| Drug | Class | Boxed warning (summary) |
|---|---|---|
| Acetaminophen | NSAIDs and acetaminophen | Hepatotoxicity: acetaminophen has been linked to acute liver failure, often with doses above the maximum daily limit or more than one acetaminophen product. (Boxed warning on the injectable and prescription combination products.) |
| Amiodarone | Antiarrhythmics | Pulmonary toxicity, hepatic injury and worsened arrhythmia; reserved for life-threatening arrhythmias and started where the patient can be monitored. |
| Apixaban | Anticoagulants | Premature discontinuation increases the risk of thrombotic events; spinal or epidural hematoma with neuraxial anesthesia. |
| Ciprofloxacin | Fluoroquinolones | Tendinitis and tendon rupture, peripheral neuropathy, central nervous system effects and worsening of myasthenia gravis. Reserved for patients without other options for uncomplicated infections. |
| Clopidogrel | Antiplatelet drugs | Reduced effectiveness in CYP2C19 poor metabolizers. |
| Clozapine | Antipsychotics | Severe neutropenia; orthostatic hypotension, bradycardia and syncope; seizures; myocarditis and cardiomyopathy; increased mortality in older adults with dementia-related psychosis; not approved for that use. |
| Enoxaparin | Anticoagulants | Spinal or epidural hematomas, which can cause permanent paralysis, in patients receiving neuraxial anesthesia or spinal puncture. |
| Fluoxetine | Antidepressants | Increased risk of suicidal thoughts and behaviors in children, adolescents and young adults (under 25). Monitor all patients for worsening depression and unusual changes in behavior, especially in the first months and after dose changes. |
| Gentamicin | Aminoglycosides | Nephrotoxicity, ototoxicity and neurotoxicity, including neuromuscular blockade and respiratory paralysis. |
| Haloperidol | Antipsychotics | Increased mortality in older adults with dementia-related psychosis; not approved for that use. |
| Ibuprofen | NSAIDs and acetaminophen | Increased risk of serious cardiovascular thrombotic events (heart attack, stroke) and serious GI bleeding, ulceration and perforation. Contraindicated around coronary artery bypass graft (CABG) surgery. |
| Isoniazid (INH) | Antitubercular drugs | Severe and sometimes fatal hepatitis, which can occur months after starting. |
| Ketorolac | NSAIDs and acetaminophen | Increased risk of serious cardiovascular thrombotic events (heart attack, stroke) and serious GI bleeding, ulceration and perforation. Contraindicated around coronary artery bypass graft (CABG) surgery. Ketorolac also carries boxed warnings for kidney injury, bleeding risk, and a maximum treatment duration of 5 days. |
| Levothyroxine | Thyroid and antithyroid drugs | Not for obesity or weight loss: doses large enough to cause weight loss can cause serious or life-threatening toxicity. |
| Lisinopril | ACE inhibitors | Fetal toxicity: stop as soon as pregnancy is detected. Drugs acting on the renin-angiotensin system can injure and kill the developing fetus. |
| Lithium | Mood stabilizers | Lithium toxicity is closely related to serum levels and can occur at doses close to therapeutic levels. Lithium should be used only where serum levels can be measured promptly. |
| Lorazepam | Benzodiazepines | Concomitant use with opioids can cause profound sedation, respiratory depression, coma and death. Risks of abuse, misuse and addiction; dependence and withdrawal reactions. |
| Losartan | Angiotensin II receptor blockers (ARBs) | Fetal toxicity: stop as soon as pregnancy is detected. |
| Metformin | Oral and non-insulin antidiabetic drugs | Lactic acidosis: rare but can be fatal. Risk rises with kidney impairment, contrast studies, surgery, hypoxia, heavy alcohol use and liver impairment. |
| Metoclopramide | Antiemetics | Tardive dyskinesia, which may be irreversible. Avoid treatment longer than 12 weeks. |
| Metronidazole | Nitroimidazoles (metronidazole) | Carcinogenic in mice and rats; avoid unnecessary use. |
| Montelukast | Asthma controller drugs | Serious neuropsychiatric events, including suicidal thoughts and actions. For allergic rhinitis, it is reserved for patients who cannot use other treatments. |
| Morphine | Opioid analgesics and antagonists | Addiction, abuse and misuse; life-threatening respiratory depression; accidental ingestion (especially by children); neonatal opioid withdrawal syndrome; risks with benzodiazepines and other CNS depressants. |
| Oxytocin | Obstetric drugs | Not for elective induction of labor (induction without a medical indication). |
| Phenytoin | Anticonvulsants (antiepileptic drugs) | Cardiovascular risk with rapid IV infusion: hypotension and arrhythmias. Do not exceed the labeled IV rate. |
| Promethazine | Antiemetics | Respiratory depression and death in children under 2; severe tissue injury, including gangrene, with the injection. |
| Risperidone | Antipsychotics | Increased mortality in older adults with dementia-related psychosis; not approved for that use. |
| Sertraline | Antidepressants | Increased risk of suicidal thoughts and behaviors in children, adolescents and young adults (under 25). Monitor all patients for worsening depression and unusual changes in behavior, especially in the first months and after dose changes. |
| Valproic acid (divalproex) | Anticonvulsants (antiepileptic drugs) | Hepatotoxicity (highest risk in children under 2), fetal risk (major birth defects and decreased IQ), and pancreatitis. |
| Warfarin | Anticoagulants | Major or fatal bleeding. Regular INR monitoring is required. |
Summaries are simplified for study. The full boxed warning is in the current FDA-approved label.
Frequently asked questions
What is a boxed warning?
A boxed warning, often called a black box warning, is the strongest warning the FDA requires on a prescription drug label. It describes a serious or life-threatening risk and how to reduce it.
Can a drug with a boxed warning still be given?
Yes. A boxed warning does not mean the drug is banned; it means the risk must be weighed, the patient monitored and the patient taught what to report.