Onset Of Symptom Relief Research Articles

Review of icatibant use in the Winnipeg Regional Health Authority

BackgroundThis is a retrospective review of the Winnipeg Regional Health Authority’s (WRHA) angioedema patients who were dispensed icatibant in hospital. Icatibant is a bradykinin B2 receptor antagonist indicated for Hereditary Angioedema (HAE) types I and II and is used off-label for HAE with normal C1INH (HAE-nC1INH) and ACE-inhibitor induced angioedema (ACEIIAE). The WRHA’s use of icatibant is regulated by the Allergist on call. We characterized icatibant's use and the timeline from patient presentation, compared the real-world experience with the FAST-3 trial and hypothesized the factors which may affect response to icatibant.MethodsBackground data were collected on patients. Angioedema attack-related data included administered medications, performed investigations and the timeline to endpoints such as onset of symptom relief. Data was analyzed in R with the package “survival.” Time-to-event data was analyzed using the Peto–Peto Prentice method or Mann–Whitney U-test. Data was also compared with published clinical trial data using the Sign Test. Fisher’s Exact Test was used to produce descriptive statistics.ResultsOverall, 21 patients accounted for 23 angioedema attacks treated with icatibant. Approximately half the patients had a diagnosis of HAE-nC1IHN and half of ACEIIAE. Of those presenting with angioedema, 65% were first treated with conventional medication. Patients without a prior angioedema diagnosis were evaluated only 40–50% of the time for C4 levels or C1INH function or level. The median time from patients’ arrival to the emergency department until the Allergy consultant’s response was 1.77 h. Patients with HAE-nC1IHN had median times to onset of symptom relief and final clinical outcome (1.13 h, p = 0.34; 3.50 h, p = 0.11) similar to those reported in FAST-3 for HAE I/II. Patients with ACEIIAE had longer median times to onset of symptom relief (4.86 h, p = 0.01) than predicted.ConclusionsHAE-nC1INH may be an appropriate indication for treatment with icatibant. Conversely, the results of this study do not support the use of icatibant for the treatment of ACEIIAE, concordant with a growing body of literature. Patients should be stratified into groups of more- or less-likely icatibant-responders through history and laboratory investigations in order to prevent potential delays.

29] Time of onset of symptom relief after intraoperative detrusor injection of botulinum toxin A in patients with neurogenic and non-neurogenic overactive bladder syndrome

ObjectiveTo investigate the controversy that still exists regarding the time of onset of symptom relief after intraoperative detrusor injection of botulinum toxin A (BOTOX) in patients with neurogenic and non-neurogenic overactive bladder syndrome (OAB), as intra-detrusor injection of botulinum toxin has emerged as a second-line option for patients with neurogenic and non-neurogenic OAB who are refractory to first-line treatment modalities.

Characterization of differential patient profiles and therapeutic responses of pharmacy customers for four ambroxol formulations

BackgroundAmbroxol relieves cough symptoms based on its secretagogue, anti-inflammatory, anti-oxidant, anti-bacterial, anti-viral, immunomodulatory and local anesthetic effects. The present study was designed to explore differential patient profiles and efficacy against acute respiratory symptoms of four formulations registered as over-the-counter medicines.MethodsNine hundred sixty-five pharmacy customers purchasing one of four branded ambroxol formulations (extended release capsules, adult syrup, pediatric syrup and soft pastilles) filled a questionnaire including a patient-adapted version of the Bronchitis Severity Scale, several questions on degree of impairment by acute cough, time to onset of symptom relief and duration of treatment. Data on pediatric syrup users were entered by their parents. Based on the exploratory character of the study, no hypothesis-testing statistical analysis was applied.ResultsUsers of the pediatric syrup and the pastilles reported somewhat less severe baseline symptoms. The patient-adapted Bronchitis Severity Scale proved feasible as a self-administered tool. Among BSS items, ambroxol formulations improved chest pain while coughing to the largest and sputum to smallest degree (− 75% vs. -40%). Reported efficacy was comparable among formulations with minor differences in favor of the pediatric syrup. Time to onset of symptom relief was less than 60 min in more than 90% of patients and occurred prior to known systemic tmax. Time to onset was the parameter with the greatest differences between formulations, being reported fastest with pastilles and pediatric syrup and, as expected, slowest with extended release capsules. All ambroxol formulations were well tolerated.ConclusionsWe conclude that over-the-counter formulations of ambroxol exhibit comparable user profiles and efficacy. Differences in speed of onset of symptom relief may involve not only those in systemic pharmacokinetics but also local anesthetic effects of immediate release formulations. Differences between pediatric and adult syrup may in part reflect reporting bias.

Early onset of efficacy in patients with functional and motility-related gastrointestinal disorders : Anoninterventional study with Iberogast®.

SummarySTW 5 (Iberogast®; Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany) contains nine plant extracts and possesses well-documented overall efficacy in functional gastrointestinal disorders (FGID). Little is known about the onset of symptom relief. Twenty-nine centers in Germany recruited 272 patients with established FGID. These patients were treated with STW 5 for approximately 3 weeks in this noninterventional study. Patients assessed the severity of their gastrointestinal complaints before and at defined times after the intake of STW 5 (10 cm visual analogue scale; VAS). Fifteen minutes after the first dose, the severity of gastrointestinal complaints had decreased by 1.4 cm (mean; initial mean: 5.2 of 10 cm). After 1 h, more than 90% of the maximum effect of 3.2 cm on the 10 cm VAS had been reached. Most patients with symptoms experienced a marked improvement within 5, 15 or 30 min of taking STW 5. Absolute improvements were larger in patients with more pronounced baseline complaints. Subgroups with upper (80% of the study population) and lower FGID (20%) did not present major differences. Neither did subgroups by age and duration of complaints. Treatment with STW 5 resulted in rapid improvement of symptoms.

Home Treatment With Conestat Alfa In Attacks Of Hereditary Angioedema Due To C1-Inhibitor Deficiency

Methods We analyzed 137 edematous episodes requiring acute treatment and occurring in 6 C1-INH-HAE patients. The patients were treated at home with a dose of 2100 U rhC1-INH per occasion. They recorded the time of rhC1INH administration, time until the symptoms stopped worsening, time to the onset of symptom relief and to the complete resolution of symptoms. Any side effects were recorded in addition. Symptom severity and patient satisfaction were measured with a visual analogue scale (VAS).

Rabeprazole for the treatment of acid-related disorders

Proton pump inhibitors are widely used for the treatment of acid-related disorders. Rabeprazole is a potent and irreversible inhibitor of H+/K+-ATPase gastric pump, and it is indicated for the treatment of gastroesophageal reflux disease, Zollinger Ellison syndrome, duodenal and gastric ulcers and for the eradication of Helicobacter pylori in combination with antibiotics. Pharmacokinetic and pharmacodynamic data show that rabeprazole achieves a pronounced acid suppression from the first administration that is maintained with repeated use; this may translate into faster onset of symptom relief for patients, particularly suitable when the indication is for the on-demand long-term maintenance of gastroesophageal reflux disease. Due to its predominantly nonenzymatic metabolism, rabeprazole has a lower potential for drug–drug interactions. The objective of this article is to update efficacy and safety data of rabeprazole in the treatment of acid-related disorders, following a previous review dated 2008.

453 A 26-Year Review of Long-term Safety of a Human Pasteurized C1 Inhibitor Concentrate

BackgroundHereditary angioedema (HAE) is a rare disorder characterized by C1 inhibitor (C1-INH) deficiency, resulting in periodic attacks of acute edema. C1-INH replacement therapy is recommended as first-line therapy for treatment of acute HAE attacks, demonstrating rapid onset of symptom relief within 30 minutes or less. CSL Behring's human pasteurized C1-INH concentrate has been marketed since 1985 for the treatment of acute HAE attacks in Germany and numerous other countries.MethodsWe reviewed spontaneous reports of adverse drug reactions (ADRs) received by CSL Behring for its human pasteurized C1-INH concentrate, covering the 26-year period from 1985 until 31 December 2010.ResultsDuring the reporting period, human pasteurized C1-INH concentrate representing more than 550,000 treatments was distributed. A total of 101 cases of suspected ADRs were reported worldwide, with 62 cases covered by the product's known safety profile: allergic- or anaphylactic-type reactions (11; in very rare cases involving shock), chills and fever (4), lack of effect (26), suspected virus transmission (6; not attributed to the product), and thrombosis (16). Only 2 cases of thrombosis occurred when the product was used in the labelled indication; causality was assessed as unlikely in both cases (pre-existing cerebromalacia in 1 patient, and unspecified underlying pro-thrombotic condition in a second patient with morbid obesity). The other 14 cases of thrombosis occurred during off-label use of the product (substantially higher doses than indicated). Three reports were no ADRs (product exposure during pregnancy, administration failure). Of 36 cases involving isolated reports of varying symptoms not covered by the known product safety profile, causality to the product was established for only 1 case (lightheadedness and dizziness). According to the Council for International Organizations of Medical Sciences criteria, the overall ADR reporting rate for human pasteurized C1-INH concentrate is “rare”.ConclusionsHuman pasteurized C1-INH concentrate has a well-established safety profile based on 26 years of post-marketing experience with more than 550,000 treatments. The product is safe and well tolerated when used at the recommended dosage in the treatment of acute HAE attacks.

Onset of action of loratadine/montelukast in seasonal allergic rhinitis patients exposed to grass pollen

Given the impact of allergic rhinitis (AR) on quality of life, it is important that AR medications have rapid onset of symptom relief. The objective of this study was to determine the onset of action of loratadine (CAS 79794-75-5)/montelukast (CAS 151767-02-1) 10 mg/10 mg (L/M) versus placebo in seasonal AR (SAR) subjects. In this single-center, double-blind, crossover study, subjects with SAR and confirmed sensitivity to grass pollen received single doses of L/M or placebo following exposure to grass pollen in the Vienna Challenge Chamber. Subjects recorded symptoms at 15-min intervals during the first 2 h post dose and at 30-min intervals during the next 2 h. After a 14-day washout, the subjects crossed over to the other treatment. The primary endpoint was onset of action of L/M, defined as the first time point at which the mean change from baseline in total symptom score became and remained significantly different with L/M versus placebo. Secondary endpoints included nasal congestion score and rhinomanometry findings. Onset of action with L/M for total symptom score was 1 h, 45 min (P < 0.01 vs placebo). Significant improvements in subject-assessed nasal congestion scores (P < 0.01) and rhinomanometry (P = 0.036) were noted with L/M as compared with placebo. Overall, L/M was well tolerated. In conclusion, L/M demonstrated rapid onset for broad symptom relief, including nasal congestion, in subjects with SAR.

Icatibant in the Treatment of Acute Attacks of Hereditary Angioedema (HAE) in Adults

Introduction: Hereditary Angioedema (HAE) is a potentially life-threatening condition consisting of recurrent episodes of limb, abdominal, genital, facial or laryngeal swelling. Unregulated bradykinin activity is known to be the main driving mechanism for the characteristic edema flares in HAE. Thus, a bradykinin receptor antagonist is a sensible treatment for acute attacks of HAE. Methods: A Pubmed literature search was conducted from 2005-present using the search terms icatibant, HOE 140, angioedema, and hereditary angioedema singly and in combination. Non-English articles were excluded. Results: Overall, there have been a total of 116 patients (314 attacks) treated with icatibant. Of these attacks, the majority reported the onset of symptom relief within two hours and the resolution of symptoms within 12–24 hours. Thirty patients (9.6%) had recurrent symptoms; five were treated with rescue Berinert, seven were treated with an additional dose of icatibant, and the remainder 18 were given either C1-INH concentrate, anti-emetics, or opiates. The most reported adverse effect from icatibant was a local reaction (swelling, burning, erythema, and itching). Icatibant use has also been reported with ACE-inhibitor induced, acquired, and HAE type III angioedema as well as in one case as prophylaxis. Conclusion: The numerable new treatments for HAE now gaining favor, including icatibant, provide an exciting opportunity for both patients and providers to take swift control of this disease process.

Hereditary angioedema: Validation of the end point time to onset of relief by correlation with symptom intensity

Time to onset of symptom relief in hereditary angioedema (HAE) is a common primary end point in clinical studies but it has never been validated by correlation with the course of HAE symptoms. This study was designed as a retrospective validation of the primary end point for a placebo-controlled phase II/III study in patients with HAE. Ninety-eight abdominal attacks were treated with 10 or 20 U/kg of a highly purified C1 esterase inhibitor (C1-INH) concentrate or placebo. The primary end point was the time to onset of symptom relief, as determined by the patients. Patients assessed the intensity of the symptoms of pain, nausea, vomiting, cramps, and diarrhea over time. By Spearman rank correlation, the primary end point was compared with the time to first reduction of (1) any symptom intensity, (2) the sum of symptom intensity scores, and (3) the intensity of the last symptom present at baseline. The C1-INH, 20 U/kg, and placebo groups were compared by one-sided two-sample Wilcoxon tests. The time to first reduction in intensity of the last symptom present at baseline had the highest correlation with the primary end point (r = 0.77). The time to onset of symptom relief and the time to the first reduction in intensity of the last symptom were significantly shorter for the C1-INH, 20 U/kg, group compared with placebo (p = 0.009 and p = 0.0036, respectively). The association with the intensity of single symptoms confirmed that the time to onset of symptom relief is an appropriate end point for assessing the efficacy of C1-INH therapy.

Fluticasone furoate nasal spray: Profile of an enhanced-affinity corticosteroid in treatment of seasonal allergic rhinitis.

Of the classes of pharmacotherapy for seasonal allergic rhinitis, intranasal corticosteroids are the preferred treatment and are recommended in practice guidelines as first-line pharmacotherapy for rhinitis with prominent nasal congestion. The enhanced-affinity intranasal corticosteroid fluticasone furoate nasal spray (GW685698X), is one of the newest additions to the armamentarium for allergic rhinitis. This review summarizes the preclinical and clinical data on fluticasone furoate nasal spray and discusses its place in pharmacotherapy for seasonal allergic rhinitis. Important attributes of fluticasone furoate in seasonal allergic rhinitis include low systemic bioavailability (<0.5%), onset of symptom relief as early as eight hours after initiation of treatment, 24-hour symptom relief with once-daily dosing, comprehensive coverage of both nasal and ocular symptoms, safety and tolerability with daily use, and availability in a side-actuated device that makes medication delivery simple and consistent. With these attributes, fluticasone furoate nasal spray has the potential to enhance patient satisfaction and compliance and reduce the need for polypharmacy in the management of seasonal allergic rhinitis.

Human C1-Esterase Inhibitor Concentrate (Berinert®)

Human C1-esterase inhibitor concentrate (C1-INH concentrate) is derived from human plasma and is indicated for the treatment of acute episodes of hereditary angioedema. Intravenous C1-INH concentrate provided rapid symptom relief in patients with acute abdominal or facial episodes associated with type I or II hereditary angioedema, according to the results of the randomized, double-blind, multicenter, placebo-controlled IMPACT-1 trial. The median time to the onset of symptom relief was significantly shorter with C1-INH concentrate 20 U/kg than with placebo (0.5 vs 1.5 hours). A subsequent noncomparative extension trial (IMPACT-2) showed the ongoing efficacy of 'on-demand' treatment with C1-INH concentrate; overall, the onset of symptom relief occurred in a median 30 minutes. Several additional studies demonstrated the efficacy of intravenous C1-INH concentrate in patients with laryngeal edema, skin swellings, or abdominal episodes associated with type I or II hereditary angioedema. Self-administered home therapy with intravenous C1-INH concentrate significantly improved health-related quality of life in patients with hereditary angioedema. Dermatology Life Quality Index and Short Form 36-item Health Survey scores were significantly improved from baseline by self-administered home therapy with C1-INH concentrate. Intravenous C1-INH concentrate was well tolerated in patients with hereditary angioedema, with no confirmed cases of viral transmission.

S1928 Detection of Gastroesophageal Reflux Disease with Impedance pH in Preoperative Lung Transplant Patients

Introduction: An empiric trial of acid suppression with a proton pump inhibitor (PPI) is widely used as a diagnostic test for gastroesophageal reflux disease (GERD). However, the report about diagnostic value of a short trial with standard dose PPI is rare. The aim of this study was to determine the onset of symptom relief with standard or double dose of lansoprazole in Korean patients with erosive esophagitis or nonerosive reflux disease (NERD). Methods: This multi-center randomized study enrolled 93 patients with erosive esophagitis (n=30) or NERD (n=63) to receive lansoprazole treatment using 30 mg or 60 mg once daily for 14 days. Between two clinical visits (at enrolment and 14 days), patients were asked to keep a diary in which they recorded severity of GERD symptoms daily. Substantial symptom relief was defined as a more than 50% reduction in total symptom score. Results: In total patients, substantial symptom relief was achieved by the end of the first week (day 6). There were no significant differences of total symptom score reductions between standard and double dose groups of patients with erosive esophagitis. But onset of substantial symptom relief was faster in the double dose group (day 2) than the standard dose group (day 6). In patients with NERD, there were no significant differences of total symptom score reductions between standard and double dose group. Onset of substantial symptom relief was same in the standard and double dose groups of patients with NERD (day 8). Conclusions: In this multi-center, randomized study of Korean patients, standard-dose lansoprazole was as effective as double-dose lansoprazole in relieving symptoms by day 14 of treatment. Onset of substantial symptom relief was slower in the patients with non-erosive reflux disease than those with erosive esophagitis.

S1925 A Multi-Center, Randomized, Comparative Study to Determine the Appropriate Dose of Lansoprazole for the Diagnostic Test in Korean Patients with Gastroesophageal Reflux Disease

Introduction: An empiric trial of acid suppression with a proton pump inhibitor (PPI) is widely used as a diagnostic test for gastroesophageal reflux disease (GERD). However, the report about diagnostic value of a short trial with standard dose PPI is rare. The aim of this study was to determine the onset of symptom relief with standard or double dose of lansoprazole in Korean patients with erosive esophagitis or nonerosive reflux disease (NERD). Methods: This multi-center randomized study enrolled 93 patients with erosive esophagitis (n=30) or NERD (n=63) to receive lansoprazole treatment using 30 mg or 60 mg once daily for 14 days. Between two clinical visits (at enrolment and 14 days), patients were asked to keep a diary in which they recorded severity of GERD symptoms daily. Substantial symptom relief was defined as a more than 50% reduction in total symptom score. Results: In total patients, substantial symptom relief was achieved by the end of the first week (day 6). There were no significant differences of total symptom score reductions between standard and double dose groups of patients with erosive esophagitis. But onset of substantial symptom relief was faster in the double dose group (day 2) than the standard dose group (day 6). In patients with NERD, there were no significant differences of total symptom score reductions between standard and double dose group. Onset of substantial symptom relief was same in the standard and double dose groups of patients with NERD (day 8). Conclusions: In this multi-center, randomized study of Korean patients, standard-dose lansoprazole was as effective as double-dose lansoprazole in relieving symptoms by day 14 of treatment. Onset of substantial symptom relief was slower in the patients with non-erosive reflux disease than those with erosive esophagitis.

M1913 A Randomized, Comparative Trial of the Speed of Onset of Symptom Relief of Gastroesophageal Reflux Disease By the Proton Pump Inhibitors: Rabeprazole vs Lansoprazole vs Omeprazole

vantaged SES. Univariate analyses did not show associations of lifestyle factors (BMI, smoking, alcohol, marital status) and change in SSS. However, employment status was associated with improvement of SSS (p=.029). In Multiple Linear Regression the set of possible predictors did not explain a significant proportion of differences in symptom severity (p=.099) only SES & employment status were significant. Employed status was associated with less improvement in SSS (2.6 pts < unemployed; p=.008) as was average SES compared to advantaged (3.6 pts < advantaged SES; p=.021). CONCLUSIONS: a) The improvement in reflux symptoms after diagnostic work-up and initiation of therapy in a routine clinical setting can be partly explained by sociodemographic factors b) Paradoxically, advantaged SES and unemployment are each associated with greater improvement of reflux symptoms.

Current Considerations in the Treatment of Generalized Anxiety Disorder

Generalized anxiety disorder (GAD) is a chronic disorder that frequently co-occurs with a variety of co-morbidities in patients with somatic conditions and other mental disorders. GAD is highly prevalent and is one of the most common anxiety disorders seen by primary care physicians. The individual and societal cost associated with GAD is high and the marked level of impairment experienced by patients with this disorder is equivalent in magnitude to that reported in patients with major depressive disorder. Furthermore, patients with GAD are at risk of suicide or suicide attempts, and are frequent users of healthcare services. Thus, GAD is a serious and chronic condition that requires appropriate long-term treatment. The focus of acute treatment for patients with GAD is the improvement of symptoms, while the primary goal of long-term clinical management is remission, i.e. the complete resolution of both symptoms and functional impairment. The consensus across current treatment guidelines is that first-line treatment for patients with GAD should consist of an antidepressant, either a selective serotonin reuptake inhibitor (SSRI) such as sertraline, paroxetine or escitalopram, or a selective serotonin noradrenaline (norepinephrine) reuptake inhibitor (SNRI) such as venlafaxine or duloxetine. However, the SSRIs and SNRIs have efficacy limitations, such as lack of response in many patients, a 2- to 4-week delay before the onset of symptom relief, lack of full remission, and risk of relapse. In addition, there are troublesome adverse effects associated with both the SSRIs and SNRIs. Evidence from early clinical studies of the atypical antipsychotics in the treatment of anxiety and GAD indicate that they may have a potential role in the treatment of GAD, either as monotherapy or as augmentation to standard treatment.

Effect of rabeprazole and omeprazole on the onset of gastro-oesophageal reflux disease symptom relief during the first seven days of treatment

Objective. Gastro-oesophageal reflux disease (GORD) symptoms have a significant impact on patients’ well-being. Onset of symptom relief is therefore an important consideration in GORD treatment. The primary objective was to compare the efficacy of rabeprazole (20 mg) and omeprazole (20 mg) regarding onset of heartburn control during the first 7 days of treatment in patients with erosive oesophagitis. Secondary objectives included maintenance of sustained heartburn control, control of other GORD symptoms (e.g. acid regurgitation, epigastric pain, dysphagia), effect on quality of life, patient satisfaction with treatment, and adverse events. Material and methods. In this multicentre, randomized, parallel-group, double-blind, comparative study, performed in Europe and Iceland, patients with endoscopically confirmed erosive oesophagitis were randomized to receive once-daily treatment with rabeprazole 20 mg (n=358) or omeprazole 20 mg (n=359) for 7 days. Symptoms were recorded (scored on a 5-point Likert scale) twice daily by the patients on their diary cards. Results. Median time to reach heartburn control was 1.5 days for both the rabeprazole and omeprazole groups (p<0.43). The results were similar between treatments for other study parameters. Both treatments were well tolerated. Conclusions. Unlike previous studies, no significant differences were found between treatments with rabeprazole (20 mg) and omeprazole (20 mg) in this study. Further studies are needed to evaluate the potential benefit of fast-acting proton-pump inhibitors, such as rabeprazole, with respect to onset of symptom control in erosive GORD.

A novel therapeutic concept for the treatment of acute angioedema attacks in hereditary angioedema patients: multiple successful treatments even in severe swelling attacks with the bradykinin-B2 receptor antagonist Icatibant

Several forms of angioedema seem to be induced by elevated bradykinin (BK) concentrations. They are either caused by increased BK production, as is the case in hereditary angioedema (HAE) involving the lack of a functional C1-esterase inhibitor, or by reduced BK inactivation (e.g. during ACE-inhibitor treatment). BK-induced angioedema does not respond to the current standard treatment for angioedema caused by increased histamine levels, corticosteroids and antihistamines. Until now acute attacks of HAE have been treated with intravenously administered C1-esterase inhibitor concentrate derived from human plasma. However, no specific treatment has been approved for ACE-inhibitor-induced angioedema. It would be necessary that such an approach inhibits directly the activation of the bradykinin-B2 receptor by BK. During the ongoing international phase III HAE study FAST2, we treated several HAE patients subcutaneously with Icatibant, a specific bradykinin-B2 receptor antagonist. In the open-label part of this study we administered Icatibant for the treatment of 21 acute HAE attacks. Eleven attacks were located in the head-neck region, of which three involved the laryngeal area, six the abdominal and four the genital area. Following treatment with Icatibant, patients reported rapid onset of symptom relief and complete remission of symptoms within a few hours. We were especially impressed by the successful treatment of the edema involving the laryngeal area. The study drug was safe and well tolerated. We have noted short-lived local injection site reactions, which resolved spontaneously without intervention. In our hands Icatibant showed high efficacy for the treatment of acute HAE attacks with a rapid onset of symptom relief. Subcutaneous administration might improve the quality of life for HAE patients. Icatibant could also represent a new therapeutic paradigm for the treatment of ACE-inhibitor-induced angioedema cases but this hypothesis needs to be tested in a clinical study.

FAMOTIDINE/ANTACID COMBINATION TABLETS ARE MORE EFFECTIVE FOR THE TREATMENT OF HEARTBURN THAN EITHER COMPONENT ALONE

Purpose: To compare heartburn relief provided by famotidine/antacid combination tablet (FACT) to its components and placebo. Objectives were to demonstrate that FACT has faster onset than famotidine (FAM) 10 mg and longer duration than antacid. Methods: Randomized, double-blind, placebo-controlled, parallel group study at 32 primary care centers in the US. A total of 1,640 adults (mean age 46 yr.) with food-induced heartburn at least 3 times per wk. (mean: 6 episodes/wk.) were randomly assigned to treat 4 episodes of heartburn with FACT (FAM 10 mg + antacid 21 mEq calcium-carbonate-magnesium hydroxide tablet) (n = 410), FAM 10 mg(n = 411), antacid 21 mEq calcium-carbonate-magnesium hydroxide (n = 414) or placebo (n = 405). Patients rated heartburn relief (adequate relief: Y or N) at 15-min. intervals for the first hour postdose and then hourly through 8 hr. postdose, use of rescue antacid, and global evaluation of treatment. Results: 1640 randomized patients treated a total of 6290 episodes, 20% of which were rated as mild, 56% moderate, 24% severe. The onset of symptom relief was significantly faster with FACT than with FAM 10 mg (p = 0.001), or placebo (p <0.001). The odds ratios indicate that heartburn episodes treated with FACT were 1.42 or 1.59 times more likely to achieve adequate relief at an earlier time point compared to episodes treated with FAM 10 mg or placebo, respectively. The proportion of episodes relieved at 15 min. was greater with FACT (33.7%) compared to FAM 10 mg (27.3%) or placebo (25.4%). Duration of effect was significantly longer with FACT than with antacid or placebo (p <0.001). The odds-ratios indicate that heartburn episodes for FACT patients were 1.60 or 2.15 times more likely to maintain adequate relief at a later time point than episodes for antacid or placebo patients, respectively. The proportion of episodes relieved for at least 7 hr. was greater with FACT (70.0%) than antacid (58.5%) or placebo (51.4%). FACT-treated patients reported better global efficacy than the other 3 treatment groups (p <0.001) and had a lower percentage of episodes that required the use of rescue medication. Comparisons of FACT with FAM 10 mg, antacid, and placebo were statistically significant for the analysis of time to rescue antacid (p <0.001). All 4 treatments were generally well-tolerated. Conclusions: FACT provides more rapid relief of heartburn than FAM 10 mg, and longer lasting relief than antacid alone.

Therapeutic choices in reflux disease: Defining the criteria for selecting a proton pump inhibitor

Gastroesophageal reflux disease (GERD) is among the most common disorders of the gastrointestinal tract, with symptoms affecting a substantial proportion of the US population on a daily basis. Heartburn and related symptoms arise from a number of pathophysiologic mechanisms, including dilated intercellular spaces, increased duration of acid reflux, greater proximal extent of reflux, and esophageal sensitivity. Chronic reflux may result in serious complications, such as esophageal erosions or ulceration, stricture, and Barrett esophagus. The goals of GERD therapy are to relieve patients' symptoms and prevent complications. Proton pump inhibitors (PPIs) represent the most effective treatment option for GERD, relieving symptoms, healing erosions, and maintaining a healed mucosa. Differences in the pharmacokinetics and pharmacodynamics among the PPIs may result in differences in intragastric pH holding time as well as the onset of symptom relief. Lansoprazole and esomeprazole produce similar degrees and onset of symptom relief, with both providing greater symptom relief as compared with omeprazole. Although manufactured as capsules containing enteric-coated granules, lansoprazole, omeprazole, and esomeprazole maintain their high level of pharmacologic efficacy when the capsule contents are emptied into soft foods or various liquids. Lansoprazole and pantoprazole also are manufactured as intravenous formulations, and lansoprazole is available as strawberry-flavored granules for oral suspension and as an orally disintegrating tablet. These alternative routes of administration are particularly beneficial in the management of acid-related disorders in infants, children, the elderly, and patients of all ages who have difficulty swallowing or are unable to swallow intact capsules or tablets and those in the critical care setting.