Ludwig Mehlburger

Effect of diabetes on lower urinary tract symptoms in patients with benign prostatic hyperplasia

PURPOSE Several studies have suggested a specific association between the presence and/or symptom intensity of benign prostatic hyperplasia (BPH) and diabetes but to our knowledge no definitive conclusion has been reached. Therefore, we examined the intensity of lower urinary tract symptoms in a large cohort of men with BPH with and without diabetes. We then determined whether the alpha1-adrenoceptor antagonist tamsulosin similarly improved lower urinary tract symptoms in patients with BPH with or without diabetes. MATERIALS AND METHODS The International Prostate Symptom Score (I-PSS), maximum flow rate and post-void residual were determined in 9,856 men with clinically diagnosed BPH, of whom 1,290 also had diabetes, at baseline and after a 12 week, open label course of 0.4 mg. tamsulosin daily. RESULTS Logistic regression of the baseline data indicated that older age and I-PSS were independently associated with a statistically significant increase in the odds ratio of having diabetes. Accordingly, diabetics had a significantly greater baseline I-PSS and smaller maximum flow rate than non-diabetic patients on age-adjusted analysis, while residual urine was not significantly altered. Tamsulosin markedly improved lower urinary tract symptoms. The extent of improvement was similar in diabetic and nondiabetic patients, although some slight differences reached statistical significance due to large patient numbers. CONCLUSIONS The severity of lower urinary tract symptoms in patients with BPH and the likelihood of having diabetes are significantly associated. Within the limitations of an open label, observational study tamsulosin appears to reduce lower urinary tract symptoms similarly in patients with BPH with or without diabetes.

TAMSULOSIN TREATMENT OF 19,365 PATIENTS WITH LOWER URINARY TRACT SYMPTOMS: DOES CO-MORBIDITY ALTER TOLERABILITY?

PURPOSE We compare the tolerability and blood pressure effects of 0.4 mg. tamsulosin once daily in patients with lower urinary symptoms suggestive of benign prostatic obstruction with or without concomitant disease and/or antihypertensive medication. MATERIALS AND METHODS Data from 2 open label, observational studies (study 1, 9,507 patients treated for 4 weeks and study 2, 9,858 patients treated for 12 weeks) were analyzed for global tolerability and effects on blood pressure stratifying for co-morbidity (none, diabetes, hypertension, other cardiovascular disease) and co-medication (diuretics, beta-blockers, calcium channel blockers, angiotensin converting enzyme inhibitors). RESULTS Overall 90 and 95% of patients in studies 1 and 2, respectively, reported good or very good tolerability. While global tolerability was slightly reduced in patients with concomitant disease or some forms of medication (p < 0.05), it was rated as good or very good by more than 90 and 95% of patients even in those groups. In control patients, that is those with neither co-morbidity nor co-medication, the tamsulosin induced blood pressure reductions were similar to those previously reported for placebo treatment but were statistically significant (p < 0.05). Mean additional blood pressure reductions in patients with concomitant disease or medication were not more than 2 mm. Hg. CONCLUSIONS Tamsulosin is well tolerated and has marginal effects on blood pressure in the majority of patients. It largely maintains its good global tolerability and minimal blood pressure effects in patients with cardiovascular co-morbidity or diabetes, or those on co-medication with antihypertensive agents.

Tamsulosin: Real Life Clinical Experience in 19,365 Patients

Objective: To compare the efficacy, global tolerability and blood pressure effects of tamsulosin (0.4 mg once daily) in subgroups of patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO). Methods: Data from two open-label, observational studies (Study I: 9,507 patients treated for 4 weeks, Study II: 9,858 patients treated for 12 weeks) were analyzed to compare efficacy, global tolerability and effects on blood pressure in subgroups of patients. Results: The efficacy of tamsulosin was largely unaffected by age or previous phytotherapy; in patients with severe symptoms, the efficacy was at least as large as in those with mild or moderate symptoms. More than 90% of patients reported a good or very good tolerability; in a multivariate analysis, this was slightly reduced in patients with concomitant disease but not affected by antihypertensive co-medication or baseline blood pressure. In patients without co-morbidity or co-medication, the tamsulosin-induced blood pressure reductions were similar to those previously reported for placebo treatment; mean additional blood pressure reductions in patients with concomitant disease or medication was not more than 2 mm Hg. Patients who had previously been treated with β-sitosterol, other plant extracts or finasteride reported tamsulosin to be more effective than their previous treatment. Patients who had previously received β-sitosterol or other plant extracts rated the global tolerability of tamsulosin to be similar to that of their previous treatment, while those who had previously received finasteride or other α1-adrenoceptor antagonists rated the global tolerability of tamsulosin to be significantly better than that of their previous treatment. Conclusions: We conclude that tamsulosin is efficacious in all types of patients with LUTS suggestive of BPO. It is globally well tolerated and has marginal effects on blood pressure, including the vast majority of patients with cardiovascular comorbidity, diabetes or on antihypertensive comedication.

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.

Does the time of administration (morning or evening) affect the tolerability or efficacy of tamsulosin

Objective To determine whether the time of dosing (morning or evening) affects the tolerability or efficacy of tamsulosin in the treatment of lower urinary tract symptoms.