Evaluation of Potential Urologic Prescription Drug Savings With Mark Cuban Cost Plus Drug Company.

INTRODUCTION: Mark Cuban Cost Plus Drug Company (MCCPDC) launched in 2022 with a goal to decrease prescription drug costs. Thus far, research has focused on possible savings if Medicare purchased its annual volume of drugs at MCCPDC prices. The aim of this study is to analyze if MCCPDC can offer savings directly to urologic patients compared with other mail-order pharmacies, local pharmacies, and with patients using health insurance. METHODS: Twelve drugs used to treat urological diseases available on MCCPDC were analyzed. Pricing data of 30-tab and 90-tab prescriptions from MCCPDC, other mail-order pharmacies, and local in-person pharmacies near our zip code 40508 (Lexington, Kentucky) were compiled. To compare if MCCPDC could offer savings to patients using health insurance to fill their prescriptions, out-of-pocket drug costs for patients from the 2020 and 2021 Medical Expenditure Panel Survey and the 2021 Medicare Part D spending data were extracted. RESULTS: Greater savings at MCCPDC were found at 90-tab prescriptions, but overall variability in prices existed. When comparing without health insurance, 9 of 12 drugs at MCCPDC were cheaper at 90 tabs with solifenacin and tadalafil saving $20 and $12 per prescription. When considering patients using insurance, abiraterone, sildenafil, and tadalafil offered savings on out-of-pocket costs at 30- and 90-tab prescriptions. CONCLUSIONS: MCCPDC may offer cheaper prices for patients filling urologic medications, especially at 90-tab prescriptions. This study is the first to show patients could save money using MCCPDC and has implications for physician counseling when prescribing common urologic drugs.

A Cost Analysis of Phosphodiesterase Type 5 Inhibitors in the United States.

OBJECTIVE: To perform a cost analysis of generic and brand-name Phosphodiesterase Type 5 (PDE5) inhibitors at different dosages and pharmacies across the US. METHODS: Using an all-payer retail pharmacy-claims database, we analyzed prescription drug data for three generic and six brand-name oral PDE5 inhibitors at different dosages across US chain and independent pharmacies in 2019. RESULTS: We obtained cash price data from 60,186 pharmacies (35,976 chain and 24,210 independent). The nationwide mean cash price per unit (PPU) ranged from $8.6 ± 5.2 (sildenafil 20 mg at chain pharmacies) to $107.1 ± 71 (Adcirca 20 mg at independent pharmacies) equal to 1145.3% difference. Chain pharmacies provided significantly lower average prices for one brand-name and six generic PDE5 inhibitors. Tadalafil PPU was cheaper at higher quantities, however, PPU increased with quantity prescribed for sildenafil. Looking at the top 10 metropolitan statistical areas, the highest PPUs were observed for tadalafil (Cialis) 10 mg and sildenafil (Viagra) 50 mg in Atlanta ($67.4 ± 8.7) and Los Angeles ($50.3 ± 24.0), while New York ($9.7 ± 2.6) and Miami ($27.9 ± 16.4) had the lowest PPUs for tadalafil (Cialis) 5 mg and sildenafil (Viagra) 100 mg, respectively. CONCLUSION: A substantial variability in PDE5 inhibitor cash prices exists across manufacturer, dosage, quantity, pharmacy type, and location. In addition, the pricing does not necessarily correlate with the regional socioeconomic factors. This highlights the importance of provider awareness and patient counseling on drug price including potentially assisting patients in identifying opportunities for cost savings.

Fetal Biometric Assessment and Infant Developmental Prognosis of the Tadalafil Treatment for Fetal Growth Restriction.

Background and Objectives: Tadalafil is expected to treat fetal growth restriction (FGR), a risk factor for stillbirth and neonatal morbidity. This study aimed to evaluate the fetal biometric growth pattern of fetuses with FGR treated with tadalafil by ultrasonographic assessment. Materials and Methods: This was a retrospective study. Fifty fetuses diagnosed with FGR and treated by maternal administration of tadalafil and ten controls who received conventional treatment at Mie University Hospital from 2015 to 2019 were assessed. Fetal biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), femur length (FL), and estimated fetal weight (EFW) at the start of treatment and at two weeks and four weeks of treatment were mainly assessed by ultrasound examination. The Wilcoxon signed-rank test was used to assess the measures. The Kyoto Scale of Psychological Development (KSPD) was used to assess the developmental prognosis on tadalafil-treated children at 1.5 years of corrected age (CA) and 3 years old. Results: The median gestational age at the start of treatment was 30 and 31 weeks in the tadalafil and control groups, respectively, and the median gestational age at delivery was 37 weeks in both groups. The Z-score of HC was significantly increased at 4 weeks of treatment (p = 0.005), and the umbilical artery resistance index was significantly decreased (p = 0.049), while no significant difference was observed in the control group. The number of cases with an abnormal score of less than 70 on the KSPD test was 19% for P-M, 8% for C-A, 19% for L-S, and 11% for total area at 1.5 years CA. At 3 years old, the respective scores were 16%, 21%, 16%, and 16%. Conclusions: Tadalafil treatment for FGR may maintain fetal HC growth and infants' neuro-developmental prognosis.

Phosphodiesterase 5 Inhibitor for Pediatric Pulmonary Arterial Hypertension: A Cost-Utility Analysis.

OBJECTIVES: Despite the growing evidence of efficacy, scarce information exists regarding the cost of tadalafil to improve the functional classes of pediatric patients with pulmonary arterial hypertension. This study aims to determine the cost-utility of tadalafil compared sildenafil to treat pediatric patients with pulmonary arterial hypertension in Colombia. METHODS: A Markov model was developed to compare expected costs, outcomes, and quality-adjusted life-years of sildenafil and tadalafil in pediatric patients with pulmonary arterial hypertension. The model was analyzed probabilistically, and a value of information analysis was conducted to inform the value of conducting further research to reduce current uncertainties in the evidence base. Cost-effectiveness was evaluated at a willingness-to-pay value of US $5180. RESULTS: The mean incremental cost of tadalafil versus sildenafil is US $15 270. The 95% credible interval for the incremental cost ranges from US $28 033.65 to US $5940.86. The mean incremental benefit of tadalafil versus sildenafil is 1.00 quality-adjusted life-years (QALY). The 95% credible interval for the incremental benefit ranges from 1.88 to 0.31 QALY. The expected incremental cost per QALY is estimated at US $15 286. There is a probability less than 1% that tadalafil is more cost-effective than sildenafil at a threshold of US $5180 per QALY. Form the value of information analysis, the theoretical upper bound on the value of further research was US $9.298 for Colombia. CONCLUSION: Our economic evaluation shows that tadalafil is not cost-effective regarding sildenafil to treat pediatric patients with pulmonary arterial hypertension in Colombia. Our study provides evidence that should be used by decision-makers to improve clinical practice guidelines.

Contemporary cost-analysis comparison of direct-to-consumer vs. traditional prescriptions of phosphodiesterase-5 inhibitors.

After a focused telehealth visit, patients can now access phosphodiesterase-5 inhibitor (PDE5 inhibitor) prescriptions through online direct-to-consumer (DTC) healthcare companies. This study seeks to quantify the cost of DTC PDE5 inhibitor treatment compared to a traditional physician visit and local pharmacy prescription. Two DTC companies, two compounding pharmacies with national reach, three online Canadian pharmacies, and sixteen American pharmacy chains were queried for prices of 90-day regimens of common PDE5 inhibitors. Prices for chains were determined using their publicly available price on GoodRx® with coupon. Cost of physician visit was determined using 2020 Center for Medicare and Medicaid Services reimbursement for a level 3 new patient visit. For sildenafil 20 mg, a physician visit and local prescription cost a low of $125.45 compared to $144.35 for compounding, $169.34 for Canadian, and $195.00 for DTC. For sildenafil 100 mg, a physician visit and local prescription cost a low of $137.16 compared to $289.35 for compounding, $200.36 for Canadian, and $900.00 for DTC. For tadalafil 5 mg, a physician visit and local prescription cost a low of $125.80 compared to $169.35 for compounding, $195.34 for Canadian, and $720.00 for DTC. For tadalafil 20 mg, a physician visit and local prescription cost a low of $161.00 compared to $289.35 for compounding, $229.00 for Canadian, and $2880.00 for DTC. Thus, local pharmacies, in conjunction with online coupons, consistently provide a markedly less-expensive option for fulfillment of PDE5 inhibitor prescriptions than online DTC services.

Discontinuation Rates of Tadalafil Alone and in Combination with a-Blockers in the Treatment of Male Lower Urinary Tract Symptoms with or without Coexisting Erectile Dysfunction: A Systematic Review and Meta-Analysis.

Purpose: We examined the discontinuation rates of tadalafil alone and in combination with a-blockers (ABs) for the treatment of male lower urinary tract symptoms (LUTS), with or without erectile dysfunction (ED). Materials and Methods: We searched the EMBASE, PubMed, Web of Science, Scopus, Cochrane Library, and ClinicalTrials.gov databases for studies published until May 15, 2022. The discontinuation rates associated with LUTS medications were subsequently analyzed by meta-analysis. Results: Forty-four studies, including 1724 discontinued patients, were included. The combined discontinuation rate was 12.78% (95% confidence interval (CI) 9.89-15.98%), and the discontinuation rates because of adverse events and lack of efficacy were 4.56% (95% CI 3.39-5.90%) and 3.30% (95% CI 1.53-5.72%), respectively. Conclusions: The discontinuation rate of tadalafil alone or in combination with ABs for LUTS with or without ED was relatively low and varied according to the study type. Patients receiving monotherapy or combination therapy were similarly likely to abandon treatment. Treatment with a fixed-dose combination was associated with better persistence than with a free-dose combination. These data may help guide clinicians in selecting drug regimens when making decisions. Factors associated with treatment withdrawal need to be determined through high-quality clinical studies to reduce the drug discontinuation rate, which will ultimately reduce healthcare costs and improve patient outcomes.

Assessment of the intracavernosal injection platelet-rich plasma in addition to daily oral tadalafil intake in diabetic patients with erectile dysfunction non-responding to on-demand oral PDE5 inhibitors.

This study aimed to evaluate the effectiveness of ICI of platelet-rich plasma (PRP) in addition to daily oral tadalafil intake in diabetic erectile dysfunction (ED) patients non-responding to PDE5 inhibitors. Overall, 48 patients complaining of ED non-responding to on-demand PDE5 inhibitors were allocated into 2 equal groups, diabetics and non-diabetics that were given a daily dose of 5 mg tadalafil plus vardenafil 20 mg on demand during the study besides being subjected to 3 doses of ICI of PRP, 4 weeks apart. Responses to on-demand PDE5 inhibitors, International index of erectile function-5 (IIEF-5) score, erection hardness scores (EHS) and pharmaco-dynamic duplex studies were assessed. After PRP injections, 33% and 50% of cases were satisfied with on-demand PDE5 inhibitors, respectively, whereas 41% and 66% of them showed improved EHS response. Compared with baseline scores, the mean IIEF-5 scores were significantly improved after PRP therapy in the diabetic ED group (12.1 vs. 8.04, p = 0.003) as well as in the non-diabetic ED group (14.8 vs. 10.2, p = 0.001) linked to pharmaco-penile duplex readings. Both good and fair diabetic control exhibited significant responses to ICI therapy of PRP compared with bad controlled cases. The significant improvement included; the IIEF-5 score increase (86.7%, 126% vs. 16.1%), improved EHS as well as penile duplex readings. Baseline HbA1C demonstrated a significant negative correlation with IIEF-5 score before (p = 0.019) and after PRP therapy (p = 0.002) respectively. It could be concluded that ICI of PRP could be an effective therapy for treating ED patients non-responding to on-demand oral PDE5 treatment.

Assessment of the value of measuring soluble fms-like tyrosine kinase-1 and placental growth factor levels following administration of tadalafil to treat fetal growth restriction.

PURPOSE: The aim of this study was to measure the blood levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) before and after tadalafil treatment in patients with fetal growth restriction. MATERIALS AND METHODS: Maternal blood was collected from 13 women before and 2 weeks after tadalafil administration in the TADAFER II trial. The tadalafil treatment was conducted in addition to the conventional FGR treatment. As a control, maternal blood was also collected from 11 women before and 2 weeks after conventional treatment for fetal growth restriction. Blood sFlt-1 and PlGF were measured and the sFlt-1/PlGF ratio was calculated. Student's t-test was used to statistically analyze differences in the sFlt-1 and PlGF levels, and in the sFlt-1/PlGF ratios. RESULTS: In both treatment groups, the levels of sFlt-1 and PlGF before and after treatment were not significantly different from each other. The sFlt-1/PlGF ratio was 2.0 ± 1.0 before and 17.6 ± 11.3 after treatment in the control group (p=.04). The sFlt-1/PlGF ratio was 2.2 ± 1.1 before and 22.2 ± 10.6 after tadalafil treatment in the tadalafil group (p=.06). The sFlt-1/PlGF ratios before and after tadalafil treatment were significantly increased in the control group. In both treatment groups, the sFlt-1/PlGF ratios before and after treatment were less than 38. CONCLUSIONS: We conclude that the levels of sFlt-1 and PlGF were not significantly different as a result of tadalafil treatment. Further studies are needed to understand the mechanism of action of tadalafil in the treatment of fetal growth restriction.

Detection Method of Falsified Medicines by Using a Low-Cost Raman Scattering Spectrometer Combined with Soft Independent Modeling of Class Analogy and Partial Least Squares Discriminant Analysis.

There are many reports of falsified medicines that may cause harm to patients. A rapid and simple method of identifying falsified medicines that could be used in the field is required. Although Raman scattering spectroscopy has become popular as a non-destructive analysis, few validation experiments on falsified medicines that are actually distributed on the market have been conducted. In this study, we validated a discriminant analysis using an ultra-compact, portable, and low-cost Raman scattering spectrometer combined with multivariate analysis. The medicines were three types of erectile dysfunction therapeutic tablet and one type of antifungal tablet: tadalafil (Cialis), vardenafil hydrochloride (Levitra), sildenafil citrate (Viagra), and fluconazole (Diflucan), which is sometimes advertised as female Viagra. For each medicine, the authentic standard product and products obtained by personal import via the internet (genuine or falsified) were used. Discriminant analyses were performed on the Raman spectra combined with soft independent modeling of class analogy (SIMCA) and partial least squares discriminant analysis (PLS-DA). It was possible to identify all falsified samples by SIMCA using the standard product model for all four products. Using the PLS-DA using the PLS models of the four standard products, falsified Levitra and Diflucan samples were classified correctly, although some falsified Cialis and all Viagra samples also belonged to the standard class. In this study, SIMCA might be more suitable than PLS-DA for identifying falsified medicines. A spectroscopic module that combines the low-cost Raman scattering spectroscopy with SIMCA might contribute to the rapid identification of falsified medicines in the field.

Assessment of Combination Therapies vs Monotherapy for Erectile Dysfunction: A Systematic Review and Meta-analysis.

Importance: Combining 2 first-line treatments for erectile dysfunction (ED) or initiating other modalities in addition to a first-line therapy may produce beneficial outcomes. Objective: To assess whether different ED combination therapies were associated with improved outcomes compared with first-line ED monotherapy in various subgroups of patients with ED. Data Sources: Studies were identified through a systematic search in MEDLINE, Cochrane Library, and Scopus from inception of these databases to October 10, 2020. Study Selection: Randomized clinical trials or prospective interventional studies of the outcomes of combination therapy vs recommended monotherapy in men with ED were identified. Only comparative human studies, which evaluated the change from baseline of self-reported erectile function using validated questionnaires, that were published in any language were included. Data Extraction and Synthesis: Data extraction and synthesis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Main Outcomes and Measures: A meta-analysis was conducted that included randomized clinical trials that compared outcomes of combination therapy with phosphodiesterase type 5 (PDE5) inhibitors plus another agent vs PDE5 inhibitor monotherapy. Separate analyses were performed for the mean International Index of Erectile Function (IIEF) score change from baseline and the number of adverse events (AEs) by different treatment modalities and subgroups of patients. Results: A total of 44 studies included 3853 men with a mean (SD) age of 55.8 (11.9) years. Combination therapy compared with monotherapy was associated with a mean IIEF score improvement of 1.76 points (95% CI, 1.27-2.24; I2 = 77%; 95% PI, -0.56 to 4.08). Adding daily tadalafil, low-intensity shockwave therapy, vacuum erectile device, folic acid, metformin hydrochloride, or angiotensin-converting enzyme inhibitors was associated with a significant IIEF score improvement, but each measure was based on only 1 study. Specifically, the weighted mean difference (WMD) in IIEF score was 1.70 (95% CI, 0.79-2.61) for the addition of daily tadalafil, 3.50 (95% CI, 0.22-6.78) for the addition of low-intensity shockwave therapy, 8.40 (95% CI, 4.90-11.90) for the addition of a vacuum erectile device, 3.46 (95% CI, 2.16-4.76) for the addition of folic acid, 4.90 (95% CI, 2.82-6.98) for the addition of metformin hydrochloride and 2.07 (95% CI, 1.37-2.77) for the addition of angiotensin-converting enzyme inhibitors. The addition of α-blockers to PDE5 inhibitors was not associated with improvement in IIEF score (WMD, 0.80; 95% CI, -0.06 to 1.65; I2 = 72%). Compared with monotherapy, combination therapy was associated with improved IIEF score in patients with hypogonadism (WMD, 1.61; 95% CI, 0.99-2.23; I2 = 0%), monotherapy-resistant ED (WMD, 4.38; 95% CI, 2.37-6.40; I2 = 52%), or prostatectomy-induced ED (WMD, 5.47; 95% CI, 3.11-7.83; I2 = 53%). The treatment-related AEs did not differ between combination therapy and monotherapy (odds ratio, 1.10; 95% CI, 0.66-1.85; I2 = 78%). Despite multiple subgroup and sensitivity analyses, the levels of heterogeneity remained high. Conclusions and Relevance: This study found that combination therapy of PDE5 inhibitors and antioxidants was associated with improved ED without increasing the AEs. Treatment with PDE5 inhibitors and daily tadalafil, shockwaves, or a vacuum device was associated with additional improvement, but this result was based on limited data. These findings suggest that combination therapy is safe, associated with improved outcomes, and should be considered as a first-line therapy for refractory, complex, or difficult-to-treat cases of ED.

Stability assessment of tamsulosin and tadalafil co-formulated in capsules by two validated chromatographic methods.

The advent of a new pharmaceutical formulation evokes the need for examining the chemical stability of their constituents and establishing proper stability-indicating methods. Herein, the stability of the newly co-formulated Tamsulosin and Tadalafil were examined under different stress conditions. The acidic degradation of Tamsulosin yielded its sulfonated derivative, while Tadalafil was susceptible to both acidic and basic degradation. Two stability-indicating chromatographic methods, namely; high-performance thin-layer chromatography and high-performance liquid chromatography, have been developed. Significant high-performance thin-layer chromatography-fractionation could be achieved by utilizing a stationary phase of silica gel 60 F254 and a mobile phase composed of ethyl acetate/toluene/methanol/ammonia (4:2:4:0.6, by volumes) with densitometric recording at 280 nm over a concentration range of 0.5-25 µg/band for both drugs. The HPLC-separation could be reached on XBridge® C18 column isocraticaly by using a mobile phase having acetonitrile/phosphate buffer, pH 6.0 (45:55, v/v) pumped at a flow rate of 1.7 mL/min and applying diode array ultraviolet-detection at 210 nm over a linearity range of 3-70 µg/mL for each drug. Specificity of the two methods was additionally assured via peak purity assessment. Moreover, the methods were distinctly exploited for evaluating the drugs' stability in accelerated stability-studied samples of Tamplus® capsules.

Hemodynamics and risk assessment 2 years after the initiation of upfront ambrisentan‒tadalafil in pulmonary arterial hypertension.

BACKGROUND: Upfront combination therapy with ambrisentan and tadalafil has been reported to improve the condition of patients with pulmonary arterial hypertension (PAH) more than with either drug alone. However, little is known about the long-term associated changes in hemodynamics and risk assessment scores. METHODS: This was a multicenter, retrospective analysis of clinical data in 106 patients with newly diagnosed PAH. Clinical evaluations, including demographics, medical history, World Health Organization (WHO) functional class (FC) and 6-minute walk distance (6MWD), right heart catheterization, and Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) risk score 2.0, were assessed over 48 months of ambrisentan‒tadalafil therapy. RESULTS: At baseline, 9 patients (9%) showed a low (<7), 48 patients (45%) showed an intermediate (7-8), and 49 patients (46%) showed a high (>8) REVEAL risk score. At a median follow-up of 2 years, 45 patients (43%) showed a low, 47 patients (44%) showed an intermediate, and 14 patients (13%) showed a high REVEAL score, along with improvements in WHO FC, 6MWD and a decrease in mean pulmonary artery pressure and N-terminal pro brain natriuretic peptide (all p < 0.001). Pulmonary vascular resistance (PVR) decreased by 37% from 11.5 ± 6.5 to 7.2 ± 4.1 Wood units (p < 0.001). A total of 61 patients (57%) remained in intermediate-risk or high-risk categories. Low-risk patients had either a decrease in PVR of >50% or a stroke volume within the limits of normal. CONCLUSIONS: Initial combination therapy with ambrisentan and tadalafil in PAH improves the REVEAL risk score in proportion to decreased PVR and preserved stroke volume but still insufficiently so in approximately 50% of the patients.

Undertreatment of overactive bladder among men with lower urinary tract symptoms in the United States: A retrospective observational study.

AIMS: To characterize the epidemiology and treatment patterns of adult men (≥40 years) diagnosed with, or treated for, overactive bladder (OAB) and/or benign prostatic hyperplasia (BPH). METHODS: This retrospective observational study used data extracted from the IBM MarketScan Commercial Claims and Encounters database and the Medicare Supplemental Coordination of Benefits database. Men with BPH and/or OAB were identified and observed to assess treatment and diagnostic patterns. RESULTS: Within the entire study sample (N = 462 400), BPH diagnosis (61.5%) and BPH treatment (73.7%) were more common than the corresponding values for OAB (25.8% and 7.0%, respectively). Notably, among diagnosed individuals, the dispensation of a corresponding treatment was more likely in individuals diagnosed with BPH (183 672 out of 284 416 = 64.6%) compared with OAB (16 468 out of 119 236 = 13.8%). Among newly diagnosed and/or treated patients (n = 196 576), only 60.3% received treatment. Among treated patients, most experienced only a single type of treatment (93.4%), 6.6% went on to receive a secondary treatment and 3.5% a tertiary. The most common primary treatment was alpha-blocker monotherapy (76.9%) followed by tadalafil monotherapy (16.4%). Among those untreated at first diagnosis, the median time between diagnosis and treatment initiation was 128 days. CONCLUSIONS: Diagnosis and management of OAB among males are challenging given the inherent overlap in symptoms observed with BPH. Unsurprisingly, we found that BPH is diagnosed and treated more frequently than OAB; but the differences between diagnosis and treatment patterns for the two conditions highlight the potential undertreatment of OAB and misdirection of therapy for men with a combination of voiding and storage symptoms.

Novel HPTLC densitometric methods for determination of tamsulosin HCl and tadalafil in their newly formulated dosage form: Comparative study and green profile assessment.

A promising combination of tamsulosin HCl and tadalafil has recently been introduced for treating two prevalent and associated urological disorders: benign prostate hyperplasia and erectile dysfunction. Novel HPTLC methods were designed and validated for assaying the cited drugs in their challenging combined formulation. Separation was achieved using HPTLC silica gel 60 F254 plates as a stationary phase with a densitometric measurement at 280 nm. The proposed methods with two different chromatographic systems were successfully applied: a conventional mixture (method I) of ethyl acetate-toluene-methanol-ammonia (5:3:2:0.5, by volume) and a greener one (method II) with ethyl acetate-ethanol-ammonia (8:2:0.1, by volume). The two methods were evaluated through a comparative study in terms of selectivity, tailing factor, developing time and concentration ranges. The greenness profile for each method was then appraised with several green guides, namely GlaxoSmithKline solvent sustainability guide, Environmental, Health and Safety (EHS) tool, National Environmental Method Index (NEMI) and Eco-scale. Moreover, method specificity and peak homogeneity were evaluated by peak purity assessment using the winCATS® software spectral correlation tool. The methods have potential for being simple, fast, economic and selective, and the greener one could be a good option for sustainable analysis of the drugs.

Phosphodiesterase Type-5 Inhibitor Prescription Patterns in the United States Among Men With Erectile Dysfunction: An Update.

BACKGROUND: While phosphodiesterase type-5 inhibitors (PDE5Is) are highly effective for the treatment of erectile dysfunction (ED) and well tolerated, updated data on prescription patterns have been limited in real-world settings. AIM: To describe men in the United States who are prescribed PDE5Is for ED treatment and to evaluate patterns of initiation, switching, and treatment overlap. METHODS: This retrospective claims study used MarketScan Commercial and Medicare Supplement Databases from January 1, 2010, to December 31, 2015, to identify initial PDE5I claims (index date) for sildenafil, tadalafil, and/or vardenafil. Adults aged ≥18 years with ED were identified between July 1, 2010, and December 31, 2014, allowing for a 6-month preindex and 12-month follow-up period from the index date. OUTCOMES: Outcomes included patient demographics and treatment-related patterns after treatment initiation. RESULTS: A total of 106,206 identified patients met all inclusion criteria. Of these, 51,694, 40,193, and 14,319 had initial claims for sildenafil, tadalafil, and vardenafil, respectively. Mean age was 50.35 years, and comorbidities included dyslipidemia (44.17%), hypertension (43.09%), diabetes (15.32%), and depression (10.61%). More patients (48.67%) initiated on sildenafil than tadalafil (37.85%) or vardenafil (13.48%). Rate of switching was lower in the 60 days after the end of day supply of the initial prescription in the sildenafil cohort (2.71%) compared with the tadalafil (2.81%) and vardenafil (3.88%) cohorts (P < .001 for sildenafil vs tadalafil or vardenafil). Treatment overlap was lower in the sildenafil cohort (0.35%) than in the tadalafil (0.75%) and vardenafil (0.62%) groups (P < .001 for sildenafil vs tadalafil or vardenafil). CLINICAL IMPLICATIONS: These findings provide insight into updated patterns of PDE5I prescriptions in the United States and may aid in clinical decision-making. STRENGTHS & LIMITATIONS: Strengths include the large sample size, long data coverage period, and the real-world nature of the study. Limitations include the retrospective study design, use of data collected with a primary focus of claims, and lack of further details regarding reasons that drive switching. Actual rates of ED and impact on prescription patterns may be underestimated because the claims database only captured patients electing to visit a health-care provider. CONCLUSION: Among men with ED in the United States, rates of switching and treatment overlap were low for all PDE5Is but were found to be the lowest for sildenafil compared with tadalafil and vardenafil. Mulhall JP, Chopra I, Patel D, et al. Phosphodiesterase Type-5 Inhibitor Prescription Patterns in the United States Among Men With Erectile Dysfunction: An Update. J Sex Med 2020;17:941-948.

Falsified vardenafil tablets available online.

It is often reported that falsified medicines have harmful effects on patients both Japan and abroad. In this study, we purchased vardenafil tablets on the internet and investigated their quality and authenticity using visual observations, authenticity investigations, non-destructive tests (handheld NIR and Raman spectroscopy), and quality analyses (active ingredient content and tablet dissolution rate). We used genuine 20-mg Levitra tablets that were sold in Japan and tablets from Bayer AG (Germany) as controls. In April 2015, we obtained 28 samples from 15 websites on the internet. Our authenticity investigations revealed that 11 (40%) were genuine products and 17 (60%) were falsified products. Handheld NIR and Raman results revealed that the falsified products had different spectra to the genuine products. Principal component analysis of the NIR and Raman spectra showed variation among the falsified products. The 11 genuine products were of good quality, and the 17 falsified products were of poor quality. The falsified products contained sildenafil (the active ingredient of Viagra) or tadalafil (the active ingredient of Cialis) instead of vardenafil. Our results show that falsified Vardenafil tablets are sold on the internet and that it is important to prevent illegal internet sales and increase consumer awareness of the presence of falsified medicines.

Smart spectrophotometric assessment of tamsulosin hydrochloride and tadalafil in their new pharmaceutical formulation for treatment of benign prostatic hyperplasia and erectile dysfunction.

A novel combination of tamsulosin hydrochloride and tadalafil is recently available for treatment of benign prostatic hyperplasia and erectile dysfunction. For the first time, four simple, accurate, smart and robust spectrophotometric methods have been suggested for their simultaneous quantification. The methods, namely; first derivative, ratio difference, derivative ratio and mean centering of ratio spectra, successfully resolved the spectral overlap of their challenging binary mixture. Calibration curves were linear at 2.0-40.0 and 2.0-55.0 µg/mL for tamsulosin hydrochloride and tadalafil, respectively. The methods were validated according to ICH guidelines and statistically compared with the official ones, revealing no considerable difference with respect to accuracy and precision. Specificity of the developed methods was assessed by evaluating various laboratory prepared mixtures. Furthermore, the methods were successfully applied for the quantification of the two drugs in their combined dosage form.

Self-Regulation in the Pharmaceutical Industry: The Exposure of Children and Adolescents to Erectile Dysfunction Commercials.

CONTEXT: Spending on direct-to-consumer advertising (DTCA) for prescription pharmaceuticals has risen to record levels, five times as much as in 1996 in inflation-adjusted dollars. Major health care provider organizations have called for additional regulation of DTCA. These organizations argue that the negative impact of such advertising outweighs the informational value claimed by the pharmaceutical industry. The industry maintains that further restrictions on DTCA are not warranted because it is successfully self-regulating via "guiding principles" for DTCA as certified by firm executives. METHODS: The authors measured recent industry spending on DTCA and used regression models of Nielsen Monitor-Plus data to assess pharmaceutical firm self-regulation after the public disclosure of noncompliance with industry self-regulatory principles, specifically regarding the exposure of children and adolescents to broadcast advertisements for erectile dysfunction drugs. FINDINGS: Public disclosure of noncompliance with self-regulatory DTCA standards did not bring advertising into compliance. Results demonstrate that firms failed to meet the industry standard during every quarter of the six-year period of this study. CONCLUSIONS: Results support previous research findings that pharmaceutical self-regulation is a deceptive blocking strategy rather than a means for the industry to police itself. Policy recommendations include broadcast restrictions on adult content and deincentivizing DTCA via tax reform.

Oxidative stress assessment in intestine of newborn rats submitted to hypoxia and reoxygenation with tadalafil.

PURPOSE: To evaluate the functional and structural response of tadalafil effects in the intestinal mucosa, using an experimental model of hypoxia and reoxygenation injury in rats. METHODS: The animals were divided into 4 groups: CTL, H/R, H/R+Td and M+Td. The newborn rats allocated in groups H/R, H/R+Td and M+Td were submitted twice a day, to a gas chamber with CO2 at 100% for 10 minutes and afterward reoxygenation with O2 at 98% for 10 minutes, in the three first days of life. Tadalafil dose was given to newborn of group H/R+Td and to the pregnant rat of group M+Td. Histological analysis was made with hematoxylin-eosin technique and oxidative stress through nitrite and nitrate levels and lipid peroxidation. RESULTS: The histological analysis showed a reduction of mucosa alterations in the groups that received tadalafil. In the oxidative stress evaluation, occurred an increase of NO levels and less lipidic peroxidation in the ileum segments that received tadalafil. CONCLUSION: Tadalafil provides tissue protection when administered independently to both, pregnant or newborns.

Oxidative stress assessment in intestine of newborn rats submitted to hypoxia and reoxygenation with tadalafil

Abstract Purpose: To evaluate the functional and structural response of tadalafil effects in the intestinal mucosa, using an experimental model of hypoxia and reoxygenation injury in rats. Methods: The animals were divided into 4 groups: CTL, H/R, H/R+Td and M+Td. The newborn rats allocated in groups H/R, H/R+Td and M+Td were submitted twice a day, to a gas chamber with CO2 at 100% for 10 minutes and afterward reoxygenation with O2 at 98% for 10 minutes, in the three first days of life. Tadalafil dose was given to newborn of group H/R+Td and to the pregnant rat of group M+Td. Histological analysis was made with hematoxylin-eosin technique and oxidative stress through nitrite and nitrate levels and lipid peroxidation. Results: The histological analysis showed a reduction of mucosa alterations in the groups that received tadalafil. In the oxidative stress evaluation, occurred an increase of NO levels and less lipidic peroxidation in the ileum segments that received tadalafil. Conclusion: Tadalafil provides tissue protection when administered independently to both, pregnant or newborns.