vardenafila 10mg
Each 10 mg film-coated tablet contains 163.4 mg of lactose (as monohydrate)
For the full list of excipients, see section 6.1.
Yellow to light yellow, round shaped, bevelled edged, film-coated tablets debossed with '338' on one side and plain on the other side.
Treatment of erectile dysfunction in adult males.
In order for vardenafil to be effective, sexual stimulation is required.
vardenafil is not indicated for use by women.
In general, the recommended dose is 10 mg taken prior to anticipated sexual activity and with or without food.
In those patients, in whom vardenafil 10 mg does not produce an adequate effect, 20 mg might be tried.
It may be taken at least 30 minutes prior to sexual activity.
The maximum dose frequency is once per day.
vardenafil 10 mg and 20 mg is intended for use prior to anticipated sexual activity and it is not recommended for continuous daily use.
In patients who anticipate a frequent use of vardenafil (i.e., at least twice weekly) a once daily regimen with the lowest doses of vardenafil might be considered suitable, based on patient choice and the physician's judgement.
In these patients the recommended dose is 5 mg taken once a day at approximately the same time of day. The dose may be decreased to 2.5 mg once a day based on individual tolerability.
The appropriateness of continued use of the daily regimen should be reassessed periodically.
Dose adjustments are not required in elderly patients.
Dose adjustments are not required in patients with mild to moderate renal impairment. For patients with severe renal impairment 10 mg is the maximum recommended dose. Once-a-day dosing of vardenafil is not recommended in patients with severe renal impairment. (See sections 4.4 and 5.2).
The recommended dose of vardenafil is 10 mg taken prior to anticipated sexual activity and with or without food. There is limited clinical data on the safety of vardenafil in patients with severe hepatic impairment (Child-Pugh Class C); if prescribed, a careful individual benefit/risk evaluation should be undertaken by the prescribing physician. There are no available data about the administration of doses higher than 10 mg of vardenafil to patients with hepatic impairment. Once-a-day dosing has not been evaluated in patients with hepatic impairment; therefore, if prescribed, a careful individual benefit/risk evaluation should be undertaken by the prescribing physician. (See sections 4.4 and 5.2).
Dose adjustments are not required in diabetic patients.
There is no relevant use of vardenafil in the paediatric population with regard to the treatment of erectile dysfunction.
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
In clinical studies, vardenafil was shown to augment the hypotensive effects of nitrates. This is thought to result from the combined effects of nitrates and vardenafil on the nitric oxide/cGMP pathway. Therefore, administration of vardenafil to patients who are using any form of organic nitrate is contraindicated. (See section 4.5).
vardenafil must not be used in men with cardiac disease for whom sexual activity is inadvisable. Physicians should consider the potential cardiac risk of sexual activity in patients with pre-existing cardiovascular disease.
The following groups of patients with cardiovascular disease were not included in clinical trials and the use of vardenafil is therefore contraindicated:
• patients with myocardial infarction within the last 90 days,
• patients with unstable angina or angina occurring during sexual intercourse,
• patients with New York Heart Association Class 2 or greater heart failure in the last 6 months,
• patients with uncontrolled arrhythmias, hypotension (< 90/50 mm Hg), or uncontrolled hypertension,
• patients with a stroke within the last 6 months.
vardenafil is contraindicated in patients who have loss of vision in one eye because of non-arteritic anterior ischaemic optic neuropathy (NAION), regardless of whether this episode was in connection or not with previous PDE5 inhibitor exposure (see section 4.4).
The co-administration of Mua Pharmacy O Dau Tai Tphcm levitra super active vs professional Best To Take On Empty Stomach , including vardenafil, with guanylate cyclase stimulators, such as riociguat, is contraindicated as it may potentially lead to symptomatic hypotension (see section 4.5).
A medical history and physical examination should be undertaken to diagnose erectile dysfunction and determine potential underlying causes, before pharmacological treatment is considered.
Prior to initiating any treatment for erectile dysfunction, physicians should consider the cardiovascular status of their patients, since there is a degree of cardiac risk associated with sexual activity. vardenafil has vasodilator properties, resulting in mild and transient decreases in blood pressure (see section 5.1) and as such potentiates the hypotensive effect of nitrates (see section 4.3).
The evaluation of erectile dysfunction should include a determination of potential underlying causes and the identification of appropriate treatment following an appropriate medical assessment. It is not known if vardenafil is effective in patients who have undergone pelvic surgery or radical non-nerve- sparing prostatectomy.
Serious cardiovascular events, including myocardial infarction, sudden cardiac death, unstable angina pectoris, ventricular arrhythmia, stroke, transient ischemic attacks, chest pain, palpitations and tachycardia, have been reported either post marketing and/or in clinical trials. Most of the patients in whom these events have been reported had pre-existing cardiovascular risk factors. However, it is not possible to definitively determine whether these events are related directly to these risk factors, to vardenafil, to sexual activity, or to a combination of these or other factors.
In patients receiving concomitant antihypertensive medicinal products, vardenafil may induce a blood pressure decrease. When initiating daily treatment with vardenafil, appropriate clinical considerations should be given to a possible dose adjustment of the antihypertensive therapy.
In patients who are taking alpha1 blockers, concomitant administration of vardenafil may lead to symptomatic hypotension in some patients (see section 4.5). The combination of vardenafil and doxazosin is not recommended.
Visual defects and cases of NAION have been reported in connection with the intake of vardenafil and other Vrouwen Die Pharmacy Slikken levitra ou viagra effets secondaires How Long Does 100 Take To Work . Analyses of observational data suggest an increased risk of acute NAION in men with erectile dysfunction following exposure to vardenafil or other Como Se Llama El Generico Del Pharmacy prescrizione online levitra Side Effects Heart Attack . As this may be relevant for all patients exposed to vardenafil, the patient should be advised that in case of sudden visual defect, he should stop taking vardenafil and consult a physician immediately (see section 4.3).
Cases of sudden hearing loss have been reported after the use of vardenafil. Although other risk factors were present in some cases (such as age, diabetes, hypertension and previous hearing loss history) patients should be advised to stop taking vardenafil and seek prompt medical attention in the event of sudden decrease or loss of hearing.
Due to increased vardenafil exposure (AUC), limited clinical experience and the lack of ability to influence clearance by dialysis, once-a-day dosing of vardenafil is not recommended in patients with severe renal impairment.
There is limited clinical data on the safety of single-dose administration of vardenafil in patients with severe hepatic insufficiency (Child-Pugh Class C). If vardenafil is prescribed, a careful individual benefit/risk evaluation should be undertaken by the prescribing physician.
Priapism and anatomical deformation of the penis
Patients who experience erections lasting 4 hours or more should be instructed to seek immediate medical assistance. If priapism is not treated immediately, penile tissue damage and permanent loss of potency may result.
vardenafil, should be used with caution in patients with anatomical deformation of the penis (such as angulation, cavernosal fibrosis or Peyronie's disease), or in patients who have conditions which may predispose them to priapism (such as sickle cell anaemia, multiple myeloma or leukaemia).
Caution should be exercised when prescribing vardenafil to patients using potent CYP3A4 inhibitors (ritonavir, saquinavir, ketoconazole, itraconazole, and erythromycin) as increased vardenafil exposure (AUC) has been observed if the medicinal products are combined (see section 4.5).
vardenafil and other treatments for erectile dysfunction
The safety and efficacy of combinations of vardenafil and other Watermelon Juice Used As Pharmacy levitra costume Herbal Reload For Sale or other treatments for erectile dysfunction have not been studied. The patients should be informed not to take vardenafil in such combinations.
vardenafil contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
Interaction studies were conducted with 10 mg and/or 20 mg vardenafil, as indicated below. With regard to those interaction studies where only the 10 mg vardenafil dose was used, clinically relevant interactions at higher doses cannot be completely ruled out.
Effects of other substances on vardenafil
vardenafil is principally metabolised by CYP3A4. A selective inhibitor of CYP3A4, ketoconazole (200 mg daily), increased vardenafil (10 mg) exposure (AUC) 2-fold and Cmax by 15 %, relative to the AUC and Cmax values for vardenafil alone. Ketoconazole (400 mg daily) increased vardenafil (20 mg) exposure (AUC) 4-fold and Cmax by 22 %. Ritonavir, a protease inhibitor (200 mg twice daily), which is an inhibitor of CYP3A4, CYP2C9, CYP2C19, and CYP2D6, increased vardenafil (20 mg) exposure (AUC) 2-fold with no change in Cmax. Although specific interactions have not been studied, other protease inhibitors, such as saquinavir, and other CYP3A4 inhibitors, such as erythromycin, clarithromycin, itraconazole and grapefruit juice should be co-administered with caution as they would be expected to increase plasma concentrations of vardenafil (see section 4.4).
Consequently the incidence of the adverse reactions listed in section 4.8 might be increased.
The role of transporters (for example p-glycoprotein) in the disposition of vardenafil is not known. Therefore there is the potential of drug interactions mediated by inhibition of transporters.
A CYP3A4 inducer, rifampicin, reduced vardenafil AUC by 88 %, relative to the AUC values for vardenafil alone (10 mg). This reduced exposure can be anticipated to decrease the efficacy of vardenafil; the magnitude of decreased efficacy is unknown. Other inducers of CYP3A4 such as phenobarbital, phenytoin and carbamazepine, may also decrease plasma concentrations of vardenafil.
Effects of vardenafil on other medicinal products
In clinical studies, vardenafil (5, 10 and 20 mg) was shown to augment the hypotensive effects of nitrates. Therefore, administration of vardenafil to patients who are using any form of organic nitrate is contraindicated (see section 4.3). Based on the results of a clinical study in which 150 subjects receiving daily doses of vardenafil 20 mg for 7 days and 0.4 mg sublingual nitroglycerin at various times, this interaction lasted for more than 24 hours and was no longer detectable when 48 hours had elapsed after the last vardenafil dose. Thus, in a patient prescribed any dose of vardenafil (2.5 mg-20 mg), where nitrate administration is deemed medically necessary in a life-threatening situation, at least 48 hours should have elapsed after the last dose of vardenafil before nitrate administration is considered. In such circumstances, nitrates should only be administered under close medical supervision with appropriate haemodynamic monitoring.
Anti-hypertensives (including calcium channel blockers)
The co-administration of doxazosin (4 and 8 mg daily) and vardenafil (5 mg daily dose and 20 mg as a single dose) increases the blood pressure-lowering effect of this alpha-blocker in a significant manner. This effect lasts at least twelve hours and may be symptomatic, including syncope. Therefore this combination is not recommended (see section 4.4).
In interaction studies performed in a limited number of healthy volunteers, these effects were not reported with alfuzosin or tamsulosin. However, caution should be exercised when using vardenafil in patients treated with any alpha-blockers, and notably in the elderly. Treatments should be initiated at minimal dosage and progressively adjusted.
In clinical pharmacology studies, the potential for vardenafil to augment the hypotensive effects of antihypertensive medicinal products was examined. Major classes of antihypertensive medicinal products were studied, including calcium channel blockers (amlodipine), angiotensin converting enzyme (ACE) inhibitors (enalapril), beta-adrenergic receptor blockers (metoprolol), thiazide diuretics (bendrofluazide), and angiotensin II receptor blockers (various types and doses, alone or in combination with thiazides, calcium channel blockers, beta-blockers, and/or alpha-blockers). vardenafil (10 mg except for studies with angiotensin II receptor blockers and amlodipine in which a 20 mg dose was applied) had no clinically significant interaction with any of these classes. In another clinical pharmacology study vardenafil (20 mg) was studied in combination with up to 4 classes of antihypertensives. In subjects taking multiple antihypertensives, the ambulatory-blood-pressure changes appeared to relate to the degree of blood-pressure control. In this regard, study subjects whose blood pressure was well controlled, the reduction was minimal and similar to that seen in healthy subjects. In study subjects whose blood pressure was not controlled, the reduction was greater although this reduction was not associated with hypotensive symptoms in the majority of subjects. In patients receiving concomitant antihypertensive medicinal products, vardenafil 20 mg may induce a blood pressure decrease, which (with the exception of alpha blockers -see above-) is, in general, minor and not likely to be clinically relevant. Analysis of phase 3 clinical trial data showed no difference in adverse events in patients taking vardenafil with or without antihypertensive medicinal products. However, appropriate clinical advice should be given to patients regarding a possible decrease in blood pressure when they are treated with antihypertensive medicinal products.
Preclinical studies showed an additive systemic blood pressure lowering effect when Tesco Pharmacy London Pharmacy viagra and levitra comparison Factory Commercial Song were combined with riociguat. In clinical studies, riociguat has been shown to augment the hypotensive effects of Unterschied Revatio Pharmacy levitra pastilla amarilla Blue Force 100 . There was no evidence of favourable clinical effect of the combination in the population studied. Concomitant use of riociguat with Side Effects Of Taking Pharmacy When Not Needed viagra vs levitra men s health Illegal Sales Uk , including vardenafil, is contraindicated (see section 4.3).
In a clinical trial that compared vardenafil 5 mg co-administered with finasteride 5 mg to placebo plus finasteride 5 mg in the relief of BPH symptoms, no new adverse reactions were identified. However, as a formal drug-drug interaction study evaluating the effects of vardenafil and 5-alpha reductase inhibitors (5-ARIs) has not been performed, caution should be exercised when vardenafil is co-administered with 5-ARIs.
When vardenafil 10 mg was administered with theophylline (a non-selective phosphodiesterase inhibitor) in a clinical pharmacology study, there was no pharmacokinetic interaction. The only pharmacodynamic effect was a small (3.5 bpm) increase in heart rate. Although this effect is minor and was of no clinical significance in this study, it should be considered when co-administering these medicinal products.
vardenafil has been demonstrated to produce an increase in the oral bioavailability of ethinylestradiol; a similar increase may be expected with oral administration of terbutaline, although the clinical consequence of this is uncertain.
Alcohol concentrations (mean maximum blood concentration 0.08 %) were not affected by co-administration with vardenafil (10 mg or 20 mg). In addition, no changes in vardenafil concentrations were seen 3 hours after co-administration with alcohol. Alcohol was administered in a manner to maximise the rate of alcohol absorption (overnight fast with no food until 2 hours after alcohol). vardenafil (20 mg) did not augment the mean blood pressure decrease produced by alcohol (0.7 g/kg or approximately 180 ml of 40 % alcohol [vodka] in an 80-kg male) but in some subjects, postural dizziness and orthostatic hypotension were observed. When vardenafil was administered with lower doses of alcohol (0.6 g/kg), hypotension was not observed and dizziness occurred with similar frequency to alcohol alone. The effect of alcohol on cognitive function was not augmented by vardenafil (10 mg).
Cytochrome P450 metabolised medicinal products
vardenafil is not expected to cause clinically significant inhibition or induction of the clearance of medicinal products metabolised by CYP450 isoforms. Studies have confirmed that vardenafil does not inhibit or induce CYP450 isoforms, including CYP3A4, CYP1A2, CYP2D6, CYP2E1, CYP2C9 and CYP2C19.
vardenafil (10 mg and 20 mg) had no clinically significant effect on exposure (AUC) to S-warfarin or R-warfarin (CYP2C9 substrate), nor did vardenafil affect changes in prothrombin time induced by warfarin.
vardenafil (10 mg and 20 mg) did not potentiate the increase in bleeding time caused by acetyl salicylic acid.
Specific interaction studies with antidiabetic medicinal products were not conducted.
vardenafil is not indicated for use by women.
There are limited data from the use of vardenafil in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development (see section 5.3). As a precautionary measure, it is preferable to avoid the use of vardenafil during pregnancy.
Available pharmacodynamic/toxicological data in animals have shown excretion of vardenafil in milk.
A risk to the suckling child cannot be excluded. vardenafil should not be used during breast feeding.
Effects were seen in dogs that might indicate impairment of fertility. Two subsequent clinical studies suggest that this effect is unlikely in humans, although a decrease in sperm concentration was seen in some men (see sections 5.1 and 5.3).
vardenafil has negligible influence on the ability to drive or use machines. Although the frequency of reports of dizziness in placebo and vardenafil arms in clinical trials was similar, patients should be aware of how they react to vardenafil, before driving or using machines.
The most commonly reported adverse reactions in patients taking vardenafil for the treatment of erectile dysfunction or benign prostatic hyperplasia were headache, dyspepsia, back pain and myalgia, in which the incidences increase with increasing dose of vardenafil. The adverse reactions reported were transient, and generally mild or moderate. The majority of headaches reported with vardenafil once-a-day dosing are experienced within the first 10 to 30 days of starting treatment.
Tabulated summary of adverse reactions
The table below lists the adverse reactions observed from spontaneous reporting and in placebo-controlled clinical trials (comprising a total of 8022 patients on vardenafil and 4422 patients on placebo) for on-demand and once-a-day treatment of erectile dysfunction and the once-a-day treatment of benign prostatic hyperplasia.
In clinical studies, vardenafil was shown to augment the hypotensive effects of nitrates. This is thought to result from the combined effects of nitrates and vardenafil on the nitric oxide/cGMP pathway. Therefore, administration of vardenafil to patients who are using any form of organic nitrate is contraindicated. (See section 4.5).
vardenafila 10mg
Each 10 mg film-coated tablet contains 163.4 mg of lactose (as monohydrate)
For the full list of excipients, see section 6.1.
Yellow to light yellow, round shaped, bevelled edged, film-coated tablets debossed with '338' on one side and plain on the other side.
Treatment of erectile dysfunction in adult males.
In order for vardenafil to be effective, sexual stimulation is required.
vardenafil is not indicated for use by women.
In general, the recommended dose is 10 mg taken prior to anticipated sexual activity and with or without food.
In those patients, in whom vardenafil 10 mg does not produce an adequate effect, 20 mg might be tried.
It may be taken at least 30 minutes prior to sexual activity.
The maximum dose frequency is once per day.
vardenafil 10 mg and 20 mg is intended for use prior to anticipated sexual activity and it is not recommended for continuous daily use.
In patients who anticipate a frequent use of vardenafil (i.e., at least twice weekly) a once daily regimen with the lowest doses of vardenafil might be considered suitable, based on patient choice and the physician's judgement.
In these patients the recommended dose is 5 mg taken once a day at approximately the same time of day. The dose may be decreased to 2.5 mg once a day based on individual tolerability.
The appropriateness of continued use of the daily regimen should be reassessed periodically.
Dose adjustments are not required in elderly patients.
Dose adjustments are not required in patients with mild to moderate renal impairment. For patients with severe renal impairment 10 mg is the maximum recommended dose. Once-a-day dosing of vardenafil is not recommended in patients with severe renal impairment. (See sections 4.4 and 5.2).
The recommended dose of vardenafil is 10 mg taken prior to anticipated sexual activity and with or without food. There is limited clinical data on the safety of vardenafil in patients with severe hepatic impairment (Child-Pugh Class C); if prescribed, a careful individual benefit/risk evaluation should be undertaken by the prescribing physician. There are no available data about the administration of doses higher than 10 mg of vardenafil to patients with hepatic impairment. Once-a-day dosing has not been evaluated in patients with hepatic impairment; therefore, if prescribed, a careful individual benefit/risk evaluation should be undertaken by the prescribing physician. (See sections 4.4 and 5.2).
Dose adjustments are not required in diabetic patients.
There is no relevant use of vardenafil in the paediatric population with regard to the treatment of erectile dysfunction.
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
In clinical studies, vardenafil was shown to augment the hypotensive effects of nitrates. This is thought to result from the combined effects of nitrates and vardenafil on the nitric oxide/cGMP pathway. Therefore, administration of vardenafil to patients who are using any form of organic nitrate is contraindicated. (See section 4.5).
vardenafil must not be used in men with cardiac disease for whom sexual activity is inadvisable. Physicians should consider the potential cardiac risk of sexual activity in patients with pre-existing cardiovascular disease.
The following groups of patients with cardiovascular disease were not included in clinical trials and the use of vardenafil is therefore contraindicated:
• patients with myocardial infarction within the last 90 days,
• patients with unstable angina or angina occurring during sexual intercourse,
• patients with New York Heart Association Class 2 or greater heart failure in the last 6 months,
• patients with uncontrolled arrhythmias, hypotension (< 90/50 mm Hg), or uncontrolled hypertension,
• patients with a stroke within the last 6 months.
vardenafil is contraindicated in patients who have loss of vision in one eye because of non-arteritic anterior ischaemic optic neuropathy (NAION), regardless of whether this episode was in connection or not with previous PDE5 inhibitor exposure (see section 4.4).
The co-administration of Pharmacy Vegetal Chino prescription levitra online pharmacy Vasafil Vs , including vardenafil, with guanylate cyclase stimulators, such as riociguat, is contraindicated as it may potentially lead to symptomatic hypotension (see section 4.5).
A medical history and physical examination should be undertaken to diagnose erectile dysfunction and determine potential underlying causes, before pharmacological treatment is considered.
Prior to initiating any treatment for erectile dysfunction, physicians should consider the cardiovascular status of their patients, since there is a degree of cardiac risk associated with sexual activity. vardenafil has vasodilator properties, resulting in mild and transient decreases in blood pressure (see section 5.1) and as such potentiates the hypotensive effect of nitrates (see section 4.3).
The evaluation of erectile dysfunction should include a determination of potential underlying causes and the identification of appropriate treatment following an appropriate medical assessment. It is not known if vardenafil is effective in patients who have undergone pelvic surgery or radical non-nerve- sparing prostatectomy.
Serious cardiovascular events, including myocardial infarction, sudden cardiac death, unstable angina pectoris, ventricular arrhythmia, stroke, transient ischemic attacks, chest pain, palpitations and tachycardia, have been reported either post marketing and/or in clinical trials. Most of the patients in whom these events have been reported had pre-existing cardiovascular risk factors. However, it is not possible to definitively determine whether these events are related directly to these risk factors, to vardenafil, to sexual activity, or to a combination of these or other factors.
In patients receiving concomitant antihypertensive medicinal products, vardenafil may induce a blood pressure decrease. When initiating daily treatment with vardenafil, appropriate clinical considerations should be given to a possible dose adjustment of the antihypertensive therapy.
In patients who are taking alpha1 blockers, concomitant administration of vardenafil may lead to symptomatic hypotension in some patients (see section 4.5). The combination of vardenafil and doxazosin is not recommended.
Visual defects and cases of NAION have been reported in connection with the intake of vardenafil and other Top 10 Pharmacy Tablets vardenafil 40 mg uk Uso Adecuado De La . Analyses of observational data suggest an increased risk of acute NAION in men with erectile dysfunction following exposure to vardenafil or other Cosas Similares Ala Pharmacy where can buy levitra online Same Effect As . As this may be relevant for all patients exposed to vardenafil, the patient should be advised that in case of sudden visual defect, he should stop taking vardenafil and consult a physician immediately (see section 4.3).
Cases of sudden hearing loss have been reported after the use of vardenafil. Although other risk factors were present in some cases (such as age, diabetes, hypertension and previous hearing loss history) patients should be advised to stop taking vardenafil and seek prompt medical attention in the event of sudden decrease or loss of hearing.
Due to increased vardenafil exposure (AUC), limited clinical experience and the lack of ability to influence clearance by dialysis, once-a-day dosing of vardenafil is not recommended in patients with severe renal impairment.
There is limited clinical data on the safety of single-dose administration of vardenafil in patients with severe hepatic insufficiency (Child-Pugh Class C). If vardenafil is prescribed, a careful individual benefit/risk evaluation should be undertaken by the prescribing physician.
Priapism and anatomical deformation of the penis
Patients who experience erections lasting 4 hours or more should be instructed to seek immediate medical assistance. If priapism is not treated immediately, penile tissue damage and permanent loss of potency may result.
vardenafil, should be used with caution in patients with anatomical deformation of the penis (such as angulation, cavernosal fibrosis or Peyronie's disease), or in patients who have conditions which may predispose them to priapism (such as sickle cell anaemia, multiple myeloma or leukaemia).
Caution should be exercised when prescribing vardenafil to patients using potent CYP3A4 inhibitors (ritonavir, saquinavir, ketoconazole, itraconazole, and erythromycin) as increased vardenafil exposure (AUC) has been observed if the medicinal products are combined (see section 4.5).
vardenafil and other treatments for erectile dysfunction
The safety and efficacy of combinations of vardenafil and other Cheapest 150 Mg Pharmacy order levitra europe Can I Get From Pharmacy or other treatments for erectile dysfunction have not been studied. The patients should be informed not to take vardenafil in such combinations.
vardenafil contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
Interaction studies were conducted with 10 mg and/or 20 mg vardenafil, as indicated below. With regard to those interaction studies where only the 10 mg vardenafil dose was used, clinically relevant interactions at higher doses cannot be completely ruled out.
Effects of other substances on vardenafil
vardenafil is principally metabolised by CYP3A4. A selective inhibitor of CYP3A4, ketoconazole (200 mg daily), increased vardenafil (10 mg) exposure (AUC) 2-fold and Cmax by 15 %, relative to the AUC and Cmax values for vardenafil alone. Ketoconazole (400 mg daily) increased vardenafil (20 mg) exposure (AUC) 4-fold and Cmax by 22 %. Ritonavir, a protease inhibitor (200 mg twice daily), which is an inhibitor of CYP3A4, CYP2C9, CYP2C19, and CYP2D6, increased vardenafil (20 mg) exposure (AUC) 2-fold with no change in Cmax. Although specific interactions have not been studied, other protease inhibitors, such as saquinavir, and other CYP3A4 inhibitors, such as erythromycin, clarithromycin, itraconazole and grapefruit juice should be co-administered with caution as they would be expected to increase plasma concentrations of vardenafil (see section 4.4).
Consequently the incidence of the adverse reactions listed in section 4.8 might be increased.
The role of transporters (for example p-glycoprotein) in the disposition of vardenafil is not known. Therefore there is the potential of drug interactions mediated by inhibition of transporters.
A CYP3A4 inducer, rifampicin, reduced vardenafil AUC by 88 %, relative to the AUC values for vardenafil alone (10 mg). This reduced exposure can be anticipated to decrease the efficacy of vardenafil; the magnitude of decreased efficacy is unknown. Other inducers of CYP3A4 such as phenobarbital, phenytoin and carbamazepine, may also decrease plasma concentrations of vardenafil.
Effects of vardenafil on other medicinal products
In clinical studies, vardenafil (5, 10 and 20 mg) was shown to augment the hypotensive effects of nitrates. Therefore, administration of vardenafil to patients who are using any form of organic nitrate is contraindicated (see section 4.3). Based on the results of a clinical study in which 150 subjects receiving daily doses of vardenafil 20 mg for 7 days and 0.4 mg sublingual nitroglycerin at various times, this interaction lasted for more than 24 hours and was no longer detectable when 48 hours had elapsed after the last vardenafil dose. Thus, in a patient prescribed any dose of vardenafil (2.5 mg-20 mg), where nitrate administration is deemed medically necessary in a life-threatening situation, at least 48 hours should have elapsed after the last dose of vardenafil before nitrate administration is considered. In such circumstances, nitrates should only be administered under close medical supervision with appropriate haemodynamic monitoring.
Anti-hypertensives (including calcium channel blockers)
The co-administration of doxazosin (4 and 8 mg daily) and vardenafil (5 mg daily dose and 20 mg as a single dose) increases the blood pressure-lowering effect of this alpha-blocker in a significant manner. This effect lasts at least twelve hours and may be symptomatic, including syncope. Therefore this combination is not recommended (see section 4.4).
In interaction studies performed in a limited number of healthy volunteers, these effects were not reported with alfuzosin or tamsulosin. However, caution should be exercised when using vardenafil in patients treated with any alpha-blockers, and notably in the elderly. Treatments should be initiated at minimal dosage and progressively adjusted.
In clinical pharmacology studies, the potential for vardenafil to augment the hypotensive effects of antihypertensive medicinal products was examined. Major classes of antihypertensive medicinal products were studied, including calcium channel blockers (amlodipine), angiotensin converting enzyme (ACE) inhibitors (enalapril), beta-adrenergic receptor blockers (metoprolol), thiazide diuretics (bendrofluazide), and angiotensin II receptor blockers (various types and doses, alone or in combination with thiazides, calcium channel blockers, beta-blockers, and/or alpha-blockers). vardenafil (10 mg except for studies with angiotensin II receptor blockers and amlodipine in which a 20 mg dose was applied) had no clinically significant interaction with any of these classes. In another clinical pharmacology study vardenafil (20 mg) was studied in combination with up to 4 classes of antihypertensives. In subjects taking multiple antihypertensives, the ambulatory-blood-pressure changes appeared to relate to the degree of blood-pressure control. In this regard, study subjects whose blood pressure was well controlled, the reduction was minimal and similar to that seen in healthy subjects. In study subjects whose blood pressure was not controlled, the reduction was greater although this reduction was not associated with hypotensive symptoms in the majority of subjects. In patients receiving concomitant antihypertensive medicinal products, vardenafil 20 mg may induce a blood pressure decrease, which (with the exception of alpha blockers -see above-) is, in general, minor and not likely to be clinically relevant. Analysis of phase 3 clinical trial data showed no difference in adverse events in patients taking vardenafil with or without antihypertensive medicinal products. However, appropriate clinical advice should be given to patients regarding a possible decrease in blood pressure when they are treated with antihypertensive medicinal products.
Preclinical studies showed an additive systemic blood pressure lowering effect when Herbal Pharmacy For Women che differenze tra viagra e levitra Nox Bitkisel were combined with riociguat. In clinical studies, riociguat has been shown to augment the hypotensive effects of Pharmacy 100 Mg Walgreens Price levitra online canada Brillianty Lyrics . There was no evidence of favourable clinical effect of the combination in the population studied. Concomitant use of riociguat with Side Effect Of Pharmacy On Women good place to buy generic levitra Pret 2013 , including vardenafil, is contraindicated (see section 4.3).
In a clinical trial that compared vardenafil 5 mg co-administered with finasteride 5 mg to placebo plus finasteride 5 mg in the relief of BPH symptoms, no new adverse reactions were identified. However, as a formal drug-drug interaction study evaluating the effects of vardenafil and 5-alpha reductase inhibitors (5-ARIs) has not been performed, caution should be exercised when vardenafil is co-administered with 5-ARIs.
When vardenafil 10 mg was administered with theophylline (a non-selective phosphodiesterase inhibitor) in a clinical pharmacology study, there was no pharmacokinetic interaction. The only pharmacodynamic effect was a small (3.5 bpm) increase in heart rate. Although this effect is minor and was of no clinical significance in this study, it should be considered when co-administering these medicinal products.
vardenafil has been demonstrated to produce an increase in the oral bioavailability of ethinylestradiol; a similar increase may be expected with oral administration of terbutaline, although the clinical consequence of this is uncertain.
Alcohol concentrations (mean maximum blood concentration 0.08 %) were not affected by co-administration with vardenafil (10 mg or 20 mg). In addition, no changes in vardenafil concentrations were seen 3 hours after co-administration with alcohol. Alcohol was administered in a manner to maximise the rate of alcohol absorption (overnight fast with no food until 2 hours after alcohol). vardenafil (20 mg) did not augment the mean blood pressure decrease produced by alcohol (0.7 g/kg or approximately 180 ml of 40 % alcohol [vodka] in an 80-kg male) but in some subjects, postural dizziness and orthostatic hypotension were observed. When vardenafil was administered with lower doses of alcohol (0.6 g/kg), hypotension was not observed and dizziness occurred with similar frequency to alcohol alone. The effect of alcohol on cognitive function was not augmented by vardenafil (10 mg).
Cytochrome P450 metabolised medicinal products
vardenafil is not expected to cause clinically significant inhibition or induction of the clearance of medicinal products metabolised by CYP450 isoforms. Studies have confirmed that vardenafil does not inhibit or induce CYP450 isoforms, including CYP3A4, CYP1A2, CYP2D6, CYP2E1, CYP2C9 and CYP2C19.
vardenafil (10 mg and 20 mg) had no clinically significant effect on exposure (AUC) to S-warfarin or R-warfarin (CYP2C9 substrate), nor did vardenafil affect changes in prothrombin time induced by warfarin.
vardenafil (10 mg and 20 mg) did not potentiate the increase in bleeding time caused by acetyl salicylic acid.
Specific interaction studies with antidiabetic medicinal products were not conducted.
vardenafil is not indicated for use by women.
There are limited data from the use of vardenafil in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development (see section 5.3). As a precautionary measure, it is preferable to avoid the use of vardenafil during pregnancy.
Available pharmacodynamic/toxicological data in animals have shown excretion of vardenafil in milk.
A risk to the suckling child cannot be excluded. vardenafil should not be used during breast feeding.
Effects were seen in dogs that might indicate impairment of fertility. Two subsequent clinical studies suggest that this effect is unlikely in humans, although a decrease in sperm concentration was seen in some men (see sections 5.1 and 5.3).
vardenafil has negligible influence on the ability to drive or use machines. Although the frequency of reports of dizziness in placebo and vardenafil arms in clinical trials was similar, patients should be aware of how they react to vardenafil, before driving or using machines.
The most commonly reported adverse reactions in patients taking vardenafil for the treatment of erectile dysfunction or benign prostatic hyperplasia were headache, dyspepsia, back pain and myalgia, in which the incidences increase with increasing dose of vardenafil. The adverse reactions reported were transient, and generally mild or moderate. The majority of headaches reported with vardenafil once-a-day dosing are experienced within the first 10 to 30 days of starting treatment.
Tabulated summary of adverse reactions
The table below lists the adverse reactions observed from spontaneous reporting and in placebo-controlled clinical trials (comprising a total of 8022 patients on vardenafil and 4422 patients on placebo) for on-demand and once-a-day treatment of erectile dysfunction and the once-a-day treatment of benign prostatic hyperplasia.
In those patients, in whom vardenafil 10 mg does not produce an adequate effect, 20 mg might be tried.
Patients with uncontrolled arrhythmias, hypotension.
01.06.2023 23:15:57
2023-06-01 23:15:57