Levitra pills dispersed 10mg N4
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Active ingredients
Vardenafil
Release form
Pills
Composition
Active ingredient: vardenafil (vardenafil) active substance concentration (mg): 10
Pharmacological effect
The drug for the treatment of erectile dysfunction, a PDE5 inhibitor. The erection of the penis is a hemodynamic process, which is based on the relaxation of the smooth muscles of the cavernous bodies and arterioles located in it. During sexual stimulation, nitric oxide (NO) is released from the nerve endings of the corpus cavernosum, activating the enzyme guanylate cyclase, which leads to an increase in the content of cyclic guanosine monophosphate (cGMP) in the cavernous bodies. As a result, the smooth muscles of the cavernous bodies relax, which increases blood flow to the penis. Vardenafil blocks PDE5, which causes splitting of cGMP, resulting in local action of endogenous NO in the cavernous bodies during sexual stimulation, which causes Levitra's ability to strengthen reaction to sexual stimulation.
Pharmacokinetics
AbsorptionAfter taking the drug inside, vardenafil is rapidly absorbed from the gastrointestinal tract. When taken on an empty stomach, Cmax in blood plasma can be reached after 15 minutes, but in 90% of cases, on average, after 60 minutes (from 30 to 120 minutes). Absolute bioavailability is about 15%. In the recommended dose range (5–20 mg), the plasma AUC and Cmax increase in proportion to the dose. The clinical effect is realized even before Cmax is reached. Onset of action after oral administration in a dose of 20 mg and 10 mg - 10 min, which provides an erection sufficient for penetration and successful completion of sexual intercourse in 34% and 40% of patients with mild and moderately mild erectile dysfunction, respectively. After 25 minutes, the effect occurs in 53% and 50% of patients, respectively, which coincides with the onset of the drug in the blood and the rapid increase in its concentration. Duration of action - 8-12 hours. When taken with a normal food containing no more than 30% fat, the pharmacokinetic parameters of vardenafil (Cmax, time to reach Cmax, AUC) do not change. When taking vardenafil along with food containing a large amount of fat (57% ), the absorption rate decreases with increasing time to reach Cmax up to 60 min, and Cmax in plasma decreases on average by 20% without a significant change in AUC. Distribution Average Vd of vardenafil in equilibrium pharmacokinetic parameters averages 208 l, which is a demo It demonstrates its good tissue distribution.Binding of vardenafil and its main metabolite (M1) to plasma proteins is up to 95%, is reversible and does not depend on the total concentration of the drug. Based on the results of measuring the content of vardenafil in sperm of healthy men 90 minutes after administration, it can be assumed that no more 0.00012% of the dose received can be determined in the semen of patients. Metabolism. Vardenafil is metabolized in the liver with the participation of mainly CYP3A4, as well as CYP3A5 and CYP2C9. The average T1 / 2 vardenafil is 4-5 hours, and M1 is about 4 hours. The blood contains a glucuronide in the form of a conjugate (glucuronic acid), which is part of the metabolite M1. The concentration of the rest of the M1 (non-glucuronic) is 26% of the concentration of the active substance. The selectivity profile for PDE in M1 is similar to that for vardenafil; The in vitro ability of M1 to suppress PDE5 is 28% compared with vardenafil, which corresponds to 7% of the drug's efficacy. Withdrawal The general clearance of vardenafil is 56 l / h, the final T1 / 2 is about 4-5 h. After oral administration, vardenafil in the form of metabolites is derived mainly through the intestines - 91-95%, to a lesser extent by the kidneys - 2-6%. Pharmacokinetics in special clinical situations In healthy elderly men (≥65 years) compared with young (≤ 45 years), hepatic clearance of vardenafil is reduced. On average, the AUC in the elderly is increased by 52%. However, there are no differences in the efficacy and safety of the drug in elderly and young patients. In patients with mild (CK> 55–80 ml / min) and moderate (CK> 30–50 ml / min), the degree of renal dysfunction of the pharmacokinetic indicators of vardenafil are comparable to indicators in healthy. In severe renal impairment (CC <30 ml / min), the average AUC increases by 21%, and Cmax decreases by 23%. There is no significant correlation between CC and vardenafil plasma concentrations (AUC and Cmax). In patients on hemodialysis, the pharmacokinetics of vardenafil have not been studied. In patients with mild and moderate hepatic impairment, vardenafil clearance decreases in proportion to the degree of impairment. With mild hepatic impairment (class A on the Child-Pugh scale), there was an increase in AUC and Cmax by 1.2 times (AUC - by 17%, Cmax - by 22%), with a moderate degree (class B on the Child-Pugh scale) 2.6 times (160%) and 2.3 times (130%), respectively, compared with healthy volunteers. Patients with severely impaired liver function (class C on the Child-Pugh scale) have not studied the pharmacokinetics of vardenafil.
Contraindications
At the beginning of treatment, the recommended dose is 10 mg (approximately 25–60 minutes before sexual contact). However, it was shown that the drug Levitra is effective when taken 4–5 hours before sexual activity. The maximum frequency of taking the drug - 1 time per day. Depending on the efficacy and tolerability of treatment, the dose may be increased to 20 or reduced to 5 mg / day. The maximum recommended dose is 20 mg 1 time per day. Sexual stimulation is necessary to ensure an adequate response to treatment.
Precautionary measures
hypersensitivity to any of the components of the drug; simultaneous use with nitrates or drugs that are donators of nitric oxide; simultaneous use with moderately active or potent inhibitors of CYP3A4, such as ketoconazole, itraconazole, ritonavir, indinavir, erythromycin and clarithromycin; drugs for the treatment of erectile dis. should not be used in men who do not show sexual activity (for example, patients with concomitant cardiovascular diseases, such as severe angina pectoris or acute heart failure (class III or IV according to the classification of the New York Heart Association). The safety of Levitra has not been studied and until relevant data are obtained, its use is not recommended in patients with the following conditions: severely impaired liver function; kidney disease in end-stage, requiring hemodialysis, arterial hypotension (MAD at rest <90 mmHg), recently suffered a stroke or myocardial infarction (within the last 6 months); unstable angina, as well as hereditary degenerative diseases of the retina, such as retinitis pigmentosa.
Use during pregnancy and lactation
Before prescribing Levitra (as well as other drugs used to treat erectile dysfunction), the doctor must evaluate the state of the cardiovascular system, since there is a risk of heart complications during sexual activity. Vardenafil has vasodilating properties that may be accompanied by slight or moderate Patients with obstruction of the outflow tract from the left ventricle, for example, with aortic stenosis, idiopathic hypertrophic subaortic stenosis,may be sensitive to the action of vasodilators, including PDE5 inhibitors. In men who do not show sexual activity, due to concomitant cardiovascular disease, drugs for treating erectile dysfunction are not prescribed. Because Levitra in therapeutic doses (10 mg) causes a prolongation of the QT interval, the drug should not be prescribed to patients with congenital prolongation of the QT interval and those taking antiarrhythmic drugs of class IA (quinidine, procainamide) or class III (amiodarone, sotalol). Safety and The effectiveness of vardenafil in combination with other drugs for the treatment of erectile dysfunction has not been studied, so their combined use is not recommended. The safety of vardenafil has not been studied and its use is not recommended in the following groups of patients: severely impaired liver function, end-stage renal disease requiring hemodialysis, arterial hypotension (systolic pressure at rest <90 mmHg), recently suffered a stroke or myocardial infarction (within the last 6 months), unstable angina Ia and hereditary degenerative diseases of the retina, for example, pigment retinit.Na intake of Levitra and other PDE5 inhibitors have been reported cases of transient loss of vision and nearteriitnoy ischemic optic neuropathy. When a sudden loss of vision occurs, the patient should stop taking Levitra and urgently consult with your doctor. Combined therapy with alpha-blockers and vardenafil may be accompanied by the development of arterial hypotension with an appropriate clinical picture, since these drugs have a vasodilating effect. The combined appointment of Levitra and alpha-blockers is permissible only if there are stable blood pressure indicators against the background of taking alpha-blockers, while Levitra should be prescribed in the minimum recommended dose of 5 mg. Levitra should not be taken at the same time with alpha-blockers, with the exception of tamsulosin, which may coincide with the time of vardenafil. In the case of receiving the selected dose of Levitra, therapy with alpha-blockers should be started in the minimum dose.A gradual increase in the dose of alpha-adrenergic blockers to patients receiving drugs from the group of PDE5 inhibitors may lead to a further decrease in blood pressure. The dose of Levitra should not exceed 5 mg when it is combined with erythromycin, ketoconazole, itraconazole. The dose of ketoconazole and itraconazole should not exceed 200 mg. Combination with indinavir and ritonavir is contraindicated. Since vardenafil was not used in patients with a tendency to bleeding and in patients with acute exacerbation of peptic ulcer, its use in these cases is possible only after a thorough assessment of the ratio of benefit and risk of therapy. Vardenafil does not affect the duration of bleeding, nor does it affect this indicator when used in combination with acetylsalicylic acid. Vardenafil does not increase platelet aggregation Caused by various drugs. At a concentration higher than therapeutic, vardenafil causes a slight increase in the antiaggregant effect of sodium nitroprusside, which is a donor of nitric oxide. The effect of vardenafil and heparin while being used on bleeding duration has not been studied. . Use in pediatricsVardenafil is not intended for use in children. Effect on the ability to drive an auto. Sports and management mechanisms Before prescribing a drug to patients who drive vehicles and work with mechanisms, it is necessary to determine their individual response to Levitra.
Dosage and administration
Indications for use Erectile dysfunction (inability to achieve and maintain an erection necessary for sexual intercourse).
Side effects
Vardenafil is metabolized predominantly with the participation of hepatic enzymes of the cytochrome P450 system, namely, the CYP3A4 isoenzyme, as well as with some participation of CYP3A5 and CYP2C isoenzymes. Inhibitors of these enzymes can reduce the clearance of vardenafil. With the simultaneous use of Levitra with ketoconazole, itraconazole, indinavir and ritonavir (potent inhibitors of CYP3A4), a significant increase in plasma vardenafil concentration can be expected.does not affect the value of AUC and Cmax vardenafil (20 mg). When used simultaneously with Levitra (5 mg), erythromycin (500 mg 3 times / day), which is a CYP3A4 inhibitor, causes an increase in AUC of vardenafil by 4 times (300%) and an increase in Cmax of vardenafil is 3 times (200%). Ketoconazole (200 mg), being a potent CYP3A4 inhibitor, when used simultaneously with Levitra (5 mg) causes an increase in AUC of vardenafil by 10 times (900%) and Cmax of vardenafil (5mg) in 4 times (300%). With simultaneous use of Levitra (10 mg) and the HIV protease inhibitor indinavir (800 mg 3 times / day) elichenie AUC vardenafil 16 times (1500%) and Cmax vardenafil 7 times (600%). 24 hours after administration, plasma concentration of vardenafil is approximately 4% of its Cmax. With simultaneous use of Levitra (5 mg) ritonavir (600 mg 2 times / day) increases 13 times the Cmax of vardenafil and 49 times its total daily AUC. The interaction is due to the fact that ritonavir, as a potent inhibitor of CYP3A4 and CYP2C9, blocks the hepatic metabolism of vardenafil. Ritonavir significantly extends T1 / 2 vardenafil to 25.7 hours. In healthy Levitra volunteers (10 mg) when taken 24-1 hours before taking nitroglycerin (400 μg sublingually) does not cause an increase in its hypotensive effect, at a dose of 20 mg in 1-4 hours prior to the use of nitrates (400 µg sublingually) enhances their hypotensive effect, but when prescribed for 24 hours, the enhancement of the hypotensive effect does not occur. Vardenafil (20 mg) does not change the AUC and Cmax indices of glibenclamide (3.5 mg glyburide) when they are used together and vice versa Pharmacokinetic and pharmacodynamic This interaction (the effect on the prothrombin time and coagulation factors II, VII, X) is not observed when vardenafil (20 mg) is combined with warfarin (25 mg). There is no significant pharmacokinetic interaction between Levitra (20 mg) and nifedipine (30 or 60 mg ): vardenafil causes in the supine position an additional decrease in systolic and diastolic blood pressure by an average of 5.9 mm Hg. st. and 5.2 mmHg. st. respectively. Since it is known that alpha-blockers cause a decrease in blood pressure, especially postural hypotension and syncope, the issue of interaction between alpha-blockers and Levitra when used together is carefully studied. Two studies of drug interactions were conducted with healthy volunteers with normal blood pressure who received alpha-blockers tamsulosin or terazosin with a rapid increase in doses to maximum or close to them within 14 days or less.After adding Levitra to the resulting therapy, hypotension developed in a significant number of study participants. Among those receiving terazosia, hypotension (systolic blood pressure in a standing position below 85 mmHg) developed more often if Levitra and terazosin were administered so as to achieve a Cmax coincidence in time than if Cmax diverged in time by 6 hours. These studies may have limited clinical significance, since they were conducted with the participation of healthy volunteers, as well as after forced titration of doses (thus, the study participants could not achieve stabilization of blood pressure while taking alpha-adrenergic blockers). Levitra's drug interaction studies were also conducted in patients with benign prostatic hyperplasia (BPH), receiving stable doses of tamsulosin or terazosin. When prescribing Levitra in doses of 5, 10 or 20 mg to patients receiving stable doses of tamsulosin, no further decrease in the average level of blood pressure was observed. With simultaneous administration of Levitra in a dose of 5 mg and tamsulosin at a dose of 0.4 mg, ortrostatic hypotension was observed in 2 of 21 patients with a drop in systolic blood pressure below 85 mm Hg. st. When taking Levitra in a dose of 5 mg and tamsulosin with a 6-hour interval, orthostatic systolic hypotension with a drop in blood pressure of less than 85 mm Hg. st. also developed in 2 of 21 patients. In a subsequent study, the simultaneous administration of Levitra in doses of 10 mg and 20 mg and tamsulosin in doses of 0.4 mg and 0.8 mg of cases of orthostatic drop in systolic blood pressure below 85 mm Hg. st. was not registered. With the simultaneous appointment of Levitra in a dose of 5 mg and terazosin in doses of 5 mg or 10 mg in one of 21 patients, symptomatic postural hypotension was observed. When taking Levitra in a dose of 5 mg and terazosin with an interval of 6 hours there were no cases of a fall in blood pressure. The results should be taken into account when deciding on the timing of prescribing drugs. Combined prescription of Levitra and alpha-blockers is permissible only if there are stable blood pressure indicators while taking alpha-blockers, while Levitra should be prescribed at the minimum recommended dose of 5 mg.You should not take Levitra at the same time with alpha-blockers, with the exception of tamsulosin, which may coincide with the reception of Levitra. Simultaneous use of digoxin (0.375 mg) and Levitra (20 mg) every other day for more than 14 days accompanied by drug interactions. Taking Maalox once (antacid, magnesium hydroxide / aluminum hydroxide) does not affect the AUC and Cmax of vardenafil. The bioavailability of vardenafil (20 mg) is also not impaired when it is combined with histamine H2 receptor blockers Dinom (150 mg 2 times / day) and cimetidine (400 mg 2 times / day). Levitra (10 mg and 20 mg) does not affect the duration of bleeding when used as monotherapy and in combination with acetylsalicylic acid in a low dose (2 tab. on 81 mg). Levitra (20 mg) does not potentiate the hypotensive effect of ethanol (0.5 g / kg body weight), the pharmacokinetics of vardenafil is not disturbed. Acetylsalicylic acid, ACE inhibitors, beta-blockers, diuretics and hypoglycemic drugs (sulfonylurea and metformin) , weak CYP3A4 inhibitors do not affect ward pharmacokinetics afila.
Overdose
On the part of the immune system: rarely - allergic edema, angioedema; rarely - an allergic reaction. From the nervous system: very often - headache; often - dizziness; infrequently - a violation of sensitivity, drowsiness, sleep disorders; rarely, fainting, amnesia, convulsions. On the part of the organ of vision: infrequently, visual impairment, hyperemia of the conjunctiva of the eyeball, disturbed color vision, pain in the eyeballs and discomfort in the eyes, photophobia; rarely, increased intraocular pressure, conjunctivitis. For the organ of hearing and labyrinth disturbances: infrequently, tinnitus, vertigo. For the cardiovascular system: often for vasodilatation; infrequently - palpitations, tachycardia; rarely - angina, myocardial infarction, ventricular tachyarrhythmias, hypotension. On the respiratory system: often - nasal congestion; infrequently - shortness of breath, congestion of the paranasal sinuses. On the part of the digestive system: often - dyspepsia; infrequently - nausea, abdominal pain, dry mouth, diarrhea, gastroesophageal reflux disease, gastritis, vomiting, increased transaminase levels. On the side of the skin and subcutaneous tissues: rarely - erythema, rash. On the part of the musculoskeletal system: infrequently - pain in back, increased levels of CPK, increased muscle tone and cramps. From the reproductive system: infrequently - increased erection; seldom - priapism. Others: infrequently - feeling unwell; rarely chest pain.
Interaction with other drugs
Do not exceed the recommended dose. With caution should be used in patients with congenital lengthening of the QT interval, with anatomical deformation of the penis (curvature, cavernous fibrosis, Peyronie's disease), with diseases predisposing to priapism (sickle cell anemia, multiple myeloma, leukemia), severe liver dysfunction, kidney disease in the terminal stage, arterial hypotension (systolic pressure at rest less than 90 mm Hg), recent stroke and myocardial infarction, unstable oh angina pectoris, congenital retinal degenerative diseases (e.g., retinitis pigmentosa) with a tendency to bleeding and exacerbation of peptic ulcer disease, aortic stenosis and idiopathic hypertrophic subaortal stenosis.
special instructions
Symptoms: it is known about the cases of taking Levitra in a dose of 80 mg 1 time / day and 40 mg 1 time / day for more than 4 weeks without the development of serious adverse reactions. However, at the same time, when applied in a dose of 40 mg 2 times / day, severe back pain is observed without signs of toxic action on the muscular and nervous system. Treatment: symptomatic and supportive therapy. Since vardenafil is highly bound to plasma proteins, and only a small amount of the drug is excreted by the kidneys, hemodialysis is unlikely to work.