Safety Reporting

Zoloft (sertraline)

2-1-02

6-12-03

February 2, 2004 Pediatric Subcommittee (PS) in conjunction with the Psychopharmacologic Drugs Advisory Committee (PDAC) requested re-analysis of Selective Serotonin Reuptake Inhibitor (SSRI) data once the cases are reclassified and for FDA to issue a warning in the interim on the potential side effects of the SSRIs. February 3, 2004 PS agreed to future update on SSRIs, neonatal withdrawal, and eye malformation; On March 22, 2004 FDA issued a Public Health Advisory; see warning at: www.fda.gov/cder/drug/antidepressants/AntidepressanstPHA.htm
June 9, 2004 PS endorsed class labeling for neonatal toxicity/withdrawal syndrome; September 13, 2004 PAC in conjunction with the PDAC Neuropsychiatry Committee after reviewing the re-analysis of pediatric cases suicidality, the committee voted for a MedGuide and "black box" warning to be applied to all antidepressants. October 15, 2004 FDA directs manufacturers of all antidepressant medications to add a "black box" warning and develop a patient medication guide (MedGuide). See templates for proposed changes labeling www.fda.gov/cder/drug/antidepressants/PI_template.pdf and MedGuide www.fda.gov/cder/drug/antidepressants/MG_template.pdf

Ditropan (oxybutynin)

2-8-02

6-12-03

June 12, 2003 PS requested future review after additional marketing experience. November 16, 2006 Preliminary reassessment. April 11, 2007 The PAC requested labeling to include additional information concerning postmarketing reports of hallucinations and agitated behavior in the pediatric population. They noted prescribers might wish to first try decreasing the dose before discontinuing, depending on the circumstances of the adverse event. See labeling changes on February 6, 2008 @ www.fda.gov/cder/foi/label/2008/017577s034,018211s017,020897s018lbl.pdf

Lipitor (atorvastatin)

2-22-02

6-12-03

June 12, 2003 PS requested future review after additional marketing experience. November 16, 2006 Committee recommended return to routine monitoring for adverse events (AEs) in all populations.

Zocor (simvastatin)

2-22-02

6-12-03

June 12, 2003 PS requested future review after additional marketing experience. November 16, 2006 Pediatric Advisory Committee recommended return to routine monitoring for AEs in all populations.

Busulfex (busulfan)

3-12-02

10-29-03

October 29, 2003 PS recommended return to routine monitoring for AEs in all populations.

Zyrtec (cetirizine)

3-13-02

10-29-03

October 29, 2003 Committee recommended return to routine monitoring for AEs in all populations.

Cozaar (losartan)

3-20-02

10-29-03

October 29, 2003 Committee recommended return to routine monitoring for AEs in all populations.

Nolvadex (tamoxifen)

5-16-02

10-29-03

October 29, 2003 Committee recommended return to routine monitoring for AEs in all populations.

Accupril (quinapril)

6-7-02

10-29-03

October 29, 2003 Committee recommended return to routine monitoring for AEs in all populations.

Serzone (nefazodone)

6-27-02

10-29-03

February 2, 2004 For additional information regarding PS recommendations and outcomes for SSRIs see Zoloft (sertraline HCl).

Paxil (paroxetine)

6-27-02

2-3-04

February 2, 2004 For additional information regarding PS recommendations and outcomes for SSRIs see Zoloft (sertraline HCl); February 3, 2004 PS agreed to future update on SSRIs, neonatal withdrawal, and eye malformation; June 9, 2004PS endorsed class labeling for neonatal toxicity/withdrawal syndrome.

Pravachol (pravastatin)

7-10-02

2-3-04

February 3, 2004 PS recommended return to routine monitoring for AEs in all populations.

Celexa (citalopram)

7-12-02

2-3-04

February 2, 2004 For additional information regarding PS recommendations and outcomes for SSRIs see Zoloft (sertraline HCl); February 3, 2004 PS agreed to future update on SSRIs, neonatal withdrawal, and eye malformation; PS requested update on QTc prolongation following future review of additional marketing experience; June 9, 2004 PS endorsed class labeling for neonatal toxicity/withdrawal syndrome; November 16, 2006 PAC requested to receive/hear the results of the division's review of the company's QTc analysis, which they thought would be more useful than additional reviews of Adverse Events Reporting System (AERS).

Navelbine (vinorelbine)

8-15-02

2-3-04

February 3, 2004 PS recommended return to routine monitoring for AEs in all populations.

Hycamtin (topotecan)

11-20-02

6-9-04

June 9, 2004 PS recommended return to routine monitoring for AEs in all populations.

Temodar (temozolomide)

11-20-02

6-9-04

June 9, 2004 PS recommended return to routine monitoring for AEs in all populations.

Effexor (venlafaxine)

12-2-02

6-9-04

February 2, 2004 For information regarding PS recommendations and outcomes for SSRIs see Zoloft (sertraline HCl); June 9, 2004 PS endorsed class labeling for neonatal toxicity/withdrawal syndrome.

Vigamox (moxifloxacin)

1-10-03

6-9-04

June 9, 2004 PS recommended return to routine monitoring for AEs in all populations.

Ciloxan (ciprofloxacin)

1-10-03

6-9-04

June 9, 2004 Committee recommended return to routine monitoring for AEs in all populations.

Monopril (fosinopril)

1-27-03

6-9-04

June 9, 2004 PS recommended return to routine monitoring for AEs in all populations.

Allegra (fexofenadine)

1-27-03

6-9-04

June 9, 2004 PS recommended return to routine monitoring for AEs in all populations.

Duragesic (fentanyl)

1-29-03

6-9-04

June 9, 2004 The PS strongly recommends that the "black box" section contain additional language indicating that: "inappropriate use may result in serious adverse effects including death" and highlight the need for qualifications of those prescribing the medication. Label updated February 2005 with black box warning and statement concerning use only in opioid tolerant patient. View updated Duragesic label and MedGuide @ www.fda.gov/medwatch/SAFETY/2005/Feb_PI/Duragesic_PI.pdf

Pediatric Subcommittee is chartered as full Pediatric Advisory Committee (PAC)

Pulmicort/Rhinocort (budesonide)

11-12-02

9-15-04

September 15, 2004 The Committee agreed with the Division of Pulmonary and Allergy Drug Products proposed label changes and recommended that a MedGuide be provided for pediatric family caregivers with respect to the new labeling for Salmeterol and Advair label changes; July 20, 2006 MedGuide approved. View @ www.fda.gov/cder/Offices/ODS/MG/budesonide.pdf

Clarinex (desloratadine)

2-12-03

9-15-04

September 15, 2004 Committee recommended return to routine monitoring for AEs in all populations.

Cutivate/Flonase/Flovent (fluticasone),
Advair (fluticasone and salmeterol)

2-25-03

9-15-04

September 15, 2004 Committee recommendation that a MedGuide be provided for pediatric family caregivers with respect to the new labeling for Salmeterol and Advair label changes; June 2006 MedGuide approved. View @ www.fda.gov/cder/Offices/ODS/MG/fluticasone_salmeterol.pdf

Ocuflox (ofloxacin)

3-12-03

9-15-04

September 15, 2004 Committee recommended return to routine monitoring for AEs in all populations.

Fludara (fludarabine)

4-03-03

9-15-04

September 15, 2004 Committee recommended return to routine monitoring for AEs in all populations.

Fosamax (alendronate)

4-28-03

9-15-04

September 15, 2004 Committee recommended return to routine monitoring for AEs in all populations.

Lotensin (benazepril)

7-2-03

2-14-05

February 14, 2005 The Committee recommended continued close monitoring of benazepril in the pediatric population for future review. March 25, 2008 Committee recommended return to routine monitoring for AEs in all population

Malarone (atovaquone/proguanil)

8-6-03

2-14-05

February 14, 2005 Committee recommended return to routine monitoring for AEs in all populations.

Brevibloc (esmolol)

8-22-03

2-14-05

February 14, 2005 Committee recommended to continue monitoring and provide future review. March 25, 2008 Committee recommended return to routine monitoring for AEs in all populations.

Viracept (nelfinavir)

9-4-03

2-14-05

February 14, 2005 Committee recommended return to routine monitoring for AEs in all populations.

Xenical (orlistat)

9-12-03

2-14-05

February 14, 2005 PAC recommended continued monitoring and future review for the risk of cholelithiasis; April 11, 2007 The PAC recommended return to routine monitoring for AEs in all populations.

Glucovance (glyburide/metformin)

10-8-03

2-14-05

February 14, 2005 Committee recommended return to routine monitoring for AEs in all populations.

Arava (leflunomide)

11-10-03

6-30-05

June 30, 2005 Committee recommended return to routine monitoring for AEs in all populations.

Concerta (methylphenidate)

12-4-03

6-30-05

June 30, 2005 Committee was informed of ongoing collaborative study between Duke University, NICHD, and NIH to assess methylphenidate clastogenic potential in children. Committee was updated on efforts to look into psychiatric behavior and cardiovascular for all therapies used for ADHD. The committee agreed to delay making labeling recommendations until the division had completed their examinations of adverse event reports in all stimulant products with respect to psychiatric and cardiovascular risk adverse events.February 21, 2007 FDA directs ADHD drug manufacturers to notify patients about cardiovascular adverse events and psychiatric adverse events. See MedGuide and label @ http://www.fda.gov/cder/drug/infopage/ADHD/default.htm  For additional information on ADHD products see Aderall XR March 22, 2006 meeting.

Zemplar (paricalcitol)

12-8-03

6-30-05

June 30, 2005 Committee recommended return to routine monitoring for AEs in all populations.

Zomig (zolmitriptan)

12-18-03

6-30-05

June 30, 2005 Committee recommended return to routine monitoring for AEs in all populations.

Ortho-Tri-Cyclen (ethinyl estradiol; norgestimate)

12-18-03

6-30-05

June 30, 2005 Committee recommended return to routine monitoring for AEs in all populations.

Cipro (ciprofloxacin)

12-18-03

6-30-05

June 30, 2005 Committee recommended return to routine monitoring for AEs in all populations.

Trusopt (dorzolamide)

1-5-04

6-30-05

June 30, 2005 Committee recommended return to routine monitoring for AEs in all populations.

Detrol;Detrol LA (tolterodine)

1-5-04

6-30-05

June 30, 2005 Committee recommended return to routine monitoring for AEs in all populations.

Agrylin (anagrelide)

5-24-04

11-18-05

November 18, 2005 Committee recommended return to routine monitoring for AEs in all populations.

Paraplatin (carboplatin)

4-30-04

11-18-05

November 18, 2005 Committee recommended return to routine monitoring for AEs in all populations.

Diflucan (fluconazole)

1-21-04

11-18-05

November 18, 2005 Committee recommended return to routine monitoring for AEs in all populations.

Camptosar (irinotecan)

3-10-04

11-18-05

November 18, 2005 Committee recommended return to routine monitoring for AEs in all populations.

Tamiflu (oseltamivir phosphate)

3-22-04

11-18-05

November 18, 2005 PAC requested follow-up within 2 years on neuropsychiatric (NP) and behavioral events. Label revised on November 13, 2006. Link to label: www.fda.gov/cder/foi/label/2006/021246s021lbl.pdf
November 16, 2006 the Committee concurred with previous PAC request for an extensive analysis including (1) a report by the sponsor on NP events; (2) requested FDA invite Japanese experts to report on their experience and ask for Japanese data on the extent of prophylactic use and AEs in said population; November 27, 2007 Committee recommended FDA continue to monitor AEs for Tamiflu on a monthly basis and recommended labeling changes to include: a description of NP symptoms which may occur due to the influenza illness, irrespective of drug therapy; to convey uncertainty in causality of the NP symptoms; to note abrupt appearance of symptoms; and to indicate that "injurious behavior" included fatal outcomes. Similar labeling changes were recommended for the other antiviral influenza medications. Labeling approved on January 17, 2008.

Vioxx (rofecoxib)

2-18-04

11-18-05

November 18, 2005 Committee recommended return to routine monitoring for AEs in all populations.

Ferrlecit (sodium ferric gluconate complex in sucrose injection)

3-24-04

11-18-05

November 18, 2005 Committee recommended return to routine monitoring for AEs in all populations.

Imitrex (sumatriptan)

2-18-04

11-18-05

November 18, 2005 Committee recommended return to routine monitoring for AEs in all populations.

Avapro (irbesartan)

9-16-04

3-22-06

March 22, 2006 Committee recommended return to routine monitoring for AEs in all populations.

Clolar (clofarabine)

3-30-04

3-22-06

March 22, 2006 Committee recommended return to routine monitoring for AEs in all populations.

Adderall XR (dextroamphetamine saccharate, amphetamine aspirate monohydrate, dextroamphetamine sulfate, amphetamine sulfate)

10-28-04

3-22-06

March 22, 2006 It was noted that ADHD medications have been shown to be effective in children properly diagnosed with ADHD. The Commitee addressed the adverse events individually: Psychosis/Mania (including hallucinations) -- Labeling for psychosis was warranted and could be further clarified; Stated that it was important to enhance the current warnings in the label regarding psychosis, mania and hallucinations; Aggression -- Parents need to contact physician if new (treatment emergent) aggression occurs or if symptoms of aggression worsen during therapy; Cardiovascular -- Did not request box warning. Committee did request strong warnings recommended MedGuide or information sheet for patients with underlying structural cardiovascular defects or cardiomyopathies; February 21, 2007 FDA directs ADHD drug manufacturers to notify patients about cardiovascular adverse events and psychiatric adverse events. See MedGuide and label @ http://www.fda.gov/cder/drug/infopage/ADHD/default.htm

Meridia (sibutramine hydrochloride monohydrate)

10-06-04

3-22-06

March 22, 2006 Committee recommended continued monitoring and requested an update on sibutramine adverse events after completion of the Subutramine Cardiovascular Outcomes (SCOUT) Study.

Rapamune (sirolimus)

11-17-04

11-16-06

November 16, 2006 Committee requested to be informed (email was adequate) about the outcome of discussions with the Sponsor about potential labeling changes concerning pericarditis. October 17, 2007 adverse reactions section of label modified to include information on pericardial effusion see label @  http://www.fda.gov/medwatch/safety/2007/Oct_PI/Rapamune_PI.pdf

Zofran (ondansetron)

12-01-04

11-16-06

November 16, 2006 Committee recommended return to routine monitoring for AEs in all populations.

Avandia (rosiglitazone)

12-09-04

11-16-06

November 16, 2006 Committee recommended that a statement regarding lack of efficacy should also be placed in the pediatric patient information part of the label. The committee noted the current statement is not helpful.

Gemzar (gemcitabine)

01-27-05

11-16-06

November 16, 2006 Committee recommended return to routine monitoring for AEs in all populations.

Invanz (ertapenem)

02-11-05

11-16-06

November 16, 2006 Committee recommended return to routine monitoring for AEs in all populations.

Zyvox (linezolid)

02-11-05

11-16-06

November 16, 2006 pending completion of the ongoing review of cardiac events for all age populations by the Office of Surveillance and Epidemiology, the committee requested a report.
November 18, 2008 Committee accepted the follow-up report that revealed no new safety signals, but requested to see the completed QT report.

Trileptal (oxcabazepine)

03-02-05

11-16-06

November 16, 2006 The Committee made no recommendation at this time contingent on hearing the division's independent analysis of the suicidality events; in particular they would like a subpopulation analysis focusing on pediatrics (over 2,000 patients) to be provided whenever the division has completed their review. March 8, 2008 Preliminary review of pediatric subpopulation.  Further evaluation of entire of adult and pediatric populations pending.

Mobic (meloxicam)

04-15-05

11-16-06

November 16, 2006 Committee recommended return to routine monitoring for AEs in all populations.

Novolog (insulin aspart recombinant)

05-24-05

11-16-06

November 16, 2006 Committee recommended return to routine monitoring for AEs in all populations.

Amaryl (glimepiride)

06-09-05

11-16-06

November 16, 2006 Committee recommended return to routine monitoring for AEs in all populations.

Norvir (ritonavir)

06-14-05

11-16-06

November 16, 2006 Committee recommended return to routine monitoring for AEs in all populations.

Lescol (fluvastatin)

12-15-2005

4-11-2007

April 11, 2007 Recommended routine monitoring for AEs in all populations.

Sandostatin (octreotide)

1-12-2005

4-11-2007

April 11, 2007 The Committee did not believe a causal link was established for necrotizing enterocolitis (NEC) or hypoxia. Because of the increased use of this product in a population at risk for NEC and hypoxia, most members recommended that information on these AEs in this high risk population be placed in the label. Recommended 1 year update focused on observed post marketing adverse events of NEC and hypoxia. Committee members inquired about the need for additional studies, including registries and/or availability of  well-controlled trials. 
November 18, 2008 Committee agreed with FDA recommendation to harmonize the LAR and Injection Solution versions of the label. Committee recommended that FDA include in the label information about serious pediatric AEs and acknowledge no causal association has been established.  Committee recommended that FDA work with NIH regarding a systematic review of actual use and AEs from off-label use. Committee recommended that FDA continue its standard, ongoing safety monitoring.

Serevent (salmeterol)

3-09-06

11-28-07

November 28, 2007 Committee recommended more extensive discussion of benefit/risk of salmeterol with pediatric use and requested a report back to the Committee after additional review of existing data. They recommended labeling changes to include: specifically identifying risks of deaths and increased hospitalizations as potential pediatric adverse risks; updated “Pediatric Use” section with additional safety information; and to provide some quantification of risks. The committee also recommended reorganization of the MedGuide to more prominently display the safety information and straightforwardly present that salmeterol should not be used as monotherapy. Labeling should also reflect the lack of certainty that corticosteroids mitigate serious adverse events.
December 10-11, 2008 A joint meeting of FDA’s Pulmonary-Allergy Drugs Advisory Committee, Drug Safety and Risk Management Advisory Committee, and Pediatric Advisory Committee met to discuss the risks/benefits of LABA medications after FDA further analysis and recommended removal of asthma indication.  http://www.fda.gov/ohrms/dockets/ac/cder08.html#PulmonaryAllergy

Provigil (modafinil)

   3-21-06

11-28-07

November 27, 2007 Committee recommended that the label include the ADHD pediatric clinical trial data and that it include stronger language that it is not approved for any pediatric indication because of safety issues. This information is also to be placed in the PPI part of the label.

Emtrivia (emtricitabine)

5-24-06

11-28-07

November 28, 2007 Committee recommended return to routine monitoring for AEs in all populations.

Gleevec (imatinib mesylate)

6-09-06

11-28-07

November 28, 2007 Committee recommended return to routine monitoring for AEs in all populations.

Azopt (Brinzolamide)

6-28-06

11-28-07

November 28, 2007 Committee recommended return to routine monitoring for AEs in all populations.

Betaxon (levobetaxolol)

6-28-06

11-28-07

November 28, 2007 No recommendations. This drug is not marketed.

Toprol XL (metoprolol)

7-27-06

3-25-08

March 25, 2008 Committee recommended return to routine monitoring for AEs in all populations.

Celebrex (celecoxib)

8-23-06

3-25-08

March 25, 2008 Committee agreed with the FDA recommendation to have a follow up once data from the postmarketing safety studies have been analyzed.

Colazal (balsalazide)

8-23-06

3-25-08

March 25, 2008 Committee agreed to be updated by email once the labeling change currently being reviewed by the FDA to add postmarking AEs seen in other 5-ASA products in the pediatric population was approved. Committee requested additional information before making a recommendation on monitoring for AEs.

Suprane (desflurane)

9-27-06

3-25-08

March 25, 2008 Committee agreed with the FDA proposal to add the adverse event “cardiac arrest” to the labeling. Some members of the committee recommended further restricting the use of this product in pediatrics in the labeling. Others deferred until additional information from pediatric anesthesiologists is provided. Committee recommended continued pediatric focused monitoring.

Eloxatin (oxaliplatin)

9-27-06

3-25-08

March 25, 2008 Committee recommended return to routine monitoring for AEs in all populations.

Coreg (carvedilol)

11-8-06

3-25-08

March 25, 2008 Committee agreed with the FDA recommendation that the labeling be revised to include information on hypoglycemia similar to the text in the propranolol labeling. The Advisory Committee recommended FDA consider adding additional information in labeling regarding PK and the dose which resulted in the inadequate exposure during the trial. Committee recommended return to routine monitoring for AEs in all populations.

Ambien (zolpidem)

11-20-06

11-18-08

November 18, 2008 Committee recommended that FDA continue its standard, ongoing safety monitoring.

Lamisil (terbinafine)

12-4-06

11-18-08

November 18, 2008 Committee recommended that FDA continue its standard, ongoing safety monitoring. 

Aldara (imiquimod)

12-13-06

11-18-08

November 18, 2008 Committee requested that text about the negative studies in children as well as local skin reactions in the genital area leading to “inability to urinate” be added to the label.  Committee requested that FDA consider including a statement in the Patient Information section that imiquimod was not shown to be effective in children less than 12 years. Committee recommended that FDA continue its standard, ongoing safety monitoring

Zyprexa (olanzapine)

1-10-07

11-18-08

 November 18, 2008 See recommendations for Risperdal.

Lamictal (lamotrigine)

2-14-07

11-18-08

November 18, 2008 Committee supported  recommendation made at the July, 2008 AC regarding labeling about suicidality. Committee recommended that FDA continue its standard, ongoing safety monitoring.

Risperdal (risperidone)

2-28-07

11-18-08  

November 18, 2008 Committee requested: (1) additional information regarding pediatric use in this class of products, (2) studies of long-term  adverse effects in pediatrics (e.g., metabolic AEs) (3) additional information on movement AEs,  and
 (4) other requests.

Betoptic S (betaxolol)

2-28-07

11-18-08

November 18, 2008 Committee recommended that FDA return to routine  monitoring for AEs 

Timolol GFS (timolol)

2-28-07

11-18-08

November 18, 2008 Committee recommended that FDA return to routine monitoring for AEs 

Levaquin (levofloxacin)

3-14-07

11-18-08

November 18, 2008 Committee recommended that FDA revise the label to include text about other drug products known to cause prolonged QT interval . FDA to continue its standard, ongoing safety monitoring.