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  • Levitra 10 mg Orodispersible Tablets
    / Bayer


    Active Ingredient
    Vardenafil 10 mg

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Orodispersible Tablets

    4 X 10 mg

    partial basket chart 28999 12462

    Dosage

    Levitra 10 mg orodispersible tablet is not bioequivalent to Levitra 10 mg film-coated tablet. The maximum dose for Levitra orodispersible tablet is 10 mg/day.
    Use in adult men: Levitra 10 mg orodispersible tablets are taken as needed approximately 25 to 60 minutes before sexual activity.
    Elderly (≥65 years old): Dose adjustments are not required in elderly patients. However, an increase to a maximum dose of Levitra 20 mg film-coated tablets should be carefully considered depending on the individual tolerability.
    Hepatic impairment: Levitra 10 mg orodispersible tablets are not indicated as a starting dose in patients with mild hepatic impairment (Child-Pugh A).
    Patients with mild hepatic impairment should start treatment with Levitra 5 mg film-coated tablets.
    Based on tolerability and efficacy, the dose may be increased to Levitra 10 mg and 20 mg film-coated tablets, or Levitra 10 mg orodispersible tablets.
    The maximum dose recommended in patients with moderate hepatic impairment (Child-Pugh B) is Levitra 10 mg as film-coated tablets.
    Levitra 10 mg orodispersible tablets are not for use in patients with moderate (Child-Pugh B) and severe hepatic impairment (Child-Pugh C).
    Renal impairment: No dose adjustment is required in patients with mild to moderate renal impairment.
    In patients with severe renal impairment (creatinine clearance <30 ml/min) a starting dose of Levitra 5 mg film-coated tablets should be considered. Based on tolerability and efficacy, the dose may be increased to Levitra 10 mg and 20 mg film-coated tablets, or Levitra 10 mg orodispersible tablets.
    Levitra orodispersible tablet is not for use in patients with end-stage renal failure.
    Paediatric population: Levitra orodispersible tablets are not indicated for individuals below 18 years of age. There is no relevant indication for use of Levitra orodispersible tablets in children and adolescents.
    Use in patients using other medicinal products
    Concomitant use of moderate or potent CYP3A4 inhibitors: Vardenafil dose adjustment is necessary if moderate or potent CYP3A4 inhibitors are given
    concomitantly.
    Method of administration: For oral use. The orodispersible tablet should be placed in the mouth on the tongue, where it will rapidly disintegrate, and then swallowed. Levitra orodispersible tablets must be taken without liquid and immediately upon release from the blister.
    Levitra orodispersible tablets can be taken with or without food.


    Indications

    Treatment of erectile dysfunction (inability to achieve or maintain penile erection sufficient for satisfactory sexual performance).
    In order for therapy to be effective, sexual stimulation is required.
    Not indicated for use by women.


    Contra-Indications

    Hypersensitivity to the active substance or to any of the excipients.
    The co-administration of vardenafil with nitrates or nitric oxide donors (such as amyl nitrite) in any form is contraindicated.
    Levitra is contraindicated in patients who have loss of vision in one eye because of non-arteritic anterior ischemic optic neuropathy (NAION), regardless of whether this episode was in connection or not with previous phosphodiesterase 5 (PDE5) inhibitor exposure.
    Medicinal products for the treatment of erectile dysfunction should generally not be used in men for whom sexual activity is inadvisable (e.g. patients with severe cardiovascular disorders such as unstable angina or severe cardiac failure [New York Heart Association III or IV]).
    The safety of vardenafil has not been studied in the following sub-groups of patients and its use is therefore contraindicated until further information is available:
    – severe hepatic impairment (Child-Pugh C),
    – end stage renal disease requiring dialysis,
    – hypotension (blood pressure <90/50 mmHg),
    – recent history of stroke or myocardial infarction (within the last 6 months),
    – unstable angina, and known hereditary retinal degenerative disorders such as retinitis pigmentosa.
    Concomitant use of vardenafil with the potent CYP3A4 inhibitors ketoconazole and itraconazole (oral form) is contraindicated in men older than 75 years.
    Concomitant use of vardenafil with HIV protease inhibitors such as ritonavir and indinavir is contraindicated, as they are very potent inhibitors of CYP3A4.
    The co-administration of PDE5 inhibitors, including vardenafil, with guanylate cyclase stimulators, such as riociguat, is contraindicated as it may potentially lead to symptomatic hypotension.


    Special Precautions

    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. Patients with left ventricular outflow obstruction, e.g. aortic stenosis and idiopathic hypertrophic subaortic stenosis, can be sensitive to the action of vasodilators including Type 5 phosphodiesterase inhibitors.
    Medicinal products for the treatment of erectile dysfunction 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).
    The safety and efficacy of combinations of Levitra orodispersible tablets with Levitra film-coated tablets or other treatments for erectile dysfunction have not been studied. Therefore the use of such combinations is not recommended.
    Tolerability of the maximum dose of Levitra 20 mg film-coated tablets may be lower in elderly patients (≥65 years old).
    Concomitant use of alpha-blockers: The concomitant use of alpha-blockers and vardenafil may lead to symptomatic hypotension in some patients because both are vasodilators. Concomitant treatment with vardenafil should only be initiated if the patient has been stabilised on his alpha-blocker therapy. In those patients who are stable on alphablocker therapy, vardenafil should be initiated at the lowest recommended starting dose of 5 mg filmcoated tablets. Patients treated with alpha-blockers should not use Levitra 10 mg orodispersible tablets as a starting dose. Vardenafil may be administered at any time with tamsulosin or with alfuzosin. With other alpha-blockers a time separation of dosing should be considered when vardenafil is prescribed concomitantly. In those patients already taking an optimised dose of vardenafil, alphablocker therapy should be initiated at the lowest dose. Stepwise increase in alpha-blocker dose may be
    associated with further lowering of blood pressure in patients taking vardenafil.
    Concomitant use of CYP3A4 inhibitors: Concomitant use of vardenafil with potent CYP3A4 inhibitors such as itraconazole and ketoconazole (oral form) should be avoided as very high plasma concentrations of vardenafil are reached if the medicinal products are combined.
    Vardenafil dose adjustment might be necessary if moderate CYP3A4 inhibitors such as erythromycin and clarithromycin, are given concomitantly.
    Concomitant intake of grapefruit or grapefruit juice is expected to increase the plasma concentrations of vardenafil. The combination should be avoided.
    Effect on QTc interval: Single oral doses of 10 mg and 80 mg of vardenafil have been shown to prolong the QTc interval by a mean of 8 msec and 10 msec, respectively. And single doses of 10 mg vardenafil co-administered concomitantly with 400 mg gatifloxacin, an active substance with comparable QT effect, showed an additive QTc effect of 4 msec when compared to either active substance alone. The clinical impact of these QT changes is unknown.
    The clinical relevance of this finding is unknown and cannot be generalised to all patients under all circumstances, as it will depend on the individual risk factors and susceptibilities that may be present at any time in any given patient. Medicinal products that may prolong QTc interval, including vardenafil, are best avoided in patients with relevant risk factors, for example, hypokalaemia, congenital QT prolongation, concomitant administration of antiarrhythmic medicinal products in Class IA (e.g. quinidine, procainamide), or Class III (e.g. amiodarone, sotalol).
    Effect on vision: Visual defects and cases of non-arteritic ischemic optic neuropathy (NAION) have been reported in connection with the intake of Levitra and other PDE5 inhibitors. Analyses of observational data suggest an increased risk of acute NAION in men with erectile dysfunction following exposure to PDE5 inhibitors such as vardenafil, tadalafil and sildenafil. As this may be relevant for all patients exposed to vardenafil the patient should be advised that in the case of sudden visual defect, he should stop taking Levitra orodispersible tablets and consult immediately a physician.
    Effect on bleeding: In vitro studies with human platelets indicate that vardenafil has no antiaggregatory effect on its own, but at high (super-therapeutic) concentrations vardenafil potentiates the antiaggregatory effect of the nitric oxide donor sodium nitroprusside. In humans, vardenafil had no effect on bleeding time alone or in combination with acetylsalicylic acid. There is no safety information available on the administration of vardenafil to patients with bleeding disorders or active peptic ulceration. Therefore vardenafil should be administered to these patients only after careful benefit-risk assessment.
    Aspartame: This medicine contains 1.80 mg aspartame in each 10 mg orodispersible tablet. Aspartame is a source of phenylalanine. It may be harmful for people with phenylketonuria (PKU), a rare genetic disorder in which phenylalanine builds up because the body cannot remove it properly.
    Sorbitol: This medicine contains 7.96 mg sorbitol in each 10 mg orodispersible tablet.


    Side Effects

    Very common and common: Headache, dizziness, flushing, nasal congestion, dyspepsia.
    See prescribing information for full details.


    Drug interactions

    Effects of other medicinal products on vardenafil
    In vitro studies: Vardenafil is metabolised predominantly by hepatic enzymes via cytochrome P450 (CYP) isoform 3A4, with some contribution from CYP3A5 and CYP2C isoforms. Therefore, inhibitors of these isoenzymes may reduce vardenafil clearance.
    In vivo studies: Co-administration of the HIV protease inhibitor indinavir (800 mg three times a day), a potent CYP3A4 inhibitor, with vardenafil (10 mg film-coated tablets) resulted in a 16-fold increase in vardenafil AUC and a 7-fold increase in vardenafil Cmax. At 24 hours, the plasma levels of vardenafil had fallen to approximately 4% of the maximum vardenafil plasma level (Cmax).
    Co-administration of vardenafil with ritonavir (600 mg twice daily) resulted in a 13-fold increase in vardenafil Cmax and a 49-fold increase in vardenafil AUC0-24 when co-administered with vardenafil 5 mg. The interaction is a consequence of blocking hepatic metabolism of vardenafil by ritonavir, a highly potent CYP3A4 inhibitor, which also inhibits CYP2C9. Ritonavir significantly prolonged the half-life of vardenafil to 25.7 hours.
    Co-administration of ketoconazole (200 mg), a potent CYP3A4 inhibitor, with vardenafil (5 mg) resulted in a 10-fold increase in vardenafil AUC and a 4-fold increase in vardenafil Cmax.
    Although specific interaction studies have not been conducted, the concomitant use of other potent CYP3A4 inhibitors (such as itraconazole) can be expected to produce vardenafil plasma levels comparable to those produced by ketoconazole. Concomitant use of vardenafil with potent CYP3A4 inhibitors such as itraconazole and ketoconazole (oral use) should be avoided. In
    men older than 75 years the concomitant use of vardenafil with itraconazole or ketoconazole is contraindicated.
    Co-administration of erythromycin (500 mg three times a day), a CYP3A4 inhibitor, with vardenafil (5 mg) resulted in a 4-fold increase in vardenafil AUC and a 3-fold increase in Cmax. Although a specific interaction study has not been conducted, the co-administration of clarithromycin can be expected to result in similar effects on vardenafil AUC and Cmax. When used in combination with a moderate CYP3A4 inhibitor such as erythromycin or clarithromycin, vardenafil dose adjustment might be necessary. Cimetidine (400 mg twice daily), a non-specific cytochrome P450 inhibitor, had no effect on vardenafil AUC and Cmax when co-administered with vardenafil (20 mg) to healthy volunteers.
    Grapefruit juice being a weak inhibitor of CYP3A4 gut wall metabolism, may give rise to modest increases in plasma levels of vardenafil.
    The pharmacokinetics of vardenafil (20 mg) was not affected by co-administration with the H2-antagonist ranitidine (150 mg twice daily), digoxin, warfarin, glibenclamide, alcohol (mean maximum blood alcohol level of 73 mg/dl) or single doses of antacid (magnesium hydroxide/aluminium hydroxide).
    Although specific interaction studies were not conducted for all medicinal products, population pharmacokinetic analysis showed no effect on vardenafil pharmacokinetics of the following concomitant medicinal products: acetylsalicylic acid, ACE-inhibitors, beta-blockers, weak CYP3A4 inhibitors, diuretics and medicinal products for the treatment of diabetes (sulfonylureas and metformin).
    Effects of vardenafil on other medicinal products:There are no data on the interaction of vardenafil and non-specific phosphodiesterase inhibitors such as theophylline or dipyridamole.
    In vivo studies: No potentiation of the blood pressure lowering effect of sublingual nitroglycerin (0.4 mg) was observed when vardenafil (10 mg) was given at varying time intervals (1 h to 24 h) prior to the dose of nitroglycerin in a study in 18 healthy male subjects. Vardenafil 20 mg film-coated tablets potentiated the blood pressure lowering effect of sublingual nitroglycerin (0.4 mg) taken 1 and 4 hours after vardenafil administration to healthy middle aged subjects. No effect on blood pressure was observed when nitroglycerin was taken 24 hours after administration of a single dose of vardenafil 20 mg film-coated tablets. However, there is no information on the possible potentiation of the hypotensive effects of nitrates by vardenafil in patients, and concomitant use is therefore contraindicated.
    Nicorandil is a hybrid of potassium channel opener and nitrate. Due to the nitrate component it has the potential to have serious interaction with vardenafil.
    Since alpha-blocker monotherapy can cause marked lowering of blood pressure, especially postural hypotension and syncope, interaction studies were conducted with vardenafil. In two interaction studies with healthy normotensive volunteers after forced titration of the alpha-blockers tamsulosin or terazosin to high doses, hypotension (in some cases symptomatic) was reported in a significant number of subjects after co-administration of vardenafil. Among subjects treated with terazosin, hypotension was observed more frequently when vardenafil and terazosin were given simultaneously than when the dosing was separated by a time interval of 6 hours.
    Based on the results of interaction studies conducted with vardenafil in patients with benign prostatic hyperplasia (BPH) on stable tamsulosin, terazosin or alfuzosin therapy:
    – When vardenafil (film-coated tablets) was given at doses of 5, 10 or 20 mg on a background of stable therapy with tamsulosin, there was no symptomatic reduction in blood pressure, although 3/21 tamsulosin treated subjects exhibited transient standing systolic blood pressures of less than 85 mmHg.
    – When vardenafil 5 mg (film-coated tablets) was given simultaneously with terazosin 5 or 10 mg, one of 21 patients experienced symptomatic postural hypotension. Hypotension was not observed when vardenafil 5 mg and terazosin administration was separated by 6 hours.
    – When vardenafil (film-coated tablets) was given at doses of 5 or 10 mg on a background of stable therapy with alfuzosin, compared to placebo, there was no symptomatic reduction in blood pressure.
    Therefore, concomitant treatment should be initiated only if the patient is stable on his alpha-blocker therapy. In those patients who are stable on alpha-blocker therapy, vardenafil should be initiated at the lowest recommended starting dose of 5 mg. Levitra may be administered at any time with tamsulosin or alfuzosin. With other alpha-blockers a time separation of dosing should be considered when vardenafil is prescribed concomitantly.
    No significant interactions were shown when warfarin (25 mg), which is metabolised by CYP2C9, or digoxin (0.375 mg) was co-administered with vardenafil (20 mg film-coated tablets). The relative bioavailability of glibenclamide (3.5 mg) was not affected when co-administered with vardenafil (20 mg).
    In a specific study, where vardenafil (20 mg) was co-administered with slow release nifedipine (30 mg or 60 mg) in hypertensive patients, there was an additional reduction on supine systolic blood pressure of 6 mmHg and supine diastolic blood pressure of 5 mmHg accompanied with an increase in heart rate of 4 bpm.
    When vardenafil (20 mg film-coated tablets) and alcohol (mean maximum blood alcohol level of 73 mg/dl) were taken together, vardenafil did not potentiate the effects of alcohol on blood pressure and heart rate and the pharmacokinetics of vardenafil were not altered.
    Vardenafil (10 mg) did not potentiate the increase in bleeding time caused by acetylsalicylic acid (2 x 81 mg).
    Riociguat: Preclinical studies showed additive systemic blood pressure lowering effect when PDE5 inhibitors were combined with riociguat. In clinical studies, riociguat has been shown to augment the hypotensive effects of PDE5 inhibitors. There was no evidence of favourable clinical effect of the combination in the population studied. Concomitant use of riociguat with PDE5 inhibitors, including vardenafil, is contraindicated.


    Pregnancy and Lactation

    Levitra is not indicated for use by women. There are no studies of vardenafil in pregnant women.
    There are no fertility data available.


    Overdose

    In single dose volunteer studies, doses up to and including 80 mg vardenafil (film-coated tablets) per day were tolerated without exhibiting serious adverse reactions. When vardenafil was administered in higher doses and more frequently than the recommended dose regimen (40 mg film-coated tablets twice daily) cases of severe back pain have been reported. This was not associated with any muscle or neurological toxicity. In cases of overdose, standard supportive measures should be adopted as required. Renal dialysis is not expected to accelerate clearance, as vardenafil is highly bound to plasma proteins and not significantly eliminated in the urine.


    Manufacturer
    Bayer Pharma AG, Germany
    Licence holder
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