Boxed warnings on drugs have received increased media attention in the United States since 2004. Among some of the more widely covered stories: • In October 2004, the FDA began requiring that boxed warnings be placed on all
antidepressant medications, warning they may result in an increased risk of
suicidal tendencies in
children and
adolescents. In May 2006, the boxed warning was expanded to
young adults aged 18–24 years old. • , the FDA has required a boxed warning on the
Depo-Provera contraceptive injection, due to the risk of significant loss of
bone density with long-term use. • In April 2005, FDA advisors requested that
Pfizer place a boxed warning on their
non-steroidal anti-inflammatory drug Celebrex (
celecoxib) for cardiovascular and gastrointestinal risks. • In 2005, the FDA issued a black box warning regarding the risk of
atypical antipsychotics being prescribed among elderly patients with dementia. This advisory was associated with a decrease in use of antipsychotics, especially in elderly patients with dementia. • ,
natalizumab (marketed as Tysabri) received a black box warning on its packaging due to increased risk of developing
progressive multifocal leukoencephalopathy (PML). Tysabri was pulled from the market in 2004, shortly after its introduction, after three cases of the rare disease were linked to its use. PML has affected approximately 212 Natalizumab recipients in 2012 (or 2.1 in every 1000 patients). Tysabri is now distributed under a controlled prescription program called TOUCH (Tysabri Outreach: Unified Commitment to Health). • , the FDA added a black box warning to the anticoagulant
warfarin due to the risk of
bleeding to death. • In February 2006, the FDA's Drug Safety and Risk Management Advisory Committee voted to include black box warnings on
methylphenidate formulations used to treat
attention deficit hyperactivity disorder, such as Ritalin (
methylphenidate), due to possible cardiovascular side-effects. A month later, the agency's Pediatric Advisory Committee effectively rejected recommending black box warnings for both cardiovascular and psychiatric adverse effects. • On November 14, 2007, the FDA added a black box warning to the
diabetes medication Avandia (
rosiglitazone), citing the risk of
heart failure or
heart attack to patients with underlying
heart disease, or are at a high
heart attack risk. • On July 8, 2008, the FDA ordered a black box warning on certain antibiotic medications containing
fluoroquinolone, which has been linked to
tendon ruptures and
tendinitis. Included were the popular drugs Cipro (
ciprofloxacin), Levaquin (
levofloxacin), Avelox (
moxifloxacin), Noroxin (
norfloxacin) and Floxin (
ofloxacin). • On July 1, 2009, the FDA required Chantix (
varenicline) to carry a boxed warning due to public reports of side effects including depression, suicidal thoughts, and suicidal actions. , the warning has been removed on the basis of updated evidence. • On October 27, 2010, the FDA issued a boxed warning regarding the use of Metacam (
meloxicam) oral suspension in
cats in the United States. Meloxicam is a
non-steroidal anti-inflammatory drug that is approved in the U.S. for a single
post-operative injection in cats. • , the FDA issued a boxed warning regarding the use of thyroid hormone stimulating agents in treatment of obesity. Data does not indicate any benefits to using these agents for weight loss. Data does indicate an increased risk of life-threatening cardiovascular events when high levels of these agents are used in hypothyroid populations. Euthyroid populations demonstrate increased CV risk at clinical doses. Hypothyroid agents should not be used in combination with sympathomimetic agents including: stimulants, and diet pills, due to increased CV risks. • In July 2013, the FDA issued a boxed warning for the antimalarial drug
mefloquine, noting the drug's adverse neuropsychiatric side effects, and emphasizing neurological effects from the drug could "occur at any time during drug use, and can last for months to years after the drug is stopped or can be permanent". == In other jurisdictions ==