Effect of felodipine on indomethacin-induced gastric ulcers in rats.

Felodipine is a calcium channel blocker with antioxidant and anti-inflammatory properties. Researchers have stated that oxidative stress and inflammation also play a role in the pathophysiology of gastric ulcers caused by nonsteroidal anti-inflammatory drugs. The aim of this study was to investigate the antiulcer effect of felodipine on indomethacin-induced gastric ulcers in Wistar rats and compare it with that of famotidine. The antiulcer activities of felodipine (5 mg/kg) and famotidine were investigated biochemically and macroscopically in animals treated with felodipine (5 mg/kg) and famotidine in combination with indomethacin. The results were compared with those of the healthy control group and the group administered indomethacin alone. It was observed that felodipine suppressed the indomethacin-induced malondialdehyde increase (P<0.001); reduced the decrease in total glutathione amount (P<0.001), reduced the decrease superoxide dismutase (P<0.001), and catalase activities (P<0.001); and significantly inhibited ulcers (P<0.001) at the tested dose compared with indomethacin alone. Felodipine at a dose of 5 mg/kg reduced the indomethacin-induced decrease in cyclooxygenase-1 activity (P<0.001) but did not cause a significant reduction in the decrease in cyclooxygenase-2 activity. The antiulcer efficacy of felodipine was demonstrated in this experimental model. These data suggest that felodipine may be useful in the treatment of nonsteroidal anti-inflammatory drug-induced gastric injury.

Effect of famotidine on cognitive and behavioral dysfunctions induced in post-COVID-19 infection: A randomized, double-blind, and placebo-controlled study.

OBJECTIVES: This is an investigation of the efficacy and safety of famotidine, a selective histamine H2 receptor antagonist, on improvement of cognitive impairment, depression and anxiety symptoms developing post-COVID-19, in a 12-week, randomized controlled trial. METHODS: A total of 50 patients with a confirmed diagnosis of COVID-19 and a score ≤ 23 on the Mini-Mental State Examination (MMSE) test or a score ≤ 22 on the Montreal Cognitive Assessment (MoCA) were randomly assigned to either the famotidine (40 mg twice daily) or the placebo group. Changes in MMSE scores at weeks 6 and 12 were the primary outcome, while changes in other scales were the secondary outcomes. Participants and evaluators were blinded. RESULTS: At weeks 6 and 12, patients in the famotidine group had significantly higher MMSE scores (p = 0.014, p < 0.001, respectively). Regarding the MoCA scale, the famotidine group had a significantly higher score at weeks 6 and 12 (p = 0.001, p < 0.001, respectively). Considering the HAM-D scale (Hamilton Depression Rating Scale), at weeks 6 and 12, the famotidine group experienced a larger reduction (p = 0.009, p = 0.02, respectively). Additionally, comparison of the HAM-A scale scores (Hamilton Anxiety Rating Scale) at weeks 6 and 12 showed a statistically significant larger reduction in the famotidine group (p = 0.04, p = 0.02, respectively). The two groups did not differ in the frequency of adverse effects. CONCLUSION: Our study supports safety and efficacy of famotidine in treating cognitive impairment, depression and anxiety symptoms induced by COVID-19. TRIAL REGISTRATION: This trial was registered at the Iranian registry of clinical trials (IRCT: www.irct.ir; registration number: IRCT20090117001556N138).

Effectiveness of oral famotidine in reducing the hematologic complications of radiotherapy in patients with esophageal and cardia cancers: a randomized controlled trial.

BACKGROUND: Chemoradiotherapy complications has always been of great concern to both clinicians and patients during the course of treatment. The purpose of the present study was to examine the effectiveness of oral famotidine on the reduction of hematologic complications of patients with esophageal and gastric cardia cancers undergoing radiotherapy. METHODS: A single-blind controlled trial was conducted on 60 patients with esophageal and cardia cancers, who were undergoing chemoradiotherapy. Patients were randomly assigned to 2 groups with 30 patients to receive either 40 mg of oral famotidine (daily and 4 h before each session) or placebo. Complete blood count with differential, platelet counts, and hemoglobin levels were obtained weekly during treatment. The main outcome variables were lymphocytopenia, granulocytopenia, thrombocytopenia, and anemia. RESULTS: The findings indicated a significant effect of famotidine on reduction of thrombocytopenia among intervention group compared to control group (P < 0.0001). Even so, the effect of intervention was not significant for other outcome variables (All, P ≥ 0.05). The lymphocyte (P = 0.007) and platelet (P = 0.004) counts were also significantly greater in famotidine group in comparison with placebo group at the end of the study. CONCLUSION: As evidenced by the findings of the current study, famotidine might be recommended as an effective radioprotective agent among patients with esophageal and gastric cardia cancers to prevent Leukocyte and platelet reduction to some extent. Trial registration This study was prospectively registered at irct.ir (Iranian Registry of Clinical Trials) with the code IRCT20170728035349N1, 2020-08-19.

Apple (Malus domestica Borkh) leaves attenuate indomethacin-induced gastric ulcer in rats.

Malus domestica Borkh, the apple tree, exhibited numerous pharmacological properties including antioxidant, neuroprotective, anti-inflammatory, anticancer and antimicrobial activities. The present work aimed to annotate the secondary metabolites from a butanol fraction of apple leaves (BLE), evaluate the gastro-protective and healing effects of this fraction against indomethacin-induced gastric ulcers in rats and to identify its mechanism of action. BLE (100, and 200 mg/kg) was orally administered in rats as an acute treatment against indomethacin-induced gastric ulcer in comparison with famotidine as reference anti-ulcer drug. The stomachs of rats were collected to determine the ulcer index, the preventive ratio, measure the activity of glutathione peroxidase (GPx), and estimate the expression of cyclooxygenase-2 (COX-2), and heat shock protein 70 (HSP70). Furthermore, we evaluated both inflammatory and oxidative stress markers in the gastric tissues. We also performed histopathological study of gastric mucosa using H&E stain and periodic Schiff base stain to evaluate both gastric injury scores and gastric mucus content respectively. Pretreatment with BLE markedly lowered the severity of gastric injury induced by indomethacin, decreased oxidative stress, inflammatory cytokines, and COX-2 expression in the examined gastric tissues. The gastric healing effect of BLE was associated with increased mucoglycoproteins, and HSP70 expression. Additionally, gastric healing effect of high dose of BLE was superior to that of famotidine in decreasing gastric injury scores, COX-2, inflammatory cytokines, lipid peroxidation and in increasing gastric mucin content, HSP70, and reduced glutathione. These findings indicate that BLE is effective in accelerating ulcer healing by boosting HSP70 expression, and decreasing COX-2 expression, oxidative stress, and gastric inflammation which might be related to the presence of 21 phytoconstituents.

Role of Famotidine and Other Acid Reflux Medications for SARS-CoV-2: A Pilot Study.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus-19 disease (COVID-19) pandemic. The H-2 blocker famotidine has been suggested as an FDA-approved drug that could potentially be repurposed for treatment of COVID-19. Famotidine has since been shown to improve patient outcomes and reduce symptom severity in patients acutely ill with COVID-19. Other studies have suggested that proton pump inhibitors (PPIs) might have an association with COVID-19. OBJECTIVE: The purpose of the present study was to determine whether famotidine or any other antireflux medications have a prophylactic or detrimental effect for SARS-CoV-2 infection when taken regularly for the management of acid reflux. METHODS: An anonymous, web-based survey was distributed via email to adult otolaryngology patients to collect demographic data, past medical history, medication history, incidence of symptoms associated with COVID-19, potential exposure to SARS-CoV-2, and results of any PCR or serological testing. Associations between reflux medications and incidence of COVID-19 cases were analyzed. Statistical analysis was performed using SPSS. Chi-square with Fisher's exact test, Point-Biserial correlation, Kendall's-tau-b, independent samples t test, and the Mann-Whitney U test were used as appropriate. A binary logistic regression model was fit to determine probability of COVID-19 cases after adjustment for other risk factors. RESULTS: There were 307 patients who responded to the survey. The average age of respondents was 52.63 ± 17.03. Famotidine use was not associated with incidence of laboratory-confirmed (P= 0.717) or symptomatically suspected (P= 0.876) COVID-19. No other reflux medications were found to be significant predictors for laboratory-confirmed or suspected COVID-19 (P> 0.05). Younger age (odds ratio [OR] = 1.043, 95% CI: 1.020-1.065, P< 0.001), high risk obesity (OR = 4.005, 95% CI: 1.449-11.069, P= 0.007), and use of a corticosteroid nasal spray (OR = 3.529, 95% CI: 1.352-9.211, P= 0.010) were significant predictors for symptomatically suspected COVID-19 cases. CONCLUSIONS: There was no association between incidence of COVID-19 and use of reflux medications, including famotidine at doses used orally to manage reflux and high dose PPIs. Reflux medications did not protect against or increase the risk of COVID-19.

Famotidine's Possible Cutaneous Rash in COVID-19 Patients: An Adverse Effect Case Series.

BACKGROUND: Various cutaneous manifestations have been observed in patients with COVID-19 infection. However, the side effects on skin of the medications used for COVID-19, such as famotidine, have not been studied. OBJECTIVE: This case series aims to present challenges in defining cutaneous manifestations of famotidine in the context of COVID-19. CASE PRESENTATION: We identified patients from Imam Khomeini hospital complex who were admitted to the ward due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), were taking famotidine and having cutaneous rash. Clinical data were obtained through observation and intervention. DISCUSSION: We found 4 SARS-CoV-2 patients with cutaneous manifestations. The mean (±SD) age of the patients was 57±2 years, 3 patients were men, and their COVID-19 symptoms appeared 10±3 days before admission. The most common symptoms were cough and shortness of breath. All the patients were admitted for hypoxemic respiratory failure. Patients received famotidine for gastrointestinal prophylaxis, and all 4 patients developed Acral macular mountainous skin lesions in the upper and lower extremities, then we discontinued famotidine and lesions were recovered completely in all patients. CONCLUSION: These cases prompted us to inform clinicians about cutaneous complications of famotidine in COVID-19 patients.

A prospective, randomized, placebo-controlled, double-blinded clinical trial comparing the incidence and severity of gastrointestinal adverse events in dogs with cancer treated with piroxicam alone or in combination with omeprazole or famotidine.

OBJECTIVE: To assess the impact of prophylactic omeprazole and famotidine on the incidence and severity of gastrointestinal (GI) adverse events (AEs) in dogs with cancer treated with single agent piroxicam. ANIMALS: 39 dogs with a cytologic or histologic diagnosis of cancer with no history of GI disease and received piroxicam. PROCEDURES: A prospective, randomized, placebo-controlled, double-blinded clinical trial was performed. All dogs received piroxicam (0.3 mg/kg [0.14 mg/lb], PO, q 24 h) and either omeprazole (1 mg/kg [0.45 mg/lb], PO, q 12 h), famotidine (1 mg/kg, PO, q 12 h), or placebo (lactose; PO, q 12 h). Monthly assessments of GI AEs were performed and scored by using the Veterinary Comparative Oncology Group's Common Terminology Criteria for Adverse Events (version 1.1). RESULTS: Compared with dogs in the placebo group, more dogs in the omeprazole group (84.6% vs 36.4%) and famotidine group (80.0% vs 36.4%) experienced GI AEs by day 56. The severity of GI AEs was higher in the omeprazole group, compared with the placebo group. CONCLUSIONS AND CLINICAL RELEVANCE: Omeprazole was not helpful in reducing the frequency or severity of GI AEs and was associated with more frequent and severer GI AEs in dogs with cancer treated with single agent piroxicam. Proton-pump inhibitors and H2-receptor antagonists should not be prescribed as prophylaxis with NSAIDs for dogs with cancer.

No association between chronic use of ranitidine, compared with omeprazole or famotidine, and gastrointestinal malignancies.

BACKGROUND: In 2019, the United States Food and Drug Administration detected above-regulation levels of the human carcinogen N-nitrosodimethylamine (NDMA) in ranitidine, resulting in a complete removal of the medication from the market. NDMA is known to cause gastrointestinal malignancies in animal models. AIM: To determine if patients who were receiving ranitidine have a higher risk of developing cancers of the digestive tract compared to patients taking other anti-reflux medications. METHODS: Using the nationwide database IBM Explorys, patients taking ranitidine were compared to patients on either famotidine or omeprazole. Incidence data of new malignancies of the oesophagus, stomach, liver, pancreas, and colon/rectum were obtained in 1-year intervals for up to 10 years. Two multivariable logistic regression models were used to calculate odds ratios (ORs), one adjusting for common risk factors for each cancer studied, and the other for demographic factors. RESULTS: Patients on ranitidine who were compared to patients on famotidine had ORs of 0.51(95% CI 0.43-0.60), 0.43(95% CI 0.36-0.51), 0.39(95% CI 0.36-0.41), 0.54(95% CI 0.49-0.62), and 0.46(95% CI 0.43-0.49) of developing oesophageal, gastric, hepatocellular, pancreatic, and colorectal cancers, respectively (P < 0.001). Patients on ranitidine compared to omeprazole had ORs of 0.62(95% CI 0.52-0.72), 0.58(95% CI 0.49-0.68), 0.81 (95% CI 0.76-0.86), 0.68(95% CI 0.60-0.76), and 0.66(95% CI 0.62-0.70) of developing oesophageal, gastric, hepatocellular, pancreatic, and colorectal cancers respectively (P < 0.001). CONCLUSIONS: Use of ranitidine was not associated with an increased odds of developing gastrointestinal malignancies compared to omeprazole or famotidine use.

The Efficacy of Famotidine in improvement of outcomes in Hospitalized COVID-19 Patients: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: This study aims to investigate the effect of Famotidine on the recovery process of COVID-19 patients. TRIAL DESIGN: This phase III randomized clinical trial was designed with two parallel arms, placebo-controlled, single-blind, and concealed allocation. PARTICIPANTS: All COVID-19 patients admitted to Shahid Mohammadi Hospital in Bandar Abbas whose PCR test results are positive for SARS-Cov-2 and sign the written consent of the study are included in the study and immunocompromised patients, end-stage renal disease, moderate renal failure (clearance Creatinine 30 to 50 ml/min) or stage 4 severe chronic kidney disease or need for dialysis (creatinine clearance lesser than 30 ml/min), history of liver disease, hepatitis C infection or alcoholism, Glucose 6 phosphate dehydrogenase deficiency(G6PD), the ratio of Alanine transaminase to Aspartate transaminase 5 times above the normal limit, history or evidence of long QT segment on Electrocardiogram, psoriasis or porphyria, pregnancy, use of oral contraceptives, Dasatinib, Neratinib, Ozanimod, Pazopanib, Rilpivirine, Siponimod and/or Tizanidine and allergies to any study drug are excluded. INTERVENTION AND COMPARATOR: Intervention group receives standard pharmacotherapy according to the treatment protocols of the National Committee of COVID-19 and oral famotidine 160 mg (Manufactured by Chemidarou Pharmaceutical Company) four times a day until the day of discharge, for a maximum of fourteen days. Comparator group receives standard drug therapy according to the treatment protocols of the National Committee of COVID-19 and placebo in the same dosage. MAIN OUTCOMES: Patients' temperature, respiration rate, oxygen saturation, lung infiltration, lactate dehydrogenase and complete blood count were measured at the baseline (before the intervention) and on day 14 after the intervention or on the discharge day. RANDOMISATION: The person who has no role in admitting patients and assigning patients to random codes preparing random sequences using online tools and by permuted block randomization method. Eligibility criteria are monitored by the person responsible for admitting patients. Codes in a random sequence are assigned to patients by the treatment team without knowing that each code is in the intervention or comparator group. Patient codes are then matched to randomly generated sequence information for interventions. BLINDING (MASKING): All participants are unaware of which group of this study they are in and after grouping patients in the groups, Patients receive Famotidine in the treatment group and receive a placebo in the control group. The lead researcher, care givers, data collectors, and outcome assessors are aware of the grouping of patients. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): As there is no prior work on this research question, so no assumptions for the sample size calculation could be made. A total of 20 patients participate in this study, which are randomly divided into two groups of 10 as intervention or control groups. TRIAL STATUS: Version 3 of the protocol was approved by the Deputy of Research and Technology and the ethics committee of Hormozgan University of Medical Sciences on August 2, 2020, with the local code 990245, and the recruitment started on August 17, 2020. recruitment ended on August 31, 2020. Since the recruitment ended earlier than expected (the expected recruitment end date was 21/12/2020), we submitted post recruitment but prior to publication of the results. TRIAL REGISTRATION: The protocol was registered before starting subject recruitment under the title: The effect of Famotidine on the improvement of patients with COVID-19, IRCT20200509047364N2, at Iranian Registry of clinical trials ( https://www.irct.ir/trial/49657 ) on 17 August 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Influence of rabeprazole and famotidine on pharmacodynamic profile of dual antiplatelet therapy in clopidogrel-sensitive patients: The randomized, prospective, PROTECT trial.

Although acid suppressants are needed to attenuate gastrointestinal bleeding (GIB) after percutaneous coronary intervention (PCI), pharmacodynamic interaction between clopidogrel and proton pump inhibitor (PPI) can increase the risk of high platelet reactivity (HPR). We sought to evaluate serial changes of platelet measures and influence of rabeprazole on platelet measures. After 600-mg clopidogrel loading for elective PCI, clopidogrel-sensitive patients were recruited and randomly assigned to add rabeprazole of daily 20 mg (n = 40) or famotidine of daily 40 mg (n = 40). Platelet measures were performed with light transmittance aggregometry and VASP-P assay. Primary endpoint was 5 µM ADP-induced platelet aggregation (PA) at 30-day follow-up. HPR was defined as 5 µM ADP-induced PA > 46%. Baseline platelet measures did not differ significantly between the groups. The 30-day level of 5 µM ADP-induced PA was similar between the famotidine vs. rabeprazole group (30.0 ± 16.4% vs. 30.2 ± 13.9%, P= .956). In addition, other platelet measures were comparable between the groups. At 30-day follow-up, the incidence of HPR was similar between the famotidine and rabeprazole groups (20.5% vs. 15.4%; P= .555). In conclusion, adjunctive use of rabeprazole showed the similar antiplatelet effect even in clopidogrel-sensitive patients compared with adjunctive famotidine, which may support the similar effect of rabeprazole and famotidine on the antiplatelet effect of dual antiplatelet therapy with clopidogrel plus aspirin.

Transient Fanconi Syndrome After Treatment with Firocoxib, Cefadroxil, Tramadol, and Famotidine in a Maltese.

Fanconi syndrome is a renal proximal tubulopathy characterized by excessive urinary loss of glucose, amino acids, several electrolytes, and bicarbonate. Here, we report the case of transient Fanconi syndrome in a dog following administration of firocoxib, cefadroxil, tramadol, and famotidine. A 10 mo old Maltese was presented with lethargy, anorexia, vomiting, and weight loss. Transient Fanconi syndrome without azotemia was associated with firocoxib, cefadroxil, tramadol, and famotidine treatment. The dog received supportive care including IV fluids, gastroprotectants, and oral nutritional supplements. Two months after initial diagnosis and treatment, the dog showed complete resolution of glucosuria and aminoaciduria. The unique features of Fanconi syndrome in this case emphasize the potential renal tubular toxicity of this widely used multiple-drug combination.

No Pharmacokinetic Interaction Between the Hepatitis C Virus Inhibitors Elbasvir/Grazoprevir and Famotidine or Pantoprazole.

Use of agents to suppress gastric acid secretion is common among patients with hepatitis C virus (HCV) infection. The aims of this open-label, three-period, fixed-sequence study were to evaluate the effect of famotidine and pantoprazole on the pharmacokinetics and safety of elbasvir/grazoprevir fixed-dose combination (FDC) in 16 healthy subjects. Elbasvir and grazoprevir each exhibited similar pharmacokinetics following single-dose administration of elbasvir/grazoprevir with or without famotidine or pantoprazole. Geometric mean ratios (GMRs) of grazoprevir AUC(0,∞), Cmax , and C24 (elbasvir/grazoprevir + famotidine or elbasvir/grazoprevir + pantoprazole vs. elbasvir/grazoprevir) ranged from 0.89-1.17. Similarly, GMRs of elbasvir AUC(0,∞), Cmax , and C24 (elbasvir/grazoprevir + famotidine or elbasvir/grazoprevir + pantoprazole vs. elbasvir/grazoprevir) ranged from 1.02-1.11. These results indicate that gastric acid-reducing agents do not modify the pharmacokinetics of elbasvir or grazoprevir in a clinically relevant manner and may be coadministered with elbasvir/grazoprevir in HCV-infected patients without restriction.

A Rare Case of Famotidine-Induced Delirium in a Peritoneal Dialysis Patient.

H2 receptor antagonists are commonly employed to manage gastro-esophageal reflux and peptic ulcer diseases with a very low incidence of side effects. Herein, we report an extremely rare incidence of famotidine-induced acute confusion in a patient with end-stage renal failure. We also discuss the pharmacokinetic properties of famotidine and its interplay with compromised renal function to result in neuropsychiatric manifestations, highlighting the importance of dosage ad ustment in individuals with renal insufficiency.

Characteristics of the Human Upper Gastrointestinal Contents in the Fasted State Under Hypo- and A-chlorhydric Gastric Conditions Under Conditions of Typical Drug - Drug Interaction Studies.

OBJECTIVE: Evaluate the impact of reduced gastric acid secretion after administration of two acid-reducing agents on the physicochemical characteristics of contents of upper gastrointestinal lumen of fasted adults. MATERIALS AND METHODS: Eight healthy male adults, fasted from food for 12 h, participated in a three-phase crossover study. Phase 1: No drug treatment prior to aspirations. Phase 2: Oral administration of 40 mg pantoprazole at ~9 am the last 3 days prior to aspirations and at ~7 am on aspiration day. Phase 3: Oral administration of 20 mg famotidine at ~7 pm prior to aspirations and at ~7 am on aspiration day. Samples from the contents of upper gastrointestinal lumen were aspirated for 50 min, after administration of 240 ml table water at ~9 am. RESULTS: Reduction of gastric acid secretion was accompanied by reduced buffer capacity, chloride ion concentration, osmolality and surface tension in stomach and by increased pH (up to ~0.7 units) in upper small intestine during the first 50 min post-water administration. The mechanism of reduction of acid secretion seems to be important for the buffer capacity in stomach and for the surface tension in upper gastrointestinal lumen. CONCLUSIONS: Apart from gastric pH, reduced acid secretion affects physicochemical characteristics of contents of upper gastrointestinal lumen which may be important for the performance of certain drugs/products in the fasted state.

Gastroprotective efficacy and safety of single-tablet ibuprofen/famotidine vs ibuprofen in older persons.

OBJECTIVES: A combination tablet of ibuprofen 800 mg and famotidine 26.6 mg given three times daily is effective for the treatment of rheumatoid arthritis and osteoarthritis and decreases the risk of developing upper gastrointestinal (GI) ulcers. This analysis evaluated the gastroprotective efficacy and safety of the single-tablet combination of ibuprofen/famotidine compared with ibuprofen alone on the basis of age and the presence of one or more risk factors for development of upper GI ulcer. METHODS: Pooled data from the 24-week, randomized, double-blind, parallel-group REDUCE-1 and REDUCE-2 trials were used. Endoscopies were performed in patients aged 40-80 years. The proportion of patients who developed ≥ 1 upper GI ulcer during treatment with ibuprofen/famotidine versus ibuprofen alone stratified on the basis of age (< 60 or ≥ 60 years) was evaluated. Further, analyses were performed on additional risk factors for ulcer development. RESULTS: Gastroprotective efficacy of the combination was not affected by age. Pooled results demonstrated statistically significantly fewer upper GI (10.0 vs 19.5%, p < 0.0001), gastric (8.9 vs 16.8%, p = 0.0004), and duodenal ulcers (1.1 vs 5.4%, p < 0.0001) in patients < 60 years treated with ibuprofen/famotidine versus ibuprofen alone compared with 12.9 vs 26.6% (p = 0.0002), 11.9 vs 23.4% (p = 0.0011), and 1.0 vs 4.5% (p = 0.0096), respectively, in patients ≥ 60 years. The ibuprofen/famotidine combination provided nearly 51 and 59% reduction in the risk of developing a GI ulcer in patients <60 years and ≥ 60 of age, respectively. Efficacy was maintained in the presence of additional risk factors, as well. CONCLUSIONS: These results indicate that the fixed-combination of ibuprofen/famotidine provides gastroprotection in those of older age, with or without additional risk factors for the development of upper GI ulcers, as compared with ibuprofen alone. US National Institutes of Health registry, http://www.clinicaltrials.gov, NCT00450658 and NCT00450216.

Analysis of an ECG record database reveals QT interval prolongation potential of famotidine in a large Korean population.

Some non-antiarrhythmic drugs have the undesirable property of delaying cardiac repolarization, an effect that can be measured empirically as a prolongation of the QT interval by surface electrocardiogram (ECG). The QT prolongation and proarrhythmia potential of famotidine are largely unknown, particularly in individuals that have cardiovascular risk factors such as abnormal electrolyte levels. Based on an analysis of QT/QTc intervals from a database of ECG recordings from a large Korean population (ECG-ViEW, 710,369 ECG recordings from 371,401 individuals), we observed that famotidine administration induced a prolonged QTc interval (above 480 ms, p < 0.05 compared to before-treatment, based on a McNemar test). Furthermore, famotidine induced QT prolongations in 10 out of 14 patients with hypocalcemia and 11 out of 13 patients with hypomagnesemia [difference of mean between before and after famotidine administration; 38.00 ms (95% confidence interval 2.72-73.28) and 67.08 ms (95% confidence interval 24.94-109.21), p < 0.05 and p < 0.01 by paired t test, respectively]. In vitro, the IC50 of famotidine for human-ether-a-go-go gene (hERG) channel inhibition was higher than 100 µM as determined by automated patch clamp hERG current assay, implying that hERG channel inhibition is not the underlying mechanism for QT prolongation. These results suggest that famotidine administration increases a proarrhythmic potential, especially in subjects with electrolytes imbalance.

Comparison of proton pump inhibitor and histamine-2 receptor antagonist in the prevention of recurrent peptic ulcers/erosions in long-term low-dose aspirin users: a retrospective cohort study.

BACKGROUND: Proton pump inhibitor and histamine-2 receptor antagonist can prevent aspirin-related ulcers/erosions but few studies compare the efficacy of these two agents. Aims. We evaluated the efficacy of omeprazole and famotidine in preventing recurrent ulcers/erosions in low-dose aspirin users. METHODS: The 24-week clinical outcomes of the patients using low-dose aspirin for cardiovascular protection with a history of ulcers/erosions and cotherapy of omeprazole or famotidine were retrospectively reviewed. The incidence of gastrointestinal symptoms, recurrent ulcers/erosions, erosive esophagitis, gastrointestinal bleeding, and thromboembolic events was analyzed. RESULTS: A total of 104 patients (famotidine group, 49 patients; omeprazole group, 55 patients) were evaluated. Famotidine group had more gastrointestinal symptoms episodes than omeprazole group (46.9% versus 23.6%, P=0.01). Fifteen famotidine group patients and 5 omeprazole group patients had recurrent ulcers/erosions (30.6% versus 9.1%, P=0.005). Lanza scale was significantly lower in omeprazole group than in famotidine group (1.2±0.7 versus 1.7±1.1, P=0.008). Only 1 famotidine group patient had ulcer bleeding. The incidences of erosive esophagitis and thromboembolic events were comparable between both groups. CONCLUSIONS: Omeprazole was superior to famotidine with less gastrointestinal symptoms and recurrent ulcers/erosions in patients using 24-week low-dose aspirin. The risk of erosive esophagitis, gastrointestinal bleeding, and thromboembolic events was similar between both groups.

Dosage effects of histamine-2 receptor antagonist on the primary prophylaxis of non-steroidal anti-inflammatory drug (NSAID)-associated peptic ulcers: a retrospective cohort study.

BACKGROUND: A histamine-2 receptor antagonist (H2RA) is one of the common gastroprotective co-therapies used with non-steroidal anti-inflammatory drugs (NSAIDs) for the prevention or treatment of peptic ulcers (PUs). To date, no study has directly compared the prophylactic effectiveness between high-dose and low-dose H2RA. OBJECTIVE: Our objective was to compare the effectiveness of high-dose versus low-dose H2RAs in the primary prophylaxis of PUs among short-term NSAID users. METHODS: A retrospective cohort study was conducted using the Clinical Data Analysis and Reporting System (CDARS) in Hong Kong. Patients aged 18 years or above who received a single prescription of oral NSAID with oral H2RA were identified within the study period (1 January 2009-31 December 2012). Patients with a history of or risk factors for PU in the corresponding 2 years prior to the index date (of the first NSAID prescription) were excluded. Log binomial regression analysis was used to calculate the relative risk of PU among NSAID users with high-dose H2RA versus low-dose H2RA exposure. RESULTS: Among the NSAID cohort (n = 102,042), 77,509 (76 %) were on low-dose H2RA and 24,533 (24 %) were on high-dose H2RA. Of the total 69 PU cases identified during the drug exposure period, 64 (0.08 %) received low-dose-H2RA and five (0.02 %) received high-dose H2RA. The overall absolute risk of PUs for NSAID users whilst on H2RA was approximately 1 per 1,479 patients. The adjusted relative risk for NSAID users receiving high-dose H2RA versus low-dose H2RA was 0.32 (95 % confidence interval [CI] 0.13-0.79). Patients aged ≥65 years, receiving a longer duration of treatment, or with concomitant use of antiplatelet agents were found to be at higher risk of PU. CONCLUSION: High-dose H2RA showed greater effectiveness than low-dose H2RA in the primary prophylaxis of NSAID-associated PUs in short-term new users.

Activity of outpatient intravenous interleukin-2 and famotidine in metastatic clear cell kidney cancer.

Outpatient daily intravenous infusions of interleukin-2 (IL-2) have been developed to maintain anticancer activity and decrease toxicity of this agent against kidney cancer. Lymphokine activated killer cell (LAK) numbers are increased with these IL-2 schedules. Famotidine may enhance the LAK activity by increasing IL-2 internalization by the IL-2 receptor on lymphocytes. Fifteen patients with metastatic clear cell kidney cancer received IL-2 18 million IU/M² intravenously over 15-30 minutes preceded by famotidine 20 mg IV daily for 3 days for 6 consecutive weeks as outpatients. Cycles were repeated every 8 weeks. Patient characteristics were seven males/eight females, median age 59 (range: 28-70), median Eastern Cooperative Oncology Group (ECOG) performance status-1; common metastatic sites were lungs (14), lymph nodes (9), liver (4), bone (4), and pancreas (4). Prior systemic therapies were oral tyrosine kinase inhibitor (8), IL-2 (6), and mTor inhibitor (2). Most common toxicities were rigors, arthralgia/myalgia, nausea/emesis, fever, and hypotension. All episodes of hypotension were reversible with intravenous fluid. No patients required hospitalization due to toxicity. One complete response (7%) and four partial responses (26%) were seen (total response rate=33%; 95% confidence interval: 15%-59%). Responses occurred in the lungs, liver, lymph nodes, and bone. Outpatient intravenous IL-2 with famotidine has activity in metastatic clear cell kidney cancer.