Moderate Drug-drug Interactions Research Articles

Prevalence of polypharmacy, drug-drug interactions, and inappropriate prescription in elderly patients with urological cancers.

e23312 Background: Around 50% of new cancer diagnoses occur in patients (pts) > 65 years. Older adults tend to have more comorbidities and therefore prescription of several drugs. Polypharmacy (PP) [defined as prescription of > 5 drugs] has been identified as a prognostic factor and might also lead to relevant drug-drug interactions (DDI) and it is also associated in occasions with inappropriate prescriptions (IP). This study aims to determine prevalence of PP, DDI and potential IP in a uro-oncology clinic. Methods: Pts ≥ 70 years with urological tumors consecutively seen in a medical oncology clinic [May 1st- August31st2023] were offered to complete a questionnaire that included questions about drugs regularly taken, doses, frequency, objective of the treatment along with some key epidemiological data. A descriptive analysis of this information was performed to identify PF along with a search for DDI ( DrugDex ®) and IP (STAR/STOPP criteria). Results: 91 pts agreed to participate and 87 complete the questionnaires. Mean age was 76 years (range 70-91) and 84.5% were men; 64%, 31 and 5% had ECOG 0,1 and 2 respectively. The predominant cancer type was bladder (41%), followed by prostate (40%) and kidney cancer (19%). Polypharmacy was identified in 54 pts (62%), with 12 pts (22%) having ≥ 10 drugs prescribed. Two cases (2%) of duplicity of treatment were found (laxative; hypnotic). Ninety-five major and 37 moderate DDI were detected, of which 8 occurred between anticancer drugs (abiraterone, pazopanib, everolimus and carboplatin) and outpatient treatments. An IP analysis is being currently conducted and data will be presented at the meeting. Conclusions: Our study shows a high prevalence of polypharmacy in older adults with urological tumors and a significant rate of drug-drug interactions including interferences with oncological treatments. These results highlight the need for careful reviewing and monitoring the drugs prescribed to our patients in the clinic and calls for strengthen collaborations with pharmacists and nurses to optimize integral management of GU cancer patients.

Development of a highly sensitive and green first-derivative synchronous fluorescence spectroscopic method for the simultaneous quantification of telmisartan and rosuvastatin: Greenness metric assessment and application to a pharmacokinetic study in rats

Hypertension and hyperlipidemia frequently coexist and are correlated with elevated cardiovascular adverse outcomes. Fixed dose combination tablets containing antihypertensive and antihyperlipidemic drugs have the potential to improve patient compliance. Telmisartan and rosuvastatin fixed dose combination tablet has been recently formulated. This study provided the first fluorescence spectroscopic method for simultaneously quantifying telmisartan and rosuvastatin in tablet dosage form and plasma. The native fluorescence spectra of telmisartan and rosuvastatin completely overlapped, making direct measurement unachievable. However, through the implementation of synchronous fluorescence measurements of telmisartan and rosuvastatin at a Δλ = 60, distinct narrow bands were observed at 358 nm and 375 nm, respectively. Regrettably, the challenge of overlapping remained unresolved. Nevertheless, by converting these synchronous spectra into first-order spectra, the problem of overlapping was completely resolved. This conversion also allowed for the selective quantification of telmisartan and rosuvastatin at 374 nm and 358 nm, respectively. The validity of this method was confirmed in accordance with ICH guidelines, yielding satisfactory results in terms of the validation characteristics. The method demonstrated linear relationships between the response and the studied drugs concentrations in working range of 50–1000 ng/mL for telmisartan and 100–2000 ng/mL for rosuvastatin. The described methodology was applied for the pharmacokinetic study of telmisartan and rosuvastatin in rat plasma after a single oral dose of 4 mg/kg telmisartan and 50 mg/kg rosuvastatin. Pharmacokinetic analyses revealed a moderate drug-drug interaction between the two drugs, which was not considered to be clinically significant. Moreover, the described method was assessed in terms of sensitivity and environmental sustainability against three previously documented methods. The comparison effectively underscores the supremacy of the proposed technique over the documented techniques.

A comprehensive evaluation in clinic and physiologically-based pharmacokinetic modeling and simulation to confirm lack of cytochrome P450-mediated drug-drug interaction potential for pomotrelvir.

Pomotrelvir is a new chemical entity and potent direct-acting antiviral inhibitor of the main protease of coronaviruses. Here the cytochrome P450 (CYP)-mediated drug-drug interaction (DDI) potential of pomotrelvir was evaluated for major CYP isoforms, starting with in vitro assays followed by the basic static model assessment. The identified CYP3A4-mediated potential DDIs were evaluated clinically at a supratherapeutic dose of 1050 mg twice daily (b.i.d.) of pomotrelvir, including pomotrelvir coadministration with ritonavir (strong inhibitor of CYP3A4) or midazolam (sensitive substrate of CYP3A4). Furthermore, a physiologically-based pharmacokinetic (PBPK) model was developed within the Simcyp Population-based Simulator using in vitro and in vivo information and validated with available human pharmacokinetic (PK) data. The PBPK model was simulated to assess the DDI potential for CYP isoforms that pomotrelvir has shown a weak to moderate DDI in vitro and for CYP3A4 at the therapeutic dose of 700 mg b.i.d. To support the use of pomotrelvir in women of childbearing potential, the impact of pomotrelvir on the exposure of the representative oral hormonal contraceptive drugs ethinyl estradiol and levonorgestrel was assessed using the PBPK model. The overall assessment suggested weak inhibition of pomotrelvir on CYP3A4 and minimal impact of a strong CYP3A4 inducer or inhibitor on pomotrelvir PK. Therefore, pomotrelvir is not anticipated to have clinically meaningful DDIs at the clinical dose. These comprehensive in vitro, in clinic, and in silico efforts indicate that the DDI potential of pomotrelvir is minimal, so excluding patients on concomitant medicines in clinical studies would not be required.

Clinical assessment of gepotidacin (GSK2140944) as a victim and perpetrator of drug-drug interactions via CYP3A metabolism and transporters.

Gepotidacin is a novel triazaacenaphthylene antibiotic in phase III development. Based on nonclinical in vitro characterization of gepotidacin metabolism, two phase I studies were conducted in healthy participants to investigate clinical drug-drug interactions (DDIs). We assessed gepotidacin as a DDI victim with a potent cytochrome P450 (CYP) 3A4/P-glycoprotein (P-gp) inhibitor (itraconazole), potent CYP3A4 inducer (rifampicin), and nonspecific organic cation transporter (OCT)/multidrug and toxic extrusion transporter (MATE) renal transport inhibitor (cimetidine) via single doses of gepotidacin before and after co-administration with multiple doses of the modulator drugs. Gepotidacin DDI perpetrator potential for P-gp inhibition (digoxin) and CYP3A4 inhibition (midazolam) was evaluated via single doses of the two-drug cocktail without and with gepotidacin. The DDI magnitudes were interpreted based on area under the concentration-time curve (AUC). A weak DDI (AUC increase 48%-50%) was observed for gepotidacin co-administered with itraconazole. A clinically significant decrease in gepotidacin plasma AUC (52%) was observed with rifampicin coadministration, indicating a moderate DDI. There was no DDI for gepotidacin with cimetidine; a unique biomarker approach showed increased serum creatinine (24%), decreased renal clearance of creatinine (21%), and N1-methylnicotinamide (39%), which confirmed extensive MATE inhibition and partial OCT2 inhibition. Gepotidacin was not a P-gp DDI perpetrator, although the maximum plasma concentration of digoxin increased (53%) and is potentially clinically relevant given its narrow therapeutic index. Gepotidacin demonstrated weak CYP3A4 inhibition with midazolam (<2-fold AUC increase). There were no new safety-risk profile findings. These results will inform the safe and efficacious clinical use of gepotidacin when co-administered with other drugs.

Trends in prescribing patterns and drug related problems of kidney disease patients.

The descriptive cross-sectional study was planned to evaluate drug-related problems, including drug-drug interactions, dose error, use of nephrotoxic drugs and polypharmacy, with special emphasis on kidney disease patients. The study was conducted from January to June 2019 in the Nephrology Ward of Ayub Teaching Hospital, Abbottabad, Pakistan. Doses of medicine and drug-drug interactions were evaluated by comparing it with standard protocols in British National Formulary and Lexicomp. Prescriptions were also evaluated for polypharmacy and use of nephrotoxic drugs. Out of 131 patients, 72 (55%) were males. Drug-drug interactions were found in 69 (52.7%) patients among whom the highest percentage was of moderate drug-drug interaction 63 (48.1%), followed by major 39 (29.8%) and minor 29 (22%) drug-drug interactions. Incidence of polypharmacy 68 (51.9%) and use of nephrotoxic drug 101 (77%) was high, while dose error was low 14 (10.7%). All drug-related problems were present with a high percentage in patients with chronic kidney diseases 29 (78.4) out of 37 (28.2%) such patients. There was significant association of chronic kidney diseases stages with drug-drug interactions, polypharmacy, dose error and prescribing drugs (p<0.05). The higher incidence of drug-related problems reflected irrational prescribing trends and deficiency of professional staff dealing with kidney disease patients.

Potentially inappropriate medications, drug-drug interactions, and prescribing practices in elderly patients: a cross-sectional study.

To evaluate potentially inappropriate medications, potential drug-drug interactions, and prescribing practices in elderly ambulatory patients. We carried out a cross-sectional study on 275 elderly patients attending different outpatient departments. We used the Screening Tool for Older Person's Prescriptions criteria version two to identify potentially inappropriate medications, IBM Micromedex, to categorize potential drug-drug interactions as major and moderate. World Health Organization prescribing indicators were used to evaluate prescribing practices. The prevalence of potentially inappropriate medications in 275 prescriptions was 21.9%. Diclofenac was the most common inappropriate drug (n=23). Metoprolol is the second most inappropriate drug (n=12). Amlodipine and clopidogrel, aspirin and furosemide, and aspirin and spironolactone together accounted for 71.42% of major interactions (n=15). Atorvastatin and clopidogrel was the most common moderate drug-drug interaction in our study (n=24). The average number of drugs per encounter, the percentage of drugs with a generic name, and the percentage of drugs from the essential drugs list must be improved. There is a need to provide awareness through education about the explicit criteria to identify potentially inappropriate medications and prescribing indicators that aid in rational prescribing in the elderly.

Prevalence and Predictors of Potentially Inappropriate Medication Use Among Elderly Patients Using Updated Beers Criteria 2019: A Single Centered Retrospective Analysis.

Inappropriate medication use poses a sizable health safety hazard in the elderly owing to aging-associated physiological and anatomic changes. Inappropriate drug prescribing and polypharmacy in this population elevate the risk of adverse drug reactions (ADR). The study aimed at assessing the prevalence and predictors of Potentially Inappropriate Medication (PIM) use in elderly patients according to updated Beers Criteria 2019. Medical records of 402 patients aged ≥65 years admitted to a tertiary care hospital from June 2018 to May 2019 were analyzed. The patients who received at least one PIM based on the 2019 Updated Beers Criteria were considered as test cases and others as control. Data were presented as descriptive statistics, and logistic regression was performed to assess the factors affecting the outcomes. The mean age was found to be 73.7 ±6.4 years in the test and 70.5±5.5 years in the control group. The prevalence of PIMs to be used with caution was found to be 54%. Whereas the prevalence of PIMs to be avoided and to be used with reduced dose was found to be 45% and 1%, respectively. The most prescribed PIMs were aspirin, diuretics, long-acting sulfonylureas, and proton pump inhibitors (PPIs). Increasing age, polypharmacy, and the number of drugs in medication history were significantly (p<0.05) correlated with a substantial risk of PIM use. The risk of developing serious and moderate drug-drug interactions (DDIs) was significantly high in the test group (p<0.05) when compared to the control group. A high prevalence of PIMs was observed in this study. Age, polypharmacy, and ≥ 3 drugs in medication history were identified as risk factors for PIM use, and at a higher risk of developing DDIs. Continuous medication reviews by clinical pharmacists can aid in reducing the occurrence of PIMs amongst geriatrics.

Medication Reconciliation and Drug–Drug Interactions: An Old Process with a New Approach

Background: The occurrence of drug–drug interactions (DDIs) and insufficient attention to medication reconciliation is one of the important challenges of pharmacotherapy in hospitalized patients. The aim of this study was to determine the extent of drug–drug interactions in patients based on medication reconciliation strategy.&#x0D; Methods: This descriptive cross-sectional study was performed for six months in patients admitted to Imam Reza Hospital in Amol, North of Iran. The data were obtained by using a medication reconciliation tool through a random sampling of patients admitted in Hospital wards from May 2014 until October 2014. A total of 200 patients were enrolled in the study. All patients had a history of medication use before admission. The drug interactions have been checked according to Drug Interaction Facts between newly prescribed drug and medication patient using before admission. The number and frequency of data were summarized by SPSS21 statistical software.&#x0D; Results: Major and Moderate DDIs were found in 7.5% and 64% of prescriptions. The most frequent DDIs were seen in those who were taking psychiatric drugs (33%) and cardiovascular drugs (30%). Most DDIs occurred among women over 60 years of age. The most frequently occurring DDIs was pharmacokinetics interaction between clopidogrel and atorvastatin (n=9). Other frequent interactions were between ceftriaxone and heparin (n=8) and metoprolol and insulin (n=3).&#x0D; Conclusion: This study showed a high rate of drug interactions and especially confirms the importance of medication reconciliation in providing a comprehensive drug history and exploring drug interactions.

Burden of comorbidities and their treatment in patients with active tuberculosis: A prospective study

Background: Patients diagnosed to have active tuberculosis (TB) may have co-existing comorbid conditions. Treatment for both conditions may lead to possible drug-related problems. Hence, the present study was designed to understand the incidence and pattern of drug-related problems. This knowledge gives a scope to minimise the occurrence and help patients to adhere to treatment.Methods: A prospective observational study was carried out for a period of 6 months. A pre-designed data collection form was used for this study that was used to document clinical data including brief history, laboratory investigations, treatment details and drug-drug interactions (DIs).Results: One hundred and five TB patients were enrolled in the study. Their mean age was 43.7 ± 16.8 years. Sixty patients were found to have comorbidities. One hundred and fifty-eight drug-related problems between comorbidities' treatment regimens and ATT were documented. DIs were the most common drug-related problems. Seventy-nine major DIs and 74 moderate DIs were documented. Nine patients had adverse drug reactions which were ATT-induced hepatotoxicity, thrombocytopenia and anaemia.Conclusions: Co-existence of comorbidities and their treatment resulted in a significant burden on patients who are diagnosed positive for TB. This can lead to treatment delay or failure or default. Strategies and programmes to tackle the burden of comorbid conditions on TB-positive patients are to be developed and implemented aggressively.

THE PREDICTORS OF POTENTIAL DRUG-DRUG INTERACTIONS AMONG DIABETIC HYPERTENSIVE ADULT OUTPATIENTS IN A KENYAN REFERRAL HOSPITAL

Objective: To characterize the predictors of potential drug-drug interactions among adult diabetic hypertensive outpatients at Kenyatta National Hospital.&#x0D; Methods: This cross-sectional study collected and analyzed data on potential drug interactions from 104 diabetic hypertensive outpatients (aged ≥18 y) at the Department of Endocrinology Outpatient Clinic of Kenyatta National Hospital from 1st May 2019 to 31st August 2019. The main outcome measure was the prevalence of potential drug-drug interactions and their predictors among the study population.&#x0D; Results: There was a female preponderance (70.2%). The mean age of the study participants was 61.6 y (SD±10.8). The prevalence of potential drug interactions was high at 57.7%. The average number of drug interactions was one interacting pair per patient, with a majority of the prescriptions (81.0%) having moderate drug-drug interactions. Patients receiving&gt;2 drugs were almost three times more likely to have drug-drug interaction compared to those prescribed ≤ 2 drugs (AOR=2.79; 95% CI: 1.11-7.28); p=0.029). Participants who were at stage 4 of hypertension were 2.5 times more likely to have a drug-drug interaction compared to the other stages of hypertension (AOR=2.52; 95% CI 1.31-4.89; p=0.007).&#x0D; Conclusion: Polypharmacy and stage 4 hypertension are independently associated with drug-drug interactions among patients with both diabetes and hypertension. Future studies should characterize the specific type of drug interactions and possible targets of minimization of drug-drug interactions.

Multiplex Analysis of 230 Medications and 30 Illicit Compounds in Dried Blood Spots and Urine.

Drugs of abuse and medication reconciliation testing can benefit from analysis methods capable of detecting a broader range of drug classes and analytes. Mass spectrometry analysis of a wide variety of commonly prescribed medications and over-the-counter drugs per sample also allows for application of a drug-drug interaction (DDI) algorithm to detect adverse drug reactions. In order to prevent adulteration of commonly collected clinical samples such as urine, dried blood spots (DBS) present a reliable alternative. A novel method is described for qualitative and quantitative multiplex analysis of 230 parent drugs, 30 illicit drugs and 43 confirmatory metabolites by HPLC-MS-MS This method is applicable to DBS specimens collected by volumetric absorptive microsamplers and confirmable in urine specimens. A patient cohort (n = 67) providing simultaneous urine specimens and DBS resulted in 100% positive predictive values of medications or illicits confirmed by detection of a parent drug and/or its metabolite during routine medication adherence analysis. An additional 5,508 DBS specimens screened (n = 5,575) showed 5,428 (97%) with an inconsistent positive compared to the provided medication list (including caffeine, cotinine or ethanol metabolites), 29 (0.5%) with no medication list and no unexpected positive results (consistent negative) and 22 (0.4%) showed all positive results matching the provided medication list (consistent positive). A DDI algorithm applied to all positive results revealed 17% with serious and 56% with moderate DDI warnings. Comprehensive DBS analysis proves a reliable alternative to urine drug testing for extended medication reconciliation, with the added advantage of detecting DDIs.

The Profile of Antihypertensive Drug Prescriptions and Interactions at Pindad General Hospital

Hypertension is a major problem in the world. World Health Organization (WHO) reported that 1.13 billion people in the world suffer from hypertension. This study aimed to determine antihypertensive prescription profile and drug interaction in outpatient installation at PINDAD General Hospital, Bandung in January 2019. This study was non-experimental observational studies with retrospective data collection. There were 381 patients with hypertension (50,13% female and 49,87% male). The most widely used antihypertensive drug is Amlodipine (33,28%) and Calcium Channel Blocker drug (34,20%). Moreover, we found 74,07% was moderate drug-drug interaction (DDI) with Amlodipine and Lisinopril as the most common cases (21,08%). We concluded that 15,7% prescription contain antihypertensive drugs and moderate DDI occurred in the use of amlodipine and lisinopril. DDI should get more attention due to the clinical manifestations that may occur in patients.

A Study on Detection of Drug-Laboratory interactions in Dermatology, in a Tertiary Care Teaching Hospital

Background: An interaction is alleged to occur once the consequences of one drug is changed by the presence of another drug, herbal medicine, food, drink or by some environmental chemical agents. As per American psychological association drug interaction is defined as chemical or physiological reaction that can occur when two different drugs are taken together. Objective: This study was conducted for the detection of various drug interactions in dermatology in a tertiary care teaching hospital. Methods: An observational, prospective study was conducted for a period of six months (July 2017 to December 2017) among 108 patients in dermatology department of Santhiram Medical College and General Hospital, Nandyal. Results: A total of 108 patients were included in the study. Among them, 63 (58.3%) were males and 45(41.7%) were females. Of total 108 prescriptions, sever drug-drug interactions were present in 42 (38.9 %) prescriptions. Whereas, moderate drug-drug interactions were found in 14 (13%) and 52 prescriptions doesn’t have drug-drug interactions respectively. The study found the associations of potential drug interactions with age, sex, number of drugs per prescription. There was a direct link between polypharmacy and occurrence of drug interactions. To lower the frequency of potential interactions it could be necessary to make a careful selection of therapeutic alternatives, and in cases without other options, patients should be continuously monitored to identify adverse events. Conclusion: we concluded that educational interventions can minimize the incidence of drug interactions.

Drug-drug interactions and pharmacists’ interventions among psychiatric patients in outpatient clinics of a teaching hospital in Saudi Arabia

BackgroundLack of recognition of labeled drug-drug interactions (DDIs) is a type of medication error of particular relevance to the treatment of psychiatric patients. Pharmacists are in a position to detect and address potential DDIs. ObjectiveThis study aimed to explore pharmacists’ role in the identification and management of DDIs among psychiatric patients in psychiatric outpatient clinics of a university-affiliated tertiary care hospital in Riyadh, Saudi Arabia. MethodThis study was a retrospective, cross-sectional medical chart review of patients visiting outpatient psychiatric clinics. It utilized medical records of patients who were taking any psychotropic medications and were prescribed at least one additional drug. The hospital Computerized Physician Order Entry system was used to identify DDIs and determine the pharmacists’ interventions. The Beers criteria were applied to detect inappropriate prescribing among older patients. ResultsOn average, the pharmacists intervened in 12 out of 213 (5.6%) cases of major or moderate DDIs. Older age, higher number of prescription medications, the severity of DDIs, and the utilization of lithium and anticoagulants were positively associated with the pharmacist undertaking an action. ConclusionFuture studies should explore the prevalence rate of harmful DDIs among psychiatric patients on a large scale and examine the effectiveness of different pharmacy policies in the detection and management of DDIs.

Evaluation of potential drug-drug interaction in indoor patients of pediatric department of tertiary care hospital

Background: Pediatric population is having high chances of drug-drug interactions (DDIs) because off-label use of drugs, weight-based dose adjustments, and pharmacokinetically, they are different from adult population. Hospitalized pediatric population is more vulnerable to face adverse consequences reserve physiology, medication dosing errors and polypharmacy. Thus, chances are more of potential DDIs (pDDIs) in pediatric patients. There has been focus mainly on adult population, less studies regarding DDIs or pDDIs in pediatric population have been documented. Aims and Objectives: The primary objective of the study is to identify pDDIs in pediatric patients. Determining prevalence, types of pDDIs, and factors associated with pDDIs are secondary objective. Materials and Methods: A prospective, observational study was conducted in pediatric ward of tertiary care hospital during April 2018–August 2018. The principal investigator collected the data from hospital case papers and recorded in pre-tested case record form. Drugs prescribed in each patient were assessed using Lexicomp software (version 4.4.0), which is internet-based free software used to predict pDDIs. DDIs were categorized in minor, moderate, and major according to their severity assessed by software. If necessary, the investigator also interviewed patients or caretaker to gather information. Results: A total of 300 patients were included during the study period. Among them, 157 (52.3%) were boys and 143 (48%) were girls. A total number of pDDIs were 235 (78%), of which 227 (97%) were minor and 3 (1.2%) were major DDIs. The most common DDI was between ondansetron and paracetamol (224). A potential major DDIs were observed between ondansetron and dextromethorphan (2) and ondansetron and phenytoin (1). Conclusion: The most common DDIs occurred with ondansetron and paracetamol, which were minor in severity. There were no clinical DDIs. Not all patients with major or moderate DDIs were suffered clinically but better to take due precautions to avoid adverse consequences.

A study on polypharmacy and drug interactions among elderly hypertensive patients admitted in a tertiary care hospital

BACKGROUND: Polypharmacy may be defined as the effects of taking multiple medications concurrently to manage coexisting health problems, such as diabetes and hypertension. Polypharmacy is an important issue in elderly patients. METHODS: A cross-sectional study was conducted in the rural tertiary care teaching hospital in Central India over 2 months. A total of 100 patients were studied. The study population included hypertensive geriatric population above 65 years admitted in the medicine ward who were willing to consent for participation. The patients with incomplete case sheets admitted in the Emergency and Intensive Care Units and with serious illness, malignancy, and other complications were excluded. RESULTS: Out of the total 403 medicine prescribed to study population, 271 potential drug–drug interactions were observed among elderly hypertensive patients. Moderate drug–drug interaction was found to be most common (50.62%) followed by mild (8.64%) and severe (7.94%). Most common potential inappropriate medicine used was spironolactone followed by diltiazem, diclofenac, olanzapine, metoclopramide, digoxin, insulin, and isopto hyoscine (Sliding scale) in the study population. CONCLUSION: In the present study, we can conclude that polypharmacy is a major risk factor for secondary morbidity in elderly patients. Polypharmacy leads to more potential drug–drug interactions and potential inappropriate medicine use. The use of medicines to disease condition is necessary, but unnecessary load of drugs to patient will increase the safety problems. Polypharmacy can be avoided by sharing treatment goals and plans. To improve drug safety in this high-risk population, appropriate prescribing might be more important than simply reducing the number of prescribed drugs.

STUDY OF DRUG-DRUG INTERACTION IN THE INPATIENTS OF A TERTIARY CARE HOSPITAL AT CALICUT

Objective: The study was conducted to monitor the potential drug-drug interactions in the prescriptions of inpatients in a tertiary care hospital based on the mechanism and severity.Methods: This prospective observational study was conducted by collecting the prescriptions containing two or more drugs. The interactions were checked using an interaction checker and were categorized into pharmacokinetic and pharmacodynamic interactions on the basis of mechanism of action and severity based on the risks or consequences of the interactions.Result: Among 150 randomly collected prescriptions, 123 (82%) prescriptions had 396 drug-drug interactions. The pharmacodynamic drug interactions (77.27%) were more common when compared to pharmacokinetic drug interactions (22.73%). There was high prevalence of drug-drug interactions among the patients above the age of 60 years (56.09%). The moderate drug-drug interactions (81.81%) were found to be more when compared to the major (10.61%) and minor (7.58%) interactions. The neurology department prescriptions were observed to have more number of drug-drug interactions (26.01%).Conclusion: A systematic approach and close monitoring of the medication chart is necessary to identify the potential drug-drug interactions. The clinicians and other health-care professionals at the study site require an awareness program in regard to identification and management of drug-drug interactions. Clinical pharmacist can play an important role in the monitoring and management of drug-drug interactions.

Physiologically-based pharmacokinetic modelling of a CYP2C19 substrate, BMS-823778, utilizing pharmacogenetic data.

Previous studies demonstrated direct correlation between CYP2C19 genotype and BMS-823778 clearance in healthy volunteers. The objective of the present study was to develop a physiologically-based pharmacokinetic (PBPK) model for BMS-823778 and use the model to predict PK and drug-drug interaction (DDI) in virtual populations with multiple polymorphic genes. The PBPK model was built and verified using existing clinical data. The verified model was simulated to predict PK of BMS-823778 and significance of DDI with a strong CYP3A4 inhibitor in subjects with various CYP2C19 and UGT1A4 genotypes. The verified PBPK model of BMS-823778 accurately recovered observed PK in different populations. In addition, the model was able to capture the exposure differences between subjects with different CYP2C19 genotypes. PK simulation indicated higher exposures of BMS-823778 in CYP2C19 poor metabolizers who were also devoid of UGT1A4 activity, compared to those with normal UGT1A4 functionality. Moderate DDI with itraconazole was predicted in subjects with wild-type CYP2C19 or UGT1A4. However, in subjects without CYP2C19 or UGT1A4 functionality, significant DDI was predicted when BMS-823778 was coadministered with itraconazole. A PBPK model was developed using clinical data that accurately predicted human PK in different population with various CYP2C19 phenotypes. Simulations with the verified PBPK model indicated that UGT1A4 was probably an important clearance pathway in CYP2C19 poor metabolizers. DDI with itraconazole is likely to be dependent on the genotypes of CYP2C19 and UGT1A4.

A drug-drug interaction study to assess the effect of the CYP1A2 inhibitor fluvoxamine on the pharmacokinetics of dovitinib (TKI258) in patients with advanced solid tumors.

Dovitinib is an orally available multi tyrosine kinase inhibitor which inhibits VEGFR 1-3, FGFR 1-3, and PDGFR. This study was performed to investigate the potential drug-drug interaction of dovitinib with the CYP1A2 inhibitor fluvoxamine in patients with advanced solid tumors. Non-smoking patients of ≥ 18years with advanced solid tumors, excluding breast cancer, were included. Patients were treated with a dose of 300mg in 5days on/2days off schedule. Steady-state pharmacokinetic assessments of dovitinib were performed with or without fluvoxamine. Forty-five patients were enrolled; 24 were evaluable for drug-drug interaction assessment. Median age was 60years (range 30-85). At steady state the geometric mean for dovitinib (coefficient of variation%) of the area under the plasma concentration-time curve (AUC0-72h) and maximum concentration (C max) were 2880ng/mLh (47%) and 144ng/mL (41%), respectively. Following administration of dovitinib in combination with fluvoxamine the geometric mean of dovitinib AUC0-72h and C max were 8290ng/mLh (60%) and 259ng/mL (45%), respectively. The estimated geometric mean ratios for dovitinib AUC0-72h and C max (dovitinib + fluvoxamine vs. dovitinib alone) were 2.88 [90% confidence interval (CI) 2.58, 3.20] and 1.80 (90% CI 1.66, 1.95). This effect is considered a moderate drug-drug interaction. Fluvoxamine co-administration resulted in a 80% increase in C max and a 188% increase in AUC0-72h of dovitinib. Given the increase in exposure to dovitinib observed, patients are at risk of dovitinib related toxicity. Dovitinib should, therefore, not be co-administered with moderate and strong CYP1A2 inhibitors, without dose reduction.

PREVAlENCE OF POTENTIAllY ADVERSE DRUG-DRUG INTERACTIONS IN HOSPITAlS OF WEST KAZAKHSTAN

Consequences of medical drugs use have been a subject of scientific research, both in terms of long-term effect on the gene pool of populations and immediate effects on human health. Drug-drug interactions (DDI) is an important and still insufficiently recognized cause of medical errors and costs for the healthcare system. We have studied the prevalence and structure of DDI in hospitals of West Kazakhstan. We performed a retrospective analysis of pharmacotherapy in a systematic sample of 730 patients with cardiovascular diseases treated in the hospitals of Aktobe, Uralsk, Atyrau cities in 2014. Potentially dangerous DDI were identified using Drug Interaction Checker source (FDA). The prevalence of major and moderate potential DDI and their structure were studied. Associations between DDI and other studied variables were estimated using odds ratios (OR) and chi-squared tests. For all estimates 95 % confidence intervals (CI) were calculated. We found a high prevalence of major and moderate DDI (53,8 (95 % CI 50,9-58,3) % and 88,1 (95 % CI 85,590,3) %, respectively. We found out that 53,8 % of patients were treated with at least one potentially inappropriate combination. The effect of age (OR 1,8, p 0,001, 95 % CI 1,4-2,5) and polypragmasy (OR 6,0, р 0,001, 95 % CI 2,7-13,1) on potentially dangerous DDI were revealed. Adverse drug effects were diagnosed in 4,1 % of patients, they were more frequently observed in patients with more prescriptions (р = 0,001). The most frequent drugs creating a dangerous combination were spironolactone, ACE inhibitors, enoxaparinm sodium, fondaparinux sodium, clopidogrel, potassium chloride, sartana.