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Levitra - a means for the treatment of erectile dysfunction. The physiological mechanism of penile erection is relaxation of smooth muscles of cavernous bodies and arterioles. When sexual stimulation of the nerve endings of the cavernous bodies released nitric oxide (of NO), activates the enzyme guanylate cyclase, and contributing to increase the content of cyclic guanosine monophosphate (cGMP), resulting in relaxation of smooth muscle of the corpus cavernosum, causing increased blood flow to the penis.
Vardenafil blocks specific phosphodiesterase type 5 (PDE-5), under the influence of which is split cGMP. It enhances the action of endogenous NO in the cavernous body during sexual arousal. Thus, when using Levitra restores erectile dysfunction and provides a natural response to sexual stimulation.
Vardenafil is rapidly absorbed after oral administration. plasma concentration after ingestion fasting reaches a maximum value for 30-120 minutes (median 60 minutes). The absolute bioavailability of approximately 15%. When receiving vardenafil with fatty food intake decreases its speed, the period of maximum concentration is increased to 60 minutes, the maximal concentration in blood plasma decreases on average by 20%; but significant changes in AUC index does not occur. When taken with food vardenafil comprising less than 30% fat, the pharmacokinetic parameters of the drug are not changed.
Vardenafil and its major metabolite approximately 95% bound to plasma proteins, and this process is reversible and not dependent on the concentration of the drug. The semen of healthy men after 90 minutes after administration of vardenafil is determined not more than 0.00012% of the administered dose. Vardenafil is metabolised predominantly influenced by hepatic enzyme CYP 3A4 (the main road), CYP 3A5 and CYP 2C9 (minor route). The total clearance of vardenafil is 56 l / h. After oral administration of vardenafil is excreted as metabolites, mainly in the feces (91-95% injected dose), to a lesser extent - in the urine (6.2% of dose). Vardenafil half-life averages 4-5 hours, the major metabolite M1 - about 4 hours.
In healthy men aged 65 years and older compared to younger patients (under 45 years) noted rate increase AUC by an average of 52%, but a significant reduction in hepatic clearance of vardenafil is not indicated. The frequency of adverse side effects of the drug is not dependent on age.
In individuals with mild, moderate and severe renal impairment (creatinine clearance 55-80, respectively, 30-50 and ≤30 mL / min), the pharmacokinetics of vardenafil practically unchanged. In patients with mild and moderately severe impaired liver function vardenafil clearance is reduced, and performance AUC and maximum concentration increase in proportion to the degree of liver dysfunction.

Indications:
erectile dysfunction (inability to achieve and maintain an erection necessary for sexual intercourse).

Application:
inside regardless of the meal. The recommended starting dose is 10 mg. The tablet should be taken for 15-25 minutes prior to sexual contact, but can be taken and for 4-5 hours. In order to achieve the desired effect when using Levitra ensure adequate sexual stimulation. Given the efficacy and tolerability of the dose can be increased to 20 mg or lower to 5 mg. The maximum recommended dose of Levitra - 20 mg, the multiplicity of reception - no more than 1 time per day.
There is no need to correct dosing regimen in elderly patients, patients with renal failure or impaired hepatic function insignificant. In patients with moderately severe hepatic impairment Vardenafil clearance function is reduced, so the initial dose should not exceed 5 mg / day. Given the efficacy and tolerability further Levitra daily dose can be increased to 10-20 mg.

Contraindications:
Hypersensitivity to the drug, the simultaneous use of nitrates or any donor of NO (drugs that produce NO), the age to 16 years, concurrent use with HIV protease inhibitors indinavir and ritonavir, as they are potent inhibitors of 3A4 SYR.

Side effects:
generally well tolerated, side effects are transient and slightly pronounced.
The most frequent (10% of cases): headache, flushing (hyperemia of the person);
frequent (1-10%): dizziness, diarrhea phenomenon, nausea, nasal congestion;
Infrequent (0.1-1%): photosensitivity of skin, hypertension, back pain, watery eyes;
unit (0.01-0.1%): hypotension, myalgia, priapism.
Noted isolated cases of anterior ischemic optic neuropathy (as a result of a decrease in up to counter its loss), which is believed to be associated with the use of PDE-5 inhibitors, which belongs to the group, and Levitra. Most of the surveyed patients were vascular risk (pronounced stagnation of the optic nerve, age 50 years and over, diabetes, hypertension, cardiovascular disease, hyperlipidemia and smoking). However, it is established whether these sporadic cases directly to the use of PDE5 inhibitors in patients undergoing vascular risk, or they should be attributed to other factors.

special instructions
Preparations for the removal of erectile dysfunction with caution prescribed for anatomical deformation of the penis such as angulation, cavernous fibrosis (Peyronie's disease), as well as in diseases that contribute to the development of priapism (sickle-cell anemia, multiple myeloma, leukemia, or leukemia).
Due to lack of information on the safety of Levitra in patients listed groups receiving the drug is not recommended in severe hepatic dysfunction, kidney disease in the terminal stage (if needed dialysis), severe hypotension (systolic blood pressure at rest ≤90 mm Hg. Art.) , unstable angina, after suffering a hemorrhagic stroke or myocardial infarction (within the last 6 months), as well as hereditary degenerative diseases of the retina (retinitis pigmentosa).
Because Levitra has not been used in patients with a tendency to bleeding, and in patients with peptic ulcer of the stomach or duodenal ulcers, prescribed the drug in such cases is possible only after a careful comparison of the expected benefits and potential risks.
Before using Vardenafil is necessary to assess the state of the cardiovascular system of the patient, because the sexual activity is associated with a specific cardiac risk. Patients with congenital prolonged intervals of Q-T, taking anti-arrhythmic drugs class Ia (quinidine, procainamide), or class III (amiodarone, sotalol), the appointment of Levitra is contraindicated.
Patients over the age of 65 years should not exceed a dose of 5 mg due to a decrease in clearance of vardenafil.
Levitra is not intended for babies, children and women.

interaction
The safety and efficacy of vardenafil in combination with other agents for the elimination of erectile dysfunction have not been established, so it is not recommended to use such a combination.
Reduced clearance of vardenafil occurred while the application of the system of selective inhibitors of cytochrome P450 enzymes CYP 3A4 (such as cimetidine, ketoconazole, itraconazole, indinavir, ritonavir, erythromycin). If necessary, any combination of these drugs Levitra daily dose should not exceed 5 mg.
Simultaneous administration of vardenafil with alpha-adrenergic blockers may cause the development of symptomatic hypotension, so Levitra should be applied not earlier than 6 hours after administration.
Inhibitors of CYP 2C9 (tolbutamide, warfarin), CYP 2D6 (selective inhibitors of reverse neuronal serotonin reuptake, tricyclic antidepressants), thiazides and thiazide diuretics, loop and potassium-sparing diuretics, ACE inhibitors, calcium channel blockers, β-adrenergic receptors and inductors metabolism CYP 450 (rifampicin , barbiturates) have no effect on the pharmacokinetics of vardenafil.
No evidence of clinically significant interaction of vardenafil with tolbutamide (250 mg) or warfarin (40 mg) that are metabolized by CYP 2C9, is not revealed.
A single dose of antacid (magnesium / aluminum hydroxide) did not affect the bioavailability of vardenafil.

Overdose
The symptoms - pain in the back; Treatment: symptomatic and supportive therapy (respectively, the clinical state of the patient). The use of hemodialysis does not increase clearance of vardenafil as he avidly binds to plasma proteins and excreted by the kidneys.

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