Kamagra: instructions for use, analogues, composition, indications
Kamagra – official instructions for use, composition, indications and contraindications. Prices and analogues of the drug Kamagra on the medical portal 103.kz
Effect of other drugs on sildenafil
In vivo studies
While taking sildenafil with CYP3A4 inhibitors (such as ketoconazole, erythromycin and cimetidine), there is a decrease in the clearance of sildenafil. In this group of patients, there is no increased frequency of side effects, however, it is necessary to begin treatment with Kamagra in the initial dose of 25 mg.
The simultaneous administration of HIV protease inhibitor ritonavir, which is a strong inhibitor of cytochrome P450, in equilibrium (500 mg twice a day) with sildenafil (100 mg in a single dose) leads to an increase in the maximum concentration (Cmax) of sildenafil by 300% (4 times), as well as an increase in plasma AUC of sildenafil by 1000% (11-fold). After 24 hours, plasma levels of sildenafil are approximately 200 ng / ml compared to approximately 5 ng / ml after taking sildenafil alone. These data are consistent with the pronounced effects of ritonavir on a wide range of cytochrome P450 substrates. Based on the above data, the simultaneous use of sildenafil with ritonavir is not recommended.
Kamagra does not affect ritonavir pharmacokinetics.
The maximum dose of sildenafil should under no circumstances exceed 25 mg within 48 hours.
The simultaneous administration of HIV protease inhibitor saquinavir, which is a CYP3A4 inhibitor, in equilibrium (1200 mg three times a day) with sildenafil (100 mg single dose) leads to an increase in Cmax of sildenafil by 140%, as well as an increase in AUC of sildenafil by 210%. Sildenafil does not affect the pharmacokinetics of saquinavir. Stronger inhibitors of CYP3A4, such as ketoconazole and itraconazole, have a more pronounced effect.
With a single dose of sildenafil in a dose of 100 mg together with erythromycin, a moderate CYP3A4 inhibitor, in equilibrium (500 mg twice a day for 5 days), an increase in systemic exposure to sildenafil by 182% (determined by the AUC value) is observed.
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Azithromycin (at a dose of 500 mg per day for 3 days) does not affect the AUC, Cmax, Tmax rates, elimination rate constant or the subsequent half-life of sildenafil or its main circulating metabolite.
Simultaneous use of cimetidine (800 mg), an inhibitor of cytochrome P450 and a nonspecific CYP3A4 inhibitor with sildenafil (50 mg dose) in healthy volunteers, causes an increase in plasma concentrations of sildenafil by 56%.
Grapefruit juice is a weak inhibitor of CYP3A4-mediated metabolism in the intestinal wall and can cause a moderate increase in plasma levels of sildenafil.
does not affect the bioavailability of sildenafil.
CYP2C9 inhibitors (tolbutamide, warfarin and phenytoin), inhibitors of CYP2D6 (selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazide and thiazide diuretics, loop and potassium-sparing diuretics, angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers, beta-adrenergic The receptors and inducers of the metabolic activity of P450 (rifampicin, barbiturates) do not affect the pharmacokinetics of sildenafil.
The simultaneous use of endothelin antagonist bosentan (moderate inducer CYP3A4, CYP2C9 and probably CYP2C19) in an equilibrium state (125 mg twice a day) with sildenafil in an equilibrium state (80 mg three times a day) leads to a decrease in AUC and Cmax values for sildenafil by 62.6% and 55.4%, respectively. Thus, it is believed that the simultaneous use of strong inducers of CYP3A4, such as rifampin, causes a more pronounced decrease in plasma concentrations of sildenafil.
Concurrent use with other PDE-5 inhibitors or other treatments for erectile dysfunction
The safety and efficacy of using sildenafil in combination with other PDE-5 inhibitors or other drugs containing sildenafil for the treatment of pulmonary arterial hypertension (PAH) or other drugs for the treatment of erectile dysfunction have not been studied. In this regard, the use of such combinations of drugs is not recommended.
Nicorandil is a hybrid of potassium channel activator and nitrate. Due to the nitrate component, it is potentially capable of entering into serious interactions with sildenafil.
The effect of sildenafil on other drugs
In vitro studies
Data on the interaction of sildenafil with non-specific phosphodiesterase inhibitors, such as theophylline or dipyridamole, are not available.
In vivo studies
In accordance with the well-known effect of sildenafil on the NO / cGMP signaling pathway, sildenafil is capable of enhancing the hypotensive effect of nitrates, namely, a significant reduction in blood pressure. Therefore, its simultaneous use with nitric oxide donors (amyl nitrite) or nitrates in any form is contraindicated.
In clinical studies, riociguat increased the hypotensive effect of PDE-5 inhibitors. There was no evidence of a favorable clinical effect when using such a combination in the studied population. Simultaneous use of riociguat with PDE-5 inhibitors, including sildenafil, is contraindicated.
Simultaneous reception with alpha-blockers
It is recommended that sildenafil be used with caution in patients taking a drug of the alpha-adrenergic blocking group, since their simultaneous use can lead to symptomatic arterial hypotension in some sensitive patients. This is most likely to occur within 4 hours after taking a dose of sildenafil. To reduce the risk of postural hypotension, the hemodynamic stability of patients receiving treatment with alpha blockers should be achieved before starting treatment with sildenafil. The possibility of using sildenafil, starting with a dose of 25 mg, should be considered. In addition, physicians should instruct patients about the actions in case of symptoms of postural hypotension.
With the simultaneous use of sildenafil and doxazosin in patients stabilized with doxazosin therapy, rare cases of symptomatic arterial hypotension, dizziness, and fainting, but not fainting have been reported.
With simultaneous use of sildenafil (50 mg dose) with tolbutamide (250 mg dose) or warfarin (40 mg dose), both of which are metabolized by CYP2C9, no significant interactions were detected.
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Sildenafil (at a dose of 50 mg) does not contribute to an increase in bleeding time caused by the administration of acetylsalicylic acid (at a dose of 150 mg).
Sildenafil (at a dose of 50 mg) does not enhance the hypotensive effect of alcohol in healthy volunteers with an average maximum blood alcohol level of 80 mg / dl.
Combination of the following classes of antihypertensive drugs: diuretics, beta-blockers, ACE inhibitors, angiotensin II antagonists, antihypertensive drugs (vasodilators and central action), adrenergic neuroblockers, calcium channel blockers and alpha-adrenoreceptor blockers – did not reveal differences taking sildenafil compared with patients receiving a placebo. In special studies of drug interactions, during which sildenafil (at a dose of 100 mg) was applied simultaneously with amlodipine in patients with arterial hypertension, an additional decrease in systolic blood pressure in the supine position was 8 mm. Hg Art. The corresponding additional decrease in diastolic blood pressure in the supine position was 7 mm. Hg Art. These additional reductions in blood pressure were similar in magnitude to those seen with sildenafil in healthy volunteers as monotherapy.
Sildenafil (at a dose of 100 mg) does not affect the pharmacokinetics in the equilibrium state of HIV protease inhibitors, saquinavir and ritonavir, both of which are substrates of CYP3A4.
When applied simultaneously with bosentan, sildenafil in equilibrium (80 mg three times a day) causes an increase in the AUC and Cmax of bosentan (125 mg twice a day) by 49.8% and 42%, respectively, in healthy male volunteers.