Vardenafil, introduced in 2003, is available in oral doses of 2.5, 5, 10, and 20 mg, while the recommended starting dose is 10 mg [9]. The medication should be taken 30 min prior to intercourse in a fasting state, as it is also affected by fatty meals. It has a higher affinity to PDE5 than sildenafil which makes it more potent and extends its duration of efficacy up to 10 h [33]. It may cause QT prolongation; thus caution should be taken when it is administered with drugs that prolong QT interval such as type 1A and type 3 antiarrhythmics or in patients with a congenitally prolonged QT syndrome [34]. A new orodispersible tablet is available which appears to have the same efficacy as the traditional tablet, but is not affected by meals [35, 36]. The pharmacokinetic characteristics of vardenafil are presented in Table 19.1.

Tadalafil was also introduced in 2003. The available oral doses are 2.5, 5, 10, and 20 mg and recommended starting dose of 10 mg [9]. It should be taken approximately 30 min before intercourse. Its unique characteristic is its extended duration of action up to 36 h and it is not affected by food [31]. A daily treatment of 2.5 or 5 mg has been approved for ED for a more spontaneous intercourse [9, 37, 38]. Pharmacokinetic data regarding tadalafil are presented in Table 19.1.

The effect of PDE5 inhibitors on blood pressure and heart rate is minimal when prescribed alone. The main metabolic pathway of PDE5 inhibitors is via cytochrome P450, specifically CYP3A4 (Table 19.1). In this regard, any inhibitors or inducers of these enzymes will influence the drugs’ concentration and dose adjustment may be needed. Therefore, caution should be taken when cytochrome P450 inhibitors are concomitantly prescribed with erythromycin, ketoconazole, itraconazole, clarithromycin, HIV protease inhibitors, or grapefruit juice [39]. Dose adjustment is necessary for ritonavir because it markedly increases PDE5 inhibitor concentrations [40]. Conversely, inducers of cytochrome P450, including carbamazepine, phenytoin, and phenobarbital, likely decrease PDE5 inhibitor levels. No notable interactions with widely prescribed medications such as warfarin, azithromycin, selective serotonin reuptake inhibitors, thiazides, angiotensin-converting enzyme inhibitors, calcium channel blockers, antacids, glyburide, digoxin, ranitidine, midazolam, lovastatin, or theophylline have been noted [40].