Pharmacoepidemiology, Volume 3, Issue 4 (December 2024) – 8 articles

Doxycycline is a semi-synthetic antibiotic in the tetracycline family. The three common subtypes of tetracyclines include naturally occurring, semi-synthetic, and new agents. Each subtype shares specific commonalities but is substantially different in various clinical applications. The mechanism of antimicrobial activity is the same across subtypes. The structural changes to the core naphthacene ring do not alter the mechanism of action but are thought to alter the rates of adverse effects and mechanisms of resistance. Tetracyclines as a class are known to cause fixed drug eruptions, but the majority of these adverse effects were associated with naturally occurring tetracyclines. Semi-synthetic tetracyclines have limited reports of fixed drug eruptions. Here, we present a case of fixed drug eruption in a patient who previously had multiple treatment courses with doxycycline. The case involves the use of doxycycline not for the treatment of an infection but as postexposure prophylactic (PEP) antibiotic therapy to prevent the acquisition of a sexually transmitted infection. Doxycycline PEP has been shown to reduce the rate of bacterial sexually transmitted infection in men who have sex with men (MSM). Doxycycline PEP is a single dose taken orally within 24–72 h of unprotected sexual intercourse. The dosing structure allows for ease of adherence but also repeatedly exposes individuals to doxycycline, putting them at risk for adverse events such as fixed drug eruptions, as illustrated by this case report. Full article

Background: Sodium–glucose cotransporter-2 inhibitors (SGLT2Is) have demonstrated effects beyond glucose-lowering, leading to their approval for treating chronic heart failure (HF) in Japan. This study examines prescription trends for SGLT2Is in patients with diabetes versus those without diabetes, focusing on their backgrounds and HF treatment status of patients without diabetes who received SGLT2I after an HF diagnosis. Methods: Using data from DeSC Healthcare Inc., we analyzed patients aged 65 and above who received their first SGLT2I prescription between October 2014 and February 2023. Patients were classified into SGLT2I-treated diabetic and non-diabetic groups. We analyzed the annual prescription trends and compared the characteristics of both groups who started SGLT2I between 2022 and 2023. Additionally, we assessed the timing of SGLT2I initiation and the use of concomitant HF treatment in patients without diabetes after HF diagnosis. Results: The proportion of patients without diabetes receiving their first SGLT2I prescription has increased since 2021. Patients without diabetes receiving SGLT2Is were older, likely owing to aging-related diseases. In patients without a confirmed diabetes diagnosis, SGLT2I was most frequently initiated at the time of HF diagnosis. Mineralocorticoid receptor antagonists (MRAs) are the most common concomitant HF medications. The increase in SGLT2I prescriptions for patients without diabetes receiving SGLT2I since 2021, particularly in older individuals, suggests that SGLT2I is being initiated either at the time of HF diagnosis or in a stepwise manner. Conclusion: In Japan, MRA is commonly used as a concomitant medication in patients without diabetes receiving SGLT2I. Full article

Background/Objectives: Several drugs used to treat prostate cancer have been reported to cause cardiovascular adverse events, and this study sought to identify the real-world risk. Methods: This study utilized real-world data from the FAERS to analyze the association between prostate cancer treatment and cardiovascular adverse events. It evaluated men treated with LHRH agonists and antagonists, antiandrogens, androgen synthesis inhibitors, and PARP inhibitors from 2003 to 2023. This study included patients treated with leuprolide, goserelin, triptorelin, degarelix, relugolix, bicalutamide, flutamide, apalutamide, nilutamide, abiraterone, enzalutamide, olaparib, rucaparib, talazoparib, and niraparib. The main outcome measure was the reported odds ratio (ROR) of adverse cardiovascular event associated with these treatments. Results: Among the 4,049,329 unique adverse event reports, 4391 cardiovascular events were identified. Leuprolide (ROR 0.481, 95% CI: 0.423–0.547), triptorelin (ROR 0.527, 95% CI: 0.305–0.909), enzalutamide (ROR 0.393, 95% CI: 0.341–0.452), and olaparib (ROR 0.145, 95% CI: 0.054–0.386) reduced the risk of myocardial infarction. Goserelin increased the risk of myocardial infarction (ROR 2.235, 95% CI: 1.367–3.654). Degarelix and relugolix both increased the risk of heart failure (ROR 3.136, 95% CI: 2.186–4.497), and enzalutamide was associated with an increased risk of heart failure (ROR 1.305, 95% CI: 1.135–1.501). Bicalutamide increased the risk of unstable angina (ROR 3.019, 95% CI: 1.621–5.622) and heart failure (ROR 3.730, 95% CI: 3.085–4.510). Niraparib increased the risk of hypertension (ROR 4.154, 95% CI: 1.709–10.092). Conclusions: These findings underscore the need for clinicians to monitor cardiac complications in patients undergoing these therapies. Full article

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as a potent therapeutic option for the management of obesity, demonstrating exceptional efficacy in several large-scale clinical trials. Despite their promising therapeutic outcomes, the rising popularity of these agents raises significant concerns, particularly regarding their off-label use by individuals seeking weight loss for aesthetic reasons rather than addressing underlying metabolic health conditions. This article critically evaluates the efficacy and safety of GLP-1 RAs in obesity management. Additionally, it explores the economic implications and ethical challenges associated with the increasing demand for GLP-1 RAs. By addressing these dimensions, this article aims to facilitate informed and responsible decision-making in clinical practice, highlighting the need for individualized patient assessments and careful consideration of both short- and long-term safety risks. Full article

Background: Antibiotic resistance represents a growing concern. A new strategy developed to treat severe infections is represented by ceftazidime/avibactam (CZA/AVI). Despite the promising activities against more pathogens, continuous monitoring is required to identify potential antibiotic resistance in clinical practice settings. Therefore, real-world data from pharmacovigilance databases can help to better define the safety profile. Methods: We analyzed all Individual Case Safety Reports (ICSRs) collected in the EudraVigilance database focusing on ICSRs with at least one adverse event (AE) potentially suggestive of drug resistance (DR) and drug ineffectiveness (DI). Results: A total of 654 ICSRs related to CZA/AVI were retrieved from EudraVigilance, of which N = 378 (57.8%) were related to male and N = 230 (35.1%) to adult patients. A total of 80.2% of all AEs were serious but with a positive outcome. Overall, we found N = 129 (19.7%) cases of potential DR or DI after CZA/AVI administration. The majority of CZA/AVI-induced DR or DI occurred in adult male patients. The most frequently reported AEs were “drug ineffective” and “pathogen resistance”. Lastly, CZA/AVI was mostly used for the treatment of “Klebsiella infection” and “Pneumonia”. Conclusions: The present study showed how pharmacovigilance could play a key role in generating evidence about the safety profile of CZA/AVI. Further studies are warranted. Full article

The state of knowledge regarding the teratogenic effects of maternal use of medications during pregnancy is constantly evolving and is often uncertain. Timely access to high-quality information may reduce prolonged harmful exposures, decrease the number of preventable birth defects, empower patients with accurate information about the risks of exposure, and prevent unnecessary patient anxiety and pregnancy termination. In this narrative review, we describe the process by which the teratogenic risk of medications is assessed by experts in medicine, genetics, and epidemiology and how identifiable risks can be effectively communicated to patients. Risk assessment of birth defects in human pregnancy involves collecting and synthesizing available data through a proper and rule-driven evaluation of scientific literature. Expert consensus is a practical approach to determine whether a given exposure produces damage after careful consideration of gestational timing, dose and route of the exposure, maternal and fetal genetic susceptibility, as well as evidence for biological plausibility. The provision of teratogen risk counseling through appropriate interpretation of information and effective knowledge translation to the patient is critical for the prevention of birth defects and maximizing healthy pregnancies. Full article

(1) Background: Although Sri Lanka is a developing country and boasts of having a well-established healthcare system along with good healthcare indices, we are still lagging in certain aspects of healthcare. One such aspect is the deficiencies in guidelines and practices related to the handling of pharmaceutical waste. (2) Methods: This was a qualitative study performed using in-depth interviews with the help of a semi-structured questionnaire conducted among staff who are working at a ministry complex in Galle, Sri Lanka. Data analysis was performed using thematic analysis, (3) Results: There were 40 participants which included 29 (72.5%) females. Three main themes were identified, namely, (I) current knowledge, (II) perceptions, and (III) practices towards storage, disposal, and misuse of pharmaceutical waste. The death of the patient, forgetting, relieving symptoms, and adverse effects were some reasons for the accumulation of unused pharmaceuticals at home. Most of the participants did not believe that the reuse of unused medications can cause various health hazards. Moreover, all participants practiced unsafe methods such as flushing down toilets, pouring into a sink, burning, etc. (4) Conclusions: The incorrect practices and poor knowledge in the handling of pharmaceutical waste and less concern for the environment highlight the need for awareness programs to the general public and establishing proper medication waste management such drug take-back systems. Full article

Dalbavancin, a semi-synthetic lipoglycopeptide with an extended half-life that allows for weekly dosing, is currently approved for the treatment of bacterial skin and soft tissue infections caused by susceptible gram-positive organisms. This case report discusses the successful treatment of septic arthritis with dalbavancin in a 38-year-old obese male. Septic arthritis, commonly caused by Staphylococcus aureus and Streptococcus species, was diagnosed in this patient following a mechanical fall that led to worsening shoulder pain. Given the patient’s morbid obesity and concerns about antibiotic penetration, dalbavancin 1500 mg IV biweekly was chosen for its extended half-life and ease of administration. This case underscores dalbavancin’s efficacy in managing septic arthritis in obese patients, offering a convenient alternative to traditional therapies that require a peripherally inserted central catheter (PICC line), frequent dosing, therapeutic monitoring, and prolonged hospital stays. Despite its higher cost, dalbavancin’s advantages include reduced need for PICC lines, additional staff and resources to monitor therapeutic drug levels, and fewer complications, which can offset some expenses. To our knowledge, this is the first documented case investigating the use of dalbavancin for enterococcal septic arthritis with a biweekly dosing regimen. Full article