Potential Drug Interactions Research Articles

Anti-Inflammatory Properties of Novel 1,2-Benzothiazine Derivatives and Their Interaction with Phospholipid Model Membranes

The design of novel anti-inflammatory drugs remains a critical area of research in the development of effective treatments for inflammatory diseases. In this study, a series of 1,2-benzothiazine was evaluated through a multifaceted approach. In particular, we investigated the potential interactions of the potential drugs with lipid bilayers, an important consideration for membrane permeability and overall pharmacokinetics. In addition, we evaluated their ability to inhibit cyclooxygenase 1 and cyclooxygenase 2 activity and selectivity using both a cyclooxygenase inhibition assay and molecular docking simulations. To evaluate their therapeutic potential, we performed in vitro assays to measure cytokine mRNA expression in inflamed cells. The antioxidant activity was evaluated using both in vitro assays, such as 2,2-diphenyl-1-picrylhydrazyl and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid scavenging, to determine the compounds’ capacity to neutralize free radicals and reduce oxidative stress. Theoretical calculations, including density functional theory, were used to predict the reactivity profiles of the compounds.

Prophylactic trimethoprim-sulfamethoxazole is safe in adult patients with primary central nervous system lymphoma receiving high-dose methotrexate.

This retrospective study investigated the potential drug-drug interactions between trimethoprim-sulfamethoxazole (TMP-SMZ) and high-dose methotrexate (HD-MTX) in adult patients with primary central nervous system lymphoma (PCNSL). A total of 143 Chinese adult patients with PCNSL who received 498 cycles of MTX were included. Differences in the pharmacokinetics of MTX, including Cmax, clearance (CL) and AUC0-48h with and without co-administration of TMP-SMZ were assessed. The incidence of MTX-related acute kidney injury (AKI), hepatotoxicity, myelosuppression, and delayed MTX elimination at 48 and 72h were also compared. Patients were divided into two cohorts for analysis: 146 cycles with TMP-SMZ exposure and 352 cycles without TMP-SMZ exposure. Patients who received TMP-SMZ concurrently with HD-MTX exhibited a 1.13-fold increase in Cmax, a 1.12-fold increase in AUC0-48h and a reduction in CL by 0.87-fold for MTX. There was no significant difference in the incidence of MTX-related AKI, hepatotoxicity, myelosuppression, or delayed MTX elimination between the two cohorts. Prophylactic TMP-SMZ might lead to increased MTX exposure but has no impact on the incidence of myelosuppression, AKI, and hepatotoxicity. These results suggested that prophylactic TMP-SMZ is safe for adult patients with PCNSL receiving HD-MTX.

Drug-Drug Interaction Potential of Mavacamten with Midazolam: Combined Results from Clinical and Model-Based Studies.

Mavacamten is a potential inducer of cytochrome P450 (CYP) 3A4 and could reduce the effectiveness of concomitant drugs that are metabolized by CYP3A4, such as midazolam. This study aimed to determine if repeat doses of mavacamten achieving clinically relevant exposures affected midazolam exposure. This was a single-center, open-label study in healthy participants. Participants received: on day 1, midazolam 5 mg; on days 2-3, mavacamten 25mg; on days 4-16, mavacamten 15 mg; and on day 17, mavacamten 15 mg and midazolam 5 mg. Plasma concentrations of mavacamten, midazolam, and the midazolam metabolite 1'-hydroxymidazolam were measured. A physiologically based pharmacokinetic (PBPK) model was used to simulate the effect of mavacamten-mediated CYP3A4 induction on midazolam exposure by CYP2C19 phenotype. Thirteen adult participants were enrolled (46.2% were female; mean [SD] age: 34.0 [9.0] years). Compared with midazolam alone, midazolam coadministered with mavacamten decreased the maximum observed plasma concentration (Cmax), area under the drug concentration-time curve (AUC) from time zero to infinity (AUC0-inf), and AUC from time zero to last measurable concentration (AUC0-last) for midazolam by 7%, 13%, and 24%, respectively; for 1'-hydroxymidazolam, AUC0-inf and AUC0-last increased by 20% and 11%, respectively. Ten participants experienced adverse events and the majority were mild in severity. The PBPK model predicted the clinical trial data well. The PBPK simulation assessed that the overall impact of mavacamten on midazolam Cmax and AUC was predicted to be weak regardless of CYP2C19 phenotype. At clinically relevant exposures, mavacamten had a negligible effect on midazolam exposure.

CYP3A4 drug metabolism considerations in pediatric pharmacotherapy

AbstractCytochrome P450 3A4 (CYP3A4) is a crucial enzyme involved in the Phase I metabolism of numerous medications used in clinical practice. Its potential significance in pediatric pharmacotherapy is underscored by the unique metabolic profile of children, which differs markedly from adults, especially in neonates, infants, and young children due to developmental changes in enzyme activity. This review explores the critical role of CYP3A4 in the metabolism of drugs used in the pediatric population, with a particular focus on combination drug therapies. Given the high potential for drug-drug interactions in combination therapies, understanding the modulation of CYP3A4 activity is essential for optimizing therapeutic outcomes and minimizing adverse effects. This paper further examines the structural similarities between these medications and bergamottin, a known CYP3A4 inhibitor found in citric fruits such as grapefruit. Variability in CYP3A4 activity, influenced by genetic polymorphisms, developmental stage, and external factors, necessitates careful consideration in the prescribing and management of drugs in children. This review corroborates the need for personalized medicine approaches and enhanced pharmacovigilance to ensure the safe and effective use of CYP3A4-metabolized drugs in the pediatric population. Graphical Abstract

Machine learning-based analysis of programmed cell death types and key genes in intervertebral disc degeneration.

Intervertebral disc degeneration (IVDD) is intricately associated with various forms of programmed cell death (PCD). Identifying key PCD types and associated genes is essential for understanding the molecular mechanisms underlying IVDD and discovering potential therapeutic targets. This study aimed to elucidate core PCD types, related genes, and potential drug interactions in IVDD using comprehensive bioinformatic and experimental approaches. Using datasets GSE167199, GSE176205, GSE34095, GSE56081, and GSE70362, relevant gene expression and clinical data were analyzed. Differential expression gene (DEG) analysis identified upregulated genes linked to 15 PCD types. Gene Set Variation Analysis (GSVA) was employed to pinpoint key PCD types contributing to disc degeneration. Core genes were identified through machine learning techniques, while immune infiltration and single-cell analysis helped identify apoptosis-related cell types. Molecular docking, along with in vivo and in vitro experiments using a murine IVDD model, validated potential drug interactions. The results identified apoptosis, autophagy, ferroptosis, and necroptosis as key PCD types in IVDD. A gene module associated with apoptosis showed a strong correlation with the severity of disc degeneration, revealing 34 central genes in the gene network. Drug screening identified Glibenclamide as effectively interacting with PDCD6 and UBE2K. Subsequent in vitro and in vivo experiments demonstrated that Glibenclamide reduced apoptosis and delayed disc degeneration progression. This study provides a comprehensive bioinformatics analysis of PCD in IVDD, identifying four primary PCD types contributing to the disease's progression. The findings offer novel insights into the molecular pathology of disc degeneration and suggest promising therapeutic strategies for future treatment development.

Evaluating Drug Interaction Risks: Nirmatrelvir & Ritonavir Combination (PAXLOVID®) with Concomitant Medications in Real-World Clinical Settings

Background: This research article delves into the battle against the COVID-19 pandemic, focusing on the efficacy and, particularly, the safety of the combination of nirmatrelvir with ritonavir, which is found in the pharmaceutical product Paxlovid®. This study aims to analyze the potential interactions of commonly prescribed medicinal products with Paxlovid®, shedding light on its utilization in specific medical fields. Methods: Prescription data from the Czech Republic’s Institute of Health Information and Statistics (IHIS CR) was analyzed, covering 4 million COVID-19 patients and 87.5 million medication records from September 2019 to February 2022. This study focused on potential drug interactions with Paxlovid among the 50 most frequently prescribed medications, with particular attention to four specialties: general medicine, internal medicine, infectious diseases, and diabetology. Results: In this study of the 50 most commonly prescribed drugs, 56% showed no interaction with Paxlovid, 30% had a potential for interaction, and 14% were not specifically mentioned in relation to Paxlovid, with no drugs found to be contraindicated overall. However, in specific medical fields, including diabetology, infectious diseases, internal medicine, and general medicine, certain drugs had potential interactions when co-administered with Paxlovid. Conclusions: Paxlovid remains a valuable option for early COVID-19 treatment but requires a careful consideration of potential drug interactions, especially in high-risk specialties. A thorough assessment of concurrent medications is essential to optimize safety and efficacy in patients receiving Paxlovid.

Warfarin pharmacokinetics and pharmacodynamics are not affected byconcomitant administration of the long-acting GLP-1 receptor agonist polyethylene glycol loxenatide.

To evaluate potential drug-drug interactions between polyethylene glycol loxenatide (PEX-168) and warfarin. This was an open-label, single-arm, two-treatment, sequential study. 16 healthy male subjects were administered warfarin (5 mg) alone on day 1 and received PEX-168 subcutaneously 200 µg once a week during days 14 - 42, with warfarin (5 mg) on day 44. Pharmacokinetics of R- and S-warfarin, as well as pharmacodynamics of warfarin, as measured by prothrombin time (PT) and international normalized ratio (INR), were assessed. The geometric mean ratios (GMRs) of area under the curve from time zero to the time of the last quantifiable concentration (AUC0-t) for PEX-168 + warfarin vs. warfarin were 0.950 (90% CI: 0.898, 1.006) for R-warfarin and 0.989 (90% CI: 0.946, 1.033) for S-warfarin. The GMRs of maximum observed plasma concentration (Cmax) values were 0.965 (90% CI: 0.893, 1.043) for R-warfarin and 0.983 (90% CI: 0.899, 1.075) for S-warfarin, both of which were contained in the interval 0.80 - 1.25. PEX-168 had no effect on the area under the effect-time curve from time 0 to 168 hours of INR and PT, as demonstrated by the GMRs of 0.987 (90% CI: 0.974, 1.000) and 0.990 (90% CI: 0.979, 1.002), respectively. Concomitant administration of PEX-168 and single-dose warfarin was well tolerated. PEX-168 had no effect on the pharmacokinetics or pharmacodynamics of warfarin.

Therapeutic drug monitoring for antimicrobial agents for people living with HIV (TAP)

Background Antimicrobial resistance (AMR) is a growing health concern, particularly in Africa, and is predicted to be the leading cause of death after cancer by 2050. Factors like overuse or inappropriate use of antibiotics, contribute to this crisis. People living with HIV (PLWH) are particularly vulnerable to AMR with potential drug-drug interactions between antiretroviral and antimicrobial agents against common organisms like Mycobacterium tuberculosis. There is limited data on the concentrations of commonly used antimicrobial agents in people living with HIV in resource-limited settings. Therapeutic Drug Monitoring (TDM) offers a promising approach to optimize antibiotic dosing and improve treatment outcomes for those with sub-optimal drug concentrations. TDM has been recommended for PLWH on anti-tuberculosis treatment due to sub-optimal drug concentrations found in a significant proportion of those with TB. Objectives The main objectives of this study are to determine the concentrations of selected antimicrobial agents in people living with HIV requiring antimicrobial therapy and to assess the utility of therapeutic drug monitoring in achieving therapeutic targets for PLWH receiving rifampicin and isoniazid for the treatment of tuberculosis Methods This prospective observational study will enroll adult PLWH receiving amoxicillin, azithromycin, ciprofloxacin, rifampicin, isoniazid, or ceftriaxone. Concentrations of these antibiotics will be measured locally using validated liquid chromatography mass spectrometry methods and high-performance liquid chromatography with ultraviolet detection. TDM with dose adjustment will be performed in a subset of participants on TB treatment. Pharmacokinetic parameters will be estimated using non-linear mixed effects models. Results This study was reviewed and approved by the research and ethics committee in February 2024. Enrolment is projected to begin by August 2024. Conclusions We anticipate that the findings from this research will characterize pharmacokinetic and pharmacodynamics relationships to predict treatment response for optimal antimicrobial therapeutic and anti-tuberculosis dosing among people living with HIV (PLWH). Clinical registration The study is registered with Pan African Clinical Trials Registry, registration number PACTR202409710100607, registration date 07 August 2024, pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=31764

Prevalence and Associated Factors of Drug-Drug Interactions in Hospitalized Diabetic Patients: A Cross-Sectional Study

Diabetes mellitus is a chronic metabolic condition frequently associated with complications and comorbidities that often require hospitalization for effective management. Such patients are often prescribed multiple medications, which elevate the risk of potential drug-drug interactions (pDDIs). Hence, this study aims to determine the prevalence, severity, common interacting pairs, and factors associated with pDDIs among hospitalized diabetes patients. The study used a retrospective cross-sectional study design conducted at Universitas Indonesia Hospital. Lexicomp® Lexi-InteractTM software was used to analyze and classify possible drug interactions. Logistic regression analysis was used to identify different factors associated with potential DDIs. Of the 200 patients, 89.0% were observed to have pDDIs. A total of 966 interactions were found, of which 75.6% were moderate, 16.2% were minor, and 8.1% were of major severity. Meanwhile, in the risk rating C category, 71.0% were predominant, followed by B and D, 15.0% and 11.0%, respectively. Multivariate regression analysis showed a statistically significant association of pDDIs with 5–8 prescribed medicines (OR=22.8; 95% CI=5.5-94.7; p<0.001), >8 prescribed medicines (OR=64.4; 95% CI=11.3-336.5; p<0.001). The findings of this study revealed that pDDIs are highly prevalent in adult inpatients with diabetes. This emphasizes the critical need for appropriate monitoring and management strategies to reduce pDDIs and their adverse consequences.

Assessment of Potential Drug-Drug Interactions of Psycholeptics and Antidepressants in Outpatient Settings.

Mental health is an important segment in preserving overall health and represents a significant public health issue. In modern times, mental health disorders have risen, often requiring complex pharmacotherapy and chronic monitoring. The aim of this research was to determine the prevalence and clinical significance of potential psychotropic drug interactions in outpatient settings and compare the differences in potential drug-drug interaction (pDDIs) exposure with age. The psychotropic drugs included antipsychotics-N05A, anxiolytics-N05B, hypnotics and sedatives-N05C, and antidepressants-N06A. This retrospective study analyzed prescribed pharmacotherapy in 492 outpatients who were treated with at least one psychotropic drug. We determined 1.64 prescribed psychotropic drugs per patient and 2.2 pDDIs that involved psychotropic drugs. In total, 2285 pDDIs were recorded, of which almost half (47.6%) were pDDIs with psychotropic drugs. More prescribed psychotropic drugs were found in patients younger than 65 years, and equal exposure to pDDIs of psychotropic drugs (p = 0.5077) was found in both age groups. The most commonly identified psychotropics involved in pDDIs were benzodiazepines, promazine, and zolpidem. The results indicate that psychotropic drug interactions represent important drug-related problems for primary health care. The widespread use of psychotropic drugs and the determined clinical significance of their interactions require pharmacist interventions which can reduce the prevalence of pDDIs and increase patient safety.

Patterns of medication use and potential drug-drug interactions in post-PCI patients: A study from Iran

BackgroundPost-percutaneous coronary intervention (PCI) patients often require complex medication regimens to prevent adverse cardiovascular events. However, these regimens can lead to potential drug-drug interactions (pDDIs) and polypharmacy, posing significant clinical challenges. This study aims to evaluate the pattern of medication use, prevalence, and correlates of pDDIs and polypharmacy among post-PCI patients in Shiraz, Iran. MethodsA cross-sectional study was conducted on 9019 PCI patients in Shiraz. Patient data, including demographics, medical history, and medication lists, were collected and analyzed. The Anatomical Therapeutic Chemical (ATC) classification system was applied. pDDIs were identified using the Lexicomp database, and their severity was classified. Factors associated with significant pDDIs and polypharmacy were assessed using multivariable modeling. ResultsThe study found that 91.6 % of patients received statin prescriptions and 94.5 % were on antiplatelet therapy. Notably, 82.8 % were identified with at least one pDDI, with 80.4 % having significant interactions (Categories C, D, or X). Common potential interactions included aspirin with clopidogrel and rosuvastatin. Polypharmacy was prevalent in 73.6 % of patients, associated with higher risks of interactions. Factors such as polypharmacy, male gender, diabetes mellitus, and heart failure were significant predictors of pDDIs. ConclusionsThe study underscores the high prevalence of pDDIs and polypharmacy among post-PCI patients, revealing a critical gap between clinical guidelines and drug interaction databases. Updating interaction databases to reflect current clinical practices and enhancing collaboration between database developers and guideline authors are essential for improving medication safety and patient outcomes.

PBPK modelling for the evaluation of drug-drug interaction between meropenem and valproic acid.

The present study aimed to quantitatively investigate the potential drug-drug interaction (DDI) mechanism between meropenem (MEPM) and valproic acid (VPA). In the present study, we firstly developed a physiologically based pharmacokinetic (PBPK) model of MEPM and VPA. The verified PBPK model was then used to quantitatively investigate the potential DDI between MEPM and VPA. The effect of genetic polymorphisms of acylpeptide hydrolase (APEH) on DDI was also evaluated. In our simulation, the plasma concentration of hydrolysate of VPAG decreased to 63% when combined with MEPM. Total plasma concentration of VPA before carbapenem use was 53.61 mg/L, whereas it was 45.42 mg/L during carbapenem use. The inhibition of hydrolysis of VPAG by MEPM alone could not result in a rapid and substantial decrease in the plasma concentration of VPA. Parameter sensitivity analysis showed that the changes of absorption played an important role in the maximum plasma concentration (Cmax) of VPA, whereas area under the plasma concentration-time profile (AUC) was more susceptible to elimination changes. In addition, a decrease in APEH activity had little impact on the plasma pharmacokinetics of VPA. The DDI between MEPM and VPA might be a comprehensive result of multiple factors. On the basis of our simulation, interval medication of MEPM injection and VPA immediate release tablet at 4-6h timed interval was recommended, or intravenous administration of VPA solution was preferred when combination regimen was necessary in a clinical setting.

Evaluating the drug-drug interactions of SHR4640 on repaglinide and midazolam in healthy subjects

ABSTRACT Background SHR4640, a highly selective URAT1 inhibitor, was evaluated to investigate its inhibitory effects on CYP2C8 and CYP3A4 in vivo clinical trial. This study assessed the pharmacokinetic (PK) impact of SHR4640 when co-administered with the CYP2C8 probe substrate repaglinide and the CYP3A4 probe substrate midazolam. Research design and methods In this single-center, randomized, double-blind, placebo-controlled study, participants were randomly allocated in a 1:1:1 ratio to SHR4640 Group A, SHR4640 Group B, and placebo group and received oral repaglinide, midazolam, SHR4640 or placebo at specific times. The primary endpoints included the main PK parameters of repaglinide and midazolam, both alone and in combination with SHR4640 (AUC0-inf, AUC0-t, and Cmax). Results The increase in the area under the concentration-time curve (AUC) for repaglinide, when co-administered with SHR4640, was less than 1.25-fold, while the AUC for midazolam exhibited a slight increase of 46%. Conclusions SHR4640 exerts a weak inhibitory effect on the AUC of CYP enzyme probe substrates and has minimal potential for drug-drug interactions and presents a favorable safety profile. Clinical trial registration www.clinicaltrials.gov identifier is NCT06196580 (Name: PK Effects of SHR4640 on Repaglinide and Midazolam, and the Impact of SHR4640 on QT Interval).

Complexity of the Therapeutic Regimen in Older Adults with Cancer: Associated Factors.

Population aging is a worldwide phenomenon and is often associated with multimorbidity and polypharmacy. Complex medication regimens are common among older adults and contribute to the occurrence of harmful health outcomes. Age is one of the main risk factors for cancer. This study aimed to determine and characterize the therapeutic complexity in older patients with cancer, and analyze the factors associated with high complexity and the impact of the oncological context. A cross-sectional study with patients aged ≥65 years with cancer was conducted in three hospitals in northern Portugal. Data collection was obtained using self-reports. The medication regimen complexity was assessed using the Medication Regimen Complexity Index (MRCI). Descriptive and association statistical analysis were performed. Logistic, linear, simple and multiple regression analysis were conducted, with and without automatic variable selection. A total of 552 patients were included (median age, 71; IQR, 68-76). The mean MRCI before the oncological context was 18.67 (SD 12.60) and 27.39 (SD 16.67) after the oncological context, presenting a statistically significant difference in the values obtained (p < 0.001). An elevated complexity was significantly associated with polypharmacy, chronic diseases and with the administration of high-risk medications (p < 0.05). High MRCI values showed a relationship with the occurrence of potential drug interactions (p < 0.001). There was no relationship with the existence of cardiac risk comorbidity. This study demonstrated the existence of high therapeutic complexity in older patients with cancer, suggesting the need for intervention to prevent medication-related problems in this vulnerable population.

Triterpenoids from Ganoderma lucidum inhibit cytochrome P450 enzymes interfering with the metabolic process of specific clinical drugs.

Ganoderma lucidum (G. lucidum), which possesses various biological effects, has been widely used as traditional medicine and functional food in Asian countries, especially China. In consideration of its various biological effects on human healthcare, G. lucidum was usually used in combination with other drugs. However, the potential drug-drug interaction induced by G. lucidum through cytochrome P450 enzymes (CYPs) remain unknown. Using the in vivo activity assay of CYPs, the inhibitory effects of G. lucidum and its constituents could be evaluated. The interference of G. lucidum on the metabolic processes of clinical drugs could be investigated. The chemical constituents of G. lucidum could be identified using LC-MS. The interaction between bioactive compounds and CYPs could be proposed through in silico docking analysis and molecular dynamics. The dichloromethane extract of G. lucidum could inhibit various CYP450 subtypes in vitro and interfere with the pharmacokinetics of four drugs in rats. Triterpenoids were identified as the main constituents of the dichloromethane extract by Q-TOF-MSn in preliminary analyses. Then, a triterpenoid library containing 66 compounds was established to evaluate their inhibitory effects against CYP 1A2, 2D6, 3A4, 2A6, 2B6, 2C9, and 2C19. CYP 1A2 was inhibited by most lanostane triterpenoids, indicating a strong affinity for these compounds. Among triterpenoids, compound 25 displayed a broad inhibitory effect against CYPs, except for CYP 3A4, 2D6, 2C9, and 2C19. Finally, compounds 6 and 25 exhibited interference with the metabolism of 16 drugs through the inhibition of CYPs in vitro. In silico molecular docking analyses for assaying the interaction between compound 25 and CYPs indicated that the hydrogen bonds formed between the hydroxyl groups and amino acid residues. G. lucidum displayed broad inhibitory effects on CYPs, with triterpenoids as the main bioactive constituents, which may induce potential drug-drug interaction. This information should be helpful for the rational use of G. lucidum in promoting human health.

Drug Interactions in People on Cannabidiol: Is There Cause for Concern?

Introduction: Cannabidiol (CBD) exhibits multiple therapeutic properties, but its use in advanced cancer patients raises concerns about potential drug-drug interactions (DDIs) due to polypharmacy. This study aims to look for evidence of DDIs between concomitant medications and CBD oil in a randomized placebo-controlled trial of CBD oil for symptom control (MedCan-1 parent study). Materials and Methods: Surrogate measures were used to identify possible drug interactions: (1) the maximum mL of oil self-selected by patients in CBD or placebo groups in relation to opioids, specific drug groups, or individual agents; (2) the occurrence of any new or worse adverse effect in relation to the study arm and the concomitant medication classes/medications of interest. Results: The dose of CBD self-selected by participants was not related to opioid use or medications, including benzodiazepines and antipsychotics. The likelihood of developing an adverse effect while on study or when taking specific medications was not increased by CBD. Participants on paracetamol tolerated a higher dose of CBD. Discussion: Concerns regarding the development of clinically significant drug interactions when taking CBD in the context of anti-cancer and other concomitant medications at least in the short term may be unfounded.

CNS histoplasmosis coexisting with pulmonary tuberculosis in a HIV negative patient: case report

BackgroundTuberculosis is a highly prevalent disease in India, while Histoplasmosis, an emerging disease, is often underreported due to limited resources in developing countries. Coinfection with both these organisms is rarely documented in immunocompetent host. Due to overlapping symptoms, it can be easily missed and treatment delays are not uncommon.Case PresentationHere, we report a case of a 62-year-old male with a chronic history of intermittent fever and dry cough, splenomegaly, lymphadenopathy, and persistent pancytopenia. He was diagnosed with tuberculosis with cartridge-based nucleic acid amplification test (CBNAAT) positivity from a paratracheal lymph node biopsy. Simultaneously, a bone marrow biopsy revealed Histoplasmosis and the patient was started on dual treatment (Itraconazole and antitubercular drugs). After an initial response, the patient developed new space-occupying cerebral lesions. CSF histoplasma antigen was also positive. The reason for treatment failure was likely to be drug interaction (suboptimal levels of itraconazole due to rifampicin). The patient received liposomal amphotericin and subsequently put on a modified antitubercular treatment regimen to avoid interaction with itraconazole. At 2-month follow-up, the patient’s condition significantly improved with a substantial resolution in CNS lesions.ConclusionsHistoplasmosis and tuberculosis have overlapping symptoms, diagnosing one does not preclude the possibility of other, even in non-HIV patients. Clinicians should also be vigilant about potential drug interactions.

Patiromer Does Not Alter Tacrolimus Pharmacokinetics in Kidney Transplant Recipients When Administered Three Hours Post-Tacrolimus.

Hyperkalemia is common in kidney transplant (KTx) recipients. Patiromer, a potassium-binding polymer used to treat acute and chronic hyperkalemia, has the potential to bind charged particles in the gastrointestinal tract and thereby potentially affect the absorption of coadministered drugs. The immunosuppressive drug tacrolimus (Tac) has a narrow therapeutic window, is susceptible to drug-drug interactions (DDIs), and a potential gastrointestinal interaction with patiromer could elevate the risk of allograft rejection. We aimed to investigate the potential DDI between patiromer and Tac pharmacokinetics in KTx with hyperkalemia by sampling capillary blood using volumetric absorptive microsampling (VAMS). Thirteen KTx recipients on Tac twice daily (BID) with plasma potassium levels of >4.6 mmol/L were included. Two 12 h Tac pharmacokinetic investigations were performed with and without 8.4 mg patiromer/d for 1 wk. Oral Tac dose remained unchanged and patiromer was administered 3 h after Tac dose. Tac sampling was self-conducted using VAMS after mastering the technique. Ten patients provided 2 evaluable pharmacokinetic profiles. The Tac area under the curve (AUC)0-12 ratio (AUCTac+patiromer/AUCTac) was 0.99 (90% confidence interval [CI], 0.86-1.14), and the Cmax ratio was 1.01 (90% CI, 0.86-1.19). Tac C0 and C12 fulfilled the bioequivalence criteria with a ratio of 0.98 (90% CI, 0.90-1.07) and 0.93 (90% CI, 0.83-1.04), respectively. When administered 3 h after the Tac morning dose, patiromer has no clinically relevant impact on Tac pharmacokinetics. We demonstrate that VAMS is a well-suited sampling method to simplify the execution of DDI studies.

Assessment of potential drug-drug interactions in hospitalized patients with infectious diseases: an experience from a secondary care hospital

Background Polypharmacy is common among hospitalized patients with infectious infections owing to comorbidities or concomitant illnesses. This raises the likelihood of drug-drug interactions and creates uncertainty for healthcare providers. This study aimed to assess the potential drug-drug interactions (pDDIs) among hospitalized patients with infectious diseases in a secondary care hospital. Methods A prospective observational study was conducted in the internal medicine ward for six months after the ethics committee’s approval. Data were collected from patient case records, and prescriptions were screened for pDDIs from a portable electronic physician information database (PEPID) resource analyzed using SPSS, version 27.0. Results In total, 148 patient case records were analyzed, and 549 pDDIs were identified, with 66.8% having at least one or more DDIs. The mean number of drug interactions was 3.70 ± 4.58 per prescription. The most frequently encountered drug interactions were drug combinations such as bisoprolol with atorvastatin and aspirin with tazobactam/piperacillin. Bivariate analysis showed that age, comorbidities, length of hospital stay, and the number of drugs prescribed were risk factors associated with DDIs (p&lt;0.05). In the multiple binary logistic regression analysis, DDIs were significantly associated with comorbidities and the number of prescribed medications (p&lt;0.0001). Conclusions This study observed the prevalence of DDIs in hospitalized patients with infectious diseases of ‘moderate’ severity. Prescription screening using a drug information database assists in early identification and prevention of DDIs, enhancing drug safety and quality of patient-centered care.

The patient's level of knowledge about analgesic drug self-medication

Introduction: Self-medication is the practice of using drugs without a doctor's prescription to overcome minor health problems, one of which is analgetic drugs to reduce pain. Although self-medication can improve the accessibility of medications, improper use can be risky for the patient's health. Adequate knowledge of the types, dosages, and ways of using analgesic medications is essential to ensure effectiveness and avoid adverse side effects. This study aims to evaluate the level of patient knowledge about analgetic drug self-medication. Methods: This study uses a quantitative design with a survey approach. Data was collected through a questionnaire distributed to 81 patients who visited the pharmacy. Results: The results of this study indicate that the percentage of respondents' answers is 8.091%. Based on these results, it can be concluded that the level of patient knowledge about self-medication of analgtic drugs is in a good category. Conclusions: The results showed that the majority of patients had sufficient knowledge about the indications and dosage of analgetic drugs, but there was a gap in understanding of potential side effects and drug interactions. This indicates the need for more intensive health education regarding self-medication, especially in the use of analgesic drugs, to reduce the risk of inappropriate use