{"id":1516,"date":"2026-05-13T14:05:32","date_gmt":"2026-05-13T14:05:32","guid":{"rendered":"https:\/\/beonemedaffairs.com\/global\/?page_id=1516"},"modified":"2026-05-16T06:02:16","modified_gmt":"2026-05-16T06:02:16","slug":"expert-digest","status":"publish","type":"page","link":"https:\/\/beonemedaffairs.com\/global\/disease-education\/hematology\/begenius\/expert-digest\/","title":{"rendered":"Expert digest"},"content":{"rendered":"\n <section class=\"hero-section webinar-hero breadlinknew\">\n            <img decoding=\"async\" src=\"https:\/\/beonemedaffairs.com\/global\/wp-content\/uploads\/sites\/2\/2026\/05\/heroimage.png\" alt=\"\" class=\"hero-banner-img\">\n            <div class=\"container\">\n                <div class=\"hero-content\">\n                    <nav class=\"hero-breadcrumb\" aria-label=\"Breadcrumb\" style=\"color:#ffffff;\"><a href=\"https:\/\/beonemedaffairs.com\/global\/\" style=\"color:#ffffff;\">HOME<\/a><span class=\"breadcrumb-separator\" style=\"color:#ffffff;\">&gt;<\/span><\/nav>                    <h1 class=\"hero-title\">BTKi pharmacotherapy: <br\/>Expert overview <\/h1>\n\t\t\t\t\t\t\t\t\t\t<div class=\"Webinars-inner-content\">\n                         <p class=\"fs-24 text-light\">Expert overview from hematologist Alessandra Tedeschi and\r\npharmacologist Federico Pea<\/p>\r\n                       \n                    <\/div>\n\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t                <\/div>\n            <\/div>\n        <\/section>\n\n\n \n\n\n\n <section class=\"expert-digest-section\">\n            <div class=\"container\">\n\t\t\t\t\t\t\t                <div class=\"content-part-expert\">\n                    <h2 class=\"intro-heading\">BTK inhibition<\/h2>\n                    <div class=\"text-part\"><p>Ibrutinib was the first-in-class BTK inhibitor, initially receiving approval for MCL in 2013.<sup>1<\/sup>\u00a0It offers deep and durable responses with an acceptable toxicity profile, but patients may experience side effects attributed to significant off-target activity.<sup>2<\/sup>\u00a0Cardiovascular adverse drug reactions are a notable challenge, with substantial real-world incidence of atrial fibrillation and hypertension among patients treated with ibrutinib.<sup>2-4<\/sup><\/p>\n<p>The next-generation BTK inhibitors zanubrutinib and acalabrutinib have greater selectivity for BTK compared with ibrutinib and have consistently demonstrated some notable advantages in terms of safety in head-to-head trials versus ibrutinib.<sup>5-7<\/sup>\u00a0Notably, zanubrutinib and acalabrutinib have favorable cardiac safety profiles compared with ibrutinib.<sup>5-7<\/sup><\/p>\n<p>Efficacy outcomes have usually been similar between BTK inhibitors in head-to-head trials. However, in the ALPINE study in relapsed\/refractory (R\/R) CLL, zanubrutinib demonstrated a better overall response rate (83.5% vs. 74.2%) and 24-month progression-free survival (78.4% vs. 65.9%; hazard ratio: 0.65; P=0.002) versus ibrutinib.<sup>7<\/sup><\/p>\n<p>These three covalent BTK inhibitors are currently approved as monotherapies by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) for the treatment of four B-cell malignancies (see Table 1).<sup>8\u201313<\/sup><\/p>\n                         \n                    <\/div>\n                <\/div>\n\t\t\t\t\t\t\t\t                <div class=\"table-expert table-expert--wide\">\n                    <div class=\"table-text-top\">\n                        <p>Table 1. BTK inhibitor approvals in B-cell malignancies and pharmacology<sup>8\u201314<\/sup><\/p>\n                    <\/div>\n                    <div class=\"table-part\">\n                        <div class=\"table-responsive\">\n                         <table class=\"expert-table\">\n<thead>\n<tr>\n<th><\/th>\n<th>Ibrutinib<\/th>\n<th>Zanubrutinib<\/th>\n<th>Acalabrutinib<\/th>\n<\/tr>\n<\/thead>\n<tbody>\n<tr>\n<td><strong>Approved indications in Europe (EMA)<\/strong><\/td>\n<td>CLL*, MCL, WM<sup>\u2020<\/sup><\/td>\n<td>CLL, MZL, WM<\/td>\n<td>CLL<sup>\u2021<\/sup><\/td>\n<\/tr>\n<tr>\n<td><strong>Approved indications in the USA (FDA)<\/strong><\/td>\n<td>CLL*, WM<sup>\u2020<\/sup><\/td>\n<td>CLL, MCL, MZL, WM<\/td>\n<td>CLL<sup>\u2021<\/sup>, MCL<\/td>\n<\/tr>\n<tr>\n<td><strong>Pharmaceutical forms in Europe (EMA)<\/strong><\/td>\n<td>Hard capsule: 140 mg<br \/>Tablets: 140 mg, 280 mg, 420 mg, and 560 mg<\/td>\n<td>Hard capsule: 80 mg<\/td>\n<td>Hard capsule: 100 mg<br \/>Tablet: 100 mg<\/td>\n<\/tr>\n<tr>\n<td><strong>Pharmaceutical forms in the USA (FDA)<\/strong><\/td>\n<td>Capsules: 70 mg and 140 mg<br \/>Tablets: 140 mg, 280 mg, and 420 mg<br \/>Oral suspension: 70 mg\/mL<\/td>\n<td>Hard capsule: 80 mg<\/td>\n<td>Hard capsule: 100 mg<br \/>Tablet: 100 mg<\/td>\n<\/tr>\n<tr>\n<td><strong>Approved dose<\/strong><\/td>\n<td>420 mg QD for CLL and WM<br \/>560 mg QD for MCL<\/td>\n<td>160 mg BID or 320 mg QD<\/td>\n<td>100 mg BID<\/td>\n<\/tr>\n<tr>\n<td><strong>IC<sub>50<\/sub> against BTK, nM<\/strong><\/td>\n<td>1.5<\/td>\n<td>0.5<\/td>\n<td>5.1<\/td>\n<\/tr>\n<tr>\n<td><strong>Potency of major active metabolite against BTK<\/strong><\/td>\n<td>~15-fold less potent compared with the parent molecule <\/td>\n<td>N\/A<\/td>\n<td>~2-fold less potent compared with the parent molecule <\/td>\n<\/tr>\n<tr>\n<td><strong>Half-life, hours<\/strong><\/td>\n<td>~4 to 6<\/td>\n<td>~2 to 4<\/td>\n<td>~0.6 to 2.8<\/td>\n<\/tr>\n<tr>\n<td><strong>Plasma protein binding, %<\/strong><\/td>\n<td>97.3\u201397.7<\/td>\n<td>~94<\/td>\n<td>97.4\u201397.5 <\/td>\n<\/tr>\n<tr>\n<td><strong>AUC<sub>0<\/sub><sub>\u2013<\/sub><sub>24h<\/sub> (CV%), ng\u00b7h\/mL<\/strong><\/td>\n<td>420 mg QD: 707\u20131,159 (50%\u201372%)<br \/>560 mg QD: 865\u2013978 (69%\u201382%)<\/td>\n<td>160 mg BID: 2,295 (37%)<br \/>320 mg QD: 2,180 (41%)<\/td>\n<td>100 mg BID: 1,843\u20131,850 (38%\u201372%) <\/td>\n<\/tr>\n<tr>\n<td><strong>fu. AUC<sub>0<\/sub><sub>\u2013<\/sub><sub>24h<\/sub>, nM\u00b7h<\/strong><\/td>\n<td>420 mg QD: 37\u201360<br \/>560 mg QD: 46\u201351<\/td>\n<td>160 mg BID: 278<br \/>320 mg QD: 267<\/td>\n<td>100 mg BID: 103<\/td>\n<\/tr>\n<tr>\n<td><strong>Plasma exposure of major active metabolite<\/strong><\/td>\n<td>1- to 2.8-fold higher than parent AUC <\/td>\n<td>N\/A<\/td>\n<td>2- to 3-fold higher than parent AUC <\/td>\n<\/tr>\n<tr>\n<td><strong>Median BTK occupancy in PBMC at trough<\/strong><\/td>\n<td>420 mg to 820 mg QD: &gt;90% <\/td>\n<td>160 mg BID: 100%<br \/>320 mg QD:100%<\/td>\n<td>100 mg BID: \u226595% <\/td>\n<\/tr>\n<tr>\n<td><strong>Median BTK occupancy in lymph node at trough<\/strong><\/td>\n<td>420 mg QD: &gt;90%<\/td>\n<td>160 mg BID: 100%<br \/>320 mg QD: 94%<\/td>\n<td>100 mg BID: 95.8%<br \/>200 mg QD: 90%<\/td>\n<\/tr>\n<tr>\n<td><strong>P-gp and brain penetration<\/strong><\/td>\n<td>Not a P-gp substrate.<\/p>\n<p>                        Brain penetration data in patients available.<\/td>\n<td>Weak P-gp substrate.<\/p>\n<p>                        Brain penetration data in patients available.<\/td>\n<td>P-gp substrate.<\/p>\n<p>                        Likely limited brain penetration.<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n                        <\/div>\n                    <\/div>\n                    <div class=\"text-part\">\n                       <div class=\"table-bottom\">\n<p>*Approved as monotherapy or with obinutuzumab, rituximab, or venetoclax for previously untreated CLL and as monotherapy or with bendamustine and rituximab for previously treated CLL. \u2020Approved as monotherapy or with rituximab for previously treated patients and untreated patients unsuitable for chemoimmunotherapy. \u2021Approved as monotherapy or with obinutuzumab. AUC, area under the curve; BID, twice a day; fu., fraction of unbound drug in plasma; IC50, half maximal inhibitory concentration; N\/A, not applicable; PBMC, peripheral blood mononuclear cell; QD, once a day.<\/p>\n<\/p><\/div>\n                    <\/div>\n                <\/div>\n\t\t\t\t\t\t\t\t                <div class=\"text-part\">\n                    <div class=\"text-part\">\n                        <h2 class=\"intro-heading marbt10\">Tolerability with BTK inhibitors<\/h2>\n                         <p class=\"txt-light\">Side effects associated with BTK inhibitors are usually manageable, but withdrawal or discontinuation of the agents may be required in some circumstances (see Table 2).2,5\u20137<\/p>\n<p>Table 2. BTK inhibitor side effect management<sup>9,11,12<\/sup><\/p>\n                    <\/div>\n                    <div class=\"table-part text-part\">\n                        <div class=\"table-responsive\">\n                            <table class=\"expert-table\">\n<thead>\n<tr>\n<th><\/th>\n<th>Dose adjustments or discontinuation<\/th>\n<\/tr>\n<\/thead>\n<tbody>\n<tr>\n<td>Ibrutinib<\/td>\n<td>\n<ul>\n<li>Ibrutinib should be withheld on the first, second, and third occurrence and discontinued after the fourth occurrence of Grade 3 or 4 non-hematological toxicities; Grade 3 or 4 neutropenia with infection or fever; and Grade 4 hematological toxicities<\/li>\n<li>Ibrutinib should be withheld on the first and second occurrence, and discontinued after the third occurrence of Grade 2 cardiac failure<\/li>\n<li>Ibrutinib should be withheld on the first occurrence and discontinued after the second occurrence of Grade 3 cardiac arrhythmias<\/li>\n<li>Ibrutinib should be discontinued after the first occurrence of Grade 3 or 4 cardiac failure or Grade 4 cardiac arrhythmias<\/li>\n<\/ul>\n<\/td>\n<\/tr>\n<tr>\n<td>Zanubrutinib<\/td>\n<td>\n<ul>\n<li>Zanubrutinib should be withheld on the first, second, and third occurrence and discontinued after the fourth occurrence of Grade \u22653 non-hematological toxicities; Grade 3 febrile neutropenia; Grade 3 thrombocytopenia with significant bleeding; Grade 4 neutropenia (lasting &gt;10 consecutive days); or Grade 4 thrombocytopenia (lasting &gt;10 consecutive days)<\/li>\n<\/ul>\n<\/td>\n<\/tr>\n<tr>\n<td>Acalabrutinib<\/td>\n<td>\n<ul>\n<li>Acalabrutinib should be withheld on the first, second, and third occurrence and discontinued after the fourth occurrence of Grade 3 thrombocytopenia with bleeding; or Grade 4 thrombocytopenia or Grade 4 neutropenia lasting longer than 7 days; or Grade 3 or greater non-hematological toxicities<\/li>\n<\/ul>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n                        <\/div>\n                    <\/div>\n                <\/div>             <\/div>\n        <\/section>\n\t\t\n\t\t\n\t\t\n\t\t\n        <!-- Companion Resource Section -->\n\t\t        <section class=\"companion-section\">\n            <div class=\"container\">\n                <h2 class=\"companion-title\"> DDI overview<\/h2>\n                <div class=\"overview-content-inner\"> <p class=\"fs-18\">Monitoring and managing the risk of potential DDIs is an important component of treatment with any drug, including BTK inhibitor therapy. Most patients with CLL, WM, MCL, or MZL are \u226560 years old at diagnosis and likely to have comorbidities that require medication.15\u201318 Acute conditions (such as infections) that require treatment will also arise over time in this patient population.<\/p>\n<p class=\"fs-18\">DDIs occur when one drug alters the activity of another drug and result from pharmacokinetic and\/or pharmacodynamic mechanisms, both of which are relevant to BTK inhibitors (see Figure 1).<sup>19<\/sup><\/p>\n<h6 class=\"fs-18\">Figure 1. DDIs with BTK inhibitors<sup>9,11,12,19,20<\/sup><\/h6>\n                  \n                <\/div>\n\t\t\t\t                <div class=\"companion-img-wrapper\">\n                    <img decoding=\"async\" src=\"https:\/\/beonemedaffairs.com\/global\/wp-content\/uploads\/sites\/2\/2026\/05\/companion-demo-img.svg\" alt=\"\">\n                <\/div> \t\t\t\t\n                <div class=\"overview-bottom-content\"><p>&nbsp;<\/p>\n<h6 class=\"fs-18\">Table 3. Potential DDIs with ibrutinib, zanubrutinib, and acalabrutinib in patients with B-cell malignancies<\/h6>\n<div class=\"interaction-strength\">\n<h5 class=\"fs-18\">Interaction strength:<\/h5>\n<ul>\n<li><span class=\"fs-14 light-red\">X MAJOR<\/span>\n<p class=\"fs-18\">(highly clinically significant)<\/p>\n<\/li>\n<li><span class=\"fs-14 light-orange\">\u26a0 MODERATE<\/span>\n<p class=\"fs-18\">(moderately clinically significant)<\/p>\n<\/li>\n<li><span class=\"fs-14 light-green\">NO KNOWN INTERACTION.<\/span><\/li>\n<li>\n<p class=\"fs-18\">Interactions may increase (\u2191) or decrease (\u2193) a patient\u2019s exposure to a BTK inhibitor.<\/p>\n<\/li>\n<\/ul>\n<\/div>\n\t\t\t\t                   \n                    <div class=\"download-btn-wrapper\">\n                        <a href=\"#\" class=\"see-all-btn\">DOWNLOAD TABLE PDF <svg xmlns=\"http:\/\/www.w3.org\/2000\/svg\"\n                                width=\"13.704\" height=\"12\" viewBox=\"0 0 13.704 12\">\n                                <path id=\"Vector\"\n                                    d=\"M0,6a.857.857,0,0,1,.856-.857h9.922L7.1,1.465A.858.858,0,1,1,8.314.251l5.138,5.142a.857.857,0,0,1,0,1.213L8.314,11.749A.858.858,0,0,1,7.1,10.535l3.677-3.678H.856A.857.857,0,0,1,0,6Z\"\n                                    fill=\"#fff\" fill-rule=\"evenodd\"><\/path>\n                            <\/svg><\/a> \n\t\t\t\t\t\t\t\t\t\t\t\n                    <\/div>\n\t\t\t\t\t<p class=\"fs-14 download-note\">This table is for educational purposes only, not professional advice, and is not intended for a comparison of the three agents. The interaction strength of potential DDIs is based on the evaluation of information within the prescribing information or summary of product characteristics of each BTK inhibitor and other published studies.8\u201313,21,22 No known interaction was assumed with a particular drug if no interaction data could be found, but this does not mean no interaction can occur in patients.<\/p>\n                   \n                <\/div>\n            <\/div>\n        <\/section>\t\t\t\t\n        <section class=\"key-takeaways-section\">\n            <div class=\"container\">\n                <h2 class=\"companion-title\"> Key takeaway messages<\/h2>\n\t\t\t\t<ul class=\"key-takeaways-list\">\n<li class=\"fs-18\">BTK inhibition has transformed outcomes for many patients with B-cell malignancies, but there are specific pharmacotherapy challenges associated with agents that are usually administered as continuous daily therapy, often over many years<\/li>\n<li class=\"fs-18\">Covalent BTK inhibitors have the same mode of action, but next-generation agents have favorable safety profiles versus ibrutinib, with acalabrutinib (ELEVATE-RR) and zanubrutinib (ALPINE and ASPEN) leading to fewer treatment discontinuations and cardiovascular adverse events compared to ibrutinib<\/li>\n<li class=\"fs-18\">Zanubrutinib has demonstrated superior efficacy versus ibrutinib in R\/R CLL, while acalabrutinib showed non-inferior efficacy compared to ibrutinib<\/li>\n<li class=\"fs-18\">Side effects associated with BTK inhibitors are usually manageable, but dose reductions or discontinuations are necessary in some circumstances<\/li>\n<li class=\"fs-18\">At initial treatment selection and in the long-term management of patients, physicians must be aware of the potential for DDIs with BTK inhibitors<\/li>\n<li class=\"fs-18\">Most of the clinically relevant DDIs with BTK inhibitors relate to concomitant usage with inhibitors or inducers of CYP3A4 and\/or agents associated with a bleeding risk<\/li>\n<\/ul>\n<p class=\"fs-18\">Please refer to the current health authority-approved product information for definitive guidance on each medicine\u2019s drug interactions and recommended management.8\u201313<\/p>\n                \n                \n                <div class=\"takeaways-bottom-content\"><p>&nbsp;<\/p>\n<h5 class=\"fs-18\">References:<\/h5>\n<ul class=\"references\">\n<li>Drugs.com. Imbruvica FDA approval history. Available at: https:\/\/www.drugs.com\/history\/imbruvica.html. Accessed June 2023.<\/li>\n<li>Buske C, Jurczak W, Salem J-E<em> et al.<\/em> Managing Waldenstr\u00f6m&#8217;s macroglobulinemia with BTK inhibitors. <em>Leukemia<\/em> 2023; 37 (1): 35\u201346.<\/li>\n<li>Baptiste F, Cautela J, Ancedy Y<em> et al.<\/em> High incidence of atrial fibrillation in patients treated with ibrutinib. <em>Open Heart<\/em> 2019; 6 (1): e001049.<\/li>\n<li>Dickerson T, Wiczer T, Waller A<em> et al.<\/em> Hypertension and incident cardiovascular events following ibrutinib initiation. <em>Blood<\/em> 2019; 134 (22): 1919\u20131928.<\/li>\n<li>Byrd JC, Hillmen P, Ghia P<em> et al.<\/em> Acalabrutinib versus ibrutinib in previously treated chronic lymphocytic leukemia: Results of the first randomized phase III trial. <em>J Clin Oncol<\/em> 2021; 39 (31): 3441\u20133452.<\/li>\n<li>Tam CS, Opat S, D&#8217;Sa S<em> et al.<\/em> A randomized phase 3 trial of zanubrutinib vs ibrutinib in symptomatic Waldenstr\u00f6m macroglobulinemia: The ASPEN study. <em>Blood<\/em> 2020; 136 (18): 2038\u20132050.<\/li>\n<li>Brown JR, Eichhorst B, Hillmen P<em> et al.<\/em> Zanubrutinib or ibrutinib in relapsed or refractory chronic lymphocytic leukemia. <em>N Engl J Med<\/em> 2023; 388 (4): 319\u2013332.<\/li>\n<li>Pharmacyclics LLC. IMBRUVICA \u2013 US prescribing information. Pharmacyclics LLC; South San Francisco, CA, USA, May 2023.<\/li>\n<li>AstraZeneca AB. Calquence 100 mg hard capsules \u2013 summary of product characteristics. AstraZeneca AB; S\u00f6dert\u00e4lje, Sweden, May 2023.<\/li>\n<li>AstraZeneca Pharmaceuticals LP. CALQUENCE (acalabrutinib) tablets, for oral use \u2013 US prescribing information. AstraZeneca Pharmaceuticals LP; Wilmington, DE, USA, August 2022.<\/li>\n<li>Janssen-Cilag International NV. IMBRUVICA 140 mg hard capsules \u2013 summary of product characteristics. Janssen-Cilag International NV; Beerse, Belgium, April 2023.<\/li>\n<li>BeiGene Ireland Ltd. BRUKINSA 80 mg hard capsules \u2013 summary of product characteristics. BeiGene Ireland Ltd; Dublin, Ireland, March 2023.<\/li>\n<li>BeiGene USA, Inc. BRUKINSA (zanubrutinib) capsules, for oral use \u2013 US prescribing information. BeiGene USA, Inc., San Mateo, CA, USA, April 2023.<\/li>\n<li>Tam CS, Ou YC, Trotman J<em> et al.<\/em> Clinical pharmacology and PK\/PD translation of the second-generation Bruton&#8217;s tyrosine kinase inhibitor, zanubrutinib. <em>Expert Rev Clin Pharmacol<\/em> 2021; 14 (11): 1329\u20131344.<\/li>\n<li>Eichhorst B, Robak T, Montserrat E<em> et al.<\/em> Chronic lymphocytic leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. <em>Ann Oncol<\/em> 2021; 32 (1): 23\u201333.<\/li>\n<li>Dreyling M, Campo E, Hermine O<em> et al.<\/em> Newly diagnosed and relapsed mantle cell lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. <em>Ann Oncol<\/em> 2017; 28 (Suppl 4): iv62\u2013iv71.<\/li>\n<li>Cheah CY, Zucca E, Rossi D<em> et al.<\/em> Marginal zone lymphoma: Present status and future perspectives. <em>Haematologica<\/em> 2022; 107 (1): 35\u201343.<\/li>\n<li>Kastritis E, Leblond V, Dimopoulos MA<em> et al.<\/em> Waldenstr\u00f6m&#8217;s macroglobulinaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. <em>Ann Oncol<\/em> 2018; 29 (Suppl 4): iv41\u2013iv50.<\/li>\n<li>Niu J, Straubinger RM and Mager DE. Pharmacodynamic drug\u2013drug interactions. <em>Clin Pharmacol Ther<\/em> 2019; 105 (6): 1395\u20131406.<\/li>\n<li>Fancher KM and Pappacena JJ. Drug interactions with Bruton&#8217;s tyrosine kinase inhibitors: Clinical implications and management. <em>Cancer Chemother Pharmacol<\/em> 2020; 86 (4): 507\u2013515.<\/li>\n<li>de Abajo FJ, Garc\u00eda-Rodr\u00edguez LA. Risk of upper gastrointestinal tract bleeding associated with selective serotonin reuptake inhibitors and venlafaxine therapy: interaction with nonsteroidal anti-inflammatory drugs and effect of acid-suppressing agents. <em>Arch Gen Psychiatry<\/em> 2008; 65 (7): 795\u2013803.<\/li>\n<li>Pilla Reddy V, Fretland AJ, Zhou D <em>et al.<\/em> Mechanistic physiology-based pharmacokinetic modeling to elucidate vincristine-induced peripheral neuropathy following treatment with novel kinase inhibitors. <em>Cancer Chemother Pharmacol<\/em> 2021; 88 (3): 451\u2013464.<\/li>\n<\/ul>\n                     \n                <\/div>\n            <\/div>\n        <\/section>\t\t<style>\n\t\t\n\t\t.expert-digest-section {padding-bottom:25px}\n\t\t.marbt10 {margin-bottom:10px !Important}\n\t\t\n\t\t.key-takeaways-section .takeaways-bottom-content ul li{    list-style-type: number;}\n\t\t.key-takeaways-list li {list-style:disc}\n\t\t.text-part,.table-responsive   {\n    font-size: 18px;\n    line-height: 1.4;\n    color: #28334a;\n    font-family: poppins;  \n    display: flex;\n    flex-direction: column;\n    gap: 15px;\n\n}\n.text-part a {color:#006d8f;text-decoration:underline}\n.text-part a:hover { text-shadow: 1px 0 0 #006d8f;}\n\t\t .text-part p {\n    font-size: 18px;\n    line-height: 1.4;\n    color: #28334a;\n    font-family: poppins;\n}\n\t\t.text-part  li {list-style:disc; font-size: 18px;\n    line-height: 1.4;\n    color: #28334a;}\n\t.text-part ul {\n    display: flex;\n    gap: 15px;\n    flex-direction: column;\n    padding-left: 20px;\n    padding-bottom: 15px;\n}\n\t\t<\/style>\n\n\n<p><\/p>\n","protected":false},"excerpt":{"rendered":"","protected":false},"author":1,"featured_media":0,"parent":1120,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"footnotes":""},"class_list":["post-1516","page","type-page","status-publish","hentry"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.6 - 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