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Introduction

Other than iatrogenic errors, relatively few acute overdoses of antineoplastic drugs have been reported. However, because of the inherently cytotoxic nature of most of these agents, an overdose is more likely to be extremely serious. In this chapter, antineoplastic drugs are classified into 15 broad categories and are listed alphabetically in Table II-10. Radiologic agents are not included in this chapter, and arsenic is discussed.

TABLE II-10. ANTINEOPLASTIC DRUGS
DrugMOAaMajor Sites of Toxicityb; Comments
AbemaciclibIG++, H+, M++, P+; Fatal venous thromboembolic events have occurred. Peak level 8 hours after oral dose.
Abiraterone acetateGEn+, H+; Risk of excess mineralocorticoid activity, adrenocortical insufficiency, low phosphate. Potent inhibitor of cytochrome P450. Peak level 2 hours after oral dose.
AcalabrutinibIC+, M++; Hemorrhagic events, some fatal, occurred in 25% of patients. Peak level 0.9 hours after oral dose.
AfatinibIC+, D++, G++, H+, P+, R+; Diarrhea may be severe. Two adolescents developed nausea, vomiting, asthenia, dizziness, headache, and elevated amylase after ingesting 360 mg. Recovered with supportive care. Peak level 2-5 hours after oral dose.
AldesleukinOAn++, C++, D+, En+, G++, M+, N+, P++, R+; Commonly causes capillary leak syndrome* resulting in severe hypotension. Respiratory distress may be life threatening.
AlectinibIC++, En++, G+, H++, M++, P+, R+; Bradyarrhythmias up to 11% of patients. Peripheral edema common. Peak level 4 hours after oral dose.
AlemtuzumabKAn++, D+, En+, G+, H+, M++; Potentially fatal infusion-related reactions. Acute infusion of up to 60 mg in 2 patients caused hypotension, sinus tachycardia.
AlpelisibIAn++, D+, En++, G++, H+, M+, P+, R+; Severe hyperglycemia, including diabetic ketoacidosis, reported. Peak level 2-4 hours after oral dose.
AltretamineAG+, M+, N+; Reversible peripheral sensory neuropathy. Pyridoxine used to prevent neuropathy during therapy. Peak level 0.5-3 hours after oral dose.
AnastrozoleGEn+, G±; High risk of osteoporosis. Acute toxic effects unlikely. Peak level within 2 hours.
ApalutamideGC+, D+, En+, M+; Ischemic cardiovascular events, QTc prolongation reported. Peak level 2 hours after oral dose.
Arsenic trioxide See “Arsenic”.
AsparaginaseOAn++, En+, G+, H++, N++, R+; A 3yo boy who received a 10-fold overdose developed hyperammonemia, increased levels of glutamic and aspartic acid, and decreased levels of glutamine and asparagine, which normalized after 1 week. Repeated plasmapheresis was performed on a 48yo with fulminant hepatic failure attributed to asparaginase.
AtezolizumabHAn++, En++, G++, H++, M++, P++, R+; Life-threatening infusion reaction.
AvapritinibIC++, D+, En++, G+, H++, M++, N++, R+; Intracranial hemorrhage reported. Low Na+, K+, Mg++, phosphorus common. Peak level 2-4 hours after oral dose.
AvelumabHAn++, C++, En++, G+, H++, M++, P+, R+; Myocardial infarction and heart failure reported. Life-threatening infusion reaction.
AxicabtageneOAn++, C++, En++, G+, H+, M++, N++, P+; Cytokine release syndrome* in 94% of patients. Very high risk for systemic infections, including CNS.
AxitinibIC++, D+, En+, G+, H+, M+, N+, P+; Severe hypertension, hemorrhage, thromboembolic events. Doses up to 20 mg twice daily have resulted in dizziness, hypertension, seizures, and fatal hemoptysis. Peak level 2.5-4.1 hours after oral dose.
AzacitidineEC+, En+, G+, H+, M++, N+, P+, R+; One patient experienced diarrhea, nausea, and vomiting after receiving a single IV dose of approximately 290 mg/m2.
BelinostatFC+, D+, En+, G+, H+, M+; Tumor lysis syndrome* and prolonged QTc seen.
BendamustineAAn+, D++, G+, M++; Potentially fatal dermatologic reactions. Watch for tumor lysis syndrome*. Of 4 patients treated at maximum single dose of 280 mg/m2, 3 showed ECG changes, including QT prolongation and left anterior fascicular block.
BevacizumabBC++, G+, M+, N+, P+, R+; Severe and fatal hemorrhages, including Gl perforation, wound dehiscence, hemoptysis, up to 5 times more frequent than in control groups. Hypertension, at times severe, common.
BexaroteneOD+, En+, G+, M+, N+; Serious lipid and thyroid abnormalities, fatal pancreatitis during therapy. Peak level 2-4 hours after oral dose.
BicalutamideGEn+, H+; Gynecomastia, hot flashes
BinimetinibIG+; Minor side effects as monotherapy. High risk for cardiomyopathy, CNS/GI bleeding, rhabdomyolysis, thrombo-embolism, hepatic and pulmonary toxicity when combined with encorafenib. Peak level 1.6 hours after oral dose.
BleomycinCAn++, D++, G+, P++; Pulmonary toxicity (eg, pneumonitis, fibrosis) in about 10% of patients. High concentration of inhaled oxygen may worsen injury. Febrile reaction in 20-25% of patients.
BlinatumomabKAn+, H+, M++, N++; Cytokine release syndrome*, tumor lysis syndrome*, pancreatitis reported.
BortezomibOAn+, C+, D+, G++, M++, N++; Peripheral neuropathy common. Overdose of twice the recommended dosage was fatal due to hypotension, thrombocytopenia.
BosutinibIAn+, D+, G++, H+, M++; Fluid retention may be severe. Peak 4-6 hours after oral dose.
Brentuximab vedotinOAn+, D+, En+, G+, H+, M++, N++; Peripheral sensory neuropathy common. Serious hyperglycemia leading to fatal DKA, fatal Stevens-Johnson syndrome reported.
BrigatinibIC+, En+, G+, H+, M+, N+, P+; Hypertension, bradycardia, rhabdomyolysis, hyperglycemia seen. Peak level 1-4 hours after oral dose.
BusulfanAD+, En+, G++, M++, N+, P++; Pulmonary fibrosis, adrenal insufficiency with chronic use. Acute overdose of 2.4 g was fatal in a 10yo, and 140 mg resulted in pancytopenia in a 4yo. A 14yo who received 9 doses of 4 mg/kg every 6 hours developed seizures. Hemodialysis may be effective.
CabazitaxelJAn++, G+, M++, N+, P+, R+; Severe hypersensitivity reaction can occur. Hematuria seen during therapy. Pulmonary complications may be fatal.
CabozantinibBC+, D++, En+, G++, H+, M++, N+; Ingestion of 200 mg daily for 9 days caused memory loss, cognitive disturbance. Risk of GI perforation and fistulas, wound complications. Hand-foot syndrome common. Peak level 2-5 hours after oral dose.
CapecitabineDC+, D+, G+, H++, M+; Prodrug, converted to 5-fluorouracil. Hemodialysis may be effective. Uridine triacetate specific antidote (see text). Peak 1-1.5 hours after oral dose.
CarboplatinLAn+, En+, Ex+, G++, H+, M++, R+; A 3yo with a cumulative dose of 4,938 mg/m2 developed grade 4 mucositits, febrile neutropenia. A dose of 3,939 mg/m2 in a 4yo resulted in ototoxicity and renal dysfunction. Early dialysis may be effective. Peritoneal dialysis was not effective in one pediatric case.
CarfilzomibOAn+, C++, En+, G+, H+, M++, P+, R+; Risk of worsening CHF, severe hypertension, sudden cardiac death. A 200 mg IV dose caused hypotension, renal insufficiency, thrombocytopenia and lymphopenia.
Carmustine (BCNU)AD+, Ex+, G++, H+, M+, P+; Flushing, hypotension, and tachycardia with rapid IV injection.
CemiplimabHAn++, D+, En+, G+, H++, N+, P++; See text section III.E (page 128).
CeritinibIC+, D+, En+, G+, H+, M+, P+, R+; bradycardia, QTc prolongation, hyperglycemia, potentially fatal pancreatitis. Peak level 4-6 hours after oral dose.
CetuximabKAn++, D++, En+, G+, M+, N+, P+; Potentially fatal infusion reaction. Low Mg2+ risk.
ChlorambucilAD+, G+, H+, M+, N++; Seizures, confusion, coma reported after overdose. Acute overdoses of 0.125-6.8 mg/kg in children caused seizures up to 3-4 hours after ingestion. Bone marrow suppression with >6.5 mg/kg. Peak level 0.8 hours after oral dose.
CisplatinLAn+, Ex+, G++, H+, M+, N+, P+, R++; Severe toxicity with doses >300 mg/m2. A 750-mg acute IV overdose was fatal. A 3yo died 18 days after inadvertently receiving 100 mg/m2 daily for 4 days. Good hydration essential. Plasmapheresis and plasma exchange may be helpful. Hemodialysis not effective. Amifostine and sodium thiosulfate have been used to reduce cytotoxic effects during therapy and may be beneficial after overdose.
CladribineDAn+, D+, M++, N++, R++; Irreversible paraparesis/quadriparesis seen in high doses.
ClofarabineDC+, D+, En++, G++, H++, M++; Systemic inflammatory response syndrome, capillary leak syndrome* possible. Severe hypokalemia, hypophosphatemia common.
CobimetinibIC+, D+, En++, G+, H+, M++, R+; Major bleeding, rhabdomyolysis, electrolyte abnormalities seen. Median peak level 2.4 hours after oral dose.
CopanlisibIC+, D+, En++, G+, H+, M++; Hypertension, hyperglycemia common.
CrizotinibIC+, G+, H+, M++, N+, P+; Life-threatening or fatal pneumonitis seen. Bradycardia, QTc prolongation possible. Vision disorders common. Peak level 4-6 hours after oral dose.
Cyclophos-phamideAC+, D+, En+, Ex+, G++, M++, P+, R++; Severe left ventricular dysfunction, respiratory distress, moderate transaminitis after 16,200 mg over 3 days. Hemodialysis may be effective. Mesna IV and formalin instilled in the bladder used for hemorrhagic cystitis.
CytarabineDAn+, En+, G++, H+, M+, N++, P++; Cytarabine syndrome: fever, myalgia, bone pain, rash, malaise. Capillary leak syndrome* with ARDS in 16% of cases. Cerebellar dysfunction may be severe. Cumulative total dose of 54 g/m2 fatal in one adult and irreversibly neurotoxic in another. Hemodialysis may be effective very soon after an overdose.
DabrafenibIAn++, C+, D+, En+, H+; Hyperglycemia, hypophosphatemia common. Risk of hemolytic anemia with G6PD deficiency. Peak level 2 hours after oral dose.
DacarbazineAAn+, C+, En+, G++, H+, M+, N+; May produce flulike syndrome. Photosensitivity risk.
DacomitinibID+, G++, H+, M+, P+, R+; Diarrhea may be fatal. Peak level 6 hours after oral dose.
Dactinomycin (actinomycin D)CD+, Ex++, G++, H+, M++, N+; A 10-fold overdose in a child resulted in severe hypotension, pancytopenia, acute renal failure, choreoathetosis. Intrathecal administration of 350 mcg in a child caused persistent paraplegia. Highly corrosive to soft tissue.
DaratumumabKAn++, C+, M++, N+, P+; Infusion reactions, some severe, in 50% of patients.
DarolutamideGH+, M+; Peak level 4 hours after oral dose.
DasatinibIC+, D+, En+, G+, M++, N+, P+; High risk for severe fluid retention, hemorrhage. QT prolongation seen. Peak level 0.5-6 hours after oral dose.
DaunorubicinCAn+, C++, Ex++, G+, M++, N+; Congestive cardiomyopathy risk after total cumulative dose >400 mg/m2. A 3yo died after receiving 17 mg intrathecally. Dexrazoxane may be cardioprotective after an acute overdose and beneficial for treatment of extravasation (see text). Plasma exchange may remove liposomal daunorubicin.
DecitabineEAn+, C+, D+, En+, G+, M++, P+; Electrolyte abnormalities (hyperglycemia, hyponatremia, hyper-/hypokalemia), peripheral edema common.
DegarelixGH+; QTc prolongation possible.
DenileukinOAn++, G+, M+; Risk of fatal hypersensitivity reaction/capillary leak syndrome*.
DinutuximabKAn++, C+, D+, En++, G+, H+, M++, N+; Capillary leak syndrome*, neuropathic pain, electrolyte abnormalities (low sodium, potassium) common.
DocetaxelJAn++, C+, D+, Ex+, G+, M++, N++, P+; Severe fluid retention and edema in 6-9% of patients. Two patients who received 150-200 mg/m2 over 1 hour developed severe neutropenia, cutaneous reactions and mild asthenia and paresthesias.
DoxorubicinCAn+, C++, D+, Ex++, G+, M++, N+; CHF and cardiomyopathy may occur after total cumulative dose >400 mg/m2. Arrhythmias after acute overdose. Two adult patients survived doxorubicin overdoses of 540 mg as a single dose and 300 mg over 2 days with severe mucositis and bone marrow suppression. Early hemoperfusion may be effective. Early plasma exchange may be helpful for liposomal doxorubicin. Dexrazoxane used for cardioprotection and extravasation (see text).
DurvalumabHD+, En+, H+, M+, P+; See text section III.E (page 128).
DuvelisibIAn+, D++, G++, H+, M++, P++; Fatal dermatologic reactions reported. Peak level 1-2 hours after oral dose.
ElotuzumabKAn+, G+, H+, M+, N+, P+; High risk for opportunistic infectious diseases.
EnasidenibOAn++, En+, G+, H+, M+, P+; Potentially fatal differentiation/tumor lysis syndromes*. Low serum calcium level common. Peak level 4 hours after oral dose.
EncorafenibID+, En+, H+, M+, R+; Serious hemorrhagic events, QT prolongation. Electrolyte abnormalities. Peak level 2 hours after oral dose.
EnfortumabKD+, En+, Ex+, G+, M+, N+, R+; Potentially fatal hyperglycemia.
EntrectinibIC+, En+, G+, H++, M++, N+, P+, R+; Hyperuricemia, hypernatremia, hypocalcemia seen. CHF, QT prolongation risk. Peak level 4-6 hours after oral dose.
EnzalutamideGC+, En+, N+; Seizures after doses of 360-600 mg. Peak level 0.5-3 hours after oral dose.
EpirubicinCC++, Ex++, G++, M++; Death from multiple-organ failure reported in a 63yo woman after a single dose of 320 mg/m2. Risk for congestive heart failure increases steeply after cumulative dose of 900 mg/m2. Acute/early cardiotoxicity manifest as arrhythmias, ECG abnormalities. Treat with dexrazoxane after overdose for cardioprotection and for extravasation (see text).
ErdafitinibID+, En+, G+, H+, M+, R+; Hyperphosphatemia in 75% of patients. Hand-foot syndrome 26%. Peak level 2.5 hours after oral dose.
Eribulin mesylateJEn+, G+, M++, N++, P+; Overdose of 4 times the therapeutic dose caused grade 3 neutropenia for 7 days and grade 3 hypersensitivity for 1 day. Watch for QTc prolongation.
ErlotinibIC+, D+, G+, H+, P+; Fatal interstitial lung disease reported. Overdoses of 1,000 mg in healthy and up to 1,600 mg in cancer patients tolerated. Peak level 4 hours after oral dose.
EstramustineAC+, En ±, G+, H±, M ±; Has weak estrogenic and alkylating activity.
EtoposideJAn+, Ex+, G+, M++, P+; A 25yo woman who took 4,900 mg over 25 days presented with fatigue, fever, cough, diarrhea, and grade 1-2 myelosuppression. Peak level 1-1.5 hours after oral dose.
EverolimusIAn+, C+, D+, En+, G+, H+, M++, P+, R+; Hyperglycemia, hyperlipidemia common. Fatal noninfectious pneumonitis seen. Peak level 1-2 hours after oral dose.
ExemestaneGEn+, G±, H+, M+; Leukocytosis 1 hour after 25-mg ingestion in a child. Peak level at 2-4 hours post ingestion.
FedratinibIEn+, G+, H+, M++, N++, R+; Fatal encephalopathy, including Wernicke's, reported. Time to peak 3 hours after oral dose.
FloxuridineDG++, M++; Prodrug of 5-fluorouracil.
FludarabineDAn+, G+, M++, N++, P+; Blindness, seizures, coma, death at high doses. Tumor lysis syndrome*.
5-FluorouracilDC+, D+, G++, M++, N+; Acute cerebellar syndrome seen. Cardiac arrest, sudden death during therapy. Severe toxicity and death with 20-25 mg/kg. Leucovorin may worsen toxicity. Uridine triacetate is a specific antidote (see text).
FlutamideGEn+, H+; Aniline metabolite of flutamide has caused methemoglobinemia. A single dose of 5 g resulted in no sequelae. Peak level 2 hours after oral dose.
FostamatinibIC+, G+, H+; Hypertension may be severe. Peak level 1.5 hours after oral dose.
FulvestrantGEn ±, G ±; Acute toxic effects unlikely.
GefitinibID+, G+, H+, N+, P+; Peak level 3-7 hours after oral dose.
GemcitabineDAn+, D+, G+, H++, M++, P++, R+; Can cause bronchospasm, severe ARDS, capillary leak syndrome*, potentially fatal hemolytic-uremic syndrome, pulmonary toxicity.
GemtuzumabKAn+, C+, G+, H+, M++; Fatal hemorrhage due to thrombocytopenia during therapy. QT prolongation.
GilteritinibIAn+, C+, D+, En+, H+, M+, N+, P+, R+; Differentiation syndrome*. QT prolongation. Electrolyte abnormalities. Peak level 4-6 hours after oral dose.
GlasdegibOC+, En+, G+, H+, M++, R++, P+; QTc prolongation risk. Hyponatremia common. Peak level 1.3-1.8 hours after oral dose.
GoserelinGC+, En+; QTc prolongation risk.
HydroxyureaDD+, G+, H+, M++; A 2yo had only mild myelosuppression after ingesting 612 mg/kg acutely. Ingestion of 60 g by an adult caused myoclonic jerks, oculogyric crisis, sinus tachycardia, and myelosuppression. Peak level 1-4 hours after oral dose.
Ibritumomab tiuxetanKAn++, D+, Ex+, G+, M++; Given with radiolabeled drug. Severe, fatal infusion reactions reported.
IbrutinibIC+, D+, G+, M++, P+, R+; Severe bleeding events have occurred. Serious arrhythmias, including fatalities, reported. A dose of 1680 mg in an adult caused reversible grade 4 transaminitis. Peak level 1-2 hours after oral dose.
IdarubicinCC+, D+, Ex++, G++, M++; Congestive heart failure may occur. Severe arrhythmias reported in one case of fatal overdose. One patient died after receiving 135 mg/m2 (>10 times the therapeutic dose) over 3 days.
IdelalisibIAn+, D++, G++, H++, M++, P++; Peak level 1.5 hours after oral dose.
IfosfamideAG++, M++, N++, R++; Hemorrhagic cystitis common. Encephalopathy up to 40% of patients. Cumulative dose of 26 g/m2/cycle caused irreversible renal failure. Combined hemodialysis and hemoperfusion reduced serum levels by 84%. Mesna (see text) decreases incidence and severity of bladder toxicity. N-acetylcystine may mitigate renal toxicity. Methylene blue may protect against and treat encephalopathy.
ImatinibIC+, D+, En+, G+, H+, M++, N+; Fluid retention and edema, muscle cramps common. Acute overdose of 6,400 mg by a 21yo caused severe vomiting, transient decrease in neutrophils, and mild transaminitis. A 53yo woman had severe abdominal pain and vomiting after ingesting 16 gm. A 47yo developed severe muscle cramps, CPK of 3,880 u/L after ingestion of 2 g. Ingestion of 400 mg by a 3yo resulted in vomiting, diarrhea, and anorexia. Another 3yo with ingestion of 980 mg developed leukopenia and diarrhea. Peak level 2-4 hours after oral dose.
InotuzumabKAn+, C+, G+, H+, M++; QT prolongation. Fatal hepatic veno-occlusive disease.
IpilimumabHD+, En+, G+, H+, N+, P+; See text section III.E (page 128).
IrinotecanNAn+, G++, H+, M++, N++, P+; Severe diarrhea may be fatal. Cholinergic syndrome during infusion.
IsatuximabKAn++, G+, M++, P+; Infusion reaction common.
IvosidenibOC+, D+, En+, G+, H+, M++, N+, P+, R+; Differentiation syndrome*. Guillain-Barre syndrome. QT prolongation. Electrolyte abnormalities. Peak 3 hours after oral dose.
IxabepiloneJAn+, C+, G+, M++, N++; One patient survived 100 mg/m2 with peripheral neuropathy, myalgia and GI symptoms. An adult received 185 mg and developed myalgia and fatigue.
IxazomibOC+, G+, H+, M++, N+; Peripheral edema, neuropathy common. Fatal thrombotic microangiopathy reported. Time to peak 1 hour after oral dose.
LapatinibIC+, D++, G++, H+, M+, P+; Left ventricular ejection fraction decrease, QT prolongation seen. Grade 3 diarrhea and vomiting in an adult after taking 3000 mg daily for 10 days. Peak level 4 hours after oral dose.
LarotrectinibIG+, H++, M++, N++, P+; Pericardial and pleural effusions seen. Time to peak 1 hour after oral dose.
LenalidomideBAn+, C+, D+, En+, G+, H++, M++, N+, P+; Risk for thromboembolic events. Tumor lysis syndrome*. Time to peak 0.5-6 hours after oral dose.
LenvatinibBC++, D+, En++, G++, H+, R++; Hypertension, cardiac dysfunction, QT prolongation. Hyponatremia, hypocalcemia (grade 3/4). Serious or fatal hemorrhage in >25%. Thromboembolic events reported. Acute overdose of 120 mg caused fatal multiorgan failure. Time to peak 1-4 hours after oral dose.
LetrozoleGEn+, G±; Grade 3/4 hypercholesterolemia. No toxicity from 62.5 mg acute overdose.
LeuprolideGC+, En+; QT prolongation possible. Acute toxic effects unlikely.
LevamisoleOG+, M+, N+; Nicotinic and muscarinic effects at cholinergic receptors. Gastroenteritis, dizziness, headache after 2.5 mg/kg dose. Fatality after ingestion of 15 mg/kg in a 3yo and 32 mg/kg in an adult. Reports of agranulocytosis from cocaine adulterated with levamisole. Peak level 1.5-2 hours after oral dose.
Lomustine (CCNU)AG++, H+, M+, P+; Two patients developed grade 4 neutropenia and thrombocytopenia approximately 2 weeks after taking 800 mg orally over 4-5 days but recovered. 1,400 mg taken over 1 week was fatal in an adult. Peak level 1-4 hours after oral dose.
LorlatinibIC++, En+, G+, H+, M+, N+, P++; PR prolongation, AV block may require a pacemaker. Risk for hyperglycemia. Time to peak 1-2 hours after oral dose.
MechlorethamineAD+, Ex++, G++, M++, N+; Powerful vesicant. Avoid contact with powder or vapors. Lymphocytopenia may occur within 24 hours. Watch for hyperuricemia.
MegestrolGEn+, G±; Acute toxic effects unlikely. Potential for adrenal insufficiency with chronic use.
MelphalanAAn+, En+, G+, M+, N+, P+; Hyponatremia, SIADH seen during therapy. A 1yo received 140 mg of IV and developed pronounced lymphopenia within 24 hours then neutropenia, thrombocytopenia, and diarrhea by day 7. Peak level at 1 hour after oral dose.
MercaptopurineDD+, G+, H++, M+; A 22-month-old who ingested 86 mg/kg had severe neutropenia with nadir at 11 days. A 2yo with a maximum potential ingestion of 400 mg (26 mg/kg) did not develop clinical or laboratory evidence of toxicity. Elevated liver enzymes occurred in a 2yo who ingested 400 mg. Peak level 1 hour after oral dose.
Methotrexate See “Methotrexate” page 316.
MidostaurinIAn+, C+, En++, G++, H++, M++, P+, R++; QT prolongation 11% incidence, renal failure 11-12%. Peak level 1-3 hours after oral dose.
MitomycinCC+, D+, Ex++, G++, H+, M++, P+, R+; Hemolytic-uremic syndrome reported with therapeutic doses. Pulmonary toxicity at an average cumulative dose of 78 mg. The incidence of renal toxicity significantly increases with total cumulative doses of 120 mg.
MitotaneOD+, En++, G+, N+; Adrenal suppression; glucocorticoid replacement during stress.
MitoxantroneNC+, Ex+, G++, M++, N+; 4 patients died of severe leukopenia and infection after overdose. Reversible cardiomyopathy in 1 overdose case. Hemoperfusion was ineffective.
MogamulizumabKAn++, D++, En+, G+, H+, M++, Infusion reactions may be life-threatening or fatal. Immune-mediated myocarditis, hepatitis, myositis, Guillaine-Barre syndrome.
Moxetumomab PasudotoxOAn++, C+, En++, M+, R++; Infusion reaction. Life-threatening capillary leak syndrome*. Severe electrolyte abnormalities. Hemolytic-uremic syndrome.
NecitumumabKAn+, D++, En++, G+, P+; Cardiopulmonary arrest in combination with gemcitabine, cisplatin. Fatal thromboembolism. Monitor serum electrolytes. Low Mg2+ 83%.
NelarabineEG+, M++, N++, P+; Paralysis, seizures, coma, ascending neuropathy during treatment.
NeratinibID+, G++, H+, N+; Time to peak 2-8 hours after oral dose.
NilotinibIC+, D+, En+, G+, H+, M++; Causes QT prolongation, cardiac and arterial vascular occlusive events, electrolyte abnormalities. Peak level 3 hours after oral dose.
NilutamideGEn+, H+, P+; Ingestion of 13 g by a 79-year-old resulted in no evidence of toxicity
NiraparibMC++, G+, H+, M++, N+, P+; Hypertensive crisis risk. Peak 3 hours after oral dose.
NivolumabHAn+, D+, En++, G++, H+, M++, N+, P+, R+; See text section III.E (page 128).
ObinutuzumabKAn++, En+, H+, M++, P+, R+; Severe infusion reactions. Tumor lysis syndrome.*
OfatumumabKAn++, D+, G+, M++, P+; Fatal infections in 17% of treated patients. Risk of serious infusion reactions, including bronchospasms, pulmonary edema. Tumor lysis syndrome*.
OlaparibMG+, M++, N+, P+, R+; Fatal pneumonitis. Peak 1.5 hours after oral dose.
OmacetaxineOAn+, En++, G+, M++, N+; May induce glucose intolerance. Grade 3/4 hyperuricemia.
OsimertinibIC+, D+, En+, H+, G+, M++, P+; QTc prolongation, fatal cardiomyopathy. Hypermagnesemia. Peak level 6 hours after oral dose.
OxaliplatinLAn+, Ex+, G+, H+, M++, N++, P+; A 64yo woman developed peripheral neuropathy, diarrhea, thrombocytopenia, and neutropenia after receiving 500 mg. A 7yo had respiratory distress, vomiting, diarrhea, myelosuppression, and neurological symptoms (nystagmus, lower limb pain/weakness, hyperextension of the right foot) after receiving 800 mg instead of 80 mg. An overdose of 500 mg IV resulted in fatality from respiratory failure, bradycardia.
PaclitaxelJAn++, C+, G+, M++, N++; Severe hypersensitivity reactions, including death, reported. Peripheral neuropathy common. Hypotension, bradycardia, ECG abnormalities, conduction abnormalities seen. Fatal myocardial infarction 15 hours into infusion reported.
PalbociclibID+, G+, H+, M++, N+, P++; Fatal interstitial lung disease/pneumonitis reported. Peak level 4-12 hours after oral dose.
PanitumumabKAn+, D++, G+, P+; Severe infusion reaction possible. Watch for electrolyte depletion, especially K+, Mg2+. Grade 3/4 venous thromboembolism 10.7% incidence.
PanobinostatFC++, En++, G++, H+, M++; Fatal cardiac ischemic events, arrhythmias, hemorrhage. Severe electrolyte abnormalities. Peak level 2 hours after oral dose.
PazopanibBC++, En+, G+, H++, M++; Hypertension, hyperglycemia common. Arterial thrombotic events, QT prolongation. Electrolyte depletion. Peak level 2-4 hours after oral dose.
PegaspargaseOAn++, En+, G+, H+, M+, N+; Bleeding diathesis from low fibrinogen and antithrombin III. Incidence of pancreatitis 18% during treatment. Hyperglycemia up to 24%.
PembrolizumabHAn++, C+, D+, En++, M+, N+, R+; Hypertension common. See text section III.E (page 128).
PemetrexedDD+, G+, H+, M++, P+; Folic acid antagonist. Leucovorin has been used for treatment of toxicity. Patients must take vitamin B12, folic acid supplements.
PemigatinibID+, En++, G+, H+, R+; Hyperphosphatemia >90% and other electrolyte abnormalities. Peak level 1 hour after oral dose.
PentostatinDAn+, C+, D+, G+, H+, M+, N+, P+, R+; Convulsions, coma at high doses.
PertuzumabKAn+, C+, D+, G++, M++, N+; Decreased left ventricular ejection fraction and congestive heart failure, peripheral neuropathy risk.
PexidartinibIC+, D+, G+, H++, M+; Severe hepatoxicity. Peak level 2.5 hours after oral dose.
Polatuzumab Vedotin-piiqKAn+, En+, G+, H++, M++, N++, R+; Neuropathy, progressive multifocal leukoencephalopathy. Tumor lysis syndrome*.
PomalidomideBAn+, C+, D+, En+, G+, H+, M++, N+, P+, R+; Fatal hepatotoxicity. Thromboembolic events. Tumor lysis syndrome*. Peak level 2-3 hours after oral dose.
PonatinibIAn+, C++, D++, En+, G+, H++, M++, N+, P+; Arterial and venous thrombosis and occlusion in at least 27% of patients. 540 mg caused QT prolongation within 2 hours and death 9 days later from pneumonia and sepsis. Ingestion of 90 mg/day for 12 days resulted in pneumonia, systemic inflammatory response syndrome*, atrial fibrillation, and a moderate pericardial effusion. Acute ingestion of 165 mg caused fatigue and non-cardiac chest pain. Peak concentration 6 hours after oral dose.
PralatrexateDAn+, C+, D+, G++, M++, P+; Mucositis is common and can be severe. Treat with leucovorin for overdose. Hemodialysis may be of benefit soon after overdose.
ProcarbazineOAn+, D+, En+, G++, M++, N++; Monoamine oxidase inhibitor activity. Disulfiram-like ethanol interaction. Coma, seizures during therapy.
RaloxifeneGIncreased risk for venous thromboembolism with chronic therapy. Ingestion of 180 mg each in two 1-year-olds resulted in ataxia, dizziness, tremor, vomiting, diarrhea, and elevated alkaline phosphatase. Peak level 0.5 hours after oral dose.
RamucirumabBAn++, C+, En+, G+, H+, M+, R++; Can cause GI hemorrhage/perforation, severe hypertension, arterial thrombotic events. Impaired wound healing. Life-threatening infusion reaction.
RasburicaseDAn++, En+, G+, H+, M+; Hemolysis in G6PD-deficient patients. Methemoglobinemia reported. Life-threatening hypersensitivity reactions, including anaphylaxis.
RegorafenibBC++, D++, En++, G+, H++, M+, N+, R+; Hypertension common and can be severe. GI perforation/fistula, wound healing complications seen. Peak level 4 hours after oral dose.
RibociclibIEn+, G+, H+, M++, P++, R+; QT prolongation. Peak level 1-4 hours after oral dose.
RituximabKAn++, C+, D+, En+, G+, H+, M++, P+, R+; Severe, fatal hypersensitivity reaction possible. Tumor lysis syndrome* has caused acute renal failure. Potentially fatal mucocutaneous reactions reported. Electrolyte disturbance.
RomidepsinFC+, En++, G+, H+, M++, N+; Risk of supraventricular and ventricular arrhythmias, QT prolongation, electrolyte disturbance (especially phosphate).
RucaparibMAn+, D+, G+, H+, M++, N+, P+, R+; Peak level 2 hours after oral dose.
RuxolitinibIC+, En+, G+, H+, M++, N+; Severe withdrawal syndrome, including septic shock-like symptoms, possible. Graft-versus-host disease. Up to 200 mg acutely tolerated with minimal symptoms. Peak level 1-2 hours after oral dose
Sactuzumab GovitecanNAn++, D+, En+, H+, G++, M++, P+; Life-threatening infusion reaction. Decreased serum sodium, calcium, phosphate. Hyper/hypomagnesemia, hyper/hypoglycemia.
SelinexorOEn++, G+, M++, N+, P+; Grade 3/4 hyponatremia. Peak level within 4 hours of oral dose.
SelumetinibIC+, D++, En+, G++, H+, M++, N+, P+, R+; Cardiomyopathy in 25% of patients. CPK elevation in 79%. Peak level 1-1.5 hours after oral dose.
Sipuleucel-TOAn++; Infusion reaction. Thromboembolic events (strokes and myocardial infarcts).
SonidegibOEn+, G+, M+, N++, R++; Hyperglycemia 51%. Musculoskeletal toxicity (spasms, myalgia), CPK elevation common. Peak level 2-4 hours after oral dose.
SorafenibBC+, D+, En+, G+, H+, M++; Risk for hypertension, hemorrhage. Hypocalcemia, hypophosphatemia common. Peak level 3 hours after oral dose.
SunitinibBC++, D+, En+, G++, H+ M+, N+; Left ventricular dysfunction (up to 27%), QT prolongation, hemorrhagic events. Hypertension can be severe. Risk of electrolyte abnormalities, hypothyroidism. No adverse reactions reported with an intentional overdose of 1,500 mg. Peak level 6-12 hours after oral dose.
TagraxofuspOAn++, C+, En+, H++, M++; Electrolyte disturbances. Capillary leak syndrome >50%.
TalazoparibMEn+, G+, H+, M++; Hyperglycemia 54%, hypocalcemia 28%. Peak level 1-2 hours after oral dose.
TamoxifenGD ±, En ±, G ±, H+; Tremors, seizures, QT prolongation with 400 mg/m2. Peak level 3-6 hours after oral dose.
TazemetostatOEn+, G+, H+, M++; Electrolyte abnormalities. Peak level 1-2 hours after oral dose.
TemozolomideAG+, H+, M++, N+; Overdose of 5,500 mg over 2 days caused pancytopenia between 1 and 4 weeks. Another overdose of 2,000 mg per day for 5 days resulted in death from multiorgan failure, pancytopenia. Peak plasma level at 1 hour after oral dose.
TemsirolimusIAn+, C+, D+, En++, G+, H+, M++, P+, R+; Hyperglycemia, hypophosphatemia, hyperlipidemia, hypertriglyceridemia common.
ThalidomideBAn+, C+, D+, H+, M++, N++, P+; Thomboembolic events, tumor lysis syndrome*. Can cause severe birth defects or fetal death. Peak level 2-5 hours after oral dose.
6-ThioguanineDG+, H+, M+, R+; Tumor lysis syndrome*. Reversible myelosuppression after oral dose of 35 mg/kg. Peak level 8 hours after oral dose.
Thiotepa (TESPA)AAn+, Ex+, G++, H+, M++, N+, R+; Bone marrow suppression usually very severe. Risk for hemorrhage.
Tisagenlec-leucelOAn++, C+, En+, G+, M++, N++, P+; Cytokine release syndrome*, neurotoxicity (seizures, encephalopathies) may be life threatening.
TopotecanNAn+, G+, M++, P+; Severe pancytopenia common. A patient who received double the IV dose developed severe neutropenia 14 days later. Fourfold increase in clearance during hemodialysis in one patient with renal failure. Peak level 1-2 hours after oral dose.
ToremifeneGD ±, En ±, G ±, H+; Risk of QTc prolongation, hypercalcemia and tumor flare. Headache and dizziness in healthy volunteers with 680 mg daily for 5 days. Peak level within 3 hours after oral dose.
TositumomabKAn+, D+, En+, G+, H+, M++, N+, P+; Given with radiolabeled iodine complex. May cause hypothyroidism. Severe, potentially fatal hypersensitivity reaction.
TrabectedinOAn+, Ex+, C+, G+, H++, M++, P+, R+; Severe rhabdomyolysis, cardiomyopathy, pulmonary embolism, fatal capillary leak syndrome reported.
TrametinibIAn+, C+, D++, En++, G+, H+; Risk for bradyarrhythmia, cardiomyopathy, QTc prolongation, hemorrhage, low Na+, Mg2+. Time to peak 1.5 hours after oral dose.
TrastuzumabKAn++, C+, G+, H+, M++, N+, P+; Can precipitate congestive heart failure. Severe, fatal hypersensitivity, and pulmonary toxicity reported. Ado-trastuzumab emtansine, a complex of a small molecule cytotoxin bound to trastuzumab, has caused fatal hepatotoxicity.
TretinoinOAn+, C+, D+, G+, H+, M+, N+, P+; Retinoic acid syndrome in 25% of patients with acute promyelocytic leukemia: fever, dyspnea, pulmonary infiltrates, and pleural or pericardial effusions. Fatal multiple-organ thrombosis reported. Acute oral overdose of 1,000 mg in a 31yo caused only diarrhea. Peak level 1-2 hours after oral dose.
TucatinibID++, En+, G++, H++, M+, R+; Palmarplantar erythrodysesthesia 63%. Decreased serum magnesium, phosphate, potassium, sodium. Peak level 2 hours after oral dose.
ValrubicinCM++; Used intravesically, but highly myelotoxic if systemically absorbed. Conventional and peritoneal dialysis ineffective.
VandetanibBC++, D++, En+, G+, H+, N+; Can cause QT prolongation, severe hypertension, hypocalcemia. Risk for hemorrhage. Peak level 4-10 hours (median 6) after oral dose.
VemurafenibIAn+, C+, D++, G+, H+, N+, R+; Severe dermatologic reactions, including Stevens-Johnson, seen. QTc prolongation 55%. Peak level 3 hours after oral dose.
VenetoclaxOC+, D+, G+, M++, N+, P+; Tumor lysis syndrome*. Peak 5-8 hours after oral dose.
VinblastineJEx++, G+, M++, N+, P+; Fatal if given intrathecally. An 83yo given 5 mg IM daily for 6 days developed neutropenia, thrombocytopenia, fever, and pneumonia and died 10 days after initial dose. A 5yo who received 10 times the intended dose developed seizures, coma, myelosuppression, and gastrointestinal symptoms but recovered. A 12yo had severe musculoskeletal pain, fever, intestinal hypotonia, severe esophagitis, and peripheral neuropathy but recovered after receiving almost double the maximum dose. Two plasma exchange transfusions were performed at 4 and 18 hours after the overdose.
VincristineJEx++, G+, M ±, N++, P+; Fatal if given intrathecally. Delayed (up to 9 days) seizures, coma after overdoses. A 13yo inadvertently given 32 mg of vincristine IV developed abdominal distension, fever, hypertension then hypotension, and died 33 hours later. A 7yo given 10 times the intended IV dose developed hypotension, ileus, urinary retention, myelosuppression, hyponatremia and respiratory distress and died 68 hours after the overdose. A 5yo who received 7.5 mg IV had fever, elevated liver enzymes, areflexia, bloody diarrhea, neutropenia, and hallucinations and died 9 days after overdose. Exchange transfusion and plasmapheresis reduced vincristine concentrations after overdoses. Leucovorin, pyridoxine, and glutamic acid may reduce the incidence of neurotoxicity.
VinorelbineJD+, Ex++, G+, H+, M++, N+, P+; Fatal if given intrathecally. A 10-fold overdose caused fever, pulmonary edema, severe mucositis, diarrhea, paralytic ileus, severe cutaneous desquamation, peripheral neuropathy, and severe bone marrow suppression.
VismodegibOEn+, G+, N+; Muscle spasms common. Low K+, Na+ risk. Peak level 2 hours after oral dose.
VorinostatFC+, G+, M+, P+; Risk of thromboembolism, hyperglycemia. Can prolong QT. Peak level at a median of 4 hours after oral dose.
ZanubrutinibIC+, D+, G+, H+, M++, P+; Atrial fibrillation/flutter reported. Fatal hemorrhagic events. Peak level 2 hours after oral dose.
Ziv-afliberceptBC++, G++, H+, M++, N+, R++, Potentially fatal bleeding events, GI perforation, compromised wound healing. Risk of severe hypertension, proteinuria.

aMOA (mechanism of action): A, alkylating agents; B, angiogenesis inhibitors, C, antibiotics; D, antimetabolites; E, DNA demethylation agents; F, histone deacetylase inhibitors; G, hormones; H, immune checkpoint inhibitors; I, kinase inhibitors; J, mitotic inhibitors; K, monoclonal antibodies; L, platinum-containing complexes; M, PARP inhibitors; N, topoisomerase inhibitors; O, miscellaneous.

bAn, anaphylaxis/allergy/drug fever or immune related; C, cardiac; D, dermatologic; En, endocrine and metabolic; Ex, extravasation risk; G, gastrointestinal; H, hepatic; M, myelosuppressive; N, neurologic; P, pulmonary; R, renal; +, mild to moderate severity; ++, severe toxicity; ±, minimal.

*See text section III for details.

Mechanism of Toxicity

In general, toxic effects are extensions of the pharmacologic properties of these drugs.

  1. Alkylating agents attack nucleophilic sites on DNA, resulting in alkylation and cross-linking and thus inhibiting replication and transcription. Binding to RNA or protein moieties appears to contribute little to cytotoxic effects.
  2. Angiogenesis inhibitors interfere with growth and survival of endothelial cells by binding to endothelial growth factors on endothelial cell receptors.
  3. Antibiotics. These drugs intercalate within base pairs in DNA, inhibiting DNA-directed RNA synthesis. Another mechanism may be the generation of cytotoxic free radicals.
  4. Antimetabolites interfere with normal nucleic acid biosynthesis at various stages. Antimetabolites may also be incorporated into nucleic acids in place of corresponding normal nucleotides.
  5. DNA demethylation agents. Hypermethylation of DNA is a common characteristic of some cancers, particularly myelodysplasias. Hypomethylation can confer direct cytotoxic effects as well as alterations of gene expression that may prevent disease progression.
  6. Histone deacetylases (HDACs) catalyze the removal of acetyl groups from lysine residues of proteins. In some cancer cells, HDACs may be overexpressed or be recruited for oncogenic transcription factors. Histone deacetylase inhibitors allow for the accumulation of acetylated histones, resulting in cell cycle arrest and apoptosis.
  7. Hormones include anti-androgens and anti-estrogens, gonadotropin-releasing hormone blockers, and aromatase inhibitors.
  8. Immune checkpoints regulate immune activation, primarily on T cells. When inhibitory signals are activated, as with cancer, anti-tumor immune response is suppressed. Immune checkpoint inhibitors work by blocking receptors such as CTLA-4, PD-1, and PD-L1.
  9. Kinase inhibitors. Mutation of various protein kinases can trigger unregulated growth of the cell. Inhibition of kinase activity can result in decreased cellular proliferation, cell cycle arrest, and apoptosis.
  10. Mitotic inhibitors act in various ways to inhibit orderly mitosis, arresting cell division.
  11. Monoclonal antibodies target antigens specific to, or overexpressed in, cancerous cells. The antibodies may be directly cytotoxic or may be used to deliver radionuclides or cytotoxins to the target cells.
  12. Platinum complexes produce intra-and/or interstrand platinum-DNA cross-links.
  13. Poly ADP-ribose polymerase (PARP) is important for repair of DNA damage, especially in some cancer cells. PARP inhibitors help prevent DNA replication, causing cell death.
  14. Topoisomerase inhibitors inhibit topoisomerase I, which relieves torsional strain during DNA replication. The cleavable complex normally formed between DNA and topoisomerase I is stabilized by these drugs, resulting in breaks in single-stranded DNA.
  15. Miscellaneous. The cytotoxic actions of other antineoplastic drugs result from a variety of mechanisms.
  16. Pharmacokinetics. Most oral antineoplastic agents are readily absorbed. As a result of rapid intracellular incorporation and the delayed onset of toxicity, pharmacokinetic values are usually of little utility in managing acute overdose.

Toxic Dose

Because of the highly toxic nature of these agents (except for hormones), exposure to even therapeutic amounts should be considered potentially serious.

Clinical Presentation

The organ systems affected by the various agents are listed in Table II-10. The most common sites of toxicity are the hematopoietic and GI systems.

  1. Leukopenia is the most common manifestation of bone marrow depression. Thrombocytopenia and anemia may also occur. Death may result from overwhelming infections or hemorrhagic diathesis. With alkylating agents, the lowest blood counts occur 1-4 weeks after exposure, whereas with antibiotics, antimetabolites, and mitotic inhibitors, the lowest blood counts occur 1-2 weeks after exposure.
  2. Gastrointestinal toxicity is also very common. Nausea, vomiting, and diarrhea often accompany therapeutic administration, and severe ulcerative gastroenteritis and extensive fluid loss may occur. Pretreatment with aprepitant and dexamethasone is often used for highly emetogenic regimens.
  3. Systemic inflammatory response syndrome (SIRS) or cytokine release syndrome may cause high fever, tachypnea, tachycardia, pulmonary edema, circulatory shock, vascular leakage, disseminated intravascular coagulation, and multi-organ system failure. Cytotoxic agents can also cause tumor lysis syndrome (hyperuricemia, hyperkalemia, renal failure) as a consequence of rapid lysis of malignant cells and release of intracellular components.
  4. Angiogenesis inhibitors can cause hemorrhage, thromboembolic events, hypertension, impaired wound healing, reversible posterior leukoencephalopathy syndrome, gastrointestinal perforation, and fistulas.
  5. Immune checkpoint inhibitors can cause potentially fatal multi-organ system immune activation, including cardiac myopathy, arrhythmias, thyroid dysfunction, diabetes mellitus and diabetic ketoacidosis, hepatitis, interstitial lung disease, and nephritis/nephropathy.
  6. Extravasation of some antineoplastic drugs at the IV injection site may cause severe local injury, with skin necrosis and sloughing. Drugs that bind to nucleic acids in DNA, such as anthracyclines (eg, daunorubicin, doxorubicin), cause direct local cell death and are more likely to cause severe injury.

Diagnosis

Is usually based on the history. Because some of the most serious toxic effects may be delayed until several days after exposure, early clinical symptoms and signs may not be dramatic.

  1. Specific levels. Not generally available. For methotrexate.
  2. Other useful laboratory studies include CBC with differential, platelet count, electrolytes, glucose, BUN and creatinine, liver enzymes, and prothrombin time. Electrocardiography and cardiac troponin may be indicated for cardiotoxic agents, and pulmonary function tests are indicated for agents with known pulmonary toxicity.
  3. Genetic polymorphisms. Some individuals are genetically predisposed to the hematopoietic and GI effects of irinotecan (eg, UGT1A1 *28/*28 genotype), and thiopurine drugs such as azathioprine and 6-mercaptopurine (eg, TPMT *2, *3A, or *3C genotypes). Tests are available through reference laboratories.

Treatment

  1. Emergency and supportive measures
    1. Maintain an open airway and assist ventilation if necessary.
    2. Treat coma, seizures, hypotension, and arrhythmias if they occur.
    3. Treat nausea and vomiting with ondansetron or metoclopramide. Consider adding a benzodiazepine. Treat fluid losses caused by gastroenteritis with IV crystalloid fluids.
    4. Bone marrow depression should be treated with the assistance of an experienced hematologist or oncologist. Transfusions of packed red blood cells and platelets may be needed for episodes of bleeding. Recombinant erythropoietin may be useful for severe anemia, and hematopoietic colony-stimulating factors may be useful for neutropenia.
    5. If severe immune response to immune checkpoint inhibitors is suspected, initiate corticosteroid therapy. Tocilizumab is approved for the treatment of severe or life-threatening cytokine release syndrome.
    6. Extravasation. Immediately stop the infusion and withdraw as much fluid as possible by applying negative pressure on the syringe. Elevate the affected limb. Surgical intervention may be necessary. Specific treatment recommendations vary by institutional preferences.
      1. Local injection with sodium thiosulfate may be helpful for extravasation from cisplatin, cyclophosphamide, doxorubicin, epirubicin, mechlorethamine, mitomycin, and vinblastine. Mix 4 mL of sodium thiosulfate 10% solution with 6 mL of sterile water for injection, and inject 3-10 mL of the mixture subcutaneously into the extravasation site.
      2. Topical application of dimethyl sulfoxide (DMSO) 99% (or 50% if readily available) may be beneficial for carboplatin, cisplatin, dactinomycin, daunorubicin, doxorubicin, epirubicin, idarubicin, mitomycin, and mitoxantrone. Apply a thin layer with a sterile gauze to the area of infiltration every 2 hours for the first 24 hours then 6-8 hours for 7-14 days (do not cover).
      3. Local injection with hyaluronidase may help diffuse the drug through the interstitial space and enhance systemic absorption. Reconstitute with normal saline and inject 150-900 units subcutaneously or intradermally. Its use may be of benefit for carmustine, paclitaxel, teniposide, vinblastine, vincristine, and vinorelbine. Do not use for doxorubicin or other anthracycline extravasation.
      4. Totect® brand of dexrazoxane is approved for the treatment of extravasation from anthracyclines: dactinomycin, daunorubicin, doxorubicin, epirubicin, and idarubicin. Give an IV infusion of 1,000 mg/m2 of body surface area (maximum, 2,000 mg) over 1-2 hours, no later than 6 hours after extravasation. Repeat the same dose 24 hours later, then 500 mg/m2 (maximum 1,000 mg) 48 hours after the first dose. Infuse in a large vein in an area remote from the extravasation. Do not use for local infiltration. Do not use DMSO for patients receiving dexrazoxane.
      5. For most chemotherapeutic agents, apply cool compresses to the extravasation site for 15 minutes 4 times daily for 2-3 days. Do not use cool compresses for vinca alkaloids (eg, vinblastine, vincristine).
      6. Apply warm compresses/heating pad intermittently (15-30 minutes 4 times a day) for 1-2 days specifically for vinblastine, vincristine, and vinorelbine. Do not apply heat for anthracyclines.
      7. Application of both cool and warm compresses has been recommended for carboplatin, carmustine, dacarbazine, docetaxel, etoposide, fluorouracil, methotrexate, oxaliplatin, and paclitaxel.
      8. Injection of hydrocortisone or sodium bicarbonate is not recommended.
  2. Specific drugs and antidotes. Very few specific treatments or antidotes are available (see Table II-10).
    1. Amifostine is approved for reduction of cumulative renal toxicity from cisplatin. It has also been used for cisplatin-induced neurotoxicity, cyclophosphamide-induced granulocytopenia, and radiation and/or chemotherapy-induced mucositis.
    2. Dexrazoxane protects against doxorubicin-induced cardiotoxicity and may be protective for other anthracyclines (epirubicin, idarubicin, and mitoxantrone).
    3. Mesna is used for the treatment of ifosfamide- and cyclophosphamide-induced hemorrhagic cystitis and hematuria.
    4. Palifermin is used to decrease the incidence and duration of severe oral mucositis in patients with hematologic malignancies receiving myelotoxic therapy.
    5. Uridine triacetate is approved for treatment of 5-fluorouracil and capecitabine toxicity. To order, call 1-800-914-0071.
  3. Decontamination. Administer activated charcoal orally if conditions are appropriate (see Table I-37). Gastric lavage is not necessary after small-to-moderate ingestions if activated charcoal can be given promptly.
  4. Enhanced elimination. Because of the rapid intracellular incorporation of most of these agents, dialysis and other extracorporeal removal procedures are generally not effective (see Table II-10 for exceptions).