in the presence of sexual arousal.
Tadalafil in healthy individuals does not cause significant changes in systolic and diastolic blood pressure, compared with placebo, in the supine position (average maximum decrease is 1.6/0.8 mmHg, respectively) and standing (average maximum decrease is 0.2/4.6 mmHg. respectively). Tadalafil does not cause a significant change in heart rate.
Tadalafil does not cause changes in color recognition (blue/green), which is explained by its low affinity for PDE6. In addition, there was no effect of tadalafil on visual acuity, electroretinogram, intraocular pressure and pupil size.
There were no clinically significant effects on sperm characteristics in men taking tadalafil in daily doses for 6 months.
Dynamico Long
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 (at a dose of 400 mg per day) increases the AUC of tadalafil by 312% and Cmax of tadalafil by 22%, and ketoconazole (at a dose of 200 mg per day) increases AUC of tadalafil by 107% and Cmax of tadalafil by 15%.
Ritonavir (at a dose of 200 mg twice daily), an inhibitor of CYP3A4, 2C9, 2C19 and 2D6 isoenzymes, increases the AUC of tadalafil 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 concentrations in blood plasma.
The role of transporters (eg, P-glycoprotein) 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 per day), reduces the AUC value of tadalafil by 88% and the Cmax of tadalafil by 46%. It can be assumed that the simultaneous use of other inducers of the CYP3A4 isoenzyme (such as phenobarbital, phenytoin or carbamazepine) may also reduce the concentration of tadalafil in the blood plasma.
Concomitant use of an antacid (magnesium hydroxide/aluminum hydroxide) and tadalafil reduces the rate of absorption of tadalafil without changing the AUC value of 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 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 (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 isoenzymes of the cytochrome P450 system.
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-warfarin or R-warfarin. Tadalafil does not affect the effect of warfarin on prothrombin time.
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 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 most patients, the decrease in blood pressure was not accompanied by symptoms of hypotension. Patients treated with antihypertensive drugs and taking tadalafil should be given appropriate clinical advice.
According to the results of two clinical studies, 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 the alpha1-blocker doxazosin (4-8 mg per day), an increase in the hypotensive effect of doxazosin was observed. Some patients experienced symptoms associated with low blood pressure, including fainting.
In clinical studies, riociguat was shown to enhance the hypotensive effect of PDE5 inhibitors. Concomitant use of riociguat with PDE5 inhibitors, including tadalafil, is contraindicated.
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 oral terbutaline. however, the clinical implications have not been established.
Tadalafil did not affect the concentration of ethanol, nor did ethanol affect the concentration of tadalafil. At high doses of ethanol (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 ethanol (0.6 g/kg), no decrease in blood pressure was observed, and dizziness occurred with the same frequency as when taking ethanol alone.
Tadalafil does not have a clinically significant effect on the pharmacokinetics or pharmacodynamics of theophylline.
Dynamico Long tablets ppo 5mg No. 14
Compound
1 tablet contains: active substance: tadalafil 2.50 mg/5.00 mg/10.00 mg/20.00 mg; excipients: lactose monohydrate (spray dried) 44.125 mg/88.25 mg/176.50 mg/353.00 mg, sodium lauryl sulfate 0.375 mg/0.75 mg/1.50 mg/3.00 mg, povidone-K12 6.25 mg/12.50 mg/25.00 mg/50.00 mg, crospovidone 6.25 mg/12.50 mg/25.00 mg/50.00 mg, sodium stearyl fumarate 0.50 mg/1, 00 mg/2.00 mg/4.00 mg; film coating: Opadry II 85F32782 yellow 2.00 mg/4.00 mg/7.00 mg/15.00 mg (partially hydrolyzed polyvinyl alcohol 0.800 mg/1.600 mg/2.800 mg/6.000 mg, macrogol-3350 0.404 mg/0.808 mg/1.414 mg/3.030 mg, titanium dioxide (E 171) 0.344 mg/0.688 mg/1.204 mg/2.580 mg, talc 0.296 mg/0.592 mg/1.036 mg/2.220 mg, yellow iron oxide dye (E 172) 0.156 mg/ 0.312 mg/0.546 mg/1.170 mg.
Pharmacokinetics
Absorption After oral administration, tadalafil is rapidly absorbed. The average maximum concentration (Cmax) in blood plasma is achieved on average 2 hours after ingestion. The rate and degree of absorption of tadalafil do not depend on the time of food intake, so DYNAMICO LONG can be used regardless of food intake. Time of administration (morning or evening) did not have a clinically significant effect on the rate and extent of absorption. The pharmacokinetics of tadalafil in healthy volunteers is linear with respect to time and dose. In the dose range from 2.5 to 20 mg, the area under the curve “interaction with other drugs”). The drug should be used with caution in patients with a predisposition to priapism (sickle cell anemia, multiple myeloma or leukemia) or in patients with anatomical deformation of the penis (angular curvature, cavernous fibrosis or Peyronie's disease). Caution should also be exercised when taken simultaneously with inhibitors of the C)YP3A4 isoenzyme (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.
Directions for use and doses
For oral administration. Use of the drug DYNAMICO LONG for the indication: erectile dysfunction (ED). 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 meal times. 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 dose is 10 mg before anticipated sexual activity, regardless of meals. In patients in whom the drug at a dose of 10 mg is not sufficiently effective, a dose of 20 mg is used. The drug should be taken at least 16 minutes before intended sexual activity. Patients can attempt sexual intercourse at any time within 36 hours after taking the drug in order to establish the optimal response time to the drug. The recommended maximum daily dose of DYNAMICO LONG is 20 mg. The maximum recommended frequency of administration is 1 time per day. Doses of 10 mg and 20 mg are used immediately before sexual activity and are not recommended for daily use. Use of the drug DYNAMICO LONG according to the indication of benign prostatic hyperplasia (BPH) or ED/BPH. The recommended dose of DYNAMICO LONG for daily use 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. In patients with mild renal failure (creatinine clearance from 51 to 80 ml/min) and moderate severity (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 DYNAMICO LONG is contraindicated.
Storage conditions
Store at a temperature not exceeding 25 °C. Keep out of the reach of children.
Best before date
2 years. Do not use after the expiration date.
special instructions
Sexual activity has a potential risk for patients with cardiovascular diseases, therefore treatment of erectile dysfunction, including with DYNAMICO LONG, 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 tadalafil with other PDE5 inhibitors and treatments for erectile dysfunction have not been studied, so 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 DYNAMICO LONG, the physician should carefully consider whether patients with cardiovascular disease would be adversely affected by these vasodilatory effects. NAPION 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. Analysis of data from episodic use of PDE5 inhibitors for 1 to 4 days in men with erectile dysfunction suggests an increased risk of developing acute NAION. The doctor should advise patients in case of sudden vision loss to stop taking tadalafil and seek medical help. Physicians should also advise patients that the risk of recurrence of NAPI is greater in patients who have previously had NAPI. Patients suspected of having BPH should undergo testing to rule out prostate cancer. The effectiveness of DYNAMICO LONG in patients who have undergone pelvic surgery or radical prostatectomy without preservation of the neurovascular bundles is unknown.
Description
Dosage 2.5 mg: round biconvex film-coated tablets from light yellow to yellow with a brownish tint, with “2.5” engraved on one side. Dosage 5 mg: oval, biconvex, film-coated tablets from light yellow to yellow with a brownish tint, with “5” engraved on one side. Dosage 10 mg: oval biconvex tablets, film-coated from light yellow to yellow with a brownish tint, with a score and engraving “1” to the left of the score and “0” to the right of the score on one side. Dosage 20 mg: oval biconvex tablets, film-coated from light yellow to yellow with a brownish tint, with a score and engraving “2” to the left of the score and “0” to the right of the score on one side.
Conditions for dispensing from pharmacies
On prescription
Dosage form
film-coated tablets
Manufacturer and organization accepting consumer complaints
Teva Pharmaceutical Enterprises Ltd.
Pharmacodynamics
Tadalafil is a reversible selective inhibitor of specific phosphodiesterase type 5 (PDE-5) of cyclic guanosine monophosphate (cGMP). When sexual arousal causes local release of nitric oxide, inhibition of PDE5 by tadalafil leads to increased concentrations of cGMP 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 arousal. In vitro studies have shown that tadalafil is a selective PDE5 inhibitor. PDE-5 is an enzyme found in the smooth muscle of the corpus cavernosum, vascular smooth muscle of the internal organs, skeletal muscle, platelets, kidneys, lungs and cerebellum. The effect of tadalafil is more pronounced in relation to PDE-5 than in relation to other phosphodiesterases. Tadalafil is 10,000 times more potent at blocking PDE-5 than PDE-1, PDE-2, PDE-4 and PDE-7 enzymes, which are found in the heart, brain, blood vessels, liver, white blood cells, skeletal muscles and other organs . Tadalafil is 10,000 times more potent at blocking PDE-5 than the PDE-3 enzyme, which is 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 approximately 700 times more potent at blocking PDE5 than the PDE6 enzyme, which is found in the retina and is responsible for phototransmission. Tadalafil is 9000 times more active in blocking PDE-5 than the enzymes PDE-8, PDE-9 and PDE-10, and 14 times more active in blocking PDE-5 than PDE-11. The tissue distribution and physiological effects of PDE-8 and PDE-11 inhibition have not yet been studied. Tadalafil improves erection and increases the possibility of successful sexual intercourse. Tadalafil in healthy volunteers 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, respectively) and in the standing position (average maximum decrease is 0. 2/4.6 mmHg, respectively). Tadalafil does not significantly change heart rate. Tadalafil does not cause changes in color recognition (blue/green), which is explained by its low affinity for PDE-6. In addition, there was 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. No adverse effects on sperm morphology or motility were observed in any of the studies. One study found a decrease in mean sperm concentration compared to placebo. Decreased sperm concentration was associated with higher ejaculation frequency. In addition, no adverse effects were observed on mean concentrations of sex hormones, testosterone, luteinizing hormone, and follicle-stimulating hormone with tadalafil compared to placebo. The effectiveness and safety of tadalafil (in doses of 2.5 mg, 5.0 mg) was studied in clinical studies. An improvement in erection was noted in patients with erectile dysfunction of all degrees of severity when taking tadalafil once a day. In primary efficacy studies of 5 mg tadalafil, 62% and 69% of attempted intercourse were successful compared with 34% and 39% of patients taking placebo. Taking 5 mg of tadalafil significantly improved erectile function for 24 hours between doses. Mechanism of action in patients with benign prostatic hyperplasia (BPH) Inhibition of PDE5 by tadalafil, leading to increased concentrations of cGMP in the corpus cavernosum of the penis, is also observed in the smooth muscles of the prostate, bladder and the vessels that supply them. Relaxation of vascular smooth muscle leads to an increase in blood perfusion in these organs, and, as a result, to a decrease in the severity of BPH symptoms. Relaxation of prostate and bladder smooth muscle may further enhance the vascular effects.
Side effects
The most common adverse events in patients with erectile dysfunction and BPH are: headache, dyspepsia, as well as back pain and myalgia. Below are the side effects that were reported during clinical trials and during post-registration use of the drug. Reported side effects were usually mild or moderate and transient. In accordance with the WHO classification, all reactions are distributed according to organ systems and frequency of development: very often (? 1/10); often (?1/100, <1/10); uncommon (?1/1000, <1/100): rare (?1/10000, <1/1000): very rare (<1/10000); frequency unknown (cannot be determined from available data). Immune system disorders: uncommon - hypersensitivity reactions; rarely - angioedema2. Nervous system disorders: often - headache; infrequently - dizziness; rarely - stroke1 (including acute hemorrhagic cerebrovascular accident), fainting, transient ischemic attacks1, migraine2, epileptic seizures2, transient amnesia. Violations of the organ of vision: infrequently - blurred visual perception, pain in the eyeball; rarely - impaired visual fields, swelling of the eyelids, conjunctival hyperemia, NAPION2, occlusion of retinal vessels2. Hearing and labyrinthine disorders: infrequently - tinnitus; rarely - sudden hearing loss. Cardiac disorders1: uncommon - tachycardia, palpitations; rarely - myocardial infarction, ventricular arrhythmias2, unstable angina2. Vascular disorders: often - “flushes” of blood to the face; uncommon - decreased blood pressure3, increased blood pressure. Disorders of the respiratory system, chest and mediastinal organs: often - nasal congestion; infrequently - shortness of breath, nosebleeds. Gastrointestinal disorders: often - dyspepsia; uncommon - abdominal pain, gastroesophageal reflux, diarrhea in patients over 65 years of age, vomiting, nausea. Disorders of the skin and subcutaneous tissues: infrequently - skin rash; rarely - urticaria, Stevens-Johnson syndrome2, exfoliative dermatitis2, hyperhidrosis (excessive sweating). Musculoskeletal and connective tissue disorders: often - back pain, myalgia, pain in the extremities. Renal and urinary tract disorders: uncommon - hematuria. Disorders of the genital organs and mammary gland: infrequently - prolonged erection; rarely - priapism, hematospermia, bleeding from the penis. General disorders: uncommon - chest pain1, peripheral edema, fatigue; rarely - facial swelling2, sudden cardiac death1,2. 1 Observed in patients with pre-existing cardiovascular risk factors. However, it is not possible to accurately determine whether these events are directly related to these risk factors, to tadalafil, to sexual arousal, or to a combination of these or other factors. 2 Adverse reactions identified during post-marketing use that were not observed during clinical placebo-controlled studies. 3 More frequently observed when tadalafil is used in patients already taking antihypertensive agents.
Use during pregnancy and breastfeeding
The drug is not intended for use in women.
Interaction
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 (at a dose of 400 mg per day) increases the AUC of tadalafil by 312% and Cmax of tadalafil by 22%, and ketoconazole (at a dose of 200 mg per day) increases AUC of tadalafil by 107% and Cmax of tadalafil by 15%. Ritonavir (at a dose of 200 mg twice daily), an inhibitor of CYP3A4, 2C9, 2C19 and 2D6 isoenzymes, increases the AUC of tadalafil 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 concentrations in blood plasma. The role of transporters (eg, P-glycoprotein) 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 per day), reduces the AUC value of tadalafil by 88% and the Cmax of tadalafil by 46%. It can be assumed that the simultaneous use of other inducers of the CYP3A4 isoenzyme (such as phenobarbital, phenytoin or carbamazepine) may also reduce the concentration of tadalafil in the blood plasma. Concomitant use of an antacid (magnesium hydroxide/aluminum hydroxide) and tadalafil reduces the rate of absorption of tadalafil without changing the AUC value of 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 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 It is known that tadalafil enhances 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 isoenzymes of the cytochrome P450 system. 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-warfarin or R-warfarin. Tadalafil does not affect the effect of warfarin on prothrombin time. 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 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 most patients, the decrease in blood pressure was not accompanied by symptoms of hypotension. Patients treated with antihypertensive drugs and taking tadalafil should be given appropriate clinical advice. According to the results of two clinical studies, 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 the alpha1-blocker doxazosin (4-8 mg per day), an increase in the hypotensive effect of doxazosin was observed. Some patients experienced symptoms associated with low blood pressure, including fainting. In clinical studies, riociguat was shown to enhance the hypotensive effect of PDE5 inhibitors. Concomitant use of riociguat with PDE5 inhibitors, including tadalafil, is contraindicated. 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 oral terbutaline. however, the clinical implications have not been established. Tadalafil did not affect the concentration of ethanol, nor did ethanol affect the concentration of tadalafil. At high doses of ethanol (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 ethanol (0.6 g/kg), no decrease in blood pressure was observed, and dizziness occurred with the same frequency as when taking ethanol alone. Tadalafil does not have a clinically significant effect on the pharmacokinetics or pharmacodynamics of theophylline.
Overdose
When a single dose of tadalafil was administered to healthy volunteers up to 500 mg and to patients with erectile dysfunction - repeatedly up to 100 mg/day, the undesirable effects were the same as when using lower doses. In case of overdose, standard symptomatic treatment should be carried out. During hemodialysis, tadalafil is practically not excreted.
Impact 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.
