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British Journal of Clinical Pharmacology Oct 2022Use of immunomodulating therapeutics for immune-mediated inflammatory diseases may cause disease-drug-drug interactions (DDDIs) by reversing inflammation-driven... (Review)
Review
AIM
Use of immunomodulating therapeutics for immune-mediated inflammatory diseases may cause disease-drug-drug interactions (DDDIs) by reversing inflammation-driven alterations in the metabolic capacity of cytochrome P450 enzymes. European Medicine Agency (EMA) and US Food and Drug Administration (FDA) guidelines from 2007 recommend that the DDDI potential of therapeutic proteins should be assessed. This systematic analysis aimed to characterize the available DDDI trials with immunomodulatory drugs, experimental evidence for a DDDI risk and reported DDDI risk information in FDA/EMA approved drug labelling.
METHOD
For this systematic review, the EMA list of European Public Assessment Reports of human medicine was used to select immunomodulating monoclonal antibodies (mAbs) and tyrosine kinase inhibitors (TKIs) marketed after 2007 at risk for a DDDI. Selected drugs were included in PubMed and Embase searches to extract reported interaction studies. The Summary of Product Characteristics (SPCs) and the United States Prescribing Information (USPIs) were subsequently used for analysis of DDDI risk descriptions.
RESULTS
Clinical interaction studies to evaluate DDDI risks were performed for 12 of the 24 mAbs (50%) and for none of the TKIs. Four studies identified a DDDI risk, of which three were studies with interleukin-6 (IL-6) neutralizing mAbs. Based on (non)clinical data, a DDDI risk was reported in 32% of the SPCs and in 60% of the USPIs. The EMA/FDA documentation aligned with the DDDI risk potential in 35% of the 20 cases.
CONCLUSION
This systematic review reinforces that the risk for DDDI by immunomodulating drugs is target- and disease-specific. Drug labelling information designates the greatest DDDI risk to mAbs that neutralize the effects of IL-6, Tumor Necrosis Factor alfa (TNF-α) and interleukin-1 bèta (IL-1β) in diseases with systemic inflammation.
Topics: Antibodies, Monoclonal; Drug Approval; Drug Interactions; Drug Labeling; Humans; Immunomodulating Agents; Inflammation; Interleukin-1beta; Interleukin-6; Pharmaceutical Preparations; Protein Kinase Inhibitors; Risk Assessment; Tumor Necrosis Factor-alpha; United States; United States Food and Drug Administration
PubMed: 35484780
DOI: 10.1111/bcp.15372 -
Journal of Patient Safety Jun 2022This systematic review aims to identify and critically evaluate the available evidence on the impact of switches in pill appearance/packaging on patient's behavior.
OBJECTIVE
This systematic review aims to identify and critically evaluate the available evidence on the impact of switches in pill appearance/packaging on patient's behavior.
METHODS
Studies from inception to March 2021 were searched across MEDLINE through PubMed, the Cochrane Library, Embase, and Scopus. Included studies carried out an original evaluation in English or Spanish language that evaluated the impact of switches in pill appearance/packaging on patient's behavior. Two authors independently extracted study data and evaluated studies for methodological quality according to the STROBE guidelines.
RESULTS
Ten studies were included, and the mean (SD) number of STROBE criteria satisfied was 17.2 (3.9). Three of 5 studies found a significant association between change in pill appearance and persistence to treatment; the 3 studies that evaluated the impact of a change on adherence to treatment found a significant association; 1 of the 2 studies that evaluated the relationship between a change a clinical outcome found a significant association with the prevalence of uncontrolled blood pressure; and 1 study showed lower rates of switchbacks to the branded product compared with patients who switched to generic drug products, with different appearance.
CONCLUSIONS
This systematic review showed an impact of the change in pill/package appearance on patients' behavior in 7 of the 10 studies included. Generic switching may lead to unintended consequences on patients' behavior, mainly regarding adherence to treatment.
Topics: Drug Packaging; Drugs, Generic; Humans
PubMed: 35452203
DOI: 10.1097/PTS.0000000000000941 -
The International Journal of Pharmacy... May 2022Dose administration aids (DAAs) or multi-compartment compliance aids are commonly used to organise doses of medications in accordance with a patient's dosing schedule....
BACKGROUND
Dose administration aids (DAAs) or multi-compartment compliance aids are commonly used to organise doses of medications in accordance with a patient's dosing schedule. Despite their widespread use, there is a paucity of information on the stability of repackaged medications in DAAs.
OBJECTIVES
The objectives of this work were to evaluate stability studies conducted on repackaged medicine in DAAs and to provide a summary of the latest stability data available.
METHODS
A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed on studies associated with repackaged medications in DAAs and drug stability. PubMed, CINAHL, EMBASE and SCOPUS were searched from January 1998 to June 2021.
KEY FINDINGS
A total of 342 articles were retrieved and 29 articles met the inclusion criteria. Data regarding medications from the reviewed papers were reported according to stability testing and physicochemical properties. The extracted data were then compared with stability information on DAA provision available on the database in the UK. This review identified several discrepancies between this dataset and reported stability and reveals a significant shortage in the stability data of medications repackaged in DAAs.
CONCLUSION
This review highlights the need for further studies to be conducted to better understand the impact of DAA repackaging on the stability, safety and efficacy of medications. It is recommended that a database of stability information of repackaged medications via systematic stability testing studies could be established, serving as a valuable resource for pharmacists when preparing DAAs without compromising patient safety.
Topics: Drug Packaging; Drug Stability; Humans; Pharmaceutical Preparations; Pharmacists
PubMed: 35435960
DOI: 10.1093/ijpp/riac001 -
Toxicology Nov 2021Phthalates are chemicals widely used in packaging and consumer products, which have been shown to interfere with normal hormonal function and development in some human...
UNLABELLED
Phthalates are chemicals widely used in packaging and consumer products, which have been shown to interfere with normal hormonal function and development in some human and animal studies. In recent decades, pregnant women's exposure to phthalates has been shown to alter the cognitive outcomes of their babies, and some studies have found delays in motor development.
METHODS
electronic databases including PubMed/MEDLINE and Scopus were searched from their inception to March 2021, using the keywords "phthalate", "cognitive" and "motor".
RESULTS
most studies find statistically significant inverse relationships between maternal urinary phthalate concentration during pregnancy and subsequent outcomes in children's cognitive and motor scales, especially in boys rather than girls. However, many associations are not significant, and there were even positive associations, especially in the third trimester.
CONCLUSION
the relationship between exposure to phthalates during pregnancy and low results on neurocognitive scales is sufficiently clear to adopt policies to reduce exposure. Further studies are needed to analyze sex differences, coordination and motor scales, and phthalate levels during breastfeeding.
Topics: Animals; Cognition; Female; Humans; Male; Maternal Exposure; Motor Skills; Phthalic Acids; Pregnancy; Prenatal Exposure Delayed Effects; Sex Factors
PubMed: 34624397
DOI: 10.1016/j.tox.2021.152980 -
Endocrine, Metabolic & Immune Disorders... Aug 2022Endocrine disrupting chemicals (EDCs) are found in plastics, personal care products, household items, and other consumer goods. Risk assessments are intended to...
BACKGROUND
Endocrine disrupting chemicals (EDCs) are found in plastics, personal care products, household items, and other consumer goods. Risk assessments are intended to characterize a chemical's hazards, identify the doses at which adverse outcomes are observed, quantify exposure levels, and then compare these doses to determine the likelihood of risk in a given population. There are many problems with risk assessments for EDCs, allowing people to be exposed to levels that are later associated with serious health outcomes in epidemiology studies.
OBJECTIVE
In this review, we examine issues that affect the evaluation of EDCs in risk assessments (e.g., use of insensitive rodent strains and absence of disease-oriented outcomes in hazard assessments; inadequate exposure assessments). We then review one well-studied chemical, Bisphenol A (BPA; CAS #80-05-7) an EDC found in plastics, food packaging, and other consumer products. More than one hundred epidemiology studies suggest associations between BPA exposures and adverse health outcomes in environmentally exposed human populations.
RESULTS
We present support for the use of systematic review methodologies in the evaluation of BPA and other EDCs. Systematic reviews would allow studies to be evaluated for their reliability and risk of bias. They would also allow all data to be used in risk assessments, which is a requirement for some regulatory agencies.
CONCLUSION
Systematic review methodologies can be used to improve evaluations of BPA and other EDCs. Their use could help to restore faith in risk assessments and ensure that all data are utilized in decision-making. Regulatory agencies are urged to conduct transparent, well-documented and proper systematic reviews for BPA and other EDCs.
Topics: Benzhydryl Compounds; Endocrine Disruptors; Humans; Phenols; Plastics; Reproducibility of Results
PubMed: 34610783
DOI: 10.2174/1871530321666211005163614 -
Basic & Clinical Pharmacology &... Jan 2022Current data on use of antihistamines during breastfeeding and risks to the breastfed infant are insufficient. The aim of this systematic review was to provide an...
Current data on use of antihistamines during breastfeeding and risks to the breastfed infant are insufficient. The aim of this systematic review was to provide an overview of studies measuring the levels of antihistamines in human breast milk, estimating the exposure for breastfed infants and/or reporting possible adverse effects on the breastfed infant. An additional aim was to review the antihistamine product labels available in the European Union (EU) and the United States. We searched seven online databases and identified seven human lactation studies that included 25 mother-infant pairs covering cetirizine, clemastine, ebastine, epinastine, loratadine, terfenadine and triprolidine. In addition, one study investigated the impact of chlorpheniramine or promethazine on prolactin levels among 17 women, and one study investigated possible adverse drug reactions in 85 breastfed infants exposed to various antihistamines. The relative infant dose was below 5% for all antihistamines, ranging from 0.3% for terfenadine to 4.5% for clemastine. Most product labels of the 10 antihistamines with available information in both the EU and the United States reported lack of evidence and recommended to avoid use during breastfeeding. The knowledge gap on antihistamines and lactation is extensive, and further human studies are warranted to ensure optimal treatment of breastfeeding women with allergy.
Topics: Breast Feeding; Drug Labeling; European Union; Female; Histamine H1 Antagonists; Humans; Infant; Lactation; Milk, Human; United States
PubMed: 34587362
DOI: 10.1111/bcpt.13663 -
Nutrients Jul 2021Bisphenol A (BPA), a ubiquitous endocrine-disrupting chemical (EDC), is increasingly hypothesized to be a factor contributing to changes in fetal growth velocity. BPA...
A Systematic Review of Bisphenol A from Dietary and Non-Dietary Sources during Pregnancy and Its Possible Connection with Fetal Growth Restriction: Investigating Its Potential Effects and the Window of Fetal Vulnerability.
Bisphenol A (BPA), a ubiquitous endocrine-disrupting chemical (EDC), is increasingly hypothesized to be a factor contributing to changes in fetal growth velocity. BPA exposure may be environmental, occupational, and/or dietary, with canned foods and plastic bottles contributing significantly. Our systematic review aims to evaluate the current literature and to investigate the role of BPA in abnormal fetal growth patterns. A search was conducted in the PubMed and Cochrane databases. A total of 25 articles met the eligibility criteria and were included in this systematic review. Eleven of them failed to show a clear relationship between BPA and abnormal fetal growth. The majority of the remaining studies (9/14) found an inverse association of BPA with indicators of fetal growth, whereas three studies suggested increased fetal growth, and two studies produced contradictory findings. Of note, both of the studies that collected a sample (amniotic fluid) directly reflecting BPA concentration in the fetus during the first half of pregnancy revealed an inverse association with birth weight. In conclusion, there is mounting evidence that combined exposure to BPA from dietary and non-dietary sources during pregnancy may contribute to abnormal fetal growth; a tendency towards fetal growth restriction was shown, especially when exposure occurs during the first half.
Topics: Animals; Benzhydryl Compounds; Birth Weight; Dietary Exposure; Endocrine Disruptors; Environmental Exposure; Female; Fetal Development; Fetal Growth Retardation; Food Contamination; Food Packaging; Gestational Age; Humans; Infant, Newborn; Phenols; Pregnancy; Risk Assessment; Risk Factors
PubMed: 34371934
DOI: 10.3390/nu13072426 -
American Journal of Preventive Medicine Aug 2021Literature suggests that cannabis legalization may increase fatal motor vehicle collisions. However, evidence on the effectiveness of interventions to prevent drugged... (Review)
Review
CONTEXT
Literature suggests that cannabis legalization may increase fatal motor vehicle collisions. However, evidence on the effectiveness of interventions to prevent drugged driving is limited.
EVIDENCE ACQUISITION
MEDLINE, PsycINFO, Web of Science, Embase, SafetyLit, Criminal Justice Database, Transport Research International Documentation, bibliographies, and relevant gray literature were searched systematically through May 2020. Randomized and nonrandomized studies of preventive interventions measuring drugged driving outcomes were included. Evidence certainty was judged per Grading of Recommendations Assessment, Development, and Evaluation guidelines to designate quality ratings from very low to high.
EVIDENCE SYNTHESIS
The search identified 11 RCTs and 17 nonrandomized studies conducted predominantly among youth (aged 15-25 years; n=33,711 of 37,117 active research participants). In the public, cannabis packaging with health warnings increases the knowledge about drugged driving effects (high certainty); roadside drug testing can reduce drugged driving among cannabis users (moderate certainty); media campaigns may increase deterrent attitudes and knowledge (low certainty); and state sanctions, including traffic offense criminalization, license withdrawal, and per se drugged driving laws, may have little or no effect on drug-related fatalities or injuries (very low-low certainty). For youth or previous offenders, motivational interviewing can prevent drugged driving and driver education programs can increase knowledge (moderate certainty), whereas drug abuse prevention, substance abuse treatment, and driver rehabilitation may prevent drugged driving (very low certainty).
CONCLUSIONS
Overall, there is evidence to support the interventions that may improve drugged driving knowledge, attitudes, and behaviors. However, the impact of such interventions on measures of drugged driving-related morbidity and mortality is uncertain. Further research is urgently required to address these gaps in knowledge.
Topics: Accidents, Traffic; Adolescent; Automobile Driving; Cannabis; Humans; Licensure; Pharmaceutical Preparations
PubMed: 34099354
DOI: 10.1016/j.amepre.2021.03.012 -
PloS One 2021Correct interpretation of drug labels instructions (DLIs) is needed for safe use and better adherence to prescribed drugs. DLIs are often too difficult for patients,...
INTRODUCTION
Correct interpretation of drug labels instructions (DLIs) is needed for safe use and better adherence to prescribed drugs. DLIs are often too difficult for patients, especially for those with limited health literacy. What is yet unknown, is how specific textual elements in DLIs (e.g., the presentation of numbers, or use of medical jargon) and patients' health literacy skills are related to the comprehension of DLIs. In order to provide concrete directions for health professionals on how to optimize drug prescriptions, we performed a systematic review to summarize the available research findings on which textual elements facilitate or hinder the correct interpretation of DLIs in relation to patients' health literacy.
METHOD
A systematic search was performed in PubMed, EMBASE, PsychINFO, and Smartcat (until April 2019) to identify studies investigating textual elements that facilitate or hinder the correct interpretation of DLIs in relation to patients' health literacy.
RESULTS
A total of 434 studies were identified of which 28 studies met our inclusion criteria. We found that textual elements contributing to the correct interpretation of DLIs were: using explicit time periods in dosage instructions, using plain language, presenting numbers in a numerical format, and providing DLIs in patients' native language. Multistep instructions per instruction line, using abbreviations and medical jargon seem to hinder the correct interpretation of DLIs. Although health literacy was taken into account in a majority of the studies, none of them assessed the effectiveness of specific textual elements on patients' comprehensibility of DLIs.
CONCLUSION
Based on our findings, we provide an overview of textual elements that contribute to the correct interpretation of DLIs. Optimizing the textual instruction on drug labels may increase the safety and adherence to prescribed drugs, taking into account that a significant proportion of patients has low health literacy.
Topics: Comprehension; Drug Labeling; Health Literacy; Humans; Medical Writing
PubMed: 34010291
DOI: 10.1371/journal.pone.0250238 -
European Journal of Clinical... Feb 2021Medicines regulatory authorities advise that patient information leaflets (PILs) should provide specific advice on what actions to take if one or more doses are missed....
PURPOSE
Medicines regulatory authorities advise that patient information leaflets (PILs) should provide specific advice on what actions to take if one or more doses are missed. We aimed to assess the content in this regard, of PILs and Summaries of Product Characteristics (SmPCs) of prescription only medicines (POMs) marketed in the UK.
METHODS
PILs and SmPCs were accessed via the electronic Medicines Compendium. The following terms were used in the advanced search facility: miss(ed), omit(ted), adhere(d), delay(ed), forgot, forget, lapse. Identified documents were screened for instructions on missed doses which were categorised according to level of specificity, and cross-referenced to the National Patient Safety Agency (NPSA) grading of risk of harm from omitted and delayed medicines. Any supporting clinical or pharmacological evidence was identified from SmPCs.
RESULTS
Two thousand two hundred eighty-four documents were identified from 7248 PILs and SmPCs relating to 1501 POMs. Seven hundred eighty-three (52%) POMs had SmPCs or PILs with no instructions on missed doses; 487 POMs (32%) included non-specific advice (e.g. "take as soon as possible"); 138 (9%) provided specific instructions; and 93 (6%) referred patients to seek medical advice. SmPCs for only 13/138 (9%) of those which included specific instructions provided any supporting clinical or pharmacological evidence. Instructions were absent for several medicines where the NPSA assessed that dose omissions may result in significant risk of harm.
CONCLUSIONS
Advice on missed doses is generally inadequate. Pharmaceutical companies and regulatory authorities should produce clear and concise instructions on what patients should do if they miss doses, with supporting evidence where necessary.
Topics: Drug Administration Schedule; Drug Labeling; Humans; Medication Adherence; Prescription Drugs; United Kingdom
PubMed: 32989529
DOI: 10.1007/s00228-020-03003-x