Safety of Intravenous Pantoprazole Sodium in Pediatric Patients Aged 1 Month to < 1 Year: A Real-World Retrospective Cohort Study.

OBJECTIVE: To estimate the incidence rates (IR) of prespecified outcomes of interest in pediatric patients (1 month to < 1 year) treated with intravenous (IV) pantoprazole using Optum's longitudinal electronic health records database (Optum Market Clarity) from the United States (US). METHODS: This real-world, non-interventional, retrospective cohort study was conducted from 01 January 2007 to 31 December 2020 in patients who received IV pantoprazole. Premature patients and those weighing < 2.36 kg were excluded. Patients were categorized based on diagnosis of gastroesophageal reflux disease (GERD) and erosive esophagitis (EE) into: Subgroup 1 (GERD and EE), Subgroup 2 (GERD and no EE), and Subgroup 3 (absence of GERD and EE). Overall IRs (per 1000 person-years [PY]) and 95% confidence intervals (CI) of outcomes were estimated (overall and subgroups) and stratified by duration of IV pantoprazole treatment (< 4 days versus ≥ 4 days). RESULTS: Of 1879 eligible patients, none were identified in Subgroup 1; 851 (45.3%) and 1028 (54.7%) patients were identified in Subgroups 2 and 3, respectively. IRs of outcomes of interest ranged from 0.0 to 742.8 per 1000 PY. IRs were highest for vomiting (742.80), diarrhea (377.77), abdominal distension (214.31), hyponatremia (204.99), and hypokalemia (203.49). IRs were comparable between Subgroups 2 and 3. For most outcomes, IRs were higher among patients treated with IV pantoprazole for ≥ 4 days versus those treated for < 4 days. CONCLUSION: These results are consistent with the known safety profile of pantoprazole and emphasize the utility of using real-world data from pediatric populations for assessment of safety outcomes.

Predicting sulforaphane-induced adverse effects in colon cancer patients via in silico investigation.

Colorectal cancer (CRC) is a significant global health burden that ranks as the third most diagnosed and second most common cause of cancer related deaths worldwide. New therapeutic strategies include chemoprevention and use of molecules which could prevent, suppress or reverse CRC progression such as sulforaphane (SFN). However, evidences about its safety in CRC patients are still lacking. The aim of this in silico investigation was to predict SFN-induced adverse effects in CRC patients by computational analysis. The study showed that 334 genes were consistently dysregulated in CRC (223 downregulated and 111 upregulated), while 38 were recognized as significant and might be used as predictive biomarkers for overall survival and metastasis (TCGA, GEO, R studio). Among them, SFN interacted with 86 genes, out of which 11 were marked as significant (correlate with overall prognosis and metastasis). Sulforaphane potentiates the overexpression of TIMP1, AURKA, and CEP55, and promotes inhibition of CRYAB, PLCE1, and MMP28, that might lead to the progression of CRC (CTD). Pathway enrichment analysis revealed that SFN stimulated Transcriptional activation of RUNX2, AURKA activation by TPX2, IL-10 signaling, while inhibited Differentiation of White and Brown Adipocyte process, an underlying pathway which inactivation led to obesity (Cytoscape ClueGo + CluePedia, DAVID). Thus, genome signature of CRC patients could serve as important factor when addressing the risk-to-benefit profile of SFN. Patients with colon cancer and increased expression of TIMP1, CCL20, SPP1, AURKA, CEP55, NEK2, SOX9 and CDK1, or downregulation of CRYAB, PLCE1, MMP28, BMP2 and PLAC8 may not be ideal candidates for SFN chemoprevention.

Efficacy and safety of sulforaphane for treatment of mild to moderate depression in patients with history of cardiac interventions: A randomized, double-blind, placebo-controlled clinical trial.

AIM: Depression has been recognized as one of the disorders associated with cardiac interventions such as percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG). In the present study, we evaluated the efficacy and safety of sulforaphane in treatment of depression induced by cardiac interventions. METHODS: After initial screening, 66 patients with previous history of at least one cardiac intervention and current mild to moderate depression were randomly assigned to two parallel groups receiving either sulforaphane (n = 33) or placebo (n = 33) for six successive weeks. Efficacy was assessed using the Hamilton Rating Scale for Depression (HAM-D) at baseline and week 2, 4, and 6. Safety of the treatments was checked during the trial period. RESULTS: Sixty participants completed the clinical trial (n = 30 in each group). Baseline demographic and clinical parameters were all similar among groups. Repeated measures analysis indicated that the sulforaphane group exhibited greater improvement in HAM-D scores throughout the trial (P < 0.001). Response to treatment (≥50% reduction in the HAM-D score) rate was higher in the sulforaphane group at trial endpoint (30% vs 6.67%, P = 0.042). Remission (HAM-D score ≤ 7) rate was also higher in the sulforaphane group; however, the difference was not significant (23.33% vs 3.33%, P = 0.052). Finally, no significant difference was observed between the two groups in terms of frequency of side effects. CONCLUSIONS: Sulforaphane could safely improve depressive symptoms induced by cardiac interventions. Further clinical trials with larger sample sizes and longer follow-up periods are warranted to confirm our results.

Evolving Role for Pharmacotherapy in NAFLD/NASH.

Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent, dynamic disease that occurs across the age spectrum and can lead to cirrhosis and hepatocellular carcinoma. There are currently no US Food and Drug Administration (FDA) approved treatments for NAFLD; however, this is a field of active research. This review summarizes emerging pharmacotherapies for the treatment of adult and pediatric NAFLD. Investigated pharmacotherapies predominantly target bile acid signaling, insulin resistance, and lipid handling within the liver. Three drugs have gone on to phase III trials for which results are available. Of those, obeticholic acid is the single agent that demonstrates promise according to the interim analyses of the REGENERATE trial. Obeticholic acid showed reduction of fibrosis in adults with nonalcoholic steatohepatitis (NASH) taking 25 mg daily for 18 months (n = 931, reduction in fibrosis in 25% vs. 12% placebo, P < 0.01). Ongoing phase III trials include REGENERATE and MAESTRO-NASH, which investigates thyroid hormone receptor-ß agonist MGL-3196. Outcomes of promising phase II trials in adults with NASH are also available and those have investigated agents, including the fibroblast growth factor (FGF)19 analogue NGM282, the GLP1 agonist liraglutide, the FGF21 analogue Pegbelfermin, the sodium glucose co-transporter 2 inhibitor Empagliflozin, the ketohexokinase inhibitor PF-06835919, the acetyl-coenzyme A carboxylase inhibitor GS-0976, and the chemokine receptor antagonist Cenicriviroc. Completed and ongoing clinical trials emphasize the need for a more nuanced understanding of the phenotypes of subgroups within NAFLD that may respond to an individualized approach to pharmacotherapy.

Cenicriviroc Treatment for Adults With Nonalcoholic Steatohepatitis and Fibrosis: Final Analysis of the Phase 2b CENTAUR Study.

BACKGROUND AND AIMS: Cenicriviroc (CVC) is a C-C chemokine receptors type 2 and 5 dual antagonist under evaluation for treating liver fibrosis in adults with nonalcoholic steatohepatitis (NASH). Year 1 primary analysis of the 2-year CENTAUR study showed that CVC had an antifibrotic effect without impacting steatohepatitis. Herein, we report the final data from year 2 exploratory analyses. APPROACH AND RESULTS: This was a randomized, controlled study of adults with NASH, nonalcoholic fatty liver disease activity score ≥4, and NASH Clinical Research Network stage 1-3 fibrosis. Participants in arms A and C received CVC 150 mg or placebo, respectively, for 2 years; arm B received placebo in year 1 and switched to CVC in year 2. Liver biopsy was performed at baseline, year 1, and year 2. Of 289 randomized participants, 242 entered year 2. At year 2, 24% of patients who switched to CVC and 17% who remained on placebo achieved ≥1-stage fibrosis improvement and no worsening of NASH (P = 0.37). Twice the proportion on CVC who achieved fibrosis response at year 1 maintained benefit at year 2 (60% arm A versus 30% arm C), including 86% on CVC who had stage 3 fibrosis at baseline. Over 2 years, a similar proportion on CVC or placebo achieved ≥1-stage fibrosis improvement and no worsening of NASH (15% arm A versus 17% arm C). In patients with fibrosis responses, we observed consistent reductions in levels of N-terminal type 3 collagen propeptide and enhanced liver fibrosis scores, while increases in aspartate aminotransferase-to-platelet ratio index and Fibrosis-4 scores were consistently observed in nonresponders. Safety profile was comparable across groups. CONCLUSIONS: CVC was well tolerated, and year 2 data corroborate antifibrotic findings from year 1. The majority on CVC who achieved fibrosis response at year 1 maintained it at year 2, with greater effect in advanced fibrosis. ClinicalTrials.gov number, NCT02217475 (CENTAUR).

Phase I dose-escalation studies of roniciclib, a pan-cyclin-dependent kinase inhibitor, in advanced malignancies.

BACKGROUND: To evaluate safety, pharmacokinetics, and maximum tolerated dose of roniciclib in patients with advanced malignancies, with dose expansion to evaluate clinical benefit at the recommended phase II dose (RP2D). METHODS: Two phase I dose-escalation studies evaluated two roniciclib dosing schedules: 3 days on/4 days off or 4 weeks on/2 weeks off. The expansion phase included patients with small-cell lung cancer (SCLC), ovarian cancer, or tumour mutations involving the CDK signalling pathway. RESULTS: Ten patients were evaluable in the 4 weeks on/2 weeks off schedule (terminated following limited tolerability) and 47 in the 3 days on/4 days off schedule dose-escalation cohorts. On the 3 days on/4 days off schedule, RP2D was 5 mg twice daily in solid tumours (n=40); undetermined in lymphoid malignancies (n=7). Common roniciclib-related adverse events included nausea (76.6%), fatigue (65.8%), diarrhoea (63.1%), and vomiting (57.7%). Roniciclib demonstrated rapid absorption and dose-proportional increase in exposure. One partial response (1.0%) was observed. In RP2D expansion cohorts, the disease control rate (DCR) was 40.9% for patients with ovarian cancer (n=25), 17.4% for patients with SCLC (n=33), and 33.3% for patients with CDK-related tumour mutations (n=6). CONCLUSIONS: Roniciclib demonstrated an acceptable safety profile and moderate DCR in 3 days on/4 days off schedule.

Acid inhibition effect of ilaprazole on Helicobacter pylori-negative healthy volunteers: an open randomized cross-over study.

OBJECTIVE: The aim of this study was to evaluate the effects and safety of different doses of ilaprazole on healthy volunteers without a Helicobacter pylori infection. METHODS: A total of 12 healthy Chinese volunteers were enrolled and divided into four groups randomly, with a 5-day treatment of oral ilaprazole 5mg, 10mg and 20mg or omeprazole 20mg, respectively. After an interval of a 14-day washout phase, each was switched to another dose group and eventually completed all four regimens. The percentage time of intragastric pH>4 was the major index. The polymorphisms of the metabolic enzyme CYP2C19 in these volunteers were also detected. RESULTS: The percentage time of intragastric pH>4 in the ilaprazole 5, 10 and 20mg groups were 80.4%, 88.1% and 91.0%, respectively, during the first 24h, compared to that of the 20mg omeprazole group (76.6%, P>0.05). Ilaprazole 20mg provided a significant higher mean 24-h pH than that of the same dose of omeprazole both on Day 1 (7.78 vs 6.67, P<0.01) and Day 5 (7.95 vs 7.44, P<0.05). No CYP2C19-dependent difference or obvious adverse effect were found in any ilaprazole groups. CONCLUSION: Low dose ilaprazole offers a gastric acid inhibition comparable to a routine dose of omeprazole, and further investigations in patients with acid-associated diseases are needed.

Ilaprazole for the treatment of duodenal ulcer: a randomized, double-blind and controlled phase III trial.

OBJECTIVE: The new proton pump inhibitor (PPI), ilaprazole performed better at the dose of 10 mg/d relative to 5 or 20 mg/d in a previous phase II trial. A larger phase III trial was carried out to confirm the efficacy and safety of ilaprazole (10 mg/d) compared with omeprazole (20 mg/d) and provide some characteristics of the relationship between ilaprazole metabolism and CYP2C19 for later studies. RESEARCH DESIGN AND METHODS: Patients with at least one endoscopically diagnosed active duodenal ulcer (DU) were enrolled in a multicenter, randomized, double-blind, positive controlled trial and then assigned randomly to the ilaprazole group (10 mg/d) or the omeprazole group (20 mg/d) with a sample allocation ratio 2:1. The course of treatment was 4 weeks. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov registration number: NCT00952978. MAIN OUTCOME MEASURES: The primary endpoint was endoscopically diagnosed ulcer healing rate at week 4. Symptom relief was evaluated as a secondary endpoint by graded scores. Safety and tolerability were evaluated on basis of clinical assessments. In addition, blood samples were collected at baseline for CYP2C19 genotypes identification. RESULTS: Efficacy analyses were based on 494 patients. At week 4, the ulcer healing rates were 93.0% in ilaprazole group and 90.8% in omeprazole group (rate difference: 2.2%; 95% confidence interval: -2.8% to 7.2%). No obvious variation of healing rate on different CYP2C19 genotypes was found in ilaprazole group. The majority of patients (>80%) became asymptomatic after treatment. Incidences of adverse drug reactions were similar between ilaprazole group and omeprazole group (8.5% vs. 11.5%). CONCLUSIONS: Ilaprazole (10 mg/d) is as effective as omeprazole (20 mg/d) in the treatment of DU with similar side effects. The efficacy of ilaprazole is not affected by CYP2C19 polymorphisms.

A new PPI, ilaprazole compared with omeprazole in the treatment of duodenal ulcer: a randomized double-blind multicenter trial.

GOALS: To investigate the efficacy and safety of a new proton pump inhibitor (PPI), ilaprazole (IY-81149) in the treatment of duodenal ulcers and provide some characteristics of the dose-response relationship for later studies. BACKGROUND: PPIs have been used therapeutically for many years, and shown great efficacy in accelerating ulcer healing. Currently researches are focused on more potent PPIs. Some preclinical studies have shown that ilaprazole might be such a new substitute. STUDY: 235 patients with at least 1 endoscopically diagnosed active duodenal ulcer were enrolled in a randomized trial. Patients were randomized into 4 groups (5, 10, and 20 mg/d ilaprazole, with 20 mg/d omeprazole as positive control) and treated for up to 4 weeks. Forty patients accepted continuous 24-hour pH measurements after the fifth dose. The primary endpoint was ulcer healing rate at week 4. RESULTS: The efficacy analyses were based on 235 patients. At week 4, 86.4%, 93.1%, 86.4%, and 89.8% patients treated with 5 mg ilaprazole, 10 mg ilaprazole, 20 mg ilaprazole, and 20 mg omeprazole once daily, respectively had ulcers healed (P=0.59). The majority of patients (>70%) became asymptomatic after 4 weeks treatment. Both drugs with stipulated dosages exhibited similar efficacy and safety profiles. Gastric acid suppression increased with increasing dose of ilaprazole in pH study. CONCLUSIONS: Ilaprazole is as tolerable, safe, and efficacious as omeprazole in the treatment of duodenal ulcers, especially at a lower dose (10 mg/d ilaprazole vs. 20 mg/d omeprazole). (ClinicalTrials.gov ID: NCT00953381).

Randomized, parallel, double-blind comparison of the ulcer-healing effects of ilaprazole and omeprazole in the treatment of gastric and duodenal ulcers.

PURPOSE: Ilaprazole (IY-81149) is a new proton-pump inhibitor (PPI) not previously studied in human patients with ulcer disease. This study evaluated and compared it with a reference PPI, omeprazole, in the treatment of gastric and duodenal ulcers. METHODS: This was a double-blind, parallel, randomized study. Patients aged 18 years and above with at least one endoscopically confirmed active non-malignant gastric/duodenal ulcer were treated with 20 mg/day omeprazole or 5 mg/day or 10 mg/day ilaprazole for four weeks. Healing of ulcer was determined by its resolution from active to scarring stage. Symptoms relief was evaluated using a graded score. Safety and tolerability were evaluated on basis of clinical assessments. Between-group differences were tested using ANOVA or ANCOVA, as appropriate. Statistical significance was assumed at a two-tailed p value of 90%) became asymptomatic after treatment. At the dosages administered, both drugs exhibited similar efficacy and a similar safety profile. CONCLUSIONS: Ilaprazole is as tolerable, safe, and efficacious as omeprazole in the treatment of gastroduodenal ulcers, at a much lower dose (5 vs. 20 mg omeprazole).

Esomeprazole versus pantoprazole for healing erosive oesophagitis.

The aim of this study was to compare the efficacy of esomeprazole and pantoprazole with regard to healing and relief from gastroesophageal reflux disease-related symptoms. I this multicentre, randomized, single-blind study 180 patients (ITT population) diagnosed with endoscopically proven GERD grade A,B,C received esomeprazole (40 mg once daily (o.d.), n = 90) orpantoprazole (40 mg o.d., n = 90). Healing and relief from GERD-related symptoms were assessed at first and final visit (after 4 or 8 weeks of treatment). Esomeprazole 40 mg provided significantly greater healing than pantoprazole 40 mg after 4 weeks of treatment in patients with EE (77.8% vs. 72.2%). Esomeprazole-treated patients were healed after up to 8 weeks of treatment similar those treated with pantoprazole (92.2% vs. 91.1%). The proportion of heartburn-free days was similar in patients treated with esomeprazole and to those treated with pantoprazole.

Intravenous pantoprazole as initial treatment in patients with gastroesophageal reflux disease and a history of erosive esophagitis: a randomized clinical trial.

We sought to evaluate safety and efficacy of IV pantoprazole when used as initial therapy in patients with gastroesophageal reflux disease (GERD) and a history of erosive esophagitis (EE) in a double-blind, placebo-controlled, randomized, parallel-group study. Patients were randomized to 7 days of once-daily IV or oral pantoprazole (40 mg) or placebo. Efficacy variables included maximal acid output, basal acid output, and changes from baseline in frequency/severity of GERD symptoms, and frequency of antacid usage. Seventy-eight patients were randomized (n=26/27/25 [IV/oral/placebo]). Mean maximal acid output was 8.4, 6.3, and 20.9 mEq/h for IV or oral pantoprazole, and placebo, respectively. For pantoprazole versus placebo, maximal and basal acid output were significantly lower (P<.001) and there was a numerical trend toward improved GERD and antacid usage. Both treatments were well tolerated. In conclusion, IV/oral pantoprazole were similarly effective in suppressing basal and pentagastrin-stimulated gastric acid secretion in GERD patients with a history of EE.

Intragastric acidity after switching from 5-day treatment with intravenous pantoprazole 40 mg/d to 5-day treatment with oral esomeprazole 40 mg/d or pantoprazole 40 mg/d: an open-label crossover study in healthy adult volunteers.

BACKGROUND: After a course of IV proton pump inhibitor therapy, patients might require continued oral antisecretory therapy. A direct comparison of therapeutic alternatives could assist physicians in decisions regarding optimal acid-suppressive therapy. Oral esomeprazole might control intragastric acidity more effectively compared with other acid-suppressive agents after IV therapy. OBJECTIVE: The aim of this study was to compare intragastric acid control on day 5 of administration of esomeprazole magnesium versus pantoprazole 40 mg PO QD after switching from 5 days of treatment with pantoprazole 40 mg IV in healthy volunteers. METHODS: This randomized, open-label, comparative, 2-way crossover study was conducted at the Oklahoma Foundation for Digestive Research, Oklahoma City, Oklahoma, between October and December 2004. Healthy, Helicobacter pylori-negative adults were randomly assigned to 1 of 2 dosing sequences: pantoprazole IV followed by esomeprazole PO or pantoprazole IV followed by pantoprazole PO. All study medications were administered for 5 days at a dose of 40 mg QD. IV pantoprazole was administered over 2 minutes; all medications were administered 30 minutes before breakfast. There was a 10- to 21-day washout period between each 10-day dosing period. All doses were administered at the study site. Before oral study drug administration on days 1 and 5, 24-hour pH monitoring was performed using a pH catheter positioned 10 cm distal to the lower esophageal sphincter in the stomach. The primary end point was percentage of time with pH >4 (%t pH >4) during the 24-hour pH-monitoring period. Tolerability was assessed using spontaneous reporting, laboratory analysis, and vital-sign measurement. RESULTS: Of 42 subjects randomized to treatment sequences, 4 were withdrawn during the study because of invalid pH data; 38 subjects (24 men, 14 women; mean [SD] age, 25.2 [8.1] years) had assessable data. Day-5 %t pH >4 was 68.5% with esomeprazole and 53.3% with pantoprazole (P < 0.001). Day-1 %t pH >4 was 62.5% with esomeprazole and 51.0% with pantoprazole (P < 0.001). The most common adverse events were rhinitis (2 subjects each with pantoprazole IV and PO; 1 subject with esomeprazole) and headache (2 subjects with esomeprazole; 1 subject with pantoprazole IV). CONCLUSIONS: The results of this study in healthy adult volunteers suggest that switching from pantoprazole 40 mg IV to esomeprazole 40 mg PO QD more effectively suppresses intragastric acid compared with switching from pantoprazole 40 mg IV to pantoprazole 40 mg PO QD. All 3 treatments were well tolerated.

[Financial restrictions in health care systems could affect treatment quality of GERD-patients]. / Wachsender Kostendruck im Gesundheitswesen kann zu einer Beeinträchtigung der Behandlungsqualität bei Refluxpatienten führen.

AIMS: To directly compare the efficacy and safety of pantoprazole 40 mg VS. omeprazole 20 mg in patients with gastroesophageal reflux disease (GERD). MATERIAL AND METHODS: 915 Patients suffering from symptomatic GERD B-D (Los Angeles classification) were included in a double-blind randomized multicenter clinical trial and treated with either pantoprazole 40 mg od or omeprazole 20 mg od for six weeks. Primary efficacy criterion was the first time to reach normal symptoms as assessed by the questionnaire ReQuest-GI. RESULTS: Compared to omeprazole 20 mg, pantoprazole 40 mg achieved a significantly faster rate of symptom relief (p = 0.0298). Thus, as assessed with the ReQuest questionnaire, patients treated with pantoprazole 40 mg experienced relief from the 7 leading GERD symptoms 2 days earlier than those treated with omeprazole 20 mg. Long-lasting sustained relief from symptoms was also achieved earlier with pantoprazole than with omeprazole; in patients treated with pantoprazole, the daily symptom load was lower than in those treated with omeprazole. After 6 weeks of treatment, over 90 percent of patients were free from symptoms in both treatment groups (93.7 % in the pantoprazole, vs. 91.8 % in the omeprazole group, PP). Both medications were well tolerated. CONCLUSIONS: GERD patients treated with pantoprazole 40 mg experience a significantly faster relief from their leading symptoms than those treated with omeprazole 20 mg.

Proton pump inhibitors and acute interstitial nephritis.

BACKGROUND & AIMS: Proton pump inhibitors (PPIs) are a widely prescribed class of drugs, and their usage worldwide is increasing. Although well-tolerated, there have been case reports and a recent case series implicating these drugs in acute interstitial nephritis (AIN) and progression to acute renal failure (ARF). The aim of this study was to investigate how widespread this complication is in Australia, to identify which PPIs are implicated, and to establish whether PPI-induced AIN is a class effect. METHODS: We undertook a retrospective case review of potential cases at 2 teaching hospitals and a review of registry data from the Therapeutic Goods Administration of Australia (TGA). Parameters sought included the drug implicated, concurrent medications, symptoms, signs, serum creatinine, and time of onset after prescription. RESULTS: We identified 18 cases of biopsy-proven PPI-induced AIN causing ARF in the retrospective case review, which is the largest hospital-based case series to date. The TGA registry data identified an additional 31 cases of "biopsy proven interstitial nephritis." An additional 10 cases of "suspected interstitial nephritis," 20 cases of "unclassified acute renal failure," and 26 cases of "renal impairment" were also identified. All 5 commercially available PPIs were implicated in these cases. CONCLUSION: With the ever more widespread use of this class of medications, PPI-induced AIN is likely to become more frequent. There is now evidence to incriminate all the commercially available PPIs, suggesting there is a class effect. Failure to recognize this entity might have catastrophic long-term consequences including chronic kidney disease. Increased awareness might facilitate more rapid diagnosis and management of this potentially reversible condition.

Lansoprazole regimens that sustain intragastric pH > 6.0: an evaluation of intermittent oral and continuous intravenous infusion dosages.

BACKGROUND: Orally and intravenously administered proton pump inhibitors have been shown to reduce rebleeding rates, surgery and transfusion requirement. AIM: To compare lansoprazole intravenous and orally disintegrating tablet (Prevacid SoluTab) regimens with a pantoprazole intravenously administered regimen in sustaining intragastric pH >6.0. METHODS: Two similarly designed three-way, randomized crossover studies each enrolled 36 Helicobacter pylori-negative healthy volunteers. Study 1 regimens included intravenously administered bolus followed by 24-h continuous infusion (lansoprazole 90 mg, 6 mg/h; lansoprazole 120 mg, 6 mg/h; pantoprazole 80 mg, 8 mg/h). Study 2 regimens included intravenous bolus followed by lansoprazole orally disintegrating tablet or intravenous continuous infusion for 24 h (lansoprazole 90 mg, lansoprazole orally disintegrating tablet 60 mg every 6 h; lansoprazole 120 mg, 9 mg/h; pantoprazole 80 mg, 8 mg/h). Percentage of time pH >6.0 was assessed with 24-h intragastric pH monitoring. RESULTS: All regimens produced comparable gastric acid suppression. In both studies, regimens superior to pantoprazole included lansoprazole 90 mg, 6-mg/h; lansoprazole 90 mg, lansoprazole orally disintegrating tablet 60 mg q.d.s. and lansoprazole 120 mg, 9 mg/h (P < or = 0.013). The lansoprazole 120-mg, 6-mg/h regimen (P = 0.082) was not superior to pantoprazole in percentage of time intragastric pH >6.0. Mild reaction at the intravenous injection site was the most frequently reported adverse event. CONCLUSIONS: The intravenous bolus and continuously infused lansoprazole or intravenous bolus and intermittent lansoprazole orally disintegrating tablet regimens are as effective as intravenous pantoprazole in sustaining intragastric pH >6.0.

Multicenter, randomized, double-blind study comparing 10, 20 and 40 mg pantoprazole in children (5-11 years) with symptomatic gastroesophageal reflux disease.

OBJECTIVE: To evaluate symptom improvement in 53 children (aged 5-11 years) with endoscopically proven gastroesophageal reflux disease (GERD) treated with pantoprazole (10, 20 and 40 mg) using the GERD Assessment of Symptoms in Pediatrics Questionnaire. METHODS: The GERD Assessment of Symptoms in Pediatrics Questionnaire was used to measure the frequency and severity over the previous 7 days of abdominal/belly pain, chest pain/heartburn, difficulty swallowing, nausea, vomiting/regurgitation, burping/belching, choking when eating and pain after eating. Individual symptom scores were based on the product of the frequency and usual severity of each symptom. The sum of the individual symptom score values made up the composite symptom score (CSS). The primary end point was the change in the mean CSS from baseline to week 8. RESULTS: Mean frequency and severity of each symptom significantly decreased (from P < 0.006 to P < 0.001) over time. Similar significant decreases in CSS at week 8 versus baseline (P < 0.001) were seen in all groups. Significant decreases from baseline in CSS were noted from weeks 1 to 8 in the 20-mg (P < 0.003) and 40-mg (P < 0.001) groups. The 20- and 40-mg doses were significantly (P < 0.05) more effective than the 10-mg dose in improving GERD symptoms at week 1. Adverse events were similar among the treatment groups. CONCLUSIONS: Pantoprazole (20 and 40 mg) is effective in reducing endoscopically proven GERD symptoms in children. Both 20 and 40 mg pantoprazole significantly reduced symptoms as early as 1 week.

Pantoprazole-induced thrombocytopenia.

OBJECTIVE: To report 2 cases of thrombocytopenia associated with pantoprazole treatment and discuss existing reports on this drug-induced adverse event. CASE SUMMARIES: This paper describes the course of thrombocytopenia associated with pantoprazole 40 mg in 2 hospitalized patients. In both cases, thrombocytopenia appeared after the initiation of pantoprazole and rapidly improved after discontinuation of pantoprazole, although complete resolution of thrombocytopenia occurred in only one patient prior to discharge from the hospital. DISCUSSION: The mechanism of drug-induced thrombocytopenia is often poorly understood, and proton-pump inhibitors are generally not strongly suspected as a cause of thrombocytopenia. However, an objective causality assessment using the Naranjo probability scale revealed a probable relationship between thrombocytopenia and pantoprazole in both of the cases. It is unknown whether this is a class effect. CONCLUSIONS: Although drug-induced thrombocytopenia with pantoprazole appears to be rare, it represents a potentially severe adverse effect. This supports the judicious prescribing of pantoprazole and possibly other proton-pump inhibitors.