Pharmacological properties of the drug Levitra™
A remedy for the treatment of erectile dysfunction. The physiological mechanism of penile erection is the relaxation of the smooth muscles of the corpus cavernosum and arterioles. During sexual stimulation, nitric oxide (NO) is released from the nerve endings of the corpus cavernosum, which activates the enzyme guanylate cyclase and increases the content of cyclic guanosine monophosphate (cGMP), resulting in relaxation of the smooth muscles of the cavernous body, causing an increase in blood flow to the penis. Vardenafil blocks specific phosphodiesterase type 5 (PDE-5), which causes the breakdown of cGMP. This enhances the action of endogenous NO in the corpus cavernosum during sexual arousal. Thus, when using Levitra, impaired erection is restored and a natural response to sexual stimulation is ensured. Vardenafil is rapidly absorbed after oral administration. Concentration in blood plasma after administration on an empty stomach reaches its maximum value within 30–120 minutes (on average after 60 minutes). Absolute bioavailability is about 15%. When taking vardenafil with fatty foods, its absorption rate decreases, the period to reach the maximum concentration increases to 60 minutes, the maximum concentration in the blood plasma decreases by an average of 20%; but there are no significant changes in AUC. 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, no more than 0.00012% of the dose taken is determined 90 minutes after taking vardenafil. Vardenafil is metabolized primarily under the influence of the liver enzymes CYP 3A4 (main route), CYP 3A5 and CYP 2C9 (minor route). The total clearance of vardenafil is 56 l/h. After oral administration, vardenafil is excreted in the form of metabolites, mainly in feces (91–95% of the administered dose), and to a lesser extent in urine (2–6% of the dose). The 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 with younger patients (up to 45 years), an average increase in AUC of 52% was noted, but no significant decrease in the hepatic clearance of vardenafil was observed. The frequency of negative side effects of the drug does not depend on age. In individuals with mild, moderate and severe renal failure (creatinine clearance 55–80, 30–50 and ≤30 ml/min, respectively), the pharmacokinetics of vardenafil remain virtually unchanged. In patients with mild to moderate hepatic impairment, vardenafil clearance is reduced, and AUC and maximum concentrations increase in proportion to the degree of hepatic impairment.
How and when are erection pills used and what is the difference between Viagra, Cialis and Levitra?
Erection pills from the group of PDE inhibitors (Viagra, Cialis, Levitra) are the first choice for any form of organic ED. They are prescribed immediately before sexual intercourse in a period of time from 30 minutes to 1 hour before planned sex. In some cases, drugs are prescribed regularly before each sexual intercourse, sometimes they are recommended to be taken only in cases where, in the opinion of the patient, there is the greatest chance of failure. These drugs have differences that are useful to know. Viagra has the greatest clinical experience, because. has been in use since 1998. This drug has already helped more than 16 million people worldwide and is the most well-studied of all erection pills. Viagra should be taken 1 hour before sexual intercourse, it works for up to 4 hours and is more likely to cause side effects after taking it compared to newer PDE inhibitors. Before taking Viagra, it is not recommended to eat rich fatty foods, because... it reduces the effectiveness of the drug. Levitra can be taken 15㪶 minutes before planned sex, its duration of action is slightly longer than that of Viagra, and the frequency of side effects is less. Cialis is taken 30 minutes before intended sexual intercourse; fatty foods do not affect its activity, and it lasts up to 36 hours and sometimes more. For this reason, Cialis is called a weekend pill, because... one tablet allows you to stay “in good shape” the whole weekend. To compare the side effect profile of all 3 drugs, you can refer again to Table 1.
What is the effectiveness of erection pills and is it possible to completely get rid of ED with their help?
The effectiveness of PDE inhibitors for various forms of ED ranges from 60 to 85%, according to various clinical studies. The tablets are designed to be taken before each sexual intercourse, i.e. when you take the pill, the erection improves; without the pill, the erection will be the same as it was recently before the start of treatment. In recent years, there have been reports that regular daily use of relatively small doses of erection pills for at least 12 weeks has a certain healing effect, i.e. improves the quality of your own natural erections. To enhance the effect of PDE inhibitors, they are used in conjunction with male sex hormones, injections of vasodilators into the penis, and operations to limit venous outflow from the penis.
What to do if erection pills don't work?
In such cases, under the supervision of a doctor, it makes sense to try second-line therapy or injections of vasodilators into the penis. If this does not help, you should resort to one of the surgical treatment options. It should be remembered that penile prosthesis has the highest effectiveness among all methods of treating ED.
The Andros clinic presents all modern methods of diagnosing and treating ED without exception. The most accurate diagnosis helps to individualize treatment and make it more effective. Mastery of the technique of implanting all types of penile prostheses allows us to achieve restoration of sexual activity even in the most seemingly hopeless cases. Contact only professionals armed with the entire arsenal of remedies and methods for treating erectile dysfunction available in the world!
Use of Levitra™
Inside, regardless of food intake. The recommended starting dose is 10 mg. The tablet should be taken 15–25 minutes before the start of sexual intercourse, but can 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 the elderly, patients with renal failure or minor liver dysfunction. In patients with moderately severe liver dysfunction, 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.
How does Levitra work?
Vardenafil, which Levitra consists of, increases blood flow to the penis and thereby helps a man get and maintain an erection. Its action is similar to that of sildenafil or Viagra, but the effect of the “blue pill” lasts 2-4, and Levitra lasts up to 5 hours.
Levitra belongs to a class of medications called phosphodiesterase type 5 (PDE5) inhibitors. These drugs prevent PDE5 from narrowing the arteries.
The active substance of Levitra affects the chain of reactions in the penis during intimacy. When a man is sexually aroused, nitric oxide is released in his penis, and this triggers the body's erection mechanism: the enzyme guanylate cyclase produces cyclic guanosine monophosphate (cGMP). This compound regulates the contraction and dilation of blood vessels in the male reproductive organ.
The vessels that supply the penis dilate, and the vessels that drain blood from it narrow. Two cavernous chambers in the penis, called corpora cavernosa, fill with blood, and due to this, an erection occurs. At the same time, another enzyme, phosphodiesterase-5, seeks to break down cGMP, interfering with erections.
When cGMP is broken down, the blood vessels return to their normal size, ending the erection. Vardenafil prevents PDE5 from destroying cGMP, allowing this important enzyme to work longer. As a result, the erection lasts longer.
Side effects of Levitra™
Usually well tolerated, side effects are transient and mild. The most common (10% of cases): headache, flushing (facial hyperemia); common (1–10%): dizziness, dyspeptic symptoms, nausea, nasal congestion; uncommon (0.1–1%): skin photosensitivity, hypertension (arterial hypertension), back pain, lacrimation; single (0.01–0.1%): arterial hypotension, myalgia, priapism. Isolated cases of anterior ischemic optic neuropathy have been reported (resulting in decreased vision up to permanent loss), which is believed to be associated with the use of PDE-5 inhibitors, to which Levitra belongs. Most of the examined patients were at vascular risk (severe optic nerve congestion, age 50 years or more, diabetes, hypertension (arterial hypertension), cardiovascular diseases, hyperlipidemia and smoking). However, it has not been established whether these isolated cases are directly attributable to the use of PDE5 inhibitors in patients at vascular risk or whether they should be attributed to other factors.
Dosage - How to take
Levitra is available in tablets of 2.5, 5, 10 and 20 mg. The initial dosage is usually 10 mg. A 10 mg dose of vardenafil is equivalent to approximately 50 mg of sildenafil or Viagra.
The tablet is taken 25–60 minutes before sex. It should be noted that the drug will not work if the man is not sexually aroused, so foreplay is usually required. The effect lasts up to 5 hours. The maximum permissible daily dose of the drug is 20 mg.
Levitra can be taken with or without food, but drinking alcohol is not recommended, as this reduces the likelihood of an erection. Drinking alcohol may also increase your risk of side effects.
The drug's manufacturer, Bayer Pharma AG, also produces lozenges called Staxyn, which must be dissolved on the tongue before swallowing. They should not be taken with any types of drinks.
Special instructions for the use of Levitra™
Drugs for erectile dysfunction are prescribed with extreme caution in cases of 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 the lack of information about the safety of Levitra 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 (resting systolic blood pressure ≤90 mm Hg) , unstable angina, after a hemorrhagic stroke or myocardial infarction (within the last 6 months), as well as with hereditary degenerative diseases of the retina (retinitis pigmentosa). Since Levitra has not been used in patients with a tendency to bleeding or in patients with peptic ulcers of the stomach or duodenum, the drug can be prescribed in such cases only after careful comparison of the expected benefits and potential risks. Before using vardenafil, it is necessary to assess the condition of the patient's cardiovascular system, since sexual activity is associated with a certain cardiac risk. For patients with congenital prolonged Q - T taking class Ia (quinidine, procainamide) or class III antiarrhythmic drugs (amiodarone, sotalol), Levitra is contraindicated. For patients over 65 years of age, it is not recommended to exceed a dose of 5 mg due to decreased clearance of vardenafil. Levitra is not intended for use by newborns, children or women.
Contraindications
Even before purchasing this product, you must inform your doctor about all your ailments and any other medications or supplements that are used for treatment, since the contraindications are quite serious.
This is especially important if you have the following conditions:
- penile pathology such as Peyronie's disease
- arrhythmia, heart failure or angina
- hearing problems
- hemophilia or bleeding disorders
- hypotension (low blood pressure) or hypertension (high blood pressure)
- liver or kidney disease
- multiple myeloma, leukemia, sickle cell disease, or other blood cell problems
- non-arterial anterior ischemic optic neuropathy
- retinal damage
- stomach ulcer
- retinitis pigmentosa, a rare genetic eye disease
You should also tell your doctor if you have ever experienced priapism, seizures, or have recently had a stroke or heart attack.
A drug such as Levitra is recommended to be purchased with a prescription at a pharmacy, but many, in order to save money, buy it online.
Levitra™ drug interactions
The safety and effectiveness of vardenafil in combination with other drugs to eliminate erectile dysfunction have not been established, therefore the use of such combinations is not recommended. A decrease in the clearance of vardenafil occurred with the simultaneous use of selective inhibitors of enzymes of the cytochrome P450 CYP 3A4 system (such as cimetidine, ketoconazole, itraconazole, indinavir, ritonavir, erythromycin). If combination with any of these drugs is necessary, the daily dose of Levitra should not exceed 5 mg. Concomitant use of vardenafil with α-adrenergic blockers may cause the development of symptomatic hypotension, so Levitra should be used no earlier than 6 hours after their administration. 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 inducers of CYP 450 metabolism (rifampicin , barbiturates) do not affect the pharmacokinetics of vardenafil. There were no signs of clinically significant interaction of vardenafil with tolbutamide (250 mg) or warfarin (40 mg), which are metabolized by CYP 2C9. A single dose of an antacid (magnesium/aluminum hydroxide) did not affect the bioavailability of vardenafil.
Levitra, 1 piece, 20 mg, film-coated tablets
Cytochrome P450 inhibitors
Vardenafil is metabolized primarily with the participation of hepatic enzymes of the cytochrome P450 (CYP) system, namely the 3A4 isoform, as well as with some participation of the CYP3A5 and CYP2C isoforms. Inhibitors of these enzymes may reduce the clearance of vardenafil.
Cimetidine
(400 mg 2 times a day): a nonspecific cytochrome P450 inhibitor does not affect the area under the concentration-time pharmacokinetic curve (AUC) and Cmax of vardenafil (20 mg) when used simultaneously.
Erythromycin
(500 mg 3 times daily): This CYP3A4 inhibitor causes a 4-fold (300%) increase in the AUC and a 3-fold (200%) increase in the Cmax of vardenafil (5 mg).
Ketoconazole
(200 mg): As a potent inhibitor of CYP 3A4, it causes a 10-fold increase (900%) in the AUC and a 4-fold increase (300%) in the Cmax of vardenafil (5 mg).
With the combined use of vardenafil (10 mg) and the HIV protease inhibitor indinavir
(800 mg 3 times a day) there is a 16-fold (1500%) increase in AUC and a 7-fold (600%) increase in Cmax of vardenafil. 24 hours after administration, the plasma concentration of vardenafil is approximately 4% of its Cmax.
Ritonavir
(600 mg twice daily): increases the Cmax of vardenafil (5 mg) by 13 times and its total daily AUC by 49 times. The interaction is due to the fact that ritonavir, being a potent inhibitor of CYP3A4 and CYP2C9, blocks the hepatic metabolism of Levitra. Ritonavir significantly prolongs Levitra's T1/2 to 25.7 hours. When vardenafil is combined with ketoconazole, itraconazole, indinavir and ritonavir (potent inhibitors of CYP 3A4), a significant increase in plasma concentrations of the drug can be expected.
Nitrates, nitric oxide donors:
in healthy volunteers, vardenafil (10 mg) when taken 24–1 hour before nitroglycerin (0.4 mg sublingually) does not increase its hypotensive effect; at a dose of 20 mg 1–4 hours before the use of nitrates (0.4 mg sublingually) it enhances their hypotensive effect.
Other:
Vardenafil (20 mg) does not change the AUC and Cmax of glibenclamide (glyburide at a dose of 3.5 mg) and vice versa when used together.
Pharmacokinetic and pharmacodynamic (effect on PT and coagulation factors II, VII, X) interactions are not observed when vardenafil (20 mg) is combined with warfarin
(25 mg).
No significant pharmacokinetic interaction is observed between vardenafil (20 mg) and nifedipine
(30 or 60 mg): vardenafil causes an additional decrease in SBP and DBP in the supine position, on average, by 5.9 and 5.2 mmHg. Art. respectively.
Since it is known that alpha-blockers
cause a decrease in blood pressure, especially postural hypotension and syncope, the issue of interaction between alpha-blockers and vardenafil when used together has been carefully studied.
Two drug interaction studies were conducted in healthy volunteers with normal blood pressure levels receiving the alpha-blockers tamsulosin
or
terazosin
with rapid (over 14 days or less) dose escalation to or near maximum doses. After adding Levitra to their therapy, hypotension developed in a significant number of study participants. Among individuals receiving terazosin, hypotension (standing SBP less than 85 mmHg) occurred more frequently when Levitra and terazosin were prescribed to coincide with the Cmax over time, compared with the situation when the Cmax diverged in time by 6 hours. These studies may have limited clinical significance, since they were conducted with the participation of healthy volunteers, and also after forced dose titration (thus, study participants were not able to achieve stabilization of blood pressure while taking alpha-blockers).
Levitra drug interaction studies have also been conducted in patients with BPH receiving stable doses of tamsulosin or terazosin. When Levitra was prescribed in doses of 5, 10 or 20 mg to patients receiving stable doses of tamsulosin, no additional reduction in mean blood pressure was observed. With the simultaneous administration of Levitra at a dose of 5 mg and tamsulosin at a dose of 0.4 mg, orthostatic arterial hypotension was observed in 2 out of 21 patients with a drop in SBP below 85 mmHg. Art. When taking Levitra at a dose of 5 mg and tamsulosin at a 6-hour interval, orthostatic systolic hypotension with a drop in SBP less than 85 mm Hg. Art. also developed in 2 patients out of 21. In a subsequent study, with the simultaneous administration of Levitra in doses of 10 and 20 mg and tamsulosin in doses of 0.4 and 0.8 mg, cases of orthostatic fall in SBP below 85 mm Hg. Art. was not registered. With the simultaneous administration of Levitra at a dose of 5 mg and terazosin at doses of 5 or 10 mg, symptomatic postural hypotension was observed in one of 21 patients. When taking Levitra at a dose of 5 mg and terazosin with an interval of 6 hours, there were no cases of drop in blood pressure. The results obtained should be taken into account when deciding when to prescribe drugs. The combined use of Levitra and alpha-blockers is permissible only if there are stable blood pressure levels while taking alpha-blockers, and Levitra should be prescribed in the minimum recommended dose of 5 mg. Levitra should not be taken at the same time as alpha-blockers, with the exception of tamsulosin, which may be taken at the same time as Levitra.
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 dose of Maalox
(antacid - magnesium hydroxide/aluminum hydroxide) does not affect the AUC and Cmax of vardenafil. The bioavailability of vardenafil (20 mg) is not impaired when combined with histamine H2 receptor antagonists: ranitidine (150 mg 2 times a day) and cimetidine (400 mg 2 times a day).
Vardenafil (10 or 20 mg) does not affect the duration of bleeding when used as monotherapy and in combination with acetylsalicylic acid
in a low dose (2 tablets of 81 mg each).
Vardenafil (20 mg) does not potentiate the hypotensive effect of alcohol (0.5 g/kg), and the pharmacokinetics of vardenafil are not affected.
Acetylsalicylic acid, ACE inhibitors, beta-blockers, diuretics and antidiabetic drugs (sulfonylureas and metformin), weak CYP3A4 inhibitors do not affect the pharmacokinetics of vardenafil.
