Special Warning : אזהרת שימוש

4.4         Special warnings and precautions for use

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).

Effect on vision
Visual defects and cases of non-arteritic ischemic optic neuropathy (NAION) have been reported in connection with the intake of Levitra and other PDE5 inhibitors. Analyses of observational data suggest an increased risk of acute NAION in men with erectile dysfunction following exposure to PDE5 inhibitors such as vardenafil, tadalafil and sildenafil (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 on Driving

4.7         Effects on ability to drive and use 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.