Levitra – improving erectile function.
Penile erection is a haemodynamic process based on the relaxation of smooth muscle of cavernous bodies and located therein arterioles. During sexual stimulation of the nerve of cavernous bodies released nitric oxide (NO), the activating enzyme guanylate cyclase, which results in an increase in the content of the cavernous bodies of cyclic guanosine monophosphate (cGMP). The result is a relaxation of smooth muscles of cavernous bodies, which increases blood flow to the penis. UroventsGMF regulated with one hand – the synthesis of guanylate cyclase, and on the other hand – the degradation (cleavage) by hydrolysis of cGMP PDE. The most famous tsGMFspetsificheskaya PDE is PDE5.
Blocking PDE5, which participates in the cleavage of cGMP enhances vardenafil local action of endogenous nitric oxide (NO) in the cavernous bodies during sexual stimulation.
Increased cGMP due intibirovaniya PDE5 causes relaxation of smooth muscle of cavernous bodies and increase the blood flow therein.
This effect has the ability Levitra® formulation enhances the natural response to sexual stimulation.
Vardenafil is a potent and highly selective inhibitor of PDE5 (the mean inhibitory concentration with respect to PDE5 – 0.7 nM). The inhibitory activity of vardenafil naFDE-5 is more pronounced than in other known PDE (15 times more than to PDE-6, 130 times greater than PDE-1, 300 times greater than PDE-11 and 1000 times greater than in the PDE-2, -3, -4, -7, -8, -9, -10). Vardenafil increased cGMP in the isolated corpus cavernosum, resulting in smooth muscle relaxation. Vardenafil causes penile erection is dependent on endogenous nitric oxide and nitric oxide donators stimulated.
Receiving vardenafil 20 mg some men caused erection (sufficient for penetration) after 15 min. A complete response was achieved after 25 minutes.
After intake of rapidly absorbed. When receiving the early peak Cmax fasted can be reached after 15 minutes, but 90% of the average Cmax achieved in 60 minutes (30 to 120 min). The absolute bioavailability is about 15%.
Due to the considerable effect of first pass absolute bioavailability is about 15%. The recommended dose range (5-20 mg) value of the index AUC (AUC) and Cmaxuvelichivayutsya proportional to dose.
When receiving vardenafil simultaneously with the diet containing high fat (57%), the rate of absorption decreases with increasing Tmax 60 min, Cmax and the average value is reduced by 20% without a significant change in AUC indicator. Upon receiving a normal diet containing no more than 30% fat, vardenafil pharmacokinetic parameters (Cmax, Tmax, AUC) are not changed. On the basis of these data can be assigned to vardenafil regardless of the meal.
Middle Vss vardenafil is 208 l, which demonstrates its good tissue distribution. Vardenafil and its major metabolite (M1) bind well to (up to 95%) to plasma proteins, and this property is reversible and not dependent on the total concentration of the drug.
After 90 minutes after administration of vardenafil is not more than 0.00012% of the administered dose can be determined in the semen of healthy patients.
Vardenafil is metabolized predominantly hepatic enzymes involving cytochrome CYP3A4, and CYP3A5 and CYP2C9 isoforms.
The average T1 / 2 vardenafil is 4-5 h and the main metabolite M1 (generated by dezetilirovaniya piperazine moiety) – about 4 hours.
The blood contains a glucuronide conjugate form (glucuronic acid), which is part of the M1 metabolite.
The concentration of the rest of the M1 metabolite (neglyukuronovoy) is 26% of the concentration of the active substance. Profile selectivity for PDE in M1 is similar to that of vardenafil; in vitro ability to inhibit PDE-5 is 28% compared to vardenafil, which corresponds to 7% efficacy.
Withdrawal. Total clearance of vardenafil is 56 l / h, the final T1 / 2 -. About 4-5 hours after oral administration of vardenafil as metabolites excreted mainly via the gastrointestinal tract (91-95% of the dose), to a lesser extent – the kidneys (% dose 2-6 ).
Elderly patients. In healthy elderly males (≥65 years) compared to younger individuals (≤45 years) hepatic clearance of vardenafil was reduced. The average AUC in the elderly increased by 52%.
Patients aged 65 years or older when receiving dispersible tablet in the mouth (10 mg) was an increase in AUC from 31 to 39% and Cmax from 16 to 21% compared to patients aged 45 years or younger. When receiving a dispersible tablet in the mouth (10 mg) for 10 days in patients aged 45 years and aged 65 years and older were observed in the plasma accumulation vardenafil.
However, the difference in efficacy and safety in patients older and younger are not marked.
Renal insufficiency. Patients with mild (Cl creatinine – 55-80 ml / min) and moderate (Clkreatinina – 30-50 ml / min), the degree of renal function vardenafil pharmacokinetic parameters are comparable with those of healthy people. In severe renal dysfunction (Cl creatinine maxsnizhaetsya by 23%. No significant correlation between creatinine clearance and vardenafil concentration in plasma (AUC and Cmax) is not observed.
In patients on hemodialysis, the pharmacokinetics of vardenafil has not been studied.
Abnormal liver function. In patients with mild to moderate hepatic impairment Vardenafil clearance is reduced in proportion to the degree of liver dysfunction. In mild hepatic failure (step A by Child-Pugh) marked increase in Cmax and AUC figures 1.2 times (AUC – 17%, C max – 22%), while moderate (stage B according to the Child-Pugh) – 2.6 (160%) and 2.3 (130%) times, respectively, compared to healthy volunteers.
Patients with severe hepatic impairment (step B of Child-Pugh) vardenafil pharmacokinetics not studied.
Bayer Pharma AG, Germany
The active ingredient is:
vardenafil 20 mg;
crospovidone – 8.85 mg;
magnesium stearate – 1.77 mg;
MCC – 141.797 mg;
colloidal silicon dioxide – 3,385 mg;
The casing film :
Macrogol 400 – 1,128 mg;
Hypromellose – 3,385 mg;
titanium dioxide – 0.925 mg;
dye Yellow iron oxide – 0.188 mg;
iron oxide red dye – 0.015 mg
Erectile dysfunction (inability to achieve and maintain an erection necessary for sexual intercourse).
- hypersensitivity to any component of the drug;
- simultaneous use with nitrates or drugs, which are nitric oxide donators;
- simultaneous application of active or moderately potent inhibitors of CYP3A4, such as ketoconazole, itraconazole, ritonavir, indinavir, erythromycin and clarithromycin;
- drugs for the treatment of erectile dysfunction should not be used in men, which is not shown sexual activity (e.g., patients with underlying heart disease such as unstable angina or acute heart failure (Class III or IV according to the classification of the New York Heart Association ).
Infectious and parasitic diseases: rare – conjunctivitis.
Disorders of immune system: Infrequent – allergic edema and angioedema; rare – allergic reactions.
Mental disorders: rarely – insomnia.
Disorders of the nervous system: very often – headache; often – dizziness; rarely – paresthesia and dysesthesia, drowsiness; rarely -obmorok, amnesia, seizures.
Violations by the organ of vision: rarely – blurred vision, redness of the conjunctiva of the eyeball, impaired color perception, pain in eyeballs and discomfort in the eyes, photophobia; rarely – increased IOP.
Violations by the organ of hearing and labyrinth disorders: rarely – ringing in the ears, vertigo.
Violations of the heart: Infrequent – palpitation, tachycardia; rarely – angina, myocardial infarction, ventricular tachyarrhythmias.
Violations by vessels: often – vasodilation; rarely – hypotension.
Violations of the respiratory system, thorax and mediastinum: often – nasal congestion; rarely – shortness of breath, nasal sinuses.
Violations of the gastrointestinal tract: often -dispepsiya; infrequently – nausea, abdominal pain, dry mouth, diarrhea, gastro-oesophageal reflux disease, gastritis, vomiting.
Violations of the liver and biliary tract: rarely – increased activity of transaminases.
Violations of the skin and subcutaneous tissue disorders: rarely – erythema, rash.
Violations by musculoskeletal and connective tissue disorders: rarely – back pain, increased CPK, increased muscle tone and spasms, myalgia.
Violations by the genitals and breast: Infrequent – increased erections; rarely – priapism.
General disorders and at the injection site: Infrequent – feeling unwell; rarely – pain in the chest.
How to accept, acceptance rate and dosage
Inside, regardless of the meal.
Early treatment recommended dose is 10 mg (approximately 25-60 minutes before sexual intercourse).
However, it was shown that the preparation is effective Levitra® and at reception for 4-5 hours before sexual activity.
The maximum frequency of ingestion – 1 time per day.
Depending on the efficacy and tolerability of treatment dose can be increased or decreased to 20 to 5 mg / day.
The maximum recommended dose – 20 mg 1 time per day.
In order to ensure an adequate response to treatment requires sexual stimulation.
In a dry place at a temperature below 30 ° C
Vardenafil is metabolized mainly involving hepatic cytochrome P450 enzyme system, namely isoform 3A4, and also with participation of some isoforms 3A5 and 2C9. Inhibitors of these enzymes may reduce vardenafil clearance.
Cimetidine (400 mg, 2 times / day): nonspecific inhibitor of cytochrome P450 has no effect on the value of AUC and Cmaxvardenafila indicators (20 mg) at their simultaneous use.
The drug Levitra® OTD contraindicated while the use of active or moderately potent inhibitors of CYP3A4, such as ketoconazole, itraconazole, ritonavir, indinavir, erythromycin and clarithromycin. The combined application of the drug Levitra® OTD with ketoconazole, itraconazole, indinavir and ritonavir (potential CYP3A4 inhibitors) can expect a substantial increase in plasma concentrations of vardenafil.
Nitrates, nitric oxide donator: receiving vardenafil (10 mg) in a period of from 24 hours to 1 hour prior to the reception of nitroglycerin (0.4 mg sublingual), does not enhance its hypotensive effect when taking in healthy subjects. At a dose of 20 mg for 1-4 hours prior to receiving nitrate (0.4 mg sublingual) vardenafil enhances their hypotensive action, but if vardenafil appointed for 24 hours, then the gain of the hypotensive action of nitrates does not occur while taking in healthy middle-aged subjects.
Nicorandil is a potassium channel activator and contains in its composition a nitro group. The presence of the nitro group in the composition of nicorandil causes high probability of its interaction with vardenafil.
However, there is insufficient information on the potential hypotensive effects of vardenafil while the use of nitrates. Therefore, this combination is contraindicated.
Vardenafil (20 mg) did not alter the parameters AUC and Cmax glibenclamide (glyburide at a dose of 3.5 mg) at their joint application. It is also shown that the pharmacokinetics of vardenafil is not changed when it is applied simultaneously with glibenclamide.
Pharmacokinetic and pharmacodynamic interaction (effect on prothrombin time and coagulation factors II, VII, X) are not marked in the combined use of vardenafil (20 mg), warfarin (25 mg). Concomitant use of 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). A combined reception vardenafil and nifedipine did not lead to significant pharmacodynamic interaction: vardenafil causes versus placebo additional reduction in systolic and diastolic blood pressure as measured in the supine position on average 5.9 mmHg and 5.2 mmHg respectively.
Since it is known that alpha-blockers cause a reduction in blood pressure, especially postural hypotension and syncope, the question of the interaction of alpha-blockers and vardenafil, when used together carefully studied.
Evaluation of blood pressure and heart rate during the 10 h after administration of vardenafil at a dosage of 5 mg or 10 mg, designated 4 hours after priemaalfuzozina, revealed no clinically significant additional reduction in the average maximum blood pressure compared to placebo. In one patient, there was a decrease in systolic blood pressure from baseline of more than 30 mm Hg After standing vardenafil 5 mg. The other patient had a systolic blood pressure decrease from baseline of more than 30 mm Hg After standing vardenafil 10 mg. Cases reducing systolic blood pressure in the standing position below 85 mm Hg in this case it has been identified. Reported the presence of dizziness in two patients after vardenafil 5 mg, one patient – receiving 10 mg vardenafil, and one – after placebo. Since for identifying potential interactions maximum 4-hour interval between meals dose was selected and vardenafil alfuzosin, compliance with the time interval between drug administration is required. Cases, fainting and in this case, while the application of vardenafil tamsulosin or terazosin been identified.
Combined assignment vardenafil and alpha-blockers is permissible only in the presence of a stable blood pressure parameters in patients receiving alpha-blockers, and the vardenafil need to assign the minimum recommended dose is 5 mg. However, the drug Levitra® OTD in the form of tablets, dispersible in the mouth, should not be administered as an initial dose in concurrent therapy with alpha-blockers. Should not take vardenafil in one and the same time, alpha-blockers, except alfuzosin and tamsulosin, reception of which could coincide with the administration of the drug Levitra® OTD. Vardenafil between reception and other alpha-blockers should be observed time interval. When concomitant administration of terazosin and vardenafil observe 6-hour interval between drug administration.
The simultaneous use of digoxin (0.375 mg) and vardenafil (20 mg) every other day for 14 days is not accompanied by their interaction.
A single dose of antacid (magnesium hydroxide / aluminum hydroxide) did not affect the AUC and Cmax parameters vardenafil.
Bioavailability vardenafil (20 mg) was also not affected by its combination with a histamine H2 receptor ranitidine (150 mg, 2 times / day).
Vardenafil (10 mg and 20 mg) did not affect the duration of bleeding when used as monotherapy and in combination satsetilsalitsilovoy acid at a low dose (2 tab. Of 81 mg).
Vardenafil (20 mg) did 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 anti-diabetic drugs (sulfonylureas and metformin), weak CYP3A4 inhibitors do not affect the pharmacokinetics of vardenafil.