American College of Clinical Pharmacology

12/18/2020

Looking to make a career change in 2021? Be sure to check out the jobs on the #ACCPJOBCTR! http://bit.ly/2J0TTKj
#pharmacology #jobsearch

12/16/2020

Don't forget to register for the ACCP Early-stage Professionals Webinar:
Navigating the Job Search During COVID and Beyond

Date: Wednesday, January 13, 2021
Time: 2:00 - 3:00 PM ET
Register today! https://bit.ly/37P2iLp

After completing this activity, the learner will be able to:
- Navigate the current landscape of job searches and hiring practices during COVID;
- Describe the current challenges and opportunities in the hiring process due to COVID;
- Utilize effective strategies to advance their professional careers.

Faculty:
Jay Chapman, Executive Director, Hughes & Associates

Alex De Piante, BS, Director of Recruiting & Account Management, Hughes &
Associates

Yi Ting (Kayla) Lien, PhD, Associate Scientist, Clinical Pharmacology Modeling &
Simulation, Genentech Inc

Patra Rungruangphol, PharmD, Clinical Research Associate, Clinical Monitoring,
IQVIA
#pharmacology #jobsearch #COVID19

12/10/2020

Torrent Pharmaceuticals Limited Issues Voluntary Nationwide Recall of Anagrelide Capsules, USP Due to Dissolution Test Failure

FDA MedWatch: Anagrelide Capsules by Torrent Pharmaceuticals: Recall - Due to Dissolution Test Failure

AUDIENCE: Patient, Health Professional, Risk Manager, Pharmacy

ISSUE: Torrent Pharmaceuticals Limited is recalling one lot of Anagrelide Capsules, due to dissolution test failure detected during routine quality testing.

Failed dissolution can result in a slower rate and extent of drug release leading to less anagrelide available in the body. For seriously ill patients with elevated platelet counts, less available anagrelide could increase the risk of clotting (blood coagulation) and clotting or bleeding events such as a heart attack or stroke which could be life-threatening.

To date, Torrent Pharmaceuticals has not received any reports of adverse events related to this recall.

For product photos, product description, NDC and lot numbers click "Read Recall" below.

BACKGROUND: Anagrelide is used to treat a blood cell disorder called thrombocythemia (also called thrombocytosis), which occurs when your body produces too many platelet cells.

Read Recall: https://bit.ly/2JRBiD0

Torrent Pharmaceuticals Limited is voluntarily recalling one lot of Anagrelide Capsules, USP to the consumer level due to dissolution test failure detected during routine quality testing.

12/09/2020

Registration is now open for the ACCP Early-stage Professionals Webinar:
Navigating the Job Search During COVID and Beyond

Date: Wednesday, January 13, 2021
Time: 2:00 - 3:00 PM ET
Register today! https://bit.ly/37P2iLp

Faculty:
Alex De Piante, BS, Director of Recruiting & Account Management, Hughes & Associates

Yi Ting (Kayla) Lien, PhD, Associate Scientist, Clinical Pharmacology Modeling & Simulation, Genentech Inc

Patra Rungruangphol, PharmD, Clinical Research Associate, Clinical Monitoring, IQVIA

Moderator:
Alexander J. Prokopienko, PharmD, PhD, Clinical Pharmacologist II, Translational Medicine, Vertex Pharmaceuticals Inc

Why is this webinar important to you?
During this webinar, attendees will learn the current landscape of hiring during COVID and effective strategies to navigate a job search. Presenters include professional recruiters and recently hired professionals that will share their perspectives and experience.
#pharmacology #jobsearch #COVID19

12/08/2020

The Journal of Clinical Pharmacology - December 2020, Vol 60, Issue 12 is now available!

*Continuing Education: Review*
Pharmacokinetic Enhancement of HIV Antiretroviral Therapy During Pregnancy
Engie Salama PharmD, Ahizechukwu C. Eke MD, MPH, Brookie M. Best PharmD, MAS, Mark Mirochnick MD, Jeremiah D. Momper PharmD, PhD
Pages: 1537-1550 | First Published: 14 August 2020

*Editor's Choice: Pediatric Pharmacology*
Dosing Recommendations for Pediatric Patients With Renal Impairment
Amer Al‐Khouja PhD, Kyunghun Park PharmD, Daijha J.C. Anderson PharmD, Caitlyn Young PharmD, Jian Wang PhD, Shiew Mei Huang PhD, Mona Khurana MD, Gilbert J. Burckart PharmD, FCP
Pages: 1551-1560 | First Published: 15 June 2020

*Pediatric Pharmacology*
Extrapulmonary Surfactant Therapy: Review of Available Data and Research/Development Issues
Silvia Foligno MD, Barbara Loi MD, Lucilla Pezza MD, Marco Piastra MD, Chiara Autilio MSc, Daniele De Luca MD, PhD
Pages: 1561-1572 | First Published: 23 June 2020

Model‐Aided Adults‐to‐Children Pharmacokinetic Extrapolation and Empirical Body Size‐Based Dosing Exploration for Therapeutic Monoclonal Antibodies—Is Allometry a Reasonable Choice?
Yan Xu MD, PhD, FCP, Brooke A. Langevin BS, Honghui Zhou PhD, FCP, FAAPS, Zhenhua Xu PhD, FCP
Pages: 1573-1584 | First Published: 23 June 2020

Population Pharmacokinetics of Brentuximab Vedotin in Adult and Pediatric Patients With Relapsed/Refractory Hematologic Malignancies: Model‐Informed Hypothesis Generation for Pediatric Dosing Regimens
Ajit Suri PhD, MBA, Diane R. Mould PhD, FCP, Gregory Song PhD, Judith Kinley PhD, Karthik Venkatakrishnan PhD, FCP
Pages: 1585-1597 | First Published: 28 June 2020

*Drug Interactions*
The Effect of GS‐548351 on the Pharmacokinetics of Midazolam Following Multiple Doses of ANS‐6637 in Healthy Adults
Haden T. Bunn PharmD, MS, Elana Rosenthal MD, Poonam Mathur DO, MPH, Mary McLaughlin RN, BSN, Michael Proschan PhD, Arjun Vijan PharmD, Julia Aepfelbacher, Shyamasundaran Kottilil MBBS, PhD, Henry Masur MD, Sarah Kattakuzhy MD, Jomy M. George PharmD
Pages: 1598-1605 | First Published: 23 June 2020

Assessment of Clinical Drug‐Drug Interactions of Elagolix, a Gonadotropin‐Releasing Hormone Receptor Antagonist
Akshanth R. Polepally PhD, Juki W. Ng PharmD, PhD, Ahmed Hamed Salem PhD, FCP, Matthew B. Dufek PhD, FCP, Apurvasena Parikh PhD, David C. Carter MD, Kent Kamradt MD, Nael M. Mostafa PhD, Mohamad Shebley PhD, FCP
Pages: 1606-1616 | First Published: 07 July 2020

*Physiologically Based Pharmacokinetic Modeling*
Application of Physiologically Based Pharmacokinetic Modeling to Predict Drug Exposure and Support Dosing Recommendations for Potential Drug‐Drug Interactions or in Special Populations: An Example Using Tofacitinib
Susanna Tse PhD, Martin E. Dowty PhD, Sujatha Menon PhD, Pankaj Gupta PhD, Sriram Krishnaswami PhD
Pages: 1617-1628 | First Published: 27 June 2020

*Pharmacometrics*
Population Pharmacokinetic Analysis of Quizartinib in Healthy Volunteers and Patients With Relapsed/Refractory Acute Myeloid Leukemia
Dongwoo Kang PhD, Elizabeth Ludwig PharmD, David Jaworowicz PhD, Hannah Huang PhD, Jill Fiedler‐Kelly MS, FISoP, Jorge Cortes MD, Siddhartha Ganguly MD, Samer Khaled MD, Alwin Krämer MD, Mark Levis MD, PhD, Giovanni Martinelli MD, Alexander Perl MD, Nigel Russell MD, Malaz Abutarif MD, PhD, Youngsook Choi MD, Jeanne Mendell PhD, MPH, Ophelia Yin PhD
Pages: 1629-1641 | First Published: 29 June 2020

Population Pharmacokinetics and Exposure‐Response Analyses for the Most Frequent Adverse Events Following Treatment With Lemborexant, an Orexin Receptor Antagonist, in Subjects With Insomnia Disorder
Bojan Lalovic PhD, Oneeb Majid PhD, Jagadeesh Aluri MS, Ishani Landry PhD, Margaret Moline PhD, Ziad Hussein PhD
Pages: 1642-1654 | First Published: 14 July 2020

*Women's Health*
A Pilot Study of the Maternal‐Fetal Pharmacokinetics of Furosemide in Plasma, Urine, and Amniotic Fluid of Hypertensive Parturient Women Under Cesarean Section
Paulo Vinicius Bernardes Gonçalves PhD, Fernanda de Lima Moreira PhD, Jhohann Richard de Lima Benzi MS, Geraldo Duarte PhD, MD, Vera Lucia Lanchote PhD
Pages: 1655-1661 | First Published: 20 June 2020

Clinical Experiences of Intravenous Hydralazine and Labetalol for Acute Treatment of Severe Hypertension in Pregnant Thai Women
Pattraporn Chera‐Aree MD, Pimrapat Tengtrakulcharoen MSc, Jarunee Leetheeragul RN, Urai Sampaojarean RN, Supitchaya Surasereewong MSc, Tuangsit Wataganara MD
Pages: 1662-1670 | First Published: 29 June 2020

*Therapeutics*
Comparison of the Effects of Low‐Molecular‐Weight Heparin and Fondaparinux on Liver Function in Patients With Pulmonary Embolism
Xu Yang MD, Nan Li MS, Tingting Guo MD, Xiaoyuan Guan MD, Jiangshan Tan MS, Xin Gao MD, Yan Wu MD, Lei Jia MD, Min Gu MD, Lu Hua MD, Hong Liu PhD
Pages: 1671-1678 | First Published: 08 July 2020

*Correction*
Pages: 1679 | First Published: 18 October 2020
This article is a correction.
http://bit.ly/2Ijxci7

12/08/2020

ACCP is pleased to announce the publication of a Policy Statement entitled “Statement of Support for U.S. Food and Drug Administration: Science & Evidence-based Review and Approval of COVID-19 Vaccines for Use in the United States,” in ACCP’s The Journal of Clinical Pharmacology.

ACCP aims to enhance public understanding of the FDA’s focus on approving vaccines for COVID-19 based on sound scientific principles and evidence-based approaches. ACCP believes transparent approaches are the foundation of the FDA’s long-standing mandate of protecting public health in the United States and the Agency consistently follows its mandate during this critical health emergency. ACCP fully supports and commends the FDA in its endeavor to approve or authorize vaccines based on science and evidence-based approaches for the prevention of COVID-19.

Dr. Donald E. Mager, President, ACCP emphasized, "The challenges of rapidly developing safe and effective vaccines for the prevention of COVID-19 make it clear that decisions must be based on the principles of clinical pharmacology and good science. In keeping with the mission of the ACCP Public Policy Committee and the traditional regulatory paradigm of the FDA, this Policy Statement should raise public awareness and support for the objective, transparent and evidence-based review and approval of COVID-19 vaccines."

Read the Policy Statement: https://bit.ly/3lTNDDI
#COVID19 #CovidVaccine #evidencebased

12/07/2020

www.accessdata.fda.gov

FDA Approves DANYELZA (Naxitamab-gqgk) for Treatment of Pediatric Patients 1 Year of Age and Older and Adult Patients with Relapsed or Refractory High-risk Neuroblastoma

On November 25, 2020, the U.S. Food and Drug Administration (FDA) approved DANYELZA (naxitamab-gqgk) for use in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment of pediatric patients 1 year of age and older and adult patients with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow who have demonstrated a partial response, minor response, or stable disease to prior therapy. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

The approved recommended dosage of DANYELZA is 3 mg/kg/day (up to 150 mg/day), administered as an intravenous infusion after dilution on Days 1, 3, and 5 of each treatment cycle (first infusion over 60 minutes and subsequent infusions over 30-60 minutes as tolerated). Treatment cycles are repeated every 4 weeks until complete response or partial response, followed by 5 additional cycles every 4 weeks. Subsequent cycles may be repeated every 8 weeks. Discontinue DANYELZA and GM-CSF for disease progression or unacceptable toxicity. Administer GM-CSF subcutaneously prior to and during each treatment cycle as recommended.

WARNING:
• Serious Infusion-Related Reactions: DANYELZA can cause serious infusion reactions, including cardiac arrest, anaphylaxis, hypotension, bronchospasm, and stridor. Premedicate prior to each DANYELZA infusion as recommended. Reduce the rate, interrupt infusion, or permanently discontinue DANYELZA based on severity.
• Neurotoxicity: DANYELZA can cause severe neurotoxicity, including severe neuropathic pain, transverse myelitis, and reversible posterior leukoencephalopathy syndrome (RPLS). Premedicate to treat neuropathic pain as recommended. Permanently discontinue DANYELZA based on the adverse reaction and severity.

DANYELZA is contraindicated in patients with a history of severe hypersensitivity reaction to naxitamab-gqgk. Reactions have included anaphylaxis. Additional information regarding dosage and administration as well as warnings and precautions about serious infusion-related reactions, neurotoxicity, hypertension, and embryo-fetal toxicity can be found in the full prescribing information linked below.

Mechanism of Action (MOA) and Pharmacokinetics (PK)

MOA: Naxitamab-gqgk is a GD2-binding monoclonal antibody.

General PK: The geometric mean (CV%) maximum plasma concentration (Cmax) of naxitamab-gqgk was 57.4 μg/mL (49%) following DANYELZA 3 mg/kg intravenous infusion over 30 minutes.

Elimination: The mean terminal half-life of naxitamab-gqgk was 8.2 days.

Metabolism: Naxitamab-gqgk is expected to be metabolized into small peptides by catabolic pathways.

Immunogenicity: In a clinical trial, 2 of 24 (8%) patients tested positive for anti-drug antibodies (ADA) after treatment with DANYELZA. In another clinical trial, 27 of 117 patients (23%) tested positive for ADA after treatment with DANYELZA by an assay that was not fully validated; therefore, the incidence of ADA may not be reliable.

Use in Specific Populations

Population pharmacokinetic analyses suggest that age (range: 1 to 34 years), sex, and race have no clinically important effect on the clearance of naxitamab-gqgk. The naxitamab-gqgk systemic exposure (AUC) at 150 mg/day (450 mg per cycle) for patients with body weight over 50 kg is not expected to differ clinically from that of the naxitamab-gqgk exposures at 3 mg/kg/day (9 mg/kg per cycle) for patients with body weight of 30 to 50 kg.

Efficacy and Safety

The efficacy of DANYELZA in combination with GM-CSF was evaluated in two open-label, single arm trials in patients with high-risk neuroblastoma with refractory or relapsed disease in the bone or bone marrow. Additional information regarding the efficacy trials can be found in the full prescribing information linked below.

The most common adverse reactions (≥25%) are infusion-related reaction, pain, tachycardia, vomiting, cough, nausea, diarrhea, decreased appetite, hypertension, fatigue, erythema multiforme, peripheral neuropathy, urticaria, pyrexia, headache, injection site reaction, edema, anxiety, localized edema, and irritability. The most common Grade 3 or 4 laboratory abnormalities (≥5%) are decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased platelet count, decreased potassium, increased alanine aminotransferase, decreased glucose, decreased calcium, decreased albumin, decreased sodium, and decreased phosphate.

________________________________________
Full prescribing information is available at https://bit.ly/3oJPv3R.

12/07/2020

ACCP is pleased to announce the release of the *Women's Health Supplement* in The Journal of Clinical Pharmacology, Volume 60, Issue S2. Guest Editors: Drs. Myong‐Jin Kim and Venkateswar Jarugula.

We hope you share with your colleagues that may find this supplement of interest.
https://bit.ly/2VURki1
#WomensHealth #pharmacology #drugdevelopment #drugdruginteraction #PBPK

12/04/2020

During this holiday season, we would like to take this opportunity to thank you for your involvement in ACCP! While 2020 has presented us with unprecedented global challenges, your support has allowed ACCP to move forward with exceptional programs that continue to support our Vision & Mission. Your contributions have made 2020 a great success and we are truly thankful for your membership.

We wish you and your family the best this holiday season and look forward to seeing you in 2021!

12/01/2020

Evaluation of Gastric pH-Dependent Drug Interactions With Acid-Reducin

FDA Announces Availability of a Draft Guidance, Evaluation of Gastric pH-Dependent Drug Interactions With Acid-Reducing Agents: Study Design, Data Analysis, and Clinical Implications

On December 1, 2020, the U.S. Food and Drug Administration (FDA) announced the availability of a draft guidance for industry titled “Evaluation of Gastric pH-Dependent Drug Interactions With Acid-Reducing Agents: Study Design, Data Analysis, and Clinical Implications.” This draft guidance describes the FDA’s recommendations regarding: (1) when clinical drug-drug interaction (DDI) studies with acid-reducing agents (ARAs) are needed; (2) the design of clinical DDI studies; (3) how to interpret study results; and (4) communicating findings in drug product labeling.

ARAs such as antacids, histamine H2-receptor antagonists (H2 blockers), and proton pump inhibitors (PPIs) are widely used, and many of these drugs are available over the counter. ARAs can affect the solubility and dissolution characteristics of orally administered drug products by elevating gastric pH. As a result, concomitant administration of a drug with an ARA could alter the bioavailability of the drug, potentially resulting in a loss of efficacy for weak-base drugs or increased adverse events for weak-acid drugs. Consequently, there is an increased risk for clinically significant DDIs with concomitant administration of drugs with ARAs. Therefore, it is important to assess the susceptibility of an investigational drug to DDIs mediated by gastric-pH changes early in drug development, characterize the DDI effect with clinical studies when needed, and communicate the relevant findings in the drug product labeling.

The “Evaluation of Gastric pH-Dependent Drug Interactions With Acid-Reducing Agents: Study Design, Data Analysis, and Clinical Implications” guidance is available at https://bit.ly/2JhPi8Z. Please refer to the draft guidance for more details. FDA is publishing this draft guidance to collect additional public comments. You may submit your comments regarding the draft guidance to the docket (Docket No. FDA-2020-D-1794) available at hthttps://bit.ly/2IA280Pp to 90 days following publication in the FEDERAL REGISTER. This draft guidance, when finalized, will represent the current thinking of the FDA on this topic. It does not establish any rights for any person and is not binding on FDA or the public. Your comments do make a difference and can impact the outcomes of FDA regulatory policy. Share your knowledge and experience and make your voice count.

Clinical Pharmacology Evaluation of Gastric pH-Dependent Drug Interactions With Acid-Reducing Agents: Study Design, Data Analysis, and Clinical Implications Guidance for Industry