Levitra

Pharmacological Properties

А remedy for the treatment of erectile dysfunction. The physiological mechanism of penile erection consists in relaxation of the smooth muscles of the cavernous body and arterioles. During sexual stimulation, nitric oxide (NO) is released from the nerve endings of the cavernous body, which activates the enzyme guanylate cyclase and contributes to an increase in the content of cyclic guanosine monophosphate (cGMP), as a result of which the smooth muscles of the cavernous body relax, causing an increase in blood flow to the penis.

Vardenafil blocks the specific phosphodiesterase type 5 (PDE-5), which breaks down cGMP. This enhances the action of endogenous NO in the cavernous body during sexual arousal. Thus, when using Levitra, impaired erection is restored and a natural response to sexual stimulation is provided.

Vardenafil is rapidly absorbed after ingestion. The concentration in the blood plasma after taking on an empty stomach reaches a maximum value within 30–120 minutes (on average, after 60 minutes). Absolute bioavailability is about 15%. When taking vardenafil with a fatty meal, its absorption rate decreases, the period of reaching the maximum concentration increases to 60 minutes, the maximum concentration in the blood plasma decreases on average by 20%; but there are no significant changes in the AUC indicator. When taking vardenafil with food containing no more than 30% fat, the pharmacokinetic parameters of the drug do not change.

Vardenafil and its main metabolite are approximately 95% bound to plasma proteins, and this process is reversible and does not depend on the concentration of the drug. In the sperm of healthy men 90 minutes after taking vardenafil, not more than 0.00012% of the dose taken is determined. Vardenafil is metabolized primarily by the hepatic enzymes CYP 3A4 (major route), CYP 3A5 and CYP 2C9 (minor pathway). The total clearance of vardenafil is 56 l/h. After oral administration, vardenafil is excreted in the form of metabolites, mainly with feces (91–95% of the administered dose), and to a lesser extent with urine (2–6% of the dose). The elimination half-life of vardenafil is on average 4-5 hours, the main metabolite M1 is about 4 hours.

In healthy men aged 65 years and older compared to patients over at a young age (up to  45 years) an increase in AUC was noted on average by 52%, but a significant decrease in the hepatic clearance of vardenafil was not noted. The frequency of negative side effects of the drug does not depend on age.

In persons with mild, moderate and severe renal insufficiency (creatinine clearance, respectively, 55–80, 30–50 and <30  ml / min), the pharmacokinetics of vardenafil practically does not change. In patients with slight and moderately impaired liver function, the clearance of vardenafil decreases, and the AUC and maximum concentration increase in proportion to the degree of impaired liver function.

Indications

Erectile dysfunction.

Apply

Inside, regardless of a meal. The recommended starting dose is 10 mg. The tablet should be taken 15-25 minutes before the onset of sexual contact, but it can also be taken 4-5 hours before. To achieve the desired effect when using Levitra, adequate sexual stimulation is necessary. Taking into account the effectiveness and tolerability of the drug, the dose can be increased to 20 mg or reduced to 5 mg. The maximum recommended dose of Levitra is 20 mg, the frequency of administration is no more than 1 time per day.

There is no need to adjust the dosage regimen in elderly people, patients with renal insufficiency or minor violations of liver function. In patients with moderately impaired liver function, the clearance of vardenafil is reduced, so the initial dose of the drug should not exceed 5 mg / day. Taking into account the effectiveness and tolerability in the future, the daily dose of Levitra can be increased to 10–20 mg.

Contraindications

Hypersensitivity to components of the drug, simultaneous use of nitrates or any NO donators (drugs that emit NO), age up to 16 years, simultaneous use of HIV protease inhibitors indinavir and  ritonavir as they are potential inhibitors of CYP3A4.

Side Effects

Usually well tolerated, side effects are transient and slightly pronounced.

Most common (>10% of cases):headache, flushing (facial flushing);

frequent (1–10%): dizziness, dyspepsia, nausea, nasal congestion;

infrequent (0.1–1%): skin photosensitivity , hypertension, back pain, lacrimation;

single (0.01–0.1%): hypotension, myalgia, priapism.

There have been isolated cases of anterior ischemic optic neuropathy (as a result, vision is reduced up to its permanent loss), which is believed to be associated with the use of PDE-5 inhibitors, to the group of which Levitra belongs. Most of the examined patients were at vascular risk (severe optic nerve congestion, age 50 years and over, diabetes, hypertension, cardiovascular disease, hyperlipidemia, and smoking). However, it has not been established whether these isolated cases of disease are directly related to the use of PDE-5 inhibitors in patients at vascular risk, or whether they should be attributed to other factors.

Special Instructions

Drugs to eliminate erectile dysfunction with  special care are prescribed for anatomical deformation of the penis, for example, during angulation , cavernous fibrosis (Peyronie's disease), and also in diseases that contribute to the development of priapism (sickle cell anemia, multiple myeloma, leukemia or leukemia). in patients of these groups, taking the drug is not recommended for severe liver dysfunction, end-stage kidney disease (if hemodialysis is necessary), severe arterial hypotension (systolic blood pressure at rest <90 mm hg st.) , unstable angina, after suffering a hemorrhagic stroke or myocardial infarction (during the last 6 months), and also with hereditary degenerative diseases of the retina (retinitis pigmentosa).

Since Levitra was not used in patients with a tendency to bleeding and in patients with peptic ulcer of the stomach or duodenum, it is possible to prescribe the drug in such cases only after a careful comparison of the expected benefit and potential risk.

Before using vardenafil, it is necessary to evaluate the state of the patient's cardiovascular system, since sexual activity is associated with a certain cardiac risk. Patients with a congenital prolonged Q–T interval taking antiarrhythmic drugs class Ia (quinidine, procainamide) or class III (amiodarone, sotalol), Levitra is contraindicated.

Patients over the age of 65 years are not recommended to exceed the dose of 5 mg due to a decrease in vardenafil clearance.

Levitra is not intended for newborns, children and women.

Interactions

Safety and efficacy of vardenafil in combination with other means to tret erectile dysfunction have not been established, therefore, the use of such combinations is not recommended.

Vardenafil clearance decreased with simultaneous use of selective inhibitors of enzymes of the cytochrome P450 CYP 3A4 system (such as cimetidine, ketoconazole, itraconazole, indinavir, ritonavir, erythromycin). If it is necessary to combine with any of these drugs, the daily dose of Levitra should not exceed 5 mg. earlier than 6 hours after taking them.

CYP 2C9 inhibitors (tolbutamide, warfarin), CYP 2D6 (selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazides and thiazide-like diuretics, Loop and potassium-sparing diuretics, ACE inhibitors, calcium antagonists, β-adrenergic blockers and CYP450 metabolism inducers (rifampicin, barbiturates) do not affect the pharmacokinetics of vardenafil.

Signs of a clinically significant interaction of vardenafil with  sp; tolbutamide (250 mg) or warfarin (40 mg), which are metabolized by CYP 2C9, was not detected.

A single dose of an antacid (magnesium / aluminum hydroxide) did not affect the bioavailability of vardenafil.

Overdose

Symptoms — back pain Treatment:symptomatic and supportive therapy (according to the clinical condition of the patient). The use of hemodialysis does not increase the clearance of vardenafil, since it actively binds to blood plasma proteins and is not excreted by the kidneys.

Storage conditions

Comparison

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See Also