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Active ingredients
Vardenafil
Release form
Pills
Composition
Active ingredient: vardenafil (Vardenafil); Active ingredient concentration (mg): 20
Pharmacological effect
The drug for the treatment of erectile dysfunction, an inhibitor of PDE5.; The erection of the penis is a hemodynamic process, which is based on the relaxation of smooth muscles of the corpus cavernosum 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, 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 enhance the response to sexual stimulation.
Pharmacokinetics
Absorption; After 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 reaching Cmax. 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 large amounts of fat ( 57%), the absorption rate decreases with increasing time to reach Cmax up to 60 min, and Cmax in plasma decreases by an average of 20% without a significant change in AUC.; Distribution; Vd varinafil average Vd in equilibrium pharmacokinetic parameters averages 208 l, which de Monsters its good distribution in tissues.The 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 min after administration, it can be assumed that more than 0.00012% of the received dose can be determined in patients' sperm.; 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; In vitro, the ability of M1 to suppress PDE5 is 28% compared with vardenafil, which corresponds to 7% of the drug's effectiveness.; Excretion; The general clearance of vardenafil is 56 l / h, the final T1 / 2 is about 4-5 h. After oral administration, vardenafil is metabolites excreted mainly through the intestines - 91-95%, to a lesser extent by the kidneys - 2-6%; Pharmacokinetics in special clinical cases; 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 is no difference in efficacy and safety of the patient 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 impairment pharmacokinetic parameters of vardenafil are comparable with indicators in healthy. In severe renal impairment (CC is less than 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 with hemodialysis, the pharmacokinetics of vardenafil has 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. In patients with severely impaired liver function (class C on the Child-Pugh scale), the pharmacokinetics of vardenafil has not been studied.
Indications
erectile dysfunction (inability to achieve and maintain an erection necessary for sexual intercourse).
Contraindications
simultaneous therapy with nitrates or drugs that are nitric oxide donors; combination with HIV protease inhibitors such as indinavir or ritonavir; hypersensitivity to the components of the drug. The drug is not intended for use in children and adolescents under the age of 16. With caution should be used in patients with congenital lengthening of the QT interval, with anatomical deformation of the penis (curvature, cavernous fibrosis, Peyroni's disease), with diseases predisposing to priapism (sickle cell anemia, multiple myeloma, leukemia), severe dysfunction of the liver, kidney disease in the terminal stage, arterial hypotension (systolic f pressure at rest is less than 90 mm Hg), recent stroke and myocardial infarction, unstable angina, hereditary degenerative diseases of the retina (eg, retinitis pigmentosa), with a tendency to bleeding and with an exacerbation of peptic ulcer, aortic stenosis and idiopathic hypopathy. stenosis.
Use during pregnancy and lactation
The drug is not intended for use in women.
Dosage and administration
The drug is taken orally, regardless of the meal. The initial recommended dose is 10 mg for 25-60 minutes before sexual contact. You can also take in the period from 4-5 h to 25 min before sexual activity. The maximum frequency of admission - 1 time / day. To achieve effectiveness, a sufficient level of sexual stimulation is required. Depending on the effectiveness and tolerability, the dose may be increased to 20 mg or reduced to 5 mg / day. The maximum daily dose is 20 mg.; Correction of the dosing regimen in elderly patients is not required.; Patients with slightly severe liver failure do not require correction of the dosing regimen. In patients with moderate hepatic impairment, the initial dose is 5 mg per day. In the future, depending on the efficacy and tolerability of the treatment, the dose can be increased to 10 mg and then to 20 mg. In patients with mild and moderate renal impairment, dosing regimen adjustment is not required
Side effects
From the side of the central nervous system and peripheral nervous system: ≥10% - headache; ≥1% - dizziness; ≥0.1% - less than 1% - drowsiness; ≥0.01% - less than 0.1% - anxiety, fainting; On the part of the cardiovascular system: ≥10% - hot flashes (intermittent sudden reddening of the face, sensation of heat); ≥0.1% - less than 1% - increased blood pressure, decreased blood pressure, orthostatic hypotension; ≥0.01% - less than 0.1% - stenocardia, myocardial ischemia; On the part of the digestive system: ≥1% - less than 10% - dyspepsia, nausea; ≥0.1% - less than 1% - change in liver function tests (increased ALT, AST, GGTP); On the part of the respiratory system: ≥1% - less than 10% - congestive hyperemia of the nasal mucosa (swelling of the mucous membrane, rhinitis, rhinorrhea); ≥0.1% - less than 1% - shortness of breath, epistaxis; ≥0.01% - less than 0.1% - laryngeal edema.; On the part of the organ of vision: ≥0.1% - less than 1% - increased tearing, visual disturbances (visual brightness); ≥0.01% - less than 0.1% - increased intraocular pressure.; Dermatological reactions: ≥0.1% - less than 1% - swelling of the face, photosensitization.; From the musculoskeletal system: ≥0.1% - less than 1% - myalgia, back pain , raising CPK; ≥0.01% - less than 0.1% - increased muscle tone; On the part of the reproductive system:> 0.01% - less than 0.1% - prolonged erection or painful erection, priapism; Others: ≥0.01% - less than 0.1% - hypersensitivity reactions.
Overdose
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.
Interaction with other drugs
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 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 magnitude 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 4 times (300%) and a 3-fold increase in Cmax of vardenafil (200%). Ketoconazole (200 mg), being a potent CYP3A4 inhibitor, when used simultaneously with Levitra (5 mg) causes an increase in AUC of vardenafil 10 times (900%) and Cmax of vardenafil (5mg) 4 times (300%). With simultaneous use of Levitra (10 mg) and HIV protease inhibitor indinavir (800 mg 3 times / day) is noted an increase in AUC of vardenafil is 16 times (1500%) and Cmax of vardenafil is 7 times (600%). 24 hours after administration, the concentration of vardenafil in plasma 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 volunteers, Levitra (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 for 1-4 h before the use of nitrates (400 µg sublingually) enhances their hypotensive effect, but when prescribed for 24 hours there is no increase in the hypotensive effect; Vardenafil (20 mg) does not change the AUC and Cmax of glibenclamide (glyburide at a dose of 3.5 mg) when used together and vice versa.; Pharmacokinetic and pharmacodynamic No significant interaction (effect on prothrombin time and coagulation factors II, VII, X) is observed with the combination of vardenafil (20 mg) with warfarin (25 mg); no significant pharmacokinetic interaction between Levitra (20 mg) and nifedipine (30 or 60 mg): vardenafil causes an additional decrease in systolic and diastolic blood pressure by an average of 5.9 mm Hg in the supine position. st. and 5.2 mmHg. st. accordingly. 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. The 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 not accompanied by drug interaction.; A single dose of Maalox (antacid, magnesium hydroxide / aluminum hydroxide) does not affect the AUC and Cmax vardenafil.; The bioavailability of vardenafil (20 mg) is also not disturbed when combined with histamine H2-receptor blockers idin (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 pills of 81 mg each); Levitra (20 mg) does not potentiate the hypotensive effect of ethanol (0.5 g / kg body weight), the pharmacokinetics of vardenafil are not disturbed. and metformin), weak inhibitors of CYP3A4 do not affect the pharmacokinetics of va denafila.
special instructions
Before prescribing Levitra (as well as other drugs used to treat erectile dysfunction), the doctor should 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 moderately reduced blood pressure.; Patients with obstruction of outflow pathways from the left ventricle, for example, with aortic stenosis, idiopathic hypertrophic subaortic stenosis, may l sensitive to the action of vasodilators, including PDE5 inhibitors. In men who do not show sexual activity, due to concomitant cardiovascular disease, drugs for the treatment of 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 effects the potency of vardenafil in combination with other drugs for the treatment of erectile dysfunction has not been studied,therefore, 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, hypotension (systolic pressure at rest less than 90 mm Hg. Art. ), recent stroke or myocardial infarction (within the last 6 months), unstable angina, as well as hereditary degenerative diseases of the retina, for example, retinitis pigmentosa.; Against the background of In the case of Levitra and other PDE5 inhibitors, transient vision loss and nonarteritis ischemic neuropathy of the optic nerve have been reported. 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. Levitra dose 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 the benefits and risks 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 the aggregation of thrombosis s caused by various drugs.At a higher therapeutic concentration, vardenafil causes a slight enhancement of the antiaggregant effect of sodium nitroprusside, which is a donor of nitric oxide. nitrates are contraindicated.; Use in pediatrics; Vardenafil is not intended for use in children.; Effects on the ability to drive cars ransporta and management mechanisms; Before the appointment of the drug to patients who are driving a vehicle and work with the mechanisms necessary to clarify their individual response to Levitra.