Clinical experience with new formulation SUBA®-itraconazole for prophylaxis in patients undergoing stem cell transplantation or treatment for haematological malignancies

2019 ◽  
Vol 74 (10) ◽  
pp. 3049-3055 ◽  
Author(s):  
Blake Nield ◽  
Stephen R Larsen ◽  
Sebastiaan J van Hal
Keyword(s):  
High Risk ◽  
Therapeutic Drug ◽  
The Novel ◽  
Haematological Malignancies ◽  
Patient Demographics ◽  
Drug Concentrations ◽  
Study Population ◽  
Trough Concentrations ◽  
New Formulation ◽  
Gastric Acid Suppression

AbstractBackgroundSUper BioAvailability-itraconazole (SUBA®-itraconazole) was introduced into Australia in April 2014 as a substitute for standard itraconazole on the basis of improved bioavailability, tolerance and interpatient variability. Shortly after its introduction, our centre converted to the novel formulation for mould prophylaxis in patients undergoing allogeneic HSCT, autologous HSCT or treatment for haematological malignancies with an intermediate/high risk of invasive fungal infection (IFI).MethodsA single-institution, investigator-initiated retrospective cohort study was conducted between June 2016 and April 2018 to assess therapeutic drug concentrations, safety and tolerability of a standard prophylactic dose of SUBA®-itraconazole.ResultsA total of 74 patients were assessed across 98 admissions with 178 measured itraconazole trough concentrations. The median duration of prophylaxis was 15.5 (1–59) days. No significant correlation was identified between trough concentrations and patient demographics including gender and weight. Drug concentrations were reduced by gastric acid suppression and diarrhoea. Therapeutic itraconazole trough concentrations (≥0.5 mg/L) were achieved at a median of 7 (95% CI = 6–8) days, with 87% of patients achieving therapeutic concentrations at day 14 (expected steady-state). One (1%) proven/probable IFI and 5 (5%) possible breakthrough IFIs were identified. Although adverse events were experienced by 42% of the cohort, only a single event was directly attributable to SUBA®-itraconazole, resulting in change of prophylactic agent.ConclusionsSUBA®-itraconazole achieved rapid therapeutic trough concentrations, was associated with low rates of IFI and was well tolerated in the study population. This formulation should be considered a realistic and safe first-line agent for the prevention of IFIs in those undergoing HSCT and intermediate/high-risk therapy for haematological malignancies.

Adverse effects and duration of treatment of TB in Canterbury, New Zealand

2021 ◽  
Vol 25 (12) ◽  
pp. 990-994
Author(s):  
J. Phillipson ◽  
N. Kuruppu ◽  
T. Chikura ◽  
C. McLachlan ◽  
L. McNeill ◽  
...  
Keyword(s):  
New Zealand ◽  
Response To Treatment ◽  
Therapeutic Drug ◽  
Duration Of Treatment ◽  
Extended Treatment ◽  
Patient Demographics ◽  
Disease Characteristics ◽  
Actual Duration ◽  
Study Population ◽  
Associated Risk Factors

BACKGROUND Treatment of TB is often extended beyond the recommended duration. The aim of this study was to assess prevalence of extended treatment and to identify associated risk factors. We also aimed to determine the frequency and type of adverse drug reactions (ADR) experienced by this study population.METHODS We performed a retrospective cohort study of all patients treated for active TB at Christchurch Hospital, Christchurch, New Zealand, between 1 March 2012 and 31 December 2018. Data for 192 patients were collected on patient demographics, disease characteristics and treatment characteristics, including planned and actual duration of treatment and ADRs.RESULTS Of 192 patients, 35 (18.2%) had treatment extended, and 85 (46.5%) of 183 with fully drug-susceptible TB received ≥9 months treatment. The most common reasons for extension were persistent or extensive disease and ADR. Extended treatment duration was not associated with any patient or disease characteristics. We found 35 (18.2%) patients experienced at least one ADR. The most common ADRs were hepatitis, rash and peripheral neuropathy.CONCLUSION TB treatment extension beyond WHO guidelines is common. Further research is needed to guide management of those with slow response to treatment. Methods for early detection of ADR, systems to improve adherence and therapeutic drug monitoring are potentially useful strategies.

scholarly journals β-Lactam Dosage Regimens in Septic Patients with Augmented Renal Clearance

2018 ◽  
Vol 62 (9) ◽  
Author(s):  
Alexandra Jacobs ◽  
Fabio Silvio Taccone ◽  
Jason A. Roberts ◽  
Frédérique Jacobs ◽  
Frederic Cotton ◽  
...  
Keyword(s):  
Creatinine Clearance ◽  
Renal Clearance ◽  
Total Body Clearance ◽  
Therapeutic Drug ◽  
Population Pharmacokinetic ◽  
Augmented Renal Clearance ◽  
Drug Concentrations ◽  
Trough Concentrations ◽  
Total Body ◽  
Body Clearance

ABSTRACTAugmented renal clearance is commonly observed in septic patients and may result in insufficient β-lactam serum concentrations. The aims of this study were to evaluate potential correlations between drug concentrations or total body clearance of β-lactam antibiotics and measured creatinine clearance and to quantify the need for drug dosage adjustments in septic patients with different levels of augmented renal clearance. We reviewed 256 antibiotic measurements (512 drug concentrations) from a cohort of 215 critically ill patients who had a measured creatinine clearance of ≥120 ml/min and who received therapeutic drug monitoring of meropenem, cefepime, ceftazidime, or piperacillin from October 2009 until December 2014 at Erasme Hospital. Population pharmacokinetic (PK) analysis of the data was performed using the Pmetrics software package for R. Fifty-five percent of drug concentrations showed insufficient β-lactam serum concentrations to treat infections due toPseudomonas aeruginosa. There were significant, yet weak, correlations between measured creatinine clearance and trough concentrations of meropenem (r= −0.21,P= 0.01), trough concentrations of piperacillin (r= −0.28,P= 0.0071), concentrations at 50% of the dosage interval (r= −0.41,P< 0.0001), and total body clearance of piperacillin (r= 0.39,P= 0.0002). Measured creatinine clearance adequately explained changes in drug concentrations in population pharmacokinetic models for cefepime, ceftazidime, and meropenem but not for piperacillin. Therefore, specific PK modeling can predict certain β-lactam concentrations based on renal function but not on absolute values of measured creatinine clearance, easily available for clinicians. Currently, routine therapeutic drug monitoring is required to adjust daily regimens in critically ill patients receiving standard dosing regimens.

scholarly journals Pharmacokinetic Analysis of Meropenem and Piperacillin in Critically-Ill Patients Requiring Continuous Ven-Venous Hemodiafiltration

2015 ◽  
Vol 6 (2) ◽  
Author(s):  
Brandon Ferlas ◽  
Kristina Nelson ◽  
Milind Junghare ◽  
Kimberly Boeser
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Pharmacokinetic Analysis ◽  
Therapeutic Drug ◽  
Complex Nature ◽  
Original Research ◽  
Beta Lactam ◽  
Post Dose ◽  
Drug Concentrations ◽  
Trough Concentrations

Background: Literature has demonstrated proper antibiotic selection and prompt initiation of antibiotics are associated with lower morbidity and mortality. Septic patients have altered pharmacokinetics and often require continuous renal replacement therapy which contributes to altered drug clearance and metabolism. The current study evaluates the pharmacokinetics of meropenem and piperacillin/tazobactam in critically-ill patients requiring continuous veno-venous hemodiafiltration. Purpose: This observational, prospective, single-center, nonrandomized study evaluated the pharmacokinetics of meropenem and piperacillin/tazobactam in critically-ill patients requiring continuous veno-venous hemodiafiltration. Methods: Plasma drug concentrations were determined via high-performance liquid chromatography using three post-dose blood samples after steady-state antimicrobial agent administration. Results: Meropenem peak drug concentrations ranged from 35.9 to 61 mcg/mL, while trough concentrations ranged from 3.9 to 16.7 mcg/mL. Piperacillin peak drug concentrations ranged from 240 to 331.8 mcg/mL, while trough concentrations ranged from 152.7 to 194.9 mcg/mL. Both drugs examined displayed peak concentrations relatively consistent with those expected from the literature, but observed trough concentrations for meropenem and piperacillin were uniformly high. Conclusions: Intravenous doses of meropenem and piperacillin result in peak drug concentrations similar to those previously reported and trough concentrations significantly greater than those in the literature. While concentrations above an organism’s MIC are desirable given the time-dependent nature of these beta-lactam antibiotics, decreased renal clearance of patients maintained on CVVHDF therapy while receiving higher doses of antimicrobials creates a situation in which drug accumulation and toxicity may occur. Given the complex nature of ICU patient care, increased pharmacovigilance and therapeutic drug monitoring are necessary in this unique population.   Type: Original Research

Association of adalimumab trough concentrations and treatment response in patients with Juvenile Idiopathic Arthritis

Rheumatology ◽  
2021 ◽  
Author(s):  
Martijn J H Doeleman ◽  
Sytze de Roock ◽  
Mohsin El Amrani ◽  
Erik M van Maarseveen ◽  
Nico M Wulffraat ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Disease Activity ◽  
Treatment Response ◽  
Therapeutic Drug ◽  
Adequate Response ◽  
Paediatric Patients ◽  
Drug Concentrations ◽  
Significant Difference ◽  
Secondary Failure ◽  
Trough Concentrations

Abstract Objective To assess the relationship of adalimumab trough concentrations and treatment response in paediatric patients with juvenile idiopathic arthritis (JIA). Methods Monocentric cohort study of JIA patients treated with adalimumab. Clinical data and samples were collected during routine follow-up. Adalimumab trough concentrations were quantified by a novel liquid chromatography-tandem mass spectrometry assay. Anti-adalimumab antibodies were measured in samples with trough concentrations ≤5mg/l. Disease activity was evaluated using the clinical Juvenile Arthritis Disease Activity Score with 71 joint-count (cJADAS71). Response to adalimumab was defined according to recent international treat-to-target guidelines. Results 35 adalimumab trough samples were available from 34 paediatric patients with JIA. Although there was no significant difference in adalimumab dose, trough concentrations were significantly lower in patients with secondary failure (median 1.0 mg/l; IQR 1.0–5.3) compared with patients with primary failure (median 13.97 mg/l; IQR 11.81–16.67) or an adequate response (median 14.94 mg/l; IQR 10.31–16.19) to adalimumab. Conclusion Adalimumab trough concentrations were significantly lower in JIA patients with secondary failure compared with patients with primary failure or an adequate response to adalimumab. Results suggest that trough concentration measurements could identify JIA patients who require increased adalimumab doses to achieve or maintain therapeutic drug concentrations.

scholarly journals Impact of dose adaptations following voriconazole therapeutic drug monitoring in pediatric patients

2019 ◽  
Vol 57 (8) ◽  
pp. 937-943 ◽  
Author(s):  
Vincent J Lempers ◽  
Edmé Meuwese ◽  
Annelies M Mavinkurve-Groothuis ◽  
Stefanie Henriet ◽  
Inge M van der Sluis ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Multiple Dose ◽  
Pediatric Patients ◽  
Therapeutic Drug ◽  
Target Attainment ◽  
Patient Demographics ◽  
Before And After ◽  
Intrapatient Variability ◽  
Trough Concentrations

Abstract Voriconazole is the mainstay of treatment for invasive aspergillosis in immunocompromised pediatric patients. Although Therapeutic Drug Monitoring (TDM) of voriconazole is recommended, it remains unknown if TDM-based dose adaptations result in target attainment. Patients <19 years from two pediatric hematologic-oncology wards were retrospectively identified based on unexplained high voriconazole trough concentrations (Cmin > 6 mg/l). Patient demographics, clinical characteristics, treatment, voriconazole dosing information, voriconazole Cmin before and after adjustment based on TDM were obtained. Twenty-one patients, median (range) age 7.0 (1.2–18.5) years, were identified in two centers. First Cmin (3.1 mg/l [0.1–13.5]) was obtained after 3 days (1–27) of treatment. The median of all Cmin (n = 485, median 11 per patient) was 2.16 mg/l (0.0 (undetectable)–28.0), with 24.1% of Cmin < 1 mg/l, 48.9% 1–4 mg/l, 9.3% 4–6 mg/l, and 17.7% > 6 mg/l. Intrapatient variability was large (94.1% for IV, 88.5% for PO). Dose increases at Cmin < 1 mg/l resulted in an increased Cmin in 76.4%, with 60% between 1 and 4 mg/l. Dose decreases at Cmin > 6 mg/l resulted in a decreased Cmin in 80%, with 51% between 1 and 4 mg/l. Overall, in 45% of the cases (33 out of 55 and 12 out of 45) therapeutic targets were attained after dose adjustment. Fifty-five percent of initial Cmin was outside the therapeutic target of 1–4 mg/l, with multiple dose adaptations required to achieve therapeutic concentrations. Only 60% and 51% of dose adaptations following sub- and supra-therapeutic Cmin, respectively, did result in target attainment. Intensive and continuous TDM of voriconazole is a prerequisite for ensuring adequate exposure in pediatric patients.

Usia Resiko Tinggi dan Perdarahan Post Partum

2018 ◽  
Vol 3 (2) ◽  
pp. 91
Author(s):  
Ani Media Harumi ◽  
Kasiati Kasiati
Keyword(s):  
High Risk ◽  
Post Partum ◽  
Chi Square ◽  
Sample Number ◽  
Chi Square Test ◽  
Study Population ◽  
Relationship Of ◽  
The Relationship

Abstract: The purpose of this study is to analyze the relationship of age high risk with the incidence ofbleeding post partum in dr. M. Soewandhie Surabaya hospital. This research is analytic with an approachof a sectional cross. The study population was all post partum mothers in the Dr. M. Soewandhie Surabayahospital in January 2016 to March 2017, which amounts to an average of 1840respondents while theresearch sample number 182. Measuring collection sheet data obtained by systematic random sampling.The Study was conducted Chi-Square test obtained mean count X2 (0,00) is less than á (0.05) thenH0 is rejected and H1 accepted it means that there is a relationship between the age of high risk withbleeding post partum. Conclusion, there is a relationship between the age of high risk with the incidenceof bleeding post partum in the Spaceof the Maternity room Dr. Moch. Soewandhie Surabayahospital.

Neuroblastoma: An Updated Review on Biology and Treatment

2020 ◽  
Vol 20 (13) ◽  
pp. 1014-1022 ◽  
Author(s):  
Suresh Mallepalli ◽  
Manoj Kumar Gupta ◽  
Ramakrishna Vadde
Keyword(s):  
Survival Rate ◽  
High Risk ◽  
Molecular Mechanisms ◽  
Definitive Treatment ◽  
Therapeutic Drug ◽  
Mycn Amplification ◽  
Dependent Manner ◽  
High Risk Patients ◽  
Treatment And Prevention ◽  
Risk Patients

Background: Neuroblastoma (NB) is the second leading extracranial solid tumors of early childhood and clinically characterized by the presence of round, small, monomorphic cells with excess nuclear pigmentation (hyperchromasia).Owing to a lack of definitive treatment against NB and less survival rate in high-risk patients, there is an urgent requirement to understand molecular mechanisms associated with NB in a better way, which in turn can be utilized for developing drugs towards the treatment of NB in human. Objectives: In this review, an approach was adopted to understand major risk factors, pathophysiology, the molecular mechanism associated with NB, and various therapeutic agents that can serve as drugs towards the treatment of NB in humans. Conclusions: Numerous genetic (e.g., MYCN amplification), perinatal, and gestational factors are responsible for developing NB. However, no definite environmental or parental exposures responsible for causing NB have been confirmed to date. Though intensive multimodal treatment approaches, namely, chemotherapy, surgery &radiation, may help in improving the survival rate in children, these approaches have several side effects and do not work efficiently in high-risk patients. However, recent studies suggested that numerous phytochemicals, namely, vincristine, and matrine have a minimal side effect in the human body and may serve as a therapeutic drug during the treatment of NB. Most of these phytochemicals work in a dose-dependent manner and hence must be prescribed very cautiously. The information discussed in the present review will be useful in the drug discovery process as well as treatment and prevention on NB in humans.

Topical Bimatoprost Insert for Primary Open-Angle Glaucoma and Ocular Hypertension Treatment - A Phase II Controlled Study

2021 ◽  
Vol 18 ◽  
Author(s):  
Francine Rubião ◽  
Alan Cezar Faria Araújo ◽  
João Bernardo Sancio ◽  
Bárbara Silva Nogueira ◽  
Juçara Ribeiro Franca ◽  
...  
Keyword(s):  
Ocular Hypertension ◽  
Primary Open Angle Glaucoma ◽  
Open Angle Glaucoma ◽  
T Test ◽  
Controlled Study ◽  
Therapeutic Drug ◽  
Eye Drops ◽  
Open Angle ◽  
Drug Concentrations

Background: The most common treatment for primary open-angle glaucoma (POAG) is the daily use of eye drops. Sustained-release drug delivery systems have been developed to improve patient adherence by achieving prolonged therapeutic drug concentrations in ocular target tissues while limiting systemic exposure. The purpose of this study is to compare the efficacy and safety of bimatoprost inserts with bimatoprost eye drops in patients with POAG and ocular hypertension (OH). Methods: We include OH and POAG patients aged between 40 and 75 years-old. Both OH and POAG patients had intraocular pressure (IOP) greater than 21 and ≤30 mmHg at 9:00 am without glaucoma medication and normal biomicroscopy. Five normal patients with IOP≤14 mmHg constitute the control group. A chitosan-based insert of bimatoprost was placed at the upper conjunctival fornix of the right eye. In the left eye, patients used one drop of LumiganTM daily at 10:00 pm. For statistical analysis, we used a two-way analysis of variance (ANOVA), Student t-test, and paired t-test. Results: Sixteen POAG and 13 OH patients with a mean age of 61 years were assessed. In both eyes, IOP reduction was similar during three weeks of follow-up (19.5±2.2 mmHg and 16.9±3.1 mmHg), insert, and eye drop, respectively; P=0.165). The percentage of IOP reduction in the third week was 30% for insert and 35% for eye drops (P=0.165). No intolerance or discomfort with the insert was reported. Among the research participants, 58% preferred the use of the insert while 25% preferred eye drops, and 17% reported no preference. Conclusions: Bimatoprost-loaded inserts showed similar efficacy to daily bimatoprost eye drops during three weeks of follow up, without major side effects. This might suggest a possible change in the daily therapeutic regimen for the treatment of POAG and OH.

scholarly journals A156 SERUM TUMOUR NECROSIS FACTOR-α ANTAGONIST DRUG CONCENTRATIONS IN PATIENTS WITH PYODERMA GANGRENOSUM ASSOSCIATED WITH INFLAMMATORY BOWEL DISEASE

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 162-163
Author(s):  
M Mikail ◽  
A Wilson
Keyword(s):  
Inflammatory Bowel Disease ◽  
Pyoderma Gangrenosum ◽  
Bowel Disease ◽  
Complete Resolution ◽  
Therapeutic Drug ◽  
Drug Concentrations ◽  
Median Serum ◽  
Inflammatory Bowel ◽  
Factor Α ◽  
Necrosis Factor

Abstract Background The utility of therapeutic drug monitoring for guiding the dosing of tumor necrosis factor-α antagonists (TNFAs) in luminal inflammatory bowel disease (IBD) is well-established and well-accepted. TNFAs, specifically infliximab and adalimumab, have become integral to the management of the rare, neutrophilic dermatosis, pyoderma gangrenosum (PG) in IBD. Little is known regarding the target serum TNFA concentrations to guide dosing to achieve resolution of PG in IBD. Aims To describe the serum TNFA concentrations (infliximab or adalimumab) associated with the resolution of PG lesions in patients with IBD. Methods Patients with IBD and associated PG treated with one of infliximab or adalimumab (collectively known as TNFAs) seen at two academic hospitals affiliated with Western University were identified. Serum TNFA concentrations were assessed at the time of PG treatment. Results Nine patients were identified. All patients had IBD-associated PG. Seven patients were treated with infliximab and 2 patients were treated with adalimumab. All patients received standard dosing. Eight patients had complete resolution of their PG, while one had near complete resolution at the time of last follow-up. A median serum infliximab concentration of 3.00 (IQR, 3.52) µg/ml at week 14 and a median serum adalimumab concentration of 2.02 (IQR, 0.98) µg/ml at week 12 were seen at the time of PG treatment. Conclusions Herein, we report low serum TNFA concentrations despite PG healing in a cohort of IBD patients. This is lower than what is in patients for successful TNFA treatment in luminal and fistulising IBD. Funding Agencies NoneNone.

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