Levitra, 20mg pills, 1pc

Composition

Active ingredient:  

vardenafil 20 mg;

Auxiliary substances:

crospovidone — 8.85 mg;

magnesium stearate-1.77 mg;

MCC-141.797 mg;

colloidal silicon dioxide-3.385 mg;

Film shell:

macrogol 400-1,128 mg; hypromellose-3,385 mg; titanium dioxide-0,925 mg; iron oxide yellow dye-0,188 mg; iron oxide red dye-0,015 mg

Pharmacological action

Levitra-improves erectile function.

Pharmacodynamics

Penile erection is a hemodynamic process based on the relaxation of the smooth muscles of the cavernous bodies and arterioles located in them. During sexual stimulation, nitric oxide (NO) is released from the nerve endings of the cavernous bodies, 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 helps to increase blood flow to the penis. The level of cGMP is regulated, on the one hand, by the synthesis of guanylate cyclase, and on the other hand, by degradation (cleavage) cGMP by hydrolysis of PDE. The most well-known PDE is cGMP-specific PDE-5.

By blocking PDE5, which is involved in the breakdown of cGMP, vardenafil enhances the local action of endogenous nitric oxide (NO) in the cavernous bodies during sexual stimulation.

An increase in cGMP levels due to PDE-5 intibation leads to relaxation of the smooth muscles of the cavernous bodies and an increase in blood flow to them.

This effect is due to the ability of Levitra® to enhance the natural response to sexual stimulation.

Vardenafil is a potent and highly selective PDE-5 inhibitor (the average inhibitory concentration relative to PDE-5 is 0.7 nM). The inhibitory activity of vardenafil on PDE-5 is more pronounced than on other known PDEs (15 times more than on PDE-6,130 times more than on PDE-1,300 times more than on PDE-11, and 1000 times more than on PDE-2, -3, -4, -7, -8, -9, -10). Vardenafil increased cGMP in the isolated cavernous body, which led to smooth muscle relaxation. Vardenafil causes penile erections that depend on endogenous nitric oxide and are stimulated by nitric oxide donors.

Taking vardenafil at a dose of 20 mg in some men caused an erection (sufficient for penetration) after 15 minutes. The full response was reached in 25 minutes.

Pharmacokinetics

Suction

After ingestion, it is rapidly absorbed. When taken on an empty stomach, an early peak Cmax can be reached in 15 minutes, but in 90% of cases, on average, Cmax is reached in 60 minutes (from 30 to 120 minutes). Absolute bioavailability is about 15%.

Due to the significant effect of the first pass, the absolute bioavailability is about 15%. In the recommended dose range (5-20 mg), the AUC (AUC) and Cmax values increase in proportion to the dose.

When taking vardenafil simultaneously with food containing a large amount of fat (57%), the absorption rate decreases with an increase in Tmax to 60 minutes, and the Cmax value on average decreases by 20% without a significant change in the AUC index. When taken with normal food containing no more than 30% fat, the pharmacokinetic parameters of vardenafil (Cmax, Tmax, AUC) do not change. Based on these data, vardenafil can be prescribed regardless of food intake.

Distribution

The average Vss of vardenafil is 208 liters, which demonstrates its good distribution in tissues. Vardenafil and its main metabolite (M1) they bind well to plasma proteins (up to 95%), and this property is reversible and does not depend on the total concentration of the drug.

90 minutes after taking vardenafil, no more than 0.00012% of the received dose can be detected in the semen of healthy patients.

Metabolism

Vardenafil is mainly metabolized by hepatic enzymes involving the cytochrome CYP3A4 system, as well as by CYP3A5 and CYP2C9 isoforms.

The average T1 / 2 of vardenafil is 4-5 hours, and the main metabolite M 1 (formed by desethylation of the piperazine part of the molecule) — 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 remaining part of the M1 metabolite (non-glucuronic acid) is 26% of the Active ingredient concentration. The PDE selectivity profile of M1 is similar to that of vardenafil; in vitro, the ability to inhibit PDE-5 is 28% compared to vardenafil, which corresponds to 7% of the drug’s effectiveness.

Output. The total clearance of vardenafil is 56 l / h, the final T1/2 is about 4-5 hours. After oral use, vardenafil in the form of metabolites is excreted mainly through the gastrointestinal tract (91-95% of the dose), to a lesser extent-by the kidneys (2-6% of the dose).

Elderly patients. In healthy older men (≥65 years) compared to younger subjects (<45 years), the hepatic clearance of vardenafil is reduced. On average, AUC increases by 52% in the elderly.

In patients aged 65 years and older, when taking tablets dispersed in the oral cavity (10 mg), there was an increase in AUC from 31 to 39% and Cmax from 16 to 21% compared to patients aged 45 years and younger. When taking one tablet dispersed in the oral cavity (10 mg) for 10 days in patients under the age of 45 years and aged 65 years and older, there was no accumulation of vardenafil in plasma.

However, there is no difference in the effectiveness and safety of the drug in elderly and young patients.

Kidney failure. In patients with mild (creatinine clearance 55-80 ml/min) and moderate (Creatinine clearance 30-50 ml/min) renal impairment, the pharmacokinetic parameters of vardenafil are comparable to those in healthy subjects. In severe renal impairment (Cl creatinine max is reduced by 23%. There is no significant correlation between creatinine clearance and vardenafil plasma concentrations (AUC and Cmax).

The pharmacokinetics of vardenafil have not been studied in patients undergoing hemodialysis.

Impaired liver function. In patients with mild to moderate hepatic impairment, vardenafil clearance decreases in proportion to the degree of hepatic impairment. In mild hepatic insufficiency (Child-Pugh stage A), there is a 1.2 — fold increase in AUC and Cmax (AUC — by 17%, Cmax-by 22%), and in moderate hepatic insufficiency (Child — Pugh stage B) – by 2.6 (by 160%) and 2.3 (by 130%) times, respectively, compared with healthy volunteers.

The pharmacokinetics of vardenafil have not been studied in patients with severe hepatic impairment (Child-Pugh stage B).

Indications

Erectile dysfunction (inability to achieve and maintain an erection necessary for sexual intercourse).

Contraindications

• hypersensitivity to any component of the drug;
• simultaneous use with nitrates or drugs that are donators of nitric oxide;
• the simultaneous use of moderately active or potent inhibitors of CYP3A4, such as ketoconazole, Itraconazole, ritonavir, indinavir, erythromycin and clarithromycin;
• pharmaceutical preparations for the treatment of erectile dysfunction should not be used in men who have not shown sexual activity (e. g. patients with concomitant cardiovascular diseases, such as unstable angina or severe heart failure (class III or IV according to the classification of new York heart Association).

Side effects

Infectious and parasitic diseases:  rarely-conjunctivitis.

Immune system disorders:  infrequently-allergic edema and angioedema; rarely-allergic reactions.

Mental disorders:  infrequently — sleep disorders.

Nervous system disorders:  very often-headache; often-dizziness; infrequently-paresthesia and dysesthesia, drowsiness; rarely-fainting, amnesia, convulsions.

Visual disturbances:  infrequently-visual disturbances, hyperemia of the conjunctiva of the eyeball, color perception disorders, pain in the eyeballs and a feeling of discomfort in the eyes, photophobia; rarely — increased IOP.

Hearing disorders and labyrinth disorders:  infrequently-ringing in the ears, vertigo.

Cardiac disorders:  infrequently-palpitations, tachycardia; rarely-angina pectoris, myocardial infarction, ventricular tachyarrhythmias.

Vascular disorders:  often-vasodilation; rarely-hypotension.

Respiratory, thoracic and mediastinal disorders:  often-nasal congestion; infrequently-shortness of breath, nasal congestion.

Gastrointestinal disorders:  often-dyspepsia; infrequently-nausea, abdominal pain, dry mouth, diarrhea, gastro-esophageal reflux disease, gastritis, vomiting.

Liver and biliary tract disorders:  infrequently-increased transaminase activity.

Skin and subcutaneous tissue disorders:  infrequently-erythema, rash.

Musculoskeletal and connective tissue disorders:  infrequently — back pain, increased CPK levels, increased muscle tone and cramps, myalgia.

Genital and breast disorders: infrequently-increased erection; rarely-priapism.

General disorders and disorders at the injection site: infrequently-feeling unwell; rarely-chest pain.

Interaction

Vardenafil is mainly metabolized with the participation of liver enzymes of the cytochrome P450 system, namely isoform 3A4, as well as with some participation of isoforms 3A5 and 2C9. Inhibitors of these enzymes may reduce the clearance of vardenafil.

Cimetidine (400 mg 2 times / day): A non-specific cytochrome P 450 inhibitor does not affect the AUC and Cmax values of Vvardenafil (20 mg) when used simultaneously.

Levitra® ODT is contraindicated when used concomitantly with moderately active or potent CYP3A4 inhibitors, such as ketoconazole, itraconazole, ritonavir, indinavir, erythromycin, and clarithromycin. With the combined use of Levitra® ODT with ketoconazole, itraconazole, indinavir and ritonavir (potential CYP3A4 inhibitors) can be expected to significantly increase the concentration of vardenafil in plasma.

Nitrates, nitric oxide donors: taking vardenafil (10 mg) in the period from 24 hours to 1 hour before taking nitroglycerin (0.4 mg sublingual) does not increase its hypotensive effect when taken in healthy subjects. At a dose of 20 mg 1-4 hours before taking nitrates (0.4 mg sublingually), vardenafil enhances their hypotensive effect, but if vardenafil is prescribed 24 hours before, then the hypotensive effect of nitrates does not increase when taken in healthy middle-aged subjects.

Nicorandil is an activator of potassium channels and contains a nitro group in its composition. The presence of a nitro group in the composition of nicorandil causes a high probability of its interaction with vardenafil.

However, there is insufficient information on the potential antihypertensive effects of vardenafil when co-administered with nitrates. In this regard, this combination is contraindicated.

Vardenafil (20 mg) does not change the AUC and Cmax values of glibenclamide (glyburide at a dose of 3.5 mg) when used together. It has also been shown that the pharmacokinetics of vardenafil do not change when it is co-administered with glibenclamide.

Pharmacokinetic and pharmacodynamic interactions (effects on prothrombin time and clotting factors II, VII, X) were not observed when vardenafil (20 mg) was co-administered with warfarin (25 mg). Concomitant use with warfarin does not alter the pharmacokinetics of vardenafil.

There was no significant pharmacokinetic interaction between vardenafil (20 mg) and nifedipine (30 mg or 60 mg). Concomitant use of vardenafil and nifedipine did not lead to a significant pharmacodynamic interaction: vardenafil caused an additional decrease in systolic and diastolic blood pressure compared to placebo when measured in the supine position by an average of 5.9 mm Hg and 5.2 mm Hg, respectively.

Since it is known that alpha-blockers cause a decrease in blood pressure, especially postural hypotension and syncope, the interaction of alpha-blockers and vardenafil when used together has been carefully studied.

Assessment of blood pressure and pulse within 10 hours after taking vardenafil at a dose of 5 mg or 10 mg, prescribed 4 hours after taking alfuzosin, did not reveal a clinically significant additional decrease in maximum mean blood pressure compared to placebo. One patient experienced a decrease in systolic blood pressure from baseline by more than 30 mm Hg in the standing position after taking vardenafil at a dose of 5 mg. Another patient experienced a decrease in systolic blood pressure from baseline by more than 30 mm Hg in the standing position after taking vardenafil at a dose of 10 mg. There were no cases of a decrease in systolic blood pressure in the standing position below 85 mm Hg in this case. Vertigo was reported in two patients after taking vardenafil 5 mg, in one patient after taking vardenafil 10 mg, and in one patient after taking placebo. Since a 4-hour interval between doses of vardenafil and alfuzosin was chosen to identify the maximum potential interactions, compliance with the time interval between taking drugs is not required. There were no cases of syncope in this case and when vardenafil was co-administered with tamsulosin or terazosin.

Concomitant use of vardenafil and alpha-blockers is permissible only if there are stable blood pressure indicators against the background of taking alpha-blockers, while vardenafil should be prescribed with the minimum recommended dose of 5 mg. However, the drug Levitra® ODT in the form of tablets dispersed in the oral cavity should not be prescribed as an initial dose when concomitant therapy with alpha-blockers. You should not take vardenafil at the same time as alpha-blockers, with the exception of tamsulosin and alfuzosin, which may coincide with taking Levitra® ODT. A time interval should be observed between taking vardenafil and other alpha-blockers. When prescribing terazosin and vardenafil at the same time, it is necessary to observe a 6-hour interval between taking drugs.

Concomitant use of digoxin (0.375 mg) and vardenafil (20 mg) every other day for more than 14 days is not accompanied by their interaction.

Single antacid dose (Magnesium hydroxide/Aluminum hydroxide) It does not affect the AUC and Cmax values of vardenafil.

The bioavailability of vardenafil (20 mg) is also not impaired when it is combined with the histamine H2-receptor blocker ranitidine (150 mg 2 times / day).

Vardenafil (10 mg and 20 mg) does not affect the duration of bleeding when used as monotherapy and in combination with low-dose acetylsalicylic acid (2 tablets of 81 mg).

Vardenafil (20 mg) does not potentiate the hypotensive effect of ethanol (0.5 g / kg body weight), the pharmacokinetics of vardenafil are not impaired.

Acetylsalicylic acid, ACE inhibitors, beta-blockers, diuretics and antidiabetic drugs (sulfonylureas and metformin), weak CYP3A4 inhibitors do not affect the pharmacokinetics of vardenafil.

How to take, course of use and dosage

Inside, regardless of food intake.

At the beginning of treatment, the recommended dose is 10 mg (approximately 25-60 minutes before sexual contact).

However, Levitra® has also been shown to be effective when taken 4-5 hours before sexual activity.

The maximum frequency of taking the drug is 1 time per day.

Depending on the effectiveness and tolerability of the treatment, the dose may be increased to 20 mg/day or reduced to 5 mg / day.

The maximum recommended dose is 20 mg once a day.

Sexual stimulation is necessary to ensure an adequate response to treatment.

Composition

Tablet Form of production

Storage conditions

In a dry place, at temperatures below 30°C

Shelf life

3 years

Active ingredient

Vardenafil

Conditions of release from pharmacies

By prescription

Dosage form

Tablets