vardenafil: prescribing information – dosing, contraindications, interactions, side effects

Treatment of erectile dysfunction in adult men. Erectile dysfunction is the inability to achieve or maintain a penile erection sufficient for satisfactory sexual performance.

In order for Levitra to be effective, sexual stimulation is required.

Posology
Use in adult men
The recommended dose is 10 mg taken as needed approximately 25 to 60 minutes before sexual activity.
Based on efficacy and tolerability the dose may be increased to 20 mg or decreased to 5 mg. The maximum recommended dose is 20 mg. The maximum recommended dosing frequency is once per day.
Levitra can be taken with or without food. The onset of activity may be delayed if taken with a high fat meal (see section 5.2).

Special populations
Elderly (>65 years old)
Dose adjustments are not required in elderly patients. However, an increase to a maximum 20 mg dose should be carefully considered depending on the individual tolerability (see sections 4.4 and 4.8).

Hepatic impairment
A starting dose of 5 mg should be considered in patients with mild and moderate hepatic impairment (Child-Pugh A-B). Based on tolerability and efficacy, the dose may subsequently be increased.

The maximum dose recommended in patients with moderate hepatic impairment (Child-Pugh B) is 10 mg (see sections 4.3 and 5.2).

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 5 mg should be considered. Based on tolerability and efficacy the dose may be increased to 10 mg and 20 mg.

Paediatric population
Levitra is not indicated for individuals below 18 years of age. There is no relevant indication for use of Levitra in children.

Use in patients using other medicinal products
Concomitant use of CYP3A4 inhibitors
When used in combination with the CYP3A4 inhibitors such as erythromycin or clarithromycin, the dose of vardenafil should not exceed 5 mg (see section 4.5).

Method of administration
For oral use.

Posology
Levitra 10 mg orodispersible tablets are not bioequivalent to Levitra 10 mg film-coated tablets (see section 5.1). 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.

Special populations
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 (see sections 4.4 and 4.8).

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 (see section 5.2).

Levitra 10 mg orodispersible tablets are not for use in patients with moderate (Child-Pugh B) and severe hepatic impairment (Child-Pugh C; see section 4.3).

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 (see section 4.3).

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 (see section 4.5).

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.

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

The co-administration of vardenafil with nitrates or nitric oxide donors (such as amyl nitrite) in any form is contraindicated (see sections 4.5 and 5.1).

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 (see section 4.4).

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 (see section 4.5).

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 (see section 4.5).

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

The co-administration of vardenafil with nitrates or nitric oxide donors (such as amyl nitrite) in any form is contraindicated (see sections 4.5 and 5.1).

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 (see section 4.4).

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 (see section 4.5).

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 (see section 4.5).

Summary of the safety profile
The adverse reactions reported with Levitra film-coated tablets or 10 mg orodispersible tablets in clinical trials were generally transient and mild to moderate in nature. The most commonly reported adverse drug reaction occurring in  10% of patients is headache.

Tabulated list of adverse reactions
Adverse reactions are listed according to the MedDRA frequency convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (1/1,000 to <1/100), rare (1/10,000 to <1/1,000) and not known (can not be estimated from available data).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

The following adverse reactions have been reported:

System Organ
Class
Very common
(1/10)
Common
(1/100 to
<1/10)
Uncommon
(1/1,000 to
<1/100)
Rare
(1/10,000 to
<1/1,000)
Not known
(cannot be estimated from the available data)
Infection and infestations

Conjunctivitis

Immune system disorders

Allergic oedema and angioedema
Allergic reaction

Psychiatric disorders

Sleep disorder
Anxiety

Nervous system disorders
Headache
Dizziness
Somnolence
Paraesthesia and dysaesthesia
Syncope
Seizure
Amnesia
Transient ischaemic attack
Cerebral haemorrhage
Eye disorders

Visual disturbance
Ocular hyperaemia
Visual colour distortions
Eye pain and eye discomfort
Photophobia
Increase in intraocular pressure
Lacrimation increased
Non-arteritic anterior ischemic optic neuropathy
Visual defects
Central Serous
Chorioretinopathy
(CSCR) (see section 4.4)
Ear and labyrinth disorders

Tinnitus
Vertigo

Sudden deafness
Cardiac disorders

Palpitation
Tachycardia
Myocardial infarction
Ventricular tachy-arrhythmias
Angina pectoris
Sudden death
Vascular disorders

Flushing

Hypotension
Hypertension

Respiratory, thoracic and mediastinal

Nasal congestion
Dyspnoea
Sinus congestion
Epistaxis

System Organ
Class
Very common
(1/10)
Common
(1/100 to
<1/10)
Uncommon
(1/1,000 to
<1/100)
Rare
(1/10,000 to
<1/1,000)
Not known
(cannot be estimated from the available data) disorders
Gastrointesti- nal disorders

Dyspepsia Gastro-oesopha geal reflux disease
Gastritis
Gastrointestinal and abdominal pain
Diarrhoea
Vomiting
Nausea
Dry mouth

Hepatobiliary disorders

Increase in transaminases
Increase in gamma-glutamyl transferase

Skin and subcutaneous tissue disorders

Erythema
Rash
Photosensitivity reaction
Stevens-Johnson syndrome
(SJS)/toxic epidermal necrolysis (TEN)
(see section 4.4)
Musculoskele- tal and connective tissue disorders

Back pain
Increase in creatine phosphokinase
Myalgia
Increased muscle tone and cramping

Renal and urinary disorders

Haematuria
Reproductive system and breast disorders

Increase in erection
Priapism
Penile
Haemorrhage
Haematospermia
General disorders and administra- tion site conditions

Feeling unwell Chest pain

Description of selected adverse reactions
Penile haemorrhage, haematospermia and haematuria have been reported in clinical trials and spontaneous post-marketing data with the use of all PDE5 inhibitors, including vardenafil.

At a dose of 20 mg Levitra film-coated tablets, elderly (≥65 years old) patients had higher frequencies of headaches (16.2% versus 11.8%) and dizziness (3.7% versus 0.7%) than younger patients (<65 years old). In general, the incidence of adverse reactions (especially “dizziness”) has been shown to be slightly higher in patients with a history of hypertension.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

Summary of the safety profile
The adverse reactions reported with Levitra film-coated tablets or 10 mg orodispersible tablets in clinical trials were generally transient and mild to moderate in nature. The most commonly reported adverse drug reaction occurring in  10% of patients is headache.

Tabulated list of adverse reactions
Adverse reactions are listed according to the MedDRA frequency convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (1/1,000 to <1/100), rare (1/10,000 to <1/1,000) and not known (can not be estimated from available data).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

The following adverse reactions have been reported:

System Organ
Class
Very common
(1/10)
Common
(1/100 to
<1/10)
Uncommon
(1/1,000 to
<1/100)
Rare
(1/10,000 to
<1/1,000)
Not known
(cannot be estimated from the available data)
Infection and infestations

Conjunctivitis

Immune system disorders

Allergic oedema and angioedema
Allergic reaction

Psychiatric disorders

Sleep disorder
Anxiety

Nervous system disorders
Headache
Dizziness
Somnolence
Paraesthesia and dysaesthesia
Syncope
Seizure
Amnesia
Transient ischaemic attack
Cerebral haemorrhage
Eye disorders

Visual disturbance
Ocular hyperaemia
Visual colour
Increase in intraocular pressure
Lacrimation increased
Non-arteritic anterior ischemic optic neuropathy
Visual defects
Central Serous

System Organ
Class
Very common
(1/10)
Common
(1/100 to
<1/10)
Uncommon
(1/1,000 to
<1/100)
Rare
(1/10,000 to
<1/1,000)
Not known
(cannot be estimated from the available data) distortions
Eye pain and eye discomfort
Photophobia
Chorioretinopathy
(CSCR) (see section 4.4)
Ear and labyrinth disorders

Tinnitus
Vertigo

Sudden deafness
Cardiac disorders

Palpitation
Tachycardia
Myocardial infarction
Ventricular tachy-arrhythmias
Angina pectoris
Sudden death
Vascular disorders

Flushing

Hypotension
Hypertension

Respiratory, thoracic and mediastinal disorders

Nasal congestion
Dyspnoea
Sinus congestion
Epistaxis

Gastrointesti- nal disorders

Dyspepsia Gastro-oesopha geal reflux disease
Gastritis
Gastrointestinal and abdominal pain
Diarrhoea
Vomiting
Nausea
Dry mouth

Hepatobiliary disorders

Increase in transaminases
Increase in gamma-glutamyl transferase

Skin and subcutaneous tissue disorders

Erythema
Rash
Photosensitivity reaction
Stevens-Johnson syndrome
(SJS)/toxic epidermal necrolysis (TEN)
(see section 4.4)

System Organ
Class
Very common
(1/10)
Common
(1/100 to
<1/10)
Uncommon
(1/1,000 to
<1/100)
Rare
(1/10,000 to
<1/1,000)
Not known
(cannot be estimated from the available data)
Musculoskele- tal and connective tissue disorders

Back pain
Increase in creatine phosphokinase
Myalgia
Increased muscle tone and cramping

Renal and urinary disorders

Haematuria
Reproductive system and breast disorders

Increase in erection
Priapism
Penile
Haemorrhage
Haematospermia
General disorders and administra- tion site conditions

Feeling unwell Chest pain

Description of selected adverse reactions
Penile haemorrhage, haematospermia and haematuria have been reported in clinical trials and spontaneous post-marketing data with the use of all PDE5 inhibitors, including vardenafil.

At a dose of 20 mg Levitra film-coated tablets, elderly ( 65 years old) patients had higher frequencies of headaches (16.2% versus 11.8%) and dizziness (3.7% versus 0.7%) than younger patients (<65 years old). In general, the incidence of adverse reactions (especially “dizziness”) has been shown to be slightly higher in patients with a history of hypertension.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

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 (see section 4.3). Vardenafil has vasodilator properties, resulting in mild and transient decreases in blood pressure (see section 5.1). 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.

Serious cardiovascular events including sudden death, tachycardia, myocardial infarction, ventricular tachy-arrythmia, angina pectoris, and cerebrovascular disorders (including transient ischaemic attack and cerebral haemorrhage), have been reported in temporal association with vardenafil. 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.

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 film-coated tablets with Levitra orodispersible 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 20 mg may be lower in elderly patients (≥65 years old) (see sections 4.2 and 4.8).

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 alpha-blocker therapy, vardenafil should be initiated at the lowest recommended starting dose of 5 mg film-coated tablets. 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 (see section 4.5). In those patients already taking an optimized dose of vardenafil, alpha-blocker 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 (see sections 4.5 and 4.3).

Vardenafil dose adjustment might be necessary if moderate CYP3A4 inhibitors such as erythromycin and clarithromycin, are given concomitantly (see sections 4.5 and 4.2).

Concomitant intake of grapefruit or grapefruit juice is expected to increase the plasma concentrations of vardenafil. The combination should be avoided (see section 4.5).

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 (see section 5.1).
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 1A (e.g.
quinidine, procainamide), or Class III (e.g. amiodarone, sotalol).

Severe cutaneous adverse reactions
Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), which can be life-threatening or fatal, have been reported in association with vardenafil treatment (see section 4.8).
If signs and symptoms suggestive of these reactions appear, vardenafil should be withdrawn immediately and should not be restarted in this patient at any time.

Effect on vision
Visual defects, including Central Serous Chorioretinopathy (CSCR), 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 (see section 4.8). 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 and consult immediately a physician (see section 4.3).

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 acetylsalicyclic acid (see section 4.5). 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.

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 (see section 4.3). Vardenafil has vasodilator properties, resulting in mild and transient decreases in blood pressure (see section 5.1). 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.

Serious cardiovascular events including sudden death, tachycardia, myocardial infarction, ventricular tachy-arrythmia, angina pectoris, and cerebrovascular disorders (including transient ischaemic attack and cerebral haemorrhage), have been reported in temporal association with vardenafil. 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.

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) (see sections 4.2 and 4.8).

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 alpha-blocker therapy, vardenafil should be initiated at the lowest recommended starting dose of 5 mg film-coated 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 (see section 4.5). In those patients already taking an optimised dose of vardenafil, alpha-blocker 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 (see sections 4.5 and 4.3).

Vardenafil dose adjustment might be necessary if moderate CYP3A4 inhibitors such as erythromycin and clarithromycin, are given concomitantly (see section 4.2 and 4.5).

Concomitant intake of grapefruit or grapefruit juice is expected to increase the plasma concentrations of vardenafil. The combination should be avoided (see section 4.5).

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 (see section 5.1).

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).

Severe cutaneous adverse reactions
Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), which can be life-threatening or fatal, have been reported in association with vardenafil treatment (see section 4.8).
If signs and symptoms suggestive of these reactions appear, vardenafil should be withdrawn immediately and should not be restarted in this patient at any time.

Effect on vision
Visual defects, including Central Serous Chorioretinopathy (CSCR), 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 (see section 4.8). 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 (see section 4.3).

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 (see section 4.5). 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.

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 (see section 4.3).

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 (see section 4.4).

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 (see sections 4.3 and 4.4).

In men older than 75 years the concomitant use of vardenafil with itraconazole or ketoconazole is contraindicated (see section 4.3).

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 (see sections 4.2 and 4.4). 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 (see section 4.4).

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 (see section 4.3).

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 (see section 4.4).

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 (see section 4.3).

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 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 (see section 4.3).

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 (see section 4.4).

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 (see sections 4.3 and 4.4).
In men older than 75 years the concomitant use of vardenafil with itraconazole or ketoconazole is contraindicated (see section 4.3).

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 (see sections 4.2 and 4.4).

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 (see section 4.4).

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 of Levitra orodispersible tablets and nitrates is therefore contraindicated (see section 4.3).

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 5mg. 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 (see section 4.4).

Levitra 10 mg orodispersible tablets should not be taken as starting dose in patients treated with alpha-blockers (see section 4.4).

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 (see section 4.3).

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

No studies on the effects on the ability to drive and use machines have been performed.

As dizziness and abnormal vision have been reported in clinical trials with vardenafil, patients should be aware of how they react to Levitra, before driving or operating machines.

No studies on the effects on the ability to drive and use machines have been performed.

As dizziness and abnormal vision have been reported in clinical trials with vardenafil, patients should be aware of how they react to Levitra orodispersible tablets, before driving or operating machines.

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.

5.
PHARMACOLOGICAL PROPERTIES

Pharmacotherapeutic group: Urologicals, Drugs used in erectile dysfunction, ATC code: G04BE09.

Vardenafil is an oral therapy for the improvement of erectile function in men with erectile dysfunction.
In the natural setting, i.e. with sexual stimulation, it restores impaired erectile function by increasing blood flow to the penis.

Penile erection is a haemodynamic process. During sexual stimulation, nitric oxide is released. It activates the enzyme guanylate cyclase, resulting in an increased level of cyclic guanosine monophosphate (cGMP) in the corpus cavernosum. This in turn results in smooth muscle relaxation, allowing increased inflow of blood into the penis. The level of cGMP is regulated by the rate of synthesis via guanylate cyclase and by the rate of degradation via cGMP hydrolysing phosphodiesterases (PDEs).

Vardenafil is a potent and selective inhibitor of the cGMP specific phosphodiesterase type 5 (PDE5), the most prominent PDE in the human corpus cavernosum. Vardenafil potently enhances the effect of endogenous nitric oxide in the corpus cavernosum by inhibiting PDE5. When nitric oxide is released in response to sexual stimulation, inhibition of PDE5 by vardenafil results in increased corpus cavernosum levels of cGMP. Sexual stimulation is therefore required for vardenafil to produce its beneficial therapeutic effects.

In vitro studies have shown that vardenafil is more potent on PDE5 than on other known phosphodiesterases (>15-fold relative to PDE6, >130-fold relative to PDE1, >300-fold relative to PDE11, and >1000-fold relative to PDE2, PDE3, PDE4, PDE7, PDE8, PDE9 and PDE10).

In a penile plesthysmography (RigiScan) study, vardenafil 20 mg produced erections considered sufficient for penetration (60% rigidity by RigiScan) in some men as early as 15 minutes after dosing.

The overall response of these subjects to vardenafil became statistically significant, compared to placebo, 25 minutes after dosing.

Vardenafil causes mild and transient decreases in blood pressure which, in the majority of the cases, do not translate into clinical effects. The mean maximum decreases in supine systolic blood pressure following 20 mg and 40 mg vardenafil were – 6.9 mmHg under 20 mg and – 4.3 mmHg under 40 mg of vardenafil, when compared to placebo. These effects are consistent with the vasodilatory effects of PDE5-inhibitors and are probably due to increased cGMP levels in vascular smooth muscle cells. Single and multiple oral doses of vardenafil up to 40 mg produced no clinically relevant changes in the ECGs of normal male volunteers.

Pharmacotherapeutic group: Urologicals, Drugs used in erectile dysfunction, ATC code: G04BE09.

Vardenafil is an oral therapy for the improvement of erectile function in men with erectile dysfunction.
In the natural setting, i.e. with sexual stimulation it restores impaired erectile function by increasing blood flow to the penis.

Penile erection is a haemodynamic process. During sexual stimulation, nitric oxide is released. It activates the enzyme guanylate cyclase, resulting in an increased level of cyclic guanosine monophosphate (cGMP) in the corpus cavernosum. This in turn results in smooth muscle relaxation, allowing increased inflow of blood into the penis. The level of cGMP is regulated by the rate of synthesis via guanylate cyclase and by the rate of degradation via cGMP hydrolysing phosphodiesterases (PDEs).

Vardenafil is a potent and selective inhibitor of the cGMP specific phosphodiesterase type 5 (PDE5), the most prominent PDE in the human corpus cavernosum. Vardenafil potently enhances the effect of endogenous nitric oxide in the corpus cavernosum by inhibiting PDE5. When nitric oxide is released in response to sexual stimulation, inhibition of PDE5 by vardenafil results in increased corpus cavernosum levels of cGMP. Sexual stimulation is therefore required for vardenafil to produce its beneficial therapeutic effects.

In vitro studies have shown that vardenafil is more potent on PDE5 than on other known phosphodiesterases (>15-fold relative to PDE6, >130-fold relative to PDE1, >300-fold relative to PDE11, and >1000-fold relative to PDE2, PDE3, PDE4, PDE7, PDE8, PDE9 and PDE10).

In a penile plesthysmography (RigiScan) study, vardenafil 20 mg produced erections considered sufficient for penetration (60% rigidity by RigiScan) in some men as early as 15 minutes after dosing.
The overall response of these subjects to vardenafil became statistically significant, compared to placebo, 25 minutes after dosing.

Vardenafil causes mild and transient decreases in blood pressure which, in the majority of the cases, do not translate into clinical effects. The mean maximum decreases in supine systolic blood pressure following 20 mg and 40 mg vardenafil were – 6.9 mmHg under 20 mg and – 4.3 mmHg under 40 mg of vardenafil, when compared to placebo. These effects are consistent with the vasodilatory effects of PDE5-inhibitors and are probably due to increased cGMP levels in vascular smooth muscle cells. Single and multiple oral doses of vardenafil up to 40 mg produced no clinically relevant changes in the ECGs of normal male volunteers.

Bioequivalence studies have shown that vardenafil 10 mg orodispersible tablet is not bioequivalent to vardenafil 10 mg film-coated tablets. Therefore the orodispersible formulation should not be used as an equivalent to vardenafil 10 mg film-coated tablets.

Absorption
In vardenafil film-coated tablets, vardenafil is rapidly absorbed with maximum observed plasma concentrations reached in some men as early as 15 minutes after oral administration. However, 90% of the time, maximum plasma concentrations are reached within 30 to 120 minutes (median 60 minutes) of oral dosing in the fasted state. The mean absolute oral bioavailability is 15%. After oral dosing of vardenafil AUC and Cmax increase almost dose proportionally over the recommended dose range (5 – 20 mg).

When vardenafil film-coated tablets are taken with a high fat meal (containing 57% fat), the rate of absorption is reduced, with an increase in the median tmax of 1 hour and a mean reduction in Cmax of 20%.
Vardenafil AUC is not affected. After a meal containing 30% fat, the rate and extent of absorption of vardenafil (tmax, Cmax and AUC) are unchanged compared to administration under fasting conditions.

Vardenafil is rapidly absorbed after administration of Levitra 10 mg orodispersible tablets without water. The median time to reach Cmax varied between 45 to 90 minutes and was similar or slightly delayed (by 8 to 45 min) compared to the film-coated tablets. Mean vardenafil AUC was increased by 21 to 29% (middle aged and elderly ED patients) or 44% (young healthy subjects) with 10 mg orodispersible tablets compared to film-coated tablets as a result of local oral absorption of a small amount of drug in the oral cavity. There was no consistent difference in mean Cmax between orodispersible tablets and film-coated tablets.

Bioequivalence studies have shown that vardenafil 10 mg orodispersible tablet is not bioequivalent to vardenafil 10 mg film-coated tablets. Therefore the orodispersible formulation should not be used as an equivalent to vardenafil 10 mg film-coated tablets.

Absorption
In vardenafil film-coated tablets, vardenafil is rapidly absorbed with maximum observed plasma concentrations reached in some men as early as 15 minutes after oral administration. However, 90% of the time, maximum plasma concentrations are reached within 30 to 120 minutes (median 60 minutes) of oral dosing in the fasted state. The mean absolute oral bioavailability is 15%. After oral dosing of vardenafil AUC and Cmax increase almost dose proportionally over the recommended dose range (5 - 20 mg).

When vardenafil film-coated tablets are taken with a high fat meal (containing 57% fat), the rate of absorption is reduced, with an increase in the median tmax of 1 hour and a mean reduction in Cmax of 20%.
Vardenafil AUC is not affected. After a meal containing 30% fat, the rate and extent of absorption of vardenafil (tmax, Cmax and AUC) are unchanged compared to administration under fasting conditions.

Vardenafil is rapidly absorbed after administration of Levitra 10 mg orodispersible tablets without water. The median time to reach Cmax varied between 45 to 90 minutes and was similar or slightly delayed (by 8 to 45 min) compared to the film-coated tablets. Mean vardenafil AUC was increased by 21 to 29% (middle aged and elderly ED patients) or 44% (young healthy subjects) with 10 mg orodispersible tablets compared to film-coated tablets as a result of local oral absorption of a small amount of drug in the oral cavity. There was no consistent difference in mean Cmax between orodispersible tablets and film-coated tablets.