American College of Clinical Pharmacology®’s Post

Register Now for the June 2024 ACCP Virtual Journal Club Webinar: Estimation of Absolute and Relative Body Fat Content Using Noninvasive Surrogates: Can DXA Be Bypassed? https://lnkd.in/ecg9uEZB hashtag #ACCPVirtualJournalClub hashtag #Pharmacokinetics Why is this article important to your practice? This study explores innovative methods to predict body fat content using easily measurable anthropometric variables like age, height, weight and waist circumference instead of relying on the expensive and less accessible dual-energy x-ray absorptiometry (DXA) scanning. This research is crucial as it provides an improved and validated algorithm for predicting absolute body fat, which can enhance clinical practices related to obesity management. Understanding these new predictive methods can directly impact practice, especially considering the critical role that body composition plays in pharmacokinetics and pharmacodynamics. Efficient and accurate body fat estimation methods are essential for optimizing drug dosing and therapeutic strategies in obese patients, thereby improving treatment outcomes and patient care. Learners that complete this activity will be provided an evidence-based, validated and predictive algorithm as an alternative to DXA scanning to accurately estimate absolute body fat. Target Audience: Interprofessional team of Physicians, Pharmacists, PhDs, Nurse Practitioners and other health care professionals who use the assessment of body fat content in clinical trials and clinical practice. Learning Objectives After completing this activity, the learner will be able to: Describe at least one limitation to the use of DXA scanning for obesity clinical trials and/or drug development; Identify at least one DXA-determined measurement that was selected as a dependent (outcome) variable in this study; List at least one surrogate variable that was predictive of DXA-determined absolute body fat; Identify which surrogate variable had the greatest impact (i.e., magnitude of change) on DXA-determined total body fat in men and women utilizing standardized regression coefficient data.

Register Now for the June 2024 ACCP Virtual Journal Club Webinar: Estimation of Absolute and Relative Body Fat Content Using Noninvasive Surrogates: Can DXA Be Bypassed? https://lnkd.in/ecg9uEZB #ACCPVirtualJournalClub #Pharmacokinetics Why is this article important to your practice? This study explores innovative methods to predict body fat content using easily measurable anthropometric variables like age, height, weight and waist circumference instead of relying on the expensive and less accessible dual-energy x-ray absorptiometry (DXA) scanning. This research is crucial as it provides an improved and validated algorithm for predicting absolute body fat, which can enhance clinical practices related to obesity management. Understanding these new predictive methods can directly impact practice, especially considering the critical role that body composition plays in pharmacokinetics and pharmacodynamics. Efficient and accurate body fat estimation methods are essential for optimizing drug dosing and therapeutic strategies in obese patients, thereby improving treatment outcomes and patient care. Learners that complete this activity will be provided an evidence-based, validated and predictive algorithm as an alternative to DXA scanning to accurately estimate absolute body fat. Target Audience: Interprofessional team of Physicians, Pharmacists, PhDs, Nurse Practitioners and other health care professionals who use the assessment of body fat content in clinical trials and clinical practice. Learning Objectives After completing this activity, the learner will be able to: Describe at least one limitation to the use of DXA scanning for obesity clinical trials and/or drug development; Identify at least one DXA-determined measurement that was selected as a dependent (outcome) variable in this study; List at least one surrogate variable that was predictive of DXA-determined absolute body fat; Identify which surrogate variable had the greatest impact (i.e., magnitude of change) on DXA-determined total body fat in men and women utilizing standardized regression coefficient data.

𝐋𝐢𝐟𝐞 𝐭𝐡𝐫𝐨𝐮𝐠𝐡 𝐭𝐡𝐞 𝐞𝐲𝐞𝐬 𝐨𝐟 𝐚 𝐃𝐚𝐭𝐚 𝐒𝐜𝐢𝐞𝐧𝐭𝐢𝐬𝐭 Are we interpreting clinical trial results correctly? A wake-up call for all those who evaluate clinical data In the ever-evolving landscape of #healthcare, the use of surrogate markers as primary endpoints in clinical trials is becoming increasingly prevalent. However, a recent study published in JAMA Network Open (https://lnkd.in/d_PjhhcD) raises important questions about the reliability of these markers in predicting actual clinical outcomes. This is a critical insight for data scientists and healthcare providers who rely on these markers to inform treatment decisions and drug approvals. Surrogate #markers, such as blood pressure or cholesterol levels, are often used in clinical trials to expedite the drug approval process. They offer a way to measure the efficacy of a treatment without waiting for long-term outcomes like survival rates or quality of life improvements. While this approach has the advantage of reducing trial duration and cost, it also comes with significant risks if the surrogate markers do not reliably predict actual clinical #outcomes. The study by Wallach et al., systematically reviewed meta-analyses of clinical trials to evaluate the association between surrogate markers and clinical outcomes in nononcologic chronic diseases. The findings were eye-opening: • For 22 out of 37 surrogate markers examined, no eligible meta-analyses were found to support their association with clinical outcomes. • Of the 15 markers that had some supporting meta-analyses, only a few showed high-strength evidence of association with clinical outcomes. The #study serves as a crucial reminder of the limitations inherent in using surrogate markers in clinical trials. This suggests that a substantial number of surrogate markers used in trials may not provide a reliable basis for predicting patient outcomes. We need to ensure that the tools and markers we use are not only usable, but also reliable predictors of patient outcomes. #ClinicalTrial #DataScientist

This is another report on surrogate markers and how they can't be a reliable way of predicting treatment outcomes. For those who don't follow closely the situation, FDA are using data from biomarkers to predict treatment outcomes to avoid waiting for full data from clinical trials. Based on these surrogate markers they grant accelerated approvals for new drugs and then request the pharma companies to run confirmatory clinical trials to provide addition evidence. While I completely understand why they are doing this I have mixed feelings about this approach. There are many diseases where there is no treatment and FDA are trying to speed up access to new treatments for these diseases. However, not having the complete data from clinical trials could lead to approving treatments which are not effective and increase the risk of additional adverse events from the treatment. Another important point is that asking the pharma companies to conduct additional clinical trials raise the overall development costs (which then raise the price of the final treatment). #FDA #acceleratedapprovals #surrogatemarkers

Plaquenil® (Hydroxychloroquine sulfate) – Risk of major congenital malformations and new risks of phospholipidosis and aggravation of myasthenia gravis symptoms ---------------------------------------------- Health Sciences Authority (HSA) in #Singapore has published A Dear Healthcare Professional (#DHPC) Letter which has been issued by Sanofi-Aventis Pte Ltd to inform healthcare professionals that the Huybrechts study published in 2021 suggested a small increase in the relative risk of major congenital malformations associated with the use of hydroxychloroquine in the first trimester of pregnancy, especially when used at a high daily dosage (≥ 400mg daily). Healthcare professionals are advised to avoid prescribing daily doses of ≥ 400mg in the first trimester of pregnancy except when, in the judgement of the healthcare professional, the individual’s benefits outweigh the risks. It is also advisable to closely monitor the pregnancy, especially during the first trimester, for early detection of major congenital malformations. If there is no alternative treatment to hydroxychloroquine, the lowest effective dose should be used. In addition, new risks of phospholipidosis and aggravation of myasthenia gravis symptoms have been reported with the use of hydroxychloroquine. Healthcare professionals are advised to discontinue hydroxychloroquine in patients if cardiac, renal, muscular or nerve toxicity is suspected or if aggravation of myasthenia gravis symptoms is suspected. The local package insert of Plaquenil® is being updated to include these information. Please refer to the letter for details. #Pharmacovigilance

Brand Name: Alben-DS Generic Name: Albendazole Therapeutic Class: Anthelmintic DESCRIPTION: Alben is a preparation of albendazole, which is a broad spectrum anthelmintic. In addition to its vermicidal properties, Alben® has been found to have both ovicidal and larvicidal activities in man. INDICATIONS: Alben is indicated in single and mixed infestations of: Enterobius vermicularis - Pinworm or threadworm Trichuris trichiura - Whipworm Ascaris lumbricoides -Large roundworm Ancylostoma duodenale - Hookworm Necator americanus - Hookworm Taenia spp - Tapeworm Strongyloides stercoralis - Threadworm DOSAGE AND ADMINISTRATION: Adults or children over 2 years of age: 400 mg (1 Alben-DS tablet or 10 mL suspension) as a single dose in cases of Enterobius vermicularis, Trichuris trichiura, Ascaris lumbricoides, Ancylostoma duodenale and Necator americanus. Children of 1-2 years of age: Recommended dose is a single dose of 200 mg [Half (2) Alben®-DS tablet or Alben® 5 mL suspension]. Children under 1 years of age: Not recommended. CONTRAINDICATIONS: Because albendazole was found to be embryotoxic and teratogenic in rat and rabbit, its use is contraindicated in pregnant women or those likely to be pregnant. For women of childbearing age (15-45 years), Alben®-DS should be administered within 7 days of the start of normal menstruation. ADVERSE REACTIONS: A few cases of gastrointestinal discomfort and headache have been reported, but no definite relationship with the drug has been shown. PHARMACEUTICAL PRECAUTION: Do not store above 30 'C. Keep away from light and wet place. Keep out of reach of children. PACKAGING: Alben-DS tablet: Box containing 5/10 strips of 10 tablets or 12/25 strips of 4 tablets. Each tablet contains Albendazole BP 400 mg. Alben® Suspension: Amber glass bottle containing 10 mL suspension. Each 5 mL contains Albendazole USP 200 mg. For Visit: https://lnkd.in/gZzMQaEK #pharmacist #MedicineShop #medicines #medicinestudent #medicinestudents #freelancing_with_pharmacist

Is (dapagliflozin) Farxiga safe in pediatric patients? As of June 2024, the FDA has approved Farxiga (dapagliflozin) to treat type-2 diabetes (T2D) in children aged 10 and older. The drug is used in addition to diet and exercise to improve glycemic control. The FDA's approval was based on positive results from the pediatric T2NOW Phase III trial. Research has shown that Farxiga can help prevent and delay cardiorenal disease, which can be important because damage to the heart, kidneys, and pancreas can lead to other organ failures and increase the risk of death from T2D, heart failure, and chronic kidney disease. #HealthCare #Pharmacy #AstraZeneca #Farxiga #DiabeticCare #Pediatric

Aspirin pharmacokinetics and pharmacodynamics through gestation: Factors impacting aspirin pharmacokinetics and pharmacodynamics through gestation The COX-1 pathway leads to production of prostaglandin G2/H2 which leads to synthesis of TXA2, which in turn stimulates platelet aggregation. This is hypothesized to lead to placental vasculopathy early in pregnancy that ultimately leads to preeclampsia and preterm birth. Platelet inhibition by aspirin depends on plasma exposure (salicylic acid) leading to COX-1 inhibition, subsequent TXA2 suppression (measured by TXB2), and ultimately inhibition of platelet aggregation (measured by PFA-100). Understanding the relationship between aspirin dose, plasma exposure, and downstream physiologic impacts is critical to identifying the optimal dose for aspirin in pregnancy for prevention of adverse outcomes. Our results demonstrate that plasma salicylic acid concentration is associated with urine thromboxane suppression, which is in turn associated with platelet inhibition. Individual covariates such as BMI and weight impact aspirin pharmacokinetics; whereas BMI, weight, and medical comorbidities impact aspirin pharmacodynamics. https://ow.ly/2yi350Te39X

📃Scientific paper: Association between 1-year changes in urinary albumin-to-creatinine ratio and kidney disease progression in Japanese individuals with diabetes: a historical cohort study Abstract: Background The National Kidney Foundation recently proposed a ≥ 30% decrease in urinary albumin–to–creatinine ratio (UACR) over 0.5–2 years as a surrogate endpoint for chronic kidney disease (CKD) progression in individuals with baseline UACR > 30 mg/g. This historical cohort study aimed to determine the applicability of a decrease in UACR, within as little as 1 year, as a surrogate endpoint for Japanese individuals with type 2 diabetes mellitus (T2D). Methods A total of 5067 individuals with T2D were divided into three groups based on 1-year change in UACR: ≥ 30% decrease (UACR decreased group), < 30% decrease and < 30% increase (UACR unchanged group), or ≥ 30% increase (UACR increased group). The primary endpoint was a composite of a ≥ 30% decline in estimated glomerular filtration rate (eGFR) or the initiation of kidney replacement therapy, whichever occurred first. Results At baseline, the proportions of individuals with normoalbuminuria, microalbuminuria, and eGFR ≥ 60 mL/min/1.73 m^2 were 68.1%, 22.1%, and 75.5%, respectively. During a median follow-up of 6.8 years, 926 individuals (18.3%) reached the composite endpoint. Adjusted hazard ratios (vs. the UACR unchanged group) for the UACR decreased and increased groups were 0.758 (95% confidence interval [CI], 0.636–0.905; P  = 0.002) and 1.304 (95% CI, 1.108–1.536; P  = 0.001), respectively. Conclusions These findings support the use of 1-year changes in UACR as a surrogate endpoint for the progression of CKD an... Continued on ES/IODE ➡️ https://etcse.fr/tXUZ ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.

WEGOVY™ is a glucagon-like peptide-1 (GLP-1) receptor agonist indicated as an adjunct to a reduced calorie diet and increased physical activity for chronic weight management in adult patients with an initial body mass index (BMI) of 30 kg/m2 or greater (obesity) and 27 kg/m2 or greater (overweight) in the presence of at least one weight-related comorbid condition (e.g., hypertension, type 2 diabetes mellitus, or dyslipidemia). ⚠️ WEGOVY™ should not be used in combination with other semaglutide-containing products or any other GLP-1 receptor agonist. ⚠️ The safety and efficacy of coadministration with other products for weight loss have not been established. ⚠️ WEGOVY™ has not been studied in patients with a history of pancreatitis. ⚠️ It is not known if Wegovy® is safe for use in children under 12 years of age. ✅️ Administer WEGOVY™ once weekly, on the same day each week, at any time of day, with or without meals. 💉 Inject subcutaneously in the abdomen, thigh or upper arm. 💉Initiate at 0.25 mg once weekly for 4 weeks. 💉In 4 week intervals, increase the dose until a dose of 2.4 mg is reached. 💉The maintenance dose of WEGOVY™ is 2.4 mg once weekly. ⚠️ In patients with type 2 diabetes, monitor blood glucose prior to starting and during WEGOVY™ treatment. ⚠️ Contraindications: ✔️Personal or family history of medullary thyroid carcinoma or in patients with Multiple Endocrine Neoplasia syndrome type 2. ✅️ The most common adverse reactions, reported are: nausea, diarrhea, vomiting, constipation, abdominal pain, headache, fatigue, dyspepsia, dizziness, abdominal distension, eructation, hypoglycemia in patients with type 2 diabetes, flatulence, gastroenteritis, and gastroesophageal reflux disease. ⚠️ WEGOVY™ delays gastric emptying. May impact absorption of concomitantly administered oral medications. Use with caution. ✅️ Use in specific popularions: ✔️Pregnancy: May cause fetal harm. ✔️Females and males of reproductive potential should discontinue WEGOVY™ at least 2 months before a planned pregnancy because of the long half-life of semaglutide. ✅️ Recommended storage: 1️⃣ Store the WEGOVY™ single-dose pen in the refrigerator from 2°C to 8°C. 2️⃣ If needed, prior to cap removal, the pen can be kept from 8°C to 30°C up to 28 days. 3️⃣ Do not freeze. Protect WEGOVY™ from light. WEGOVY™ must be kept in the original carton until time of administration. 4️⃣ Discard the WEGOVY™ pen after use. ⚠️ Do not use your WEGOVY™ pen without receiving training from your healthcare provider. ✅️ Choose your injection site.Your healthcare provider can help you choose the injection site that is best for you ✅️ Another person may give the injection in the upper arm. ✅️ Do not inject into an area where the skin is tender, bruised, red, or hard. Avoid injecting into areas with scars or stretch marks. ✅️ You may inject in the same body area each week, but make sure it is not in the same spot each time. Reference: BNF, 2024