Levitra 20 mg
Pharmacokinetics Levitra:
Once inside quickly absorbed. When you receive an empty stomach early peak Cmax can be reached in 15 minutes, but 90% of the average Cmax is achieved within 60 min (from 30 to 120 min). The absolute bioavailability of approximately 15% of. At the recommended dose range (5-20 mg), the value index "area under the curve of the concentration-timeģ (AUC) and C max increased proportionally to the dose.
Metabolism. Vardenafil is metabolized predominantly liver enzymes with izoformyCYP3A4, as well as CYP3A5 and CYP2C9 cytochrome P450. The average T1 / 2 vardenafil is 4-5 h, and the major metabolite M1 - about 4 hours in the blood contained glucuronide metabolite M1. The concentration of the rest of the metabolite M1 is 26% of the concentration of active substance. Profile of selectivity on phosphodiesterase M1 is similar to those of vardenafil; in vitro the ability to inhibit PDE-5 is 28% compared with vardenafilom, which corresponds to 7% of the effectiveness of the drug.
Stain. The total clearance of vardenafil is 56 l / h, the final T1 / 2 - about 4-5 hours after oral administration vardenafil in the form of metabolites derived primarily through the gastrointestinal tract (91-95% of the dose), to a lesser extent - by the kidneys (2-6% dose ).
Elderly patients. In healthy older men ( 65 years) compared with young individuals ( 45 years) hepatic clearance of vardenafil reduced. The average AUC in the elderly increased by 52%. However, the difference in efficacy and safety in patients older and younger age were not observed.
Renal failure. Patients with mild (Cl creatinine> 55-80 ml / min) and moderate (Cl creatinine> 30-50 ml / min) the degree of renal dysfunction vardenafil pharmacokinetic parameters are comparable to those in healthy people. In severely impaired renal function (Cl creatinine <30 ml / min), the mean value of the index AUC increased by 21% and Cmax decreased by 23%. Significant correlation between creatinine clearance and the concentration of vardenafil in the plasma (AUC and Cmax) are not marked.
Patients who are on hemodialysis, pharmacokinetics of vardenafil has not been studied.
Abnormal liver function. In patients with mild and moderate hepatic impairment clearance of vardenafil is reduced proportionally to the degree of dysfunction of the liver. Mild hepatic failure (stage A to Child-Pugh) noted an increase in AUC and Cmax of 1,2 times (AUC - 17%, C max - 22%), and at a moderate (stage B in Child-Pugh) - 2,6 (160%) and 2,3 (130%) times respectively compared with healthy volunteers.
Patients with severe hepatic impairment (stage B of Child-Pugh), the pharmacokinetics of vardenafil has not been studied.
Pharmacodynamics Levitra: Erection of the penis is a hemodynamic process, based on the relaxation of smooth muscles of cavernous bodies and placed them in arterioles. During sexual stimulation of the nerve endings cavernosa released nitric oxide (NO), activates the enzyme guanylate cyclase, which leads to increased concentration of solids in the cavernous cyclic Guanosine monophosphate (cGMP). The result is relaxation of smooth muscles of cavernous bodies, which increases blood flow to the penis.
By blocking specific types of fifth fosfodiesterazu (PDE-5), which participates in the cleavage of cGMP, vardenafil enhances the local action of endogenous nitric oxide (NO) in cavernous bodies during sexual stimulation.
This effect determines the ability to Levitra enhance response to sexual stimulation.
Prescribed Levitra: Erectile dysfunction (inability to achieve and maintain an erection necessary for sexual intercourse).
Contraindications Levitra: hypersensitivity to any component of the drug;
the simultaneous application of nitrate or drugs, which are donators of nitrogen oxide;
combination with HIV protease inhibitors such as indinavir or ritonavir.
Precautions:
- congenital prolongation of the interval QT;
- anatomical deformity of the penis (distortion, cavernous fibrosis, Peyronie's disease);
- diseases predisposing to priapism (sickle cell anemia, multiple myeloma, leukemia);
- severe dysfunction of the liver;
- kidney disease in the terminal stage;
- hypotension (SBP alone - less than 90 mm Hg. Art.)
- recent stroke and myocardial infarction;
- unstable angina
- hereditary degenerative diseases of the retina (e.g. retinitis pigmentosa);
- tendency to bleeding and exacerbation of peptic ulcer;
- aortic stenosis and idiopathic hypertrophic subaortalny stenosis.
Side effects:
Levitra, generally has slight side effects, usually slightly or moderately expressed and are transient in nature.
These placebo-controlled clinical studies
The rate of -> 1%
Nervous system: dizziness, headache.
Vascular system: "tides" (sensation of heat, redness of skin, "hot flashes").
Respiratory system: congestive hyperemia of the nasal mucosa (mucosal edema, rhinitis, rhinorrhea).
Digestive system: dyspepsia, nausea.
The data of all clinical studies
The most typical -> 10%
Nervous system: headache.
Vascular system: "tides" (sensation of heat, redness of skin, "hot flashes").
Typical -> 1 - <10%
Nervous System: dizziness.
Respiratory system: congestive hyperemia of the nasal mucosa (mucosal edema, rhinitis, rhinorrhea).
Digestive system: dyspepsia, nausea.
Atypical -> 0,1 - <1%
Nervous system: drowsiness.
Bodies of view: an increased watery, blurred vision (luminance of view).
Vascular system: hypertension, hypotension, orthostatic hypotension.
Respiratory system: dyspnea, epistaxis.
Digestive system: changes in liver function tests (increased levels of ALT, AST), raising gammaglutamiltranspeptidazy (GGTP).
Skin: facial swelling, photosensitivity reaction.
Musculoskeletal: myalgia, back pain, increased creatine kinase.
Rare -> 0,01 - <0,1%
Immune System: hypersensitivity reaction.
Psychiatric disorders: anxiety.
Nervous system: syncope.
Bodies of view: increased intraocular pressure.
Cardiovascular system: angina pectoris, myocardial ischemia.
Respiratory system: laryngeal edema.
Musculoskeletal system: increased muscle tone.
Reproductive system: the extension of an erection or painful erections, priapism.
There are rare post marketing surveillance reports of cases of anterior ischemic optic neuropathy (PINZN), leading to visual impairment (including permanent loss of vision), related in time with the reception of the PDE-5 inhibitors, including and Levitra, patients, many of which have the associated risk factors for this condition as an anatomical defect of the optic nerve, age over 50 years, diabetes mellitus, hypertension, coronary heart disease, hyperlipidemia and smoking. Unknown is whether the development PINZN directly with the use of PDE-5 inhibitors, or with an individual patient associated cardiovascular risk factors, and anatomic defects, or with a combination of these factors, or other reasons.
Cases of visual impairment, including temporary or permanent loss of vision, which are linked in time with the reception of the PDE-5 inhibitors, including and Levitra. Not established, whether these cases directly with the reception of the PDE-5 inhibitors, or with concomitant vascular risk factors, or other reasons.
Interaction levitra:
Inhibitors of cytochrome P450Vardenafil is metabolized primarily involving the liver enzyme cytochrome P450 (CYP), namely, isoforms 3A4, as well as with some participation isoforms CYP3A5 and CYP2S. Inhibitors of these enzymes may decrease the clearance of vardenafil.
Cimetidine (400 mg 2 times a day): nonspecific inhibitor of cytochrome P450 has no effect on the value of AUC and C max parameters vardenafil (20 mg) in their simultaneous application.
Erythromycin (500 mg 3 times a day): This is an inhibitor of CYP 3A4 is 4-fold (300%) increase in AUC and 3-fold (200%) increase in Cmax vardenafil (5 mg).
Ketoconazole (200 mg): being a powerful inhibitor of CYP 3A4, is a 10-fold increase (900%) AUC and a 4-fold increase (300%) Cmax vardenafil (5 mg).
With the combined use of vardenafil (10 mg) and an inhibitor of HIV-protease indinavir (800 mg 3 times daily) indicated 16-fold (1500%) increase in AUC and 7-fold (600%) increase in vardenafil Cmax. At 24 h after administration of vardenafil in the plasma concentration of approximately 4% of its C max.
Ritonavir (600 mg twice a day): increases 13 times C max vardenafil (5 mg) and 49 times its total daily rate of AUC. The interaction due to the fact that ritonavir, as a potent inhibitor of CYP3A4 and CYP2C9, blocking hepatic metabolism of Levitra. Ritonavir is a much longer T1 / 2 Levitra until 25.7 h. In the combined use of vardenafil with ketoconazole, itraconazole, indinavir and ritonavir (potent inhibitors of CYP 3A4) can expect a significant increase in drug concentration in plasma.
Overdose Levitra:
We know of cases receiving vardenafil 80 mg 1 time per day and 40 mg 1 every day for over 4 weeks without development of serious adverse reactions. At the same time, the application of the drug in a dose of 40 mg 2 times a day there are marked back pain with no signs of toxic effects on the muscular and nervous systems.Treatment: the appointment of a standard maintenance therapy. Hemodialysis does not increase excretion of the drug because vardenafil is well connected with blood plasma proteins and only a small amount of drug released by the kidneys.
Dosing and dose of Levitra:
Inside, regardless of the meal.At the beginning of treatment recommended dose is 10 mg (approximately 25-60 minutes before sexual intercourse). However, it was shown that Levitra is effective in the hiring process for 4-5 hours before sexual activity. The maximum frequency of drug administration - 1 times per day. Depending on the effectiveness and tolerability of treatment dose can be increased to 20 mg or decreased to 5 mg per day. The maximum recommended dose - 20 mg 1 time per day. To ensure adequate response to treatment is required sexual stimulation.
Elderly patients (over 65). The initial dose is 5 mg, as in this age group decreased clearance of vardenafil.
Children (ages up to 16 years). The use of Levitra is not indicated for patients in this age category.
Abnormal liver function. In patients with minor liver dysfunction (stage A to Child-Pugh) change the dosage is not required. In patients with moderate violation (stage B in Child-Pugh), liver function the initial dose is 5 mg / day. In the future, depending on the effectiveness and tolerability of treatment dose can be increased to a maximum of 10 mg.
Renal. Change of dosing regimen is not required in patients with insignificant (Cl creatinine> 50-80 ml / min), moderate (Cl creatinine> 30-50 ml / min) and severe (Cl creatinine <30 ml min) decrease in kidney function.
Cautions:
Prior to the appointment of drugs used to treat erectile dysfunction, the physician should assess the state of the cardiovascular system of the patient, because there is the risk of complications from heart during sexual activity. Vardenafil has vasodilating properties, which may be accompanied by a slight or moderate BP reduction. Patients with obstruction of the outflow from the left ventricle (eg aortic stenosis, idiopathic hypertrophic subaortalnym stenosis) may be sensitive to the action of vasodilators, including inhibitors of PDE-5.Although the development of myocardial infarction is associated in time with the reception of vardenafil and with sexual activity, but not yet established is whether the emergence of the disease directly from the application of vardenafil, or with sexual activity, or with concomitant diseases, or with a combination of these factors.
Men who do not show sexual activity because of concomitant cardiovascular disease, drugs to treat erectile dysfunction should not be applied.
Since Levitra in therapeutic doses (10 mg) causes lengthening of the interval QT, patients with congenital prolongation of the QT interval and those who take antiarrhythmic drugs class IA (quinidine, procainamide) or class III (amiodarone, sotalol), this drug should not be appointed.
Safety and efficacy of vardenafil in combination with other drugs for the treatment of erectile dysfunction was not studied, so their combined use is not recommended.
During the course of Levitra and other PDE-5 inhibitors have been reported cases of transient vision loss. In the event of sudden loss of vision should stop taking Levitra and immediately consult a physician.
Combined therapy of alpha-blockers and vardenafilom may be accompanied by the development of arterial hypotension with the appropriate clinical picture, because these drugs have vasodilating effect.
If you take doses of vardenafil therapy of alpha-blockers should be started in the lowest dose. The gradual increase in the dose of alpha-blockers in patients receiving drugs from the group of inhibitors of PDE-5, may be accompanied by further reduction of BP.
The dose of vardenafil should not exceed 5 mg. The dose of ketoconazole and itraconazole at the same time should not exceed 200 mg.
Vardenafil does not affect the duration of bleeding, including in combined therapy with acetylsalicylic acid.
Vardenafil does not increase platelet aggregation induced by various drugs. At concentrations above the therapeutic, vardenafil causes a slight strengthening antiaggregant of sodium nitroprusside, which is a donor of nitric oxide.
The combined purpose vardenafil and heparin on duration of bleeding is not known.
The drug is not indicated for use in women, infants and children.
Impact on management of vehicles and machinery
Before you drive vehicles and machinery, patients need to know how they react to the reception Levitra.
