Prescribing trends of glaucoma drugs in six major cities of China from 2013 to 2017.

OBJECTIVE: To evaluate the prescribing trends of glaucoma drugs in six major cities of China from 2013 to 2017. METHODS: A descriptive analysis using pharmacy prescription data was conducted. Outpatient prescription data was extracted from the Hospital Prescription Analysis Cooperative Project. Prescribing patterns, trends of visits, and corresponding expenditures for glaucoma medications were analyzed. RESULTS: A total of 84297 ambulatory prescriptions were included in the current study. Visits by glaucoma patients increased from 13808 in 2013 to 20060 in 2017. Over the same period, the yearly expenditure for glaucoma drugs increased from 2.33 million to 3.95 million Chinese Yuan (CNY). Among all the six classes of glaucoma drugs (prostaglandin analogues, carbonic anhydrase inhibitors, α-receptor agonists, ß-receptor antagonists, cholinergic agonists and fixed combinations), ß-receptor antagonists were the most commonly prescribed in 2013, accounting for 34.3% of patients, but gradually decreased to 27.1% in 2017. Prostaglandin analogues became the most frequently prescribed drugs in 2017, accounting for 30.2% of the visits. Prostaglandin analogues are the most expensive and yielded a total expenditure of 2.34 million CNY in 2017, followed by carbonic anhydrase inhibitors, α-receptor agonists, ß-receptor antagonists, fixed combinations, and cholinergic agonists. Combination therapy became increasingly prescribed in 2017. CONCLUSION: Glaucoma prescribing practices exhibited substantial changes over the study period. The number of glaucoma prescriptions continuously increased from 2013 to 2017, leading to increased prescription costs. These findings implied a similar trend observed in previous studies, as well as recommendations in the appropriate guidelines.

Fifteen Minute Test May Save 15% or More on Rosacea Treatment.

Rosacea is a common inflammatory skin condition that impacts a large portion of fair-skinned populations. The redness associated with rosacea can be a significant challenge. Brimonidine sulfate and oxymetazoline HCL were both recently approved by the FDA for the management of facial redness. These agents, however, are costly, and not all patients respond to the medication. Herein, we describe a clinical pearl that helps to optimize patient selection for the medications. This saves the patient and the health care system both time and money. J Drugs Dermatol. 2018;17(5):692-693.

Role of Topical Oxymetazoline for Management of Erythematotelangiectatic Rosacea.

OBJECTIVE: To review and summarize topical oxymetazoline's pharmacology, pharmacokinetics, efficacy, safety, cost, and place in therapy for persistent redness associated with erythematotelangiectatic rosacea. DATA SOURCES: Literature searches of MEDLINE (1975 to September 2017), International Pharmaceutical Abstracts (1975 to September 2017), and Cochrane Database (publications through September 2017) using the terms rosacea, persistent redness, α -agonist, and oxymetazoline. STUDY SELECTION AND DATA EXTRACTION: Results were limited to studies of human subjects, English-language publications, and topical use of oxymetazoline. Relevant materials from government sources, industry, and reviews were also included. DATA SYNTHESIS: Data support the efficacy of oxymetazoline for persistent facial redness. Little study beyond clinical trials cited in the drug approval process has been conducted. Current data suggest that oxymetazoline is similar in safety and efficacy to brimonidine. Head-to-head comparisons of topical α-agonists for erythema caused by rosacea are needed. CONCLUSION: The topical α-agonist, oxymetazoline, is safe and effective for reducing persistent facial redness associated with erythematotelangiectatic subtype of rosacea. Health care practitioners selecting among treatments should consider not only the subtype of rosacea but also individual patient response, preference, and cost.

Noradrenaline is as Effective as Terlipressin in Hepatorenal Syndrome Type 1: A Prospective, Randomized Trial.

OBJECTIVES: Hepatorenal syndrome (HRS) is a functional renal failure occurring in end stage liver disease, which is associated with poor prognosis. Terlipressin has been shown to be effective in treatment of HRS. More recently, it was suggested that noradrenaline, an alpha-adrenergic drug may be also effective in HRS. We aimed to compare the efficacy of noradrenaline versus terlipressin in treatment of HRS type 1. METHODS: Consecutive patients with cirrhosis and HRS type 1 were enrolled and randomised into 2 groups- Group A received intravenous noradrenaline infusion (0.5-3 mg/h) and group B received intravenous terlipressin (0.5-2 mg/6h) for 2 weeks. Intravenous albumin (20 g/day) was given to both groups. RESULTS: Out of 55 cirrhotics screened, 41 were randomised into group A (n=21) or group B (n=20). Baseline characteristics of the two groups were similar. HRS reversal was seen in 47.6%(10/21) patients in group A, and 45% (9/20) patients in group B (p=1.00). In both groups, there was a significant decrease in serum creatinine from baseline (group A- 3.1±1.4 mg/dl to 2.2±1.3 mg/dl, p=0.028; group B- 3.4±1.6 mg/dl to 2.3±1.3 mg/dl, p=0.035). Both the groups showed a significant increase in mean arterial pressure (group A- 77.3±8.6 mmHg to 103.4±8.3 mmHg, p=0.0001; group B- 76.8±11.6 mmHg to 100±9.4 mmHg, p=0.0001). Noradrenaline was associated with fewer adverse events and was significantly cheaper than terlipressin. Lower baseline MELD score was an independent predictor of response to treatment. CONCLUSIONS: Noradrenaline is as effective and safe as terlipressin in the treatment of HRS type 1.

[Dexmedetomidine]. / Dexmedetomidin.

Dexmedetomidine is a highly selective α2-receptor agonist with sedative, analgetic and anxiolytic effects. It is chemically related to clonidine and has been an authorized drug in Europe since September 2011. Dexmedetomidine enables a level of sedation in which mechanically ventilated patients may be woken by verbal stimulation (Richmond agitation sedation scale RASS 0--3). In this respect dexmedetomidine achieves the same desired effect as propofol and midazolam; however, in direct comparison to a sedation regime with benzodiazepines, dexmedetomidine reduces the prevalence, duration and severity of delirium in intensive care. Patients sedated by dexmedetomidine can statistically be extubated earlier and an influence on duration of stay in the intensive care unit (ICU) has not been shown. Daily therapy costs are approximately 5 times higher than those of propofol but an objective standpoint in relation to clinical cost efficiency is unattainable.

Update on the role of alpha-agonists in glaucoma management.

Glaucoma is the second most common cause of world blindness (following cataract) with estimated cases reaching 79.6 million by 2020. Although the etiology of glaucoma is multi-factorial, intraocular pressure (IOP) is the only modifiable factor in glaucoma management proven to alter the natural course of the disease. Among various classes of IOP-lowering medications currently available, alpha-adrenergic receptor agonists are used either as monotherapy, as second-line therapy, or in fixed combination with beta-blockers. Non-selective adrenergic agonists such as epinephrine and dipivefrin are infrequently used today for the treatment of glaucoma or ocular hypertension, and have been replaced by the alpha-2-selective agonists. The use of apraclonidine for IOP reduction in glaucoma or OHT is limited due to a high rate of follicular conjunctivitis. The alpha-2-selective agonist in use today is brimonidine. The brimonidine-purite formulations are preferred to brimonidine-benzalkonium chloride (BAC) formulations due better tolerability while maintaining similar efficacy. Brimonidine is also effective when used in combination with a beta-blocker. Using brimonidine-timolol fixed combination (BTFC) as first-line therapy has an added potential for neuroprotection. This would be a valuable strategy for glaucoma treatment, for patients who are intolerant of prostaglandin analogs, or for patients where prostaglandin analogues are contraindicated as first-line therapy, such as in patients with inflammatory glaucoma.

An updated focused review of dexmedetomidine in adults.

OBJECTIVE: To evaluate recent comparative studies regarding the safety and efficacy of dexmedetomidine in adults. DATA SOURCES: Articles evaluating safety and efficacy of dexmedetomidine were identified from an English-language MEDLINE search (1996-July 2009), with a focus on data published since our previous review in 2007 to the present. MeSH terms included dexmedetomidine, medetomidine, alpha2-agonist, and sedation. References from selected articles were also reviewed for additional material. STUDY SELECTION AND DATA EXTRACTION: Experimental and observational English-language studies that focused on the efficacy, safety, and pharmacoeconomics of dexmedetomidine in humans were selected. DATA SYNTHESIS: Dexmedetomidine is an 2-agonist used for sedation during procedures and in critical illness. Compared with placebo, use of dexmedetomidine during procedures was associated with decreased use of rescue midazolam and a similar degree of sedation compared with various agents used during surgery or for procedures. Use of long-term (>24 h) dexmedetomidine sedation is comparable to sedation with benzodiazepines in critically ill patients. In a Phase 4 study, dexmedetomidine was safe in dosages up to 1.4 microg/kg/hour for greater than 24 hours and did not produce rebound tachycardia or hypertension when abruptly discontinued. One small randomized controlled trial demonstrated decreased incidence of delirium, the primary endpoint, with dexmedetomidine compared with midazolam or propofol for sedation after cardiac valve surgery. Many, but not all, studies suggest that dexmedetomidine has a promising role in prevention and treatment of delirium in critically ill patients when delirium was studied as a secondary endpoint. CONCLUSIONS: Dexmedetomidine is an alternative for procedural sedation and can be used long-term (>24 h) in critically ill patients, in dosages up to 1.5 microg/kg/hour. More studies are needed to better define the role of dexmedetomidine in preventing and treating delirium.

Randomised controlled study-efficacy of clonidine versus carbamazepine in children with ADHD.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is one of the most common childhood psychiatric disorder with a prevalence of 8-12%. Even though psychostimulants remain the treatment of choice, its cost and availability in developing countries limits the usage of the drug. In view of free availability and low cost, a Randomized controlled study was carried out using two second line drugs (clonidine and carbamazepine) in a tertiary care hospital, Pondicherry, South India. OBJECTIVE: To compare the efficacy of clonidine and carbamazepine in children with ADHD. METHOD: With approval of ethics committee, a prospective, Double-blind, Randomized controlled study of clonidine and carbamazepine was conducted with 50 children with ADHD (age group 4-12 years), over a period of 2 years (2005-07) in a tertiary care hospital, Pondicherry, South India. RESULTS: Clonidine was effective in improving the hyperactivity and impulsivity symptoms in children with ADHD as compared to carbamazepine. Statistical significant improvement was not noted with respect to inattention symptoms and other comorbid conditions. CONCLUSION: Clonidine can be a safer and cheaper alternative in treatment of children with ADHD, with a predominant effect on their hyperactivity and impulsivity symptoms.

Silodosin: a selective alpha1A-adrenergic receptor antagonist for the treatment of benign prostatic hyperplasia.

BACKGROUND: Silodosin is a new alpha(1)-adrenergic receptor antagonist that is selective for the alpha(1A)-adrenergic receptor. It was approved by the US Food and Drug Administration (FDA) in 2008 for the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). OBJECTIVE: This article reviews the pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, and dosage and administration of silodosin in adult male patients with BPH. METHODS: A search of MEDLINE (1950-October 8, 2009), International Pharmaceutical Abstracts (1970-October 8, 2009), and the Iowa Drug Information Service database (1966-October 8, 2009) was conducted using the terms silodosin, KMD-3213, benign prostatic hyperplasia, and alpha(1)-adrenergic receptor antagonist. Reports of research and review articles published in English were identified and evaluated, and the bibliographies of these articles were reviewed for additional relevant publications. A search of the FDA Web site was performed, and abstracts and posters presented at scientific meetings of the American Urological Association were reviewed. RESULTS: By antagonizing alpha(1A)-adrenergic receptors in the prostate and urethra, silodosin causes smooth muscle relaxation in the LUT. Silodosin has greater affinity for the alpha(1A)-adrenergic receptor than for the alpha(1B)-adrenergic receptor (by a factor of 583), minimizing the propensity for blood pressure-related adverse effects mediated by alpha(1B) blockade. In 3 controlled clinical studies in patients with BPH-related LUTS (1 published; 2 presented in the prescribing information and published in a pooled analysis), patients receiving silodosin at a total daily dose of 8 mg had significant improvements in the International Prostate Symptom Score (IPSS) and maximum urinary flow rate (Q(max)) compared with those receiving placebo (both, P < 0.05). The most commonly reported adverse effect was abnormal or retrograde ejaculation (>22%), and the incidence of orthostatic hypotension was low (<3%). CONCLUSIONS: In the small number of clinical trials reviewed, silodosin was associated with significant reductions in IPSS and Q(max) compared with placebo. To determine whether silodosin's selectivity for the alpha(1A)-adrenergic receptor translates into a clinical advantage relative to other available agents, long-term studies evaluating the comparative efficacy and tolerability of silodosin and other alpha(1)-blockers (specifically tamsulosin) are necessary.

Costs and persistence of carbonic anhydrase inhibitor versus alpha-2 agonists, associated with beta-blockers, in glaucoma and ocular hypertension: an analysis of the UK-GPRD database.

OBJECTIVE: To compare the effectiveness and associated costs of carbonic anhydrase inhibitors + beta-blocker versus alpha-2 adrenergic agonists + beta-blocker in glaucoma therapy, as documented by The United Kingdom General Practitioner Research Database (UK-GPRD). RESEARCH DESIGN: Patient chart analysis. METHODS: Patient records were screened for diagnoses of ocular hypertension or glaucoma, and for surgery, laser therapy or medication specific to glaucoma. Selected patients were those prescribed either carbonic anhydrase inhibitors + beta-blocker or alpha-2 adrenergic agonists + beta-blocker. Treatment failure was defined as a glaucoma prescription change, i.e. addition, cessation or replacement of medication, surgery or laser therapy. Times to treatment failure were compared with an adjusted Cox model. MAIN OUTCOME MEASURES: Treatment persistence and cost. RESULTS: Included patients were those treated with either carbonic anhydrase inhibitors + beta-blocker (n = 5581) or alpha-2 adrenergic agonists + beta-blocker (n = 1164). The average age at diagnosis was 68.1 years and 48.2% were male. Treatment failure at one year was significantly (p < 0.001) less frequent after carbonic anhydrase inhibitors + beta-blocker (57% of patients) than after alpha-2 adrenergic agonists + beta-blocker (64.3%). The hazard ratio for failure was lower (0.82: p < 0.0001) with carbonic anhydrase inhibitors + beta-blocker following adjustment for age, gender, comorbidities and duration of follow-up. Adjusted annual costs of glaucoma management were pound 348.04 for carbonic anhydrase inhibitors + beta-blocker and pound 356.80 for alpha-2 adrenergic agonists + beta-blocker. CONCLUSIONS: According to UK-GPRD information, glaucoma therapy with carbonic anhydrase inhibitors + beta-blocker is more persistent than with alpha-2 adrenergic agonists + beta-blocker at a similar cost.

Costs and persistence of brimonidine versus brinzolamide in everyday glaucoma care: an analysis conducted on the UK General Practitioner Research Database.

OBJECTIVE: To compare the persistence and costs of brimonidine versus brinzolamide therapy according to data collected by the UK General Practitioner Research Database (GPRD). METHODS: Patients with diagnoses of ocular hypertension or glaucoma, or treated for glaucoma by surgery or laser therapy were identified. Selected patients were prescribed either brimonidine or brinzolamide as monotherapy. Treatment failure was defined as a glaucoma prescription change (adding, removing or replacing a drug, or initiating surgery or laser therapy). Times to treatment failure were compared with an adjusted Cox model using a propensity score method. RESULTS: A total of 2,172 patients received brimonidine and 485 brinzolamide. Mean age was 69.5 years and 46.4% were male. Age and gender did not differ significantly whereas disease duration was longer with brinzolamide. Treatment failure at 1 year was experienced by 47.7% of patients given brinzolamide and by 55.9% given brimonidine (p<0.001). The hazard ratio for failure was less with brinzolamide (0.79: p<0.001) compared to brimonidine, after adjusting for age, gender, comorbidities and duration of follow-up. Adjusted annual costs of glaucoma management (in pound2005) were significantly (p<0.0042) lower with brinzolamide (pound196) than brimonidine (pound230). CONCLUSIONS: According to data from everyday practice collected by the UK GPRD, brinzolamide was found to be more persistent than brimonidine when given as glaucoma monotherapy. Patients continued longer with brinzolamide treatment at a lower cost.

Daily cost of glaucoma medications in China.

PURPOSE: To determine and compare the daily cost of various glaucoma medications in China. MATERIALS AND METHODS: The majority of glaucoma medications commercially available in China were included in this research. The total number of drops in 1 bottle of each medication was counted drop by drop. The mean volume per bottle of each medication was calculated. The cost per drop, number of days for both eyes usage per bottle, and daily cost was calculated. RESULTS: (1) The volume per drop ranged from 0.03 mL (brinzolamide 1%, travoprost 0.004%, bimatoprost 0.03%, and latanoprost 0.005%) to 0.05 mL (timolol 0.5%-Chengrui and pilocarpine 0.5% and 2%-Zhenrui). (2) The cost per bottle ranged from $0.69 (US dollar) (timolol 0.5%-Malaisuan Saimaluo'er) to $40.78 (latanoprost 0.005%). (3) The number of days for both eyes usage per bottle ranged from 52 days (bimatoprost 0.03%) to 11 days (pilocarpine nitrate 0.5%-Zhenrui). (4) The daily cost for both eyes usage from expensive to cheap were latanoprost 0.005%-$0.91, travoprost 0.004%-$0.77, brimonidine 0.2%-$0.61, bimatoprost 0.03%-$0.46, D-timolol 1%-$0.36, brinzolamide 1%-$0.34, pilocarpine 2%-Zhenrui-$0.28, levobunolol 0.5%-$0.25, betaxolol 0.25%-$0.24, pilocarpine 0.5%-Zhenrui-$0.18, pilocarpine 2%-Huming-$0.16, carteolol 1%-Mikelan-$0.15, carteolol 2%-Mikelan-$0.15, pilocarpine 1%-Huming-$0.10, timolol 0.5%-Chengrui-$0.08, timolol 0.5%-Malaisuan Saimaluo'er-$0.03. CONCLUSIONS: The daily cost of glaucoma medications in China ranged much more wildly than developed countries. These data may be useful in selecting medications for glaucoma therapy. The ophthalmic solution of prostaglandins is powerful in reducing intraocular pressure. However, its high price should be considered when selecting glaucoma medications in China.

A fluorescence optosensor for analyzing naphazoline in pharmaceutical preparations. Comparison with other sensors.

We have developed an optical sensor for determining and quantifying naphazoline (NPZ) based on its inherent fluorescence property. We have placed a non-ionic-exchanger solid support (Amberlite XAD-7) in a flow cell in the light path of the excitation beam and the fluorescence signal for NPZ is continuously monitored at lambda(exc/nm)=294/306 nm. The response time for this sensor is acceptably fast, 80s, obtaining a detection limit of 2.6 ng mL(-1) with standard deviations of 2.0% at 125 ng mL(-1). This device has been satisfactorily applied to two commercial formulations and its selectivity has been demonstrated with an interference study. The advantages have been compared with the only published sensor for determining NPZ in pharmaceutical preparations and with other analytical methods in the literature.

Medical therapy cost considerations for glaucoma.

PURPOSE: To determine the calculated daily patient cost (cost minimization) of medical glaucoma therapy and review cost trends. DESIGN: Experimental, controlled, prospective study. METHODS: The actual volume of various glaucoma medications or glaucoma medications with redesigned bottles was determined for most commercially available sizes of the tested products. The drops per milliliter based on the actual volume and the daily costs of the dosage schedules recommended by the manufacturers were compared. The cost of each bottle of medication was determined from the average wholesale price (AWP) in the United States. A comparison to 1999 prices where applicable will be analyzed to review costing trends. RESULTS: The generic timolol products (range, US dollars 0.38-US dollars 0.46 per day) were similar on a cost per day basis vs Betimol (Santen, Napa Valley, California, USA), Optipranolol (Bausch and Lomb Pharmaceuticals, Tampa, Florida, USA) and Timoptic (Merck, West Point, Pennsylvania, USA). Their percentage cost increase ranged from 5% to 22% since 1999, except for generic timolol XE gel-forming solution (48%). Betagan (Allergan, Irvine, California, USA), Betoptic S (Alcon Laboratories, Fort Worth, Texas, USA), and Ocupress (Novartis, Duluth, Georgia, USA) ranged from US dollars 0.88 to US dollars 1.11 per day, and their percentage cost increase ranged from 33% to 53%. Some brand-only products have raised their AWPs a greater percentage, including Betoptic S (37%), Iopidine (Alcon, Fort Worth, Texas, USA) (50%), Ocupress (Novartis Ophthalmics, Duluth, Georgia, USA) (53%), and Pilopine gel (Alcon, Fort Worth, Texas, USA) (32%). The mean cost per day for the topical carbonic anhydrase inhibitors Azopt (Alcon Laboratories; US dollars 1.33 per day) and Trusopt (Merck; US dollars 1.05 per day) differed from 1999 when prices were almost identical. Cosopt (Merck; timolol 0.5% plus dorzolamide 2%, US dollars 1.04 per day) was less than the cost of separate bottles of a topical carbonic anhydrase inhibitor and a beta-blocker. The selective alpha-2 agonist brimonidine 0.15% with Purite (Alphagan-P, Allergan, 5 ml) twice daily was US dollars 1.29 per day. The prostaglandin analogs were comparably priced with Lumigan (Allergan) US dollars 0.95 per day, Xalatan (Pharmacia and Upjohn, Kalamazoo, Michigan, USA) US dollars 1.25 per day, Travatan (Alcon Laboratories) US dollars 1.01 per day, and Rescula (Novartis) US dollars 0.90 per day. CONCLUSIONS: All generic timolol, Betimol, Optipranolol, Timoptic, and Timoptic XE (Merck) ranged from US dollars 0.38 to US dollars 0.50 per day. Other beta-blocker products were about twice as costly, ranging from US dollars 0.88 to US dollars 1.11 per day. Cosopt (US dollars 1.05 per day) was less costly than separate bottles of a topical beta-blocker and a topical carbonic anhydrase inhibitor dosed three times daily or twice daily. The prostaglandin analogs ranged from US dollars 0.90 per day (Rescula) to US dollars 1.25 per day (Xalatan). Newer glaucoma medications exhibit similar costs per day in many cases, compared with more traditional medications, especially with greater price increases in older brand-only products.

Cost analysis of glaucoma medications: a 3-year review.

PURPOSE: To evaluate yearly cost of glaucoma medications at a university-affiliated teaching hospital with its own health maintenance organization from 1998 through 2000. METHODS: We retrieved data from the Scott and White prescription claims file for 1,484 patients concerning Health Plan glaucoma-medication prescriptions for the years 1998 through 2000. Patient inclusion criteria were as follows: 1) use of a single or fixed-combination topical glaucoma medication during all four quarters of at least one full-year, 2) treatment of both eyes, 3) participation in the Health Plan prescription program, and 4) prescriptions filled at pharmacies participating in the Health Plan prescription program. RESULTS: Over this 3-year period, the most costly medication per patient per year was dorzolamide hydrochloride-timolol maleate (Cosopt; Merck, West Point, PA [$470]), followed by betaxolol hydrochloride (Betoptic-S; Alcon, Fort Worth, TX [$370]), latanoprost (Xalatan; Pharmacia and Upjohn, Kalamazoo, MI [$352]), dorzolamide hydrochloride (Trusopt; Merck, West Point, PA [$288]), brimonidine tartrate (Alphagan; Allergan Pharmaceuticals, Irvine, CA [$273]), brinzolamide (Azopt; Alcon, Fort Worth, TX [$243]), timolol maleate 0.5% in a gel-forming solution (Timoptic-XE 0.5%; Merck, West Point, PA [$190]), carteolol hydrochloride (Ocupress; Otsuka Pharmaceutical, Rockville, MD [$183]), generic levobunolol hydrochloride 0.5% ($138), metipranolol (Optipranolol; Bausch and Lomb Pharmaceuticals, Tampa, FL [$135]), and generic timolol maleate 0.5% ($133). CONCLUSION: Differences in yearly cost exist among topical glaucoma medications.