Digoxin Tablets Research Articles

JAMP digoxin tablets recalled due to possible incorrect dose

JAMP digoxin tablets recalled due to possible incorrect dose

Successful management of massive digoxin overdose using DIGIFab and therapeutic plasma exchange: a case report

BackgroundDespite the efficacy and safety of DIGIFab, it is relatively expensive and has limited availability. In addition, alternative interventions, such as therapeutic plasma exchange, may need to be considered in massive digoxin overdoses. Although few case reports describe its efficacy.Case presentationWe report a case of a 17-year-old white male patient brought by family members to our emergency department in Riyadh, Saudi Arabia. After intentionally ingesting 48 mg of digoxin tablets to commit suicide, the patient’s initial digoxin serum level was 8.04 ng/mL. The patient was resuscitated in the emergency department. After admission to the intensive care unit, the patient underwent therapeutic plasma exchange, because of insufficient DIGIFab doses. Afterward, the serum digoxin levels drastically decreased, and his symptoms reverted. The patient was successfully managed and discharged 7 days after admission.ConclusionDespite insufficient evidence and a limited number of case reports describing the use of extracorporeal treatment in digoxin overdose, we noted the significant impact of therapeutic plasma exchange on our patient. However, therapeutic plasma exchange’s use in routine treatment requires stronger evidence to confirm its benefits.

Severe Digoxin Toxicity in a Child Managed with Cholestyramine. A Case Report.

ABSTRACT Digoxin toxicity is a common problem in clinical practice because its therapeutic window is relatively narrow (from 0.5 to 2 ng/ml). The toxic effects occur at concentrations > 2.8 ng/ml and are mainly related to disturbances of cardiac function and of circulatory system as well as GI and CNS disturbances. We report a case of digoxin toxicity in a 2.5years old male child who accidently ingested 15 tablets of digoxin x 0.25mg. During his stay in pediatric ICU, typical symptoms of toxicity were observed. Digoxin-specific antibody (Fab) fragments have become the mainstay of treatment in severe digoxin toxicity. However, due to its high cost and limited availability, alternative measures are used to manage severe intoxications in countries like Pakistan, where Fab fragments are not available. Here we successfully treated severe digoxin intoxication with Cholestyramine.

UPLC-MS-based Method Development, Validation, and Optimization of Dissolution Using Quality by Design Approach for Low Dose Digoxin: A Novel Strategy

Background: Digoxin, a cardiac glycoside is the one of the most significant drugs of choice for the congestive heart failure treatment. As Digoxin is a BCS class IV drug, the dissolution is a critical quality attribute for its tablet formulation. Methods: Current work aims to quantify the dissolution drug release for low dosage digoxin of 0.0625mg tablets with targeted drug release of more than 80% at 60 minutes by highly sensitive, fast, and versatile UPLC-MS technique. UPLC-MS method operated by positive ionization mode with ACQUITY UPLC C18 (2.1 cm x 100 mm, 1.8 µm) column and flow rate of 0.3ml/min has been developed and validated for parameters like linearity, precision, accuracy, ruggedness, limit of detection (LOD) and limit of quantification (LOQ) as per the ICH guidelines. Results: LOD was found to be 21 ng/mL. Collision energy for digoxin was observed as 35eV for QDa mass detector along with 803.5m/z precursor ion and 651m/z daughter ion. An optimal custom experimental design was employed to optimize the final dissolution conditions. The critical dissolution factors selected for optimization were pH of dissolution media, dissolution media volume, rpm (rotations per minute). The %drug release (DR) was selected as a critical quality attribute with the desired response of drug release >80% at 60minutes. Outcomes of the design were further evaluated by statistical tools including ANOVA. The final optimized dissolution method consists of 500mL of pH 7.4 buffer with a USP apparatus of I (Basket) rotating at 120 rpm. Conclusion: In this current work, we have optimized the dissolution conditions by QbD, and developed a sensitive UPLC-MS method for quantification of digoxin, that can be used in routine quality control purposes efficiently in dissolution testing and quantification of batches of low dose digoxin tablets.

Efficacy and Safety of Fuzi Formulae on the Treatment of Heart Failure as Complementary Therapy: A Systematic Review and Meta-Analysis of High-Quality Randomized Controlled Trials

Objective Heart failure is a major public health problem worldwide nowadays. However, the morbidity, mortality, and awareness of heart failure are not satisfied as well as the status of current treatments. According to the standard treatment for chronic heart failure (CHFST), Fuzi (the seminal root of Aconitum carmichaelii Debx.) formulae are widely used as a complementary treatment for heart failure in clinical practice for a long time. We are aiming to assess the efficacy and safety of Fuzi formulae (FZF) on the treatment of heart failure according to high-quality randomized controlled trials (RCTs). Methods RCTs in PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), and Wanfang Database were searched from their inception until June 2019. In addition, the U.S. National Library of Medicine (clinicaltrials.gov) and the Chinese Clinical Trial Registry (http://www.chictr.org.cn) were also searched. We included RCTs that test the efficacy and safety of FZF for the treatment of heart failure, compared with placebo, CHFST, or placebo plus CHFST. The methodological quality of included studies were evaluated by the Cochrane Collaboration's tool for assessing risk of bias. RCTs with Cochrane risk of bias (RoB) score ≥4 were included in the analysis. The meta-analysis was conducted through RevMan 5.2 software. The GRADE approach was used to assess the quality of the evidence. Results Twelve RCTs with 1490 participants were identified. The studies investigated the efficacy and safety of FZF, such as FZF plus the CHFST vs placebo plus CHFST (n = 4), FZF plus CHFST vs CHFST (n = 6), FZF plus digoxin tablets (DT) plus CHFST vs placebo plus DT plus CHFST (n = 1), and FZF plus placebo plus CHFST vs placebo plus DT plus CHFST (n = 1). Meta-analysis indicated that FZF have additional benefits based on the CHFST in reducing plasma NT-proBNP level, MLHFQ scores, Lee's heart failure scores (LHFs), and composite cardiac events (CCEs). Meanwhile, it also improved the efficacy on TCM symptoms (TCMs), NYHA functional classification (NYHAfc), 6MWD, and LVEF. Adverse events were reported in 6 out of 12 studies without significant statistical difference. However, after assessing the strength of evidence, it was found that only the quality of evidence for CCEs was high, and the others were either moderate or low or very low. So we could not draw confirmative conclusions on its additional benefits except CCEs. Further clinical trials should be well designed to avoid the issues that were identified in this study. Conclusion The efficacy and additional benefits of FZF for CCEs were certain according to the high-quality evidence assessed through GRADE. However, the efficacy and additional benefits for the other outcomes were uncertain judging from current studies. In addition, the safety assessment has a great room for improvement. Thus, further research studies are needed to find more convincing proofs.

Analisis Kadar Digoksin Dalam Sediaan Tablet Generik Dari 4 Pabrik Dengan Metode KCKT

Digoxin tablets is an inotropic drug that can increase the strength of heart contractions in patients with heart failure. The purpose of these study was to determine the digoxin levels in the generic digoxin tablet preparations from 4 factories and compare the results of the determination with Indonesian Pharmacope 5th. edition requirement. In these study, the method used for determining digoxin tablet wa HPLC, using C18 column (4.6 mm x 150 mm ) as stationary phase, aquadest : acetonitrile (75:25) as mobile phase, 0.5 mL / min flow rate, and UV detector with 220 nm wavelength. The analytical methods were validated based on linearity, LoD and LoQ, accuracy and precision. The linearity test results from 7 variations of concentration (5, 10, 15, 20, 25, 30, and 35 ppm) with correlation coefficient (r) = 0.9973. LoD and LoQ values ​​were 0.0006 mg / L and 0.0021 mg / L, and accruracy is 101.58% and RSD value is 0.924%. From the results of study, obtained the following levels of samples A 97.12%, samples B 89.64%, samples C 92.23% and sample D 102.54%. Based on the results of these study, 3 out of 4 samples were eligible and the last not eligible with Indonesian Pharmacope 5th edition, which contained not less than 90.0% digoxin and not more than 105.0% of the amount stated on the label.

Suicide tree poisoning

Poisoning accounts to 0.33-7.6% paediatric emergency admissions, which are accidental or unintentional. Yellow oleander, an ornamental plant with a scientific name “Thevetia peruviana”. All the parts of the tree are poisonous hence, known as “Suicide Tree”. Trees are easily accessible and swallowing of seeds which are the most toxic, is the preferred mode of intentional poisoning in South India. Ingestion of one seed is equivalent to 100 digoxin tablets. The phytotoxins of the plant can cause local gastric irritation and severe cardiotoxic manifested as arrhythmias, conduction defects which if left untreated is fatal. Management includes gastric decontamination, specific antidotes anti-digoxin Fab and Fructose 1,6 diphosphate administration, cardioversion and cardiovascular supportive care. Here, authors report an adolescent female presenting with sinus bradycardia following intentional consumption of the yellow oleander seeds.

Taking the Wrong Medication of Digoxin Tablets

Introduction: Although cardiac glycosides toxicity is common in patients taking these kinds of drugs, poisoning occurs rarely in healthy individuals. This case report describes a one-month duration of mistaken consumption of digoxin tablets in a patient that referred to the hospital with gastrointestinal poisoning manifestations. Case Presentation: The case was a 75-year-old female with a history of hypertension, hyperthyroidism, and digestive problems with common symptoms of gastrointestinal toxicity, nausea, and vomiting; mild digoxin toxicity was found rather than a simple gastrointestinal poisoning based on further investigations. Conclusions: Careful examination and EKG evaluation are essential to exclude drug toxicity in all patients referring to the hospital with gastrointestinal symptoms.

Burns Cardiomyopathy in a Nigerian Child

DCM following thermal injury is rare, it has been reported in nearly 7% of children who sustained more than 70% burn injuries. The cardiomyopathy following burns often presents weeks to months after the injury.The cause is unknown although inflammatory mediators may play an aetiologic role. The cardiomyopathy resulting from this is reversible with appropriate medical management. To the best of the authors’ knowledge, there are no reported cases in African children hence we present an eight year boy in apparent sound state of health before the burns he suffered. He developed features of congestive cardiac failure due to onset of dilated cardiomyopathy secondary to the injuries suffered from burns. He was commenced on tablet enalapril, digoxin, multivitamins, aspirin and calcium tablets. He improved clinically, his ejection fraction gradually improved on echocardiography was discharged after six weeks on admission. His became symptom free remarkably and he resumed school. He has been stable on follow, the last ejection fraction on follow up one year after diagnosis was 56%. Key words: Burns, Cardiomyopathy, Nigeria, Child.

Tablet splitting: is it worthwhile? Analysis of drug content and weight uniformity for half tablets of 16 commonly used medications in the outpatient setting.

Tablet splitting is a well-established medical practice in clinical settings for multiple reasons, including cost savings and ease of swallowing. However, it does not necessarily result in weight-uniform half tablets. To (a) investigate the effect of tablet characteristics on weight and content uniformity of half tablets, resulting from splitting 16 commonly used medications in the outpatient setting and (b) provide recommendations for safe tablet-splitting prescribing practices. Ten random tablets from each of the selected medications were weighed and split by 5 volunteers (2 men and 3 women aged 25-44 years) using a knife. The selected medications were mirtazapine 30 mg, bromazepam 3 mg, oxcarbazepin 150 mg, sertraline 50 mg, carvedilol 25 mg, bisoprolol fumarate 10 mg, losartan 50 mg, digoxin 0.25 mg, amiodarone HCl 200 mg, metformin HCl 1,000 mg, glimepiride 4 mg, montelukast 10 mg, ibuprofen 600 mg, celecoxib 200 mg, meloxicam 15 mg, and sildenafil citrate 50 mg. The resulting half tablets were evaluated for weight and drug content uniformity in accordance with proxy United States Pharmacopeia (USP) specification (95%-105% for digoxin and 90%-110% for the other 15 drugs). Weight and drug content uniformity were assessed by comparing weight or drug content of the half tablets with one-half of the mean weight or drug content for all whole tablets in the sample. The percentages by which the weight and drug content of each whole tablet or half tablet differed from sample mean values were calculated. Other relevant physical characteristics of the 16 products were measured. A total of 52 of 320 half tablets (16.2%) and 48 of 320 half tablets (15.0%) fell outside of the proxy USP specification for weight and drug content, respectively. Bromazepam, carvedilol, bisoprolol, losartan, digoxin, and meloxicam half tablets failed the weight and content uniformity test; however, the half tablets for the rest of the medications passed the test. Mean percent weight loss after splitting was less than 1.5% for all drugs. Bromazepam, carvedilol, and digoxin showed the highest powdering loss during the tablet-splitting process. Tablet splitting could be safer and easier when drug- and patient-specific criteria have been met. Tablet size, shape, and hardness may also play a role in the decision to split a tablet or not. Tablets containing drugs with a wide therapeutic index and long half-life might be more suitable candidates for division. Dose variation exceeded a proxy USP specification for more than one-third of sampled half tablets of bromazepam, carvedilol, bisoprolol, and digoxin. Drug content variation in half tablets appeared to be attributed to weight variation due to fragment or powder loss during the splitting process.

Psicoprofilaxis Obstétrica: Actualización, definiciones y conceptos

Determination of therapeutic range and study of biopharmaceutical equivalence of two multisource Digoxin tablets of 0.25mg

The practice and clinical implications of tablet splitting in international health

ObjectiveTablet splitting is frequently performed to facilitate correct dosing, but the practice and implications in low-income settings have rarely been discussed.MethodsWe selected eight drugs, with narrow therapeutic indices or critical dosages, frequently divided in the Lao PDR (Laos). These were split, by common techniques used in Laos, by four nurses and four laypersons. The mean percentage deviation from the theoretical expected weight and weight loss of divided tablets/capsules were recorded.ResultsFive of eight study drugs failed, on splitting, to meet European Pharmacopoeia recommendations for tablet weight deviation from the expected weight of tablet/capsule halves with 10% deviating by more than 25%. There was a significant difference in splitting accuracy between nurses and laypersons (P = 0.027). Coated and unscored tablets were less accurately split than uncoated (P = 0.03 and 0.0019 for each half) and scored (0.0001 for both halves) tablets.ConclusionThese findings have potential clinical implications on treatment outcome and the development of antimicrobial resistance. Investment by drug companies in a wider range of dosage units, particularly for narrow therapeutic index and critical dosage medicines, is strongly recommended.

GW24-e2910 Research on Effects of Qishen Granule on Hemodynamics in Mini Pigs with Cardiac Functional Insufficiency and Qi-deficiency and Blood Stasis Syndrome Induced by Ameroid Constricting Ring

ObjectivesTo explore the effects of Qishen Granule, a compound Chinese herbal medicine, on hemodynamics in a mini pig model of cardiac functional insufficiency and qi-deficiency and blood stasis syndrome induced...

PP212—Bioavailability of Digoxin Tablets, Low Therapeutic Index Drug, Determined by Emit

PP212—Bioavailability of Digoxin Tablets, Low Therapeutic Index Drug, Determined by Emit

Severe suicidal digoxin toxicity managed with resin hemoperfusion: A case report

Owing to its wide and easy availability, digoxin has got a significant abuse potential and may be used for suicidal purposes. Digoxin-specific antibody (Fab) fragments have become the mainstay of therapy for severe digoxin toxicity and have significantly helped in reducing mortality. However, due to its high cost and limited availability alternative measures may need to be used to manage severe intoxications especially in countries like India, where Fab fragments are unavailable. Here, we present a case of a young female who presented to our casualty with alleged history of consumption of 17.5 mg of digoxin tablets. After admission to ICU, she developed atrioventricular blocks with hemodynamic instability which had to be managed with temporary pacemaker. Her serum digoxin levels were high (12.63 ng/ml) and in the absence of Fab fragments, resin hemoperfusion was done which drastically reduced the serum digoxin levels and reverted the symptoms.

KARIN AĞRISI İLE ACİL SERVİSE BAŞVURAN DİGOKSİN İNTOKSİYONU; OLGU SUNUMU

Digoxin is a cardiac glycoside which has a narrow therapeutic range. Findings related to digoxin toxicity is not only related to the cardiac, gastrointestinal and neurological systems, particularly in a multisystem related symptoms, it can lead to digoxin toxicity. An 82-year-old female patient was admitted our emergency service with the abdominal pain, nausea and vomiting complaints. When the patient’s medical background was queried, it was found out that she had used digoxin tablets. Low ventricular response to atrial fibrillationin in the patient's ECG, and due to high levels of serum digoxin, digoxin intoxication was suspected. With the patient's symptoms and the ECG have improved after discontinuation of digoxin, it was confirmed that the diagnosis was digoxinin toxication. As a result, we suggest that emergency room physicians should consider narrow range of therapeutic drugs such as digoxin in elderly patients which have nausea, vomiting, abdominal pain.

Dissolution Profiles of Lanoxin Tablets in Media Supplemented with Soluble and Insoluble Forms of Fiber

Lanoxin (digoxin) is available as 125 µg or 250 µg tablets for oral administration used to treat heart failure and arrhythmias. The objective of this study was to develop and investigate a comparativedissolutionstudy performed on lanoxin tablets in presence of insoluble or soluble forms of fiber. This study was performed to understand possible influence of fiber (psyillium husk, wheat dextrin, or powdered cellulose)on dissolutionof lanoxin in physiological relevant temperature and pH.Dissolutiontesting was performed using a USP dissolution testing apparatus II paddlerotating at 100 r/min, in 600 mL simulated gastric fluid (pH 1.2) which was maintained at (37 +/- 0.5 °C). A floating cellulose dialysis tube was used to collect sampling fractions. Quantification was performed using a developed and validated high performance liquid chromatographic (HPLC) method. Results indicate that the presence of psyillium husk in the dissolution medium hindered digoxin release. Statistical results reveal that the release profiles of digoxin in presence of wheat dextrin or powdered cellulose did not influence drug release.

Retrospective Review of Digoxin Exposures to a Poison Control System following Recall of Digitek® Tablets

In April 2008, Digitek® digoxin tablets were recalled by the manufacturer as possibly containing double the labeled amount of drug. The recall to March 2006 involved 800 million tablets. The aim of this study was to evaluate whether there was any increase in the number of calls to a poison control system, and any increase in the severity of exposures after the recall compared with before the recall. A retrospective review of all digoxin exposures to a poison control system from March 2004 to February 2008 was conducted, with data extracted from an electronic database (California Poison Control System). Total numbers of exposures were identified. Cases with moderate, major, and death outcomes were also identified and tallied. Chi-squared analysis was performed. Prior to the recall, there were 679 digoxin exposures. 148 (22%) were listed with moderate, major, or death as outcome. After the recall, there were a total of 610 cases, 165 (27%) with moderate, severe, or death as outcome. There was a statistically significant increase in the total number of moderate, major, and death outcomes after the period of the manufacturing error compared with before (p = 0.028). During the period of manufacturing error, there was a statistically significant increase in digoxin exposures with moderate, major, or death outcomes. The recall of Digitek® tablets may have increased moderate, major, or death outcomes from digoxin exposures in a poison control system database.

Digoxin bioequivalence study: determination in human plasma by microparticle enzyme immunoassay

In this study a bioanalytical method for digoxin quantification was developed using Abbott AxSYM Digoxin II with fluorescence detection to assess the bioequivalence of two digoxin tablet formulations (Digox 0.25 mg tablet from Pharlab Ind. Ltd., Brazil as test formulation and Digoxin 0.25 mg tablet from Laboratório Glaxo SmithKline, Brazil as reference formulation). 30 healthy volunteers (both sexes) received a single oral dose of digoxin in an open, randomized, two-period crossover study with a seven half-life washout interval of at least (21 days). Plasma samples were obtained over a 288-h interval after each oral administration of digoxin. The present method utilizes microenzyme particle immunoassay technology, in which the digoxin in the sample binds to anti-digoxin-coated microparticles and after separation; digoxin-alkaline phosphatase conjugate binds to the available sites remaining. Digoxin concentrations are calculated from the fluorescent products generated as a result of substrate (4-methylumbelliferyl) passage through the matrix cell. The method was shown to be specific and sensitive with good accuracy and precision. The geometric mean and 90% confidence intervals (CI) for the Digox/Digoxin ratio were 107.62% (96.71 - 119.80%) for AUC0-t, 97.15% (80.54 - 117.19%) for AUC0-inf, and 91.23% (83.55 - 99.62%) for Cmax. Since the 90% CI for the parameters were all within the 80 - 125% interval proposed by the US Food and Drug Administration Agency, the two formulations were considered bioequivalent in terms of rate and extent of absorption.

Successful Treatment of Propafenone, Digoxin and Warfarin Overdosage with Plasma Exchange Therapy and Rifampicin

We report here the successful treatment of a 16-year-old female who ingested 20 tablets of digoxin each containing 0.25 mg (total dose ingested equivalent to 0.1 mg/kg), 32 tablets of warfarin each containing 5mg (equivalent to 3.2 mg/kg), and approximately 15 tablets of propafenone each containing 300 mg (equivalent to 90 mg/kg). The patient developed hypotension and sinus bradycardia necessitating external cardiac pacing 17 hours after drug ingestion. In addition to gastric lavage, activated charcoal, blood alkalinisation, administration of vitamin K and temporary cardiac pacing, the authors performed plasma exchange for drug removal and administered rifampicin in order to increase the metabolism of digoxin, propafenone and warfarin. The patient was discharged without any sequelae. Plasma exchange may be lifesaving in drug ingestions where there is a low volume of distribution and high plasma protein binding. Rifampicin, an inducer of cytochrome p450, may be used in intoxications for elimination of drugs with inactive metabolites.