Drug (date of most recent available labeling)

Indication

Reason for boxed warning

Alternatives

Antiemetics

Droperidol (Inapsine®) 12/2001

Nausea and vomiting; neuroleptic anesthesia

Prolonged QT interval, torsades de pointes

Ondansetron^b, metoclopramide prochlorperazine, promethazine, propofol^c

Metoclopramide (Reglan®) 9/2011

Nausea and vomiting; gastroparesis

Tardive dyskinesia

Ondansetron^b, droperidol, prochlorperazine, promethazine, propofol^c

Prochlorperazine (Compazine®) 12/2010

Nausea and vomiting

Increased risk of mortality (cardiovascular, infectious) in elderly patients with dementia-related psychosis

Ondansetron^b, droperidol, metoclopramide, promethazine, propofol^c

Promethazine (Phenergan®) 9/2009

Nausea and vomiting

Tissue damage on extravasation or intra-arterial injection, potentially fatal respiratory depression in pediatric patients <2 years, worsening of Parkinsonian symptoms in older patients

Ondansetron^b, droperidol, prochlorperazine, promethazine, propofol^c

Antimicrobials

Fluoroquinolones: ciprofloxacin (Cipro®), levofloxacin (Levaquin ®), moxifloxacin (Avelox®), norfloxacin (Noroxin®), ofloxacin 4/2012 (levofloxacin)

Prophylaxis and treatment of bacterial infections

Tendinitis, tendon rupture, exacerbation of muscle weakness in myasthenic patients

Depends on targeted pathogen

Analgesics and anxiolytics

Acetaminophen (Tylenol®) – mandates boxed warning when added to other drugs

Acute and chronic pain

Hepatotoxicity in doses exceeding 4,000 mg daily (adults)

NSAIDs, opioids, regional/neuraxial analgesia

Buprenorphine (Buprenex®, Butrans®) 7/2012

Opioid withdrawal, chronic pain

Respiratory depression, diversion/misuse, overdose if patch exposed to heat, overdose with accidental ingestion by children

Other opioids, NSAIDs, acetaminophen

Fentanyl patch (Duragesic® patch) 7/9/2012

Acute and chronic pain

Respiratory depression, diversion/misuse, overdose with CYP3A4 inhibitors, overdose if patch exposed to heat, overdose with accidental exposure in children

Other opioids, NSAIDs, acetaminophen, regional/neuraxial analgesia

Hydromorphone (Dilaudid®, Dilaudid-HP®, Exalgo®) 3/2013

Acute and chronic pain

Respiratory depression, diversion/misuse, overdose with high potency version, overdose with crushing/chewing extended release version, overdose with accidental ingestion by children

Other opioids, NSAIDs, acetaminophen, regional/neuraxial analgesia

Ketorolac (Toradol®) 3/2013

Acute pain

Cardiovascular events, myocardial infarction and stroke; GI events, bleeding, ulcer, perforation; renal impairment; bleeding risk; hypersensitivity including anaphylaxis; contraindicated in pregnant women or nursing mothers; should be used for <5 days

Acetaminophen, ibuprofen, opioids

Methadone (Dolophine®) 7/2012

Opioid withdrawal, chronic pain

Respiratory depression, QT prolongation, torsades de pointes, overdose with accidental ingestion by children, should be prescribed by professionals knowledgeable in using opioids for chronic pain

Shorter-acting opioids, NSAIDs, acetaminophen, regional/neuraxial analgesia

Midazolam (Versed®) 6/2010

Anxiety, procedural sedation

Respiratory depression; in older patients, risk of impaired psychomotor function, syncope, falls; seizures in neonates; use only in hospitals or ambulatory care settings

Anxiety, low doses; procedural sedation, fentanyl, propofol

Nonselective NSAIDs: ibuprofen (Advil®, Motrin®) 9/2007

Acute and chronic pain

Cardiovascular events, myocardial infarction and stroke; GI events, bleeding, ulcer, perforation

Short-term use of nonselective NSAIDs; acetaminophen, opioids, regional/neuraxial analgesia

Oxymorphone (Opana ®) 7/2012

Acute and chronic pain

Respiratory depression, diversion/misuse, overdose if mixed with alcohol, overdose with accidental ingestion by children

Other opioids, NSAIDs, acetaminophen, regional/neuraxial analgesia

Local anesthetics

Bupivacaine^d (Marcaine®) 1/2012

Local, regional, neuraxial anesthesia

Cardiac arrest when 0.75 % solution used for obstetrical epidural anesthesia, chondrolysis when used for continuous intra-articular infusion

Lower concentration of bupivacaine for obstetrical anesthesia, avoidance of intra-articular infusion (e.g., single-shot or continuous nerve blockade, neuraxial anesthesia)

Other drugs

Amiodarone^d (Cordarone®) 11/2011

Atrial fibrillation

Hypersensitivity pneumonitis, hepatotoxicity, heart block

Metoprolol, diltiazem

Bumetanide (Bumex®) 1/2010

Fluid overload

Profound diuresis with water and electrolyte depletion

Lower doses, furosemide, hydrochlorothiazide

Dantrolene (Dantrium®) – oral formulation only 7/2012

Treatment of malignant hyperthermia, neuroleptic malignant syndrome, spasticity

Hepatic injury/hepatitis (potentially fatal)

Malignant hyperthermia, none; spasticity, baclofen, diazepam

Low-molecular-weight heparins: dalteparin (Fragmin®), enoxaparin (Lovenox®) 4/2011 (enoxaparin)

Prophylactic or therapeutic anticoagulation

Spinal/epidural hematoma risk with neuraxial anesthesia

Unfractionated heparin

Nimodipine (Nimotop®) 1/2006

Hypertension in subarachnoid hemorrhage

Hypotension when contents of oral capsules extracted and injected intravenously

Nicardipine, oral dosing of nimodipine

Protamine 1/2008

Reversal of heparin anticoagulation

Severe hypotension, catastrophic pulmonary vasoconstriction, cardiovascular collapse, noncardiogenic pulmonary edema; not to be used in bleeding not associated with heparin exposure

(None)

Quetiapine (Seroquel®) 11/2011

Psychosis

Increased risk of mortality (cardiovascular, infectious) in elderly patients with dementia-related psychosis, suicidality in children and young adults with concomitant psychiatric disease

Haloperidol

Sodium nitroprusside (Nipride®) 8/2007

Hypertension

Cyanide intoxication, hypotension

Nitroglycerin, nicardipine

Succinylcholine (Anectine®) 9/2010

Neuromuscular blockade

Rhabdomyolysis with hyperkalemia

Non-depolarizing neuromuscular blockers

Warfarin (Coumadin®) 10/2011

Therapeutic anticoagulation

Major or fatal bleeding

Unfractionated or low-molecular-weight heparins, dabigatran, rivaroxaban