FDA Black Box Warning
FDA Black Box Warning
FDA Black Box Warning
In July 2011, the Food and Drug Administration (FDA) requested the revision of the product label for the antipsychotic drug quetiapine (SEROQUEL, SEROQUEL XR) to warn against use with certain classes of drugs known to cause an arrhythmia (alteration in heartbeat rhythm).
Quetiapine falls in the family of atypical antipsychotic drugs widely prescribed for both schizophrenia and bipolar disorder. The classes of drugs that are listed in the revised label and that may have a risk of bad interactions with quetiapine include antiarrhythmics, antibiotics, anti-infectives, antipsychotics and opioids. Twelve examples of drugs in these classes appear in the table below.
|Drug Class||Generic Name||Brand Name|
|antibiotic||gatifloxacin*†||withdrawn from market|
|thioridazine*||MELLARIL and many generics|
* Do Not Use
** Limited Use (offers limited benefit or benefits certain people or conditions)
*** Last-Choice Drug
† The oral and injectable forms of fluoroquinolone antibiotic gatifloxacin (TEQUIN) have been withdrawn from the market for safety reasons. Gatifloxacin is still available as ZYMAR and ZYMAXID eye drops.
Heart rhythm disturbances such as arrhythmia (in this case, drug-induced prolongation of the QT interval in the heart) can cause the heart to stop suddenly (cardiac arrest).
The revised label includes postmarketing study findings of QT prolongation in patients taking quetiapine along with medications known to cause electrolyte imbalance or increased QT intervals. Though this effect was seen in 17 patients who took more than the recommended dosage of the drug, the original label’s mentioning of a QT effect did not provide information on specific classes of drugs to avoid.
The link between cardiac arrest and quetiapine use with these drug families must now be added to the substantial list of possible adverse effects of quetiapine that should be considered before using this drug. These effects include increased risk of death in elderly patients with dementia and an increased risk of suicidal thinking and behavior in children, adolescents and young adults taking antidepressants for major depressive disorder and other psychiatric disorders. (See black box warnings.)
Other potentially adverse reactions listed in the “Warnings and Precautions” section of the quetiapine product label include:
- High blood sugar (hyperglycemia)
- High cholesterol and triglyceride levels (fat in the blood)
- Weight gain
- Tardive dyskinesia (involuntary, uncontrollable movements of the mouth, tongue, trunk and limbs)
- Decreased blood pressure
- Increased blood pressure in children and adolescents
- Low white blood cell count
Quetiapine’s economic — but illegal? — success
Quetiapine has been a remarkable economic success for its manufacturer, AstraZeneca. In 2010, more than 12 million prescriptions were ordered, approaching $4 billion in sales.
Part of quetiapine’s success may have been due to AstraZeneca illegally marketing the drug, inadequately disclosing potential adverse effects and withholding negative clinical trial results about the drug’s safety and effectiveness. AstraZeneca allegedly promoted quetiapine for unapproved uses to treat both children and the elderly, specifically in nursing homes. Among the unapproved uses were Alzheimer’s disease, dementia, anxiety, depression, sleep disorders and post-traumatic stress disorder. In March 2011, the manufacturer agreed to pay $68.5 million to 36 states and the District of Columbia to settle a lawsuit charging it with the illegal marketing of quetiapine.
Since 2005, Worst Pills, Best Pills News has covered issues involving quetiapine, including its association with drug-induced akathisia (uncontrollable motor restlessness), prescription-drug deaths in military personnel and other drug interactions, as well the effects for which there are now warnings on the quetiapine label: suicidal thoughts in young adults and off-label use for elderly patients with dementia.
What You Can Do
You should not discontinue the use of any medication used for treating depression without first consulting the prescribing doctor.
You should consult your physician if you are being treated with quetiapine and have been prescribed any of the 12 drugs listed in the table, however this list is not exhaustive.
Consumers may report serious adverse events with drugs or product quality problems to the FDA’s MedWatch Adverse Event Reporting program online or by regular mail, fax or phone.
- Online: www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm
- Regular mail: Use postage-paid, pre-addressed FDA form 3500 and mail to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787
- Fax: (800) FDA-0178
- Phone: (800) FDA-1088