Budget impact modeling for a single-tablet formulation of ibuprofen and famotidine for prevention of upper gastrointestinal ulcers in patients with osteoarthritis and/or rheumatoid arthritis.

BACKGROUND: Single-tablet ibuprofen/famotidine is approved by the US Food and Drug Administration for the relief of signs and symptoms of rheumatoid arthritis and osteoarthritis and to decrease the risk of developing upper gastrointestinal (GI) ulcers in patients taking ibuprofen for those indications. Currently, little is known about the cost impact of gastroprotective therapies, and an estimate of the financial consequences of adopting these therapies will be helpful to decision makers. OBJECTIVES: The goal of this study was to review a model that evaluates the expected financial impact to US health care plans from the introduction of single-tablet ibuprofen/famotidine into the chronic NSAID user population. METHODS: A budget impact model, considering a typical health plan of 1 million enrollees, was used to compare patients receiving: (1) single-tablet ibuprofen/famotidine; (2) chronic NSAID treatment plus any GI-protective agent; and (3) chronic NSAID treatment without a GI-protective agent. RESULTS: The expected medication cost for single-tablet ibuprofen/famotidine was $734,192 ($81,577 in year 1, $244,731 in year 2, and $407,884 in year 3), corresponding to a total per-member per-month cost of $0.020 ($0.007 in year 1, $0.020 in year 2, and $0.034 in year 3). Considering anticipated decreases in the use of other NSAIDs, the use of GI-protective agents, and GI complications, the total expected 3-year drug cost for single-tablet ibuprofen/famotidine was offset by 50%, representing an estimated total budget impact of $364,396 or $0.010 per member per month. Sensitivity analyses of cost and market share variables and clinical and drug characteristics identified the most influential variables to be the cost of the drug and persistence to the ibuprofen/famotidine formulation, respectively. CONCLUSIONS: The expected decrease in treatment costs for less serious GI-related complications illustrates the benefits of single-tablet ibuprofen/famotidine as a gastroprotective therapy in patients receiving chronic NSAID treatment, with a modest financial impact on total health care costs.

Selection of generic preparations of famotidine orally disintegrating tablets for use in unit-dose packages.

Changes in the hardness, dissolution, and the disintegration time of brand name and generic preparations (6 preparations) of famotidine orally disintegrating tablets were investigated. Tablets had been stored in a thermo-hygrostat-controlled environment set to simulate the home conditions of patients up to 8 weeks after unit-dose packaging. Among the tablets in unit-dose packaging prepared immediately after blister packs (BP) were opened, one generic had decreased hardness to less than 2.0 kg after 1 week, 55.1% of its initial hardness value, and a shorter disintegration time of about 1/5 of its initial disintegration time. Generics met the standard for dissolution 8 weeks after unit-dose packaging. The decrease in hardness after unit-dose packaging is presumed to be associated with additives, and particularly the types and amounts of binding agents, but evidence of this association was lacking. The hardness noted in drug interview forms (IFs) and the state of sales of bulk tablet packages must be determined to facilitate the selection of generics that remain hard even after unit-dose packaging.

Development of a canine model to enable the preclinical assessment of pH-dependent absorption of test compounds.

A preclinical canine model capable of predicting a compound's potential for pH-dependent absorption in humans was developed. This involved the surgical insertion of a gastrostomy feeding tube into the stomach of a beagle dog. The tube was sutured in position to allow frequent withdrawal of gastric fluid for pH measurement. Therefore, it was possible to measure pH in the stomach and assess the effect of gastric pH-modifying agents on the absorption of various test compounds. Fasted gastric pH in the dog showed considerable inter- and intra-animal variability. Pretreatment of pentagastrin (6 µg/kg intramuscularly) 20 min prior to test compound administration was determined to be adequate for simulating fasting stomach pH in humans. Pretreatment with famotidine [40 mg orally] 1 h prior to test compound administration was determined to be adequate for simulating human gastric pH when acid-reducing agents are coadministered. Pentagastrin and famotidine pretreatments were used to test two discovery compounds and distinct differences in their potential for pH-dependent absorption were observed. The model described herein can be used preclinically to screen out compounds, differentiate compounds, and support the assessment of various formulation- and prodrug-based strategies to mitigate the pH effect.

Tratamiento de la infección por helicobacter pylori en pacientes con úlcera duodenal: estudio de costo beneficio / Treatment of helicobacter pylori infection in patients with duodenal ulcer: a cost benefit study

Background: Epidemiological differences suggest that treatments for H. pylori eradication should be locally validated. Aim: To perform a cost benefit study of different treatment options for H. pylori infection. Patients and methods: One hundred and sixty-seven patients with active duodenal ulcer and H. pylori infection who completed a 2-week treatment with one of the following regimens were included: famotidine plus amoxycillin plus metronidazole (FAM), omeprazole plus amoxycillin plus tinidazole (OAT) or lansoprazole plus clarithromycin plus amoxycillin in 3 (LAC1) or 2 (LAC2) daily doses. We compared efficacy, adverse effects and cost. Results: Eradication rate was 74.6, 72.9, 96.4 y 91.7 percent for FAM, OAT, LAC1 and LAC2 respectively (p<0.05). Direct cost ranged from US$ 50 for FAM to US$ 220 for LAC1. A decision analysis was carried out in a model including direct and indirect costs and considering retreatment with antibiotics after the first treatment failure and one-year treatment with H2-blockers in case of a second failure. FAM was selected as the most cost-effective option, with an estimated cost of about US$ 300 ñ 148 per patient. However, cost associated to LAC2 was very similar (US$ 320 ñ 58) and the lower standard deviation suggests less variation. Sensitivity analyses, considering reasonable fluctuation in parameters such as eradication rate, cost and follow-up period suggest that a regimen containing a proton pump inhibitor, clarithromycin and amoxycillin may be the most cost-effective treatment. Conclusions: These results should be confirmed in other settings, specially in ordinary clinical practice, far from clinical research

[Intravenous treatment with quamatel in reflux-esophagus and erosive gastritis]. / Intravenozno lechenie s quamatel pri reflux-ezofagit i eroziven gastrit.

Organism's good tolerance toward Ranitidin and Famotidin makes possible an application of doses higher than the ones put into everyday practice. This is a very favorable circumstance considering the fact that according to some authors the decreasing of acidity in oesophagus apparently depends on the applied dose of the medicine. Thus the treatment with famotidin 2 x 40 mg allows an additional decreasing of acidity in lower oesophagus. We investigate the effect of intravenous application of famotidin (quamatel) in dose 2 x 20 mg and 2 x 40 mg as monotherapy in cases of reflux-oesophagitis and erosive gastritis as well as organism's tolerance toward it. There are 23 patients studied--17 men and 6 women, between 18 and 70 years old. The diagnoses are: reflux-oesophagitis--23, chronic erosive gastritis and reflux-oesophagitis--8. The patients are selected according to clinical criteria--scalding and/or pain in the oesophagus accompanied with acidity in the mouth cavity. The diagnoses are put gastoscopically. The results of the intravenous applying of quamatel are accounted in reference to the clinical complaints (scalding and/or pain in the oesophagus, acidity in mouth cavity) as well as to the endoscopic and histologic changes in the oesophagus and stomach mucosa. In patients with chronic erosive oesophagitis the efficiency of treatment was confirmed with complete epithelization of the erosions in 22 of 23. The short-period use of large doses 2 x 40 mg quickly improves the clinic symptoms and decreases the period of epithelization twice. The clinic experience shows that the intravenous form of quamatel remains the most effective in cases of short-term and intensive therapy of erosive gastritis with accomplicated hard and emergency clinical cases when the aim is to be avoided the peroral application of anti-ulcer means. An important advantage of the intravenous treatment with quamatel is its low price.

Antiulcer drug prescribing in hospital successfully influenced by "immediate concurrent feedback".

OBJECTIVE: To determine whether immediate concurrent feedback (ICF) focused on inpatient omeprazole prescribing achieved more rational and cost-effective antiulcer drug prescribing and usage. METHODS: In a 1400-bed teaching hospital, an audit (by specially trained personnel) was conducted to monitor inpatient prescribing of omeprazole (1) in preference to H2-antagonists and other drugs according to agreed criteria (Helicobacter pylori eradication, severe reflux esophagitis, rapid ulcer healing deemed urgent because of severe symptoms or complications, high-dose steroid therapy of > or =30 mg/day prednisolone) and (2) appropriateness of intravenous dosing (oral route not feasible or contraindicated). After baseline monitoring for 1 month, followed by relevant antiulcer drug therapy education, ICF was instituted for 1 year. This entailed explanatory memoranda requesting a change in prescribing issued to the respective medical teams of patients whose omeprazole prescription did not "conform." The main outcomes of the study were omeprazole prescription numbers per month and the proportion conforming, defined daily doses of antiulcer drugs used and corresponding expenditures, and pertinent antiulcer drug utilization data from 9 other local hospitals. RESULTS: Baseline omeprazole prescribing conformed in 32 of 173 (18%) of the patients compared with 451 of 546 (83%) during institution of ICF (P < 0001; chi2 test). Correspondingly, average overall omeprazole and ranitidine usage (inpatient and outpatient) and expenditure decreased (44% and 45%, respectively); collectively, use of less expensive alternatives increased about 61%. Estimated savings averaged about HK$150,000 ($20,000) per month. No comparable changes in usage were noted in 9 other local hospitals. CONCLUSION: Regarding hospital antiulcer drugs, this ICF strategy was associated with more rational prescribing and usage, and an important saving of resources.

Safety and cost of rapid i.v. injection of famotidine in critically ill patients.

The safety and cost of famotidine in intensive care patients given the drug by rapid i.v. injection or slow i.v. infusion were studied. All patients admitted to the medical-coronary care and surgical intensive care units (ICUs) at a university teaching hospital over a two-month period who had orders for at least one dose of famotidine injection for any indication were randomly assigned to receive the drug by rapid i.v. injection or slow i.v. infusion via volumetric chamber. Data on patient demographics, drug administration time, adverse effects, cardiovascular variables, and costs (including drug acquisition, supply, and nursing personnel costs) were collected prospectively. Fifty-three patients received famotidine by i.v. injection (a total of 1041 doses) and 52 by i.v. infusion (1006 doses). The mean +/- S.D. duration of famotidine administration was 44 +/- 12 seconds in the i.v.-injection group and 19 +/- 5 minutes in the i.v.-infusion group. Adverse effects possibly related to famotidine occurred in three injection-group patients and two infusion-group patients. No significant difference between the groups in cardiovascular variables (mean arterial pressure, heart rate, and respiratory rate) was noted. Cost savings for the injection group relative to the infusion group totaled $2886 for the two-month study period. Half of the savings came from reduced supply costs and half from reduced personnel costs. The annualized savings to the institution would be about $17,300. Rapid i.v. injection of famotidine appeared to be as safe in ICU patients as giving the drug by slow i.v. infusion and was less costly.

Assessment of 24-hour gastric pH measurements in trauma patients receiving intravenous famotidine by intermittent bolus versus continuous infusion administration.

OBJECTIVE: To compare the effects of intermittent bolus versus continuous infusion intravenous famotidine on gastric pH in critically ill trauma patients. DESIGN: Twenty patients were randomized to receive famotidine by intermittent bolus or continuous infusion for 24 hours. Patients fasted during the study period. Hourly gastric pH measurements were made using an indwelling sensor/sump tube. SETTING: The study was conducted in a university teaching hospital. PARTICIPANTS: Adult patients admitted to the neurosurgical or surgical/trauma intensive care unit within 72 hours of traumatic injury were enrolled in the study if they had two consecutive hourly gastric pH readings of < 4 without receiving antacids, sucralfate, or histamine2-antagonists. MAIN OUTCOME MEASURES: Groups were compared with regard to (1) total dose of famotidine received/24 hours, and (2) number of dosage changes required to maintain a gastric pH value of > or = 4. RESULTS: The median dose of famotidine required to maintain a gastric pH > or = 4 was 50 mg/24 h (25th-75th percentiles = 40-55 mg) in the intermittent bolus group compared with 42 mg/24 h (25th-75th percentiles = 42-52 mg) in the continuous infusion group (p = 0.9577). A dosage increase was required by 5 of 8 patients (62 percent) receiving intermittent bolus therapy, whereas only 2 of 8 patients (25 percent) in the continuous infusion group required a dosage adjustment (p = 0.315, power = 0.318). CONCLUSIONS: Intravenous famotidine (40-50 mg/d) effectively controlled gastric pH in critically ill trauma patients. Patients treated with intermittent bolus therapy required slightly more drug and more frequent dosage adjustments to achieve a gastric pH > or = 4. These differences did not reach statistical significance.

Influence of histamine receptors on basal left ventricular contractile tone in humans: assessment using the H2 receptor antagonist famotidine and the beta-adrenoceptor antagonist esmolol as pharmacologic probes.

Histamine has a positive inotropic action in humans. Recent controversial data have suggested that histamine2 (H2) receptor blockade depresses overall left ventricular systolic performance in healthy volunteers. To explore the possibility that H2 receptors positively influence basal left ventricular contractile tone, 10 normal subjects were studied by using imaging and Doppler echocardiography and calibrated subclavian pulse data in a blinded, randomized, two-period crossover trial with measurements obtained at the end of each 7-day period. Oral drug administration consisted of either the potent H2 antagonist famotidine (40 mg/day) or placebo. Left ventricular circumferential end-systolic wall stress-rate-corrected velocity of fiber shortening (Vcfc) relations were generated over a range of loads with methoxamine. Contractility was assessed by using Vcfc at a common end-systolic wall stress. During each study, data were obtained before and during high dose intravenous esmolol administration to determine the contributions, if any, of sympathetic reflex responses. Famotidine did not alter blood pressure, left ventricular percent fractional shortening, circumferential end-systolic wall stress, stroke volume index, cardiac index, total vascular resistance or ventricular contractile state in comparison with placebo but did decrease heart rate by 3 beats/min (p less than 0.05). With beta-adrenergic blockade, no differences in contractility were evident between esmolol alone and famotidine plus esmolol. Thus, H2 receptor blockade with famotidine does not alter myocardial mechanics or cardiac sympathetic tone, suggesting that in humans basal left ventricular contractile state is not physiologically dependent on the H2-mediated effects of histamine.

Implementing therapeutic interchange of intravenous famotidine for cimetidine and ranitidine.

The steps taken to implement a therapeutic interchange program for i.v. histamine H2-receptor antagonists and to determine the potential cost savings are described. A literature review conducted by pharmacists at a 273-bed nonteaching community hospital showed that i.v. famotidine was as safe and effective as i.v. cimetidine or ranitidine and that it was feasible to add famotidine to total parenteral nutrition (TPN) solutions. Because of famotidine's cost advantage, it was proposed that i.v. famotidine be used in place of specific dosage regimens of i.v. ranitidine or cimetidine and in TPN solutions ordered for patients receiving concurrent H2-antagonist therapy. The approval of the hospital attorney and hospital gastroenterologists was secured, and a formal proposal was submitted. The pharmacy department distributed a memorandum describing the advantages of famotidine, conducted inservice education sessions, and sought the compliance of physicians by placing reminders on order forms and patient charts and by contacting physicians directly. The program was implemented in May 1989. During the first three months, only one physician insisted that patients receive i.v. ranitidine rather than famotidine. It was projected that the interchange of i.v. famotidine for cimetidine or ranitidine would result in a total savings of $37,565 during the first year due to reductions in the cost of drugs, supplies, and nursing labor. The acceptance of a therapeutic interchange program for H2 antagonists was excellent, and the projected savings are substantial.

Continuous intragastric pH monitoring: a real progress in the assessment of antisecretory drugs.

24 hour intragastric pH recording by means of an indwelling minielectrode which is connected to an ambulatory apparatus is unquestioned in the assessment of the pharmacodynamic properties of potent antisecretory drugs. pH measurements obtained with this continuous monitoring have been shown to be more accurate than those provided by the traditional hourly nasogastric aspiration method. We used this technique to evaluate the effects on gastric acidity of placebo, ranitidine 150mg, famotidine 20mg and nizatidine 150mg in fifteen patients with healed duodenal ulcer. These medications were orally administered at 22:00hr in a double-blind fashion on four separate occasions at least one week apart. All H2-receptor blockers were more effective than placebo in suppressing both circadian (p less than 0.001) and nocturnal (p less than 0.0001) gastric acidity, while there was no significant difference between the effects of the three active agents in the same time periods. During morning hours (8:00-12:00) both ranitidine and nizatidine did not differ from placebo, and famotidine produced more acid inhibition than nizatidine (p less than 0.03). However, in the same period the percent of time spent above pH 4.0 was significantly superior (p less than 0.00001) for both famotidine (33%) and ranitidine (14.2%) with respect to nizatidine (6%) and placebo (8.4%). Therefore, after bedtime dosing, the action of nizatidine is more confined to the nocturnal period than those of ranitidine and famotidine.

Ulcera peptica: los nuevos farmacos son opciones terapeuticas ventajosas? / Peptic ulcer: are new drugs advantageous therapeutic options?

Se hace una revision de aspectos farmacologicos de antiacidos y antagonistas H2 en el tratamiento de la ulcera duodenal, se establecen diferencias, entre los farmacos del ultimo grupo, en relacion a sus ventajas terapeuticas y efectos colaterales, se establece por ultimo el costo de un curso de tratamiento de 8 semanas con Ranitidina y Famotidina, dandose enfasis a la relacion costo/beneficio