Intravenous Formulation Research Articles

A Comparison Between Enteral and Intravenous Nimodipine in Subarachnoid Hemorrhage: A Systematic Review and Network Meta-Analysis.

Our objective was to compare the effectiveness of intravenous and enteral nimodipine in preventing poor outcome from delayed cerebral ischemia in patients with subarachnoid hemorrhage. We performed a systematic search and a network meta-analysis using the following databases: PubMed, Scopus, the Cochrane Central Register of Controlled Trials, and Google Scholar. Risk of Bias 2 tool was used to assess risk of bias of included studies. A ranking among methods was performed on the basis of the frequentist analog of the surface under the cumulative ranking curve. Published studies that met the following population, intervention, comparison, outcomes and study(PICOS) criteria were included: patients with subarachnoid hemorrhage aged 15years or older (P); nimodipine, intravenous and oral formulation (I); placebo or no intervention (C); poor outcome measured at 3months (defined as death, vegetative state, or severe disability), case fatality at 3months, delayed cerebral ischemia, delayed ischaemic neurologic deficit, and vasospasm measured with transcranial Doppler or digital subtraction angiography (O); and randomized controlled trials (S). No language or publication date restrictions were applied. Ten studies were finally included, with a total of 1527 randomly assigned patients. Oral and intravenous nimodipine were both effective in preventing poor outcome, delayed cerebral ischemia, and delayed ischaemic neurological deficit. Neither treatment was effective in improving case fatality. Evolving clinical protocols over a 30-year period and the risk of bias of the included studies may limit the strength of our results. Enteral and intravenous nimodipine may have a similar effectiveness in terms of preventing poor outcome, delayed cerebral ischemia, and delayed ischaemic neurological deficit. More research may be needed to fully establish the role of intravenous nimodipine in current clinical practice.

A Randomized controlled trial of the Effect of intraVenous iron on Anaemia in Malawian Pregnant women (REVAMP): Statistical analysis plan

Background: Anaemia affects more than half of Africa’s pregnancies. Standard care, with oral iron tablets, often fails to achieve results, with compliance and gastrointestinal side-effects being a significant issue. In recent years, intravenous iron formulations have become safe, effective, and quick to administer, allowing the complete iron requirements of pregnancy to be provided in one 15-minute infusion. The Randomized controlled trial of the Effect of intraVenous iron on Anaemia in Malawian Pregnant women (REVAMP) will evaluate whether a modern intravenous iron formulation, ferric carboxymaltose (FCM), given once during the second trimester is effective and safe in improving maternal and neonatal outcomes for treatment of moderate to severe anaemia in sub-Saharan Africa. The objective was to publish the detailed statistical analysis plan for the REVAMP trial prior to unblinding the allocated treatments and performing the analysis. Methods: REVAMP is a multicentre, two-arm, open-label, parallel-group randomized control trial (RCT) in 862 pregnant women in their second trimester. The trial statistician developed the statistical analysis plan in consultation with the trial management team based on the protocol, data collection forms, and study outcomes available in the blinded study database. Results: The detailed statistical analysis plan will support the statistical analyses and reporting of the REVAMP trial after unblinding the treatment allocations. Conclusions: A statistical analysis plan allows for transparency as well as reproducibility of reporting and statistical analyses.

A simple extemporaneous oral suspension of aprepitant yields sufficient pharmacokinetic exposure in children.

Aprepitant is used for the treatment of chemotherapy induced nausea and vomiting. A liquid formulation is needed for treatment of young children. However, the commercial (powder for) suspension was not available worldwide for a prolonged period of time and, therefore, a 10 mg/mL aprepitant oral suspension was extemporarily prepared to prevent suboptimal antiemetic treatment. The current pharmacokinetic study was developed to investigate whether this extemporaneous oral suspension offers an appropriate treatment option. From 49 pediatric patients (0.7-17.9 years) 235 plasma concentrations were collected. Patients were either treated with our extemporaneous oral suspension (n = 26; 53%), commercially available capsules (n = 18; 37%), or the intravenous prodrug formulation of aprepitant (fosaprepitant, n = 5; 10%). Pharmacokinetic analyses were performed using nonlinear mixed effects modelling. A one-compartment model adequately described the pharmacokinetics of aprepitant in children. The bioavailability of the extemporaneous oral suspension was not significantly different to that of the capsules (P = 0.26). The observed bioavailability throughout the total population was 83% (95% CI 69%-97%). The absorption of the extemporaneous oral suspension was 39.4% (95%CI 19.5-57.4%) faster than that of capsules (mean absorption time of 1.78 h (95%CI 1.32-2.35), but was comparable to that of the commercial oral suspension. The median area under the curve after (fos)aprepitant was 22.2 mg/L*h (range 8.9-50.3 mg/L*h) on day 1. Our extemporaneous oral suspension is an adequate alternative for the commercially (un)available oral suspension in young children. An adequate exposure to aprepitant in children was yielded and the bioavailability of the extemporaneous suspension was comparable to capsules.

Insight into the in vivo fate of intravenous herpetrione amorphous nanosuspensions by aggregation-caused quenching probes

Intravenous nanosuspensions are attracted growing attention as a viable strategy for development of intravenous formulations of poorly water-soluble drugs. However, only few information about the biological fate of intravenous nanosuspensions is currently known, especially amorphous nanosuspensions are not reported yet. In this study, the in vivo fate of herpetrione (HPE) amorphous nanosuspensions following intravenous administration was explored by using an aggregation-caused quenching (ACQ) probe and HPLC methods. The ACQ probe is physically embedded into HPE nanoparticles via anti-solvent method to form HPE hybrid nanosuspensions (HPE-HNSs) for bioimaging. HPE-HNSs emit strong and stable fluorescence, but fluorescence quenches immediately upon the dissolution of HPE-HNSs, confirming the self-discrimination of HPE-HNSs. Following intravenous administration of HPE-HNSs, integral HPE-HNSs and HPE show similar degradation and biodistribution, with rapid clearance from blood circulation and obvious accumulation in liver and lung. Due to the slower dissolution and enhanced recognition by reticulo-endothelial system, 450 nm HPE-HNSs accumulate more in liver, lung and spleen than that of 200 nm HPE-HNSs. These results demonstrate that integral HPE-HNSs determine the in vivo performance of HPE-HNSs. This study provides insight into the in vivo fate of intravenous amorphous nanosuspensions.

Population Pharmacokinetic Modelling of Acetaminophen and Ibuprofen: the Influence of Body Composition, Formulation and Feeding in Healthy Adult Volunteers.

Background and ObjectiveCombined acetaminophen and ibuprofen are common antipyretic and analgesic drugs. Formulation and feeding affect drug absorption. Drug clearance has a nonlinear relationship with total body weight. The covariate effect of fat mass on acetaminophen and ibuprofen pharmacokinetics remains unexplored. This study sought to quantify acetaminophen and ibuprofen pharmacokinetics with intravenous, tablet, sachet and oral suspension formulations in fed and fasted states.MethodsPooled time–concentration data for acetaminophen and ibuprofen were available from fasting and fed healthy adults. Data from intravenous, tablet, sachet and suspension formulations were analysed using nonlinear mixed-effects models. Body composition was considered as a covariate on clearances and volumes of distribution (Vd). Size metrics investigated were total body weight, fat and fat-free mass. Theory-based allometry was used to scale pharmacokinetic parameters to a 70 kg individual. A factor on absorption half-life and lag time quantified delays due to feeding for oral formulations. Pharmacokinetic-pharmacodynamic simulations were used to explore the time courses of pain response for acetaminophen and ibuprofen for each formulation.ResultsPooled data included 116 individuals (18–49 years, 49–116 kg) with 6095 acetaminophen and 6046 ibuprofen concentrations available for analysis. A two-compartment pharmacokinetic model with first-order elimination described disposition for both drugs. Normal fat mass was the best covariate to describe acetaminophen clearance (CL), with a factor for fat contribution (FFATCL) of 0.816. Acetaminophen volume of distribution was described using total body weight. Normal fat mass was the best covariate to describe ibuprofen clearance (FFATCL = 0.863) and volume of distribution: (FFATV = 0.718). Clearance and central volume of distribution were 24.0 L/h/70 kg and 43.5 L/h/70 kg for acetaminophen. Ibuprofen clearance and central volume of distribution were 3.79 L/h/70 kg and 10.5 L/h/70 kg. Bioavailability and absorption half-life were 86% and 12 min for acetaminophen and 94% and 27 min for ibuprofen. Absorption lag times were 5.3 min and 6.7 min for acetaminophen and ibuprofen, respectively. Feeding increased both absorption half-life and absorption lag time when compared to the tablet formulation under fasting conditions. Feeding had the most pronounced effect on the lag time associated with tablet formulation for both drugs. Time to a pain score reduction of 2 points (visual analogue score, 0–10) differed by only 5–10 min across all formulations for acetaminophen and ibuprofen.ConclusionFat mass was an important covariate to describe acetaminophen and ibuprofen pharmacokinetics. The absorption half-lives of acetaminophen and ibuprofen were increased in fed states. The delay in absorption, quantified by a lag time, was protracted for both drugs.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13318-022-00766-9.

Detectable Serum Concentration with Prophylactic Inhaled Tobramycin in Lung Transplant Recipients

<h3>Purpose</h3> Inhaled tobramycin (iTOBI) is used in bilateral lung transplant recipients (LTRs) to prevent PsA colonization. Pharmacokinetic studies show that iTOBI is not systemically absorbed, making it an alternative to intravenous formulations. Case reports exist of LTRs on iTOBI developing renal failure with detectable tobramycin troughs (DTTs). The purpose of this review is to describe the incidence of DTT in LTRs receiving iTOBI immediately post-transplant. <h3>Methods</h3> This single-center, retrospective review included patients in their index lung transplant admission who received iTOBI with a DTT (≥ 0.5 mg/L). All LTRs received iTOBI 300 mg q12hr prophylaxis for at least one month with levels drawn for cause when concerned for accumulation. Primary outcome was the number of LTRs with DTTs. Secondary outcomes included duration of therapy and incidence of SCr increase ≥ 0.3 mg/dL within 48 hours (AKI). Descriptive statistics were used to analyze baseline characteristics and outcomes. <h3>Results</h3> We reviewed 211 LTRs from January 2014 to August 2021. Twenty patients (9.5%) met inclusion criteria with 32 DTTs and 4 were excluded due to undetectable troughs. Median time to initial DTT was 10 (2-34) days of therapy. AKI occurred within a week prior to 84% of DTT, with a median of 3 days to elevated trough. Median time to DTT clearance (undetectable level or resumption of therapy) was 2 days. Therapy was discontinued in 10% of patients due to concern for nephrotoxicity (Table 1). <h3>Conclusion</h3> iTOBI therapy may cause systemic drug levels in the early post-transplant phase. Given known association of systemic tobramycin with nephrotoxicity, particularly in the presence of nephrotoxic medications, iTOBI trough surveillance may be prudent to guide therapy. Rapid DTT clearance may render repeat levels unnecessary. Larger studies are needed to assess the renal risk, timing of iTOBI accumulation in LTRs and thresholds for serum monitoring.

Anaphylactic reaction to mannitol as excipient

Introduction ( contexte de la recherche ) Perioperative anaphylaxis requires thorough explorations. When no active substance is detected as responsible for the anaphylaxis, investigations of potential responsible excipients should be performed. We describe the case of a patient who experienced a perioperative anaphylactic reaction attributed to mannitol. 0. A 15 year-old teenager was admitted to a tertiary care hospital for extraction of her wisdom teeth under general anaesthesia (GA). At the end of the surgery, she suffered from tachycardia, hypotension, bronchospasm and urticaria. She was immediately treated with epinephrine and transferred to the intensive care unit (ICU). One hour after the reaction, her tryptase level was 15.5 μg/L, and it was 14 μg/L two hours after. Her basal level of tryptase was 3.6 μg/L. The patient was discharged from the ICU 24 h later (total recovery) and was further referred to the allergy team for investigations. Drugs used during the GA were Rocuronium, Sufentanyl, Remifentanyl, Dexamethasone, Ketoprofen and Paracetamol. Skin pricks tests (SPT) and intradermal testing (IDT) at the recommended concentrations were performed for all drugs except for paracetamol (given orally in the ICU and well tolerated after the reaction). Skin testing was negative for all drugs, as were oral challenges (OC) for dexamethasone and ketoprofen. Serum specific IgE dosages for quaternary ammonium, latex, chlorhexidine were also negative. In absence of an obvious culprit, SPT and IDT for the intravenous form of paracetamol (containing mannitol) were performed. The SPT exhibited negative result, but the IDT of the pure dilution 10 mg/ml and the 1/10 (1 mg/ml) dilution were positive. It was then decided to perform SPT and IDT for mannitol 10% and 20%, at 1/100 and 1/10 dilutions, which turned out positive (but negative on 2 controls). An OC with an effervescent tablet of paracetamol (2000 mg) containing mannitol was realised and was negative. Oral mannitol was well tolerated. Our clinical case raises awareness about the possible allergy to mannitol when administered through the intravenous route even though the oral route is well tolerated.

Analysis of Adverse Events and Intravenous Iron Infusion Formulations in Adults With and Without Prior Infusion Reactions

Although iron deficiency is common, it remains unclear which iron repletion strategy is associated with the lowest rate of infusion-related adverse events, and how patients with history of infusion reaction should be managed. To evaluate rates of infusion reactions among 4 commonly used intravenous iron repletion strategies and determine how readministration was managed in patients with history of reaction. This cohort study included all patients receiving intravenous iron infusion from January 1, 2015, to September 7, 2021, at 6 centers in Portland, Oregon. Participants included a total of 12 237 patients with iron deficiency, not restricted by etiology. Statistical analysis was performed from September to October 2021. Type of intravenous iron formulation and concurrent administration of diphenhydramine, epinephrine, famotidine, and/or hydrocortisone, used as surrogate maker of infusion reaction. Incidence of adverse events, including severe events requiring epinephrine, stratified by type of iron formulation, and in patients who received premedication or with history of infusion-related reaction receiving subsequent doses. Among 35 737 unique iron infusions (12 237 patients [9480 (77.5%) women; 717 (5.9%) Black; 10 250 (83.7%) White; mean (SD) age of 51 (20) years]), comprising 22 309 iron sucrose doses, 9067 iron dextran total doses (1771 preceded by test dose, 56 test doses alone), 3147 ferumoxytol doses, and 1214 ferric carboxymaltose doses, incidence of adverse events was 3.9% (n = 1389; 95% CI, 3.7%-4.1%). Rate of infusion events differed among iron formulations: 4.3% (n = 970; 95% CI, 4.1%-4.6%) iron sucrose, 3.8% (n = 345, 95% CI: 3.4%-4.2%) iron dextran (test and full doses or test dose alone), 1.8% (n = 57; 95% CI, 1.4%-2.3%) ferumoxytol, and 1.4% (n = 17, 95% CI, 0.8%-2.3%) ferric carboxymaltose (P < .001). Severe adverse events were exceedingly rare with only 2 documented epinephrine administrations, both associated with iron dextran. Incidence of adverse events among those who received premedication was 23-fold higher compared with those who did not (38.6% vs 1.7%, χ21 = 7324.8; P < .001). Among 873 patients with history of infusion reaction who underwent readministration, the majority received the same formulation, which was associated with significantly higher reaction rate particularly if premedication was administered (68% [95% CI, 64%-72%] vs 32% [95% CI, 26%-41%], respectively), compared with those who received an alternate formulation (21% [95% CI, 11%-35%] vs 5% [95% CI, 2%-12%], respectively) (P < .001). These data, and the preponderance of published evidence, suggest that intravenous iron is generally well tolerated with exceedingly low risk of severe reaction, use of premedication and test doses are unnecessary, and that optimal prevention and management of infusion-related reactions warrant further study.

Risks for Anaphylaxis With Intravenous Iron Formulations : A Retrospective Cohort Study.

The risks for anaphylaxis among intravenous (IV) iron products currently in use have not been assessed. To compare risks for anaphylaxis among 5 IV iron products that are used frequently. Retrospective cohort study using a target trial emulation framework. Medicare fee-for-service data with Part D coverage between July 2013 and December 2018. Older adults receiving their first administration of IV iron. The primary outcome was the occurrence of anaphylaxis within 1 day of IV iron administration, ascertained using a validated case definition. Analysis was adjusted for 40 baseline covariates using inverse probability of treatment weighting. The adjusted incidence rates (IRs) for anaphylaxis per 10000 first administrations and odds ratios (ORs) were computed. The adjusted IRs for anaphylaxis per 10000 first administrations were 9.8 cases (95% CI, 6.2 to 15.3 cases) for iron dextran, 4.0 cases (CI, 2.5 to 6.6 cases) for ferumoxytol, 1.5 cases (CI, 0.3 to 6.6 cases) for ferric gluconate, 1.2 cases (CI, 0.6 to 2.5 cases) for iron sucrose, and 0.8 cases (CI, 0.3 to 2.6 cases) for ferric carboxymaltose. Using iron sucrose as the referent category, the adjusted ORs for anaphylaxis were 8.3 (CI, 3.5 to 19.8) for iron dextran and 3.4 (CI, 1.4 to 8.3) for ferumoxytol. When cohort entry was restricted to the period after withdrawal of high-molecular-weight iron dextran from the U.S. market in 2014, the risk for anaphylaxis associated with low-molecular-weight iron dextran (OR, 8.4 [CI, 2.8 to 24.7]) did not change appreciably. Anaphylactic reactions requiring hospitalizations were observed only among patients using iron dextran or ferumoxytol. Generalizability to non-Medicare populations. The rates of anaphylaxis were very low with all IV iron products but were 3- to 8-fold greater for iron dextran and ferumoxytol than for iron sucrose. None.

Peri-lymphatic Hypopigmentation Following Intralesional Triamcinolone: An Unusual Case Presentation

Corticosteroids are one of the most common drugs to be used and abused in the field of medicine and surgery. It can be used as topical, oral, intravenous, intra-articular and intralesional forms. Intralesional route of administration have the advantage of achieving high concentration of drug locally with minimal systemic absorption and side effects. However adverse effects like local atrophy, ulceration, infections etc. can occur. We report a case of 20-year-old male, who presented with linear hypopigmentation following intralesional steroids which is a rarer side effect and has been highlighted in this case report.

Guideline for the treatment of chronic lymphocytic leukaemia

Guideline for the treatment of chronic lymphocytic leukaemia

Double-blind, placebo-controlled evaluation of biorest liposomal alendronate in diabetic patients undergoing PCI: The BLADE-PCI trial

Diabetes mellitus (DM) is an important predictor of neointimal hyperplasia (NIH) and adverse clinical outcomes after percutaneous coronary intervention (PCI). LABR-312, a novel intravenous formulation of liposomal alendronate, has been shown in animal models to decrease NIH at vascular injury sites and around stent struts. The aim of the Biorest Liposomal Alendronate Administration for Diabetic Patients Undergoing Drug-Eluting Stent Percutaneous Coronary Intervention trial was to assess the safety, effectiveness, and dose response of LABR-312 administered intravenously at the time of PCI withDES in reducing NIH as measured by optical coherence tomography postprocedure in patients with DM. Patients with DM were randomized to a bolus infusion of LABR-312 vs placebo at the time of PCI. Dose escalation of LABR-312 in the study arm was given: 0.01 mg, 0.03 mg, and 0.08 mg. The primary endpoint was the in-stent %NIH volume at 9 months as measured by optical coherence tomography. From September 2016 to December 2017, 271 patients with DM undergoing PCI were enrolled; 136 patients were randomized to LABR-312 infusion and 135 patients were randomized to placebo. At 9-month follow-up, no difference was seen in the primary endpoint of %NIH between LABR-312 and placebo (13.3% ± 9.2 vs 14.6% ± 8.5, P=.35). No differences were present with the varying LABR-312 doses. Clinical outcomes at 9 months were similar between groups. Among patients with DM undergoing PCI with drug-eluting stents, a bolus of LABR-312 injected systematically at the time of intervention did not result in a lower rate in-stent %NIH volume at 9-month follow-up.

Glioblastoma multiforme targeted delivery of docetaxel using bevacizumab-modified nanostructured lipid carriers impair in vitro cell growth and in vivo tumor progression

Glioblastoma multiforme (GBM) is the most common malignant brain cancer, characterized by high invasiveness and poor prognosis. Docetaxel (DTX) is a chemotherapeutic drug with promising anti-tumor properties. However, conventional intravenous formulations exhibit side effects of systemic biodistribution and low brain bioavailability, limiting their clinical use. The current work aimed to evaluate the effect of DTX-loaded nanostructured lipid carriers (NLC) functionalized with bevacizumab (BVZ-NLC-DTX) against GBM using in vitro and in vivo models. The NLC was obtained by the fusion-emulsification method followed by sonication, with narrow size distribution, negative zeta potential, and low polydispersity index. NLC showed DTX entrapment efficiency above 90%. BVZ coupling efficiency was 62% and BVZ integrity after functionalization was confirmed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Calorimetry studies confirmed thermal stability and molecular dispersion of DTX in the lipid matrix. NLC showed a sustained DTX release over 84 h. In vitro anti-tumor assays shown that BVZ-NLC-DTX selectively increased the cytotoxic of DTX in cells overexpressing VEGF (U87MG and A172), but not in peripheral blood mononuclear cells (PMBCs), promoting cell death by apoptosis. BVZ functionalization did not impair cellular uptake. An in vivo orthotopic rat model demonstrated that free-DTX was not capable of reducing tumor growth whereas BVZ-NLC-DTX reduced up to 70% tumor volume after 15-days of treatment. Therefore, this study contributes to understanding new nanotechnology-based vehicles capable of reaching the brain more efficiently and repurposing the use of anti-cancer drugs in GBM treatment.

A PBPK Model of Ternary Cyclodextrin Complex of ST-246 Was Built to Achieve a Reasonable IV Infusion Regimen for the Treatment of Human Severe Smallpox.

ST-246 is an oral drug against pathogenic orthopoxvirus infections. An intravenous formulation is required for some critical patients. A ternary complex of ST-246/meglumine/hydroxypropyl-β-cyclodextrin with well-improved solubility was successfully developed in our institute. The aim of this study was to achieve a reasonable intravenous infusion regimen of this novel formulation by a robust PBPK model based on preclinical pharmacokinetic studies. The pharmacokinetics of ST-246 after intravenous injection at different doses in rats, dogs, and monkeys were conducted to obtain clearances. The clearance of humans was generated by using the allometric scaling approach. Tissue distribution of ST-246 was conducted in rats to obtain tissue partition coefficients (K p ). The PBPK model of the rat was first built using in vivo clearance and K p combined with in vitro physicochemical properties, unbound fraction, and cyclodextrin effect parameters of ST-246. Then the PBPK model was transferred to a dog and monkey and validated simultaneously. Finally, pharmacokinetic profiles after IV infusion at different dosages utilizing the human PBPK model were compared to the observed oral PK profile of ST-246 at therapeutic dosage (600 mg). The mechanistic PBPK model described the animal PK behaviors of ST-246 via intravenous injection and infusion with fold errors within 1.2. It appeared that 6h-IV infusion at 5 mg/kg BID produced similar Cmax and AUC as oral administration at 600 mg. A PBPK model of ST-246 was built to achieve a reasonable regimen of IV infusion for the treatment of severe smallpox, which will facilitate the clinical translation of this novel formulation.

Factors affecting voriconazole concentration to dose ratio changes according to route of administration

BackgroundVoriconazole (VRCZ) is commonly used as oral and intravenous (IV) formulations. Few studies have comprehensively analysed the variation factors for the weight-corrected VRCZ serum concentration/dose (C/D) ratio based on the...

Pharmacokinetics and Safety of the Nucleoside Analog Antiviral Drug Galidesivir Administered to Healthy Adult Subjects.

Galidesivir (BCX4430) is an adenosine nucleoside analog broadly active in cell culture against multiple RNA virus families, and active in animal models of viral diseases associated with Ebola, Marburg, yellow fever, Zika, and Rift Valley fever. Current studies demonstrated the pharmacokinetics and safety of the first-in-human evaluations of galidesivir as intramuscular (IM) and intravenous (IV) formulations. Two double-blind, placebo-controlled, dose-ranging studies were conducted enrolling 126 healthy subjects. Study 1 evaluated the safety and tolerability of IM galidesivir over single day dosing, single day dosing ± lidocaine, and 7-day dosing with lidocaine. Study 2 evaluated the safety and tolerability of single ascending doses of IV galidesivir. Safety and tolerability were evaluated via clinical and laboratory monitoring. The plasma concentration-time profile of galidesivir at doses 0.3 to 10mg/kg IM was characterized by rapid absorption, an initial rapid distribution and clearance phase, and an extended terminal elimination phase. The initial rapid distribution and extended terminal elimination were mimicked in the profile of galidesivir at doses 5 to 20mg/kg IV. No fatal events or related serious adverse events were reported. No clinically significant dose-related trends in laboratory values, vital signs, electrocardiograms, or echocardiograms were noted. Galidesivir was safe and generally well tolerated.

Vitamin C-induced Hemolysis: Meta-summary and Review of Literature.

ABSTRACTVitamin C is increasingly being used, and even high doses are considered safe. However, complications including hemolysis have been reported. We performed a systematic search from PubMed, Science Direct, and Google Scholar databases from January 1975 till July 31, 2021. Search terms used were “Vitamin C” OR “ascorbic acid” AND “haemolysis” OR “haemolytic anaemia.” Data regarding patient's demographics, outcomes and dose, duration, and form of vitamin C were extracted. Fourteen case reports matched the selected criteria, with age ranging from 3 weeks to 75 years with 78.6% being males. About 71.4% were diagnosed to have glucose-6-phosphate dehydrogenase (G6PD) deficiency but previous hemolysis was reported in only two patients, and 57.1% were prescribed vitamin C for nutritional supplementation. The dose ranged from 1 to 200 g/day with 57.1% receiving intravenous formulations. Half of these patients developed other complications including acute kidney injury (AKI), disseminated intravascular coagulation, oxalosis, and methemoglobinemia. About 78.6% developed complications within 3 days of starting vitamin C and only one death was reported. Vitamin C is generally a safe drug but it should be prescribed with caution and only when benefits outweigh the risks. Physicians should be aware of potential complications like severe hemolysis and AKI, especially when using high doses and in G6PD deficiency.How to cite this articleJuneja D, Jain R, Nasa P. Vitamin C-induced Hemolysis: Meta-summary and Review of Literature. Indian J Crit Care Med 2022;26(2):224–227.

Decrease of voriconazole trough levels during therapy with enteral nutrition: a case report

BackgroundVoriconazole (VRCZ) is the first-line therapy for chronic pulmonary aspergillosis and is available in both intravenous and oral formulations. The bioavailability of the oral form is estimated to be over 90% in healthy volunteers. Some drugs are reported to interact with enteral nutrition (EN), but there are few reports about the trough levels of VRCZ during EN therapy. Here, we describe changes in the VRCZ trough levels in a patient receiving continuous EN therapy.Case presentationThe patient was a 58-year-old man with esophageal cancer and a history of partial pulmonary resection due to aspergilloma. He was taking oral VRCZ tablets and his VRCZ trough level was about 2 μg/mL before esophageal cancer surgery. Following esophagectomy, VRCZ was restarted on postoperative day 16. Crushed VRCZ tablets were administered via a jejunostomy tube because of swallowing difficulty. He was also receiving EN, which was interrupted only during the administration of VRCZ. When we checked his VRCZ level 5 days after restarting VRCZ, the trough level was 0.80 μg/mL. After increasing the VRCZ dose, reducing EN, and changing the administration route from jejunostomy tube to oral, his trough level increased to 1.87 μg/mL.ConclusionsA decrease in the VRCZ trough level was observed when VRCZ was administered via a jejunostomy tube while the patient was receiving continuous EN. Careful monitoring of VRCZ levels is needed in such cases.

Efgartigimod: First Approval.

Efgartigimod (efgartigimod alfa-fcab, Vyvgart™) is a first-in-class neonatal Fc receptor antagonist being developed by argenx for the treatment of autoimmune diseases including myasthenia gravis. In December 2021, intravenous efgartigimod received its first approval in the USA for the treatment of generalized myasthenia gravis in adults who are anti-acetylcholine receptor (AChR) antibody positive. Intravenous efgartigimod has also been evaluated for generalized myasthenia gravis in various other countries, with the agent subsequently approved in Japan in January 2022 for generalized myasthenia gravis patients regardless of antibody status and in preregistration stage in the EU. Several clinical studies of intravenous and subcutaneous formulation of efgartigimod are also being investigated for other autoimmune diseases including bullous pemphigoid, chronic inflammatory demyelinating polyradiculoneuropathy, immune thrombocytopenia, autoimmune myositis and pemphigus. This article summarizes the milestones in the development of efgartigimod leading to this first approval for generalized myasthenia gravis.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40265-022-01678-3.

Safety and Efficacy of Subcutaneous Rituximab in Previously Untreated Patients with CD20+ Diffuse Large B-Cell Lymphoma or Follicular Lymphoma: Results from an Italian Phase IIIb Study.

Subcutaneous (SC) rituximab may be beneficial in terms of convenience and tolerability, with potentially fewer and less severe administration-related reactions (ARRs) compared to the intravenous (IV) form. This report presents the results of a phase IIIb study conducted in Italy. The study included adult patients with CD20+ DLBCL or FL having received at least one full dose of IV RTX 375 mg/m2 during induction or maintenance. Patients on induction received ≥4 cycles of RTX SC 1400 mg plus standard chemotherapy and FL patients on maintenance received ≥6 cycles of RTX SC. Overall, 159 patients (73 DLBCL, 86 FL) were enrolled: 103 (54 DLBCL, 49 FL) completed induction and 42 patients with FL completed 12 maintenance cycles. ARRs were reported in 10 patients (6.3%), 3 (4.2%) with DLBCL and 7 (8.1%) with FL, all of mild severity, and resolved without dose delay/discontinuation. Treatment-emergent adverse events (TEAEs) and serious adverse events occurred in 41 (25.9%) and 14 patients (8.9%), respectively. Two patients with DLBCL had fatal events: Klebsiella infection (related to rituximab) and septic shock (related to chemotherapy). Neutropenia (14 patients, 8.9%) was the most common treatment-related TEAE. Two patients with DLBCL (2.8%) and 6 with FL (7.0%) discontinued rituximab due to TEAEs. 65.2% and 69.7% of patients with DLBCL and 67.9% and 73.6% of patients with FL had complete response (CR) and CR unconfirmed, respectively. The median time to events (EFS, PFS, and OS) was not estimable due to the low rate of events. At a median follow-up of 29.5 and 47.8 months in patients with DLBCL and FL, respectively, EFS, PFS, and OS were 70.8%, 70.8%, and 80.6% in patients with DLBCL and 77.9%, 77.9%, and 95.3% in patients with FL, respectively. The switch from IV to SC rituximab in patients with DLBCL and FL was associated with low risk of ARRs and satisfactory response in both groups. This trial was registered with NCT01987505.