Tadalafil,already registered in the treatment of erectile dysfunction, has been approved,with a dosage of 5mg, with a centralized European procedure in the treatment ofsigns and symptoms of benign prostatic hypertrophy (BPH). Tadalafil, suchas sildenafil and vardenafil, is a reversible selective inhibitor of phospho diesterase type 5, present in a high concentration in the smooth muscle of the cavernous bodies of the penis where the enzyme favors the degradation ofcyclic guanosine monophosphate (cGMP). The increase in cGMP results in are laxation of smooth muscle cells: vasodilation, which allows an increase in blood flow in the corpus cavernosum of the penis, underlies the mechanism of erection. An increase in cGMP was also observed in the smooth muscle of the prostate, the bladder and their vascular system. The effect of vascular relaxation increases blood perfusion at the pelvic level and is associated with relaxation of the prostate and bladder smooth muscle. Tadalafi is available on RXShopMD.
Currently, alpha-blockers are the first choice drugs in the treatment of urinary tract obstruction symptoms associated with IPB . In cases where the prostate is larger than 30 ml, the use of a 5-alpha reductase inhibitor (dutasteride or finasteride) is recommended. The association between an alpha-blocker and a 5-alpha reductase inhibitor is an option in patients with moderate-to-severe urinary symptoms and an enlarged prostate (> 30 ml) . The registration studies that assessed the efficacy and safety of tadalafil in the treatment of urinary disorders by IPB are 4 double-blind, 12-week RCTs and one year open-label extension study. The 2,500 patients enrolled overall, aged 62-65, had a score in the International Prostate Symptoms Score (IPSS, ranging from 0 to 35 points) ≥13. In all studies, the main outcome measure was the change in the IPSS score at 12 weeks; the secondary end point was the score (from 0 to 13) in the Impact Index of Benign Prostatic Hyperplasia (BII) that measures the impact of the disease on the state of subjective well-being and daily activities.
Tadalafil, at a dose of 5 mg / day, produced a mean reduction in IPSS compared to placebo from a minimum of -1.9 to a maximum of -2.6. In one of the studies which also included tamsulosin (0.4mg / day) as an active control, the improvement of the IPSS was respectively 2.1 and 1.5 points. According to a specific study, a 3-point variation in the IPPS score corresponds to a “slight” improvement in symptoms. Regarding the BII score, the average variation went from -0.6 to -0.9; the minimum threshold for a “mild” clinical benefit was calculated as 0.5 points.
Two studies evaluated changes in erectile dysfunction in terms of the International Index of erectile function score; in the first study all patients with urinary symptoms of prostatic hypertrophy also had a history of erectile dysfunction , in the other about 50% of patients had both pathologies. The improvement of sexual function detected in the tadalafil group has certainly broken the double blindness becoming a pro-tadalafil factor in the detection of urinary symptoms. Tadalafil did not statistically improve the urinary flow rate 4 , 7. In a 12-week RCT, which specifically assessed urodynamic parameters in patients with urinary symptoms from BPH, there were no differences between tadalafil (20mg per day) and placebo in the pressure of the bladder detrusor to the maximum urinary flow, in the flow velocity, in the index of bladder obstruction or bladder capacity.
The most common adverse events of tadalafil are those already known: headache, dyspepsia, gastro-oesophageal reflux disease, hot flushes, back pain, myalgia, pain in extremities. In the open-ended 1-year study extension, 58% of patients reported one or more undesirable effects that resulted in 4.7% and prompted 5.2% of patients to discontinue treatment. The most frequent were dyspepsia and gastro-oesophageal reflux, headache and low back pain. The three deaths associated with the use of tadalafil, two from myocardial infarction and one from subarachnoid hemorrhage, occurred in patients with pre-existing cardiovascular risk factors 1. In the post-marketing surveillance phase, cases of non-arteritic anterior ischemic optic neuropathy (NAION), retinal vascular occlusion, and other eye disorders were reported. A sudden decrease or loss of hearing has also been reported in a small number of patients.