Gastrointestinal Tolerability Research Articles

Gastrointestinal Tolerability of Delayed-Release Dimethyl Fumarate in a Multicenter, Open-Label Study of Patients With Relapsing Forms of Multiple Sclerosis (P2.227)

Gastrointestinal Tolerability of Delayed-Release Dimethyl Fumarate in a Multicenter, Open-Label Study of Patients With Relapsing Forms of Multiple Sclerosis (P2.227)

Tolerance and Cognitive Function Effects of a Proprietary Spearmint Extract in Men and Women with Self‐Reported Memory Impairment ‐ A Pilot Study (LB402)

This pilot trial assessed the tolerance of a proprietary extract from Mentha spicata L. and its effects on cognition in subjects with self‐reported memory impairment. Subjects (N = 11) consumed 900 mg of the extract daily for 30 d. Participants were 73% female and 27% male with a mean age and body mass index of 58.7 y and 27.4 kg/m2. Tolerance was assessed by evaluation of gastrointestinal (GI) tolerability, adverse events, and clinical laboratory tests at baseline and the end of treatment (EOT). Acute cognitive effects were evaluated by comparing pre‐dose vs. 0.5 to 4 h post‐dose values at baseline and EOT. Subjective cognition was also assessed at the EOT. Consumption of the extract for 30 d did not significantly alter GI symptoms and subjective cognition improved (3.5 vs. 4.0; P = 0.063). No serious adverse events or clinically relevant findings in the safety parameters were observed. Cognitive function task scores suggest improved reasoning (24.7 vs. 33.4 points; P = 0.023), attention/concentration (18.0 vs. 40.5 points; P = 0.002), and planning (29.8 vs. 44.1 points; P = 0.088) from baseline after 30 d of treatment. Day one, subjects experienced acutely improved attention/concentration from pre‐ supplementation vs. 2 h (63.4 vs. 82.4 points, P = 0.042 and 18.0 vs. 34.8 points, P = 0.025) and 4 h (63.4 vs. 92.5 points, P = 0.001 and 18.0 vs. 39.8 points, P = 0.002). These results suggest the extract was well‐tolerated and may improve certain aspects of cognitive function. Further investigation in a randomized, controlled trial is underway.Grant Funding Source: Kemin Foods, L.C.

Managing flushing and gastrointestinal events associated with delayed-release dimethyl fumarate: Experiences of an international panel

Strategies for monitoring and managing the known adverse event (AE) profile of therapies for relapsing–remitting multiple sclerosis have become key to the optimization of patient outcomes. Delayed-release dimethyl fumarate (DMF) was associated with an increased risk of flushing and gastrointestinal (GI) AEs in clinical trials. A survey of clinicians with significant research experience using delayed-release DMF was conducted to provide guidance to clinicians using delayed-release DMF in clinical practice on the management of flushing and GI tolerability AEs. Recommendations for prophylaxis included educating the patient about flushing and GI AEs associated with delayed-release DMF and recommending administration with food. A variety of symptomatic treatments were utilized during the delayed-release DMF clinical trials in patients presenting with delayed-release DMF–related flushing or GI AEs that were severe or bothersome enough to warrant pharmacological intervention.

The transdermal formulation of rivastigmine improves caregiver burden and treatment adherence of patients with Alzheimer's disease under daily practice conditions

BackgroundRivastigmine is the only cholinesterase inhibitor (ChEI) available as transdermal patch. The patch was developed to improve gastrointestinal tolerability and treatment adherence to higher dosages as compared with oral medication. Preferences of patients and caregivers for the patch were reported; however, neither patient compliance nor caregiver burden has yet been measured under routine practice conditions.MethodsThis was a prospective, multi-centre, observational study in patients with Alzheimer's disease treated with rivastigmine patch in Germany. To compare the transdermal with oral dosage forms, physicians were asked to enrol patients who recently switched from oral to transdermal medication. Beyond effectiveness and tolerability, outcome measures were drug adherence evaluated by the Morisky questionnaire, and caregiver burden, measured as the daily time expenditure for dressing the patient, controlling appearance and administration of medication.ResultsIn total, 1104 outpatients (57.5% female gender; mean age 77 ± 7 years) were enrolled in 220 sites. After 6 months of treatment, 67.5% of patients had an improved Clinical Global Impression and the Mini-Mental State Examination score increased from 19.0 ± 5.1 to 20.0 ± 5.2 (p < 0.001); 84.1% of patients were still on treatment, 64.6% on the target dose of 9.5 mg/day. Compliance and patient satisfaction with therapy continuously increased over the study period and average time savings of caregivers added up to 20 min/day. In general, tolerability was deemed good and there were no unexpected adverse events.ConclusionsTransdermal rivastigmine is an effective treatment alternative, which may improve adherence and treatment satisfaction of the patient and relieve the caregiver. Controlled parallel-group trials are warranted.Clinical trials registration: none (observational study).

A novel cobiotic containing a prebiotic and an antioxidant augments the glucose control and gastrointestinal tolerability of metformin: a case report

The gut microbiome plays an important role in regulation of metabolic processes, including digestion, absorption, and synthesis of bioactive molecules that signal physiological host mechanisms. Changes in the human gut microbiome are associated with type 2 diabetes and insulin resistance. Water-soluble dietary fibres like inulin and beta-glucan are fermented in the colon, and beta-glucan increases viscosity. Blueberries improve insulin sensitivity through an antioxidant effect. A cobiotic, consisting of purified inulin, sugar-free blueberry pomace extract, and an oat preparation of purified beta-glucan was developed for twice a day (bid) consumption as a smoothie drink to repair the gastrointestinal dysbiosis in type 2 diabetes. A 30-year-old man presented with new onset type 2 diabetes and a fasting glucose (FBS) of 375 mg/dl. Metformin 500 mg bid was initiated and increased to 1 g bid after 1 week. During the first 9 days of metformin treatment, he developed diarrhoea, but his FBS only dropped to 325 mg/dl. The cobiotic bid was added on the 9th day of metformin treatment, and after 2 days, his FBS dropped to 175 mg/dl. After 8 weeks on metformin and the cobiotic, his blood sugar was 100 mg/dl and he lost 5.5 kg. His stools became soft and formed on the cobiotic, reverted to diarrhoea when off of it for 2 days, and returned to normal on resuming the cobiotic formulation. Metformin is a safe, effective and inexpensive generic medication favouring weight loss, recommended as initial treatment of type 2 diabetes by the American Diabetes Association. However, a 20% incidence of diarrhoea limits its tolerability. A safe food supplement that can increase the efficacy of metformin and its tolerability, as occurred in this case report, would have significant positive public health consequences. A controlled clinical trial of the cobiotic with metformin is planned.

The Mu-Opioid Receptor Agonist/Noradrenaline Reuptake Inhibition (MOR–NRI) Concept in Analgesia: The Case of Tapentadol

Tapentadol is a novel, centrally-acting analgesic drug, with an analgesic efficacy comparable to that of strong opioids such as oxycodone and morphine. Its high efficacy has been demonstrated in a range of animal models of acute and chronic, nociceptive, inflammatory, and neuropathic pain as well as in clinical studies with moderate to severe pain arising from a number of different etiologies. At the same time, a favorable gastrointestinal tolerability has been demonstrated in rodents and humans, and advantages over morphine regarding tolerance development and physical dependence were shown in animal studies. Furthermore, a low level of abuse and diversion is beginning to emerge from first post-marketing data. Tapentadol acts as a μ-opioid receptor (MOR) agonist and noradrenaline reuptake inhibitor (NRI). Both mechanisms of action have been shown to contribute to the analgesic activity of tapentadol and to produce analgesia in a synergistic manner, such that relatively moderate activity at the two target sites (MOR and noradrenaline reuptake transporter) is sufficient to produce strong analgesic effects. It has been suggested that tapentadol is the first representative of a proposed new class of analgesics, MOR-NRI. This review presents the evidence that has led to this suggestion, and outlines how the pharmacology of tapentadol can explain its broad analgesic activity profile and high analgesic potency as well as its favorable tolerability.

Journal of Diabetes News

Journal of Diabetes News

Comparison of the effectivity of oral and intra-articular administration of tenoxicam in patients with knee osteoarthritis

Background and objectivesTenoxicam is widely used in osteoarthritis treatment and we aimed to compare the effectivity of oral and intra-articular administration of tenoxicam in osteoarthritis treatment. MethodsThis study was performed between 2011 and 2012 by retrospectively analyzing and comparing the findings of 60 patients who were clinically and radiologically diagnosed with knee degenerative osteoarthritis in Bünyan state hospital pain policlinic. 60 patients included in the study were divided into two groups. The first group (tenoxicam IA, n=30) included patient findings of those subjected to intra-articular injection of 20mg tenoxicam to the knee once a week for three weeks and the second group (oral tenoxicam, n=30) included patients who were administered 20mg oral tenoxicam once a day for three weeks. All patients were clinically evaluated pre-treatment and in the 1st week, 1st month and 3rd month post-treatment according to specified criteria. Results and conclusionsTwenty two of 60 patients included in the study were male and 38 were female. In both groups significant improvements were detected in all of the observed parameters: visual analog scale, Western Ontario McMaster Osteoarthritis Index (pain, physical activity, knee stiffness) and Lequesne index scores and in the evaluations performed in 1st week, 1st month and 3rd month with respect to pre-treatment values. Besides, a better compliance to treatment and gastrointestinal system tolerability in tenoxicam IA group was also observed. Intra-articular tenoxicam administration could be thought as an alternative treatment method in patients with knee osteoarthritis who cannot use oral tenoxicam especially due to systemic gastrointestinal system side effects and those who have difficulties in adapting to treatment.

Compliance and efficacy of extended release Metformin and immediate release thrice daily Metformin in type-2 Diabetes Mellitus- A comparative study

Aim of study: Metformin is a first-line pharmacological treatment for patients with type 2 diabetes mellitus because of its favorable overall profile, including its glucose-lowering ability, weight-neutral effects, and low risk of hypoglycemia; however, gastrointestinal (GI) intolerance may limit use in some patients. Extendedrelease metformin improves GI tolerability, allows once-daily dosing,improves compliance in patients. Conclusion: Patients with type 2 DM who had been receiving thrice daily MIR achieved comparable glycemic control when therapy was switched to once or twice daily MXR at the same daily dose. I. Introduction Metformin hydrochloride has been widely used as an effective and generally well-tolerated glucoselowering agent for >40 years and is the most frequently prescribed first-line therapy for patients with type 2 diabetes . Metformin typically reduces basal and postprandial hyperglycemia by ∼25% in >90% of patients when given alone or with other therapies during a program of managed care. An extended release formulation (MXR approved in October 2000 allows once daily dosing. This newer formulation release the active drug through active hydrated polymers which expand after uptake of fluids. This prolongs gastric residence time. Extended-release metformin showed slightly lower maximum concentrations, longer times to maximum concentration (7–8 vs. 4–5 h), and similar bioavailability compared with immediate-release products. This extended release could potentially reduce dosing frequency to once daily compared with two or three times daily for immediate-release formulations. which produces slower drug action in the upper GI tract allowing once a day dosing. II. Materials And Methods We conducted a clinical trial involving 75 patients with T2DM who were on at least 1 gm of MIR with or without other antihyperglycemic agents. Eligibility criteria included an age of atleast 40 years, a BMI of 20 or higher, and fasting capillary glucose of 1.4 mg% for women) hepatic dysfunction, congestive heart failure, major psychiatric disorder ,alcohol and/ or substance abuse ,seizure disorders, or a history of malignancy or steroid intake, pregnant or breastfeeding women were excluded from the study. Patients could be receiving long term insulin therapy or any other anti hyperglycemic therapy apart from MIR. After a lead in period of three months, during which patients were on weight maintenance diet and 1000-2000mg of MIR (in 2 or 3 divided doses) all patients who were at least 80% compliant with the drug treatment(as determined by tablets count and interviews) were entered in the study. At the visit of trial(visit 0) all eligible patients with T2DM were switched over to one particular brand of MIR while the dose of MIR and other hypoglycemic agents were kept the same. Baseline measurement included a two point glucose profile (Fasting, 2 hour PP), Serum Lipid profile (Total Cholesterol), low density lipoprotein cholesterol (LDL), High Density Lipoprotein (HDL) and Triglycerides (TG) are concentrations, standard laboratory tests (haematology, serum chemistry profile, urine analysis) and electrocardiography (ECG). A record of body weight, blood pressure and other vital signs were maintained. After one month (Visit 1) a subjects were assessed and then switched over to 500mg lesser dose of MXR which was given in the form of a single dose after dinner. Whereas the other antihyperglycemic agents were continued. Patients were subsequently called for 3 or more monthly intervals.

Effectiveness and tolerability of low-dose oral oxycodone/naloxone added to anticonvulsant therapy for noncancer neuropathic pain: an observational analysis

Background:Opioids may alleviate chronic neuropathic pain (NP), but are considered second/third-line analgesia due to their poor gastrointestinal (GI) tolerability. A fixed combination of prolonged-release oxycodone and naloxone (OXN) has been developed to overcome the GI effects. The aim of this analysis was to evaluate analgesic effectiveness and tolerability of low-dose OXN in patients with moderate-to-severe noncancer NP despite analgesia.Methods:This retrospective observation of consecutive adult patients, treated open-label for 8 weeks at a single Italian centre, evaluated effectiveness (pain intensity numerical rating scale [NRS], Patients’ Global Impression of Change [PGIC], Douleur Neuropathique 4 inventory [DN4] and Chronic Pain Sleep Inventory [CPSI]), doses of daily OXN and adjuvant medication, rescue paracetamol use, bowel function index (BFI), laxative use, and safety.Results:Of 200 patients (mean age 65.9 years; 54% female) with NP included in the analysis; 97% completed 8 weeks’ treatment. At the observation start, all patients were taking anticonvulsants and complained of constipation, and 60% were receiving opioids. Pain intensity and DN4 score decreased significantly by endpoint (NRS p < 0.0001; DN4 p < 0.0001) and need for rescue analgesics abated. Reduction in pain intensity throughout the observation was similar regardless of NP aetiology. According to PGIC, 87.8% of patients were much/extremely improved, CPSI (p < 0.0001) and BFI were significantly improved (p < 0.0001) and laxative use decreased. No differences were found between patients <65 years vs those ≥65 years. OXN was generally well tolerated.Study limitations:Study limitations including the retrospective observational design, the lack of a control group and the single-centre design may limit the generalizability of our findings.Conclusions:Low-dose OXN (25.0 ± 12.5 mg/day) added to anticonvulsants was highly effective in controlling noncancer NP of varied aetiology, with reduced need for rescue analgesia and improved quality of sleep, and was well tolerated, with improved bowel function and reduced laxative use. The efficacy and tolerability of OXN demonstrated in this real-world setting suggest its utility in this difficult to manage patient population.

Efficacy and Gastrointestinal Tolerability of Oral Oxycodone/Naloxone Combination for Chronic Pain in Outpatients With Cancer

Combination opioid agonist/antagonist therapy has been shown to preserve bowel function in patients with chronic cancer pain. This retrospective study evaluated the efficacy and tolerability of prolonged-released fixed-dose oxycodone-naloxone (PR OXN) in consecutive outpatients with chronic cancer pain. Of 206 patients prescribed PR OXN (mean age 61.3 ± 12.9 years; 52.9% female), 31.5% were opioid naïve. PR OXN was associated with a significant decrease in pain score measured on a visual analogue scale over 28 days (P < .0001), without adverse effects on bowel function, nor change in laxative use. PR OXN efficacy and tolerability were similar in opioid-naïve and -experienced patients, and among age-stratified subgroups. No severe side effects occurred. In a real-life outpatient setting, PR OXN provided analgesia without bowel dysfunction in patients with chronic cancer pain.

Efficacy and gastrointestinal tolerability of ML3403, a selective inhibitor of p38 MAP kinase and CBS-3595, a dual inhibitor of p38 MAP kinase and phosphodiesterase 4 in CFA-induced arthritis in rats

Mitogen-activated protein kinase (MAPK) p38 inhibitors have entered the clinical phase, although many of them have failed due to high toxicity and lack of efficacy. In the present study we compared the effects of the selective p38 inhibitor ML3403 and the dual p38-PDE4 inhibitor CBS-3595, on inflammatory and nociceptive parameters in a model of polyarthritis in rats. Male Wistar rats (180-200 g) were used for the complete Freund's adjuvant (CFA)-induced arthritis model and they were evaluated at 14-21 days. We also analysed the effects of these pharmacological tools on liver and gastrointestinal toxicity and on cytokine levels. Repeated CBS-3595 (3 mg/kg) or ML3403 (10 mg/kg) administration produced significant anti-inflammatory actions in the chronic arthritis model induced by CFA. CBS-3595 and ML3403 treatment also markedly reduced the production of the proinflammatory cytokine IL-6 in the paw tissue, whereas it widely increased the levels of the anti-inflammatory cytokine IL-10. Moreover, CBS-3595 produced partial anti-allodynic effects in the CFA model at 4 and 8 days after treatment. Notably, ML3403 and CBS-3595 did not show marked signs of hepatoxicity, as supported by unaltered histological observations in the liver sections. Finally, both compounds were safe in the gastrointestinal tract, according to evaluation of intestinal biopsies. CBS-3595 displayed a superior profile regarding its anti-inflammatory effects. Thus p38 MAPK/PDE4 blocking might well constitute a relevant strategy for the treatment of RA.

Comparison of extended release GLP-1 receptor agonist therapy versus sitagliptin in the management of type 2 diabetes

Exenatide once weekly (EQW), the first glucose-lowering agent for type 2 diabetes that is dosed one time per week, contains exenatide encapsulated in microspheres of a dissolvable matrix, which release active agent slowly and continuously into the circulation following subcutaneous injection. In two direct head-to-head comparisons, EQW resulted in better long-term glucose control, greater reductions in fasting plasma glucose, and more significant weight loss than sitagliptin. In other trials, glucose-lowering effects of EQW compared favorably with those of metformin, pioglitazone, and basal insulin. Patients on EQW exhibited a higher incidence of nausea than those on sitagliptin, although gastrointestinal adverse events occurred primarily during the first 6–8 weeks of therapy and declined thereafter. EQW was also associated with a lower incidence of nausea than two other glucagon-like peptide-1 receptor agonists, exenatide twice daily and liraglutide. Mild hypoglycemic episodes were uncommon with EQW, although risk of hypoglycemia increased in combination with sulfonylureas. When choosing between EQW and a dipeptidyl peptidase-4 (DPP-4) inhibitor, such as sitagliptin, clinicians and patients should consider the differences between the two medications in terms of glucose control (EQW superior to DPP-4 inhibitors), weight control (EQW superior to DPP-4 inhibitors), gastrointestinal tolerability during treatment initiation (EQW inferior to DPP-4 inhibitors), and mode of administration (once-weekly subcutaneous administration versus once-daily oral administration).

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are Associated with a High Incidence of Gastrointestinal Side-Effects

Inhibition of the cyclooxygenase &nbsp;(COX) enzyme is the basis for both the efficacy and toxicity of NSAIDs. The aim of this study was to avaluate the non-steroidal anti-inflammatory drugs were used in neuro polyclinic hospital of Dr. Mintohardjo Jakarta, and to evaluate gastrointestinal tolerability of meloxicam 15 mg compared with diclofenac sodium 100 mg. The methode of this study was cross-sectional observation and&nbsp; cohort prospective on December 2010-March 2011. The data of dyspepsia associated were used non-steroidal anti-inflammatory drugs consist of pain in upper abdomen, nausea, vomiting, upper &nbsp;abdominal bloating and early satiety collected with PADYQ (The porto alegre dyspeptic symptoms questionnaire) were assessed at baseline and after 2 and 4 weeks of treatment. The non-steroidal anti-inflammatory drugs used in neuro polyclinic hospital of Dr. Mintohardjo Jakarta were meloxicam (48.21%), diclofenac sodium (31.07%), mefenamic acid (15.36%), piroxicam (3.93%)&nbsp; dan acetaminophen (1.43%). Insiden of adverse event after 2 weeks treatment was significantly lower in the meloxicam group compared with diclofenac sodium group in pain in upper abdomen and&nbsp;upper abdominal bloating (p=0.020 and&nbsp; p=0.037). These result suggest that meloxicam was much better tolerated than diclofenac sodium after 2 weeks treatment.

Gastrointestinal tolerability events in relapsing–/INS;remitting multiple sclerosis patients treated with BG-12 (dimethyl fumarate): Integrated analysis of DEFINE and CONFIRM

Background: Oral BG-12 (dimethyl fumarate) demonstrated an acceptable safety profile in the Phase 3 DEFINE and CONFIRM studies. Common adverse events (AEs) included flushing and gastrointestinal (GI) events.

Neuroradiological efficacy of oral BG-12 for relapsing–/INS;remitting multiple sclerosis (RRMS): Integrated analysis of the Phase 3 DEFINE and CONFIRM studies

Neuroradiological efficacy of oral BG-12 for relapsing–/INS;remitting multiple sclerosis (RRMS): Integrated analysis of the Phase 3 DEFINE and CONFIRM studies

Efficacy and Safety of Lixisenatide Once Daily Versus Exenatide Twice Daily in Type 2 Diabetes Inadequately Controlled on Metformin

OBJECTIVETo compare efficacy and safety of lixisenatide once daily versus exenatide twice daily in type 2 diabetes inadequately controlled with metformin.RESEARCH DESIGN AND METHODSAdults with diabetes inadequately controlled (HbA1c 7–10%) with metformin were randomized to lixisenatide 20 μg once daily (n = 318) or exenatide 10 μg twice daily (n = 316) in a 24-week (main period), open-label, parallel-group, multicenter study. The primary objective was a noninferiority assessment of lixisenatide versus exenatide in HbA1c change from baseline to week 24.RESULTSLixisenatide once daily demonstrated noninferiority in HbA1c reduction versus exenatide twice daily. The least squares mean change was −0.79% (mean decrease 7.97 to 7.17%) for lixisenatide versus −0.96% (mean decrease 7.96 to 7.01%) for exenatide, and treatment difference was 0.17% (95% CI, 0.033–0.297), meeting a predefined noninferiority upper CI margin of 0.4%. Responder rate (HbA1c <7.0%) and improvements in fasting plasma glucose were comparable. Both agents induced weight loss (from 94.5 to 91.7 kg and from 96.7 to 92.9 kg with lixisenatide and exenatide, respectively). Incidence of adverse events (AEs) was similar for lixisenatide and exenatide, as was incidence of serious AEs (2.8 and 2.2%, respectively). Discontinuations attributable to AEs occurred in 33 lixisenatide (10.4%) and 41 exenatide (13.0%) patients. In the lixisenatide group, fewer participants experienced symptomatic hypoglycemia (2.5 vs. 7.9%; P < 0.05), with fewer gastrointestinal events (especially nausea; 24.5 vs. 35.1%; P < 0.05).CONCLUSIONSAdd-on lixisenatide once daily in type 2 diabetes inadequately controlled with metformin demonstrated noninferior improvements in HbA1c, with slightly lower mean weight loss, lower incidence of hypoglycemia, and better gastrointestinal tolerability compared with exenatide twice daily.

A pooled analysis of patient-specific factors and efficacy and tolerability of tapentadol extended release treatment for moderate to severe chronic pain

To evaluate via retrospective analysis the efficacy and tolerability of tapentadol extended release (ER; 100-250 mg bid) based on patient-specific factors, including baseline pain intensity, prior opioid experience, gender, and body mass index (BMI). Data were pooled from three randomized, double-blind phase III studies of similar design that evaluated the efficacy and tolerability of tapentadol ER for the management of moderate to severe, chronic osteoarthritis knee pain (NCT00421928, NCT00486811) or low back pain (NCT00449176). In the original trials, patients were recruited at primary, secondary, and tertiary care centers, institutional settings, and private practices in North America, Europe, Australia, and New Zealand. Data were analyzed separately for groups of patients divided by baseline pain intensity, prior opioid experience, gender, and BMI. Patients received twice-daily placebo, tapentadol ER (100-250 mg), or oxycodone HCl controlled release (CR; 20-50 mg) for a 3-week titration and 12-week maintenance period. Changes from baseline in average pain intensity (11-point numerical rating scale) at week 12 of the maintenance period and for the overall maintenance period. Efficacy and tolerability were evaluated in 2,968 and 2,974 patients, respectively. The efficacy of tapentadol ER was shown in subpopulations divided by baseline pain intensity, prior opioid experience, gender, and BMI. Tapentadol ER was also shown to be well tolerated and associated with better gastrointestinal tolerability than oxycodone CR in the evaluated subpopulations (divided by prior opioid experience and gender). Results suggest that tapentadol ER (100-250 mg bid) provides similar pain relief and tolerability, regardless of baseline pain intensity, prior opioid experience, gender, or BMI.

English

Non Steroidal anti-inflammatory Drugs (NSAIDs) are most commonly prescribed drugs constituting more than 20% of all drug prescriptions. Prescription pattern study of NSAID was conducted in Medicine OPD of a rural teaching hospital with the objective of analyzing prescribing trend of NSAIDs, to evaluate co-prescription of Gastro-protective agents (GPAs) with NSAIDs and to determine number of prescribed NSAIDs falling within Drug utilization (DU) 90% segment. Overall 200 NSAID prescriptions were analysed. Prevalence of NSAID prescription was 25.71%. Paracetamol (36%) was the commonest drug prescribed. In general non-selective NSAIDs were more commonly prescribed (79.5%) and selective COX-2 inhibitors were least prescribed (1%). High prevalence of nimesulide prescription (19.5%) was a significant finding. Co-prescription of GPAs was high (61%). Four drugs (paracetamol, diclofenac, nimesulide and aceclofenac) fall within DU90% segment. In general prescription pattern requires further rationalization of NSAID usage as more number of drugs constitutes DU90% segment. KEY WORD: Prescription pattern, NSAID, DU90%, GPAs co-prescription. INTRODUCTION: The treatment of pain and inflammation is an important area of therapeutics. Over the past two decades, non steroidal anti-inflammatory drugs (NSAIDs) have played a central role in these indications. NSAIDs constitute the largest single group of drugs used worldwide, constituting more than 20% of all drug prescriptions 1 . In India over 400 formulations of NSAIDs are marketed, resulting in wide spread exposure of patients to this class of drugs and its adverse effects 2 . For all these reasons, studies that evaluate the pattern, extent and frequency of NSAID prescriptions are valuable. The demonstration of two unique isoforms of cyclooxygenase (designated as COX-1 and COX- 2) has led to a greater understanding of the mechanisms of action of NSAIDs and their toxicity 3 . The beneficial anti-inflammatory effect of the NSAIDs had been attributed to inhibition of COX-2, while the gastrointestinal (GI), renal and anti-platelet adverse effects were attributed to COX-1 inhibition 4 . Prescription pattern of NSAID changed frequently over a period of time. With the introduction of the selective COX-2 inhibitors, it has been suggested that they may be more cost-effective because of their improved GI tolerability and a reduction in concomitant prescription of antiulcer agents. This has led to an increase of almost 50% in the total number of NSAID prescriptions dispensed, with COX-2 drugs accounting for two thirds of this increase 3 . Before withdrawal of Rofecoxib, the prescriptions of COX-2 selective inhibitors had accounted for 37% of the total NSAID prescriptions dispensed. After its withdrawal in 2004, following the emergence of evidence of increased cardiovascular morbidity in the APPROVe (Adenomatous Polyp Prevention on Vioxx) study, COX-2 inhibitors represented less than 16% of the

Patient considerations in the use of tapentadol for moderate to severe pain

Poorly controlled acute and chronic pain can increase morbidity, impair quality of life and prolong disability. Over 80 percent of post surgical patients report moderate to severe uncontrolled postoperative pain. Over-reliance on potent opioid agonists can lead to several opioid related side effects such as gastrointestinal intolerability, respiratory depression and cognitive impairment. A recently approved dual acting central analgesic tapentadol may offer improved tolerability over traditional opioid agonists while having multimodal opioid and nonopioid analgesic benefits. Tapentadol, classified by the US Food and Drug Administration as a class 2 opioid, is currently marketed in the United States as immediate release (IR) NUCYNTA® for moderate to severe acute pain in tablets of 50 mg, 75 mg, and 100 mg, and as extended release (ER) NUCYNTA ER® for the treatment of chronic moderate to severe pain in tablets of 50 mg, 100 mg, 150 mg, 200 mg, and 250 mg. Tapentadol is a low affinity mu opioid receptor agonist and a norepinephrine reuptake inhibitor. Tapentadol has no active metabolites and this property makes it useful in patients with hepatic and renal failure. Clinical trials with tapentadol IR showed that there was improved gastrointestinal tolerability and similar pain relief as compared to oxycodone IR. Tapentadol ER allows for twice daily dosing. Clinical trials showed that tapentadol ER could effectively relieve moderate to severe chronic pain and was associated with significantly fewer gastrointestinal adverse effects as compared to oxycodone controlled release. Tapentadol ER is indicated and has Food and Drug Administration approval for the treatment of chronic painful diabetic neuropathy. The most common side effects of tapentadol are nausea (30%), vomiting (18%), dizziness (24%), and somnolence (15%). Tapentadol, due to its potential synergistic effects on norepinephrine levels, is contraindicated in patients who have taken monoamine oxidase inhibitors within the last 14 days. Caution has to be exercised with the use of tapentadol IR and tapentadol ER in the presence of other central nervous system depressants such as neuroleptics, opioids, illicit drugs, muscle relaxants, sedatives, and anxiolytics.