J Clin Pharm Ther [JOURNAL]
Sun
200 papers
Safety and efficacy of sofosbuvir-based medication regimens with and without ribavirin in hepatitis C patients: A systematic review and meta-analysis.
Elshafie S, Trivedi-Kapoor R, Ebell M
J Clin Pharm Ther · 2022 Aug · PMID 35678040 · Full text
WHAT IS KNOWN AND OBJECTIVE: Sofosbuvir (SOF) is a new and highly effective medication that dramatically improved hepatitis C virus (HCV) management. However, ribavirin (RBV) is still added to SOF-based medication regime...
WHAT IS KNOWN AND OBJECTIVE: Sofosbuvir (SOF) is a new and highly effective medication that dramatically improved hepatitis C virus (HCV) management. However, ribavirin (RBV) is still added to SOF-based medication regimens in several clinical scenarios, despite its well-known toxicities. The aim of our study is to systematically review and analyse the impact of adding RBV to SOF-based medication regimens on clinical outcomes among HCV patients. METHODS: Included studies were randomized trials comparing the same SOF-based medication regimens with and without RBV in HCV patients and measuring serious adverse events (SAEs) and/or sustained virologic response at 12 weeks post-treatment (SVR-12). Two investigators independently searched PubMed and Cochrane Library through September 2021. The Cochrane Risk of Bias tool was used to assess trials quality. Clinical outcomes were analysed as risk ratios (RR) using a random effects model using R version 4.1.2. RESULTS AND DISCUSSION: Our study included a total of 26 trials with 5058 HCV patients. Quality assessment showed moderate risk of bias for most trials. Upon adding RBV, there was no significant difference in SAEs (RR 1.07, 95% CI: 0.77-1.48, I = 10%), nor an impact on SVR-12 (RR 1.00, 95% CI: 0.98-1.01, I = 41%). There was no evidence of publication bias for either outcome. Subgroup analysis consistently showed lack of benefit among HCV subgroups. Additionally, NCT01826981 was identified as the main source of heterogeneity in the SVR-12 outcome. WHAT IS NEW AND CONCLUSION: Our findings suggest nonsignificant differences in safety and efficacy between SOF-based medication regimens with and without RBV which should be considered in clinical practice.
A retrospective observational study of the treatment with polymyxin B for liver transplantation recipients infected by multidrug-resistant gram-negative bacteria.
Yu LL, Shi XP, Huang JF … +3 more , Gong Y, Cui CX, Wang T
J Clin Pharm Ther · 2022 Oct · PMID 35670240 · Full text
WHAT IS KNOWN AND OBJECTIVE: Only a few studies about polymyxin B (PMB) against multidrug-resistant gram-negative bacteria (MDR GNB) infection were conducted in liver transplantation recipients (LTRs). The purpose of thi...
WHAT IS KNOWN AND OBJECTIVE: Only a few studies about polymyxin B (PMB) against multidrug-resistant gram-negative bacteria (MDR GNB) infection were conducted in liver transplantation recipients (LTRs). The purpose of this study was to investigate the efficacy and safety of PMB in the treatment of MDR-GNB in liver transplant recipients and to determine the risk factors affecting clinical cure and 30-day all-cause mortality. METHODS: Data of LTRs receiving PMB from January 2016 to February 2020 were collected. Clinical cure and 30-day all-cause mortality were the main efficacy outcomes, while the incidence of nephrotoxicity, neurotoxicity, and hyperpigmentation of PMB was the main safety outcome. RESULTS AND DISCUSSION: Data of 42 LTRs were included. Clinical cure with PMB was observed in 27 recipients (64.3%), and the 30-day all-cause mortality rate was 31.0% (13/42). The incidence of acute kidney injury (AKI), neurotoxicity, and hyperpigmentation was 57.1% (16/28), 4.8% (2/42), and 16.7% (7/42), respectively. Logistic regression analysis showed that Acute Physiology and Chronic Health Evaluation (APACHE) II score (OR, 1.203; 95% CI, 1.016-1.423, p = 0.032) was an independent risk factor for 30-day all-cause mortality, whereas renal replacement therapy (OR, 0.128; 95% CI, 0.019-0.860, p = 0.034) was an independent risk factor for clinical cure with PMB. WHAT IS NEW AND CONCLUSIONS: This is the first study to evaluate the application of PMB in LTRs. If there were no better therapeutic options left for LTRs other than PMB, it can be used against MDR GNB infection in LTRs. We should closely observe adverse events or reactions, and adjust the dose based on the balance of efficacy and safety.
Discoidin domain receptor 1 may be involved in biological barrier homeostasis.
Li X, Chen H, Zhang D
J Clin Pharm Ther · 2022 Dec · PMID 35665520 · Publisher ↗
WHAT IS KNOWN AND OBJECTIVE: Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase involved in the pathological processes of several diseases, such as keloid formation, renal fibrosis, atherosclerosis, tumours...
WHAT IS KNOWN AND OBJECTIVE: Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase involved in the pathological processes of several diseases, such as keloid formation, renal fibrosis, atherosclerosis, tumours, and inflammatory processes. The biological barrier is the first line of defence against pathogens, and its disruption is closely related to diseases. In this review, we attempt to elucidate the relationship between DDR1 and the biological barrier, explore the potential biological value of DDR1, and review the current research status and clinical potential of DDR1-selective inhibitors. METHODS: We conducted an extensive literature search on PubMed to collect studies on the relevance of DDR1 to biological barriers and DDR1-selective inhibitors. With these studies, we explored the relationship between DDR1 and biological barriers and briefly reviewed representative DDR1-selective inhibitors that have been reported in recent years. RESULTS AND DISCUSSION: First, the review of the potential mechanisms by which DDR1 regulates biological barriers, including the epithelial, vascular, glomerular filtration, blood-labyrinth, and blood-brain barriers. In the body, DDR1 dysfunction and aberrant expression may be involved in the homeostasis of the biological barrier. Secondly, the review of DDR1 inhibitors reported in recent years shows that DDR1-targeted inhibition is an attractive and promising pharmacological intervention. WHAT IS NEW AND CONCLUSIONS: This review shows that DDR1 is involved in various physiological and pathological processes and in the regulation of biological barrier homeostasis. However, studies on DDR1 and biological barriers are still scarce, and further studies are needed to elucidate their specific mechanisms. The development of targeted inhibitors provides a new direction and idea to study the mechanism of DDR1.
Effectiveness and safety of sacubitril/valsartan for patients with hypertension and heart failure in the real-world setting: A retrospective study in China.
Zuo C, Li X, Fan L … +5 more , Li J, Tian D, Chen C, Li X, Lv Q
J Clin Pharm Ther · 2022 Oct · PMID 35649528 · Publisher ↗
WHAT IS KNOWN AND OBJECTIVE: Hypertension (HP) is associated with heart failure (HF). Sacubitril/valsartan (sac/val) has been approved for primary HP by China Food and Drug Administration (CFDA) in June 2021. The present...
WHAT IS KNOWN AND OBJECTIVE: Hypertension (HP) is associated with heart failure (HF). Sacubitril/valsartan (sac/val) has been approved for primary HP by China Food and Drug Administration (CFDA) in June 2021. The present study aimed to provide evidence on the effectiveness and safety of sac/val in Chinese patients complicated with HP and HF. METHODS: This retrospective study was conducted on adult patients diagnosed with HP and HF and treated with sac/val between July 2020 and December 2020. The potential risk factors for the discontinuation events caused by sac/val-related adverse events (AEs) were explored. The data, including blood pressure (BP), cardiac indicators, corresponding values on echocardiographic parameters, unplanned visits, and AEs throughout 3-12 months, were collected. RESULTS AND DISCUSSION: A total of 446 eligible patients were included in this study. The discontinuation events of sac/val were mainly attributed to its AEs (hypotension, hyperkalemia, and deterioration in kidney function). Univariate analysis revealed that history of chronic kidney disease, atrial fibrillation, higher values of serum creatinine, serum uric acid, serum N-terminal pro B-type natriuretic peptide, and lower estimated glomerular filtration rate were potential risk factors for discontinuation. Patients who maintained sac/val therapy throughout 3-12 months showed significantly improved values of clinical BP, cardiac indicators, and echocardiographic parameters compared to those at baseline (p < 0.0001). WHAT IS NEW AND CONCLUSION: Sac/val was effective on BP and improved cardiac function in patients complicated with HP and HF. The physicians should focus on patients with renal dysfunction to take timely precautions to improve tolerability for sac/val.
Does eltrombopag lead to thrombotic events? A pharmacovigilance study of the FDA adverse event reporting system.
Jiang JJ, Zhao B, Li J
J Clin Pharm Ther · 2022 Oct · PMID 35644838 · Publisher ↗
WHAT IS KNOWN AND OBJECTIVE: Eltrombopag is an orally bioavailable drug developed as a second-line treatment for immune thrombocytopenia. However, there are limited reports on thrombotic events related to eltrombopag use...
WHAT IS KNOWN AND OBJECTIVE: Eltrombopag is an orally bioavailable drug developed as a second-line treatment for immune thrombocytopenia. However, there are limited reports on thrombotic events related to eltrombopag use. This study aimed to assess the relationship between eltrombopag and thrombotic events in a large population extracted from the Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: A total of 525 FAERS reports on thrombotic events associated with eltrombopag alone and 59 on those associated with the simultaneous use of eltrombopag and glucocorticoids, from Q1 2004 to Q3 2021, were included. Reports of thrombotic events were analysed using the following algorithms: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS). The time to onset and outcomes of thrombotic events between the two groups were also analysed. RESULTS AND DISCUSSION: A total of 525 reports of thrombotic events with eltrombopag were identified. Compared with eltrombopag alone, the concomitant use of eltrombopag and glucocorticoids was associated with a higher incidence of thrombotic events based on higher ROR (9.92, 95% two-sided CI 7.58-12.97 vs. 3.46, 95% two-sided CI 3.17-3.77), PRR (9.06, χ = 427.37 vs. 3.37, χ = 881.55), IC (3.18, 95% one-sided CI = 2.43 vs. 1.75, 95% one-sided CI = 1.6), and EBGM (9.06, 95% one-sided CI = 7.23, vs 3.36, 95% one-sided CI = 3.13). WHAT IS NEW AND CONCLUSION: Our findings support an association between thrombotic events and eltrombopag use. Moreover, concomitant use of eltrombopag and glucocorticoids appeared to result in an even higher incidence of thrombotic events.
Tall man lettering application in medication information systems as a quality and safety strategy in hospital organization.
Iglesias Gomez R, Font Noguera I, Correa Ballester M … +2 more , Ruiz Caldes MJ, Poveda Andres JL
J Clin Pharm Ther · 2022 Oct · PMID 35641241 · Publisher ↗
WHAT IS KNOWN AND OBJECTIVE: The technique of highlighted capital letters, Tall Man lettering, is a tool that allows differentiating the names of similar drugs in a way that contributes to reduce medication errors relate...
WHAT IS KNOWN AND OBJECTIVE: The technique of highlighted capital letters, Tall Man lettering, is a tool that allows differentiating the names of similar drugs in a way that contributes to reduce medication errors related to the drug identification. The objective was to implement and monitor the application protocol of the Tall Man lettering tool in drug information systems in the healthcare environment to improve the quality of care and patient safety in the pharmacy service and the medical institution. METHODS: Scope: Tertiary general hospital with 1000 beds in which a Tall Man lettering application protocol was approved in the pharmacy service information systems. DESIGN: Retrospective observational study. PERIOD: 2019-2021. POPULATION: Information systems and databases used in the pharmacy service. Working group: Made up of people in charge of information areas and systems. IMPLEMENTATION: Five phases were defined: organization of the working group, selection of drug names and information systems, establishment of actions, their execution, and results monitoring. VARIABLES: Number of pharmaceutical specialties, names of active ingredient and brands incorporated in the information systems. RESULTS AND DISCUSSION: The application of Tall Man lettering was authorized in 13/13 information systems, six have been fully implemented and seven are in the database update phase. Of the implanted systems, a total of 210 drug names have been modified (168/210 active ingredient and 42/210 brand names), corresponding to 659 pharmaceutical specialties. WHAT IS NEW AND CONCLUSION: The application of Tall Man lettering in hospital information systems is a tool for improving the quality of the pharmacy service and guarantees the safety of medicines in the hospital.
Validation of the Augmented Renal Clearance in Trauma Intensive Care scoring system for augmented renal clearance prediction in a trauma subgroup of a mixed ICU population.
Jabamikos C, Fang YT, Nguyen KD … +8 more , Sananikone A, Archambault K, Bing E, Chagnon M, Husainalamoodi O, Marsot A, Duceppe MA, Perreault MM
J Clin Pharm Ther · 2022 Oct · PMID 35633117 · Publisher ↗
WHAT IS KNOWN AND OBJECTIVE: Augmented renal clearance is prevalent in trauma patients and leads to subtherapeutic levels of renally eliminated medications with potentially unfavourable clinical outcomes. The Augmented R...
WHAT IS KNOWN AND OBJECTIVE: Augmented renal clearance is prevalent in trauma patients and leads to subtherapeutic levels of renally eliminated medications with potentially unfavourable clinical outcomes. The Augmented Renal Clearance of Trauma in Intensive Care (ARCTIC) score has been developed to predict augmented renal clearance in critically ill trauma patients. Our primary objective was to validate this score among the trauma subgroup of a mixed intensive care patient cohort. METHODS: This single-centre, retrospective, observational cohort study assessed augmented renal clearance using a timed 24-h urine collection performed weekly. ARC was defined as a measured creatinine clearance of ≥130 ml/min/1.73 m . ARCTIC score performance was evaluated through a receiver operator characteristic curves and analysis of sensitivities and specificities for the trauma subgroup, the medical/surgical subgroup and the pooled cohort. RESULTS AND DISCUSSION: Augmented renal clearance was observed in 33.9% (n = 58) of trauma patients (n = 171) and 15.7% (n = 24) of medical/surgical patients (n = 153). Examination of different cutoffs for the ARCTIC score in our trauma population confirmed that the optimal cutoff score was ≥6. Comparison between ROC curves for ARCTIC score and for regression model based upon our data in trauma patients indicated validation of the score in this subgroup. Comparison of sensitivities and specificities for ARCTIC score between trauma (93.1% and 41.6%, respectively) and medical/surgical subjects (87.5% and 49.6%, respectively) showed no clinical nor statistical difference, suggesting validation for the medical/surgical subgroup as well. WHAT IS NEW AND CONCLUSION: In our mixed ICU population, the ARCTIC score was validated in the trauma subgroup. We also found that the score performed well in the medical/surgical population. Future studies should assess the performance of the ARCTIC score prospectively.
Plasma trough concentration distribution and safety of high-dose teicoplanin for patients with augmented renal clearance.
Hu S, Wang T, You H … +3 more , Chen S, Zhang T, Dong Y
J Clin Pharm Ther · 2022 Oct · PMID 35633105 · Publisher ↗
WHAT IS KNOWN AND OBJECTIVE: There are few reports on the distribution of the plasma trough concentration (C ) of teicoplanin in patients with augmented renal clearance (ARC) and on the safety of a high-dose regimen (HD;...
WHAT IS KNOWN AND OBJECTIVE: There are few reports on the distribution of the plasma trough concentration (C ) of teicoplanin in patients with augmented renal clearance (ARC) and on the safety of a high-dose regimen (HD; 800 mg loading dose for q12h three times followed by an 800 mg qd maintenance dose). The objective of this study was to determine the C values of teicoplanin in ARC patients using HD teicoplanin to provide a reference for individualized medication. METHODS: Data on patients treated with teicoplanin from January 2019 to January 2021 were collected retrospectively and divided into ARC (creatinine clearance rate [CCr] >130 ml/min, n = 22) and non-ARC (60 ml/min ≤ CCr ≤130 ml/min, n = 24) groups. The C values in the two patient groups were analysed during the HD and the low-dose regimen (LD; all other regimens) on the third day of medication and during the dose maintenance period. Liver and kidney function indexes were also analysed before and after medication. RESULTS AND DISCUSSIONS: On the third day of the HD, C did not differ significantly between the ARC and non-ARC groups (17.3 ± 9.2 mg/L [mean ± SD] vs. 15.5 ± 7.9 mg/L, p = 0.663), while C in the ARC group was significantly lower for the LD (6.8 ± 3.9 mg/L, p = 0.039). During the dose maintenance period, C in the ARC group when receiving the HD (18.3 ± 5.1 mg/L) was significantly lower than that in the non-ARC group (25.5 ± 11.9 mg/L, p = 0.016) and significantly higher than that for the LD (12.2 ± 6.3 mg/L, p = 0.022). Nephrotoxicity and hepatotoxicity incidence rates did not differ significantly between these groups. WHAT IS NEW AND CONCLUSION: These results suggest that it is necessary to apply a loading dose of 800 mg (but not higher) q12h three times for patients with ARC, with 800 mg needed as a maintenance dose during severe infection, and 600 mg or 400 mg for mild infection.
Addition of roxadustat to erythropoiesis-stimulating agent (ESA) effectively corrects ESA-hyporesponsive anaemia in patients on peritoneal dialysis.
Dai S, Chen Y, Hao C … +4 more , Ge X, Xie Q, Shang D, Zhu T
J Clin Pharm Ther · 2022 Oct · PMID 35633100 · Publisher ↗
WHAT IS KNOWN AND OBJECTIVE: Erythropoiesis-stimulating agent (ESA) hyporesponsiveness is an important cause for the undertreatment of anaemia. A decrease in haemoglobin (Hb) levels was observed during the initial stage...
WHAT IS KNOWN AND OBJECTIVE: Erythropoiesis-stimulating agent (ESA) hyporesponsiveness is an important cause for the undertreatment of anaemia. A decrease in haemoglobin (Hb) levels was observed during the initial stage of the conversion from ESA to roxadustat. The study aims to investigate the effectiveness and safety of adding roxadustat to an ESA for the treatment of ESA-hyporesponsive anaemia in patients on peritoneal dialysis (PD). METHODS: Patients on PD with ESA-hyporesponsive anaemia were enrolled from January 2020 to April 2020 with a 24-week follow-up period. Patients were treated with roxadustat at a starting dose of 50 or 100 mg thrice weekly without changing the ESA dose. Roxadustat and ESA dose adjustments were made as needed to maintain Hb levels within 11.0 to 13.0 g/dl. Efficacy outcomes and safety were assessed. RESULTS AND DISCUSSION: Nine patients were recruited in the study. Both the cumulative responsive rate and maintenance rate of Hb > 11 g/dl were 100%. Six patients required ESA dose reduction from ≥15,000 UI/week to ≤7000 IU/week at week 24. No drug-related severe adverse events were observed in this study. WHAT IS NEW AND CONCLUSION: The addition of roxadustat effectively and smoothly corrected anaemia in patients who were hyporesponsive to ESA, and permitted reduction of the ESA dose.
SARS-CoV-2 neutralizing antibodies for COVID-19: Outcomes for bamlanivimab versus bamlanivimab-etesevimab combination in a racially diverse cohort of patients with significant comorbidities.
Monday LM, Brar I, Alangaden G … +1 more , Ramesh MS
J Clin Pharm Ther · 2022 Sep · PMID 35633095 · Full text
WHAT IS KNOWN AND OBJECTIVE: Anti-spike monoclonal antibodies (MAB) including bamlanivimab (BAM) and bamlanivimab/etesevimab (BAM/E) have shown reduced hospitalization rates for non-severe coronavirus disease 2019 (COVID...
WHAT IS KNOWN AND OBJECTIVE: Anti-spike monoclonal antibodies (MAB) including bamlanivimab (BAM) and bamlanivimab/etesevimab (BAM/E) have shown reduced hospitalization rates for non-severe coronavirus disease 2019 (COVID-19) in clinical trials. Recent data have provided real-world hospitalization rates for high-risk patients treated with BAM, however, data on a similar cohort treated with BAM/E are lacking. METHODS: This retrospective cohort study evaluated outpatients ≥18 years with laboratory-confirmed mild/moderate COVID-19 who received MAB from 1 December 2020 to 19 April 2021. Use of BAM monotherapy changed to BAM/E combination on 27 March 2021. Primary outcome was overall rate of COVID-19 related-hospitalization, including comparison of hospitalization rates between MAB-formulation groups. Secondary outcomes were 30-day mortality and length of stay (LOS). RESULTS AND DISCUSSION: The population included 643 patients (BAM and BAM/E); median age was 58 years, 43% were male, median BMI was 33 kg/m , and 24% self-identified as Black. Patients in the BAM/E combination group were significantly younger with higher median BMI and a longer time from symptom onset to infusion. The incidence of 30-day COVID-19 related hospitalization was similar between patients receiving either BAM or BAM/E combination (7.8% and 7.2%, respectively). WHAT IS NEW AND CONCLUSION: This study represents the first such publication of real-world BAM/E hospitalization outcomes. Hospitalization rates utilizing BAM/E were comparable to BAM in our real-world study.
Rapid, simple, and economical LC-MS/MS method for simultaneous determination of ceftazidime and avibactam in human plasma and its application in therapeutic drug monitoring.
Cheng Y, Chen M, Zhang B … +7 more , Lin H, Li X, Cai Y, Zhang H, Que W, Liu M, Qiu H
J Clin Pharm Ther · 2022 Sep · PMID 35633089 · Publisher ↗
WHAT IS KNOWN AND OBJECTIVE: Carbapenem-resistant Gram-negative bacterial pathogens continue to threaten public health. Avibactam (AVI), a novel non-β-lactam β-lactamase inhibitor, has been approved for use with ceftazid...
WHAT IS KNOWN AND OBJECTIVE: Carbapenem-resistant Gram-negative bacterial pathogens continue to threaten public health. Avibactam (AVI), a novel non-β-lactam β-lactamase inhibitor, has been approved for use with ceftazidime (CAZ) mainly against carbapenem-resistant Enterobacteriaceae. Therapeutic drug monitoring (TDM) is urgently needed to optimize dosage regimens to maximize efficacy, minimize toxicity, and delay the emergence of resistance. This study aims to develop and validate a rapid, simple, and economical LC-MS/MS method for simultaneous determination of CAZ/AVI in human plasma. METHODS: Samples were processed by simple protein precipitation, and gradient elution strategy was applied to separate CAZ and AVI on a reverse-phase C18 column; with subsequent detection by the mass spectrometer in a positive and negative ion switching mode. Plasma samples from patients were analysed. RESULTS AND DISCUSSION: A 4-min run of LC-MS/MS was developed. The precision, trueness, matrix effect, extraction recovery, carry-over, dilution integrity, and stability were all acceptable for a bioanalytical method. The method was successfully applied to the determination of CAZ and AVI in patients, and a considerable PK variability of CAZ/AVI was observed among patients. WHAT IS NEW AND CONCLUSION: A robust, rapid, simple, and economical LC-MS/MS method for the simultaneous determination of CAZ and AVI was developed. The considerable PK variability of CAZ/AVI among patients demonstrates the clinical significance of TDM.
Carglumic acid in methylmalonic acidemia: Use of breast milk as an alternative vehicle to water.
García-Díaz HC, Parramón-Teixidó CJ, Clemente-Batista S … +3 more , Jiménez-Lozano I, Montaner-Ramón A, Del Toro M
J Clin Pharm Ther · 2022 Sep · PMID 35633061 · Publisher ↗
WHAT IS KNOWN AND OBJECTIVE: Carbaglu® or N-carbamylglutamate (NCG) is not recommended for administration in a vehicle other than water. We aim to report the use of breast milk (BM) as an alternative vehicle in a neonate...
WHAT IS KNOWN AND OBJECTIVE: Carbaglu® or N-carbamylglutamate (NCG) is not recommended for administration in a vehicle other than water. We aim to report the use of breast milk (BM) as an alternative vehicle in a neonate rejecting NCG diluted in water. CASE SUMMARY: A neonate diagnosed with methylmalonic acidemia presented symptomatology of acidemia and hyperammonemia. After the patient refused oral NCG administration, a dissolution test was conducted in BM showing correct dissolution. The NCG-BM solution was tolerated and plasma ammonium concentrations remained within range in subsequent analytical controls. WHAT IS NEW AND CONCLUSION: BM as a vehicle for NCG is a safe and effective option for patients who refuse suspension in water and could lead to better treatment compliance in paediatric patients.
Medications used in paediatric intensive care by continuous infusion: Do the technical aspects of the package inserts corroborate scientific evidence?
de Paiva AM, Tinoco MS, Veloso JC … +3 more , Gonçalves MO, Fontes JS, Baldoni AO
J Clin Pharm Ther · 2022 Sep · PMID 35596237 · Publisher ↗
WHAT IS KNOWN AND OBJECTIVE: Hospitalized paediatric patients are three times more likely to experience medication errors with the potential to cause harm, when they are compared to adults. The lack of research in paedia...
WHAT IS KNOWN AND OBJECTIVE: Hospitalized paediatric patients are three times more likely to experience medication errors with the potential to cause harm, when they are compared to adults. The lack of research in paediatrics, difficulties that are derived as indications and the parameters of safety and effectiveness of pharmacological therapy in children. To analyse whether the technical and legal aspects of the package insert for medicines used in paediatric intensive care units (ICU) using a continuous infusion (CI) pump corroborate the recommendations of clinical protocols and legal provisions. METHODS: A documentary study, in which technical and legal information contained in the package inserts of medications commonly used via CI in neopediatric ICUs was analysed. The consultation of the medication package insert was carried out through the electronic portal of the National Health Surveillance Agency (Agência Nacional de Vigilância Sanitária - ANVISA). Information on the use of medications in the neonatal and paediatric populations via CI was sought in the medication package insert. To analyse the legal aspects, ANVISA's RDC no. 47/2009 was used. In order to compare the technical information, the Micromedex NeoFax®, Micromedex Paediatrics®, and Lexicomp® databases were consulted. RESULTS AND DISCUSSION: Of the 13 medications analysed, 46% (n = 6) had some non-compliance with RDC 47/2009. Only 46% (n = 6) of the medications are indicated for paediatric use and only the medication package insert for midazolam (7.7%) contained the information considered essential for use via CI in paediatrics. WHAT IS NEW AND CONCLUSION: This is an innovative study that identifies the weaknesses of the medication package inserts for medications used by CI in paediatric ICUs. Failure to comply with legal recommendations can make medication administration difficult and increase the probability that errors will occur; and the absence of specific technical information can make care difficult and compromise patient safety. It is important that there is supervision by regulatory agencies and the contribution of health professionals so that non-conformities are reported and corrected, to guarantee safe care for paediatric patients in intensive care.
Impact of trimethoprim on serum creatinine, sodium, and potassium concentrations in patients taking trimethoprim-sulfamethoxazole without changes in glomerular filtration rate.
Yokoyama S, Nakagawa J, Aiuchi N … +2 more , Seito T, Niioka T
J Clin Pharm Ther · 2022 Sep · PMID 35545234 · Publisher ↗
WHAT IS KNOWN AND OBJECTIVE: Trimethoprim (TMP) inhibits the Na /K -ATPase present in the basement membrane of distal tubular epithelial cells. However, hyponatremia and hyperkalemia may develop in patients taking TMP-su...
WHAT IS KNOWN AND OBJECTIVE: Trimethoprim (TMP) inhibits the Na /K -ATPase present in the basement membrane of distal tubular epithelial cells. However, hyponatremia and hyperkalemia may develop in patients taking TMP-sulfamethoxazole (SMX). In addition, because TMP inhibits drug transporters, such as organic cation transporter 2 and multidrug and toxin extrusion protein 2-K in proximal tubules, reversible increases in the concentration of serum creatinine (SCr), the substrate of these transporters, may occur. Here, we investigated variability in SCr, serum sodium (Na ), and serum potassium (K ) concentrations after initiation of TMP-SMX treatment and evaluated the risk of hyponatremia and hyperkalemia in patients with increased SCr concentrations without changes in the glomerular filtration rate (GFR). METHODS: In this retrospective study, all patients aged 20 years or older who received oral TMP-SMX during hospitalization were enrolled. The patients with estimated creatinine (Cr) clearance (eCCr) lower than 30 mL/min were excluded, as were patients taking drugs that were likely to induce renal dysfunction, drugs other than glucocorticoids that were likely to induce electrolyte imbalances, or drugs other than TMP that inhibit tubular Cr secretion. Additionally, those with SCr concentrations elevated more than 30% from baseline or serum blood urea nitrogen concentration levels above 20 mg/dL during follow-up were also excluded. RESULTS AND DISCUSSION: In total, 111 patients were enrolled in the study. The common independent variable affecting the change rate in SCr, Na , and K concentrations (ΔSCr, ΔNa , and ΔK ) from baseline to the highest value during the follow-up period (14 days after initiation of TMP-SMX treatment) was the daily dose of TMP. There were significant correlations between ΔSCr and ΔNa or ΔK (ρ = -0.199, p = 0.036 and ρ = 0.244, p = 0.010, respectively). Kaplan-Meier curves for hyponatremia and hyperkalemia with greater than or equal to grade 1 severity showed different profiles when the TMP dose varied (≤ 160 vs. > 160 mg/day; p = 0.005 and 0.008). The cumulative incidences of both adverse effects were 64.7% (median: 7 days) and 29.4% in patients taking more than 160 mg/day TMP and 35.2% and 6.7% in patients taking 160 mg/day TMP or less. Thus, TMP may affect the kinetics of Cr, Na , and K in the proximal and distal tubules in a dose-dependent without changing the GFR. WHAT IS NEW AND CONCLUSION: This study is the first report to demonstrate the degree of changes in SCr, Na , and K concentrations after initiation of TMP-SMX treatment. If SCr is elevated after initiation of TMP-SMX treatment, clinicians should be aware of decreased Na and increased K concentrations. TMP may increase the risks of hyponatremia and hyperkalemia in a dose-dependent manner without altering GFR.
Successful treatment of severe quetiapine intoxication with CytoSorb hemoadsorption.
Reuchsel C, Gonnert FA
J Clin Pharm Ther · 2022 Sep · PMID 35537706 · Publisher ↗
WHAT IS KNOWN AND OBJECTIVE: While many drug poisonings are successfully treated with specific antidotes, intoxications with tricyclic antidepressants and/or atypical neuroleptics still represent a major challenge. Besid...
WHAT IS KNOWN AND OBJECTIVE: While many drug poisonings are successfully treated with specific antidotes, intoxications with tricyclic antidepressants and/or atypical neuroleptics still represent a major challenge. Besides conventional approaches, a new hemoadsorption device might represent an opportunity for therapeutic detoxification. CASE SUMMARY: We report a 64-year-old female patient who attempted suicide by ingesting an unknown dose of quetiapine. Following application of all available standard diagnostic and therapeutic measures, she was admitted to the intensive care in a deeply somnolent state. Gastroscopy was performed necessitating analgo-sedation, intubation, and mechanical ventilation. Since quetiapine is in principle not dialysable, CytoSorb hemoadsorption was commenced resulting in a clear and rapid decrease in plasma levels of quetiapine and its metabolite norquetiapine over the next few hours. The next day, analgesia was stopped, the patient became alert, and cooperative so that she could be extubated without issues. CytoSorb blood purification therapy was discontinued after 2 days. One day later, the patient was transferred to a psychiatric clinic. WHAT IS NEW AND CONCLUSION: We were able to quickly and efficiently reduce quetiapine and norquetiapine to non-toxic serum levels and to stabilize a critical situation using CytoSorb. Therefore, in the absence of a proven beneficial treatment regimen, the use of CytoSorb might represent an alternative for life-threatening complications of quetiapine intoxication. In particular, intoxications caused by lipophilic agents should be further evaluated.
Clinical development of anticancer drugs can be enhanced using efficacy data of small population clinical trials.
Sawachi K, Matsumaru N, Tsukamoto K
J Clin Pharm Ther · 2022 Sep · PMID 35524471 · Publisher ↗
WHAT IS KNOWN AND OBJECTIVE: Although there are accelerated approval pathways based on data of small populations and surrogate endpoints, the concern that these pathways authorize the use of inefficacious drugs based on...
WHAT IS KNOWN AND OBJECTIVE: Although there are accelerated approval pathways based on data of small populations and surrogate endpoints, the concern that these pathways authorize the use of inefficacious drugs based on limited data from earlier phase clinical trials remains. We retrospectively investigated the efficacy of anticancer drugs, which were approved or whose development was terminated in small and large clinical trials, and verified whether small clinical trials could reflect the results for efficacy in large clinical trials. METHODS: All anticancer drugs approved in Japan or whose development was terminated from 2015 to 2019 were searched. The median overall survival (OS), median progression-free survival (PFS), and overall response rates (ORR) between small clinical trials (sample size ≤100) and large clinical trials (sample size >100) with identical target populations and treatment settings were compared. Simple linear regression analysis, Spearman's correlation analysis, and paired sample t-test were performed. RESULTS AND DISCUSSION: A total of 61 comparable small and large clinical trials were identified. For all endpoints, statistically significant linear trends and correlation were detected (p < 0.001). There were no statistically significant differences in the median PFS and ORR between small and large clinical trials. The mean differences of both clinical trials were -0.102 months and -1.531%, respectively. WHAT IS NEW AND CONCLUSION: Even when the sample size of the clinical trial was increased, the efficacy data of anticancer drugs could not be changed significantly. These results supported the accelerated approval pathway based on the promising efficacy data of small populations in anticancer drug development.
Pharmaceutical care education at pharmacy colleges in the Middle East and North Africa region: A systematic review.
Boura F, Awaisu A, ElGeed H … +2 more , Katoue M, Kheir N
J Clin Pharm Ther · 2022 Aug · PMID 35509234 · Publisher ↗
WHAT IS KNOWN AND OBJECTIVE: New pharmacy curricula include content that equip students with a bundle of professional and interpersonal skills that allows the provision of evidence-based patient-centred pharmaceutical ca...
WHAT IS KNOWN AND OBJECTIVE: New pharmacy curricula include content that equip students with a bundle of professional and interpersonal skills that allows the provision of evidence-based patient-centred pharmaceutical care (PC). PC has been adopted as a practise model underpinning these new roles for pharmacists in developed countries. However, anecdotal evidence suggests that countries in the Middle East/North Africa (MENA) region have been relatively slow in including PC in pharmacy education. There seems to be a need to more accurately describe the extent to which PC is included in pharmacy education in the MENA region. The objective of this systematic review was (a) to determine the status of PC education in schools and colleges of pharmacy in the MENA region and (b) to identify pharmacy students' and/or educators' perceptions and attitudes towards PC, preparedness level to PC provision and perceived barriers to implement this practise model in countries of the MENA region. METHODS: A comprehensive literature search was conducted using MEDLINE, EMBASE, SCOPUS, International Pharmaceutical Abstract and ProQuest databases to identify articles published from 2000 to 2021. Selection of studies for inclusion in the review was based on a pre-determined eligibility criterion to retrieve original research articles addressing the review objectives. RESULTS: Nine articles were eligible for inclusion in the review. The majority of the studies (n = 8) employed a survey-based research method. The studies were conducted in Jordan (n = 4), Kuwait (n = 2), Qatar (n = 2), Saudi Arabia (n = 1) and United Arab Emirates (n = 1). The findings suggest that pharmacy students had overall positive attitude and perception towards PC and some studies reported that students expressed good preparedness levels to implement most of the PC aspects. Several barriers to the implementation of PC were reported such as the slow educational reforms in pharmacy programs and a number of organizational and professional barriers. The studies provided recommendations for improvements in the pharmacy curricula to support pharmacy students' preparation to become competent PC practitioners. WHAT IS NEW AND CONCLUSION: The literature describing PC education in the MENA region is limited. Joint efforts among educational institutions and health authorities are needed to support PC implementation. There is a need to conduct further research to explore the status of PC education and practise in the different countries within the MENA region. This can drive future directions of pharmacy education to meet the needs of the pharmacy profession and healthcare systems in these countries.
Pharmacokinetics, safety and efficacy of intra-articular non-steroidal anti-inflammatory drug injections for the treatment of osteoarthritis: A narrative review.
Selig DJ, Kress AT, Horton IM … +3 more , Livezey JR, Sadik EJ, DeLuca JP
J Clin Pharm Ther · 2022 Aug · PMID 35505520 · Full text
WHAT IS KNOWN AND OBJECTIVE: Osteoarthritis (OA) is a common cause of joint disease and activity limitation in adults. Common therapies to treat OA-related pain are oral and topical non-steroidal anti-inflammatory drugs...
WHAT IS KNOWN AND OBJECTIVE: Osteoarthritis (OA) is a common cause of joint disease and activity limitation in adults. Common therapies to treat OA-related pain are oral and topical non-steroidal anti-inflammatory drugs (NSAIDs) and intra-articular (IA) corticosteroids. However, prolonged courses of oral NSAIDs are associated with systemic adverse effects and repeat IA corticosteroid injections may cause cartilage degeneration. IA NSAIDs may be an alternative therapy possibly minimizing systemic side effects while maintaining efficacy. Therefore, we sought to summarize the pharmacokinetics, safety and efficacy of IA NSAIDs to help providers make a more informed decision on the use of IA NSAIDs. METHODS: We searched the National Library of Medicine Database with terms "intraarticular and nsaid", yielding 1032 results. Only traditional formulations of NSAIDs were considered for inclusion. Animal studies were included if animals were healthy or if the method of arthritis induction was a reasonable model of osteoarthritis. Human studies were included if humans were healthy or if the primary disease studied was osteoarthritis of a large joint. Of 1032 results, 31 research articles met the inclusion criteria and were summarized in this review. RESULTS AND DISCUSSION: We found that single doses of IA NSAIDs provided far less total systemic and synovial exposure compared to a one week course of oral NSAIDs, but maximum concentrations to the synovium with IA administration were much higher. IA NSAIDs had an excellent safety profile in small animals, large animals and humans, although these injections were associated with non-specific cartilage inflammation in healthy animals. In animal models, IA NSAIDs had similar efficacy to PO NSAIDs in treating OA-related pain. In humans, IA NSAIDs had similar efficacy to PO NSAIDS and IA corticosteroids in treating OA-related pain; however, many trials did not have a placebo control and outcome measures were heterogeneous. WHAT IS NEW AND CONCLUSION: Overall, single doses of IA NSAIDs appear safe and efficacious across animals and humans. The optimal use of IA NSAIDs is still to be determined and further research is needed. However IA NSAIDs may be an additional beneficial therapy to treat OA-related pain. Potential uses may be to augment IA corticosteroids injections, to interrupt multiple IA corticosteroid injections or as an alternative in patients that are high risk for corticosteroid-related adverse events.
Rivaroxaban population pharmacokinetic and pharmacodynamic modeling in Iranian patients.
Esmaeili T, Rezaee M, Abdar Esfahani M … +3 more , Davoudian A, Omidfar D, Rezaee S
J Clin Pharm Ther · 2022 Aug · PMID 35504629 · Publisher ↗
WHAT IS KNOWN AND OBJECTIVE: Although predictable pharmacokinetic and pharmacodynamic of rivaroxaban allow fixed dosing regimens without routine coagulation monitoring, there is still the necessity to monitor and predict...
WHAT IS KNOWN AND OBJECTIVE: Although predictable pharmacokinetic and pharmacodynamic of rivaroxaban allow fixed dosing regimens without routine coagulation monitoring, there is still the necessity to monitor and predict the effects of rivaroxaban in specific conditions and different populations. The current study was designed and conducted to analyze the rivaroxaban population pharmacokinetics in Iranian patients and establish a pharmacokinetic/pharmacodynamic model to predict the relationship between rivaroxaban concentration and its anticoagulant activity. METHODS: A sequential nonlinear mixed effect pharmacokinetic/pharmacodynamic modeling method was used to establish the relation between rivaroxaban concentration and anti-factor Xa activity, prothrombin time, and activated partial thromboplastin time (aPTT) as pharmacodynamic biomarkers in a population of sixty-nine Iranian patients under treatment with oral rivaroxaban. Rivaroxaban plasma concentration was quantified by a validated high-performance liquid chromatography-tandem mass spectrometry. RESULTS AND DISCUSSION: The typical population values (inter-individual variability%) of the oral volume of distribution and clearance for a one-compartment model were 61.2 L (21%) and 3.68 L·h (61%), respectively. Creatinine clearance and Child-Turcotte-Pugh score were found to affect the clearance. A direct link linear structural model best fitted the data for both prothrombin time and aPTT. The baseline estimates of aPTT and prothrombin time in the population were 35.0 (15%) and 12.6 (2%) seconds, respectively. The slope of the relationship between apTT, prothrombin time, and rivaroxaban concentration was 0.033 (28%) and 0.018 (54%) s·ml·ng , respectively. The selected model for anti-factor Xa activity consisted of a direct link inhibitory E model with Hill coefficient. The maximum level of inhibition (E ) was 4 IU·ml . The concentration of rivaroxaban producing 50% of the maximum inhibitory effect (EC ) was 180 (24%) ng·ml , and Hill coefficient (γ) was 1.44 (108%). No covariates showed a statistically significant effect on PT and activated partial thromboplastin time prolonging properties and anti-factor Xa activity. WHAT IS NEW AND CONCLUSION: Our results confirmed that pharmacokinetic/pharmacodynamic models similar to those of the other studies describe the relationship between the rivaroxaban concentration and its anticoagulant effect in Iranian patients. However, considerable differences were observed in the parameters of the pharmacodynamics-pharmacokinetic models with the results of other reports that can explain the unpredictable effects of rivaroxaban in some patients.
Impact of expedited programs in the United States, as foreign regulatory factors, on clinical development time in Japan.
Tajima G, Matsumaru N, Tsukamoto K
J Clin Pharm Ther · 2022 Sep · PMID 35488803 · Publisher ↗
WHAT IS KNOWN AND OBJECTIVE: Regulatory authorities in several regions have introduced a number of expedited programs (EPs) to promote the development of innovative drugs for patients in their own countries. The EPs in t...
WHAT IS KNOWN AND OBJECTIVE: Regulatory authorities in several regions have introduced a number of expedited programs (EPs) to promote the development of innovative drugs for patients in their own countries. The EPs in the United States (US), alone or in combination, have been successful in shortening the clinical development time in the US. We examined whether US-EPs, as well as other related factors, have an impact on the clinical development time in Japan to obtain new insights for more efficient drug development. METHODS: In total, 168 drugs approved as new molecular entities (NMEs) in Japan and approved in the US between 2012 and 2019 were surveyed. We compared the clinical development time in Japan for those drugs with or without US-EPs. We also examined the impact of overlapping designations of US-EPs on clinical development time in Japan. Multiple regression analysis was performed to identify associated factors related to clinical development time in Japan, including US-EPs. RESULTS AND DISCUSSION: The clinical development time in Japan was significantly shorter at 37.4 [Interquartile range, IQR, 28.7-48.9] months for Accelerated Approval (AA), 42.2 [30.0-53.6] months for Breakthrough Therapy (BT), 42.3 [29.3-56.4] months for Fast Track (FT), 44.5 [30.7-60.0] months for US Priority Review, and 45.2 [31.3-61.8] months for US Orphan Designation. Multiple regression analysis revealed that AA (p = 0.008), FT (p = 0.013), Japan Priority Review, and the difference in development initiation dates between the US and Japan were significant factors related to a decrease in the clinical development time in Japan, whereas Japan Orphan Designation and the development of anticancer drugs were significant factors linked to an increase in the clinical development time. WHAT IS NEW AND CONCLUSION: US-EPs were associated with a decrease in the clinical development time in Japan for the drugs that were approved as NMEs in Japan and approved in the US. This association was not restricted to particular therapeutic areas or development strategies. Stakeholders involved in drug development, including the drug developers and regulatory authorities in Japan, should realize these effects for efficient drug development.
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