Review Update: QT Prolongation with Citalopram and Escitalopram Pediatric Advisory Committee Meeting November 16, 2006 Prepared by M. Lisa Jones, MD Division.

Slides:

Advertisements

Similar presentations

Antiepileptic Drugs and Suicidality: Background Evelyn Mentari, M.D., M.S. Clinical Safety Reviewer Division of Neurology Products/CDER Food and Drug Administration.

Advertisements

Suicidality and Anti-epileptic Drugs: Status of Clinical Trial Data Analysis Evelyn Mentari, MD, MS Division of Neurology Products.

Alternative medicines include: Sertraline (optimum alternative as similar indications, low interaction propensity, good tolerability, generic, NICE approved)

GENERALIZED ANXIETY DISORDER IN PRIMARY CARE Curley Bonds, MD Medical Director Didi Hirsch Mental Health Services Professor & Chair Charles R. Drew University.

Telithromycin Integrated Summary of Safety Anti-Infective Drugs Advisory Committee January 8, 2003 Charles Cooper, M.D. Medical Officer Division of Anti-Infective.

QTc Trials Presented By: Ad Roffel, Ph.D. PRA International EDS NL P.O. Box 200, 9470 AE Zuidlaren, The Netherlands Tel: Fax:

William H. Maisel, MD, MPH Director, Medical Device Safety Institute Beth Israel Deaconess Medical Center Statement to the FDA Risk Communication Advisory.

Pramlintide Acetate Safety Review Dragos Roman MD Center for Drug Evaluation and Research.

Safety Review for Plan B Daniel Davis, MD, MPH Division of Reproductive/Urologic Drugs.

Evaluation of Cardiac Safety by ECG Findings: Focus on QTc Duration Joel Morganroth, M.D. Clinical Professor of Medicine University of Pennsylvania Chief.

The Risks of Cough/Cold Preparations to Young Children Michael Shannon, MD, MPH Children’s Hospital Boston Harvard Medical School.

Pediatric AC 6/9/041 Neonatal withdrawal syndrome with Serotonin Reuptake Inhibitors Office of Drug Safety Review Kathleen Phelan, R.Ph., Safety Evaluator.

An Update on NSAID Labeling and Data Review DSaRM Advisory Committee February 10, 2006 Sharon Hertz, M.D. Deputy Director Division of Anesthesia, Analgesia,

Addiction Treatment Works! Through Collaboration and Problem Solving amongst all disciplines.

Adverse Event Tracking as mandated by the Best Pharmaceuticals for Children Act Dr. Solomon Iyasu Medical Team Leader Division of Pediatric Drug Development.

Investigational New Drug Application (IND)

Overview of Issues for Psychopharmacological Drugs Advisory Committee June 16, 2003 WBC Monitoring for Clozapine Judith A. Racoosin, MD, MPH Safety Team.

RELATIVE TOXICITY OF CITALOPRAM AND OTHER SSRIs IN OVERDOSE GK Isbister 1,2, IM Whyte 1,2, AH Dawson 1,2 1 Department of Clinical Toxicology, Newcastle.

Pediatric Advisory Committee April 11, Update to the Committee: Oxybutynin Central Anticholinergic Effects Pediatric Advisory Committee Meeting.

Food and Drug Administration Division of Pulmonary and Allergy Drug Products Pulmonary-Allergy Drugs Advisory Committee Meeting July 13, 2005 Safety of.

Macrolide Antibiotics and Torsade de Pointes Postmarketing Analysis Telithromycin (Ketek™) Advisory Committee April 26, 2001 Douglas N. Shaffer, MD, MHS.

CTD, Safety Tanja Braakman Genzyme Europe BV Pharmacovigilance Department.

Augmentin ES  for acute otitis media Mamodikoe Makhene, M.D. Prepared for Anti-infectives Advisory Committee meeting January 30, 2001.

Key Compliance Risks in Clinical Trials Kathleen Meriwether Principal, ERNST & YOUNG, LLP Fraud Investigation & Dispute Services.

Joint Meeting of Anti-Infective Drugs & Drug Safety and Risk Management Advisory Committees December 14-15, 2006 Ketek  (telithromycin) Regulatory History.

1 Update to Post Exclusivity Pediatric Adverse Event Review: Simvastatin Pediatric Advisory Committee Meeting November 16, 2006 Jean Temeck, MD, Acting.

1 Antidepressants and Suicidality in Adults: Data Overview M. Lisa Jones MD, MPH Medical Reviewer Division of Psychiatry Products Psychopharmacologic Drugs.

1 One Year Post Exclusivity Adverse Event Review: Fexofenadine Pediatric Subcommittee of the Anti-infective Drugs Advisory Committee Meeting June 9, 2004.

Jeffrey Jonas, MD Vice President CNS - Forest Research Institute Citalopram and Escitalopram Pediatric Safety Data.

Population-Based Epidemiologic Safety Studies: Overview and Challenges Drug Safety and Risk Management Advisory Committee Silver Spring, Maryland June.

Plans for Analysis of Patient Level Data for Pediatric Studies Psychopharmacologic Drugs Advisory Committee and Pediatric Subcommittee of the Anti-Infective.

1 QT Evaluation Studies: Pharmacometric Considerations Leslie Kenna, Peter Lee and Yaning Wang Office of Clinical Pharmacology and Biopharmaceutics CDER/FDA.

Antidepressants and Suicide Risk in Children and Adolescents: Weighing the Evidence Jill A. Morris, PA-S.

1 Lotronex Postmarketing Experience Ann Corken Mackey, R.Ph., M.P.H. Allen Brinker, M.D., M.S. Zili Li, M.D., M.P.H., formerly of ODS Office of Drug Safety.

VIOXX ™ Gastrointestinal Outcome Research (VIGOR) Arthritis Advisory Committee Meeting February 8, 2001 Lourdes Villalba, M.D. DAAODP, CDER, FDA.

Cardiovascular Drugs That Prolong The QT Interval

Suicide and Mental Health in Virginia: Marc Leslie Virginia Violent Death Reporting System Office of the Chief Medical Examiner Virginia Department.

1 Vaccines and Related Biologic Products Advisory Committee (VRBPAC) May 16, 2007 FluMist ® Influenza Virus Vaccine Live, Intranasal Safety and Effectiveness.

History of Pediatric Labeling

Sertraline Use in Pediatric Population: A Risk Benefit Discussion Steven J. Romano, MD September 13, 2004 Steven J. Romano, MD September 13, 2004 Joint.

1 QTc and Quinolones: recent regulatory actions Joyce Korvick M.D., M.P.H. Office of Drug Evaluation IV Division of Special Pathogens FDA.

Use of Antipsychotic Drugs in Dementia Josepha A. Cheong, MD University of Florida Departments of Psychiatry and Neurology Chief, Division of Geriatric.

Prospective controlled study of QTc prolongation by droperidol in healthy volunteers Anesthetic & Life Support Drugs Advisory Committee Meeting November.

1 A review of the safety of Moxifloxacin Hydrochloride Leonard Sacks MD Medical officer/DSPIDP.

Teriparatide or LY Eli Lilly & Company NDA Metabolic-Endocrine Drugs Metabolic-Endocrine Drugs Advisory Committee Advisory Committee Bethesda,

Macrolide Antibiotics and Torsade de Pointes Postmarketing Analysis

General Regulatory Issues in the Development of Drugs Intended for Treatment of Chronic Illness Sharon Hertz, M.D. Medical Officer Division of Anesthetic,

Plenary III: There is No Health Without Mental Health.

OTC NSAID and ASA GI Bleeding Analysis of Spontaneous Reports Nonprescription Drugs Advisory Committee Meeting Joyce P. Weaver, Pharm.D. Office of Drug.

1 One Year Post Exclusivity Adverse Event Review: Sumatriptan Pediatric Advisory Committee Meeting November 18, 2005 Susan McCune, M.D. Medical Officer.

1 One Year Post Exclusivity Adverse Event Review: Ciprofloxacin Pediatric Subcommittee of the Anti-infective Drugs Advisory Committee Meeting June 9, 2004.

Postmarketing Pharmacovigilance Practice at FDA Lanh Green, Pharm.D., M.P.H. Office of Surveillance and Epidemiology June 21, 2006.

1 Risk Intervention Study: Cisapride Evelyn M Rodriguez MD, MPH Director, DDREII, OPDRA.

Zelnorm ® (tegaserod) Division of Gastrointestinal and Coagulation Drug Products Division of Drug Risk Evaluation Gary Della’Zanna, D.O., M.Sc., F.A.C.O.S.

1 Overview of Pediatric Safety Reporting and Role of the Committee Pediatric Advisory Committee Meeting November 18, 2005 Solomon Iyasu, M.D., M.P.H. Acting.

Chronic pelvic pain Journal Club 17 th June 2011 Dr Claire Hoxley (GPST1) Dr Harpreet Rayar (GPST2)

1 Tedisamil for Conversion of Atrial Fibrillation Thomas A. Marciniak, M.D. Division of Cardiovascular and Renal Products U.S. Food & Drug Administration.

Food and Drug Administration Division of Pulmonary and Allergy Drug Products Summary Comments - Orally Inhaled and Intranasal Budesonide and Fluticasone.

REGULATORY HISTORY of ZOMETA and AREDIA JAW OSTEONECROSIS (ONJ) Oncologic Drug Advisory Committee March 4, 2005 Nancy S. Scher, M.D.

1 One Year Post Exclusivity Adverse Event Review: Glimepiride Pediatric Advisory Committee Meeting November 16, 2006 Hari Cheryl Sachs, MD, FAAP Medical.

1 Update to Post Exclusivity Pediatric Adverse Event Review: Atorvastatin Pediatric Advisory Committee Meeting November 16, 2006 Jean Temeck, MD, Acting.

QTc Prolongation during Therapeutic Hypothermia: Does it deserve attention? Umashankar Lakshmanadoss MD, Saadia Sherazi MD, Lohith Reddy MD, Carlos Palacio.

Department of Pharmacy, Ditmanson Medical Foundation Chia-Yi Christian Hospital Suspect Moxifloxacin Induced Torsades de Pointes: A case report Ya-Wen.

1 Psychopharmacologic Drugs Advisory Committee and Pediatric Subcommittee of the Anti-Infective Drugs Advisory Committee February 2, 2004 Office of Drug.

Viagra (sildenafil citrate): Extensive Clinical and Post-Marketing Experience Michael Sweeney, MD Senior Medical Director Pfizer Inc.

Recent FDA Activities in Safe Use of Opioids Bob Rappaport, M.D. Director, Division of Anesthesia, Analgesia, and Addiction Products Center for Drug Evaluation.

Clinical Trials.

Pediatric Inactivated Influenza Vaccine Safety VAERS Reports for Trivalent Inactivated Influenza Vaccine (TIV) in Infants/Toddlers Ann McMahon, MD, MS.

Statement on Concerta and Methylphenidate for the June 30, 2005 Pediatric Advisory Committee The FDA has identified two possible safety concerns with.

Relapses or deteriorates

Presentation transcript:

Review Update: QT Prolongation with Citalopram and Escitalopram Pediatric Advisory Committee Meeting November 16, 2006 Prepared by M. Lisa Jones, MD Division of Psychiatry Products (DPP)

Summary of Past Review 3-4 msec QT prolongation for both CT (citalopram) and SCT (escitalopram) compared to placebo in Phase 3 trials AERS reviews found cases suggestive of QT-prolonging effect Study (DB, PC Phase 1 CT study) found QTcF of 7-9 msec CT-Pimozide interaction study with elements supportive of an association between CT and QT prolongation

Labeling Request Current CT/SCT labeling on the QT interval describes the Phase 3 study data Based on the findings in other data sources (previous slide), in 5/06 the Division requested the addition of an expanded labeling statement regarding QT interval prolongation

Ongoing Review Overview 1.Sponsor June-July 2006 Submissions –Rebuttal of Points in the DPP Letter –Medicaid Analysis –GPRD Analysis –Post-marketing (AERS) Data Analysis 2.Updated FDA AERS Search 3.Additional FDA review of previously submitted data

Sponsor June-July 2006 Submissions

Sponsor 2006 Submissions: Sponsor Response to DPP Labeling Letter 1.Disagreed with FDA conclusions on CT- pimozide interaction study 2.Reiterated belief that Study was unreliable due to QT data collection methods (manual read) 3.Characterized post-marketing cases as confounded by concomitant drugs and medical conditions

Sponsor 2006 Submissions: Medicaid Analysis Sponsor examined TdP-related adverse events in the Medicaid claims database Compared patients treated with CT or SCT to patients treated with other SSRI/SNRIs Found similar rates of TdP-related events for CT 0.99 ( ) and SCT 1.04 ( ) relative to other SSRI/SNRIs

Sponsor 2006 Submissions: GPRD Analysis General Practice Research Database – UK primary care records (35 million PYs) Searched for “QT-related events” in depressed patients (age 18-70) treated with at least one antidepressant Found adjusted OR of 0.9 ( ) for CT compared to other SSRIs

Sponsor 2006 Submissions: AERS Data Searched AERS MedWatch database for cases with QT-related MedDRA terms (e.g. QT prolonged, cardiac arrest) and a SSRI/SNRI as a suspect drug Found increased risk with CT (OR: 1.58) and SCT (OR: 1.56) use relative to SSRI/SNRIs –Sponsor cited preferential use in medically compromised patients

FDA AERS Search Update

AERS Search: Pediatric Pts. Searched for cases in pts.  17 years old from 8/03 to 8/06 Used QT-related preferred terms –QT [c] prolonged, Sudden Death, Death, Ventricular Arrhythmia, Cardiac Arrest Search resulted in 3 cases

Pediatric AERS Case 1 Literature report of a 12-year-old female who concomitantly took an unknown dose of CT with 4-5 grams of diphenhydramine (treatment details unavailable) Treated in ER for altered mental status, followed by bradycardia, wide complex rhythm on ECG and cardiac arrest Patient died as a result of cardiac arrest

Pediatric AERS Case 2 17-year-old male hospitalized for seizures, intermittent tachyarrhythmias and wide QRS complex rhythms on ECG following an intentional overdose (2400 mg) of CT Resolved with supportive care Patient’s medical history included marijuana use and asthma No information on concomitant drugs

Pediatric AERS Case 3 14-year-old male developed QT prolongation while taking CT (40 mg/day) for depression and anxiety Six months after beginning treatment, he was diagnosed by a cardiologist with QT prolongation (QTc interval 445 msec) The pt.’s drugs were discontinued (CT, atomoxetine) and QTc decreased to 408 msec (No re-challenge)

Ongoing Review

Ongoing FDA Review Further analysis of Study and CT- Pimozide interaction study Review of the sponsor’s Medicaid and GPRD analyses AERS datamining analysis of SCT/CT compared to other antidepressants, including non-SSRIs

Summary of Update This update on Celexa provides information on the recent pediatric-related labeling changes and on the ongoing analysis of QT interval data within the Division of Psychiatry Products –Does the Committee have any comments? The FDA suggests that this product return to routine monitoring –Does the Committee agree?