Levitra is an orally consumed drug that can be used to treat erectile dysfunction.
Doctors advise against using the drug if you are allergic to any ingredient in it or if you are taking medications containing nitrates, alpha–blockers.
Also do not take it if you are taking or using nitroglycerin (eg, tablet, patch, ointment), nitrates (eg, isosorbide), or certain antiarrhythmics (eg, amiodarone, quinidine);you have had a heart attack, stroke, or life-threatening irregular heartbeat within the past 6 months; you have certain eye problems (eg, retina diseases such as retinitis pigmentosa), uncontrolled chest pain, uncontrolled high blood pressure, low blood pressure, irregular heartbeat (eg, congenital QT prolongation), severe heart failure, severe liver problems, or end-stage kidney disease that requires dialysis.
Active ingredient: vardenafil (vardenafil) Concentration of active ingredient (mg): 20
A drug for the treatment of erectile dysfunction, PDE5 inhibitor. Penile erection 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 cavernous bodies, which activates 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 are relaxed, which contributes to an increase in blood flow to the penis. Vardenafil blocks PDE5, under the influence of which the breakdown of cGMP occurs, as a result of this the local action of endogenous NO in the cavernous bodies during sexual stimulation increases, which determines the ability of Levitra to increase response to sexual stimulation.
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). The absolute bioavailability is about 15%. In the recommended dose range (5-20 mg), the AUC and Cmax in blood plasma increase in proportion to the dose. The clinical effect is realized even before the Cmax is reached. The onset of action after oral administration at a dose of 20 mg and 10 mg is 10 minutes, which provides an erection sufficient for penetration and successful completion of intercourse in 34% and 40% of patients with mild to moderately mild erectile dysfunction, respectively. After 25 minutes, the effect occurs in 53% and 50% of patients, respectively, which coincides in time with the onset of the appearance of the drug in the blood and a rapid increase in its concentration. The duration of action is 8-12 hours. When taken with 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 simultaneously with food containing a large amount of fat (57% ), the absorption rate decreases with an increase in the time to reach Cmax up to 60 min, and Cmax in blood plasma decreases on average by 20% without a significant change in AUC.Distribution The average Vd of vardenafil in the equilibrium state of pharmacokinetic parameters averages 208 l, which demonstrates its good distribution in tissues. The binding of vardenafil and its main metabolite (M1) to blood 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 the semen of healthy men 90 minutes after administration, it can be assumed that no more 0.00012% of the received dose 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 of vardenafil is 4-5 hours, and M1 is about 4 hours. The blood contains glucuronide in the form of a conjugate (glucuronic acid), which is part of the M1 metabolite. 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 total clearance of vardenafil is 56 l / h, the final T1 / 2 is about 4-5 hours. through the intestine – 91-95%, to a lesser extent by the kidneys – 2-6%. Pharmacokinetics in special clinical cases In healthy elderly men (?65 years old) compared with young (?45 years old) hepatic clearance of vardenafil is reduced. On average, the AUC in the elderly increases by 52%. However, there are no differences in the efficacy and safety of the drug in elderly and young patients. In patients with mild (CC> 55-80 ml / min) and moderate (CC> 30-50 ml / min) degree of renal impairment, the pharmacokinetic parameters of vardenafil are comparable to those in healthy people. In severe renal impairment (CC less than 30 ml / min), the average AUC increases by 21%, and Cmax decreases by 23%. There is no significant correlation between CC and the concentration of vardenafil in plasma (AUC and Cmax). In patients on hemodialysis, the pharmacokinetics of vardenafil has not been studied. In patients with mild and moderate impairment of liver function, the clearance of vardenafil decreases in proportion to the degree of its impairment. With a mild degree of liver failure (class A on the Child-Pugh scale), there is an increase in AUC and Cmax indicators 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 severe hepatic impairment (class C on the H scaleid-Pugh) the pharmacokinetics of vardenafil have not been studied.
Depending on the effectiveness and tolerability, the dose can be increased to 20 mg or decreased to 5 mg / day. The maximum daily dose is 20 mg. Correction of the dosage regimen in elderly patients is not required. In patients with mild hepatic insufficiency, correction of the dosage regimen is not required. In patients with moderate hepatic impairment, the initial dose is 5 mg per day. In the future, depending on the efficacy and tolerability of treatment, the dose can be increased to 10 mg and then to 20 mg.In patients with mild and moderate impairment of renal function, correction of the dosage regimen is not required
simultaneous therapy with nitrates or drugs that are donors of nitric oxide; 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. It should be used with caution in patients with congenital lengthening of the QT interval, with anatomical deformity of the penis (curvature, cavernous fibrosis, Peyronie’s disease), with diseases predisposing to priapism (sickle cell anemia, multiple myeloma, leukemia), severe liver dysfunction, end-stage kidney disease, arterial hypotension (systolic pressure at rest less than 90 mm Hg), recent stroke and myocardial infarction, unstable angina pectoris, hereditary degenerative diseases of the retina (for example, retinitis pigmentosa), with a tendency to bleeding and with exacerbation of peptic ulcer disease, aortic stenosis and idiopathic hypertrophic subaortic stenosis.
Application during pregnancy and lactation
Before prescribing Levitra (as well as other drugs used to treat erectile dysfunction), the doctor should assess the state of the cardiovascular system, since there is a risk of developing complications from the heart during sexual activity. Vardenafil has vasodilating properties, which may be accompanied by slight or moderate a decrease in blood pressure. 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 are not shown sexual activity due to concomitant cardiovascular disease, drugs for the treatment of erectile dysfunction are not prescribed.Since Levitra in therapeutic doses (10 mg) causes 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 (chi nidine, procainamide) or class III (amiodarone, sotalol). The safety and efficacy 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: severe liver dysfunction, kidney disease in the terminal stage, requiring hemodialysis, arterial hypotension (systolic pressure at rest less than 90 mm Hg. Art.), a recent stroke or myocardial infarction (within the last 6 months), unstable angina pectoris, as well as hereditary degenerative diseases of the retina, for example, retinitis pigmentosa. While taking Levitra and other PDE5 inhibitors, cases of transient visual loss and non-arteritis ischemic neuropathy of the optic nerve. If a sudden loss of vision occurs, the patient should stop taking Levitra and urgently consult with the attending physician. 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 in the presence of stable blood pressure while 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 as alpha-blockers, with the exception of tamsulosin, which may coincide with vardenafil. In the case of taking a selected dose of Levitra, therapy with alpha-blockers should be started at the minimum dose. A gradual increase in the dose of alpha-blockers for patients receiving drugs from the group of PDE5 inhibitors can lead to a further decrease in blood pressure. The dose of Levitra should not exceed 5 mg when combined with erythromycin, ketoconazole, itraconazole. The dose of ketoconazole and itraconazole should not exceed 200 mg. The combination with indinavir and ritonavir is contraindicated. Since vardenafil has not been used in patients those with a tendency to bleeding and in patients with exacerbation of peptic ulcer disease, its appointment in these cases is possible only after a careful assessment of the balance of benefits and risks of therapy. Vardenafil does not affect the duration of bleeding, and it also does not 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 the therapeutic one, vardenafil causes a slight increase in the antiplatelet effect of sodium nitroprusside, which is a donor of nitric oxide. The effect of vardenafil and heparin with simultaneous use on the duration of bleeding has not been studied. The effect of vardenafil on the hypotensive effect of nitrates in patients has not been studied, therefore the combined administration of Levitra and nitrates is contraindicated .Use in pediatrics Vardenafil is not intended for use in children.Effect on the ability to drive vehicles and use mechanisms Before prescribing the drug to patients who drive vehicles and work with mechanisms, it is necessary to find out their individual reaction to Levitra.
Method of administration and dosage
Indications for use erectile dysfunction (inability to achieve and maintain an erection necessary for sexual intercourse).
Vardenafil is metabolized mainly with the participation of hepatic enzymes of the cytochrome P450 system, namely, the CYP3A4 isoenzyme, as well as with some participation of the 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 the plasma concentration of vardenafil can be expected. influence on the value of AUC and Cmax of vardenafil (20 mg) .When used simultaneously with Levitra (5 mg), erythromycin (500 mg 3 times / day), which is an inhibitor of CYP3A4, causes an increase in AUC of vardenafil 4 times (300%) and an increase in Cmax vardenafil 3 times (200%). Ketoconazole (200 mg), being a potent inhibitor of CYP3A4, when used simultaneously with Levitra (5 mg) causes an increase in vardenafil AUC 10 times (900%) and Cmax of vardenafil (5 mg) 4 times ( 300%) .With the simultaneous use of Levitra (10 mg) and the HIV protease inhibitor indinavir (800 mg 3 times / day), there is an increase in vardenafil AUC 16 times (1500%) and vardenafil Cmax 7 times (600%). 24 hours after administration, the plasma concentration of vardenafil is approximately 4% of its Cmax. With the simultaneous use of Levitra (5 mg), ritonavir (600 mg 2 times / day) increases the Cmax of vardenafil 13 times and 49 times its total daily AUC. The interaction is due to the fact that ritonavir, being a potent inhibitor of CYP3A4 and CYP2C9, blocks the hepatic metabolism of vardenafil. Ritonavir significantly lengthens the T1 / 2 of vardenafil to 25.7 hours In healthy volunteers, Levitra (10 mg), when taken 24-1 hours before taking nitroglycerin (400 ?g sublingual), does not increase its hypotensive effect, at a dose of 20 mg for 1-4 hours before the use of nitrates (400 mcg sublingually) enhances their hypotensive effect, but when administered within 24 hours, the hypotensive effect does not increase. 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 interactions (effects on prothrombin time and coagulation factors II, VII, X) are 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 in the supine position causes an additional decrease in systolic and diastolic blood pressure by an average of 5.9 mm Hg. Art. and 5.2 mm Hg. Art. Since it is known that alpha-blockers cause a decrease in blood pressure, especially postural hypotension and fainting, the question of the interaction of alpha-blockers and Levitra when used together has been carefully studied. Two studies of drug interaction were conducted with the participation of healthy volunteers with normal blood pressure who received the alpha-blockers tamsulosin or terazosin with a rapid increase in doses to the maximum or close to them within 14 days or less. After adding Levitra to the received therapy, arterial hypotension developed in a significant number of study participants. Among persons receiving terazosia, arterial hypotension (systolic blood pressure in a standing position below 85 mm Hg) developed more often if Levitra and terazosin were prescribed in such a way as to achieve coincidence of Cmax in time than if Cmax diverged in time by 6 hours. These studies may be of limited clinical relevance as they were conducted in healthy volunteers and
also after forced titration of doses (thus, the study participants were unable to achieve stabilization of blood pressure while taking alpha-blockers). Studies of drug interactions Levitra were also carried out in patients with benign prostatic hyperplasia (BPH) receiving stable doses of tamsulosin or terazosin. When Levitra was prescribed in doses of 5, 10 or 20 mg to patients receiving stable doses of tamsulosin, no additional decrease in the average blood pressure was observed. With the simultaneous administration of Levitra at a dose of 5 mg and tamsulosin at a dose of 0.4 mg, orthostatic arterial hypotension was observed in 2 out of 21 patients with a drop in systolic blood pressure below 85 mm Hg. Art. When taking Levitra at 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. Art. also developed in 2 of 21 patients. In a subsequent study, the simultaneous administration of Levitra at doses of 10 mg and 20 mg and tamsulosin at doses of 0.4 mg and 0.8 mg in cases of orthostatic drop in systolic blood pressure below 85 mm Hg. Art. was not registered. With the simultaneous administration of Levitra at a dose of 5 mg and terazosin at doses of 5 mg or 10 mg, symptomatic postural hypotension was observed in one of 21 patients. When taking Levitra at a dose of 5 mg and terazosin with an interval of 6 hours, there were no cases of a drop in blood pressure. The results obtained should be taken into account when deciding on the time of prescribing drugs. The combined appointment of Levitra and alpha-blockers is permissible only if there are stable blood pressure indicators while taking alpha-blockers, while Levitra must be prescribed in 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 in time with taking Levitra. Simultaneous use of digoxin (0.375 mg) and Levitra (20 mg) every other day for more than 14 days accompanied by drug interactions. A single dose of maalox (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 ranitidine (150 mg 2 times / days) 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 tablets, 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 hypo glycemic drugs (sulfonylurea and metformin), weak inhibitors of CYP3A4 do not affect the pharmacokinetics of vardenafil.
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. From the side of the cardiovascular system: ?10% – hot flashes (periodic sudden facial flushing, feeling of heat); ?0.1% – less than 1% – increased blood pressure, decreased blood pressure, orthostatic hypotension; ?0.01% – less than 0.1% – angina pectoris, myocardial ischemia. From the digestive system: ?1% – less than 10% – dyspepsia, nausea; ?0.1% – less than 1% – change in liver function tests (increased ALT, AST, GGTP). From the respiratory system: ?1% – less than 10% – congestive hyperemia of the nasal mucosa (edema of the mucous membrane, rhinitis, rhinorrhea); ?0.1% – less than 1% – shortness of breath, epistaxis; ?0.01% – less than 0.1% – laryngeal edema. From the side of the organ of vision: ?0.1% – less than 1% – increased tearing, visual impairment (brightness of vision); ?0.01% – less than 0.1% – increased intraocular pressure. Dermatological reactions: ?0.1% – less than 1% – facial edema, photosensitivity. From the musculoskeletal system: ?0.1% – less than 1% – myalgia, back pain, increased CPK ; ?0.01% – less than 0.1% – increased muscle tone. On the part of the reproductive system: more than 0.01% – less than 0.1% – lengthening of erection or painful erection, priapism. Other: ?0.01% – less than 0.1% – hypersensitivity reactions …
Interaction with other drugs
Do not exceed the recommended doses.Caution should be used in patients with congenital prolongation of the QT interval, with anatomical deformity of the penis (curvature, cavernous fibrosis, Peyronie’s disease), with diseases that predispose to priapism (sickle cell anemia, multiple myeloma, leukemia), severe liver dysfunction, end-stage kidney disease, hypotension (systolic pressure at rest less than 90 mm Hg), recent stroke and myocardial infarction, unstable angina pectoris, hereditary degenerative retinal diseases (eg, retinitis pigmentosa), with a tendency to bleeding and with exacerbation of peptic ulcer disease, aortic stenosis and idiopathic hypertrophic subaortic stenosis.
there are known cases of taking Levitra at 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 used in a dose of 40 mg 2 times / day, severe pain in the lower back is observed without signs of toxic effects 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 be effective.