Use Of Medicines In Pregnancy Research Articles

Use of Physiologically Based Pharmacokinetic Modeling for Hepatically Cleared Drugs in Pregnancy: Regulatory Perspective

AbstractPhysiologically based pharmacokinetic modeling could be used to predict changes in exposure during pregnancy and possibly inform medicine use in pregnancy in situations in which there is currently limited or no available clinical PK data. The Medicines and Healthcare Product Regulatory Agency has been evaluating the available models for a number of medicines cleared by hepatic clearance mechanisms. Models were evaluated for metoprolol, tacrolimus, clindamycin, ondansetron, phenytoin, caffeine, fluoxetine, clozapine, carbamazepine, metronidazole, and paracetamol. The hepatic metabolism through cytochrome P450 (CYP) contributes significantly to the elimination of these drugs, and available knowledge of CYP changes during pregnancy has been implemented in the existing pregnancy physiology models. In general, models were able to capture trends in exposure changes in pregnancy to some extent, but the magnitude of pharmacokinetic change for these hepatically cleared drugs was not captured in each case, nor were models always able to capture overall exposure in the populations. A thorough evaluation was hampered by the lack of clinical data for drugs cleared by a specific clearance pathway. The limited clinical data, as well as complex elimination pathways involving CYPs, uridine 5′‐diphospho‐glucuronosyltransferase and active transporter for many drugs, currently limit the confidence in the prospective use of the models. Pregnancy‐related changes in uridine 5′‐diphospho‐glucuronosyltransferase and transport functions are emerging, and incorporation of such changes in current physiologically based pharmacokinetic modeling software is in progress. Filling this gap is expected to further enhance predictive performance of models and increase the confidence in predicting PK changes in pregnant women for hepatically cleared drugs.

Pharmacovigilance system role in safe use of medicines in pregnancy and breastfeeding

Pharmacovigilance system role in safe use of medicines in pregnancy and breastfeeding

COVID-19-related medicine utilization study in pregnancy: The COVI-PREG cohort.

The objective of this study was to describe the use of COVID-19-related medicines during pregnancy and their evolution between the early/late periods of the pandemic. Pregnant women who tested positive for SARS-CoV-2 from March 2020 to July 2021 were included using the COVI-PREG registry. Exposure to the following COVID-19-related medicines was recorded: antibiotics, antivirals, hydroxychloroquine, corticosteroids, anti-interleukin-6 and immunoglobulins. We described the prevalence of medicines used, by trimester of pregnancy, maternal COVID-19 severity level and early/late period of the pandemic (before and after 1 July 2020). We included 1964 pregnant patients who tested positive for SARS-CoV-2. Overall, 10.4% (205/1964) received at least one COVID-19-related medicine including antibiotics (8.6%; 169/1694), corticosteroids (3.2%; 62/1964), antivirals (2.0%; 39/1964), hydroxychloroquine (1.4%; 27/1964) and anti-interleukin-6 (0.3%; 5/1964). The use of at least one COVID-19-related medicine was 3.1% (12/381) in asymptomatic individuals, 4.2% (52/1233) in outpatients, 19.7% (46/233) in inpatients without oxygen, 72.1% (44/61) in those requiring standard oxygen, 95.7% (22/23) in those requiring high flow oxygen, 96.2% (25/26) in patients who required intubation and 57.1% (4/7) among patients who died. The proportion who received medicines to treat COVID-19 was higher before than after July 2020 (16.7% vs. 7.7%). Antibiotics, antivirals and hydroxychloroquine had lower rates of use during the late period. Medicine use in pregnancy increased with disease severity. The trend towards increased use of corticosteroids seems to be aligned with changing guidelines. Evidence is still needed regarding the effectiveness and safety of COVID-19-related medicines in pregnancy.

The Use of Pregnancy Physiologically Based Pharmacokinetic Modeling for Renally Cleared Drugs.

Physiologically based pharmacokinetic modeling (PBPK) could be used to predict changes in exposure during pregnancy and possibly inform medicine use in pregnancy in situations where there are currently no available clinical data. The Medicines and Healthcare Product Regulatory Agency has been evaluating the available models for a number of medicines cleared by the kidney. Models were evaluated for ceftazidime, cefuroxime, metformin, oseltamivir, and amoxicillin. Because the passive renal process contributes significantly to the renal elimination of these drugs and changes of the process during pregnancy have been implemented in existing pregnancy physiology models, simulations using these models can reasonably describe the pharmacokinetics of ceftazidime changes during pregnancy and appears to generally capture the changes in the other medicines; however, there are insufficient data on drugs solely passively cleared to fully qualify the models. In addition, in many cases, active transport processes are involved in a drug's renal clearance. Knowledge of changes in renal transport functions during pregnancy is emerging, and incorporation of such changes in current physiologically based pharmacokinetic modeling software is a work in progress. Filling this gap is expected to further enhance predictive performance of the models and increase the confidence in predicting pharmacokinetic changes in pregnant women for other renally cleared drugs.

Determining antenatal medicine exposures in South African women: a comparison of three methods of ascertainment

BackgroundIn the absence of clinical trials, data on the safety of medicine exposures in pregnancy are dependent on observational studies conducted after the agent has been licensed for use. This requires an accurate history of antenatal medicine use to determine potential risks. Medication use is commonly determined by self-report, clinician records, and electronic pharmacy data; different data sources may be more informative for different types of medication and resources may differ by setting. We compared three methods to determine antenatal medicine use (self-report, clinician records and electronic pharmacy dispensing records [EDR]) in women attending antenatal care at a primary care facility in Cape Town, South Africa in a setting with high HIV prevalence.MethodsStructured, interview-administered questionnaires recorded self-reported medicine use. Data were collected from clinician records and EDR on the same participants. We determined agreement between these data sources using Cohen’s kappa and, lacking a gold standard, used Latent Class Analysis to estimate sensitivity, specificity and positive predictive value (PPV) for each data source.ResultsBetween 55% and 89% of 967 women had any medicine use documented depending on the data source (median number of medicines/participant = 5 [IQR 3–6]). Agreement between the datasets was poor regardless of class except for antiretroviral therapy (ART; kappa 0.6–0.71). Overall, agreement was better between the EDR and self-report than with either dataset and the clinician records. Sensitivity and PPV were higher for self-report and the EDR and were similar for the two. Self-report was the best source for over-the-counter, traditional and complementary medicines; clinician records for vaccines and supplements; and EDR for chronic medicines.ConclusionsMedicine use in pregnancy was common and no single data source included all the medicines used. ART was the most consistently reported across all three datasets but otherwise agreement between them was poor and dependent on class. Using a single data collection method will under-estimate medicine use in pregnancy and the choice of data source should be guided by the class of the agents being investigated.

The Italian Network for Monitoring Medication Use During Pregnancy (MoM-Net): Experience and Perspectives.

There is an acute need for research to acquire high-quality information on the use of medicines in pregnancy, both in terms of appropriateness and safety. For this purpose, the Italian Medicines Agency established a Network for Monitoring Medication use in pregnancy (MoM-Net) through the conduction of population-based studies using administrative data available at regional level. This paper aimed to describe the experiences and challenges within the network. MoM-Net currently involves eight regions and several experts from public and academic institutions. The first study conducted aimed to identify drug use before, during and after pregnancy investigating specific therapeutic categories, analysing regional variability and monitoring drug use in specific subpopulations (i.e. foreign women/multiple pregnancies). Aggregated demographic, clinical, and prescription data were analysed using a distributed network approach based on common data model. The study population included all women delivering during 2016–2018 in the participating regions (n = 449,012), and corresponding to 59% of deliveries in Italy. Seventy-three per cent of the cohort had at least one drug prescription during pregnancy, compared to 57% before and 59% after pregnancy. In general, a good adherence to guidelines for pregnant women was found although some drug categories at risk of inappropriateness, such as progestins and antibiotics, were prescribed. A strong variability in the use of drugs among regions and in specific subpopulations was observed. The MoM-Net represents a valuable surveillance system on the use of medicines in pregnancy, available to monitor drug categories at high risk of inappropriateness and to investigate health needs in specific regions or subpopulations.

Evaluation of the knowledge, attitude, and behaviors of physicians and pharmacists regarding the use of medicines in pregnancy

Evaluation of the knowledge, attitude, and behaviors of physicians and pharmacists regarding the use of medicines in pregnancy

Pharmacokinetic Characterization to Enable Medicine Use in Pregnancy, the Potential Role of Physiologically-Based Pharmacokinetic Modeling: A Regulatory Perspective.

CPT: Pharmacometrics & Systems PharmacologyVolume 9, Issue 10 p. 547-549 PerspectiveOpen Access Pharmacokinetic Characterization to Enable Medicine Use in Pregnancy, the Potential Role of Physiologically-Based Pharmacokinetic Modeling: A Regulatory Perspective Susan Cole, Susan Cole orcid.org/0000-0002-4582-6231 Medicines and Healthcare Products Regulatory Agency, London, UKSearch for more papers by this authorPaola Coppola, Corresponding Author Paola Coppola paola.coppola@mhra.gov.uk orcid.org/0000-0002-6001-1647 Medicines and Healthcare Products Regulatory Agency, London, UK Correspondence: Paola Coppola (paola.coppola@mhra.gov.uk)Search for more papers by this authorEssam Kerwash, Essam Kerwash orcid.org/0000-0003-4368-8565 Medicines and Healthcare Products Regulatory Agency, London, UKSearch for more papers by this authorJanet Nooney, Janet Nooney Medicines and Healthcare Products Regulatory Agency, London, UKSearch for more papers by this authorSiu Ping Lam, Siu Ping Lam Medicines and Healthcare Products Regulatory Agency, London, UKSearch for more papers by this author Susan Cole, Susan Cole orcid.org/0000-0002-4582-6231 Medicines and Healthcare Products Regulatory Agency, London, UKSearch for more papers by this authorPaola Coppola, Corresponding Author Paola Coppola paola.coppola@mhra.gov.uk orcid.org/0000-0002-6001-1647 Medicines and Healthcare Products Regulatory Agency, London, UK Correspondence: Paola Coppola (paola.coppola@mhra.gov.uk)Search for more papers by this authorEssam Kerwash, Essam Kerwash orcid.org/0000-0003-4368-8565 Medicines and Healthcare Products Regulatory Agency, London, UKSearch for more papers by this authorJanet Nooney, Janet Nooney Medicines and Healthcare Products Regulatory Agency, London, UKSearch for more papers by this authorSiu Ping Lam, Siu Ping Lam Medicines and Healthcare Products Regulatory Agency, London, UKSearch for more papers by this author First published: 02 August 2020 https://doi.org/10.1002/psp4.12551Citations: 4AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat It is generally recommended that use of medicines should be avoided during pregnancy; however, sometimes the use of a medicine is essential to safeguard the health of the mother and baby. A limited number of medicines are, however, specifically licensed for use in pregnancy. This article considers the potential of physiologically-based pharmacokinetic (PBPK) modeling as a predictive tool to investigate the expected systemic exposure of medicines in pregnant women and to support possible dosing adjustment to maintain efficacy. Use of Medicines During Pregnancy Self-reported medicine use by pregnant women surveyed in Europe, the Americas, and Australia in 2011 revealed that more than 80% of women used at least one medicinal product during pregnancy. Some regional differences existed; however, 67% of women self-reported use of nonprescription or over-the-counter medicines, whereas 17% of women reported medicine use for chronic conditions.1 Treatments are often essential for pregnant women with underlying conditions where poor maternal health can itself pose risks for the pregnancy, for example, depression, epilepsy, or cardiovascular conditions. In addition, treatment with antiviral agents are required, e.g., for HIV patients to prevent transmission of the virus or for malaria treatment. Other medicines may be required for conditions such as pre-eclampsia or diabetes that may develop during pregnancy. There is, however, limited scientific information to support the safe and optimal use of medicines in pregnancy. Only five prescription medicines (i.e., amoxicillin, labetalol, diazoxidine injection, doxylamine succinate/pyridoxine hydrochloride, sodium feredetate) are specifically licensed in the United Kingdom for nonobstetric use in pregnancy. The necessity to treat the mother needs to be balanced against potential adverse effects on the fetus. The benefit-risk decision to inform medicine use in pregnancy relies on the available information about the effect of the medicine on pregnancy outcomes and the effect of pregnancy on the medicine. Changes in drug systemic exposure during pregnancy could increase risks for mother and baby. Particularly, underexposure may lead to loss of efficacy and reduced control of maternal health with associated risks for fetal development, whereas overexposure could result in exposing the mother and the fetus to unnecessarily high doses, increasing the risk of adverse effects. Optimal formulations and dosages are not usually investigated in pregnant women, and for most medications it is unknown whether a single dosing regimen will be sufficient throughout pregnancy or whether one or several changes would be required as pregnancy advances. At the time of licensing, most new medicines in the European Union advise avoiding use in pregnancy because of a lack of sufficient studies in pregnant women. The European Medicines Agency and US Food and Drug Administration recommend that marketing authorization applicants should perform, where possible, pharmacokinetic (PK) and pharmacodynamic studies in pregnant women to understand better how pregnancy affects the blood levels of medicines commonly used, particularly during the first trimester, and to develop evidence-based dosing and frequency of administration guidance for use in pregnancy.2, 3 However, concerns about taking part in clinical trials because of unknown benefit-risk profiles of investigational medicines in both the mother and fetus may lead to difficulties in recruiting pregnant women, which in turn limits the generation of data. The resulting lack of information on safety and appropriate doses leads to health care professionals being reluctant to prescribe newer medicines during pregnancy, which may be more efficacious and/or have a better general safety profile than older medicines. The Importance of PK Characterization of Medicine in Pregnant Women It is known that considerable physiological changes occur during all gestational trimesters and that these may alter the way the body normally deals with administered medicines, consequently, the PK and/or pharmacodynamics of medicines may change. As pregnancy advances, clinically important alterations in the absorption, distribution, metabolism, and excretion of medicines can be observed. Nausea, vomiting, and alterations in gastric pH and gastrointestinal tract motility may alter the absorption process, which, conversely, may be enhanced by the increased cardiac output and intestinal blood flow. The central volume of distribution increases during pregnancy because of a plasma volume increase of up to ~ 42% by the third trimester, and an increase in blood flow to the uterus will mean increased delivery of lipophilic medicines to the placenta and the fetus. Metabolizing enzymes (e.g., cytochrome P450) may have increased, or decreased, activity during pregnancy leading to altered drug clearance. The renal glomerular filtration rate also increases throughout pregnancy and can lead to higher clearance of renally excreted medicines (e.g., lithium, digoxin). The expression and activities of transporters, which are extensively expressed in several organs, including the placenta–fetus compartment, are also expected; however, limited data are currently available in this area.4 A Role for PBPK Modeling? PBPK modeling is increasingly used in drug development and regulatory submissions, and the purpose of the models has expanded from the assessment of drug interactions to the assessment of PK in special populations.5 PBPK modeling uses a mathematical approach to develop an understanding of how drug systemic exposure can be influenced by changes in physiology. Several papers have been published on the use of PBPK modeling to describe anatomical and physiological changes during pregnancy, and these models have been evaluated with different test drugs eliminated via filtration, transport, or metabolism.6-8 Most models relate to the late second/third gestational trimester, and an extensive understanding of the impact of physiological changes throughout pregnancy on medicine PK and pharmacodynamics is yet to be completed. PBPK methodology could be used as a predictive tool to support a benefit-risk decision and for selection of the adequate dose in pregnancy. In the US FDA's draft guidance,3 modeling and simulations, including PBPK, are suggested to support the design of clinical PK studies in pregnant women. It is apparent that modeling could also be used to identify which medicines are more likely to be affected by pregnancy and, therefore, would be a priority to obtain clinical data in pregnant women. Eventually, there may be situations where the confidence in the PBPK model is such that it can be used to support extrapolation of efficacy and safety data from healthy volunteers to pregnant women without any clinical data. Dosing based solely on PK, whether measured or predicted, is considered an extrapolation in EU regulatory terms, and a framework has recently been published for children.9 This framework could be usefully applied to pregnancy. A comprehensive PBPK pregnancy model framework could bridge the gaps in data to support a prospective investigation of the exposure–response relationship, which is essential for predicting necessary dose changes to maintain maternal health. Medicines and Healthcare Products Regulatory Agency Project on PBPK Modeling for Drug Use in Pregnancy The Medicines and Healthcare Products Regulatory Agency (MHRA) is collaborating with the Bill and Melinda Gates Foundation in Seattle, WA, to evaluate existing PBPK models to inform dosing in pregnant women in the United Kingdom. The project aims to generate new insights on drug disposition during pregnancy that can have an impact on the health of pregnant women and give obstetricians further clarity on optimal doses of medicines in pregnant women, when such treatments are considered necessary. It also aims to increase clinician's awareness in the use of predictive tools such as PBPK models to support more informed dosing in pregnancy. The project will facilitate the provision of quantitative PK data to support dose selection for medicines of interest and to fill gaps in the knowledge to inform an improved benefit-risk assessment of the medicines in pregnancy. The focus of this work is to use PBPK modeling to use the available PK data to understand existing system components concerning pregnancy in PBPK models (virtual pregnant population model). The initial phase of the project will focus on maternal exposure. It is intended that future work would focus on exposure of the fetus. This will assist in the understanding of passage of drugs across the placenta and as a minimum should be useful to highlight those drugs for which exposure to the fetus would not be predicted. The MHRA has identified a list of medicines commonly used in pregnancy for which the impact of pregnancy on their PK will be investigated using currently available information and PBPK modeling. This list includes approximately 200 medicines in several therapeutic areas, including diabetes, epilepsy, antidepressants, antibiotics, antihypertensives, pain killers, corticosteroids, antivirals, immunosuppressants, anesthetics, and antihistamines. Clinical PK data in pregnancy will be collected from the literature, clinical trial databases, or data held in-house from historical regulatory submissions and used to qualify/validate the available PBPK models. Depending on an understanding of the uncertainties in the models, confidence in them to support regulatory decisions can be addressed. Drug systemic exposures predicted in a virtual pregnant population can, as a minimum, support optimal design of any planned PK trials and could inform the information given to trial participants on the risks and benefits of investigational medicines. High confidence in the models would be required, however, for high-impact applications,10 such as to inform doses in pregnancy without any clinical data in this population. The MHRA will also work with healthcare professionals. Throughout the project, training sessions and workshops will be organized to introduce PK and PBPK to obstetricians and physicians. Findings from the PBPK modeling will be used as case examples to facilitate physicians’ understanding of quantitative methods and conversely to receive feedback from physicians on further improving predictability of PBPK models. Conclusion Clinical studies in pregnant women are required to inform and ensure the safe and effective use of medicines in this population. However, most clinical trials normally exclude pregnant women based on possible risks to the fetus. PBPK models can provide a conceptual understanding and useful quantitative data on PK. This can be used to support benefit-risk assessment and dose selection or to indicate medicines where further clinical data are required during different stages of pregnancy, especially where there is currently a sparsity of data. The confidence in these models needs to be assessed before their full utility, e.g., high-impact uses in regulatory applications and for potential use by clinicians in the field, can be concluded. Further details and results will be made publicly available in the future. Acknowledgments The authors would like to thank Ping Zhao for his review. Funding This project received a grant from the Bill & Melinda Gates Foundation, Seattle, WA, USA. Conflict of Interest All authors declared no competing interests for this work. Disclaimer The views expressed in this article are the personal views of the authors and may not be understood or quoted as being made on behalf of or reflecting the position of the regulatory agency or other organizations with which the authors are affiliated. References 1Lupattelli, A. et al. Medication use in pregnancy: a cross-sectional, multinational web-based study. BMJ Open 4, e004365 (2014). CrossrefCASPubMedWeb of Science®Google Scholar 2 European Medicines Agency. EMA guideline on the exposure to medicinal products during pregnancy: need for post-authorisation data. November 2005. EMEA/CHMP/313666/2005. <https//www.ema.europa.eu> Google Scholar 3 US FDA. Pregnant women: scientific and ethical considerations for inclusion in clinical trials. Guidance for inustry. April 2018. <https://www.fda.gov/> Google Scholar 4Feghali, M. et al. Pharmacokinetics of drugs in pregnancy. Semin. Perinatol. 39, 512– 519 (2015). CrossrefPubMedWeb of Science®Google Scholar 5Ke, A. et al. Drug dosing in pregnant women: challenges and opportunities in using physiologically based pharmacokinetic modeling and simulations. CPT Pharmacometrics Syst. Pharmacol. 7, 103– 110 (2018). Wiley Online LibraryCASPubMedWeb of Science®Google Scholar 6Ke, A. et al. A PBPK model to predict disposition of CYP3A-metabolized drugs in pregnant women: verification and discerning the site of CYP3A induction. CPT: Pharmacometrics Syst. Pharmacol. 1, 1– 10 (2012). Wiley Online LibraryGoogle Scholar 7Ke, A. et al. Expansion of a PBPK model to predict disposition in pregnant women of drugs cleared via multiple CYP enzymes, including CYP2B6, CYP2C9 and CYP2C19. Br. J. Clin. Pharmacol. 77, 554– 570 (2013). Wiley Online LibraryCASWeb of Science®Google Scholar 8Dallmann, A. et al. Physiologically based pharmacokinetic modeling in pregnancy: a systematic review of published models. Clin. Pharmacol. Ther. 104, 1110– 1124 (2018). Wiley Online LibraryPubMedWeb of Science®Google Scholar 9 European Medicines Agency. Reflection paper on the use of extrapolation in the development of medicines for paediatrics. October 2018. EMA/189724/2018. <https://www.ema.europa.eu/> Google Scholar 10Manolis, E. et al. The role of modeling and simulation in development and registration of medicinal products: output from the EFPIA/EMA modeling and simulation workshop. CPT: Pharmacometrics Syst Pharmacol 2, e31 (2013). Wiley Online LibraryCASPubMedGoogle Scholar Citing Literature Volume9, Issue10October 2020Pages 547-549 This article also appears in:Pregnancy ReferencesRelatedInformation

Knowledge about Medicine Use in Pregnancy: A National Study among Pharmacy Students in Jordan.

Knowledge of medication use during pregnancy presents a concern to pharmacists upon graduation since they will be responsible for drug-related inquiries and counselling pregnant women about their medications. The present study aimed to assess undergraduate senior pharmacy students' knowledge about medication use during pregnancy in Jordan. A cross-sectional survey was conducted in Jordanian universities. A total of 409 senior pharmacy students participated in the study. The results found that the majority of the students (60.6%) did not have enough instruction on medications during pregnancy through their undergraduate study. Overall, only 2.5% of the participating students were considered to have good knowledge about medicine use during pregnancy and accordingly, the majority (52.6%) were not confident to recommend medicines for pregnant women in the future. In view of that, participating students suggested the addition of an obligatory course to the current curriculum. Students in public universities, Pharm.D. students, and those in their sixth year of study were more knowledgeable than others (P > 0.05). It was concluded that pharmacy students have low knowledge regarding medication use in pregnancy. The results call for a reassessment of the current pharmacy curriculum.

Predicting the safety of medicines in pregnancy: A workshop report

The framework for developmental toxicity testing has remained largely unchanged for over 50 years and although it remains invaluable in assessing potential risks in pregnancy, knowledge gaps exist, and some outcomes do not necessarily correlate with clinical experience. Advances in omics, in silico approaches and alternative assays are providing opportunities to enhance our understanding of embryo-fetal development and the prediction of potential risks associated with the use of medicines in pregnancy. A workshop organised by the Medicines and Healthcare products Regulatory Agency (MHRA), “Predicting the Safety of Medicines in Pregnancy – a New Era?”, was attended by delegates representing regulatory authorities, academia, industry, patients, funding bodies and software developers to consider how to improve the quality of and access to nonclinical developmental toxicity data and how to use this data to better predict the safety of medicines in human pregnancy. The workshop delegates concluded that based on comparative data to date alternative methodologies are currently no more predictive than conventional methods and not qualified for use in regulatory submissions. To advance the development and qualification of alternative methodologies, there is a requirement for better coordinated multidisciplinary cross-sector interactions coupled with data sharing. Furthermore, a better understanding of human developmental biology and the incorporation of this knowledge into the development of alternative methodologies is essential to enhance the prediction of adverse outcomes for human development. The output of the workshop was a series of recommendations aimed at supporting multidisciplinary efforts to develop and validate these alternative methodologies.

Correction: Social Media Surveillance of Multiple Sclerosis Medications Used During Pregnancy and Breastfeeding: Content Analysis

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Social Media Surveillance of Multiple Sclerosis Medications Used During Pregnancy and Breastfeeding: Content Analysis.

BackgroundMultiple sclerosis (MS) is a chronic neurological disease occurring mostly in women of childbearing age. Pregnant women with MS are usually excluded from clinical trials; as users of the internet, however, they are actively engaged in threads and forums on social media. Social media provides the potential to explore real-world patient experiences and concerns about the use of medicinal products during pregnancy and breastfeeding.ObjectiveThis study aimed to analyze the content of posts concerning pregnancy and use of medicines in online forums; thus, the study aimed to gain a thorough understanding of patients’ experiences with MS medication.MethodsUsing the names of medicinal products as search terms, we collected posts from 21 publicly available pregnancy forums, which were accessed between March 2015 and March 2018. After the identification of relevant posts, we analyzed the content of each post using a content analysis technique and categorized the main topics that users discussed most frequently.ResultsWe identified 6 main topics in 70 social media posts. These topics were as follows: (1) expressing personal experiences with MS medication use during the reproductive period (55/70, 80%), (2) seeking and sharing advice about the use of medicines (52/70, 74%), (3) progression of MS during and after pregnancy (35/70, 50%), (4) discussing concerns about MS medications during the reproductive period (35/70, 50%), (5) querying the possibility of breastfeeding while taking MS medications (30/70, 42%), and (6) commenting on communications with physicians (26/70, 37%).ConclusionsOverall, many pregnant women or women considering pregnancy shared profound uncertainties and specific concerns about taking medicines during the reproductive period. There is a significant need to provide advice and guidance to MS patients concerning the use of medicines in pregnancy and postpartum as well as during breastfeeding. Advice must be tailored to the circumstances of each patient and, of course, to the individual medicine. Information must be provided by a trusted source with relevant expertise and made publicly available.

Medicines in pregnancy.

Medicine use in pregnancy is extremely common, but there are significant knowledge gaps surrounding the safety, dosage and long-term effects of drugs used. Pregnant women have been purposively excluded from clinical trials of the majority of treatments for conditions that may occur concurrently with pregnancy. There is minimal information on the pharmacokinetics of many existing treatments and no systematic capture of long-term outcome data to help inform choices. Treatments commonly used in pregnancy are thus often old and untested, not optimised in dose, and prescribed off-label without adequate safety information. In addition, there has been a staggering lack of investment in drug development for obstetric conditions for decades. This is a major public health concern, and pregnancy complications are the leading cause of mortality in children under five years old globally, and health in pregnancy is a major determinant of women’s long-term health and wellbeing. There is an acute need for adequate investment and legislation to boost inclusion of pregnant women in clinical studies, capture high-quality information on medication use in pregnancy in general, and encourage new medicinal product development for obstetric conditions.

Herbal medicine use by pregnant women in Bangladesh: a cross-sectional study

BackgroundHerbal medicines in pregnancy are increasingly used worldwide with prevalence of up to 67%. Although this popularity is mainly because of the common belief that these medicines are safe, recent reports suggest that several herbal medicines are potentially harmful to mother and fetus if used in pregnancy.MethodsThis cross-sectional study was conducted in July and August of year 2017, at maternity wards of two public hospitals in Dhaka, Bangladesh. Postpartum women were interviewed via the structured questionnaire to collect information regarding socio-demographic and health characteristics, patterns of herbal medicines used in the previous pregnancy, and outcome of pregnancy.ResultsTwo hundred forty-three postpartum women participated in the study, with 70% of them using at least one modality of herbal medicines in previous pregnancy. Ginger, black seed, lemon tea, prune, and mustard oil were most commonly used herbal medicines. Herbal medicines were mostly used for pregnancy-related symptoms such as nausea, vomiting, and cold. Fifteen (8.8%) herbal medicine users reported side effects.ConclusionsThis study highlights popularity of herbal medicines during pregnancy in Bangladesh. Previous herbal medicine users and unemployed women turned significantly more to herbal medicines during pregnancy. Reports of side effects and use of some potentially harmful modalities warrant awareness regarding proper use of herbal medicines in pregnancy and its pharmacovigilance.

Complementary medicine products used in pregnancy and lactation and an examination of the information sources accessed pertaining to maternal health literacy: a systematic review of qualitative studies

BackgroundThe prevalence of complementary medicine use in pregnancy and lactation has been increasingly noted internationally. This systematic review aimed to determine the complementary medicine products (CMPs) used in pregnancy and/or lactation for the benefit of the mother, the pregnancy, child and/or the breastfeeding process. Additionally, it aimed to explore the resources women used, and to examine the role of maternal health literacy in this process.MethodsSeven databases were comprehensively searched to identify studies published in peer-reviewed journals (1995–2017). Relevant data were extracted and thematic analysis undertaken to identify key themes related to the review objectives.ResultsA total of 4574 articles were identified; 28 qualitative studies met the inclusion criteria. Quantitative studies were removed for a separate, concurrent review. Herbal medicines were the main CMPs identified (n = 21 papers) in the qualitative studies, with a smaller number examining vitamin and mineral supplements together with herbal medicines (n = 3), and micronutrient supplements (n = 3). Shared cultural knowledge and traditions, followed by women elders and health care professionals were the information sources most accessed by women when choosing to use CMPs. Women used CMPs for perceived physical, mental-emotional, spiritual and cultural benefits for their pregnancies, their own health, the health of their unborn or breastfeeding babies, and/or the breastfeeding process. Two over-arching motives were identified: 1) to protect themselves or their babies from adverse events; 2) to facilitate the normal physiological processes of pregnancy, birth and lactation. Decisions to use CMPs were made within the context of their own cultures, reflected in the locus of control regarding decision-making in pregnancy and lactation, and in the health literacy environment. Medical pluralism was very common and women navigated through and between different health care services and systems throughout their pregnancies and breastfeeding journeys.ConclusionsPregnant and breastfeeding women use herbal medicines and micronutrient supplements for a variety of perceived benefits to their babies’ and their own holistic health. Women access a range of CMP-related information sources with shared cultural knowledge and women elders the most frequently accessed sources, followed by HCPs. Culture influences maternal health literacy and thus women’s health care choices including CMP use.

Medicamentos en el embarazo. Clasificaciones teratogénicas y otras fuentes de información

The available teratogenic risk classifications are ambiguous and are often difficult to interpret. There are no evidence-based clinical guidelines on risk/benefit assessment to help with decision-making when drug treatment is considered in pregnancy. Studies available in humans are limited, and at best may show an association between the drug and the undesirable effect. Specific changes have been made in the data sheets to improve information on the use of medicines in pregnancy, but it is not enough. The quality of studies in pregnant women has improved, but some training in epidemiology and statistics is required to interpret them. A personalised selection of the safest drug must take into account the risk/benefit ratio of the drug as well as and the expected outcome of an untreated disease.

Use of antimigraine medications and information needs during pregnancy and breastfeeding: a cross-sectional study among 401 Norwegian women

Migraine is highly prevalent among women of fertile age. The main objectives of this study were to describe the prevalence and patterns of use of antimigraine medications during pregnancy and breastfeeding and to identify maternal and migraine-related factors associated with medication use during pregnancy. The study is a cross-sectional internet-based survey among pregnant women and new mothers with migraine conducted in Norway from October 1, 2013 to February 1, 2014. Descriptive statistics were used to explore patterns of medication use, and logistic regression analysis was performed to examine the association between maternal socio-demographic and migraine-related factors and use of antimigraine medications during pregnancy. Of the total 401 respondents, 34.9% were pregnant and 65.1% had delivered within the last 18months. The majority reported use of antimigraine medications during pregnancy (73.3%) and postpartum (64.8%), yet less than a third considered their migraine to be optimally treated during pregnancy (31.7%) and the breastfeeding period (27.2%). The patterns of medication use markedly changed during pregnancy and postpartum. Women with moderate or severe migraine were more likely to use antimigraine medications during pregnancy compared to women with mild migraine. Despite the fact that antimigraine medications were commonly used, the majority of the women felt that their migraine was suboptimally treated during pregnancy and postpartum. There was a decline in the use of medicines in pregnancy and postpartum, and the patterns of use markedly changed. Efforts to improve treatment of women with migraine during pregnancy and breastfeeding should be undertaken.

Website review: Pregnancy and breastfeeding medicines guide

This website lives up to its description of a quick reference guide for healthcare professionals that provides practical and unbiased specialised information on medicine use in pregnancy and breastfeeding. The online format has replaced the hard copy version which was last published in November 2014. The guide includes an A-Z listing of over 900 evidence-based individual medicine monographs which support prescribing during pregnancy and breastfeeding. It also includes summaries of therapeutic groups such as antidepressants and antihistamines with general advice about the pharmacological management of common conditions such as nausea and vomiting in pregnancy, and constipation. One hopes that the online format makes this resource more appealing to pharmacists in the community as it is clearly far superior to other prescribing references such as MIMS. The guide would also be a very useful resource for busy obstetricians in private practice (as well as hospital antenatal clinics). This guide includes medicines available in Australia but not in the USA (e.g. cyproterone). There is often limited or no information about these drugs in other resources.1-3 Annual subscription is $170 making this a little pricier than your average reference book. However, the guide has monthly updates which include information about new drugs, as well as updated data about older medicines or therapeutic groups. Overall I think this is an excellent resource and congratulate the authors on putting it all together in such a user-friendly format. I would recommend it to all maternity hospitals and community pharmacies to optimise medicine use and prescribing in pregnant and breastfeeding women.

Safety classification of herbal medicines used in pregnancy in a multinational study.

BackgroundThe use of herbal medicines for health prevention and ailments is an increasing trend worldwide. Women in pregnancy are no exception; the reported prevalence of herbal medicine use in pregnancy ranges from 1 to 60 %. Despite a common perception of safety, herbal medicines may have potent pharmacological actions, and historically, have been used for this reason.MethodsA multinational, cross-sectional study on how women treat disease and pregnancy-related health ailments was conducted between October 2011 and February 2012 in Europe, North America, and Australia. This study’s primary aim was to evaluate and classify the herbal medicines used according to their safety in pregnancy and, secondly, to investigate risk factors associated with the use of contraindicated herbal medicines during pregnancy.ResultsIn total, 29.3 % of the women (n = 2673) reported the use of herbal medicines in pregnancy; of which we were able to identify 126 specific herbal medicines used by 2379 women (89.0 %). Twenty seven out of 126 herbal medicines were classified as contraindicated in pregnancy, and were used by 476 women (20.0 %). Twenty-eight were classified as safe for use in pregnancy and used by the largest number of women (n = 1128, 47.4 %). The greatest number was classified as requiring caution in pregnancy; these sixty herbal medicines were used by 751 women (31.6 %). Maternal factors associated with the use of contraindicated herbal medicines in pregnancy were found to be working in the home, having a university education, not using folic acid, and consuming alcohol. Interestingly, the recommendation to take a contraindicated herbal medicine was three times more likely to be from a healthcare practitioner (HCP) than an informal source.ConclusionBased on the current literature the majority of women in this study used an herbal medicine that was classified as safe for use in pregnancy. Women who reported taking a contraindicated herb were more likely to have been recommended it use by an HCP rather than informal source(s), indicating an urgent need for more education among HCPs. The paucity of human studies on herbal medicines safety in pregnancy stands in stark contrast to the widespread use of these products among pregnant women.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-016-1079-z) contains supplementary material, which is available to authorized users.

Prevalence and Pattern of Herbal Medicine Use in Pregnancy among Women Attending Clinics in a Tertiary Hospital in Imo State, South East Nigeria

Prevalence and Pattern of Herbal Medicine Use in Pregnancy among Women Attending Clinics in a Tertiary Hospital in Imo State, South East Nigeria