Drug Interaction Probability Scale Research Articles

Potentially Life-Threatening Interaction between Opioids and Intrathecal Baclofen in Individuals with a Childhood-Onset Neurological Disorder: A Case Series and Review of the Literature.

Spasticity and dystonia are movement impairments that can occur in childhood-onset neurological disorders. Severely affected individuals can be treated with intrathecal baclofen (ITB). Concomitant use of ITB and opioids has been associated with central nervous system (CNS) depression. This study aims to describe the clinical management of this interaction, based on a case series and review of literature. Four individuals with childhood-onset CNS disorders (age 8-24) and CNS-depressant overdose symptoms after the concomitant use of ITB and opioids are described. The Drug Interaction Probability Scale (DIPS) was calculated to assess the cause-relationship (doubtful <2, possible 2-4, probable 5-8, and highly probable >8) of the potential drug-drug interaction. A literature review of similar previously reported cases and the possible pharmacological mechanisms of opioid-baclofen interaction is provided. After ITB and opioid co-administration, three out of four patients had decreased consciousness, and three developed respiratory depression. DIPS scores indicated a possible cause-relationship in one patient (DIPS: 4) and a probable cause-relationship in the others (DIPS: 6, 6, and 8). Discontinuation or adjusting ITB or opioid dosages resulted in clinical recovery. All patients recovered completely. In the literature, two articles describing nine unique cases were found. Although the opioid-ITB interaction is incompletely understood, concomitant use may enhance the risk of symptoms of CNS-depressant overdose, which are potentially life-threatening. If concomitant use is desirable, we strongly recommend to closely monitor these patients to detect interaction symptoms early. Awareness and monitoring of the potential opioid-ITB interaction is essential to reduce the risk of severe complications.

Potential Drug-Nutrient Interactions of 45 Vitamins, Minerals, Trace Elements, and Associated Dietary Compounds with Acetylsalicylic Acid and Warfarin-A Review of the Literature.

In cardiology, acetylsalicylic acid (ASA) and warfarin are among the most commonly used prophylactic therapies against thromboembolic events. Drug-drug interactions are generally well-known. Less known are the drug-nutrient interactions (DNIs), impeding drug absorption and altering micronutritional status. ASA and warfarin might influence the micronutritional status of patients through different mechanisms such as binding or modification of binding properties of ligands, absorption, transport, cellular use or concentration, or excretion. Our article reviews the drug-nutrient interactions that alter micronutritional status. Some of these mechanisms could be investigated with the aim to potentiate the drug effects. DNIs are seen occasionally in ASA and warfarin and could be managed through simple strategies such as risk stratification of DNIs on an individual patient basis; micronutritional status assessment as part of the medical history; extensive use of the drug-interaction probability scale to reference little-known interactions, and application of a personal, predictive, and preventive medical model using omics.

Prevalence and clinical significance of potential drug-drug interactions among lung transplant patients.

Background: Drug-drug interactions (DDIs) are a major but preventable cause of adverse drug reactions. There is insufficient information regarding DDIs in lung transplant recipients. Objective: This study aimed to determine the prevalence of potential DDIs (pDDIs) in intensive care unit (ICU) lung transplant recipients, identify the real DDIs and the most frequently implicated medications in this vulnerable population, and determine the risk factors associated with pDDIs. Methods: This retrospective cross-sectional study included lung transplant recipients from January 2018 to December 2021. Pertinent information was retrieved from medical records. All prescribed medications were screened for pDDIs using the Lexicomp® drug interaction software. According to this interaction software, pDDIs were classified as C, D, or X (C = monitor therapy, D = consider therapy modification, X = avoid combination). The Drug Interaction Probability Scale was used to determine the causation of DDIs. All statistical analysis was performed in SPSS version 26.0. Results: 114 patients were qualified for pDDI analysis, and total pDDIs were 4051. The most common type of pDDIs was category C (3323; 82.0%), followed by D (653; 16.1%) and X (75; 1.9%). Voriconazole and posaconazole were the antifungal medicine with the most genuine DDIs. Mean tacrolimus concentration/dose (Tac C/D) before or after co-therapy was considerably lower than the Tac C/D during voriconazole or posaconazole co-therapy (p < 0.001, p = 0.027). Real DDIs caused adverse drug events (ADEs) in 20 patients. Multivariable logistic regression analyses found the number of drugs per patient (OR, 1.095; 95% CI, 1.048-1.145; p < 0.001) and the Acute Physiology and Chronic Health Evaluation II (APACHE Ⅱ) score (OR, 1.097; 95% CI, 1.021-1.179; p = 0.012) as independent risk factors predicting category X pDDIs. Conclusion: This study revealed a high incidence of both potential and real DDIs in ICU lung transplant recipients. Immunosuppressive drugs administered with azole had a high risk of causing clinically significant interactions. The number of co-administered drugs and APACHE Ⅱ score were associated with an increased risk of category × drug interactions. Close monitoring of clinical and laboratory parameters is essential for ensuring successful lung transplantation and preventing adverse drug events associated with DDIs.

The Risk of Drug Interactions in Older Primary Care Patients after Hospital Discharge: The Role of Drug Reconciliation.

Drug-drug interactions (DDIs) represent an important clinical problem, particularly in older patients, due to polytherapy, comorbidity, and physiological changes in pharmacodynamic and pharmacokinetic pathways. In this study, we investigated the association between drugs prescribed after discharge from the hospital or clinic and the risk of DDIs with drugs used daily by each patient. We performed an observational, retrospective, multicenter study on the medical records of outpatients referred to general practitioners. DDIs were measured using the drug interaction probability scale. Potential drug interactions were evaluated by clinical pharmacologists (physicians) and neurologists. Collected data were analyzed using the Statistical Package for the Social Sciences. During the study, we evaluated 1772 medical records. We recorded the development of DDIs in 10.3% of patients; 11.6% of these patients required hospitalization. Logistic regression showed an association among DDIs, sex, and the number of drugs used (p = 0.023). This observational real-life study shows that the risk of DDIs is common in older patients. Physicians must pay more attention after hospital discharge, evaluating the treatment to reduce the risk of DDIs.

Reduced blood glucose levels by the combination of vadadustat in an elderly patient with chronic kidney disease who was receiving mitiglinide and sitagliptin: a case report

BackgroundOur case is the first report showing the development of hypoglycemia following the administration of vadadustat in a patient with chronic kidney disease being treated with mitiglinide and sitagliptin, possibly due to drug–drug interaction between vadadustat and sitagliptin under the administration of mitiglinide.Case presentationA 72-year-old man with type 2 diabetes mellitus had received sitagliptin 50 mg once daily and mitiglinide 10 mg three times daily over the last 3 years. He initiated vadadustat 300 mg once daily orally on day X owing to renal anemia (hemoglobin A1c: 7.4% and estimated glomerular filtration rate: 28.0 mL/min/1.73 m2). On day 23, he developed hypoglycemia with a blood glucose level of 67 mg/dL. The mean blood glucose level ± standard deviation was lower in the first 24 days of co-administration of vadadustat (before breakfast: 94 ± 14 mg/dL, before lunch: 109 ± 24 mg/dL, and before dinner: 126 ± 39 mg/dL) than in the last 2 weeks (before breakfast: 108 ± 14 mg/dL, before lunch: 122 ± 24 mg/dL, and before dinner: 158 ± 39 mg/dL). Considering the timing of the concomitant administration of vadadustat, hypoglycemia may have been caused by the drug–drug interaction between sitagliptin and vadadustat, and he discontinued treatment with vadadustat. The mean blood glucose levels improved two weeks after the discontinuation of vadadustat (before breakfast: 121 ± 25 mg/dL, before lunch: 147 ± 38 mg/dL, and before dinner: 161 ± 36 mg/dL). The drug interaction probability scale was classified as "Probable" (5 points).ConclusionsHypoglycemia was observed when sitagliptin, mitiglinide, and vadadustat were concomitantly administered, which may have resulted in a drug–drug interaction between vadadustat and sitagliptin via OAT3 inhibition in the renal tubules.

The Safety of Drug Treatment in Patients with Neuropathic Pain: Data from Ambulatory Care in a Real-Life Setting

Introduction: Drug treatment can be related to the development of adverse drug reactions (ADRs). Aim: In this paper, we evaluated ADRs in patients admitted to the Ambulatory of Pain Medicine of the University Hospital Renato Dulbecco in Catanzaro. Methods: We conducted a prospective analysis between 1 February 2021 and 20 July 2023 on patients with neuropathic pain referred to the Ambulatory of Pain Medicine of “Renato Dulbecco” University Hospital in Catanzaro (Calabria, Italy). Patients aged &gt;18 years with clinical signs of neurologic pain and a score upon completing the Douleur Neuropathique en 4 Questions (DN4) questionnaire of ≥4 were included. The association between drugs and ADR or between drugs and drug–drug-interactions (DDIs) was evaluated using Naranjo’s probability scale and Drug Interaction Probability Scale (DIPS), respectively. Results: During the study period, we analyzed 2370 patients referred to the ambulatory of pain medicine. After the evaluation of inclusion and exclusion criteria, 33.5% of patients were enrolled. All patients presented at least one comorbidity and daily used a mean of five drugs (range 3–11). Using the Naranjo score, the development of ADRs was documented in 112 patients (score 6). Using parametric and non-parametric statistical analysis, we failed to report an association between ADR and dosage or ADR and patient characteristics. Conclusion: Our results show the development of ADRs in 18% of patients with neuropathic pain. This low percentage of drug interaction could be a limitation in real life because it is probably due to the site of the study and the appropriate prescription of drugs. Therefore, it shows that it is necessary to motivate healthcare to pay attention to the prescription of drugs in poly-treated patients to reduce the risk of ADRs.

Prevalence and types of drug interactions in hospitalized pediatric patients in Mexico City

ObjectiveDrug-drug interactions may modify the therapeutic effect or the safety profile of the medicines used in pediatric populations. Although interest on potential drug interactions in these age groups has increased, information on clinically relevant drug-drug interactions is still scarce. The aim of this study was to explore the prevalence and characteristics of potential and clinically relevant drug-drug interactions among pediatric patients hospitalized in two pediatric hospitals of Mexico City. MethodA cross-sectional study was conducted on patient records in critical, oncological, burns and other non-critical services by a pediatric resident physician at both hospitals. Micromedex® was used as a source of potential drug-drug interactions data. Subsequently, each interaction's prevalence, severity and evidence level were estimated. Additionally, drug-drug interaction causality with regard to diverse clinical outcomes of hospitalized patients was determined through the Drug Interaction Probability Scale. The clinical consequences of each interaction were classified by severity. ResultsThe observed prevalence of one or more potential drug-drug interactions in hospitalized patients was 61.3% (52.2-70.4%), whilst the prevalence of real drug-drug interactions was 3.6% (0.1-7.1%). Of potential drug-drug interactions, 60.5% were considered major and only 5.1% contraindicated. These were generally more common in intensive care and burn units. The main pharmacological agents involved in potential drug-drug interactions were opioids analgesics and anti-infective and neurologic agents. Four clinically relevant drug-drug interactions required a regimen change and another prompted an extension of the patient's hospital stay. ConclusionsPotential drug-drug interactions were common in the pediatric patients studied, whereas the frequency of real drug-drug interactions was low. However, some drug-drug interactions required medical actions in addition to routine monitoring. More information is needed on real drug-drug interactions as those related to failed efficacy might be underestimated.

Signal Detection and Assessment of Herb-Drug Interactions: Saudi Food and Drug Authority Experience.

Numerous investigations on herbal medicine that have been undertaken in the past several years demonstrate the general acceptance of its safety. The Saudi Food and Drug Authority (SFDA) established the Herb-Drug Interaction (HDI) project to detect and assess potential HDIs to ensure safety. The aim is to detect safety signals and assess them based on available evidence. First, SFDA-registered herbal products (n=30) were selected and prioritized based on commonly used herbs. Second, reported potential HDIs were retrieved from the World Health Organization global database of individual case safety reports (VigiBase), AdisInsight®, and the Natural Medicines database. We excluded drugs non-registered by SFDA and labeled interactions in the product information of SFDA, the US Food and Drug Administration (FDA), and the European Medicines Agency (EMA). Finally, a comprehensive evaluation of potential HDIs was carried out using several evidence sources: literature, global cases, local cases, and other relevant documents. The Drug Interaction Probability Scale (DIPS) scale was used to assess the probability of a causal relationship between the interacting herb and drug and the event. The search yielded 566 potential signals, and 41 had published evidence and were referred for assessment. The assessment results using DIPS were: 22 possible (53.6 %), 7 probable (17%), and 12 doubtful (29.2%) interactions. The recommendation was to include probable HDIs in the product information, including turmeric-tacrolimus, etoposide-Echinacea, Ginkgo biloba-ibuprofen, green tea-warfarin, and licorice-thiazides interactions. The HDI project assessed the screening and identification of potential HDIs. The action plan of this project can be used in post-marketing activities to identify potential drug interactions.

Evaluation of drug interaction between cyclosporine and lercanidipine: a descriptive study

ObjectivesCyclosporine is an immunosuppressive drug with a high potential for drug interactions that is frequently used in renal transplant patients. The purpose of this study was to assess the change...

Use of tramadol and the risk of bleeding complications in patients on oral anticoagulants: a systematic review and meta-analysis.

This systematic review and meta-analysis aimed to determine whether tramadol intake increases the risk of bleeding in patients receiving oral anticoagulants. This systematic review was registered on PROSPERO, CRD42022327230. We searched PubMed and Embase up to 14 April 2022, and references and citations of included studies were screened. Comparative and non-comparative studies exploring bleeding complications among adult patients on oral anticoagulants and tramadol were included. Risk of bias was assessed using an adaptation of the Drug Interaction Probability Scale for case reports and case series and the Newcastle-Ottawa Scale for comparative studies. A meta-analysis was performed for the risk of serious bleeding (leading to hospitalisation or death) associated with tramadol in patients on vitamin K antagonists. A total of 17 studies were included: 1 case series, 12 case reports, 2 case-control studies and 2 cohort studies. Most of the studies described tramadol-vitamin K antagonists' concomitant use; one case-control study also assessed dabigatran and rivaroxaban; one case report involved dabigatran. Among case reports/series, a total of 33 patients had a bleeding complication while using tramadol and an oral anticoagulant. The 4 comparative studies reported an increased bleeding risk during tramadol and vitamin K antagonist intake which was statistically significant in one study; the pooled risk ratio of serious bleeding was 2.68 [95% CI: 1.45 to 4.96; p < 0.001]. This systematic review confirms an association between tramadol use and risk of bleeding in patients on vitamin K antagonists. Evidence is too limited to assess whether this risk extends to patients on direct oral anticoagulants, and further studies are needed.

Novel Method for Early Prediction of Clinically Significant Drug-Drug Interactions with a Machine Learning Algorithm Based on Risk Matrix Analysis in the NICU.

Aims: Evidence for drug–drug interactions (DDIs) that may cause age-dependent differences in the incidence and severity of adverse drug reactions (ADRs) in newborns is sparse. We aimed to develop machine learning (ML) algorithms that predict DDI presence by integrating each DDI, which is objectively evaluated with the scales in a risk matrix (probability + severity). Methods: This double-center, prospective randomized cohort study included neonates admitted to the neonatal intensive care unit in a tertiary referral hospital during the 17-month study period. Drugs were classified by the Anatomical Therapeutic Chemical (ATC) classification and assessed for potential and clinically relevant DDIs to risk analyses with the Drug Interaction Probability Scale (DIPS, causal probability) and the Lexicomp® DDI (severity) database. Results: A total of 412 neonates (median (interquartile range) gestational age of 37 (4) weeks) were included with 32,925 patient days, 131 different medications, and 11,908 medication orders. Overall, at least one potential DDI was observed in 125 (30.4%) of the patients (2.6 potential DDI/patient). A total of 38 of these 125 patients had clinically relevant DDIs causing adverse drug reactions (2.0 clinical DDI/patient). The vast majority of these DDIs (90.66%) were assessed to be at moderate risk. The performance of the ML algorithms that predicts of the presence of relevant DDI was as follows: accuracy 0.944 (95% CI 0.888–0.972), sensitivity 0.892 (95% CI 0.769–0.962), F1 score 0.904, and AUC 0.929 (95% CI 0.874–0.983). Conclusions: In clinical practice, it is expected that optimization in treatment can be achieved with the implementation of this high-performance web tool, created to predict DDIs before they occur with a newborn-centered approach.

Real clinical impact of drug-drug interactions of immunosuppressants in transplant patients.

The main objective was to determine the prevalence of real drug–drug interactions (DDIs) of immunosuppressants in transplant patients. We conducted a prospective, observational 1‐year study at a tertiary hospital, including all transplanted patients. We evaluated data from monitoring blood concentrations of immunosuppressive drugs and adverse drug events (ADEs) caused by DDIs. The DDIs were classified as C, D, or X according to their Lexi‐Interact rating (C = monitor therapy, D = consider therapy modification, X = avoid combination). The clinical importance of real DDIs was expressed in terms of patient outcomes. The causality of DDIs was determined using Drug Interaction Probability Scale. The data were analyzed using Statistical Package for Social Sciences v. 25.0. A total of 309 transplant patients were included. Their mean age was 52.0 ± 14.7 years (18–79) and 69.9% were male. The prevalence of real DDIs was 21.7%. Immunosuppressive drugs administered with antifungal azoles and tacrolimus (TAC) with nifedipine have a great clinical impact. Real DDIs caused ADEs in 22 patients. The most common clinical outcome was nephrotoxicity (1.6%; n = 5), followed by hypertension (1.3%; n = 4). Suggestions for avoiding category D and X DDIs included: changing the immunosuppressant dosage, using paracetamol instead of non‐steroidal anti‐inflammatory drugs, and interrupting atorvastatin. The number of drugs prescribed and having been prescribed TAC was associated with an increased risk of real DDIs. There are many potential DDIs described in the literature but only a small percentage proved to be real DDIs, based on the patients´ outcomes.

Influenza Vaccination and Myo-Pericarditis in Patients Receiving Immune Checkpoint Inhibitors: Investigating the Likelihood of Interaction through the Vaccine Adverse Event Reporting System and VigiBase.

Background: Evidence on whether the influenza vaccine could exacerbate immune-related adverse events, including myopericarditis (MP), in patients treated with immune checkpoint inhibitors (ICIs), is still conflicting. We explored this issue through a global real-world approach. Methods: We queried the Vaccine Adverse Event Reporting System (VAERS) and VigiBase to retrieve cases of MP in which the influenza vaccine and ICIs were recorded as suspect and were concomitantly reported. For the included cases, causality assessment and Drug Interaction Probability Scale (DIPS) algorithms were applied. Results: There were 191 and 399 reports of MP with the influenza vaccine that were retrieved (VAERS and VigiBase, respectively). No case of MP reporting the concomitant use of ICIs and the influenza vaccine was found in VAERS, while three cases of myocarditis were retrieved in VigiBase. All of the cases were unclassifiable for a causality assessment because of the lack of data concerning latency. According to the DIPS, one report was categorized as possible and two as doubtful. Conclusion: The paucity of cases coupled with the doubtful causality assessment make the potential interaction between influenza vaccines and ICIs in cancer patients negligible from clinical and epidemiological standpoints. These findings support the cardiovascular safety of the influenza vaccination, which remains strongly recommended in cancer patients, especially in the current COVID-19 era.

Evidence of Clinically Meaningful Drug-Drug Interaction With Concomitant Use of Colchicine and Clarithromycin.

Colchicine is currently approved for the treatment of gout and familial Mediterranean fever, among other conditions. Clarithromycin, a strong inhibitor of CYP3A4 and P-glycoprotein, dramatically increases colchicine's half-life, augmenting the risk of a life-threatening adverse reaction when used inadvertently with colchicine. The aim of this study was to examine the evidence and clinical implications of concomitant use of colchicine and clarithromycin. Case reports of colchicine-clarithromycin co-administration were searched using the FDA's Adverse Event Reporting System (FAERS) database. PubMed, EMBASE, and Web of Science electronic databases were also searched from January 2005 through November 2019 for articles reporting colchicine-clarithromycin concomitant use. Individual reports were reviewed to identify consequences of coadministration, dose, days to onset of interaction, symptoms, evidence of renal disease, time to resolution of symptoms, and Drug Interaction Probability Scale (DIPS) rating. The FAERS search identified 58 reported cases, nearly 53% of which were from patients aged between 65 and 85years. Of 30 reported deaths, 11 occurred in males, and 19 in females. Other frequent complications reported in FAERS included diarrhea (31%), pancytopenia (22%), bone marrow failure (14%), and vomiting (14%). From published literature, we identified 20 case reports of concomitant exposure, 19 of which were rated 'probable' and one 'possible' according to DIPS rating. Of these cases, four 'probable' patients expired. The documented onset of colchicine toxicity occurred within 5days of starting clarithromycin, and death within 2weeks of concomitant exposure. Clinical manifestations of colchicine-clarithromycin interaction may resemble other systemic diseases and may be life threatening. Understanding this clinically meaningful interaction can help clinicians avoid unsafe medication combinations.

P280 Concomitant use of ivabradine and cyp3a4 inhibitors in critical cardiac patients

Abstract Background In recent years there have been warnings concerning drug-induced life-threatening arrhythmias. Drug interactions can increase the risk of QT interval prolongation via interaction of pharmacokinetic mechanism. Some drugs such as Ivabradine does not affect the repolarization or affect the QT interval themselves. However, it can increase the risk of QT prolongation when taken with drugs that block the metabolic breakdown which inhibit the CYP3A4 enzyme particularly. Predisposing factors of QT prolongation include female sex, age over 65 years, brady-arrhythmia, electrolyte disturbances (hypokalemia, hypomagnesaemia), cardiac disease (congestive heart failure, ventricular hypertrophy, myocardial infarction, atrial fibrillation), impaired hepatic/renal function and hypothyroidism. Purpose To assess potential Ivabradine – CYP3A4 inhibitor interactions in a Cardiac Critical Care Unit (CCCU). Method We prospectively observed patients admitted at CCCU received Ivabradine and CYP3A4 inhibitor (QTprolonging agent) concomitantlyfrom Feb 2018 to July 2018 at National Heart Institute, Malaysia. We use a clinical drug decision support system (CDDSS) to identify the potential drug-drug interactions (PDDI) and assessed the likelihood of drug - drug interactions (DDI) using Drug Interaction Probability Scale (DIPS). Results Patients admitted at CCCU co-administered with Ivabradine and CYP3A4 inhibitors (amiodarone/azithromycin) were analyzed. The severity level for both potential Ivabradine – Azithromycin and Ivabradine – Amiodarone interactions were alerted by the CDDSS as Major. Total 10 (M = 70%) patients were screened. The mean age was ± 57 years old. They had no previous exposure to both or one of the medications before. All patients had underlying cardiac disease. The left ventricular ejection fractions (LVEF) ranged from 15% - 65%. Adverse drug event (ADE) occurred in 7 (70%) patients [Male = 5 (71%), Female = 2 (67%)]. 70% of patients had prolonged QT interval induced by Ivabradine – Amiodarone and Ivabradine – Azithromycin All patients had QTc interval &amp;lt; 500 ms before co-administration and had a change of ± 100 ms after coadministration. The onset of ADE ranged from day 2 to day 5 in all patients. One had life threatening arrhythmia; ventricular fibrillation and require defibrillator and another one patient had non-sustained ventricular tachycardia. The most common precipitating factor was underlying cardiac disease. All suspected precipitating drug was discontinued. DIPS revealed; 57% patients scored 9 points (highly probable DDI) and the rest scored between 5-7 points (probable DDI). Conclusion Ivabradine potentially associated to fatal arrhythmia when it is co-administered with CYP3A4 inhibitor. Hence, the physician should reconsider such combination within the correct clinical context to avoid cardiovascular deterioration especially in a critical care setting.

Natural Health Product-Drug Interaction Causality Assessment in Pediatric Adverse Event Reports Associated with Attention-Deficit/Hyperactivity Disorder Medication.

Background: Some pediatric patients with attention-deficit/hyperactivity disorder (ADHD) use natural health products (NHPs) such as herbal remedies. Although herbal remedies are generally considered to be safe when they are used appropriately, they may contain active components that can interact with medications being used concurrently, with potential for NHP-drug interactions leading to adverse events. Objectives: The objectives of this study were (1) to identify adverse event reports (AERs) involving commonly used herbal remedies and ADHD prescription medicines in children and adolescents; (2) to evaluate the quality of collected AERs; and (3) to assess whether NHP-drug interactions can be causally linked to reported adverse events. Methods: We systematically searched the FDAble database (FDAble.com) for herbal remedies commonly used by patients (4-18 years old) also taking ADHD drugs from 1997 to 2015. We assessed the completeness of the AERs and used three causality assessment tools modified for NHPs (Naranjo Adverse Drug Reaction Probability Scale, HORN Drug Interaction Probability Scale, and World Health Organization Uppsala Monitoring Centre Scale). Results: Of the 23 identified AERs involving both an herbal remedy and an ADHD prescription medication, most involved multiple (>3) substances with inadequate detail to assess multiple potential interactions. Following data extraction and evaluation of completeness, five AERs involving only one herbal remedy and one ADHD medication were evaluated for causality. An NHP-drug interaction was assessed to be probable in one case and to be possible in another. Both these reports involved a methylphenidate formulation and St. John's wort. Conclusions: Eighteen of the 23 identified AERs involving both an herbal remedy and an ADHD drug also involved other multiple ingredient products. The reporting quality was poor for the five AERs examined. Further research is needed to study the interaction between St. John's wort and methylphenidate.

DRUG UTILIZATION EVALUATION OF BENZODIAZEPINES IN A TERTIARY CARE HOSPITAL

Objective: To assess the rationale use of benzodiazepines among various departments in a multi-speciality hospital.&#x0D; Methods: A prospective study was conducted with a sample size of 200 for a period of six months. Data was collected from patients based on inclusion and exclusion criteria. Naranjo Adverse Drug Reaction Probability Scale and Drug Interaction Probability Scale (DIPS) were used as a study tool to measure the causality of adverse drug reactions and drug interactions. Based on the dosage of various benzodiazepines DDD was calculated and compared with WHO Anatomical Therapeutic Chemical (ATC) classification Defined Daily Dose (DDD).&#x0D; Results: BZD’s were mostly prescribed in males (74.5%) and married patients (86.5%) were more exposed to benzodiazepines compared to others. Lorazepam (70.1%) was found to be the most commonly used drug, mainly prescribed for sedation, followed by anxiety. DDD was calculated and majority of patients had DDD in accordance with WHO standard. Based on cost analysis, Clobazam was found to be the high cost and Lorazepam being the low-cost drug. The results of drug utilization evaluation of benzodiazepines study were compiled and reported to the respected department physician and their feedback was collected.&#x0D; Conclusion: The study showed a rational utilization of benzodiazepines and the negative outcomes of BZDs can be reduced by providing drug-related information to the prescribers and consumers.

Adverse drug reactions caused by drug–drug interactions in cardiovascular disease patients: introduction of a simple prediction tool using electronic screening database items

Objective: Cardiovascular disease (CVD) drugs have been frequently implicated in adverse drug reaction (ADR)-related hospitalizations. Drug–drug interactions (DDIs) are common preventable cause of ADRs, but the impact of DDIs in the CVD population has not been investigated. Hence, the primary aim of the study was to identify DDIs associated with ADRs in CVD patients at hospital admission. The second aim was to develop a simple tool to identify high-risk patients for DDI-related adverse events.Methods: An observational study was conducted on the Cardiology Ward of University Clinical Hospital Center. Data were obtained from medical charts. A clinical panel identified DDIs implicated in ADRs, using LexiInteract database and Drug Interaction Probability Scale. Statistics were performed using PASW 22 (SPSS Inc.).Results: DDIs contributed to hospital admission with a total prevalence of 9.69%. DDI-related ADRs affected mainly cardiac function (heart rate or rhythm, 41.07%); bleeding and effect on blood pressure were equally distributed (17.86%). Non-cardiovascular ADRs were found in 23.21% of DDIs. After admission, 73% of the identified DDIs led to changes in prescription. Prediction ability of calculated DDI adverse event probability scores was rated as good (AUC = 0.80, p < .001).Conclusions: CVD patients are highly exposed to adverse DDIs; about one in ten patients hospitalized with CVD might have a DDI contributing to the hospitalization. Given the high prevalence of CVD, DDI-related harm might be a significant burden worldwide. Identification of patients with high DDI adverse event risk might ease the recognition of DDI-related harm and improve the use of electronic databases in clinical practice.

A Prospective Study on Clinically Significant Drug – Drug Interactions by Systematic Review of Case files in a South Indian Tertiary Care Hospital

<p style="text-align: justify;"><strong>Objectives:</strong> The main objective of the study was to recognize potential drug-drug interactions, thus reducing their potential risk and improving pharmaceutical care by minimizing problems that may arise out of improper medication. <strong>Methodology:</strong> A prospective interventional study of a duration of 6 months was conducted in three phases (Pre interventional, Interventional and Post interventional) among 200 inpatients (in the age group of 18 years and above) of Pulmonology, Nephrology, Gastroenterology and General Medicine Departments of a tertiary care referral hospital. <strong>Results:</strong> Out of a total of 495 interactions, 368 (74.34%) interactions occurred in the Pre interventional phase and 127 (25.65%) interactions in Post interventional phase. There was a statistically significant reduction in drug-drug interactions occurring in the Post interventional phase (<em>P</em> value &lt;0.05) which suggests encouraging the intervention of clinical pharmacists in assessing and controlling potential drug-drug interactions.<strong> Conclusion:</strong> Among the conclusions of this study are that a wide number of DDIs exist within a hospital environment. Further, that a majority of the DDIs may be reduced by a significant amount via means of contact programs with both physicians as well as subjects. This may include distributing information letters to physicians concerned and providing bedside patient counseling as was carried out in this study. In conclusion, our study suggests that a clinical pharmacist could make statistically provable improvements in minimizing harmful outcomes of DDIs by means of calculated study and information disbursal of the given medical scenario. <p style="text-align: justify;"><strong> Key words:</strong> Drug drug interactions, Drug Interaction probability scale, Lexicomp, Pharmacodynamic , Pharmacokinetic.

Concomitant use of capecitabine and proton pump inhibitors - Is it safe?

Capecitabine is a commonly used oral chemotherapy agent. Recent data suggest that concurrent use of proton pump inhibitors may reduce the efficacy of capecitabine by decreasing its absorption through increased gastric pH. Since proton pump inhibitors are widely used, we evaluated the supportive evidence for the probability of occurrence and potential seriousness of this drug interaction. The probability of occurrence was evaluated based on the clinical, pharmacokinetic and in vitro evidence using the Drug Interaction Probability Scale. The possibility of seriousness was assessed based on the potential impact on the therapeutic intent of capecitabine therapy. The probability of occurrence of the interaction is doubtful. Clinical findings from two retrospective post hoc analyses showed inconsistent trends towards reduced survival. Pharmacokinetics studies found no significant decrease in systemic capecitabine level with concurrent gastric acid suppression with antacid or food intake. In vitro data do not support the proposed mechanism of reduced capecitabine absorption due to increased gastric pH. The possibility of seriousness varies depending on the treatment intent of capecitabine therapy. The most and least serious possible outcome would be reduced possibility of cure or survival and symptom control, respectively. Although the possible outcome may be serious, the probability of interaction between capecitabine and proton pump inhibitors is doubtful. Therefore, we suggest that intervention should be limited to minimal change to existing therapy plan. This may include routinely ascertaining the need for proton pump inhibitor use. Alternate acid suppressing agents may be considered based on the therapeutic intent of capecitabine therapy.