An Actual Use Study of Tamsulosin in Men with Bothersome Urinary Symptoms in a Simulated Over-the-Counter Setting.

INTRODUCTION: We assessed the ability of men with bothersome urinary symptoms to use an over-the-counter tamsulosin (0.4 mg) product concordant with the information in the proposed drug facts label in a simulated over-the-counter setting. METHODS: Eligibility for this 24-week study was determined by a phone interview. Men who reported not using (nonprescription users) or using (prescription users) a prescription medicine for benign prostatic hyperplasia at screening/baseline reviewed the proposed over-the-counter tamsulosin product. They could then choose to purchase this product and enter the actual use phase. The primary objective was to assess the proportion of nonprescription users compliant with "stop use" directions (performance threshold upper bound of 95% CI 10% or less). Secondary objectives included assessing the proportion of nonRx users compliant with other prespecified instructions on the proposed drug facts label and evaluating adverse events. Analyses were based on outcomes mitigated by a panel of urologists. RESULTS: Of the 4,508 men screened 3,929 were eligible for product review and 1,117 entered the home use phase. Overall 1,074 men (nonprescription users 924, prescription users 150) purchased and used tamsulosin. Mean±SD age was 62.6±10.7 and 66.5±8.8 years, respectively. The primary end point was met, as only 2 of 924 nonprescription users (0.2%, 95% CI 0.0-0.8) reported a "stop use" condition within the first 12 weeks and did not appropriately stop use or initiate contact with a doctor. No unexpected safety concerns were observed. CONCLUSIONS: Results indicate that self-directed use by men interested in using an over-the-counter tamsulosin product was in line with the drug facts label instructions implemented in this study and no unexpected safety concerns were identified.

Pharmacokinetics of BILR 355 after multiple oral doses coadministered with a low dose of ritonavir.

The pharmacokinetics and safety of BILR 355 following oral repeated dosing coadministered with low doses of ritonavir (RTV) were investigated in 12 cohorts of healthy male volunteers with a ratio of 6 to 2 for BILR 355 versus the placebo. BILR 355 was given once a day (QD) coadministered with 100 mg RTV (BILR 355/r) at 5 to 50 mg in a polyethylene glycol solution or at 50 to 250 mg as tablets. BILR 355 tablets were also dosed at 150 mg twice a day (BID) coadministered with 100 mg RTV QD or BID. Following oral dosing, BILR 355 was rapidly absorbed, with the mean time to maximum concentration of drug in serum reached within 1.3 to 5 h and a mean half-life of 16 to 20 h. BILR 355 exhibited an approximately linear pharmacokinetics for doses of 5 to 50 mg when given as a solution; in contrast, when given as tablets, BILR 355 displayed a dose-proportional pharmacokinetics, with a dose range of 50 to 100 mg; from 100 to 150 mg, a slightly downward nonlinear pharmacokinetics occurred. The exposure to BILR 355 was maximized at 150 mg and higher due to a saturated dissolution/absorption process. After oral dosing of BILR 355/r, 150/100 mg BID, the values for the maximum concentration of drug in plasma at steady state, the area under the concentration-time curve from 0 to the dose interval at steady state, and the minimum concentration of drug in serum at steady state were 1,500 ng/ml, 12,500 h.ng/ml, and 570 ng/ml, respectively, providing sufficient suppressive concentration toward human immunodeficiency virus type 1. Based on pharmacokinetic modeling along with the in vitro virologic data, several BILR 355 doses were selected for phase II trials using Monte Carlo simulations. Throughout the study, BILR 355 was safe and well tolerated.

Use of 0.06% ipratropium bromide nasal spray in children aged 2 to 5 years with rhinorrhea due to a common cold or allergies.

BACKGROUND: Rhinorrhea from common colds or allergies in children is similar to that in adults, yet there are few data on the use of ipratropium bromide nasal spray in children younger than 5 years. OBJECTIVE: To evaluate the safety and efficacy of 0.06% ipratropium bromide nasal spray in 2- to 5-year-old children with rhinorrhea from a common cold or allergies. METHODS: A total of 230 children (43 with common colds and 187 with allergies) participated in an open-label, multicenter study. Patients with a common cold received ipratropium bromide nasal spray (84 microg per nostril) 3 times daily for 4 days; those with allergies received ipratropium bromide nasal spray (42 microg per nostril) 3 times daily for 14 days. RESULTS: In the common cold and allergy groups, 91% and 90% of the parents, respectively, found that ipratropium bromide was either "very useful" or "somewhat useful." Furthermore, 67% and 91% of parents in the common cold and allergy groups, respectively, found that administration of a nasal spray was either "extremely easy" or "very easy." Symptom scores were improved from baseline in both groups. The nasal spray was well tolerated and was not associated with serious or systemic anticholinergic adverse effects. Most adverse events were infrequent and mild to moderate, and study discontinuation due to an adverse event occurred in less than 3% of patients. CONCLUSIONS: The 0.06% ipratropium bromide nasal spray, 42 or 84 microg per nostril 3 times daily, is easy to administer, safe, and effective for the control of rhinorrhea in children aged 2 to 5 years with a common cold or allergies.