Vardenafil

Single oral doses of 10 mg and 80 mg of vardenafil have been shown to prolong the QTc interval by a mean of 8 msec and 10 msec, respectively. And single doses of 10 mg vardenafil co-administered concomitantly with 400 mg gatifloxacin, an active substance with comparable QT effect, showed an additive QTc effect of 4 msec when compared to either active substance alone. The clinical impact of these QT changes is unknown.

The clinical relevance of this finding is unknown and cannot be generalised to all patients under all circumstances, as it will depend on the individual risk factors and susceptibilities that may be present at any time in any given patient. Medicinal products that may prolong QTc interval, including vardenafil, are best avoided in patients with relevant risk factors, for example, hypokalaemia, congenital QT prolongation, concomitant administration of antiarrhythmic medicinal products in Class 1A (e.g. quinidine, procainamide), or Class III (e.g. amiodarone, sotalol).

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.

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. Vardenafil may be administered at any time with tamsulosin or with alfuzosin. With other alpha-blockers a time separation of dosing should be considered when vardenafil is prescribed concomitantly. In those patients already taking an 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 intake of grapefruit or grapefruit juice is expected to increase the plasma concentrations of vardenafil. The combination should be avoided.

Vardenafil dose adjustment might be necessary if moderate CYP3A4 inhibitors such as erythromycin and clarithromycin, are given concomitantly.

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.

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.

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.

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).

Vardenafil is not indicated for use by women. There are no studies of vardenafil in pregnant women.

Vardenafil is not indicated for use by women.

Fertility

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 vardenafil, before driving or operating machines.

Summary of the safety profile

The adverse reactions reported with vardenafil 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:

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 vardenafil 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.