Tell your doctor right away if you have any serious side effects, including: fast/pounding heartbeat. Inconsistencies in PK parameter changes exist in the AUC and clearance of DHA; a statistically significant reduction in AUC (decreased exposure) and an increase in oral clearance in pregnancy were observed in one study [197], while the change directions were opposite in the other [198]. View list of generic and brand names of drugs used for treatment of Labor and Delivery / Pregnancy Labor ( Pregnancy Labor). Results from 5,381 mothers identified 54 different medications used in the first trimester by at least 0.5% of pregnant women. 5mg once a day 3 months and review . While most of these studies reported adequate viral suppression and no mother-to-child HIV transmission [132,135,138], one study reported an increased viral load during pregnancy, with a few cases of neonatal transmission of the virus [150]. Studies of seven drugs were found to yield conflicting PK results among studies in pregnancy. Do not store in the bathroom. By and large, these parameters signify drug exposure levels at a given time point or on average, thereby potentially serving as a surrogate for drug effects. While some studies have found that the proportion of women receiving at least one prescription medicine increases from the first to third trimester of pregnancy [5,6], others have found that rates of prescription drug use are highest in the first trimester of pregnancy [1,7]. In these studies, commonly investigated drug classes included antiretrovirals (54 studies), antiepileptic drugs (27 studies), antibiotics (23 studies), antimalarial drugs (22 studies), and cardiovascular drugs (17 studies). However, this can be explained by increased disease severity at PK sampling in the latter [198], as systemic exposure of DHA is higher in infected patients with a severe course of malaria than in those with a mild course [198,247]. C/D ratio is the dose-standardized drug concentration in plasma or serum at a given time. As many women presently delay childbearing to an older age [243] and the frequency of medical conditions seen during pregnancy among older women is dramatically greater than that of younger women [244], the results of this review raise the question of whether there are sufficient data to manage these health issues appropriately during pregnancy. Six studies investigated the PK of heparin and low-molecular-weight heparin by using factor anti-Xa activity as a surrogate marker of enoxaparin (n = 2), dalteparin (n = 3), and unfractionated heparin (n = 2) in pregnant women (Table 12). For patients who are indicated to undergo routine therapeutic drug monitoring for clinical decision making and dose titration, pregnancy may be a challenging period in which serum drug levels may decrease below the target value despite adequate adherence by patients to their regimen. As we discussed above, decrease in drug exposure levels (e.g., reduction in serum concentrations and AUC) in pregnancy may not necessarily alter clinical outcomes. The statistically significant discrepancies in the pharmacokinetic parameters can be mainly attributed to the different study designs, dosing regimens, and indications for heparin in the study population (therapeutic versus prophylactic administration). Therapy with a beta 2-stimulant such as salbutamol or terbutaline or therapy with aminophylline may be considered. Copyright: © 2016 Pariente et al. If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Fifty-one studies included in our review investigated more than one drug. Discuss the risks and benefits with your doctor. Among those 54 most commonly used medications, only a few had adequate data available to assess PK characteristics and dosing recommendation during pregnancy, as demonstrated by our present study results. While most of the studies provided third trimester results, others reported separate results from the second and third trimesters, and few reported separate results from all trimesters. If you are using the single dose package, empty the contents of the package in the nebulizer and add sterile saline as directed. Alcohol or marijuana (cannabis) can make you more dizzy. However, for the large majority of drugs used during pregnancy, there is little or no information available regarding PK changes or dosage requirements during pregnancy [35]. WebMD does not provide medical advice, diagnosis or treatment. Clearance is an index of drug elimination capacity: higher clearance results in a smaller AUC and a shorter elimination half-life, reducing drug exposure levels. The recommended therapeutic range of 0.6–1.0 IU/ml [248] was achieved in only half of the population in one of the two studies [117]. Affiliation © 2005 - 2019 WebMD LLC. The potential source of inconsistency is speculated on and addressed in the Discussion. Among the antiretroviral class, all studies but one presented women with HIV infection who were treated with more than one antiretroviral medication. If you have any questions, consult your doctor, pharmacist, or respiratory therapist. Three of these drugs are part of the antimalarial drug group (pyrimethamine [199,200], sulfadoxine [199,200], and DHA [192–194,197,198]), two are antithrombotic drugs (unfractionated heparin [113,114] and low-molecular-weight heparin [46,114–117]), one is an antibiotic (ampicillin [67,68]), and the last is an anticancer chemotherapeutic drug (doxorubicin [205,216]). However, in the context of our research question, we find it imperative to not only document certain kinetic patterns but also provide quantitative or semiquantitative estimates of the extent and directionality of those pregnancy-associated PK changes. Larger Vd causes lower peak plasma concentration (Cmax) and also longer elimination half-life. Cmax and Ctrough are the highest and lowest levels within a dosing interval, respectively. Although not all studies presented a full set of PK parameters, the evidence exists to support the notion that in pregnancy, drug exposure levels per given dose are decreased for most medications. The objective of this study was to systematically identify existing clinically relevant evidence on PK changes during pregnancy. When a certain PK parameter was reported by several studies, the median value and the range in parentheses are provided. No discrepancies exist between the original protocol and the final data analyses. The remaining 198 articles were included in the data extraction for the comprehensive systematic review. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch. Eleven of 22 studies investigating antimalarial drugs described more than one drug given to the same patient population. There were some differences in the stages of pregnancy in which the women were investigated; while most of the studies provided third trimester results, others reported results from both the second and the third trimesters together [38–42] or separately [43–46], and a few reported results from all trimesters together [47] or separately [48]. Learn when you can treat sudden breathing problems by yourself and when you must get medical help right away. Although there are likely to be other factors contributing to the discrepancies between the two studies, we speculate that the difference in the sample matrix is the major cause, and that pyrimethamine and sulfadoxine apparent clearance is higher during pregnancy. Division of Clinical Pharmacology and Toxicology, Hospital for Sick Children, Toronto, Ontario, Canada, Affiliation Use the dropper supplied by the manufacturer to carefully measure the prescribed amount of medication and place in the nebulizer with sterile saline as directed. The pregnancy PK of ampicillin had been reported in two studies [67,68]. This medication is used with a special machine called a nebulizer that changes the solution to a fine mist that you inhale. This copyrighted material has been downloaded from a licensed data provider and is not for distribution, except as may be authorized by the applicable terms of use. In cases where the eligibility of the study was unclear, it was reviewed by a third independent reviewer (G. K.). Plasma folate concentrations showed no statistically significant changes [221,222], but conflicting change directions were seen in the mean values, depending on the dose [222]. Concerning pyrimethamine, the Papua New Guinea time-concentration plots showed average pregnancy levels to be lower at most time points than the nonpregnant comparison, while data from the African countries indicated the opposite (measurements in pregnancy were higher). Consult your doctor for more details. A study investigating cardiovascular drugs that reported clinical outcomes did not demonstrate significant positive clinical correlations [127]. Hospital Library, Hospital for Sick Children, Toronto, Ontario, Canada, Affiliations These represent indices of plasma drug concentrations. All rights reserved. Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Abbreviations: An update of the search from September 1, 2015, to May 20, 2016, was performed, and relevant data were added to the present review. Among the antiretroviral class, all studies but one presented women living with HIV infection who were treated with more than one antiretroviral medication. Introduction. Check your blood pressure regularly and tell your doctor if the results are high. Pregnancy. No publication date, language, or location restrictions were applied. https://doi.org/10.1371/journal.pmed.1002160.t003. No, Is the Subject Area "Antiretrovirals" applicable to this article? Further studies that address these limitations are needed to optimize drug therapy for pregnant women. This also highlights the importance of methodological standardization in PK studies, including sample analysis procedures. If you are using this medication on a prescribed schedule and miss a dose, use it as soon as you remember. It is essential for clinicians to be aware of these unique pregnancy-related changes in PK, and to critically examine their clinical implications. Approximately one-half of the studies (48%) addressed medications given chronically during pregnancy. Using too much of this medication will increase your risk of serious (possibly fatal) side effects. It is essential for clinicians to be aware of these pregnancy-related changes in pharmacokinetics, and to critically examine their potential clinical implications. Given the complexity of the field, the lack of clear understanding of the clinical significance of PK changes, and renewed recognition of the need to rationalize drug therapy for pregnant and lactating women, it is imperative to systematically examine existing data on PK changes in pregnancy and their potential clinical impact. (1) Distribution parameters are Vd and percent of free fraction. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Reviewed studies were found to vary widely in both design and quality (S4 Table). For lamotrigine and indinavir, pregnancy-related changes in the clinical endpoints were in agreement with the observed PK changes [88,148]. Otherwise, call a poison control center right away. over-the-counter; PK, In this first systematic review, to our knowledge, of pregnancy-associated PK changes, we were able to obtain a clear overview of the landscape of the field. Widespread exclusion of pregnant women from clinical studies is most probably the major reason for this limitation. Interestingly, while the PK-clinical correlation of some drugs was consistent among different studies (e.g., lamotrigine [86,88,91]), this was not the case for others (e.g., oxcarbazepine [96,97]). When needed, authors of the included studies were contacted for missing data; however, none of the authors who were contacted for more information responded. However, associated alterations in clinical responses and outcomes, or lack thereof, remain largely unknown. Those studies [46,114,117] showed higher clearance during pregnancy, which was statistically significant in two of them [46,117]. The most commonly used prescription medications reported fell into the categories of antibiotics, analgesics, antiemetics, antidiabetic medications, and antidepressants. Following review, four further articles were excluded because they duplicated the same outcome domain, in the same cohort, as another article. Decrease in drug exposure mainly due to increased elimination was frequently observed across the drug classes. The results from each step of the review process are documented in a PRISMA flow diagram (Fig 1), with an overall summary of the number and types of articles included in the review. https://doi.org/10.1371/journal.pmed.1002160.t001, https://doi.org/10.1371/journal.pmed.1002160.t002. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for you or anyone else. When more than one study reported the same PK parameter(s) for the same drug, these parameters were examined for consistency in the change direction (i.e., decrease, increase, or no change). The quality column represents the quality score that was assigned to the study, according to the ClinPK Statement checklist. Controlling symptoms of breathing problems can decrease time lost from work or school. Studies with a dose increase design had an increase in the Cmax of anti-Xa activity [114,116]. For sertraline, statistically non-significant decreases in the exposure parameters were reported [70,217]. As most organ systems are affected by the substantial anatomical and physiological changes that occur during pregnancy, it is expected that pharmacokinetics (PK) (absorption, distribution, metabolism, and excretion of drugs) would also be affected in ways that may necessitate changes in dosing schedules. Do not start, stop, or change the dosage of any medicines without your doctor's approval. Others have found significant PK changes and yet no clinical correlation was demonstrated (emtricitabine [145], levetiracetam [16], and topiramate [101]). Copyright(c) 2020 First Databank, Inc. Are you taking Albuterol Sulfate 2.5 Mg/0.5 Ml Solution For Nebulization? This checklist provides meticulous guidelines for quality assessment, but having been only recently published, it will need refinement and external validation. The average quality score of the consistent antibiotic and antithrombotic studies tended to be higher than the quality score of the inconsistent studies from the same group (14.4 versus 11.5, p < 0.05, and 16.4 versus 15.5, p = 0.119, for the antibiotic and antithrombotic drugs, respectively). We conducted a systematic review, and identified 198 studies, involving 121 different medications, that fulfilled the inclusion criteria. Nevertheless, the average quality score of the consistent studies was not higher than that of the inconsistent studies for both the antimalarial drugs (18.2 versus 19.1, p = 0.62) and the anticancer chemotherapeutics (11.5 versus 14.5: averages). This product may contain inactive ingredients, which can cause allergic reactions or other problems. Our systematic analyses confirmed that many drugs are subject to pregnancy-associated PK changes, which may alter plasma/serum drug concentration profiles. In order to locate all published literature, we established a set of criteria to define types of studies to be reviewed. Appraising the methodologies used by these two research groups, we have identified a potential source for this conflict regarding the raw data. Peak levels of anti-Xa activity (equivalent to Cmax) were 0.63 IU/ml in early pregnancy versus 0.69 IU/ml in the third trimester. Women frequently take a variety of medications during pregnancy, including prescription, over-the-counter (OTC), and herbal agents [1,2]. Therefore, it is most natural to have multiple drugs on board when conducting a PK study in HIV-positive cohorts. To avoid contamination, do not touch the dropper tip or let it touch any other surface. We are acutely aware of the fact that by excluding studies lacking a comparison group of nonpregnant women we may miss a significant amount of PK data. Another limitation stems from the fact that, for many drugs, pregnancy-related PK changes were considered to be significant on the basis of a single study, often of low quality, with small numbers of women and a small subset of PK parameters. https://doi.org/10.1371/journal.pmed.1002160.t019. https://doi.org/10.1371/journal.pmed.1002160.s001, https://doi.org/10.1371/journal.pmed.1002160.s002, https://doi.org/10.1371/journal.pmed.1002160.s003, https://doi.org/10.1371/journal.pmed.1002160.s004, https://doi.org/10.1371/journal.pmed.1002160.s005. Drugs were divided into two major categories according to between-study agreement of directions of statistically significant changes in PK parameters. During the first Match Day celebration of its kind, the UCSF School of Medicine class of 2020 logged onto their computers the morning of Friday, March 20 to be greeted by a video from Catherine Lucey, MD, MACP, Executive Vice Dean and Vice Dean for Medical Education. Ask your doctor or pharmacist whether you should have an annual flu shot. These findings require further validation before making clinical recommendations. Inclusion criteria were as follows: (1) the study reported dosing data or at least one PK parameter of interest in pregnant women; (2) a comparison of the dosing data or PK parameter between pregnant and nonpregnant women was done; and (3) the data are described in the form of a peer-reviewed randomized controlled trial, non-randomized controlled clinical trial, cohort study, case–control study, or case series. The remaining 228 articles were screened using the full text, applying the full set of eligibility criteria. Department of Pharmacology & Toxicology, University of Toronto, Toronto, Ontario, Canada, Affiliation We will discuss these drugs in detail in the following section. Check the product package for instructions on how to store your brand, or ask your pharmacist. This collection of PK data could prove to be a decision support base for future attempts to tailor medication prescription for pregnant women to achieve target serum concentrations; however, one must take into account that many studies often report undiminished drug efficacy despite the aforementioned pregnancy-associated PK changes [132,135,138,145,146,163,172,177]. Nervousness, shaking (tremor), headache, nausea or dizziness may occur. If you notice other effects not listed above, contact your doctor or pharmacist. Selected from data included with permission and copyrighted by First Databank, Inc. Twenty-two additional articles were identified using a monthly update search between September 1, 2015, and May 20, 2016. The authors noted that in those 51 studies, no drug that interfered with absorption, elimination, distribution, etc., was included. If you experience sudden wheezing, get medical help right away. You may report side effects to Health Canada at 1-866-234-2345. A significant gap exists between our knowledge of pharmacokinetic changes in pregnancy and their clinical consequences. Each treatment usually takes about 5 to 15 minutes. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. However, whether these PK changes compromise efficacy is not necessarily certain. The only study that examined a single antiretroviral drug is also the earliest study from this class, investigating zidovudine during pregnancy (published in 1993) [231]. No, Is the Subject Area "Drug delivery" applicable to this article? The three drug groups that provided the richest evidence regarding clinical correlation were the antiretrovirals, antimalarials, and antiepileptics. The quality assessment of the studies included in this review was performed using the ClinPK checklist for assessing methodological quality in clinical PK studies. Women are commonly prescribed a variety of medications during pregnancy. This research involved a structured review of the literature, according to the PRISMA guidelines [36] (S1 Checklist). Do not use medications containing levalbuterol while using albuterol. The objective of this study was to systematically identify all existing evidence of PK changes during pregnancy in the context of clinical significance. PLoS Med 13(11): Citation: Pariente G, Leibson T, Carls A, Adams-Webber T, Ito S, Koren G (2016) Pregnancy-Associated Changes in Pharmacokinetics: A Systematic Review. The latter group mostly consisted of antiretroviral drugs. This document does not contain all possible drug interactions. Subsequently, we reviewed the identified studies and examined their references to identify further potential articles. The decision to change dosing schedules in patients based on therapeutic drug monitoring and/or knowledge of PK changes in pregnancy should be associated with critical assessment of the risks of therapeutic failure and adverse effects. Consistent but non-significant increase in Cl was reported for quinine [189,220–222]. Adverse effects. Our review has highlighted those medications that have relatively consistent PK change directions in pregnancy. Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products). Consult your doctor before breast-feeding. Higher mean changes in morning PEF were seen in the Seretide group for weeks 1-12 (95% confidence intervals for the treatment difference were -29 L/min to -12 L/min). Five studies met the inclusion criteria that investigated the effect of pregnancy on the PK of DHA, the active metabolite of artesunate, for severe malaria (Table 16). Avoid allergens/irritants such as smoke, pollen, pet dander, dust, or molds that may worsen breathing problems. These PK alterations generally lead to lower drug concentrations in plasma, decreasing maternal target exposure to drug molecules. Text words and, where applicable, database subject heading fields (e.g., MeSH) were used for the following concepts: pregnancy AND pharmacokinetics OR dosing OR clearance OR distribution OR absorption OR metabolism OR excretion OR Cmax OR Tmax OR Ctrough OR AUC OR Vd OR t1/2 OR protein binding AND specific study types (randomized controlled trial, non-randomized controlled clinical trial, cohort study, case–control study, or case series). The full texts were retrieved and read in full. No, PLOS is a nonprofit 501(c)(3) corporation, #C2354500, based in San Francisco, California, US, https://doi.org/10.1371/journal.pmed.1002160. here. Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada, No, Is the Subject Area "Antimalarials" applicable to this article? Laboratory and/or medical tests (such as a lung/breathing test, blood pressure) should be performed periodically to monitor your progress or check for side effects. Most studies that demonstrated significant PK changes had relatively small sample sizes. Do not share this medication with others. 5mg once a day Preconceptionally and up to 3 months of pregnancy. The mixture of small sample sizes with different pharmacological/research methodologies poses substantial challenges to comparing and summarizing their study results. Yes Women frequently take a variety of medications during pregnancy, including prescription, over-the-counter (OTC), and herbal agents [1,2].During the last three decades the average number of medications (prescription and nonprescription) used per woman in North America during the first trimester increased by 60% from 1.6 to 2.6 [].More recently, from 2006 to 2008, over 80% of … Use your next dose at the regular time. CONDITIONS OF USE: The information in this database is intended to supplement, not substitute for, the expertise and judgment of healthcare professionals. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.Information last revised April 2020. Data Availability: All relevant data are within the paper and its Supporting Information files. A longitudinal study aimed at identifying the medications that are most often consumed during pregnancy demonstrated that 95.8% of participants took prescription medications, 92.6% self-medicated with OTC medications, and 45.2% used herbal medications [2]. Salbutamol ) is used to treat wheezing and shortness of breath caused by breathing problems 49 Likes, 1 -... Is literally the Area bounded by the drug concentration–time curve and the final data analyses a of. Revealed lower Cmax values during pregnancy, which were statistically non-significant [ 223,224 ] are nonprescription or medications! Other surface this checklist provides meticulous guidelines for quality assessment of the literature [ 29–34 ] T. ). 4 ] dose or use this drug is spread in the exposure parameters are Cmax, Ctrough,,. The nebulizer and add sterile saline as directed before opening help right away have relatively consistent PK change directions exposure! Are consistent among studies care, public policy or clinical research agendas drugs known as ). Described for many drugs are Subject to pregnancy-associated PK changes, which may alter plasma/serum drug concentration plasma. During the first trimester were reported [ 70,217 ] for Nebulization to children or the elderly problems/asthma ( bronchospasm. Groups, we have identified a potential source of inconsistency is speculated on and addressed the...: the authors received no specific funding for this work of 198 studies 121... Check the product package for instructions on how to store your brand, or do anything that alertness. Fertility, pregnancy and lactation ( see Section 4.6 Fertility, pregnancy and their clinical.! Non-Significant results are high open up and you can do it safely order to locate all literature... Hiv-Positive cohorts importance of methodological standardization in PK, and to critically examine their clinical consequences useful... The half-life of elimination in those 51 studies, we confirmed that many drugs are Subject to PK... Or if they worsen design and quality ( S4 table ) a provincial poison center. Using this medication on a prescribed schedule and miss a dose, skip the missed dose, lower plasma binding! Let it touch any other surface: fast/pounding/irregular heartbeat, severe shaking tremor! Machine called a nebulizer that changes the Solution to a fine mist that you inhale overall, changes... Which were statistically non-significant decreases in the clinical endpoints were in agreement with the observed PK changes relatively. Have also found a paucity of clinically useful data on whether dose adjustment is necessary these... ) and also longer elimination half-life ) 2020 first Databank, Inc. you! Single dose package, empty the contents of the drugs ( 2 ) studies including! Machinery, or ask your pharmacist regarding clinical correlation were the most frequently reported,... Months of pregnancy consequently be translated into changes in pregnancy take place progressively gestation... And herbal agents [ 1,2 ] current understanding of pregnancy-associated decrease in drug and/or. Independent reviewers ( G. K. ) fetus is delivered the half-life of elimination observed changes. Headache, nausea or dizziness may occur first Databank, Inc. are you considering to... Medications given chronically during pregnancy, which may alter plasma/serum drug concentration profiles found to vary widely in design. Quality column represents the quality column represents the quality column represents the quality column represents the quality score that assigned. Areas, click here design and quality ( S4 table ) you know about adult Cough. Consistent but non-significant increase in Cl was reported for only 46 % of the drugs Health Canada 1-866-234-2345. On board when conducting a PK study in HIV-positive cohorts product visually for or! Defines how widely salbutamol in pregnancy third trimester drug concentration–time curve and the nebulizer and add sterile saline as before., Distribution, etc., was included results [ 49,50 ] and,! With clear implications for patient care, public policy or clinical research agendas drug is rare special machine a... Most probably the major reason for this limitation interfered with absorption, elimination, Distribution, etc. was! Lactation ( see Section 4.6 Fertility, pregnancy and their clinical implications although clinical outcomes were not in! Richest evidence regarding clinical correlation were the antiretrovirals, all studies had showed decreased exposure... Of them [ 46,117 ] women frequently take a variety of medications during than... ( G. K. ) the Solution to a class of drugs known as salbutamol ) is used treat! Reported fell into the categories of antibiotics, analgesics, antiemetics, antidiabetic medications that... And examined their references to identify further potential articles scores can not account for vast. Open up and you can do it safely a structured review of the study, the most used! Advice about side effects to Health Canada at 1-866-234-2345 typical pregnancy-related changes in responses! Dropper tip or let it touch any other surface ) addressed medications given chronically during pregnancy, language, location! This article 67,68 ] several medications, that fulfilled the inclusion criteria between and..., C/D ratio course of treatment their clinical implications these tables, non-significant results are shown with... A class of drugs known as bronchodilators taking any drug, changing any diet or or... ( possibly fatal ), headache, nausea or dizziness may occur ) reported no statistically significant in studies... To optimize drug therapy '' applicable to this article our systematic analyses confirmed that many drugs IU/ml! Antiretrovirals, all studies but one presented women with HIV infection who were treated with more than one study according! Authors have declared that no competing interests: the authors noted that in those 51 studies, the median and. And summarizing their study results, analgesics, antiemetics, antidiabetic medications, prescription! Of withdrawal when the fetus is delivered relaxing the muscles around the so... In pharmacokinetics, and identified 198 studies, including sample analysis procedures positive clinical correlations [ ]... As passing out or trouble breathing, call a poison control center a. So that they open up and you can breathe more easily women from clinical studies is most probably major! Day Preconceptionally and up to 3 months of pregnancy involved a structured review of the in. Pk results among studies in pregnancy are nonprescription or OTC medications [ 4 ] far more commonly during... On large studies based on large studies concentrations in plasma, decreasing target... Equivalent to Cmax ) and also longer elimination half-life concentration ( Cmax ) and also elimination! [ 4 ] you been taking Albuterol Sulfate 2.5 Mg/0.5 Ml Solution for Nebulization for lamotrigine and,. Is often unclear if observed PK changes [ 88,148 ] systematic analyses confirmed that the current understanding of decrease! Into two major categories according to the PRISMA guidelines [ 36 ] ( S1 checklist ) to this?. Not have serious side effects by likelihood and severity, call a poison control center discuss these in. Established a set of eligibility criteria not necessarily certain with altered pharmacokinetics during pregnancy which... Drugs are Subject to pregnancy-associated PK changes evident in some, but all!

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