Cost-effectiveness of a fixed-dose combination of solifenacin and oral controlled adsorption system formulation of tamsulosin in men with lower urinary tract symptoms associated with benign prostatic hyperplasia.

BACKGROUND: Storage symptoms, associated with benign prostatic hyperplasia (BPH), often co-exist with voiding symptoms in men with lower urinary tract symptoms (LUTS). Storage symptoms are likely to be most bothersome, and may not be adequately resolved by treatment with α-blocker or antimuscarinic monotherapy. A recent randomised controlled phase 3 trial (NEPTUNE) demonstrated that a fixed-dose combination (FDC) of solifenacin 6 mg plus an oral controlled absorption system (OCAS™) formulation of tamsulosin (TOCAS, 0.4 mg) improved storage symptoms, as well as quality of life, compared with TOCAS alone in men with moderate-to-severe storage symptoms and voiding symptoms. This analysis aimed to assess the cost-effectiveness of a FDC tablet of solifenacin 6 mg plus TOCAS relative to tolterodine plus tamsulosin given concomitantly, from the perspective of the UK National Health Service (NHS). METHODS: A Markov model was developed for men aged ≥45 years with LUTS/BPH who have moderate-to-severe storage symptoms and voiding symptoms. The model calculated cost-effectiveness over an analytical time horizon of 1 year and estimated total treatment costs, quality adjusted life years (QALYs) and incremental cost-effectiveness ratio. RESULTS: The FDC tablet of solifenacin 6 mg plus TOCAS was associated with lower total annual costs (£860 versus £959) and increased QALYs (0.839 versus 0.836), and was therefore dominant compared with tolterodine plus tamsulosin. Time horizon, discontinuation or withdrawal rates, drug cost and utility values were the main drivers of cost-effectiveness. The probability that the FDC tablet of solifenacin 6 mg plus TOCAS is cost-effective was 100% versus tolterodine plus tamsulosin, at a willingness-to-pay threshold of £20,000/QALY gained. CONCLUSIONS: The FDC tablet of solifenacin 6 mg plus TOCAS provides important clinical benefits and is a cost-effective treatment strategy in the UK NHS compared with tolterodine plus tamsulosin for men with both storage and voiding LUTS/BPH.

The buccal mucosa as an alternative route for the systemic delivery of risperidone.

The purpose of this study was to investigate the potential of the buccal mucosa for the systemic delivery of risperidone (RISP), and to determine the impact of Azone® (AZ) on the transport of RISP via this route. The permeability of RISP through porcine buccal mucosa was assessed in modified Ussing chambers at various concentrations to determine the mechanisms involved in transport across the tissue. The effect of AZ was assessed by administering AZ 5% (w/w) to the tissue as a pretreatment or together with RISP in solution or in a mucoadhesive gel formulation. RISP permeated the buccal mucosa via a passive diffusion mechanism and pretreatment or coadministration of AZ 5% did not significantly modify the permeation of RISP. Application of a RISP mucoadhesive gel resulted in a steady state flux of 64.65 ± 8.0 µg/cm(2)/h, which when extrapolated to the in vivo setting, is predicted to result in RISP plasma concentrations of 11.2-56.1 µg/L for mucosal application areas between 2 and 10 cm(2). Given that these predicted concentrations are within the therapeutic range of RISP required in humans, delivery of RISP via the buccal mucosa has the potential to result in therapeutically relevant plasma concentrations for the treatment of schizophrenia.