Development of a New Jelly Coating Technology (Oral Jelly Coating) to Improve Prescribed Medication Adherence.

Tablets are the most commonly prescribed dosage form for oral drug administration. Historically, improvement of medication adherence of tablets has been facilitated through, for example, the use of smaller tablets, distinctive shaped tablets and sugar-coated tablets. In addition, new formulation technologies such as orally disintegrating tablets (OD tablets), micro tablet-type granules, jellies, and film formulations are making it possible to create more easily ingested dosage forms. We have developed a new oral jelly coating formulation that can be applied to any sized tablet without reducing the size of the formulation. It was found that this new jelly layer formed on the tablet surface improved the tablet's slipperiness with an appropriate amount of water, while ensuring no change in the dissolution profile. In addition, the jelly layer was ensured storage stability over time without affecting the dissolution profile. Although further studies are needed, this coating technology can quickly change the tablet surface to a jelly-like state after the tablet is taken, giving the tablet the same slipperiness as if it were taken in jelly, making it easier to pass through the pharynx, and thus improving medication adherence.

Does the presence of coexisting diseases modulate the effectiveness of a low-dose estrogen/progestin, ethinylestradiol/drospirenone combination tablet in dysmenorrhea? Reanalysis of two randomized studies in Japanese women.

BACKGROUND: The purpose of this study was to investigate the effectiveness of a combination of ethinylestradiol (EE) and 0.02 mg/drospirenone (DRSP) 3 mg in Japanese women with dysmenorrhea and in particular to determine whether or not the presence of specific coexisting organic diseases (eg, endometriosis, uterine fibroids, uterine adenomyosis) has an impact on treatment. METHODS AND RESULTS: Four hundred and ten patients with dysmenorrhea aged 20 years or older (315 without coexisting organic disease, 28 with endometriosis, 37 with uterine fibroids, and 46 with uterine adenomyosis [some patients had multiple coexisting organic diseases]) were enrolled and treated with EE/DRSP in either a 16-week comparator study or a 52-week long-term safety study. Evaluations included changes in total dysmenorrhea score, visual analog scale for dysmenorrhea, severity of symptoms, hormone levels, endometrial thickness, and safety outcomes. In both studies, the total dysmenorrhea score was significantly (P<0.001) decreased from baseline during treatment with EE/DRSP. Time-dependent changes in visual analog score for dysmenorrhea and alleviation of symptoms, such as lower abdominal pain, low back pain (lumbago), headache, and nausea/vomiting, were similar in all patient groups with and without any specific coexisting organic diseases. These improvements with EE/DRSP were observed for both short-term (16 weeks) and long-term (52 weeks) use. These effects were associated with suppressed increases in serum estradiol and progesterone levels and decreased endometrial thickness. The safety profile of EE/DRSP was similar in all patients, irrespective of the presence of coexisting organic diseases. CONCLUSION: EE/DRSP may be prescribed for patients with dysmenorrhea irrespective of the presence of any specific coexisting organic diseases.

Burden of menstrual symptoms in Japanese women - an analysis of medical care-seeking behavior from a survey-based study.

BACKGROUND: Menstrual symptoms are associated with various health problems in women of reproductive age, and this may impact their quality of life. Despite this, Japanese women are likely to hesitate seeking a specialist's medical help for their menstrual symptoms. PURPOSE: To study subject parameters including symptom severity, gynecological disorders, and treatments in medical care-seeking women (outpatient) and women opting for self-care (nonvisit), to identify reasons why Japanese women do not see a gynecologist, and to document the benefit of gynecologist visits by assessing the impact on women's daily lives. METHODS: Two online surveys were conducted among women aged 15-49 years. Sampling was structured to approximate the age and geographic distribution in Japan. Results of the first survey and part of the second survey on the overall current burden of menstrual symptoms are reported in a separate publication. Further outcomes from the second survey reported in this paper included data from the outpatient (n=274) and nonvisit (n=500) groups on symptom severity, gynecological disorders, medical treatment use, reasons for not seeking medical care, and the improvement of daily life. RESULTS: The outpatient group tended to have greater symptom severity compared to the nonvisit group. Uterine fibroids, dysmenorrhea, endometriosis, and premenstrual syndrome were the most commonly self-reported diagnoses, and oral contraceptives were frequently prescribed at gynecologist visits. Nonvisit group subjects felt that gynecologist consultations were unnecessary or felt resistant to them. Daily life was significantly improved after medical treatment from a gynecologist visit with associated economic savings, whilst the nonvisit group had no change after taking over-the-counter drugs to relieve their menstrual symptoms. CONCLUSION: The present study results indicate that Japanese women who were suffering from menstrual symptoms could benefit from visiting a gynecologist for easing their symptoms, hence improving their daily life.

Safety of gadopentetate dimeglumine after 120 million administrations over 25 years of clinical use.

PURPOSE: We evaluated the safety of gadopentetate dimeglumine (Gd-DTPA), the first contrast agent for magnetic resonance imaging, using pharmacovigilance data for spontaneously reported adverse events (AEs) after 120 million cumulative administrations worldwide. METHODS: We analyzed spontaneously reported AEs for Gd-DTPA for pre-specified time periods between 1988 and 2011. RESULTS: Since the market introduction of Gd-DTPA in 1988, its global utilization reached 120 million cumulative administrations in 2011, more than 80% of which was by the USA, countries in the European Union (EU), and Japan. The global AE reporting rate was 21.2 in 100,000 administrations in 1988 and 14.4 in 100,000 administrations by 2011. Regional differences included higher reporting rates in the USA and Japan, and reporting rates lower than global rates in the EU. The reported rate of global serious AEs changed from 1.4 in 100,000 administrations in 1988 to 4.0 in 100,000 administrations in 2011. The highest number of reports of nephrogenic systemic fibrosis (NSF) was received from 2006 to 2008. Since 2009, no report of a current onset of NSF has been received. The reduced report rate of NSF may be due to increased awareness about the use of gadolinium-based contrast agents (GBCAs). CONCLUSION: After more than 120 million cumulative administrations, Gd-DTPA is a widely used GBCA that shows a consistently low and stable incidence of AEs.

Burden of menstrual symptoms in Japanese women: results from a survey-based study.

UNLABELLED: . OBJECTIVE: Menstrual symptoms are associated with various health problems in women and may also significantly impact their lives. This study aims to assess the current burden of menstrual symptoms in Japanese women. METHODS: Two online surveys were conducted among women aged 15-49 years, where sampling was designed to approximate the age and geographic distribution in Japan. The first survey collected data on menstrual symptom severity based on a modified, 35-item, Japanese version of the Menstrual Distress Questionnaire (mMDQ), current treatments, and impact on work productivity. The second survey collected costs of outpatient treatment within the previous 3 months. Additional outcomes of the second survey will be presented in a separate paper. RESULTS: In this study, 19,254 women had menses, with 74% suffering from menstrual symptoms. A total of 50% reported pain and 19% reported heavy bleeding. Increasing severity of menstrual symptoms and self-reported heavy bleeding were related to more outpatient visits and greater work productivity loss. Among subjects with heavy bleeding, increasing severity of symptoms was related to greater interference with daily life. The estimated annual economic burden extrapolated to the Japanese female population was 683 billion Japanese Yen (JPY) or ~8.6 billion United States Dollars (USD). LIMITATIONS: The study population may be biased due to the online survey method. CONCLUSIONS: To the authors' knowledge, this is the first large-scale research assessing outcomes by severity categories for all menstrual symptoms and women's perception of bleeding. A large proportion of women suffer from menstrual symptoms, and symptom severity impacts women's lives. Menstrual symptoms lead to significant economic burden, mainly due to work productivity loss. However, the majority of women do not visit a gynecologist, even when their menstrual symptoms are severe. Thus, increasing public awareness on the recently available medical treatments has the potential to improve the overall burden of menstrual problems.

Metabolic effects of 20-kilodalton human growth hormone (20K-hGH) for adults with growth hormone deficiency: results of an exploratory uncontrolled multicenter clinical trial of 20K-hGH.

The biological effects of 20-kDa human GH (20K-hGH), which is produced in the pituitary by alternative splicing of GH mRNA and comprises approximately 6% of all GH in serum, have not been reported. We have investigated the metabolic effects of recombinant 20K-hGH in adult patients with GH deficiency in an exploratory study. Three doses of 20K-hGH (0.006, 0.012, and 0.024 mg/kg.d), were administered for 16 wk to three groups (consisting of 18 or 19 subjects), respectively. The 20K-hGH dose-dependently increased serum IGF-I and IGFBP-3 levels, and the lowest dose (0.006 mg/kg) was enough to normalize both hormones by wk 4. Serum osteocalcin levels and urinary deoxypyridinoline excretion were also dose-dependently increased. There was a significant decrease in body fat mass with an increase of lean body mass at the lowest dose of 0.006 mg/kg.d. Blood glucose and serum insulin were increased significantly at 4 wk only in the high-dose group (0.024 mg/kg). Glucose tolerance was slightly impaired in 26-39% of patients in all treatment groups as judged by oral glucose tolerance tests, but there was no development of overt diabetes. The major adverse event in the 20K-hGH treatment was peripheral edema, similar to the incidence reported for 22K-hGH. The data demonstrated that 20K-hGH had metabolic effects comparable to those of 22K-hGH in humans. The results suggest that 20K-hGH could be used to treat GH-deficient patients, although further studies may be required to investigate the optimum dose and superiority of 20K-hGH over 22K-hGH in a comparative study.