Supplementary Appendix

Transcription

1 Supplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Hwang TJ, Bourgeois FT, Seeger JD. Drug safety in the digital age. N Engl J Med 2014;370: DOI: /NEJMp

2 Wikipedia Traffic 175% Average % change in page views from baseline period (-60 to -10 days) 150% 125% 100% 75% 50% 25% 0% -25% Days relative to announcement Figure S1. Trends in Wikipedia page views over a 120-day window around the date of the FDA safety warning. The two-day spike in viewership after the warning is indicated in red. The persistence of a new baseline of page views after the warning is indicated in blue (blue trend line at average 30% higher views than baseline). 2

3 90% High Prevalent Cumulatie probability of accurate Wikipedia update 80% 70% 60% 50% 40% 30% 20% Low Prevalent P = 0.03 Log-rank χ 2 = % 0% Time elapsed (weeks) Figure S2. Cumulative probability plot of accurate Wikipedia updates after FDA safety warning for drugs used to treat common (prevalence >1 million individuals in the US) and less common diseases. Drugs affected by the FDA safety warnings in our sample were categorized into the high- and low-prevalent groups, according to estimates of disease prevalence for on-label indications, i.e. the uses approved by the FDA at the time of the warning. The primary outcome measure was whether the Wikipedia page was accurately updated with the FDA safety warning after it was issued. Time elapsed is shown in weeks following the date of the announcement. The difference in the two survival trends was statistically significant at P < 0.05 (log-rank test for equality of survivor functions). 3

4 A B Figure S3. Screenshots of Wikipedia page for aliskiren (Tekturna) on April 21, 2012 after a FDA safety announcement on April 20, 2012 relating to the contraindication with angiotensin receptor blockers in patients with diabetes (panel A) and prior to the announcement (panel B) as of February,

5 Table S1. Study sample of Drug Safety Communications Date Drug Name Brand Generic FDA Safety Warning 12/19/2012 Pradaxa dabigatran etexilate mesylate Pradaxa (dabigatran etexilate mesylate) should not be used to prevent stroke or blood clots (major thromboembolic events) in patients with mechanical heart valves 12/19/2012 Incivek telaprevir FDA is adding a boxed warning to the Incivek drug label stating that Incivek combination treatment must be immediately stopped in patients experiencing a rash with systemic symptoms or a progressive severe rash. 12/17/2012 Xyrem sodium oxybate The combined use of Xyrem (sodium oxybate) with alcohol or central nervous system (CNS) depressant drugs can markedly impair consciousness and may lead to severe breathing problems (respiratory depression). 7/23/2012 Ampyra dalfampridine Risk of seizures in patients with multiple sclerosis (MS) who are starting Ampyra (dalfampridine) 6/26/2012 Cefepime cefepime There have been cases of a specific type of seizure called nonconvulsive status epilepticus associated with the use of cefepime, primarily in patients with renal impairment who did not receive appropriate dosage adjustments of cefepime. The cefepime label is being revised to highlight this risk. 5/7/2012 Revlimid lenalidomide The FDA is informing the public of an increased risk of second primary malignancies (new types of cancer) in patients with newly-diagnosed multiple myeloma who received Revlimid (lenalidomide). 4/20/2012 Tekturna aliskiren FDA is warning of possible risks when using blood pressure medicines containing aliskiren with other drugs called angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in patients with diabetes or kidney (renal) impairment. These drug combinations should not be used (are contraindicated) in patients with diabetes. In addition, a new warning is being added to avoid use of these drug combinations in patients with kidney impairment. 2/8/2012 Victrelis boceprevir Drug interactions between the hepatitis C virus (HCV) protease inhibitor Victrelis (boceprevir) and certain ritonavir-boosted human immunodeficiency virus (HIV) protease inhibitors (atazanavir, lopinavir, darunavir) can potentially reduce the effectiveness of these medicines when they are used together. 1/20/2012 Tysabri natalizumab Testing positive for anti-jc virus (JCV) antibodies has been identified as a risk factor for progressive multifocal leukoencephalopathy (PML). PML is a rare but serious brain infection associated with use of Tysabri (natalizumab) for the treatment of multiple sclerosis (MS) or Crohn's disease. 1/13/2012 Adcetris brentuximab vedotin Two additional cases of progressive multifocal leukoencephalopathy (PML), a rare but serious brain infection that can result in death, have been reported with the lymphoma drug Adcetris (brentuximab vedotin). Due to the serious nature of PML, a new Boxed Warning highlighting this risk has been added to the drug label. 12/19/2011 Multaq dronedarone Healthcare professionals should not prescribe Multaq to patients with AF who cannot or will not be converted into normal sinus rhythm (permanent AF), because Multaq doubles the rate of cardiovascular death, stroke, and heart failure in such patients. Healthcare professionals should monitor heart (cardiac) rhythm by electrocardiogram (ECG) at least once every 3 months. If the patient is in AF, Multaq should be stopped or, if clinically indicated, the patient should be cardioverted. Patients prescribed Multaq should receive appropriate antithrombotic therapy. 5

6 10/25/2011 Xigris drotrecogin alfa Eli Lilly and Company announced a worldwide voluntary market withdrawal of Xigris. In a recent study, Xigris failed to show a survival benefit for patients with severe sepsis and septic shock. Xigris treatment should not be started in new patients. Xigris treatment should be stopped in patients being treated with Xigris. 10/11/2011 Sprycel dasatinib Sprycel (dasatinib) may increase the risk of a rare, but serious condition in which there is abnormally high blood pressure in the arteries of the lungs (pulmonary arterial hypertension [PAH]). 9/1/2011 Saphris asenapine maleate Serious allergic reactions have been reported with the use of the antipsychotic medication Saphris (asenapine maleate) 8/24/2011 Celexa citalopram hydrobromide Celexa (citalopram hydrobromide; also marketed as generics) should no longer be used at doses greater than 40 mg per day because it can cause abnormal changes in the electrical activity of the heart. 8/3/2011 Diflucan fluconazole Chronic, high doses ( mg/day) of the antifungal drug Diflucan (fluconazole) may be associated with a rare and distinct set of birth defects in infants whose mothers were treated with the drug during the first trimester of pregnancy. 7/26/2011 Zyvox linezolid FDA has received reports of serious central nervous system (CNS) reactions when the antibacterial drug linezolid (marketed as Zyvox) is given to patients taking psychiatric medications that work through the serotonin system of the brain (serotonergic psychiatric medications). Linezolid should generally not be given to patients taking serotonergic drugs. 6/16/2011 Chantix varenicline Chantix (varenicline) may be associated with a small, increased risk of certain cardiovascular adverse events in patients who have cardiovascular disease. 6/15/2011 Actos pioglitazone Use of the diabetes medication Actos (pioglitazone) for more than one year may be associated with an increased risk of bladder cancer 6/8/2011 Zocor simvastatin FDA is recommending limiting the use of the highest approved dose of the cholesterol-lowering medication, simvastatin (80 mg) because of increased risk of muscle damage. Simvastatin 80 mg should be used only in patients who have been taking this dose for 12 months or more without evidence of muscle injury (myopathy). Simvastatin 80 mg should not be started in new patients, including patients already taking lower doses of the drug. 3/4/2011 Topamax topiramate FDA informing the public of new data that show that there is an increased risk for the development of cleft lip and/or cleft palate (oral clefts) in infants born to women treated with topiramate (Topamax and generic products) during pregnancy. 1/14/2011 Multaq dronedarone FDA is alerting healthcare professionals and patients about cases of rare, but severe liver injury, including two cases of acute liver failure leading to liver transplant, in patients treated with the heart medication dronedarone (Multaq). 6