Evaluation Of Potential Drug Interactions Research Articles

Immunosuppressive therapy and oral anticoagulation in kidney transplant recipients: Direct oral anticoagulants versus vitamin-k antagonists

Backgrounddirect oral anticoagulants (DOACs) are an alternative to conventional antagonist of vitamin-K (AVK). However, immune suppressive drugs (ISDs) may interfere with DOACs pharmacokinetic. Aim of this studyevaluate safety and efficacy profile of DOACs compared to AVK in kidney transplant recipients (KTRs) treated with ISDs. Methodsa multi-center study from 4 Italian University hospitals enrolling consecutive KTRs on DOACs or AVK was carried out. Sixty-six patients on DOACs were compared with fifty patients on AVK with similar clinical features. Serial evaluation of renal function and serum levels of ISDs during 18 months follow-up (FU) was performed. ResultsMean age of DOACs patients was 67±9 and mean eGFR was 58,3± 30,4mL/min/1.73m2. ISDs included tacrolimus (n=47, 71%), cyclosporin (n=13, 20%), everolimus (n=10, 7%) and sirolimus (n=4, 6%). After 14 days of DOACs therapy initiation there was a slight increase of serum levels of tacrolimus (+0.19±0.67 p=0.80) and cyclosporine (+0.12±0.25 p=0.94) not statistically significant. Levels of Tacrolimus and cyclosporin were stable at serial evaluation during 18-months follow-up. There were no thromboembolic events among patients treated with DOACs or AVK and no differences in term of major bleeding (6% vs 4% p=0.69), at long-term follow-up. There was no difference in term of eGFR decline from start therapy to 18 months FU between DOACs vs AVK therapy (-3.9±1 vs -3.8±2 p=0.82). ConclusionDOACs have similar safety and efficacy than AVK among KTRs treated with ISDs. However, careful evaluation of potential drug interaction and ISDs serum levels is needed.

Evaluation of Potential Drug Interactions Detected in Critical Patients in Different Electronic Databases

Evaluation of Potential Drug Interactions Detected in Critical Patients in Different Electronic Databases

Evaluation of Potential Drug Interactions with AiDKlinik® in a Random Population Sample.

PurposeUndesirable drug interactions are frequent, they endanger the success of therapy, and they lead to adverse drug reactions. The present study aimed to evaluate statistically potentially drug interactions in a locally circumscribed, random sample population.Patients and MethodsIn a random sample population of 264 patients taking medications, we performed analyses with the drug information system AiDKlinik®. Statistical analysis was performed using SAS version 9.4.ResultsStatistically potentially drug interactions were recorded in 82/264 (31.1%) subjects, including 39/82 (47.56%) men, and 43/82 (52.43%) women (χ2= 0.081; p = 0.776). The average number of potential possible interactions detected per person was 1.60 ± 1.21. The regression model with the variables age, body-mass-index and number of long-term-medications shows a significant association between the number of long-term medications taken and the number of moderately severe and severe reactions to drug interactions (F(3.239) = 28.67, p < 0.0001; (t(239) 8.28; p < 0.0001)). After backward elimination, the regression model showed a significant interaction with the number of long-term medications (t (240) = 8.73, p < 0.0001) and body-mass-index (t (240) = 2.02, p = 0.0442). In descriptive analysis, the highest percentages of potential drug interactions occurred in 42/82 (51.22%) subjects with body mass indices (BMIs) >25 kg/m2 and in 28/82 (34.15%) subjects aged 61–70 years.ConclusionNumber of long-term medications use, age, and obesity may lead to increased drug–drug interactions in a random population sample.

Avaliação de interações medicamentosas potenciais em pacientes oncopediátricos internados

Avaliação de interações medicamentosas potenciais em pacientes oncopediátricos internados

Evaluation of potential drug interactions with sodium zirconium cyclosilicate: a single-center, open-label, one sequence crossover study in healthy adults.

BackgroundSodium zirconium cyclosilicate (SZC; formerly ZS-9) is an oral potassium binder for the treatment of hyperkalemia in adults. SZC acts in the gastrointestinal tract and additionally binds hydrogen ions in acidic environments like the stomach, potentially transiently increasing gastric pH and leading to drug interactions with pH-sensitive drugs. This study assessed potential pharmacokinetic (PK) interactions between SZC and nine pH-sensitive drugs.MethodsIn this single-dose, open-label, single-sequence cross-over study in healthy adults, amlodipine, atorvastatin, clopidogrel, dabigatran, furosemide, glipizide, levothyroxine, losartan or warfarin were each administered alone and, following a washout interval, with SZC 10 g. Maximum plasma concentration (Cmax), area under the plasma concentration–time curve from 0 to the last time point (AUC0–t) and AUC extrapolated to infinity (AUCinf) were evaluated. No interaction was concluded if the 90% confidence interval for the geometric mean ratio (SZC coadministration versus alone) of the PK parameters was within 80–125%.ResultsDuring SZC coadministration, all PK parameters for amlodipine, glipizide, levothyroxine and losartan showed no interaction, while reductions in clopidogrel and dabigatran Cmax, AUC0–t and AUCinf (basic drugs) were <50% and increases in atorvastatin, furosemide and warfarin Cmax (acidic drugs) exceeded the no-interaction range by ˂2-fold.ConclusionsSZC coadministration was associated with small changes in plasma concentration and exposure of five of the nine drugs evaluated in this study. These PK drug interactions are consistent with transient increases in gastric pH with SZC and are unlikely to be clinically meaningful.

Green analytical method for the simultaneous analysis of cytochrome P450 probe substrates by poly(N-isopropylacrylamide)-based temperature-responsive chromatography

High-performance liquid chromatography (HPLC) is the most common analytical method practiced in various fields and used for analysis of almost all drug compounds in the pharmaceutical industries. During drug development, an evaluation of potential drug interaction with cytochrome P450 (CYP) is essential. A “cocktail” approach is often used in drug development to evaluate the effect of a drug candidate on multiple CYP enzymes in a single experiment. So far, simultaneous analysis of multiple CYP substrates, which have greatly different structure and physicochemical properties, has required organic solvents and mobile phase gradient methods. However, despite the recent emphasis on environmental protection, analytical methods that use only aqueous solvents without the use of organic solvents for separation have not been studied well. This study sought to develop the simultaneous analysis of multiple CYP substrates by using poly(N-isopropylacrylamide) (PNIPAAm)-based temperature-responsive chromatography with only aqueous solvents and isocratic methods. Good separation of multiple CYP substrates was achieved without using organic solvents and any gradient methods by temperature-responsive chromatography utilizing a P(NIPAAm-co-n-butyl methacrylate (BMA))- and P(NIPAAm-co-N-acryloyl L-tryptophan methyl ester (L-Trp-OMe))-grafted silica column. Overall, PNIPAAm-based temperature-responsive chromatography represents a remarkably simple, versatile, and environmentally friendly bioanalytical method for CYP substrates and their metabolites.

Evaluation of Potential Drug Interaction of Analgesic in Cancer Patient Receiving Palliative Care in Dharmais Cancer Hospital

Analgesics are mostly used in cancer patients receiving palliative care to improve the quality of life of patients. Besides analgesics, cancer patients receiving palliative care were also given other drugs in combination to overcome other symptoms of cancer, and this combination could potentially cause drug interactions. This study was aimed to analyze the potential of drug interactions with analgesics in cancer patients. The study design was cross-sectional with a retrospective method and descriptive study. The sample of this study was cancer palliative care patient’s prescription at Dharmais Cancer Hospital in the period of January – December 2017. The sample analyzed in this study consisted of 273 prescriptions. This study found that there were 191 prescriptions (69.9%) of analgesics which potential- ly interacted with 316 interaction cases. Fentanyl and morphine with 61 cases (19.3%), morphine and gabapentin with 60 cases (18.9%) and morphine and amitriptyline with 33 cases (10.4%) were observed as the three most analgesics-other drugs interaction. Based on severity levels, there were 73.5% of major interaction, 26.3% of moderate interaction, and 0.2% of minor interaction. This study concluded that high occurrence of drug interactions was observed in analgesic drugs, therefore close monitoring is needed in cancer patient receiving palliative care.

Evaluation of potential drug interactions in hospital admission

Introduction: In clinical practice, drugs association is common and can lead to drug interactions (MI), which can lead to an avoidable adverse events that may need a for pharmaceutical intervention. Objective: The objective of this study is to identify and evaluate the drug interactions present on prescriptions of patients at the adult medical clinic of a hospital in Rio de Janeiro, at admission moment. Method: Cross-sectional study involving the analysis of information through the database (e-sus). Interactions were classified according to the Micromedex database. Results: A total of 177 prescriptions were evaluated. The main underlying disease was the neoplasias (36.16%), and the main cause of hospitalization was pain (8.5%). Of the prescriptions evaluated, 81.93% had some potential MI. A total of 180 types of MI were identified, representing 600 IM. Considering the degree of severity, 60% (358) were classified as severe MI, 38% (229) moderate, 1% (7) low and contraindicated. The most prevalent drug involved in MI was dipyrone (43.8%). The most frequent severe MI was between Dipirona + Enoxaparin (9.4%). Among moderate MI, Dipirone + Captopril (14.8%) was the most frequent and among the low ones, Furosemide + Hydralazine (42.9%). The contraindicated MI appeared in a similar way with 16.7% each. According to the scientific evidence found, serious MI had mostly reasonable documentation (59.5%), while the moderate ones had the majority of documentation classified as good (48.9%). Conclusion: In this context it is reasonable to consider that the pharmaceutical analysis of prescription at the patient admission may contribute to preventing drug-related adverse events.

Evaluation of Potential Drug Interactions and Related Factors in Patients Admitted in Department of Cardiology of Farshchian Heart Hospital of Hamadan

Evaluation of Potential Drug Interactions and Related Factors in Patients Admitted in Department of Cardiology of Farshchian Heart Hospital of Hamadan

Interações medicamentosas e consequentes intervenções farmacêuticas na Unidade de Terapia Intensiva de um hospital privado em Macapá, Amapá

Introduction: Patients admitted to Intensive Care Units (ICU) are submitted to multiple drug treatments, considering the severity of their problems. Drug interaction is defined as an event caused by the modification of the effect or use of a drug in the body. The evaluation of potential drug interactions can help the multiprofessional team to promote a quality treatment, avoiding harmful interactions, reducing the length of hospitalization and consequently reducing costs. Objective: To evaluate the main drug interactions observed in the ICUs of a private hospital in the city of Macapa, Brazil, through the analysis of the prescriptions and the consequent interventions adopted in order to minimize their risks. Method: Prescriptions of patients admitted to the ICU were evaluated for the presence of potential drug interactions and their respective classification according to their risk and mechanism. A brief bibliographic study about the main interactions was carried out in order to highlight its mechanism and the measures adopted by the multidisciplinary team. Results: We observed that the majority of the interactions, both in the adult ICU and in the neonatal ICU, were considered of moderate risk. Pharmacokinetic interactions were more common in the adult ICU, while pharmacodynamics predominated in the neonatal intensive care unit. Management during the administration of medications was the most appropriate intervention for most cases of drug interactions. Conclusions: Monitoring of potential interactions in critically ill patients seeks to ensure patient safety in order to reduce the potential risks to which they are exposed.

In vitro evaluation of potential drug interactions mediated by cytochrome P450 and transporters for luseogliflozin, an SGLT2 inhibitor

1. We evaluated potential in vitro drug interactions of luseogliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, mediated by CYP inhibition, CYP induction and drug transporters using human liver microsomes, primary hepatocytes and recombinant cells-expressing efflux or uptake transporters, respectively.2. Human CYP inhibition studies indicated that luseogliflozin was a weak inhibitor for CYP2C19 with an IC50 value of 58.3 μM, whereas it was not an inhibitor of the other eight major isoforms that were tested. The exposure of primary hepatocytes to luseogliflozin for 72 hrs weakly induced CYP3A4 at a concentration of 10 μM, whereas it did not induce CYP1A2 or CYP2B6 at concentrations of 0.1–10 μM.3. An in vitro transport study suggested that luseogliflozin is a substrate for human P-glycoprotein (P-gp), but not for breast cancer resistance protein (BCRP), organic anion transporting polypeptide (OATP) 1B1 and OATP1B3, organic anion transporter (OAT) 1 and OAT3, or organic cation transporter (OCT) 2. Luseogliflozin weakly inhibited OATP1B3 with an IC50 value of 93.1 μM, but those for other transporters are greater than 100 μM.4. Based on the therapeutic plasma concentration of the drug, clinically relevant drug interactions are unlikely to occur between luseogliflozin and coadministered drugs mediated by CYPs and/or transporters.

Inhibition and induction of cytochrome P450 and the clinical implications.

The cytochrome P450s (CYPs) constitute a superfamily of isoforms that play an important role in the oxidative metabolism of drugs. Each CYP isoform possesses a characteristic broad spectrum of catalytic activities of substrates. Whenever 2 or more drugs are administered concurrently, the possibility of drug interactions exists. The ability of a single CYP to metabolise multiple substrates is responsible for a large number of documented drug interactions associated with CYP inhibition. In addition, drug interactions can also occur as a result of the induction of several human CYPs following long term drug treatment. The mechanisms of CYP inhibition can be divided into 3 categories: (a) reversible inhibition; (b) quasi-irreversible inhibition; and (c) irreversible inhibition. In mechanistic terms, reversible interactions arise as a result of competition at the CYP active site and probably involve only the first step of the CYP catalytic cycle. On the other hand, drugs that act during and subsequent to the oxygen transfer step are generally irreversible or quasi-irreversible inhibitors. Irreversible and quasi-irreversible inhibition require at least one cycle of the CYP catalytic process. Because human liver samples and recombinant human CYPs are now readily available, in vitro systems have been used as screening tools to predict the potential for in vivo drug interaction. Although it is easy to determine in vitro metabolic drug interactions, the proper interpretation and extrapolation of in vitro interaction data to in vivo situations require a good understanding of pharmacokinetic principles. From the viewpoint of drug therapy, to avoid potential drug-drug interactions, it is desirable to develop a new drug candidate that is not a potent CYP inhibitor or inducer and the metabolism of which is not readily inhibited by other drugs. In reality, drug interaction by mutual inhibition between drugs is almost inevitable, because CYP-mediated metabolism represents a major route of elimination of many drugs, which can compete for the same CYP enzyme. The clinical significance of a metabolic drug interaction depends on the magnitude of the change in the concentration of active species (parent drug and/or active metabolites) at the site of pharmacological action and the therapeutic index of the drug. The smaller the difference between toxic and effective concentration, the greater the likelihood that a drug interaction will have serious clinical consequences. Thus, careful evaluation of potential drug interactions of a new drug candidate during the early stage of drug development is essential.

Amiodarone: A Postmarketing Evaluation of Monitoring for Drug-Induced Toxicity

Amiodarone, an antiarrhythmic drug with predominantly class III effects, has demonstrated serious adverse drug reactions and interactions. The Departments of Pharmacy and Cardiology retrospectively evaluated the monitoring parameters at this institution. Criteria based on current literature were developed. Twenty-six patients were administered amiodarone, qualifying for entry into the audit. Of these patients, seven were excluded because their medical records were unavailable or incomplete. The 19 eligible patients were hospitalized during initiation of therapy and followed in the Outpatient Cardiology Clinic. The collected data extracted from the medical charts were compared with the following elements of the criteria selected: baseline evaluation prior to the start of therapy; monitoring for signs of pulmonary, hepatic, thyroid, cardiac, ophthalmologic, neurologic, and dermatologic toxicity; and evaluation of potential drug interactions with digoxin and warfarin-type anticoagulants. The percentage of criteria elements appropriately monitored on each patient ranged from 82 to 100 percent, with an average of 91 percent. The most frequently overlooked parameters were warning the patient of a possible photosensitivity reaction, decreasing the digoxin dose if the patient was concurrently taking amiodarone, and performing a slit-lamp examination every six months. Frequent examination of the patient's total organ system and laboratory tests, in addition to patient education, are essential to safe monitoring of amiodarone therapy.