levitra 10 mg kullananlar

levitra 10 mg kullananlar

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Levitra 10 mg orodispersible tablets

Levitra contains vardenafil, a member of a class of medicines called phosphodiesterase type 5 inhibitors. They are used for the treatment of erectile dysfunction in adult men, a condition which implies difficulties in getting or keeping an erection.

At least one in ten men has trouble getting or keeping an erection at some time. There may be physical or psychological causes, or a mixture of both. Whatever the cause is, due to muscle and blood vessel changes not enough blood stays in the penis to make it hard and keep it hard.

Levitra will only work when you are sexually stimulated. It reduces the action of the natural chemical in your body which makes erections go away. Levitra allows an erection to last long enough for you to satisfactorily complete sexual activity.

Do not take Levitra

  • If you are allergic (hypersensitive) to vardenafil or any of the other ingredients of Levitra. See the ingredients in section 6. Signs of an allergic reaction include a rash, itching, swollen face or lips and shortness of breath.
  • If you are taking medicines containing nitrates, such as glycerol trinitrate for angina, or nitric oxide donors , such as amyl nitrite. Taking these medicines with Levitra could seriously affect your blood pressure.
  • If you are taking ritonavir or indinavir, medicines used to treat human immunodeficiency virus (HIV) infections.
  • If you are over 75 years of age and are taking ketoconazole or itraconazole, anti-fungal medicines
  • If you have a severe heart or liver problem
  • If you are having kidney dialysis
  • If you have recently had a stroke or heart attack
  • If you have or have had low blood pressure
  • If your family has a history of degenerative eye diseases (such as retinitis pigmentosa )
  • If you have ever had a condition involving loss of vision due to damage to the optic nerve from insufficient blood supply known as non-arteritic ischemic optic neuropathy (NAION).

Take special care with Levitra

  • If you have heart trouble. It may be risky for you to have sex
  • If you suffer from irregular heart beat (cardiac arrhythmia) or inherited heart diseases affecting your electrocardiogram
  • If you have a physical condition affecting the shape of the penis. This includes conditions called angulation, Peyronie’s disease and cavernosal fibrosis
  • If you have an illness that can cause erections which won’t go away (priapism ). These include sickle cell disease, multiple myeloma and leukaemia
  • If you have stomach ulcers (also called gastric or peptic ulcers)
  • If you have a bleeding disorder (such as haemophilia)
  • If you are using any other treatments for erection difficulties, including Levitra film-coated tablets. See “Using other medicines”.
  • If you experience sudden decrease or loss of vision, stop taking Levitra and contact your doctor immediately.

Children Levitra is not intended for use by children or adolescents under 18.

Using other medicines
Please tell your doctor or pharmacist if you are using or have recently used any other medicines, including medicines obtained without a prescription.
Some medicines may cause problems, especially these:

  • Nitrates, medicines for angina, or nitric oxide donors , such as amyl nitrite. Taking these medicines with Levitra could seriously affect your blood pressure. Talk to a doctor without taking Levitra
  • Medicine for the treatment of arrhythmias, such as quinidine, procainamide, amiodarone or sotalol
  • Ritonavir or indinavir, medicines for HIV.Talk to a doctor without taking Levitra
  • Ketoconazole or itraconazole, anti-fungal medicines
  • Erythromycin, or clarithromycin, macrolide antibiotics
  • Alpha-blockers, a type of medicine used to treat high blood pressure and enlargement of the prostate (as benign prostatic hyperplasia).

Do not use Levitra orodispersible tablets combined with any other treatment for erectile dysfunction, including Levitra film-coated tablets.

Taking Levitra with food and drink

  • You can take Levitra orodispersible tablets with or without food, but do not take this medicine with any liquid.
  • Don’t drink grapefruit juice when you use Levitra. It can interfere with the usual effect of the medicine.
  • Alcoholic drink can make erection difficulties worse.

Pregnancy and breast-feeding
Levitra is not for use by women.

Driving and using machines
Levitra might make some people feel dizzy or affect their vision. If you feel dizzy, or if your vision is affected after taking Levitra don’t drive or operate any tools or machines.

Important information about some of the ingredients of Levitra 10 mg orodispersible tablets:

  • Aspartameis a source of phenylalanine, and may be harmful for people with a disorder called phenylketonuria.
  • Sorbitol: If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

Always take Levitra exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure. The usual dose is 10 mg.

Take Levitra about 60 minutes before sexual activity. With sexual stimulation you may achieve an erection anywhere from 25 minutes up to four to five hours after taking Levitra.

  • Do not remove the orodispersible tablet from the blister until you are going to take it. With dry hands, pull the blister edge from the blister holder and press gently on top to release the tablet on your hand.Do not crush the tablet.
  • Place the entire orodispersible tablet in the mouth, on the tongue, where it will dissolve in seconds, then swallow with saliva. The orodispersible tablet must be taken without any liquid.

Do not take Levitra orodispersible tablets with any other forms of Levitra .

Do not takeLevitra more than once a day.

Tell your doctor if you think Levitra is too strong or too weak. He or she may suggest a switch to an alternative Levitra formulation with a different dose, depending on how well it works for you.

If you take more Levitra than you should
Men who take too much Levitra may experience more side effects or may get severe back pain. If you take more Levitra than you should, tell your doctor.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

Like all medicines, Levitra can cause side effects, although not everybody gets them. Most of the effects are mild or moderate.

Partial, sudden, temporary or permanent decrease or loss of vision in one or both eyes has been experienced by patients. Stop taking Levitra and contact your doctor immediately.
Sudden decrease or loss of hearing has been reported.

The chance of having a side effect is described by the following categories:

Very common(affects more than 1 user in 10)

Common(affects 1 to 10 users in 100)

  • Dizziness
  • Flushing
  • Blocked or runny nose
  • Indigestion

Uncommon(affects 1 to 10 users in 1,000)

  • Swelling of skin and mucous tissue including swollen face, lips or throat.
  • Sleep disorder
  • Numbness and impaired perception of touch
  • Sleepiness
  • Effects on vision; redness of the eye, effects on colour vision, eye pain and discomfort, light sensitivity
  • Ringing in the ears; vertigo
  • Fast heart beat or pounding heart
  • Breathlessness
  • Stuffy nose
  • Acid reflux, gastritis, abdominal pain, diarrhoea, vomiting; feeling sick (nausea), dry mouth
  • Raised levels of liver enzymes in your blood
  • Rash, reddened skin
  • Back or muscle pain; increase in blood of a muscle enzyme (creatine phosphokinase), muscle stiffness
  • Prolonged erections
  • Malaise

Rare(affects 1 to 10 users in 10,000)

  • Inflammation of the eyes (conjunctivitis)
  • Allergic reaction
  • Anxiety
  • Fainting
  • Amnesia
  • Seizure
  • Increased pressure in the eye (glaucoma), lacrimation increased
  • Effects on the heart (such as heart attack, altered heart beat or angina)
  • High or low blood pressure
  • Nose bleed
  • Effect on results of blood tests to check liver function.
  • Sensitivity of the skin to sun light
  • Painful erections
  • Chest pain

If any of the side effects gets serious or if you notice any side effects not listed in this leaflet, please tell your doctor.

Keep out of the reach and sight of children.

Do not use Levitra after the expiry date which is stated on the carton after “EXP”. The expiry date refers to the last day of that month.

Store in the original package in order to protect from humidity and light.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

Levitra is a medicine that contains the active substance vardenafil. It is available as round, orange film-coated tablets (5, 10 and 20 mg) and as round, white orodispersible tablets (10 mg). Orodispersible tablets are tablets that dissolve in the mouth.

Levitra is used to treat adult men (aged 18 years or over) with erectile dysfunction (sometimes called impotence), when they cannot get or keep a hard penis (erection) sufficient for satisfactory sexual activity. For Levitra to be effective, sexual stimulation is required.

The medicine can only be obtained with a prescription.

The recommended dose of Levitra is 10 mg, taken as one or two film-coated tablet about 25 to 60 minutes before sexual activity or as an orodispersible tablet (taken without liquid) about 60 minutes before sexual activity. If Levitra film-coated tablets are taken with a high fat meal, the onset of activity may be delayed. The dose of the film-coated tablets may be increased to a maximum of 20 mg or decreased to 5 mg, depending on the effectiveness of treatment and any side effects.

A starting dose of 5 mg should be considered for patients with mild and moderate liver problems. The dose may need to be adjusted in patients taking other medicines that inhibit enzymes that break down Levitra. For full details, see the package leaflet.

The maximum recommended dosing frequency is one tablet or orodispersible tablet per day.

The active ingredient of Levitra, vardenafil, belongs to a group of medicines called phosphodiesterase type 5 (PDE5) inhibitors. It works by blocking the phosphodiesterase enzyme which normally breaks down a substance known as cyclic guanosine monophosphate (cGMP). During normal sexual stimulation, cGMP is produced in the penis, where it causes the muscle in the spongy tissue of the penis (the corpora cavernosa ) to relax. This allows blood to flow into the corpora. producing the erection. By blocking the breakdown of cGMP, Levitra restores erectile function. Sexual stimulation is still needed to produce an erection.

Levitra tablets were compared with placebo (a dummy treatment) in four main studies including a total of 2,431 men with erectile dysfunction aged 20 to 83 years. One of these studies was carried out in diabetic men and another in men who had had their prostate gland removed.

The effectiveness of orodispersible tablets and placebo were compared in two main studies involving a total of 686 men with erectile dysfunction aged 21 to 84 years.

In all of the studies, the main measure of effectiveness was the ability to get and maintain an erection. This was recorded in two questionnaires completed at home. The studies lasted 12 weeks.

Levitra tablets and orodispersible tablets were significantly more effective than placebo for all measures in all of the studies.

The most common side effect with Levitra (seen in more than 1 patient in 10) is headache. Flushing (reddening of the skin) is also seen in more than 1 patient in 10 taking the film-coated tablets. For the full list of all side effects reported with Levitra, see the package leaflet.

Levitra should not be used in people who may be hypersensitive (allergic) to vardenafil or any of the other ingredients. It must not be used when sexual activity is inadvisable, such as in men with severe heart disease. It must also not be used in patients who have ever had loss of vision because of a problem with blood flow to the nerve in the eye (non-arteritic anterior ischemic optic neuropathy or NAION). Levitra must not be taken with nitrates (medicines used to treat angina). Because Levitra has not been studied in patients with severe liver or kidney disease, patients who have hypotension (low blood pressure) or patients who have had a stroke or a heart attack within the last six months must not use it. Levitra must not be taken with ketoconazole and itraconazole (used to treat fungal infections) in men over 75 years of age, or with ritonavir or indinavir (used to treat HIV infection).

Caution is needed when Levitra is taken with some other medicines. See the package leaflet for full details.

The CHMP decided that Levitra’s benefits are greater than its risks and recommended that it be given marketing authorisation.

The European Commission granted a marketing authorisation valid throughout the European Union for Levitra on 6 March 2003. The marketing authorisation holder is Bayer Schering Pharma AG. The marketing authorisation is valid for an unlimited period.

For more information about treatment with Levitra, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This summary was last updated in 07-2010. Levitra Page

Erectile dysfunction is the inability to get or keep an erection. ED usually has a physical cause.

LEVITRA helps improve erectile function by increasing blood flow to the penis. LEVITRA has helped many men and it may help you, too.

LEVITRA can cause your blood pressure to drop suddenly to an unsafe level if it is taken with certain other medicines. With a sudden drop in blood pressure, you could get dizzy, faint, or have a heart attack or stroke.

If, like millions of other men, you have noticed changes in your erections, you can do something about it. Talking to your doctor is the first step.

Did you know
ED usually has
a physical cause?

Erectle Dysfunction Treatment - LEVITRA
See your doctor.

Indication
LEVITRA is a prescription medicine used for the treatment of erectile dysfunction (ED) in men.

Important Safety Information

  • LEVITRA can cause your blood pressure to drop suddenly to an unsafe level if it is taken with certain other medicines. With a sudden drop in blood pressure, you could get dizzy, faint, or have a heart attack or stroke.
  • Do not take LEVITRA if you:
    • Take any medications called "nitrates" (often used to control chest pain, also known as angina), or if you use recreational drugs called "poppers" like amyl nitrate and butyl nitrate. Nitrates may cause abnormally low blood pressure and LEVITRA may increase that risk
    • Take riociguat (Adempas ® ), a guanylate cyclase stimulator. a medicine that treats pulmonary arterial hypertension and chronic-thromboembolic pulmonary hypertension
    • Have been told by your healthcare provider not to have sexual activity because of health problems. Sexual activity can put an extra strain on your heart, especially if your heart is already weak from a heart attack or heart disease
  • Tell all your healthcare providers that you take LEVITRA. If you need emergency medical care for a heart problem, it will be important for your healthcare provider to know when you last took LEVITRA.
  • LEVITRA does not protect a man or his partner from sexually transmitted diseases, including HIV.
  • Before taking LEVITRA, tell your doctor about all your medical problems, including if you:
    • have heart problems such as angina, heart failure, irregular heartbeats, or have had a heart attack—ask your doctor if it is safe for you to have sexual activity
    • have low blood pressure or have high blood pressure that is not controlled
    • have pulmonary hypertension
    • have had a stroke
    • have had a seizure
    • or any family members have a rare heart condition known as prolongation of the QT interval (long QT syndrome)
    • have liver problems
    • have kidney problems and require dialysis
    • have retinitis pigmentosa, a rare genetic (runs in families) eye disease
    • have ever had severe vision loss, or if you have an eye condition called non-arteritic anterior ischemic optic neuropathy (NAION)
    • have stomach ulcers
    • have a bleeding problem
    • have a deformed penis shape or Peyronie's disease
    • have had an erection that lasted more than 4 hours
    • have blood cell problems such as sickle cell anemia, multiple myeloma, or leukemia
    • have hearing problems
  • Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. LEVITRA and other medicines may affect each other. Especially tell your doctor if you take any of the following:
    • Ritonavir (Norvir ® ) or indinavir sulfate (Crixivan ® ), saquinavir (Fortavase ® or Invirase ® ) or atazanavir (Reyataz ® ), or other HIV protease inhibitors
    • Ketoconazole or itraconazole (such as Nizoral ® or Sporanox ® )
    • Erythromycin or clarithromycin
  • Tell your doctor if you take alpha-blockers. These include Hytrin ® (terazosin HCl), Flomax ® (tamsulosin HCl), Cardura ® (doxazosin mesylate), Minipress ® (prazosin HCl), Uroxatral ® (alfuzosin HCl), or Rapaflo ® (silodosin). Alpha-blockers are sometimes prescribed for prostate problems or high blood pressure. In some patients, the use of PDE5 inhibitor drugs, including LEVITRA, with alpha-blockers can lower blood pressure significantly, leading to fainting.
    • Contact the prescribing physician if alpha-blockers or other drugs that lower blood pressure are prescribed by another healthcare provider
  • Tell your doctor if you take medicines that treat abnormal heartbeat. These include quinidine, procainamide, amiodarone, and sotalol. Patients taking these drugs should not use LEVITRA.
  • Do not use LEVITRA with other medicines or treatments for ED.
  • Take LEVITRA exactly as your doctor prescribes. LEVITRA comes in different doses (2.5 mg, 5 mg, 10 mg, and 20 mg). For most men, the recommended starting dose is 10 mg. Do not take more than one tablet of LEVITRA per day. Doses should be taken at least 24 hours apart. Some men can take only a low dose of LEVITRA because of medical conditions or medicines they take. Your doctor will prescribe the dose that is right for you.
    • If you are older than 65 or have liver problems, your doctor may start you on a lower dose of LEVITRA
    • If you have prostate problems or high blood pressure for which you take medicines called alpha-blockers, your doctor may start you on a lower dose of LEVITRA
    • If you are taking certain other medicines, your doctor may prescribe a lower starting dose and limit you to one dose of LEVITRA in a 72-hour (3-day) period.
  • The most common side effects with LEVITRA are headache, flushing, stuffy or runny nose, indigestion, upset stomach, dizziness, and back pain.
  • LEVITRA may uncommonly cause:
    • An erection that lasts more than 4 hours. Get medical help right away to avoid lasting damage to your penis
    • Color vision changes. such as seeing a blue tinge to objects or having difficulty telling the difference between the colors blue and green
  • In rare instances, men taking PDE5 inhibitors (oral erectile dysfunction medicines, including LEVITRA) reported a sudden decrease or loss of vision in one or both eyes or a sudden decrease or loss in hearing, sometimes with ringing in the ears and dizziness. It is not possible to determine whether these events are related directly to the PDE5 inhibitors, to other diseases or medications, to other factors, or to a combination of factors. If you experience sudden decrease or loss of vision or hearing, stop taking LEVITRA and contact a doctor right away.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Please read the Patient Information and discuss it with your doctor.

The physician Prescribing Information is also available.

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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 the 20 mg dose 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.

Post-marketing reports of another medicinal product of this class

Serious cardiovascular reactions, including cerebrovascular haemorrhage, sudden cardiac death, transient ischaemic attack, unstable angina and ventricular arrhythmia have been reported post-marketing in temporal association with another medicinal product in this class.

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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard .

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

5.1 Pharmacodynamic 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.

A single dose, double blind, crossover, randomised trial in 59 healthy males compared the effects on the QT interval of vardenafil (10 mg and 80 mg), sildenafil (50 mg and 400 mg) and placebo. Moxifloxacin (400 mg) was included as an active internal control. Effects on the QT interval were measured one hour post-dose (average tmax for vardenafil). The primary objective of this study was to rule out a greater than 10 msec effect (i.e. to demonstrate lack of effect) of a single 80 mg oral dose of vardenafil on QTc interval compared to placebo, as measured by the change in Fridericia's correction formula (QTcF=QT/RR1/3) from baseline at the 1 hour post-dose time point. The vardenafil results showed an increase in QTc (Fridericia) of 8 msec (90% CI: 6-9) and 10 msec (90% CI: 8-11) at 10 and 80 mg doses compared to placebo and an increase in QTci of 4 msec (90% CI: 3-6) and 6 msec (90% CI: 4-7) at 10 and 80 mg doses compared to placebo, at one hour post-dose. At tmax. only the mean change in QTcF for vardenafil 80 mg was out of the study established limit (mean 10 msec, 90% CI: 8-11). When using the individual correction formulae, none of the values were out of the limit.

In a separate post-marketing study of 44 healthy volunteers, single doses of 10 mg vardenafil or 50 mg sildenafil were co-administered concomitantly with 400 mg gatifloxacin, a drug with comparable QT effect. Both vardenafil and sildenafil showed an increase of Fridericia QTc effect of 4 msec (vardenafil) and 5 msec (sildenafil) when compared to either drug alone. The actual clinical impact of these QT changes is unknown.

Further information on clinical trials with vardenafil 10 mg orodispersible tablets

Efficacy and safety of vardenafil 10 mg orodispersible tablets were separately demonstrated in a broad population in two studies including 701 randomized erectile dysfunction patients who were treated up to 12 weeks. The distribution of patients in the predefined subgroups was covering elderly patients (51%), patients with history of diabetes mellitus (29%), dyslipidemia (39%) and hypertension (40%).

In pooled data from the two vardenafil 10 mg orodispersible tablets trials, IIEF-EF domain scores were significantly higher with vardenafil 10 mg orodispersible tablet versus placebo.

A percentage of 71% of all sexual attempts reported in the clinical trials had successful penetration compared to 44% of all attempts in the placebo group. These results were also reflected in subgroups, in elderly patients (65%), in patients with history of diabetes mellitus (63%), patients with history of dyslipidemia (66%) and hypertension (70%) of all sexual attempts reported had successful penetration.

About 63% of all reported sexual attempts with vardenafil 10 mg orodispersible tablets were successful in terms of erection maintenance compared to about 26% of all placebo-controlled sexual attempts. In the predefined subgroups 57% (elderly patients), 56% (patients with history of diabetes mellitus), 59% (patients with history of dyslipidemia) and 60% (patients with history of hypertension) of all reported attempts with vardenafil 10 mg orodispersible tablets were successful in terms of maintenance of erection.

Further information on clinical trials

In clinical trials vardenafil was administered to over 17,000 men with erectile dysfunction (ED) aged 18 - 89 years, many of whom had multiple co-morbid conditions. Over 2,500 patients have been treated with vardenafil for six months or longer. Of these, 900 patients have been treated for one year or longer.

The following patient groups were represented: elderly (22%), patients with hypertension (35%), diabetes mellitus (29%), ischaemic heart disease and other cardiovascular diseases (7%), chronic pulmonary disease (5%), hyperlipidemia (22%), depression (5%), radical prostatectomy (9%). The following groups were not well represented in clinical trials: elderly (>75 years, 2.4%), and patients with certain cardiovascular conditions (see section 4.3). No clinical trials in CNS diseases (except spinal cord injury), patients with severe renal or hepatic impairment, pelvic surgery (except nerve-sparing prostatectomy) or trauma or radiotherapy and hypoactive sexual desire or penile anatomic deformities have been performed.

Across the pivotal trials, treatment with vardenafil (film-coated tablets) resulted in an improvement of erectile function compared to placebo. In the small number of patients who attempted intercourse up to four to five hours after dosing the success rate for penetration and maintenance of erection was consistently greater than placebo.

In fixed dose studies (film-coated tablets) in a broad population of men with erectile dysfunction, 68% (5 mg), 76% (10 mg) and 80% (20 mg) of patients experienced successful penetrations (SEP 2) compared to 49% on placebo over a three month study period. The ability to maintain the erection (SEP 3) in this broad ED population was given as 53% (5 mg), 63% (10 mg) and 65% (20 mg) compared to 29% on placebo.

In pooled data from the major efficacy trials, the proportion of patients experiencing successful penetration on vardenafil were as follows: psychogenic erectile dysfunction (77-87%), mixed erectile dysfunction (69-83%), organic erectile dysfunction (64-75%), elderly (52-75%), ischaemic heart disease (70-73%), hyperlipidemia (62-73%), chronic pulmonary disease (74-78%), depression (59-69%), and patients concomitantly treated with antihypertensives (62-73%).

In a clinical trial in patients with diabetes mellitus, vardenafil significantly improved the erectile function domain score, the ability to obtain and maintain an erection long enough for successful intercourse and penile rigidity compared to placebo at vardenafil doses of 10 mg and 20 mg. The response rates for the ability to obtain and maintain an erection was 61% and 49% on 10 mg and 64% and 54% on 20 mg vardenafil compared to 36% and 23% on placebo for patients who completed three months treatment.

In a clinical trial in post-prostatectomy patients, vardenafil significantly improved the erectile function domain score, the ability to obtain and maintain an erection long enough for successful intercourse and penile rigidity compared to placebo at vardenafil doses of 10 mg and 20 mg. The response rates for the ability to obtain and maintain an erection was 47% and 37% on 10 mg and 48% and 34% on 20 mg vardenafil compared to 22% and 10% on placebo for patients who completed three months treatment.

In a flexible-dose clinical trial in patients with Spinal Cord Injury, vardenafil significantly improved the erectile function domain score, the ability to obtain and maintain an erection long enough for successful intercourse and penile rigidity compared to placebo. The number of patients who returned to a normal IIEF domain score (≥26) were 53% on vardenafil compared to 9% on placebo. The response rates for the ability to obtain and maintain an erection were 76% and 59% on vardenafil compared to 41% and 22% on placebo for patients who completed three months treatment which were clinically and statistically significant (p<0.001).

The safety and efficacy of vardenafil was maintained in long term-studies.

The European Medicines Agency has waived the obligation to submit the results of studies in all subsets of the paediatric population in the treatment of the erectile dysfunction. See section 4.2 for information on paediatric use.

5.2 Pharmacokinetic properties

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.

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 vardenafil 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.

In subjects taking vardenafil 10 mg orodispersible tablets with a high fat meal no effect on vardenafil AUC and tmax was observed, while vardenafil Cmax was reduced by 35% in the fed condition. Based on these results vardenafil 10 mg orodispersible tablets can be taken with or without food.

If vardenafil 10 mg orodispersible tablets are taken with water, the AUC is reduced by 29%, Cmax remains unchanged and median tmax is shortened by 60 minutes compared to intake without water. Vardenafil 10 mg orodispersible tablets must be taken without liquid.

The mean steady state volume of distribution for vardenafil is 208 l, indicating distribution into the tissues.

Vardenafil and its major circulating metabolite (M1) are highly bound to plasma proteins (approximately 95% for vardenafil or M1). For vardenafil as well as M1, protein binding is independent of total drug concentrations.

Based on measurements of vardenafil in semen of healthy subjects 90 minutes after dosing, not more than 0.00012% of the administered dose may appear in the semen of patients.

Vardenafil in film-coated tablets is metabolised predominantly by hepatic metabolism via cytochrome P450 (CYP) isoform 3A4 with some contribution from CYP3A5 and CYP2C isoforms.

In humans the one major circulating metabolite (M1) results from desethylation of vardenafil and is subject to further metabolism with a plasma elimination half-life of approximately 4 hours. Parts of M1 are in the form of the glucuronide in systemic circulation. Metabolite M1 shows a phosphodiesterase selectivity profile similar to vardenafil and an in vitro potency for phosphodiesterase type 5 of approximately 28% compared to vardenafil, resulting in an efficacy contribution of about 7%.

The mean terminal half-life of vardenafil in patients receiving vardenafil 10 mg orodispersible tablets ranged between 4 – 6 hours. The elimination half-life of the metabolite M1 is between 3 to 5 hours, similar to parent drug.

The total body clearance of vardenafil is 56 l/h with a resultant terminal half-life of approximately 4-5 hours. After oral administration, vardenafil is excreted as metabolites predominantly in the faeces (approximately 91-95% of the administered dose) and to a lesser extent in the urine (approximately 2-6% of the administered dose).

Pharmacokinetics in special patient groups

Hepatic clearance of vardenafil in healthy elderly volunteers (65 years and over) was reduced as compared to healthy younger volunteers (18 - 45 years). On average elderly males taking vardenafil film-coated tablets had a 52% higher AUC, and a 34% higher Cmax than younger males (see section 4.2).

Vardenafil AUC and Cmax in elderly patients (65 years or over) taking vardenafil orodispersible tablets were increased by 31 to 39% and 16 to 21%, respectively, in comparison to patients aged 45 years and below. Vardenafil was not found to accumulate in the plasma in patients aged 45 years and below or 65 years or over following once-daily dosing of vardenafil 10 mg orodispersible tablets over ten days.

In volunteers with mild to moderate renal impairment (creatinine clearance 30 – 80 ml/min), the pharmacokinetics of vardenafil were similar to that of a normal renal function control group. In volunteers with severe renal impairment (creatinine clearance < 30 ml/min) the mean AUC was increased by 21% and the mean Cmax decreased by 23%, compared to volunteers with no renal impairment. No statistically significant correlation was observed between creatinine clearance and vardenafil exposure (AUC and Cmax ) (see section 4.2). Vardenafil pharmacokinetics has not been studied in patients requiring dialysis (see section 4.3).

In patients with mild to moderate hepatic impairment (Child-Pugh A and B), the clearance of vardenafil was reduced in proportion to the degree of hepatic impairment. In patients with mild hepatic impairment (Child-Pugh A), the mean AUC and Cmax increased 17% and 22% respectively, compared to healthy control subjects. In patients with moderate impairment (Child-Pugh B), the mean AUC and Cmax increased by 160% and 133% respectively, compared to healthy control subjects (see section 4.2). The pharmacokinetics of vardenafil in patients with severely impaired hepatic function (Child-Pugh C) has not been studied (see section 4.3).

5.3 Preclinical safety data

Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction.

6. Pharmaceutical particulars

8. Marketing authorisation number(s)

EU/1/03/248/001 Levitra 5 mg film-coated tablet, pack size 2 tablets

EU/1/03/248/002 Levitra 5 mg film-coated tablet, pack size 4 tablets

EU/1/03/248/003 Levitra 5 mg film-coated tablet, pack size 8 tablets

EU/1/03/248/004 Levitra 5 mg film-coated tablet, pack size 12 tablets

EU/1/03/248/005 Levitra 10 mg film-coated tablet, pack size 2 tablets

EU/1/03/248/006 Levitra 10 mg film-coated tablet, pack size 4 tablets

EU/1/03/248/007 Levitra 10 mg film-coated tablet, pack size 8 tablets

EU/1/03/248/008 Levitra 10 mg film-coated tablet, pack size 12 tablets

EU/1/03/248/009 Levitra 20 mg film-coated tablet, pack size 2 tablets

EU/1/03/248/010 Levitra 20 mg film-coated tablet, pack size 4 tablets

EU/1/03/248/011 Levitra 20 mg film-coated tablet, pack size 8 tablets

EU/1/03/248/012 Levitra 20 mg film-coated tablet, pack size 12 tablets

EU/1/03/248/021 Levitra 5 mg film-coated tablet, pack size 20 tablets

EU/1/03/248/022 Levitra 10 mg film-coated tablet, pack size 20 tablets

EU/1/03/248/023 Levitra 20 mg film-coated tablet, pack size 20 tablets

9. Date of first authorisation/renewal of the authorisation

Date of first authorisation: 6 March 2003

Date of latest renewal: 6 March 2008

10. Date of revision of the text

Detailed information on this medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu .

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