Dynamico Long, 5 mg, film-coated tablets, 28 pcs.
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 TAB P.P.O. 20MG N1
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 the Cmax of tadalafil by 22%, and ketoconazole (at a dose of 200 mg per day) increases the AUC of tadalafil by 107% and the 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 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 alpha1A 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, but the clinical consequences 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), 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 reduction 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.
