Post-Marketing AE Reports of Topical Calcineurin Inhibitors Pediatric Advisory Subcommittee of the Anti-Infective Drugs Advisory Committee Marilyn R. Pitts,

Slides:

Advertisements

Similar presentations

Dermatologic and Ophthalmic Drugs Advisory Committee July 12, Clinical Wrap-Up Denise Cook, M.D. Medical Officer Division of Dermatology and Dental.

Advertisements

Nonclinical Pharmacology/ Toxicology Data for PROTOPIC  (Tacrolimus ointment for Atopic Dermatitis) Barbara Hill, Ph.D. Division of Dermatologic and Dental.

Pediatric Subcommittee of the AIDAC October 29-30, 2003 Topical Immunosuppressants Bindi M. Nikhar, M.D., FAAP Division of Dermatologic and Dental Drug.

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

1 One Year Post Exclusivity Adverse Event Review: Fentanyl Transdermal System Pediatric Subcommittee of the Anti-infective Drugs Advisory Committee Meeting.

MRSA Barbara Kilian, MD St.Luke’s Roosevelt Academic Associate Program Fall 2005.

Postmarketing Risk Assessment of Drug Products Division of Drug Risk Evaluation Office of Drug Safety Center for Drug Evaluation and Research.

1 One Year Post Exclusivity Adverse Event Review: Atovaquone-Proguanil Pediatric Advisory Committee Meeting February 14, 2005 Alan M. Shapiro, MD, PhD,

1 One Year Post-Exclusivity Adverse Event Review: Ertapenem Pediatric Advisory Committee Meeting November 16, 2006 Alan M. Shapiro, MD, PhD, FAAP Medical.

Arthritis Advisory Committee March 4, 2003 Presented at the Arthritis Advisory Committee meeting on March 4, 2003 by Jeffrey N. Siegel, M.D.

1 The Chemoprevention of Sporadic Colorectal Cancer Issues Surrounding a Benefit/Risk Analysis in Clinical Trials Mark Avigan MD CM Medical Officer Division.

Vaccines and Related Biological Products Advisory Committee Presentation on Sanofi Pasteur’s H5N1 Vaccine Andrea N. James, M.D. Senior Medical Officer.

1 Advisory Committee Meeting, 15 February, FDA Perspective Topical Immunosuppressants Bindi Nikhar, MD. Division of Dermatologic and Dental Drugs.

1 One Year Post-Exclusivity Adverse Event Review for Tamiflu® (oseltamivir) Pediatric Advisory Committee Meeting November 18, 2005 Melissa M. Truffa, R.Ph.

1 Topical Immunosuppressants (Calcineurin Inhibitors) - Animal Toxicology Pediatric Advisory Committee Meeting February 15, 2005 Barbara Hill, Ph.D. Division.

1 Post-marketing review of Movement Disorders and Neuroleptic Malignant Syndrome associated with metoclopramide Mary Ross Southworth, PharmD Safety Evaluator,

1 One Year Post Exclusivity Adverse Event Review as Mandated by the Best Pharmaceuticals for Children Act Presented at the Psychopharmacologic Drugs Advisory.

POSTMARKETING ADVERSE DRUG EXPERIENCE INSPECTIONAL PROGRAM CDR Thomas R. Berry, RPh FDA, Investigator RAL-RP / ATL-DO.

1 Topical Antifungals for T. Pedis Labeling Issues Daiva Shetty, M.D. Division of Over-the-Counter Drug Products (HFD-560) Food and Drug Administration.

Center for Drug Evaluation and Research Patterns of Prescription Weight-Loss Drug Use Endocrinologic and Metabolic Drugs Advisory Committee Meeting Rockville,

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

1 One Year Post Exclusivity Adverse Event Review: Ofloxacin Ophthalmic Pediatric Advisory Committee Meeting September 15, 2004 Hari Cheryl Sachs, MD, FAAP.

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

Postmarketing Safety Assessment of Osteonecrosis of the Jaw Pamidronate & Zoledronic Acid Division of Drug Risk Evaluation Office of Drug Safety FDA Carol.

Nonprescription Drugs Advisory Committee and the Dermatologic and Ophthalmic Drugs Advisory Committee March 24, 2005 Rx Topical Corticosteroids HPA Axis.

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

Clinical Review of Protopic Safety, Potential Risk, and Efficacy Martin M. Okun, M.D., Ph.D. Lisa Mathis, M.D. Division of Dermatologic and Dental Drug.

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

Joint Dermatologic and Ophthalmic Drugs & Drug Safety and Risk Management Advisory Committee February 26 & 27, Overview Isotretinoin Pregnancy Exposures:

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

Anti-Infective Drugs Advisory Committee Meeting December 15, Data Mining Analysis of Multiple Antibiotics in AERS Jonathan G. Levine, PhD Mathematical.

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

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

1 Agenda  Overview –Burt Adelman MD  Efficacy and Pharmacodynamics –Akshay Vaishnaw MD, PhD  Safety –Gloria Vigliani MD  Alefacept Risk Benefit Profile.

1 One Year Post Exclusivity Adverse Event Review Update: Orlistat Pediatric Advisory Committee Meeting April 11, 2007 Hari Cheryl Sachs, MD, FAAP Medical.

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.

FDA Case Studies Pediatric Oncology Subcommittee March 4, 2003.

Elizabeth Gorevski Kingsbrook Jewish Medical Center Brooklyn, NY.

1 One Year Post Exclusivity Adverse Event Review: Budesonide & Fluticasone Pediatric Advisory Committee Meeting September 15, 2004 Joyce Weaver, PharmD,

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

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

1 Assessing Cancer Risk & Assuring Safe Use of Topical Immunosuppressants: Recent History Susan K. Cummins, MD, MPH Medical Team Leader OCTAP and OPT.

How Clinicians Use Data For Clinical Decision Making March 5, 2003 Anti-Infective Drug Advisory Committee How Clinicians Use Data For Clinical Decision.

Review of Reported Adverse Events and Poisonings Associated with Cough and Cold Products in Young Children Joint Meeting of the Nonprescription Drugs Advisory.

Locatelli F et al. Proc ASH 2013;Abstract 4378.

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.

Pediatric Subcommittee of the AIDAC October 29-30, Topical Immunosuppressants (Calcineurin Inhibitors) - Animal Toxicology October 30, 2003 Barbara.

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.

Topical Corticosteroid Adverse Events in Pediatric Patients Analysis of Postmarketing Reports Pediatric Advisory Subcommittee of the Anti-Infective Drugs.

1 11/8/00 Efficacy and Safety of Tacrolimus Ointment Ira D. Lawrence, M.D., F.A.C.P. Senior Vice President Research and Development Fujisawa Healthcare,

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

1 Update to Post-Exclusivity Pediatric Adverse Event Review: Oxybutynin Pediatric Advisory Committee Meeting November 16, 2006 Lisa Mathis, MD, Associate.

1 Daptomycin Safety Review Chuck Cooper, M.D. Medical Officer Division of Anti-Infective and Ophthalmology Products March 6, 2006 Advisory Committee Meeting.

Overview of Pediatric Drug Development Dianne Murphy, MD Director Office of Counterterrorism and Pediatric Drug Development Center for Drug Evaluation.

1 Zithromax  (Azithromycin) Oral Suspension Single-Dose & 3-day Treatment of Acute Otitis Media Anti-Infective Drugs Advisory Committee November 7, 2001.

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.

1 One Year Post Exclusivity Adverse Event Review: Glyburide-Metformin Pediatric Advisory Committee Meeting February 14, 2005 Hari Cheryl Sachs, MD, FAAP.

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

TM Influenza Vaccine Safety in Children: Data from VAERS John Iskander MD MPH Gina Mootrey DO MPH Penina Haber MPH Roseanne English-Bullard BS.

Slideset on: Emery S, Neuhaus JA, Phillips AN, et al. Major clinical outcomes in antiretroviral therapy (ART)-naive participants and in those not receiving.

The Epidemiology of Varicella Disease in New York City, Janelle A. Anderson, MPH CDC/CSTE Applied Epidemiology Fellow New York City Department.

Campos M et al. Proc EHA 2013;Abstract B2009.

Campos M et al. Proc EHA 2013;Abstract B2009.

Data Mining AERS FDA’s (Spontaneous) Adverse Event Reporting System Division of Drug Risk Evaluation Office of Drug Safety Carolyn McCloskey, M.D., M.P.H.

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

Presentation transcript:

Post-Marketing AE Reports of Topical Calcineurin Inhibitors Pediatric Advisory Subcommittee of the Anti-Infective Drugs Advisory Committee Marilyn R. Pitts, Pharm.D., Safety Evaluator, Office of Drug Safety October 30, 2003 Pediatric Advisory Subcommittee of the Anti-Infective Drugs Advisory Committee Marilyn R. Pitts, Pharm.D., Safety Evaluator, Office of Drug Safety October 30, 2003 Center for Drug Evaluation and Research

2 Outline Background Drug Use Methods AERS Adverse Event Profile –Pediatric subgroup –Death/Hospitalized cases –Malignant and non-malignant cases –Infection cases Summary Background Drug Use Methods AERS Adverse Event Profile –Pediatric subgroup –Death/Hospitalized cases –Malignant and non-malignant cases –Infection cases Summary

3 Topical Calcineurin Inhibitors Pimecrolimus 1% Tacrolimus 0.03% & 0.1% Approved:12/13/200112/08/2000 2nd Line Tx:Yes Indication:Mild to mod. atopic dermatitis… Mod. To Severe atopic dermatitis… Approved for children < 2 No

4 # Prescriptions & Appearances IMS Health National Prescription Audit Plus TM, IMS National Disease & Therapeutic Index Audit TM Since Approval Pimecrolimus 1% Topical Tacrolimus 0.03%, 0.1% Total Rx3,230,0002,004,000 Appearances 0 to 2 yrs17%8% Appearances 3 to 16 yrs36%29%

5 Some Common Elements in Product Labeling Pimecrolimus 1% Topical Tacrolimus 0.03% + 0.1% Varicella zosterYes Herpes SimplexYes Eczema herpeticumYes LymphadenopathyYes Local Skin rxnYes Systemic AbsorptionYes

6 AERS Electronic Database –Adverse Event Reporting System 1969 – SRS 1997 – replaced by AERS ~ 3 million AE reports for drugs –Medwatch forms –Adverse Event Reporting System 1969 – SRS 1997 – replaced by AERS ~ 3 million AE reports for drugs –Medwatch forms

7 Methods Separate search of AERS database: –All reports with pimecrolimus as suspect agent –All reports with tacrolimus administered topically as suspect agent Separate search of AERS database: –All reports with pimecrolimus as suspect agent –All reports with tacrolimus administered topically as suspect agent

Pimecrolimus 1% Cream Approved 12/13/2001

9 Pimecrolimus – Overall Findings (Adult and Pediatric, n = 79) Location:US (64), Foreign (15) Gender:Female (53), Males (23), NR (3) Age:< 2 years (14) 2 to 16 years (17) Adverse Events: 60% - labeled 90% - involved the skin Cases of Interest: Hospitalization (7) Tumor growth (2) Pediatric (32)

10 Demographics of Pimecrolimus Pediatric Cases (32) Indications:Atopic or allergic dermatitis (25) Location:US (23), Foreign (9) Gender:Male (16), Female (16) Age:2 months – 15 years, median = 2 years (n = 30) < 2 years (14) AEsSkin reactions predominate Non-malignant tumor (2) Infections (7)

11 Hospitalized Pimecrolimus Pediatric Cases (n = 4) Ages:4 months, 6 months, 9 months and 18 months 18 month oldStaph aureus + axillary adenitis. Hosp for drainage, irrigation and IV Abx. 9 month oldOsteomyelitis, osteitis & soft tissue infection 20 days after starting pimecrolimus.

12 Pimecrolimus Associated Pediatric Infection Cases (7) Location:US (4), foreign (3) Age Range:9 months to 15 years, median = 18 months (n = 7) Outcome:Hospitalization (2) Other (2) Infections Seen: Abscess, Bronchitis, Eczema herpeticum + infected eyes, Scarlatina, Soft tissue infection, Staph aureus + adenitis, Strep throat

13 Non-Malignant Tumor Growth Pimecrolimus Pediatric Cases (2) OnsetType 5 year old49 daysGranulomatous lymphadenitis w/ reactive hyperplasia Unknown ageNRFacial tumor

Topical Tacrolimus Ointment 0.03%, 0.1% Approved 12/08/2000

15 Topical Tacrolimus – Overall Findings (Adult and Pediatric, n = 183) Location:US (164), Foreign (19) Gender:Female (103), Male (74), NR (6) Age:< 2 years (7) 2 to 16 years (29) Adverse Events: 95% - labeled 50% - involved the skin Cases of Interest: Death (3), Hosp (18) Pediatric (36) Malignancy (5) Acute Renal Failure (4)

16 Topical Tacrolimus Death Cases (3) OnsetAdverse Event 28 year old 1 monthsKaposi’s sarcoma 54 year old 3 monthsNon-Hodgkin’s lymphoma 3 year old9 monthsStreptococcal pneumonia, sepsis

17 Demographics of Topical Tacrolimus Pediatric Cases (36) Indication:Atopic dermatitis Location:US (35), Foreign (1) Gender:Male (18), Female (13), NR (5) Age:< 2 yrs (7) 2 to 16 (29) Product:0.03% (21), 0.1% (10), NR (5) AEsSkin and application site rxn predominated Infections (10) Serum levels (2)

18 Topical Tacrolimus Associated Pediatric Infection Cases (10) Location:US (9), foreign (1) Age Range:13 months to 16 years, median = 4 years (n = 10) Outcome:Death (1), Hospitalization (3) Other (6) Infections Seen: Pneumonia/sepsis, eczema herpeticum, staph aureus sepsis, chickenpox, warts, strep sepsis, herpes zoster, herpes simplex keratitis, erythema infectiosum

19 Malignancies Associated with Topical Tacrolimus (5) Location:US (4), foreign (1) Age Range:28 to 56 years, median = 52 years (n = 5) Outcome:Death (2) Other (3) Onset:1 month to 6 months (median = 3.5) Malignancies Seen: Anaplastic large cell lymphoma w/mets, B cell lymphoma, Kaposi's sarcoma, non-Hodgkin's lymphoma

20 Overall Summary Pimecrolimus & Topical Tacrolimus AERS Post-Marketing AE Reports –Serious Outcomes –Malignancies –Infections –Pediatric AE Reports off label use in children < 2 years old (pimecrolimus, topical tacrolimus) adult topical tacrolimus product use in children AERS Post-Marketing AE Reports –Serious Outcomes –Malignancies –Infections –Pediatric AE Reports off label use in children < 2 years old (pimecrolimus, topical tacrolimus) adult topical tacrolimus product use in children

21 Acknowledgements Mark Avigan, M.D., C.M., Acting Director, DDRE, Office of Drug Safety Renan Bonnel, Pharm.D., M.Ph., Safety Evaluator, DDRE, Office of Drug Safety Claudia B. Karwoski, Pharm.D., Team Leader, DDRE, Office of Drug Safety Division of Dermatological and Dental Drug Products Office of Counter-Terrorism and Pediatric Drug Development Mark Avigan, M.D., C.M., Acting Director, DDRE, Office of Drug Safety Renan Bonnel, Pharm.D., M.Ph., Safety Evaluator, DDRE, Office of Drug Safety Claudia B. Karwoski, Pharm.D., Team Leader, DDRE, Office of Drug Safety Division of Dermatological and Dental Drug Products Office of Counter-Terrorism and Pediatric Drug Development