Sildenafil

4th Quarter, 2003--- Two new ED drugs, vardenafil (Levitra, Bayer) and tadalafil (Cialis, Lilly/ICOS), have completed extensive clinical testing, and both drugs have gained FDAs approval. Both are inhibitors of type 5 phosphodiesterase (PDE-5), thus sharing the same basic mechanism of sildenafil (Viagra, Pfizer), which was approved in March, 1998. All three are taken orally prior to planned sexual activity, acting to increase blood flow in the penis in response to sexual stimulation. However, there are important differences between the three, differences that could influence safety, specificity, duration of action, and ultimately, public acceptance within this class of drug.

The direct intracellular mediator of the nitric oxide pathway is cGMP. PDE catalyzes the degradation of cGMP. This pathway is active in numerous organ systems, and as of this writing, a number of different PDEs are known. The various PDEs differ in their physiologic roles and tissue distribution. Type 5 PDE is concentrated in the penile smooth muscle of the corpus cavernosum, where its normal function is to inhibit erection by degradation of cGMP, the mediator of erection. Viagra and the new drugs Cialis and Levitra all inhibit PDE-5, which is an inhibitor for corporal smooth muscle relaxation, resulting in increased blood flow in the penis in response to sexual stimulation.

No head-to-head trial comparing the 3 PDE inhibitors has been performed. However, some differences between the 3 are basic: a table has been created to illustrate the major differences. An obvious proviso is that extensive data are available on Viagra (more than 20 million men treated, more than 1100 peer-reviewed articles as of Feb. ’03), but only limited data on Cialis and Levitra. Drs. Gresser and Gleiter from the U. Tubingen in Germany have compared the three drugs via literature review (Eur. J. Med. Res. 7:435, 2002) In brief, efficacy is approximately 70% with all 3 drugs. The side effect profile is similar among the 3 drugs, except that blue discoloration of vision (overlap with PDE-6 in the retina) is seen only with Viagra (<0.5%) and muscle aches only with Cialis (~5%). Otherwise, vasodilatory side effects (headaches, nasal congestion, flushing) are common with all, but are mild, and only rarely cause men to drop out of clinical trials (2-3% quit rate). All 3 will carry a contra-indication in men using organic nitrates. Otherwise, the long half-life of Cialis (17.5 hours) is noteworthy, earning this drug the nickname ‘weekender,’ as a single dose taken on Friday would still be exerting an effect Sunday (or even Monday).