Crushed Tablets Research Articles

The Use of Liquid Tranexamic Acid for Pediatric Patients with Bleeding Disorders

Introduction: Antifibrinolytics are widely used in the prevention and treatment of bleeding, they can be used as a monotherapy for mild bleeding/minor procedures and as adjunctive therapy in combination with other hemostatic agents for moderate/severe bleeding and major procedures. Tranexamic acid (TXA) and aminocaproic acid (6-ACA) are the only agents licensed for at-home administration. TXA is available in tablet and intravenous dosage forms, while 6-ACA is available in tablet, oral solution, and intravenous dosage forms. 6-ACA oral solution (AAOS) is the only commercially-available option for those who cannot swallow tablets, however, barriers to its use include insurance denial and high cost/copayment. TXA tablets can be crushed and mixed into an aqueous solution and is stable for up to 31 days3, thus crushing a tablet into water for immediate use should not affect its efficacy. We report our experience using crushed tranexamic acid tablets in water (cTXAw) in young patients with bleeding disorders. Methods: In this single-center, IRB-exempt retrospective chart review at Mayo Clinic Rochester, MN eligible patients were less than 10 years of age and who had been prescribed any formulation of TXA from December 2018 to July 2022. For patients prescribed cTXAw, data collection included age, sex, TXA dose, indication for use, clinical outcome, and side effects attributed to cTXAw. Bleeding outcomes were defined as major, clinically relevant non-major, and minor bleeding according to ISTH criteria. To create the cTXAw, a TXA 650 mg tablet was crushed and dissolved in 10 ml water resulting in a 65 mg/ml solution. Once dissolved, patients/caregivers were instructed to immediately draw up and administer the appropriate weight-based dose and then discard the excess cTXAw. The procedure was repeated with each dose. Results: Our electronic medical record search identified 666 patients who received TXA of whom 32 were prescribed cTXAw, of whom 7 were prescribed tranexamic acid to be used on as needed basis and it was not used. The remaining 25 had documented use of the medication (table 1); median age was 3 years ( 10 days - 9 years ) and 19 (76%) were male. Bleeding disorders included: von Willebrand disease (52%), hemophilia (20%), Factor VII deficiency (12%), inherited platelet disorders (8%), and immune thrombocytopenia (8%). Twenty-five patients received 32 courses of cTXAw for 21 procedures and 11 bleeding events for a mean duration of 6 days (1 - 14 days). Most patients received 25 mg/kg (28/32, 88%), the rest received 10 mg/kg (4/32, 12%). TXA was used as monotherapy in 24 occasions (75%; 15 procedures and 9 bleeding events) and as adjunctive therapy in 8 (25%; 6 procedures and 2 bleeding events); 6 received factor replacement and 2 received DDAVP. Type of factor and indication included: FVIII for circumcision (n=2), VWF concentrate for tonsillectomy and adenoidectomy (n=2), FVIII for oral bleeding (n=1), VWF concentrate for hypospadias repair (n=1). None of the 21 procedures (5 circumcision, 5 dental procedures, 5 myringotomy tube placement, 3 tonsillectomy and adenoidectomy, 2 endoscopies, 1 hypospadias repair) were complicated by bleeding as defined by ISTH criteria. Out of 11 bleeding events (4 oral bleeding, 4 frequent epistaxis, 2 hematomas, 1 laceration), 9 had effective hemostasis with the use of cTXAw (82%), one had no response (9%; used for recurrent epistaxis in addition to DDAVP), one had no reported outcome (9%). None of the patients reported side effects from using cTXAw. Using tranexamic acid represents a significant cost savings to families and the health care system. The median age of patients in this study was 3 years of age, and the average 3-year-old weighs 14 kg4. Average wholesale price (AWP) for TXA is $5.21 per 650 mg tablet, thus a course of cTXAw at 25 mg/kg/dose (350 mg) every 6 hours for 6 days costs AWP $125. A similar regimen using 6-ACA is 50 mg/kg/dose (700 mg) every 6 hours for 6 days4. The AWP for 6-ACA is $13.47 per mL of the 250 mg/mL oral solution. For the same 3-year-old, a course of therapy of 6-ACA oral solution costs $905. Of our 13 patients who had also been prescribed AAOS before cTXAw, 8 (61.5%) patients were documented as unable to receive the AAOS due to either prohibitive cost or insurance denial. Conclusions: Crushed TXA tablets in water (cTXAw) appears to be effective, safe, and cost-effective for young patients with bleeding disorders. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Efficacy of Crushed Delayed-Release Posaconazole Tablets in Rhino-Orbito-Cerebral Mucormycosis.

A significant proportion of patients with Rhino-orbito-cerebral mucormycosis (ROCM) develop oroantral fistulas. Due to the unclear efficacy of crushed delayed-release posaconazole tablets (DRPT) via nasogastric tube in this group of patients, clinicians often use inferior alternatives like posaconazole suspension. In this prospective study, we report good plasma concentrations (median, 2,639 ng/mL; interquartile range [IQR], 1,690 to 3,575 ng/mL; and range, 1,004 to 4,835ng/mL) and complete cure and survival at 3 and 6 months in 19 such patients.

Relative bioavailability of crushed tebipenem administered through a nasogastric tube with and without enteral feeding.

Tebipenem pivoxil hydrobromide is an orally bioavailable carbapenem prodrug of the active agent tebipenem with broad-spectrum activity against drug-resistant Enterobacterales. This study aimed to evaluate the relative bioavailability of crushed tebipenem tablets administered via nasogastric tube (NGT) with or without concomitant enteral feeds. This Phase 1, open label study randomized 12 healthy subjects to receive a crushed tebipenem tablet via NGT (n = 6) or via NGT with concomitant Osmolite® enteral feeds (n = 6) on Study Day 1, followed by oral administration of tebipenem whole tablet (reference formulation) on Study Day 2. Tebipenem plasma concentrations were measured by LC with mass spectrometry. Bioequivalence was determined using pharmacokinetic parameters derived through non-compartmental analyses. Mean ± SD tebipenem pharmacokinetic parameters in plasma for subjects who received a crushed tablet via NGT (relative to whole tablet) and a crushed tablet with enteral feeds (relative to whole tablet) were as follows: maximum total plasma concentration (Cmax), 11.1 ± 3.9 (12 ± 3.4) and 10.2 ± 1.9 (10 ± 4) mg/L; area under the curve (AUC0-8), 17.5 ± 3.5 (17.9 ± 2.3) and 15 ± 4.3 (13.4 ± 5.3) mg•h/L. Using the 90% CI criteria, Cmaxand AUC0-8 values for tebipenem were found to be bioequivalent following alternative methods of administration compared with oral dosing of the whole tablet. The three methods of administration were well tolerated. Results demonstrate that tebipenem maintained bioequivalence when crushed and administered via NGT with and without accompanying enteral feeds in healthy subjects, relative to whole tablet oral administration. Data therefore support alternative methods of tebipenem administration depending on patient condition.

Basis to Aid Crisis: Favipiravir Oral Solution for Hospital Compounding During COVID-19 Drug Shortage

The COVID-19 pandemic outbreak has been overwhelming the healthcare system worldwide. A rapidly growing number of younger pediatric patients in Thailand necessitated the formulation of favipiravir, the most locally accessible antiviral agent against COVID-19, into a child-friendly dosage form as a safer alternative to a dispersion of crushed tablets in simple syrup. While striving to quickly develop a liquid formulation that is feasible for any local hospital production units, an oral solution was chosen due to its simplicity. Despite the large dose and poor aqueous solubility of favipiravir, a combination of pH control and use of poloxamer as a solubilizing agent has enabled us to streamline the manufacturing process of a 200 mg/15 mL oral solution for hospital compounding. To ensure its efficacy and safety, a specification for quality control was also established in accordance with the ICH quality guidelines and USP. The finished product stability was subsequently demonstrated under the conditions of 5°C ± 3°C, 25°C ± 2°C/75% RH ± 5% RH, 30°C ± 2°C/75% RH ± 5% RH, and 40°C ± 2°C/75% RH ± 5% RH. The results indicated that our formulation can be stored at 30°C ± 2°C/75% RH for 30 days, which will very well serve the need to allow drug distribution and patient use during the crisis, while the shelf-life can be extended to 60 days when stored at 5°C ± 3°C. Thus, accessibility to an essential medical treatment has been successfully enhanced for pediatric patients in Thailand and neighboring countries during the COVID-19 outbreak.

Results from in vitro and in vivo studies evaluating the bioavailability, effects of food, and administration as crushed tablet suspension on vericiguat pharmacokinetics

ObjectiveThis article describes in vitro and in vivo studies that aimed to further characterize the biopharmaceutical properties and pharmacokinetic (PK) profile of vericiguat and to guide dosing recommendations.MethodsFive open-label, phase I studies characterized the biopharmaceutical aspects of vericiguat, including absolute bioavailability, bioavailabilities of different formulations, dose proportionality, and food effect. Area under the curve (AUC) and maximum plasma concentrations (Cmax), determined by a noncompartmental analysis, were compared by analysis of variance, and a mixed-effects power model was used to assess dose proportionality. The effect of food on the dissolution of vericiguat was evaluated in vitro using media simulating the gastrointestinal tract under fed and fasted conditions. In vitro dissolution of intact vs crushed vericiguat tablet was assessed in quality control medium (HCl at pH 2), acetate buffer at pH 4.5, and phosphate buffer at pH 6.8.ResultsDissolution of vericiguat increased under fed conditions. In healthy subjects, exposure (AUC and Cmax) increased ~ 40% with food vs fasted state (10 mg intact tablet) confirming a food effect on vericiguat bioavailability. Interindividual variability in exposure decreased ~ 20%, irrespective of meal type. Absolute bioavailability of vericiguat 10 mg (intact tablets, fed) was 93%. Vericiguat 2.5–10 mg demonstrated dose proportionality (intact tablets, fed) in healthy subjects. Dissolution studies showed no differences between the formulations, and this was confirmed with in vivo studies.ConclusionVericiguat tablets should be administered with food and may be crushed for patients who have difficulty swallowing.Graphical

Acceptability of Prednisolone in an Open-Label Randomised Cross-Over Study-Focus on Formulation in Children.

Developing acceptable medicines for children is a complicated task. Several factors must be considered, including age, physiology, texture preference, formulation, and legal framework among others. In the development of new paediatric medicines, these factors are assessed. However, for older medicines, e.g., prednisolone, acceptability is still a challenge. This study was an open-label randomised three-arm cross-over study investigating different formulations of prednisolone (crushed tablets, whole tablets, and oral solution) in paediatric patients with asthma and asthma-like symptoms. Participants were randomised into two different formulations on two consecutive days. For each formulation, the child or caregiver was asked to evaluate acceptability using a modified five-point Wong Baker Face scale. An analysis of variance (ANOVA) model was used to test for significance. For the 41 children, included mean age was 4.7 years (SD ± 3.6), and mean weight was 21 kg (SD ± 10.8). Sixty-one percent were boys. The participants were divided accordingly into three age groups: 6 to 23 months (N = 11), 2 to 5 years (N = 14), and 6–11 years (N = 16). The overall acceptability was low, with only 23 out of 71 scores rating the treatment either 1 or 2 (32%). The ANOVA test showed a significant difference in acceptability score between crushed tablets and whole tablets (p < 0.003). The mean acceptability score for the crushed tablet was the least favourable at 3.9 compared to oral solution (3.1), oro-dispersible tablet (2.8), and whole tablets (2.4). This is problematic in long-term treatment and for the youngest children who cannot swallow tablets. The improvement of age-appropriate and acceptable formulations is necessary.

Plasma Clozapine and Norclozapine After Use of Either Crushed Tablets or Suspension Compared With Tablets.

With clozapine, either crushed tablets suspended in an aqueous medium or proprietary suspension is sometimes prescribed as an alternative to tablets, but bioequivalence data are scant. We compared clozapine dose, and plasma clozapine and N -desmethylclozapine (norclozapine) concentrations after use of either tablets or crushed tablets/suspension in samples submitted for clozapine therapeutic drug monitoring, 1993 to 2017. There were 846 patients (1646 samples) given crushed tablets/suspension and 6065 patients (10,779 samples) given tablets. The median dose (mg d -1 ) was significantly higher in men (500 vs 450) and women (500 vs 400) given crushed tablets/suspension, but the median plasma clozapine and norclozapine concentrations (mg L -1 ) were significantly lower (men: 0.29 and 0.22 vs 0.39 and 0.28; women: 0.35 and 0.26 vs 0.50 and 0.32, respectively). A subgroup of 480 patients was prescribed either crushed tablets/suspension (1016 samples) or tablets (1259 samples) at different times. The median dose was again significantly higher in men (500 vs 500) and women (500 vs 450), but the median plasma clozapine and norclozapine concentrations were significantly lower (men: 0.29 and 0.22 vs 0.32 and 0.24; women: 0.30 and 0.24 vs 0.38 and 0.29, respectively). Poor adherence, sedimentation of suspension before use, and incomplete dosage are potential contributors to the lower median plasma clozapine and norclozapine concentrations observed after use of either crushed clozapine tablets or suspension as compared with tablets. Those administering crushed tablets/suspension should be aware of these factors.

Development of Advanced 3D-Printed Solid Dosage Pediatric Formulations for HIV Treatment.

The combination of lopinavir/ritonavir remains one of the first-line therapies for the initial antiretroviral regimen in pediatric HIV-infected children. However, the implementation of this recommendation has faced many challenges due to cold-chain requirements, high alcohol content, and unpalatability for ritonavir-boosted lopinavir syrup. In addition, the administration of crushed tablets has shown a detriment for the oral bioavailability of both drugs. Therefore, there is a clinical need to develop safer and better formulations adapted to children’s needs. This work has demonstrated, for the first time, the feasibility of using direct powder extrusion 3D printing to manufacture personalized pediatric HIV dosage forms based on 6 mm spherical tablets. H-bonding between drugs and excipients (hydroxypropyl methylcellulose and polyethylene glycol) resulted in the formation of amorphous solid dispersions with a zero-order sustained release profile, opposite to the commercially available formulation Kaletra, which exhibited marked drug precipitation at the intestinal pH.

Prevalence of pharmacist knowledge on beyond-use date (BUD) of various non-sterile compounding drugs in Indonesia.

Objective:In extemporaneous compounding, drugs’ stability is indicated by beyond-use date (BUD), which is different from the expiration date determined by manufacturers, hence, pharmacists are required to provide proper BUD information to patients. A recent study showed that BUD knowledge in the North Jakarta community is low, therefore, this study aims to examine the prevalence of Indonesian pharmacists’ BUD knowledge regarding various non-sterile dosage forms.Methods:This cross-sectional study involved Indonesian pharmacists’ knowledge of serving extemporaneous prescriptions. Recruitment was carried out through the purposive and snow-balling sampling method, while data were obtained by filling out a validated authors’ designed questionnaire, with total 34 questions, and collected in September 2021 and then analyzed using the chi-square test.Results:Among the 221 total respondents, 93.7% had BUD knowledge, while 12.7% responded that BUD and expiration date are similar. Regarding BUD for crushed tablets, dry syrup without preservatives, and ointment without moisture, there were 13.1%, 82.8%, and 29.4% responded rightly, respectively. Furthermore, there was no correlation between BUD knowledge and respondents’ characteristics, including health-care workplace and location, as well as gender, and age with p>0.05.Conclusion:Based on the results, the Indonesian pharmacists were considered to have inadequate BUD knowledge, specifically on crushed tablets and ointment, and this might affect drugs’ safety.

Enteral feeding tube administration with therapeutic drug monitoring of crushed posaconazole tablets and opened isavuconazonium sulfate capsules.

Isavuconazole and posaconazole are commonly used for both prophylaxis and treatment of invasive fungal infections. These agents are formulated for oral administration as a capsule and delayed release (DR) tablet or suspension, respectively. In patients unable to swallow, alternative means of administration, such as crushing posaconazole DR tablets and opening isavuconazole capsules, may be used to avoid IV administration or use of posaconazole suspension, which often produces subtherapeutic concentrations. To assess the feasibility of achieving target plasma drug concentrations with enteral feeding tube (EFT) administration of crushed posaconazole DR tablets and opened isavuconazole capsules. We retrospectively reviewed pharmacy records to identify patients receiving EFT administration of posaconazole or isavuconazole with concurrent therapeutic drug monitoring from October 2019 to June 2021. Plasma concentrations of either agent as well as clinical outcomes were documented. We identified 37 patients receiving 38 courses of EFT isavuconazole or posaconazole. The majority of patients received primary prophylaxis following lung transplantation (64.9%). Plasma concentrations upon first assessment were therapeutic in the majority of patients (posaconazole 71.5%, isavuconazole 83.3%) with a mean level of 1.61 ± 0.77 mg/L for posaconazole and 2.07 ± 1.1 mg/L for isavuconazole. Of those that were subtherapeutic on initial assessment, all but one subsequently achieved target levels upon dose titration. Standard maintenance doses were used in all isavuconazole and most posaconazole patients. Our case series demonstrates that isavuconazole and posaconazole can be administered via EFT with concurrent therapeutic drug monitoring to achieve target plasma concentrations in the majority of patients.

Alternative Routes of Administration of Clozapine.

Clozapine is the only antipsychotic with proven effectiveness in treatment-resistant schizophrenia. It is usually administered using commercially available oral tablets, but not all patients are willing or able to take medicines in this way. Orodispersible clozapine tablets are available from several manufacturers and may be useful where swallowing solid dosage forms is difficult, or as an aid to observe compliance. Liquid formulations of clozapine can be prepared extemporaneously or purchased commercially, but most preparations are suspensions (clozapine is poorly soluble) and patients may find them unpalatable. The administration of clozapine (suspension or crushed tablets) via enteral feeding tubes (predominantly nasogastric) has been reported both in medically unwell patients and in patients refusing clozapine. Enteral administration is likely to be superseded by intramuscular clozapine, which has recently been re-introduced and is being widely used in some countries. Successful use of this formulation in enforced treatment strategies has been described by several authors with good long-term outcomes when switched to oral treatment. Intramuscular clozapine has also been used in physically ill patients who are unable to take any form of enteral medication. Other methods of delivery (transdermal, nasal) are not yet commercially available, but offer promise of further treatment options for this group of seriously ill patients.

Process performance of a new liquid medication dispensing robot

ObjectivesLiquid medications provide an alternative to splitting pills and dosages by measuring an amount of liquid rather than crushing tablets or opening capsules. Special attention should also be paid to...

A systematic approach for assessing the suitability of enteral feeding tubes for the administration of controlled-release pellet formulations

Enteral nutrition plays an important role for patients who are unable to properly swallow food. In such patients, enteral feeding tubes are often used, through which food, but often also oral medications, are administered. However, this can pose the risk of tube clogging. Compared to the administration of crushed tablets, multiparticulate dosage forms are often considered easier to administer and furthermore have the advantage of enabling the administration of even controlled-release preparations. The objective of this systematic study was to identify tube- and formulation-related factors that contribute to successful administration of coated pellet formulations via a variety of commercially available feeding tube devices. The suitability of enteral feeding tubes for the administration of controlled-release pellet formulations that differed in size and type of starter core and functional coating was investigated in a stepwise approach using a novel in vitro setup. Results of the study indicate that pellet diameter and inner diameter of the feeding tube are by no means reliable parameters for estimating the tube’s suitability for pellet administration, but that many other tube and formulation-related factors and combinations thereof must be considered to ensure safe and effective drug administration via enteral feeding tubes.

Preparation and Evaluation of a Powdered Rebamipide Mouthwash as In-Hospital Formulation: Considering Dispersion before Use in Patients.

In Japan, rebamipide (RB) mouthwash (RB-MW) for oral mucositis induced by cancer chemotherapy has been prepared using in-hospital formulation. Usually, RB-MW is prepared by dispersing crushed commercial RB tablets in the dispersion medium; however, uniformity is difficult to obtain due to low solubility. The current study aims is to prepare homogenously dispersed formulations using the fine particles of crushed tablets by a method that is convenient for hospital use. Commercial RB tablets were pre-milled at different milling times as “RB-Ts”. A ground mixture was then prepared by co-grinding the RB-Ts with HPC-L or PVP K30 via a benchtop ball milling machine (MM400). The physicochemical properties of samples were evaluated for PXRD, FTIR, turbidity, particle size, and solubility. Although the milling of RB tablets decreased the crystallinity, the length of milling time did not affect them. In contrast, grinding using MM400 significantly decreased RB crystallinity; their PXRD patterns showed a halo, suggesting the amorphization of RB crystals by grinding. Although solubility and turbidity seemed to be affected by the type of polymer rather than the particle size, every ground mixture showed high dispersibility. Thus, grinding the RB-Ts with polymers appeared to be the most promising way to obtain stable dispersion as an in-hospital formulation.

Highly sensitive electrochemical determination of rutin based on the synergistic effect of 3D porous carbon and cobalt tungstate nanosheets

Rutin, a flavonoid found in fruits and vegetables, is a potential anticancer compound with strong anticancer activity. Therefore, electrochemical sensor was developed for the detection of rutin. In this study, CoWO4 nanosheets were synthesized via a hydrothermal method, and porous carbon (PC) was prepared via high-temperature pyrolysis. Successful preparation of the materials was confirmed, and characterization was performed by transmission electron microscopy, scanning electron microscopy, and X-ray photoelectron spectroscopy. A mixture of PC and CoWO4 nanosheets was used as an electrode modifier to fabricate the electrochemical sensor for the electrochemical determination of rutin. The 3D CoWO4 nanosheets exhibited high electrocatalytic activity and good stability. PC has a high surface-to-volume ratio and superior conductivity. Moreover, the hydrophobicity of PC allows large amounts of rutin to be adsorbed, thereby increasing the concentration of rutin at the electrode surface. Owing to the synergistic effect of the 3D CoWO4 nanosheets and PC, the developed electrochemical sensor was employed to quantitively determine rutin with high stability and sensitivity. The sensor showed a good linear range (5–5000 ng/mL) with a detection limit of 0.45 ng/mL. The developed sensor was successfully applied to the determination of rutin in crushed tablets and human serum samples.

Outcomes of Simulation in Resident Imaging-Guided Breast Biopsy Training.

IntroductionWe evaluate diagnostic radiology residents’ perceptions of an ultrasound-guided and stereotactic breast biopsy simulator used at an academic medical center. This simulator is low-cost and easily reproducible. We aim to understand if this simulator improves residents’ self-reported confidence in performing breast biopsy procedures on live patients.MethodsTwenty-eight diagnostic radiology residents were instructed in how to perform ultrasound-guided breast biopsies and stereotactic breast biopsies using real biopsy and imaging equipment, but with tissue models in lieu of live persons. The hands-on experience was preceded by a didactic lecture. The ultrasound-guided tissue model was created with blueberries that were inserted in tofu, and the stereotactic tissue model was created by placing crushed calcium carbonate tablets into cored eggplant. Residents were asked to fill out a survey before and after participating in the simulation, where they self-reported their confidence level at performing ultrasound-guided and stereotactic breast biopsies.ResultsTwenty-eight diagnostic radiology residents participated in the simulation. All residents completed the pre-simulation survey and of these residents, twenty-one completed the post-simulation survey. Prior to the simulation residents reported a median confidence level of 3.5 out of 10 in performing ultrasound-guided breast biopsies, and a median confidence level of 1.0 out of 10 in performing stereotactic-guided breast biopsies. After the simulation, residents reported a median confidence level of 7.0 out of 10 in performing ultrasound-guided breast biopsies, and a median confidence level of 3.0 out of 10 in performing stereotactic-guided breast biopsies. Increases in resident confidence level were statistically significant for both biopsy types (p < 0.01). ConclusionSimulated biopsies can increase the confidence of diagnostic radiology residents that are learning to perform breast biopsies before they perform real biopsies on live patients. Providing simulation training and thereby improving resident confidence may help reduce physician error and patient harm due to poor biopsy techniques.

The Pharmacokinetics of Crushed Levetiracetam Tablets Administered to Neonates.

Intravenous phenobarbital remains the first-line therapy in the management of neonatal seizures. Shortages of intravenous phenobarbital in South Africa necessitated the addition of oral levetiracetam as part of management of neonatal seizures. We evaluated the pharmacokinetics of crushed immediate-release levetiracetam tablets administered to neonates to terminate seizures. A prospective, observational study of neonates admitted with seizures to Tygerberg Hospital. Participants received crushed levetiracetam (diluted in saline) given orally or via naso-/orogastric tube. At steady-state, pharmacokinetic sampling was performed at pre-dose, 1.5, 2.5 and 4 h post-dose. Maximum concentration (Cmax), time to Cmax (Tmax), trough concentrations (Ctrough) and area under the concentration-time curve (AUC0-12) were calculated using non-compartmental analysis. Seizure termination and safety profiles were documented. Nineteen participants were grouped into three dosing ranges: (i) 5-15 mg/kg/12-hourly, (ii) 15-25 mg/kg/12-hourly and (iii) 25-35 mg/kg/12-hourly. Range 1 demonstrated AUC0-12 167.0 ± 45.6 h*μg/mL, Cmax 19.19 ± 4.12 μg/mL and Ctrough 9.99 ± 3.86 µg/mL. Range 2, AUC0-12 316.5 ± 108.4 h*μg/mL, Cmax 35.12 ± 10.54 µg/mL and Ctrough 19.25 ± 8.48 µg/mL. Range 3, AUC0-12 290.9 (range 176.14-405.59) h*μg/mL, Cmax 36.11 (range 27.58-44.64) µg/mL and Ctrough 13.03 (2.98-23.07) µg/mL. Seizures terminated in 17/19 (90%) neonates by day 3 and 19/19 (100%) by day 4 post-levetiracetam initiation. Crushed levetiracetam has comparable pharmacokinetics to historical data. No pharmacokinetic differences were observed between oral vs. naso-/orogastric administration. Crushed levetiracetam tablets can be considered for neonates in low-resource settings where intravenous and syrup access is limited. Intravenous preparations of antiepileptic medications are used in the management of neonatal seizures. Various established standard of care intravenous antiepileptic medicines are unavailable nationally and internationally due to reasons outside our control. This stock shortage included intravenous phenobarbitone which is the first-line treatment for paediatric seizures. Due to phenobarbital shortage, levetiracetam has been identified by the neonatologists at Tygerberg Hospital, Cape Town, South Africa, as a suitable treatment option due to its efficacy and safety profile. However, intravenous levetiracetam and oral syrup is not registered in South Africa. Levetiracetam tablets are being crushed, dissolved and administered to neonates. There are no data available on the absorption of crushed levetiracetam tablets administered to neonates via a nasogastric tube. This study characterized the pharmacokinetic profile of crushed levetiracetam administered to neonates. We selected neonates receiving levetiracetam from the neonatal wards at Tygerberg hospital and drew blood to analyse the levetiracetam concentrations at 4 different time points. We found that the overall exposure of crushed levetiracetam tablets were comparable to the exposures achieved in historical data of the unaltered formulations. We concluded that crushed levetiracetam tablets can be considered for neonates in low resource settings where intravenous and syrup access is limited.

Hyperbaric oxygen therapy and fluorescence angiography in arterial insufficiency secondary to injection of crushed hydromorphone

Introduction: Foreign body emboli can lead to acute arterial insufficiency. We present a case report of upper extremity arterial insufficiency in an intravenous (IV) drug user secondary to intra-arterial injection of crushed tablet particles successfully treated with hyperbaric oxygen (HBO2) therapy. Case: A 37-year-old right-hand-dominant male developed pain and swelling of the left hand after attempting to inject crushed hydromorphone tablets into his venous circulation. Angiography revealed incomplete distal filling of the proper digital arteries, princeps pollicis, and radialis indicis branches of the left hand. The patient was treated with HBO2 for acute arterial insufficiency, secondary to these findings. Fluorescence angiography was performed prior to, during and after completion of HBO2, which showed improved perfusion of the hand upon completion of serial imaging. The patient underwent subsequent partial amputation of the left second digit and removal of the thenar and third finger pads. Discussion: Much of the literature on treatment of arterial insufficiency with HBO2 are in relation to chronic problem wounds. However, there is limited data on adjunctive treatment with HBO2 for foreign body embolism. Fluorescence angiography and clinical exam were used to track tissue perfusion and progression throughout course of therapy with HBO2. Conclusion: Acute arterial insufficiency induced by foreign body embolism was successfully treated with HBO2 and provided increased tissue salvage of the patient’s hand. The use of fluorescence angiography as a secondary measure of perfusion can provide additional insight regarding qualitative tissue oxygenation and may be a viable tool to track patient progress during HBO2 treatment.

Intestinal schistosomiasis among preschool and school-aged children in a rural setting near Alexandria: initiative for elimination.

To assess the status of intestinal schistosomiasis among preschool-aged (PSAC) and school-aged children (SAC) and to compare the efficacy of praziquantel (PZQ) in both groups. The study was conducted on 400 children; 103 PSAC and 297 SAC. Diagnosis of Schistosoma mansoni was based on triplicate Kato-Katz thick smears from a single stool sample. To identify the missed cases by Kato-Katz, 120 randomly selected negative cases (38 PSAC and 82 SAC) were screened by real-time PCR. All S.mansoni-positive cases by Kato-Katz were treated by crushed PZQ tablets. Four weeks after treatment, the cure rate was assessed by Kato-Katz smears and real-time PCR. The prevalence of S.mansoni with Kato-Katz was 7.8% among PSAC and 7.4% among SAC. Most of children (63.3%) had light-intensity infection. The cure rate was 100% among PSAC by both techniques, and 91%, and 77.2% among SAC by Kato-Katz and real-time PCR, respectively. In the 120 stool samples screened by real-time PCR, S.mansoni prevalence was 25%; 15.8% and 29.3% were among PSAC and SAC respectively. Treated cases showed a lower range of Ct values than untreated cases. Two melting temperature ranges (Tm=83-87°C and 89-93°C) were recognised among uncured cases which may point to S.mansoni genetic variability. Continuous monitoring and inclusion of PSAC in schistosomiasis control programmes are crucial. Real-time PCR and other molecular tools are recommended for evaluation of the true prevalence, assessment of cure and further studies on genetic diversity.

P0341 / #1086: HYDROGENIONIC POTENTIAL OF SILDENAFIL CITRATE IN TABLETS AFTER TRITURATION AND DILUTION WITH FIVE SOLUTIONS

Aims & Objectives: Sildenafil citrate is employed for pulmonary arterial hypertension treatment in neonates and children. In Brazil, the drug is only available as tablets. The pharmaceutical derivation (trituration and dilution) is performed in order to fractionate doses and obtain a liquid presentation capable to be taken by children. Nurses and pharmacists commonly perform sildenafil citrate pharmaceutical derivation and there is lack of evidences regarding stability. The aim of this study was to verify the pH of crushed sildenafil citrate tablets after dissolution with five diluents. Methods: Experimental study developed under controlled environmental conditions. Tablets of 25 mg of sildenafil citrate, from the same manufacture and batch number, were crushed and diluted in 20 ml of each diluent (distilled water, mineral water, grape juice, apple juice and whole milk), dissolved in vortex magnetic stirrer before pH analysis (pH analyzer Kasvi, China), and measured in triplicates. Data obtained is presented according to mean and standard deviation. Results: The pH of the studied solutions were: distilled water 6.55(±0.36), mineral water 5.09(±0.11), grape juice 3.30(±0.02), apple juice 3.76(±0.02) and whole milk 6.58(±0.04). After pharmaceutical derivations the pH of sildenafil citrate in distilled water 4.88(±1.18); in mineral water 4.96(±0.66); grape juice 3.41(±0.07); apple juice 3.99(±0.16) and whole milk 6.34(±0.16). The sildenafil citrate tablets were not completely dissolve in grape juice.Conclusions: The pH of sildenafil citrate solutions presented variation from 3.41 to 6.34. The future direction of the study is this analyses of sildenafil citrate pharmacology stability in different solutions.