Latest News
New applications
Recent data have indicated a potential association between epidemiological, physiologic, pathophysiologic, and treatment aspects of ED and lower urinary tract symptoms (LUTS) secondary to BPH. The 17.5 hour half-life of tadalafil makes it the most suitable PDE5 inhibitor for once-daily dosing in a trial of LUTS secondary to BPH. McVary and associates reported a multicentered, randomized, double-blind, placebo controlled study of 281 men with LUTS secondary to BPH who were randomly assigned to once-daily tadalafil 5 mg for 6 weeks, followed by dose escalation to 20 mg for 6 weeks, or 12 weeks of placebo. They reported modest decreases in International Prostate Symptom Score (IPSS), with a mean change from baseline to 6 weeks of −2.8 with tadalafil 5 mg versus −1.2 with placebo (p < 0.003), and to 12 weeks of −3.8 with tadalafil 5/20 mg versus −1.7 with placebo (p < 0.001).
Once-daily dosing
The latest innovation in the treatment of ED has arrived in the form of a simpler, once-daily dosing schedule for tadalafil, unlinking the temporal association of the medication and the sexual encounter. The unnatural process of taking a medication just prior to sex is a negative aspect of ED treatment for many patients. The 17.5 hour half-life of tadalafil lends itself to daily dosing because steady-state plasma concentrations are attained within five days of initiating daily dosing. Additionally, at steady-state concentration, the daily exposure is 1.6-fold greater than the same dose taken intermittently. Therefore, after 5 days of once-daily dosing, the plasma concentration of tadalafil (Cialis) achieved with a 2.5 mg and 5 mg dose is 4 mg and 8 mg, respectively. The FDA announced approval for once-daily dosing of tadalafil in January 2008 after a thorough review of the studies outlined below.
ED after prostate cancer treatment
All of the available prostate cancer treatments, including radical prostatectomy, external beam radiation therapy, brachytherapy, cryotherapy, androgen-deprivation therapy, and even active surveillance alone, can result in ED. ED after prostate cancer treatment includes both organic and psychogenic causes, as significant anxiety and depression may result from a diagnosis of prostate cancer, leading to psychogenic ED.
The most important risk for organic ED after prostate cancer treatment of any type is damage to the cavernosal nerves. Walsh first described the technique for sparing the bilateral neurovascular bundles to better preserve erectile function, and a bilateral nerve sparing radical prostatectomy (BNSRP) is the surgical standard for prostate cancer today. Approximately 155,000 prostatectomies were performed in the United States in 2005 according to hospital discharge data. Potency in men after open BNSRP has a wide reported range of 10% to 97% in the literature. Of 1288 men who underwent radical prostatectomy as part of the Prostate Cancer Outcomes Study, only 28% had erections sufficient for intercourse at 5 years.
ED secondary to diabetes mellitus
ED is a common problem afflicting over a third of all men with diabetes mellitus type 2, and diabetes is independently responsible for a 3- to 4-fold increase in the risk of ED according to a survey of 1460 diabetic men. ED is strongly related to the severity of diabetes, with a higher incidence in patients with a long history of diabetes, patients using insulin, and patients with microvascular complications of diabetes. Diabetic men with ED also have significantly worse disease-specific health-related quality of life.
Safety and drug interactions
As with every PDE5 inhibitor, tadalafil is absolutely contraindicated with nitrate medications for angina pectoris secondary to the potentiated hypotensive effect the drugs can have together. Because of the longer half-life, treatment with nitrate medications must be deferred for at least 48 hours after ingestion of tadalafil, compared with 24 hours for sildenafil (Viagra) and vardenafil (Levitra).
The cardiac effects of PDE5 inhibitors have received considerable attention because the drugs were originally studied as a treatment for angina pectoris secondary to their action of smooth muscle relaxation. All of the PDE5 inhibitor trials have tediously monitored study participants’ vital signs, particularly heart rate and blood pressure, monitored drug effects on cardiac electrophysiology, and tabulated the numbers of cardiovascular adverse events.
Adverse events
A large study of 2102 men from 11 different multicentered, randomized, double-blind, placebo controlled trials of tadalafil reported the drug is well tolerated overall. Fifty-one percent of men using tadalafil 20 mg had at least one adverse event (AE), but only 3.2% discontinued treatment. The most common AEs reported with the 20 mg dose were headache (15%), dyspepsia (8%), and back pain (5%) (Table 1). Most AEs are a result of vasodilation of vascular beds other than in the penis.
Difficult-to-treat ED
In the two trials mentioned in the previous section, the patient population was largely a primary care population of relatively healthy men with ED of varying severities and etiologies. To the contrary, a multicentered, randomized, double-blind, placebo controlled trial evaluated how tadalafil 20 mg improved ED in men presenting to tertiary care centers with more severe, organic ED and with more comorbid medical conditions than previous studies.
Tadalafil is an orally administered drug for treating impotence (erectile dysfunction), that initially was developed by the biotechnology company ICOS, and then developed and marketed world-wide as Cialis, by Lilly ICOS, LLC, the joint venture of ICOS Corporation and Eli Lilly and Company. Cialis tablets, in 5mg, 10mg, and 20mg doses, are yellow, film-coated, and almond-shaped.
