Inappropriate use of proton pump inhibitors in non-critical indoor patients in a tertiary care teaching hospital in Eastern India

Background: Proton pump inhibitors are one of the most commonly used drugs worldwide. Often they are used for inappropriate indications too, imposing economic burden to patients and governments. Many studies have showed equipotent efficacy of oral and intravenous proton pump inhibitor therapy. Despite that, most of the hospitalized patients receive intravenous proton pump inhibitor without appropriate indications. This study aimed to assess use of proton pump inhibitors in government hospital.Methods: It was an observational cross-sectional study done in the general medicine department of a tertiary care teaching hospital in Eastern India, including 800 noncritical patients. Objective was to assess the use of proton pump inhibitors (indications, route of administration, dosing frequency).Results: 100% patient received intravenous proton pump inhibitor irrespective of diagnosis. 80% of them received it twice daily and 18% received it once daily. Majority of the patients received intravenous proton pump inhibitor despite taking other drugs by oral route.Conclusions: Most of the PPI administration was done without appropriate indication. All patients received Intravenous proton pump inhibitors, which may impose economic burden on a government hospital. Majority of the patients received proton pump inhibitors twice daily. These approaches are not cost effective and need to be rectified.

Evaluation of the long-term safety and effectiveness of tadalafil once daily in Chinese men with erectile dysfunction: Interim results of a multicenter, randomized, open-label trial / 亚洲男科学杂志(英文版)

Once-daily tadalafil administration has been well established; however, studies about tadalafil once-daily treatment in the Chinese population are lacking. In this phase 4, postmarketing study, we ascertained the long-term safety and effectiveness of tadalafil 2.5 mg and 5.0 mg once daily in Chinese men with erectile dysfunction (n = 635). The primary endpoint of the study was safety at 12 months as assessed by the proportion of patients experiencing at least one treatment-emergent adverse event (serious or nonserious). The secondary endpoints included safety and effectiveness, measured by the International Index of Erectile Function-Erectile Function (IIEF-EF) domain scores. Similar adverse events to the known safety profile of tadalafil, such as nasopharyngitis, upper respiratory tract infection, headache, and dizziness, were detected. No new cardiovascular safety concerns were observed. After 3 months of treatment, significant increases in IIEF-EF domain scores were detected for both 2.5-mg (least squares [LS] mean change: 6.3; 95% confidence interval [CI]: 5.4-7.1; P < 0.001) and 5.0-mg (LS mean change: 7.4; 95% CI: 6.8-7.9; P < 0.001) tadalafil doses, and significance was maintained up to 12 months. In addition, approximately 40% of patients regained normal erectile function (IIEF-EF ≥26) following 1 year of tadalafil once-daily treatment. The findings in this study provide evidence for the extended effectiveness and tolerability of tadalafil, demonstrating no new safety concerns, in a Chinese population and make once-daily tadalafil administration a viable option for improving sexual performance and satisfaction in Chinese men with erectile dysfunction.

Pharmacokinetics of once daily prolonged-release formulation of tacrolimus in children with primary nephrotic syndrome / 北京大学学报(医学版)

Objective:Tacrolimus prolonged-release(PR) formulation is a new once-daily formulation of the calcineurin inhibitor tacrolimus,which is currently used in adult liver or kidney transplant patients,and is also gradually widely used in children with nephrotic syndrome.The present study was undertaken to preliminarily investigate the pharmacokinetic characteristics of tacrolimus PR in pediatric nephrotic syndrome recipients.Methods:This single-center open-label prospective study was performed in pediatric nephrotic syndrome recipients.Pharmacokinetic samples were collected from eight pediatric subjects with nephrotic syndrome from Department of Pediatric Nephrology in Peking University First Hospital between June and August 2011.They followed administration of single oral doses of tacrolimus PR formulation at 0.02 mg/kg (n =2),0.05 mg/kg (n =2) and 0.10 mg/kg (n =4).Blood samples were taken before the dose and 1,2,4,6,8,10,12 and 24 h after drug intake.No other medicines or interacting food or drinks were taken during the study period.Blood concentrations were measured using an enzyme multiplied immunoassay technique.Pharmacokinetic analysis was performed using WinNolin Phoenix software Version 6.0 (Pharsight,Cary,NC,USA).Results:The pharmacokinetic data were best described by a non-compartment model.Pharmacokinetic parameters of tacrolimus PR formulation in the 3 ascending doses groups (0.02 mg/kg,0.05 mg/kg and 0.10 mg/kg) were as follows:the maxi mum drug concentrations (Cm=/D) were (1.7 ± 1.0) μg/L,(3.1 ± 1.9) μg/L,(8.0 ± 3.5) μg/L,respectively;Areas under the drug concentration-time curve (AUCo-∞/D) were (47.2 ± 47.1) h · μg/ L,(84.0 ± 13.1) h · μg/L,(175.6 ± 107.1) h · μg/L,respectively;Oral clearance rates were (0.8±0.9) L/(h·kg),(0.4±0.1) L/(h · kg),(1.9 ±1.3) L/(h · kg),respectively;Body weight normalized distribution volumes were (7.0 ± 3.4) L/kg,(12.4 ± 8.4) L/kg and (73.6 ± 68.6) L/kg,respectively.Both mean Cmax normalized level for the administered dose (Cmax/D) and mean AUC0-∞ normalized level for the administered dose (AUC0-∞/D) were higher in the 0.05 mg/kg dosage group than in the 0.02 and 0.10 mg/kg dosage group.There were two peaks in the drug concentrations in every dose group;a primary peak appeared at the end of about 2 h followed by a small secondary peak at h 12,which was more noticeable in the 0.10 mg/kg dose group than in the two lower dosages.Conclusion:The pharmacokinetic characteristics of tacrolimus PR formulation were initially explored in pediatric patients with nephritic syndrome.The data presented form a basis for subsequent larger scale studies on pharmacokinetics of tacrolimus PR formulation in nephritic syndrome children.

Comparison of efficacies of once-daily dose multimatrix mesalazine and multiple-dose mesalazine for the maintenance of remission in ulcerative colitis: a randomized, double-blind study

BACKGROUND/AIMS: This study compared the efficacy of once-daily administration of multimatrix mesalazine 2.4 g/day with multiple-dose mesalazine for the maintenance of remission. METHODS: In this multicenter, randomized, double-blind study, 203 patients with ulcerative colitis in remission received multimatrix mesalazine 2.4 g/day once-daily or time-dependent (controlled-release) mesalazine 2.25 g/day 3 times-daily for 48 weeks. The primary efficacy endpoint was the proportion of patients without rectal bleeding. RESULTS: The proportion of patients without rectal bleeding during the 48-week treatment period in the per protocol set was 84.8% (84/99) in the multimatrix mesalazine 2.4 g/day group and 78.0% (78/100) in the controlled-release mesalazine 2.25 g/day group. The difference between the 2 treatment groups was 6.8% (two-sided 95% confidence interval, −3.9% to 17.6%). The noninferiority margin of −10% was met in the comparison of multimatrix mesalazine 2.4 g/day once-daily with controlled-release mesalazine 2.25 g/day. Multimatrix mesalazine 2.4 g/day once-daily demonstrated consistent efficacy in all subgroups. There was no difference between the 2 treatment groups with regard to safety. CONCLUSIONS: A once-daily dose of 2 multimatrix mesalazine tablets (2.4 g) was not inferior to controlled-release mesalazine 2.25 g/day 3 times-daily in maintaining absence of rectal bleeding in ulcerative colitis.

Risk Factors for the Adverse Events after Conversion from Twice-Daily to Once-Daily Tacrolimus in Stable Liver Transplantation Patients

Despite the therapeutic equivalence between twice-daily and once-daily tacrolimus, patient safety after conversion is still a concern. We reviewed 218 liver transplantation (LT) patients who converted twice-daily to once-daily tacrolimus between May 2011 and January 2014. Thirty (13.8%) patients had adverse events after conversion, with a liver function test (LFT) abnormality being the most common adverse event (n = 17). Despite the decrease in serum tacrolimus of > 30% after conversion, none of the patients who were converted to a dosage ratio (once-daily tacrolimus dosage: twice-daily tacrolimus dosage) > 1 had an LFT abnormality. Most patients with an LFT abnormality improved after increasing the once-daily tacrolimus dosage (n = 2), returned to a previous medication, and/or added another immunosuppressant (n = 15). One patient had acute cellular rejection, which improved after steroid pulse treatment, and another patient had graft failure. In patients with a dosage ratio ≤ 1, the conversion time within 5 years after LT was the only significant risk factor for an LFT abnormality after conversion (odds ratio: 11.850, 95% confidence interval: 1.321–106.325, P = 0.027). In conclusion, the dosage ratio and time after LT should be carefully considered during conversion from twice-daily to once-daily tacrolimus.

Single Center Experiences of Conversion from Twice-daily Tacrolimus (Prograf) to Once-daily Tacrolimus (Advagraf) in Stable Liver Transplant Recipients / 대한이식학회지

BACKGROUND: Patient adherence to immunosuppressant regimens after organ transplant is crucial to preserve graft function, and simplifying the regimen improves adherence. In this study, our experience of conversion from twice-daily (b.i.d.) to once-daily (q.d.) tacrolimus (TAC) in stable liver transplant recipients is reviewed and the proper conversion regimen is investigated. METHODS: Between November 2011 and August 2012, the regimen was converted in 32 stable liver transplant recipients, and data on the conversions gathered retrospectively from medical records. TAC trough level, dose, and laboratory findings were evaluated at preconversion and 1 to 12 months after conversion. RESULTS: Conversion from b.i.d. to q.d. regimen was based on 1:1 proportion in 16 patients and dose escalation in 16 patients. The mean conversion time after transplant was 56.8 months (range; 21~94). Reconversion to b.i.d. regimen was needed in nine patients. Among these patients, seven patients needed titration due to elevated liver enzyme. The trough level decreased significantly after conversion (from 4.7 to 3.1 ng/mL) in patients with conversion at 1:1 proportion, while increasing slightly without statistical significance (3.7 to 4.0 ng/mL) in patients with dose escalation. At 1 year after conversion, dose adjustment was required to preserve trough level and graft function in 14 patients. CONCLUSIONS: Based on our results, TAC q.d. formulation can be a useful option to improve adherence in stable liver transplant recipients. However, dose titration should be considered for preserving proper trough level in case of low TAC level or TAC single regimen.

Mesalazine sustained-release granules taking once daily or multi-times daily in the treatment of mild to moderate active ulcerative colitis：a randomised controlled clinical trial / 中华消化杂志

Objective To investigate the efficacy ,safety and compliance of mesalazine sustained‐release (SR) granules taking once daily or multi‐times daily in the treatment of patients with mild to moderate active ulcerative colitis .Methods Sixty patients with mild to moderate active ulcerative colitis were divided into group A ,B and C with 20 patients in each group .Group A received mesalazine SR granules 4 g once daily ,Group B with 2 g each time and twice daily ,Group C with 1 g each time and four times daily . The total course was eight weeks . The vital signs ,Mayo score ,compliance and adverse effects of patients were monitored at 0 ,4th ,8th weeks .At 0 and 8th weeks ,colonoscopy were performed . The parameters of efficacy assessment were clinical complete remission rate , clinical remission rate , efficacy rate ,mucosal healing rate ,remission time and safety .The F test ,t test or Chi‐square test was performed for comparison among groups .Results The clinical complete remission rate of group A ,B and C was 20% (4/20) ,10% (2/20) and 10% (2/20) ,respectively .The clinical complete remission rate was 70% (14/20) ,65% (13/20) and 70% (14/20) ,respectively .The efficacy rate was 95% (19/20) ,85%(17/20) and 90% (18/20) ,respectively .The mucosal healing rate was 70% (14/20) ,60% (12/20) and 50% (10/20) ,respectively .The side effects rate was 20% (4/20) ,15% (3/20) and 20% (4/20) .There was no significant difference between groups (all P > 0 .05) .The remission time of group A and B was (15 .4 ± 3 .7) days and (15 .6 ± 2 .9) days ,which were both shorter than that of group C (18 .4 ± 3 .6) days ,and the differences were statistically significant (t= 2 .661 and 2 .710 ,both P< 0 .05) .There was no significant difference among three groups in gender ,disease course , severity , location and clinical remission rate of sub‐groups .Conclusions The efficacy and safety of mesalazine SR granules taking once daily or multi‐times daily are similar in the treatment of patients with mild to moderate active ulcerative colitis .Once daily have better compliance than other regimens .

The Efficacy and Safety of Tadalafil 5 mg Once Daily in the Treatment of Erectile Dysfunction After Robot-Assisted Laparoscopic Radical Prostatectomy: 1-Year Follow-up

PURPOSE: To evaluate the efficacy and safety of tadalafil 5 mg once daily use in the treatment of erectile dysfunction (ED) after robot-assisted laparoscopic radical prostatectomy (RALP). MATERIALS AND METHODS: The study retrospectively evaluated 92 patients who underwent RALP at Dong-A University Hospital. The patients were surveyed by use of the abridged five-item version of the International Index of Erectile Function (IIEF-5) questionnaire, which was self-administered before surgery and at 6 months and 1 year after surgery. The 92 patients were classified into the tadalafil group (n=47) and the non-tadalafil group (n=45). Each group was then classified depending on the nerve-sparing (NS) procedure used: bilateral NS or unilateral NS. RESULTS: At 6 months, the total IIEF-5 scores of the tadalafil group and the non-tadalafil group were 10.0+/-3.4 and 7.0+/-4.0, respectively. At 1 year, the total IIEF-5 score in the tadalafil group was significantly greater than that in the non-tadalafil group (13.2+/-5.6 vs. 7.7+/-4.8, p<0.0001). Statistically significant improvements (p<0.05) were observed in the tadalafil group for all 5 domains of the IIEF-5 score, whereas in the non-tadalafil group there was no significant improvement in any of the domains at 1 year. The reported side effects were flushing (8.5%, n=4), headache (4.3%, n=2), and dizziness (2.1%, n=1). CONCLUSIONS: In ED patients after NS RALP, a once-daily dose of tadalafil 5 mg was well tolerated and significantly improved EF compared with that in the non-tadalafil group.

Study of Efficacy and Safety in the Administration of 400 mg of Amikacin Sulfate Administered Once Daily to Elderly Patients / 医薬品情報学

<b>Objective: </b>In previously reported comparisons of aminoglycoside antimicrobials administered once daily versus multiple administration, toxicity was found to be equal or lower while efficiency remained high.  However, there are few reports on the clinical condition of targeted elderly persons.  The objective of this study was to evaluate the once-daily dosing regimen of 400 mg of AMK involving elderly pneumonia patients aged 75 years or older with regard to clinical evaluation including the efficacy and toxicity.<br><b>Methods: </b>A survey to clinically evaluate the efficacy and toxicity of 400 mg AMK administered once daily for 30 min at 24 h intervals was carried out.  One hundred twenty-seven patients with pneumonia and who were 75 years or older at Funabashi General Hospital were targeted, with the aim of an expected clinical effect of <i>C</i>_max/MIC≥ 8-10.  Serum concentration monitoring was carried out after administration began.<br><b>Results: </b>There were 121 patients (95.3%) of controlled AMK concentration with a trough serum concentration of <10 μg/mL, which is a safe concentration range.  There were 6 patients (4.7%) where trough serum concentration in the toxic range >10 μg/mL, with an average at 15.1±5.0 μg/mL, and the average administration days were 7.5 ± 3.3 days.  Moreover, before/after AMK administration, there were 3 patients (2.4%) where CRE values increased more than a 150% over the previous values, and were evaluated as renal dysfunction.  Average trough serum concentration at that time was 3.6 ± 1.1 μg/mL, and average number of days of administration were 13 ± 1.4 days.  Patients of trough serum concentration in the toxic range >10 μg/mL were not included.  The average peak serum concentration calculated by Winter’s pharmacokinetic parameter and the 1-compartment model was 35.3 ± 8.0 μg/mL, and the average <i>C</i>_max/MIC which correlates with the AMK effect was 9.9 ± 2.2.  The treatment was effective for 83 (65.4%) of the 127 patients.<br><b>Conclusion: </b>By once-daily administration of AMK 400 mg to aged persons 75 years or older, change in trough serum concentration into a safe range and <i>C</i>_max/MIC≥ 8-10, the level at which clinical effectivity can be expected, could be achieved.  This administration method is shown to be useful in maintaining AMK in the target serum concentration range for aged persons.

Once-Daily Gentamicin Administration for Community-Associated Methicillin Resistant Staphylococcus aureus in an in vitro Pharmacodynamic Model: Preliminary Reports for the Advantages for Optimizing Pharmacodynamic Index

PURPOSE: Community-associated methicillin resistant Staphylococcus aureus (CA-MRSA) infections are increasing. Although gentamicin (GEN) is usually susceptible against CA-MRSA, GEN is rarely considered for treatment as monotherapy. We employed an in vitro pharmacodynamic model (IVPDM) to compare efficacies of GEN against CA-MRSA with two dosing regimens [thrice-daily (TD), once-daily (OD)]. MATERIALS AND METHODS: Using two strains of CA-MRSA, we adopted IVPDM comprised of two-compartments with a surface-to-volume ratio of 5.34 cm-1. GEN regimens were simulated with human pharmacokinetic data of TD and OD. Experiments were performed over 48 hours in triplicate for each strain and dosing regimen. RESULTS: MICs of GEN for YSSA1 and YSSA15 were 1 and 2 mg/L, respectively. In OD, indices of peak/MIC were > 8.6 at least, in contrast to or = 3-log10 reduction in CFU/mL was demonstrated prior to 4 hours in TD and OD, and continued until 8 hours for both strains. However, reductions in the colony counts at 24 and 48 hours were significantly larger for OD compared to TD in both strains (p < 0.001). During TD, resistance developed in YSSA1 and small colony variants (SCVs) were documented in YSSA15. No resistance or SCVs were observed during OD in both strains. CONCLUSION: TD and OD showed the same killing slopes until 8 hours. After the 24 hours of experiments, OD of GEN would be advantageous not only in having more reductions in colony counts, but also suppressing the development of resistance or SCVs for 48 hours.

The Effectiveness of Once-daily Intravenous Busulfan as a Conditioning Regime for Hematopoietic Stem Cell Transplantation in Children with Acute Myelogenous Leukemia / 대한혈액학회지

BACKGROUND: There have recently been some reports suggesting that once-daily intravenous busulfan (IV Bu) as a conditioning regime for hematopoietic stem cell transplantation (HSCT) possibly reduces the toxicities without influencing the clinical outcome as compared with the traditional 4 times daily dosage schedule. We report here on the clinical outcome of once-daily IV Bu as a conditioning regime for HSCT in children with AML at a single treatment center. METHODS: We retrospectively analyzed nine AML children who received HSCT with using the once-daily IV Bu (110~130 mg/m2 on 4 consecutive days) conditioning regimen at the Department of Pediatrics, Pusan National University Hospital from 2003 to 2007. RESULTS: The median age at HSCT was 8.25 years. As for the conditioning regimens, the HLA-matched sibling peripheral HSCT (N=4) was Flu/Bu, the CBT and unrelated BMT (N=4) was Flu/Bu/ATG and the autologous HSCT (N=1) was Bu/Cy. There was only one case of primary graft failure in an unrelated donor CBT recipient. The median time to neutrophil engraftment was 14 days and the median time to platelet engraftment was 19 days. The transplant-related toxicities were acceptable; there were no case with CNS toxicity and VOD was observed in two cases (1 mild case of VOD and 1 moderate case of VOD). Acute GVHD was noted in two cases (1 case of grade I and 1 case of IV). With a median follow up of 33 months, there were two cases of relapse and two cases of death. CONCLUSION: Once-daily IV Bu as a conditioning regimen for HSCT in children with AML was well tolerated and convenient with relatively moderate toxicities, but additional studies are needed to determine the therapeutic efficacy and pharmacokinetics of once-daily IV Bu in children who are undergoing HSCT.

The glycemic control in Chinese type 2 diabetic out-patients receiving oral antidiabetic agents and the efficacy and safety of optimized modified-release gliclazide treatment / 中华内分泌代谢杂志

Objective To evaluate the current state of glycemie control in Chinese patients with type 2 diabetes mellitus who have received oral antidiabetic agents in the out-patient clinic,and the efficacy and safety of optimized regiments of gliclazide modified-release tablets (Diamicron MR, SERVIER, Tianjin) in patients with failed glycemic control (HbA1c 6.5%). Methods The patients with type 2 diabetes were enrolled from 54 hospitals in more than 20 cities and received long-term (more than 3 months) oral antidiabetic agents. HbA1c was measured and the success rate of HbA1c reduction was evaluated. The patients who failed to achieve glycemic control (HbA1c 6. 5%) and received daily multiple-dosing insulin secretagogues were provided with the optimized treatment regimen, consisting of replacing daily multiple-dosing insulin secretagogues with single-dosing gliclazide sustained-release tablets. Clinical efficacy and safety were evaluated after three months treatment. Results The survey of glycemic control revealed that the mean HbA1c of 5 586 patients with diabetes mellitus was (7.97±2.89)% ,and the success rate (HbA1c≤6.5%) was 14. 1%. Further more, HbA1c decreased from (8.23±4.00)% before optimization to (6.86±2.24)% after optimization with the average decrement of 1.37% (P<0. 001) and the success rate was raised to 34. 1%. The gliclazide modified-release tablets were well tolerated by most patients, only 2.6% of whom were reported to experience unconfirmed hypoglycemia. Conclusion The success rate of glycemic control was low in Chinese out-patients with type 2 diabetes mellitus receiving oral antidiabetic agents in the clinic. The optimized regimen of gliclazide modified-release tablets taken once daily can down-regulate glycemic levels and increase the success rate of HbA1c reduction,and thus plays efficiently and safely a key role in the optimized management of type 2 diabetes mellitus.

Once daily dosing of aminoglycoside in children / 소아과

Aminoglycosides are frequently used antibiotics in children. The multiple daily dosing (MDD) in infants and children is twice or three times daily depending on age. Recent studies in adults have shown that once daily dosing (ODD) maximizes the bactericidal activity and might minimize the toxicity of antibiotics. So, I reviewed many studies about efficacy, toxicity and cost effectiveness of ODD of aminoglycosides in children. Most studies suggest that ODD compared with MDD of aminoglycosides is theoretically more efficacious and has no higher toxicity in infants and children. But, the total number of patients included in the studies is not large. Multi-center, controlled prospective studies are required in larger numbers of infants and children to determine the efficacy and safety of the ODD regimen in children before ODD of aminoglycosides can be recommended for routine use.

The Comparison of Clinical Efficacy and Side Effects of Once Daily Versus Divided Doses of Gentamicin in Acute Pyelonephritis / 감염

BACKGROUND: Once daily dose of aminoglycoside has been used recently in the gram-negative infection for the purpose of improving efficacy. The clinical efficacy and side effects of once daily versus divided doses of gentamicin were compared in acute pyelonephritis. METHOD: Gentamicin (3-5mg/kg/day) was administered into 3 divided doses intravenously in 15 patients of the divided dose group, and the same dose was administered at a time in 19 patients of the once daily dose group. The duration of treatment was 6-14 days. RESULTS: The clinical outcome of all patients was favorable, and nephrotoxicity or ototoxicity was not detected in any patients. E. coli were isolated from 12 patients in the divided dose group, and 15 patients in the once daily dose group. They were all eradicated after treatment. The mean peak serum concentrations of gentamicin were 5.33+/-1.99;g/mL in the divided dose group, and 14.79+/-5.71g/mL in the once daily dose group. The trough concentrations were not different significantly between two groups(0.69+/-0.58;g/mL in the divided dose group vs. 0.35+/-0.45g/mL in the once daily dose group). The number of patients with peak concentration over 5.0g/mL was 8 out of 15 in the divided dose group. CONCLUSION: The once daily dose of gentamicin was as effective as the divided dose, and the nephrotoxicity or ototoxicity was not observed in both groups.

Effect of Nitrendipine on the Blood Pressure of Mild Hypertensives

Fifty patients with mild essential hypertension were studied to evaluate the efficacy of once-daily regimen of nitrendipine, 10~20mg daily for 12 weeks. 1) Thirty-Seven patients completed the study and showed -9% change in mean arterial headache etc. 2) Eight patients were dropped out because of side reaction, namely flushing, palpitation, headache etc. 3) Ambulatory blood pressure monitoring before and after treatment in 3 patients confirmed the drug efficacy revealing 9% decrement in mean blood pressure and 46% decrease in % elevated BP. 4) Twenty patients who were controlled with other hypotensive drugs were well controlled & maintained the blood pressure in normal range after switching to nitrendpine 10~20mg daily. In conclusion, citrendipine is a safe and good antihypertensive calcium antagonist in the treatment of mild hypertensives with 10~20mg of once-daily dosage.