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Drug Safety - Case Reports Dec 2015Drugs represent one of the etiologic causes of acute rhabdomyolysis (AR) with drug-induced rhabdomyolysis most commonly associated with HMG-CoA reductase inhibitors. AR... (Review)
Review
BACKGROUND
Drugs represent one of the etiologic causes of acute rhabdomyolysis (AR) with drug-induced rhabdomyolysis most commonly associated with HMG-CoA reductase inhibitors. AR etiology can also result from the use of diclofenac, a non-steroidal anti-inflammatory drug, and omeprazole, a proton pump inhibitor. Cases of AR triggered by pantoprazole have never before been reported, although it has been observed that its inclusion in multiple drug therapies can result in muscle events.
CASE PRESENTATION
A 45-year-old man presenting with complaints of fatigue and extensive body pain was diagnosed with acute rhabdomyolysis. His symptoms started on the fourth day of the concomitant use of diclofenac and pantoprazole. The patient was using diclofenac 50-mg tablets once daily for 1 month and pantoprazole 40-mg tablets once daily during the previous week for headaches and pyrosis, resulting in an increase in his creatinine kinase levels to 3114 IU/L (reference range 24-190 IU/L) on the fifth day of concomitant use. His creatinine kinase levels returned to normal and his complaints disappeared after the seventh day of discontinuation of both treatments.
DISCUSSION
A third case of diclofenac-induced rhabdomyolysis was defined in which, different from previous cases, AR was detected during the concomitant use of diclofenac and pantoprazole. The timing of the symptom development and the limited number of AR cases induced by diclofenac and pantoprazole suggested a drug interaction.
CONCLUSION
The close relationship between diclofenac and pantoprazole, and the cytochrome P450 and P-glycoprotein systems offers a strong indication that a drug interaction may be occurring. While evaluating the side effects of drugs in patients undergoing monotherapy, clinicians should also consider the mechanisms that play a part in drug absorption and distribution.
PubMed: 27747722
DOI: 10.1007/s40800-015-0012-6 -
Frontiers in Veterinary Science 2021Ruminant species are at risk of developing abomasal ulceration, but there is a lack of pharmacokinetic data for anti-ulcer therapies, such as the proton pump inhibitor...
Ruminant species are at risk of developing abomasal ulceration, but there is a lack of pharmacokinetic data for anti-ulcer therapies, such as the proton pump inhibitor pantoprazole, in goats. The primary study objective was to estimate the plasma pharmacokinetic parameters for pantoprazole in adult goats after intravenous administration. A secondary objective was to describe the pharmacokinetic parameters for the metabolite, pantoprazole sulfone, in goats. Pantoprazole was administered intravenously to six adult goats at a dose of 1 mg/kg. Plasma samples were collected over 36h and analyzed via reverse phase high performance liquid chromatography for determination of pantoprazole and pantoprazole sulfone concentrations. Pharmacokinetic parameters were determined by non-compartmental analysis. Plasma clearance, elimination half-life, and volume of distribution of pantoprazole were estimated at 0.345 mL/kg/min, 0.7 h, and 0.9 L/kg, respectively following IV administration. The maximum concentration, elimination half-life and area under the curve of pantoprazole sulfone were estimated at 0.1 μg/mL, 0.8 h, and 0.2 hrμg/mL, respectively. The global extraction ratio was estimated 0.00795 ± 0.00138. All animals had normal physical examinations after conclusion of the study. The reported plasma clearance for pantoprazole is lower than reported for foals, calves, and alpacas. The elimination half-life appears to be < that reported for foals and calves. Future pharmacodynamic studies are necessary for determination of the efficacy of pantoprazole on acid suppression in goats.
PubMed: 34631865
DOI: 10.3389/fvets.2021.744813 -
European Journal of Case Reports in... 2023Pantoprazole is one of the most widely used proton pump inhibitors, but anaphylaxis occurs rarely during its use. The purpose of reporting these two cases is to show...
INTRODUCTION
Pantoprazole is one of the most widely used proton pump inhibitors, but anaphylaxis occurs rarely during its use. The purpose of reporting these two cases is to show that pantoprazole is not a drug without problems; it can also cause anaphylactic reactions.
CASES DESCRIPTION
A 42-year-old woman presented to the emergency department due to dyspeptic complaints. Immediately at the end of the infusion of pantoprazole, there started to be numbness of the tongue, itching all over the body, and difficulty in breathing. Half an hour after taking a pantoprazole 40 mg capsule, a 58-year-old woman started to experience redness of the face, thickening of the tongue, itching, bloating, and dizziness. Arterial pressure was 80/60 mmHg, pulse 150/minute, while saturation had dropped to 88%. In both cases, fluids, adrenaline, antihistamines, methylprednisolone, and calcium were immediately started. After the improvement of their general conditions, both patients were discharged home.
DISCUSSION
The first case relates to anaphylaxis after the intravenous administration of pantoprazole, and the second case relates to the appearance of anaphylaxis after its oral administration.
CONCLUSION
Health workers need to be informed about the possibility of anaphylaxis in patients taking both oral and parenteral pantoprazole.
LEARNING POINTS
PPIs are generally safe, with a low percentage of side effects of 1-3%.Although hypersensitive reactions to PPIs are rare, cases of anaphylactoid reactions have also been reported in the literature.Anaphylaxis caused by taking pantoprazole should be considered in the differential diagnosis of anaphylaxis in both oral and parenteral administration of the drug.Doctors and pharmacists should be very careful when prescribing pantoprazole and other PPIs, especially to the elderly.
PubMed: 37680781
DOI: 10.12890/2023_004017 -
Frontiers in Veterinary Science 2022Development of abomasal ulceration is a large concern, especially within calves; however, there is a paucity of research into the use of gastro protectants in ruminant...
INTRODUCTION
Development of abomasal ulceration is a large concern, especially within calves; however, there is a paucity of research into the use of gastro protectants in ruminant species. Proton pump inhibitors, such as pantoprazole, are widely used in humans and companion animals. Their efficacy in ruminant species is undetermined. The objectives of this study were to 1) estimate the plasma pharmacokinetic parameters for pantoprazole in neonatal calves after three days of intravenous (IV) or subcutaneous (SC) administration, and 2) measure the effect pantoprazole had on abomasal pH over the treatment period.
METHODS
Pantoprazole was administered to 6 Holstein-Angus cross bull calves at a dose of 1 mg/kg (IV) or 2 mg/kg (SC), once a day (every 24 h) for three days. Plasma samples were collected over a 72 h period and analyzed HPLC-UV for determining pantoprazole concentrations. Pharmacokinetic parameters were derived via non-compartmental analysis. Abomasal (n= 8) samples were collected abomasal cannulas over a 12 h period, per calf per day. Abomasal pH was determined a bench top pH analyzer.
RESULTS
Following Day 1 of IV administration, plasma clearance, elimination half-life, and volume of distribution of pantoprazole were estimated at 199.9 mL/kg/h, 1.44 h, and 0.51 L/kg, respectively. On Day 3 of IV administration, the reported values were 192.9 mL/kg/h, 2.52 h, and 1.80 L/kg mL, respectively. Elimination half-life and volume of distribution (V/F) of pantoprazole following SC administration were estimated at 1.81 h and 0.55 L/kg, respectively, on Day 1; and 2.99 h and 2.82 L/kg, respectively, on Day 3.
DISCUSSION
The reported values for IV administration were similar to those previously reported in calves. SC administration appears to be well absorbed and tolerated. The sulfone metabolite was detectable for 36 h after the last administration for both routes. Abomasal pH was significantly higher than the pre-pantoprazole pH 4, 6, and 8 h after administration in both the IV and SC groups. Further studies of pantoprazole as a treatment/preventative for abomasal ulcers are warranted.
PubMed: 36794231
DOI: 10.3389/fvets.2022.1101461 -
PloS One 2024Abomasal ulcers are recognized in sheep of all ages, but research regarding therapeutic interventions is limited. Proton Pump Inhibitors (PPIs) such as pantoprazole, are...
Abomasal ulcers are recognized in sheep of all ages, but research regarding therapeutic interventions is limited. Proton Pump Inhibitors (PPIs) such as pantoprazole, are clinically used with a paucity of evidence regarding efficacy in mature sheep. Intravenous and subcutaneously administered pantoprazole dosed at 1.0 mg/kg in adult sheep will increase the pH of abomasal fluid compared to pre-administration baseline. The objectives were to assess the effect of pantoprazole, after single and multiple administration, on abomasal fluid pH in adult sheep. A third objective was to describe the pharmacokinetic parameters of IV and SC pantoprazole. Four clinically healthy adult Southdown ewes previously fitted with a gastrostomy tube in the abomasum were utilized in this randomized, 2-way cross-over trial. Ewes received pantoprazole (1.0 mg/kg) as a single and 3-dose regimen (every 24 hours). After a 10 day washout period the reverse treatment was applied. Blood for analysis of pantoprazole concentration was collected intermittently for 24 hours, and abomasal fluid pH was measured at intervals for a 96-hour period. The pH of the abomasal fluid was higher in pantoprazole treatments for up to 24 hours after dosing. Following intravenous administration of pantoprazole to study ewes, elimination half-life, volume of distribution, and clearance of pantoprazole was estimated as 3.29 hours, 0.35 L/kg, and 65.26 mL/hr/kg respectively. After subcutaneous dosing, maximum concentration, time to maximum concentration, half-life of elimination, and volume of distribution, were estimated as 2604 ng/mL, 0.55 hours, 2.48 hours, and 0.37 L/kg. Additionally, the bioavailability was estimated as 83.33%. Pantoprazole administered IV or SC may be useful for treatment or prevention of abomasal ulcers in adult sheep.
Topics: Animals; Pantoprazole; Sheep; Female; Injections, Subcutaneous; Hydrogen-Ion Concentration; Proton Pump Inhibitors; Abomasum; Administration, Intravenous; Cross-Over Studies; Injections, Intravenous
PubMed: 38865425
DOI: 10.1371/journal.pone.0304533 -
Saudi Pharmaceutical Journal : SPJ :... Mar 2022have a major role in nosocomial infections leading to high morbidity and mortality. Increased resistance to various antifungals, especially azoles is a significant...
have a major role in nosocomial infections leading to high morbidity and mortality. Increased resistance to various antifungals, especially azoles is a significant problem. One of the main mechanisms for azole resistance is the up-regulation of efflux pump genes including and . In the current study, clinical isolates were identified to the species level and the antifungal susceptibility (AFS) of different was determined by disk diffusion method. Furthermore, the main mechanisms of azole resistance were investigated. Finally, haloperidol and pantoprazole were tested for their potential synergistic effect against fluconazole-resistant isolates. One hundred and twenty-two clinical isolates were used in this study. 70 isolates were (57.4%), the non-albicans include: (20.5%), (6.6%), (5.7%), (4.9%) and (4.9%). The AFS testing showed that resistance to fluconazole and voriconazole were 13.1% (n = 16) and 9.8% (n = 12), respectively. Among the 16 resistant isolates, eight isolates (50%) were strong biofilm producers, seven (43.8 %) formed intermediate biofilm and one had no biofilm. All resistant strains overexpressed efflux pumps. Using RT-PCR, the efflux genes , and were over-expressed in azole resistant isolates. Haloperidol-fluconazole and pantoprazole-fluconazole combinations reduced the MIC of fluconazole in resistant isolates. The current study showed an increase in azole resistance of . The majority of resistant isolates form biofilm, and overexpress efflux pumps. Pantoprazole and Haloperidol showed a noteworthy effect as efflux pump inhibitors which oppose the fluconazole resistance in different .
PubMed: 35498219
DOI: 10.1016/j.jsps.2022.01.011 -
Paediatric Drugs Oct 2018Pharmacokinetic data for proton pump inhibitors (PPIs), acid-suppression drugs commonly prescribed to children, are lacking for obese children who are at greatest risk...
BACKGROUND AND AIMS
Pharmacokinetic data for proton pump inhibitors (PPIs), acid-suppression drugs commonly prescribed to children, are lacking for obese children who are at greatest risk for acid-related disease. In a recent multi-center investigation, we demonstrated decreased, total body weight adjusted, apparent clearance (CL/F) of the PPI pantoprazole for obese children compared with their non-obese peers. Subsequently, we developed a population-based pharmacokinetic (PopPK) model to characterize pantoprazole disposition and evaluated appropriate pantoprazole dosing strategies for obese pediatric patients, using simulation.
METHODS
Pharmacokinetic data from the only prospective study of PPIs in obese children (aged 6-17 years; n = 40) included 273 pantoprazole and 256 pantoprazole-sulfone plasma concentrations, after single oral-dose administration, and were used for pantoprazole model development and covariate analysis (NONMEM). Model evaluation was performed via bootstrapping and predictive checks, and the final model was applied to simulate systemic pantoprazole exposures for common dosing scenarios.
RESULTS
A two-compartment PopPK model, which included CYP2C19 genotype and total body weight, provided the best fit. Resultant, typical, weight-normalized pantoprazole parameter estimates were different than previously reported for children or adults, with significantly reduced pantoprazole CL/F for obese children. Of the dosing scenarios evaluated, the weight-tiered approach, approved by the US Food and Drug Administration, achieved pantoprazole exposures [area under the curve (AUC)] within ranges previously reported as therapeutic, without over- or under-prediction for obese children.
CONCLUSIONS
Our data argue against empiric dose escalation of PPIs for obese children and support current FDA-approved pediatric weight-tiered dosing for pantoprazole; however, 3- to 5-fold inter-individual variability in pantoprazole AUC remained using this dosing approach.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Administration, Oral; Adolescent; Area Under Curve; Body Weight; Child; Female; Humans; Male; Metabolic Clearance Rate; Models, Biological; Obesity; Pantoprazole; Prospective Studies; Proton Pump Inhibitors
PubMed: 30097906
DOI: 10.1007/s40272-018-0305-1 -
The Journal of Pediatrics Feb 2018To assess appropriate pantoprazole dosing for obese children, we conducted a prospective pharmacokinetics (PK) investigation of pantoprazole in obese children, a patient... (Clinical Trial)
Clinical Trial
OBJECTIVE
To assess appropriate pantoprazole dosing for obese children, we conducted a prospective pharmacokinetics (PK) investigation of pantoprazole in obese children, a patient population that is traditionally excluded from clinical trials.
STUDY DESIGN
A total of 41 obese children (6-17 years of age), genotyped for CYP2C19 variants *2, *3, *4, and *17, received a single oral dose of pantoprazole, ~1.2 mg/kg lean body weight (LBW), with LBW calculated via a validated formula. Ten post-dose pantoprazole plasma concentrations were measured, and PK variables generated via noncompartmental methods (WinNonlin). Linear and nonlinear regression analyses and analyses of variance were used to explore obesity, age, and CYP2C19 genotype contribution to pantoprazole PK. PK variables of interest were compared with historic nonobese peers treated with pantoprazole.
RESULTS
Independent of genotype, when normalized to dose per kg total body weight, pantoprazole apparent clearance and apparent volume of distribution were significantly lower (P < .05) and systemic exposure significantly higher (P < .01) in obese vs nonobese children. When normalized per kg LBW, these differences were not evident in children ≥12 years of age and markedly reduced in children <12 years of age.
CONCLUSIONS
LBW dosing of pantoprazole led to pantoprazole PK similar to nonobese peers. Additional factors, other than body size (eg, age-related changes in CYP2C19 activity), appear to affect pantoprazole PK in children <12 years of age.
TRIAL REGISTRATION
ClinicalTrials.gov: NCT02186652.
Topics: Administration, Oral; Adolescent; Area Under Curve; Body Weight; Child; Cytochrome P-450 CYP2C19; Drug Dosage Calculations; Female; Gastroesophageal Reflux; Genotype; Humans; Male; Pantoprazole; Pediatric Obesity; Prospective Studies; Proton Pump Inhibitors
PubMed: 29389444
DOI: 10.1016/j.jpeds.2017.10.011 -
JGH Open : An Open Access Journal of... Feb 2024Combining proton pump inhibitors (PPIs) with prokinetics can provide synergistic action in patients with gastroesophageal reflux disease (GERD) and overlapping...
Efficacy and safety of pantoprazole and itopride in patients with overlap of gastroesophageal reflux disease and dyspepsia: A prospective, open-label, single-arm pilot study.
BACKGROUND AND AIM
Combining proton pump inhibitors (PPIs) with prokinetics can provide synergistic action in patients with gastroesophageal reflux disease (GERD) and overlapping dyspepsia, but data regarding this is lacking.
METHODS
This single-center, prospective study evaluated the efficacy and safety of 6-week treatment with fixed-drug combination (FDC) of pantoprazole (PPI) and itopride (prokinetic) in 50 patients with ≥3 month history of GERD and overlapping dyspepsia refractory to pantoprazole. Efficacy was assessed as reduction in GERD symptom assessment scale (GSAS) distress score for 15 symptoms from baseline to week 6. Adverse events (AEs) were monitored up to week 6.
RESULTS
Although heartburn was the most common symptom at week 6 (26.8%), its frequency significantly decreased from baseline (84.0%; <0.01). A similar trend was observed for other symptoms: pressure/discomfort inside chest (19.5%), belching (14.6%), regurgitation (12.2%), bloating (9.8%), flatulence (9.8%), early satiety (7.3%), acidic/sour taste in mouth (7.3%), nausea (7.3%), frequent gurgling in stomach/belly (4.9%), and pressure/lump in throat (2.4%). Mean distress scores of all symptoms markedly decreased at week 6. Three AEs ( = 2) of moderate intensity were reported.
CONCLUSION
The FDC of pantoprazole and itopride showed favorable efficacy and safety in patients with GERD and overlapping dyspepsia refractory to pantoprazole monotherapy. Nevertheless, further studies are warranted.
PubMed: 38344252
DOI: 10.1002/jgh3.12988