Factors Associated With Nocturia-Related Quality of Life in Men With Lower Urinary Tract Symptoms and Treated With Tamsulosin Oral Controlled Absorption System in a Non-Interventional Study.

Nocturia impairs quality of life (QoL). We have performed a non-interventional study in which men with lower urinary tract symptoms (LUTS) were treated for at least 3 months with tamsulosin oral controlled absorption system (0.4 mg q.d.). Other than observing efficacy and tolerability of this drug formulation, the study was designed to explore the relative roles of number of nocturia episodes and of non-urological causes of nocturia on nocturia-related QoL at baseline and treatment-associated changes thereof. The study enrolled 5775 men seeking treatment of their LUTS. Tamsulosin improved LUTS, e.g. International Prostate Symptom Score from 19.5 ± 5.9 to 10.1 ± 4.9 (means ± SD). This was associated by clinically meaningful improvements in the Nocturia QoL score (from 45 ± 19 to 73 ± 17 points) and other QoL scores. Number of nocturnal voids was the key driver of all QoL scores at baseline; change of number of nocturia episodes that of improvement of all QoL scores upon treatment. In contrast, non-urological causes of nocturia such as heart failure, diabetes, sleep apnea, fluid or alcohol intake or use of diuretics or hypnotics had only small if any effects on baseline QoL or treatment-associated improvements thereof. The observed effects of non-urological causes on QoL apparently were largely driven by their effect on number of nocturnal voids. These data further support the idea that improvement of nocturia may be an important treatment goal in male LUTS.

Effects of strong CYP2D6 and 3A4 inhibitors, paroxetine and ketoconazole, on the pharmacokinetics and cardiovascular safety of tamsulosin.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Tamsulosin metabolism involves both CYP2D6 and 3A4. However, data on potential drug-drug interactions between tamsulosin and inhibitors of CYP2D6 and 3A4 are limited and information on potential pharmacodynamic consequences of such pharmacokinetic interactions is missing. WHAT THIS STUDY ADDS: This study provides information on the drug-drug interactions of tamsulosin with strong CYP2D6 and strong CYP3A4 inhibitors after single dose administration in healthy subjects. AIM: To determine the effect of the strong CYP2D6 inhibitor paroxetine and strong CYP3A4 inhibitor ketoconazole on the pharmacokinetics and safety (orthostatic challenge) of tamsulosin. METHODS: Two open-label, randomized, two-way crossover studies were conducted in healthy male volunteers (extensive CYP2D6 metabolizers). RESULTS: Co-administration of multiple oral doses of 20 mg paroxetine once daily with a single oral dose of the 0.4 mg tamsulosin HCl capsule increased the adjusted geometric mean (gMean) values of C(max) and AUC(0,∞) of tamsulosin by factors of 1.34 (90% CI 1.21, 1.49) and 1.64 (90% CI 1.44, 1.85), respectively, and increased the terminal half-life (t(1/2) ) of tamsulosin HCl from 11.4 h to 15.3 h. Co-administration of multiple oral doses of 400 mg ketoconazole once daily with a single oral dose of the 0.4 mg tamsulosin increased the gMean values of C(max) and AUC(0,∞) of tamsulosin by a factor of 2.20 (90% CI 1.96, 2.45) and 2.80 (90% CI 2.56, 3.07), respectively. The terminal half-life was slightly increased from 10.5 h to 11.8 h. These pharmacokinetic changes were not accompanied by clinically significant alterations of haemodynamic responses during orthostatic stress testing. CONCLUSION: The exposure to tamsulosin is increased upon co-administration of strong CYP2D6 inhibitors and even more so of strong 3A4 inhibitors, but neither PK alteration was accompanied by clinically significant haemodynamic changes during orthostatic stress testing.

Association of hypertension with symptoms of benign prostatic hyperplasia.

PURPOSE: We determined whether the intensity of benign prostatic hyperplasia (BPH) symptoms and arterial hypertension are associated. MATERIALS AND METHODS: Baseline data from a large sample of men seeking treatment for BPH symptoms were analyzed retrospectively. BPH symptom intensity (assessed by the International Prostatic Symptom Score [I-PSS] or urinary flow rate [Qmax]) and blood pressure were determined in 9,857 patients with BPH. Normotension was defined as a diastolic blood pressure of 90 mm Hg or less, the absence of the diagnosis hypertension and the lack of antihypertensive medication (in 4,725). Hypertension was concomitantly defined as a diastolic blood pressure of greater than 90 mm Hg (in 1,727), being diagnosed with hypertension (1,950) or the current prescription of anti-hypertensive drugs (3,360 patients). RESULTS: When age and presence of hypertension were used as the independent explanatory variables, each year of age contributed 0.13 points and measured hypertension 1.60 points to I-PSS as the dependent response variable. Similar results were obtained with Qmax as the dependent response variable. In a logistic regression procedure using age, I-PSS and Qmax as the independent explanatory variables, each year of age and each I-PSS point significantly increased the risk of being hypertensive by 5.3% and 5.0%, respectively, while Qmax did not yield a statistically significant contribution to that risk. CONCLUSIONS: We conclude that a significant, age independent association exists between BPH symptoms and hypertension. This finding indicates a common pathophysiological factor for both disease states such as increased sympathetic activity.