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

Published byRosanna Mildred Rogers Modified over 9 years ago

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

1 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)

2 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 92104 (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

3 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

4 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

5 Sponsor June-July 2006 Submissions

6 Sponsor 2006 Submissions: Sponsor Response to DPP Labeling Letter 1.Disagreed with FDA conclusions on CT- pimozide interaction study 2.Reiterated belief that Study 92104 was unreliable due to QT data collection methods (manual read) 3.Characterized post-marketing cases as confounded by concomitant drugs and medical conditions

7 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 (0.92-1.06) and SCT 1.04 (0.96-1.12) relative to other SSRI/SNRIs

8 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 (0.6-1.4) for CT compared to other SSRIs

9 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

10 FDA AERS Search Update

11 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

12 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

13 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

14 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)

15 Ongoing Review

16 Ongoing FDA Review Further analysis of Study 92104 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

17 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?

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