Alkylating agents

G+, N+, M+

Reversible peripheral sensory neuropathy.

An+, D++, G+, M++

Potentially fatal dermatologic reactions. Watch for tumor lysis syndrome.

D+, En+, G+, M+, N+, P++

Pulmonary fibrosis, adrenal insufficiency with chronic use. Acute overdose of 2.4 g was fatal in a 10-year-old, and 140 mg resulted in pancytopenia in a 4-year-old. High doses cause coma, seizures. Hemodialysis may be effective.

D+, Ex+, G++, H+, M+, P+

Flushing, hypotension, and tachycardia with rapid IV injection.

D+, 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 serum level 0.8 hours after oral dose. Not dialyzable.

Al++, C+, D+, En+, G++, M++, R+

Severe left ventricular dysfunction, moderate transaminitis after 16,200 mg over 3 days. Hemodialysis may be effective. Mesna and N-acetylcysteine have been used investigationally to reduce hemorrhagic cystitis.

Al+, An+, En+, G++, H+, M+, N++

May produce flulike syndrome. Photosensitivity reported.

En±, G±, H±, M±

Has weak estrogenic and alkylating activity.

AI++, M++, N++, G++, R++

Hemorrhagic cystitis, somnolence, confusion, hallucinations, status epilepticus, coma seen during therapy. Combined hemodialysis and hemoperfusion reduced serum levels by 84%. Methylene blue may protect against and treat encephalopathy.

Al+, G+, H+, M+, P+

Thrombocytopenia, leukopenia, liver and lymph node enlargement seen after overdose. 1400 mg taken over one week was fatal in an adult. Peak level 1–4 hours after oral dose.

D+, Ex++, G++, M++, N+

Lymphocytopenia may occur within 24 hours. Watch for hyperuricemia.

An+, G+, M+, N+, P+

Hemodialysis may be effective although of questionable need (normal half-life only 90 minutes). Peak level at 1 hour after oral dose.

An+, G++, M++

Bone marrow suppression usually very severe.

Al+, G+, M+, N+

Overdose of 5500 mg over 2 days caused pancytopenia between 1 and 4 weeks. Peak plasma level at 1 hour after oral dose.

Antibiotics

An++, 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.

Al++, D+, Ex++, G++, M++, N+

A 10-fold overdose in a 1-year-old child resulted in severe hypotension, pancytopenia, acute renal failure, choreoathetosis. Highly corrosive to soft tissue.

Al+, An+, C++, Ex++, G++, M++

Congestive cardiomyopathy may occur after total cumulative dose >600 mg/m2.

Al+, An++, C++, D+, Ex++, G++, M++, N+

Cardiotoxicity and cardiomyopathy may occur after total cumulative dose >450 mg/m2. Arrhythmias after acute overdose. Hemoperfusion may be effective. Dexrazoxane is given for cardioprotection and extravasation.

Al+, C++, Ex++, G++, M++

Death from multiple-organ failure reported in a 63-year-old woman after a single dose of 320 mg/m2. Risk for congestive heart failure increases steeply after cumulative dose of 900 mg/m2.

Al+, C+, Ex++, G++, M++

Congestive heart failure, acute life-threatening arrhythmias may occur.

Al+, C+, D+, Ex++, G++, H+, M++, P+, R+

Hemolytic-uremic syndrome reported with therapeutic doses.

An+, C+, Ex+, G++, M++

Four patients died of severe leukopenia and infection after overdose. Reversible cardiomyopathy in one overdose case. Hemoperfusion was ineffective.

M++

Used intravesically, but highly myelotoxic if systemically absorbed.

Antimetabolites

C+, D+, G+, M+

Prodrug, converted to 5-fluorouracil. Hand-foot syndrome common. Peak level 1–1.5 hours after oral dose.

An+, D+, M++, N++, R++

Irreversible paraparesis/quadriparesis seen in high doses.

C+, D+, G++, H+, M++

Systemic inflammatory response syndrome, capillary leak possible.

An+, 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.

Al+, G++, M++

Prodrug of 5-fluorouracil.

G+, M++, N++, P+

Blindness, seizures, coma, death at high doses. Peak level 1 hour after oral dose.

Al+, C+, D+, G++, M++, N+

Acute cerebellar syndrome seen. Cardiac arrest, sudden death during therapy. Coronary vasospasm with angina may occur. Vistonuridine is a specific antidote. Peak level 30 minutes after oral dose (percentage absorbed highly variable).

An+, D+, G+, H+, M+, P++, R+

Can cause bronchospasm, severe ARDS.

D+, G+, H++, M+

Hemodialysis removes drug but of questionable need (half-life, 20–60 minutes). A 22-month-old child who ingested 86 mg/kg had severe neutropenia. Nadir at 11 days. Peak level 1 hour after oral dose.

Al+, D+, G++, H+, M++, N+, P+, R+

Peak serum level 1–2 hours after oral dose. Folinic acid (leucovorin [See Leucovorin Calcium]) is a specific antidote. Hemoperfusion questionably effective. Urinary alkalinization and repeat-dose charcoal may be helpful.

An+, D+, G++, H+, M++, P+

Folic acid antagonist. Leucovorin may be useful. Patients must take daily vitamin B12 , folic acid.

C+, D+, G+, H+, M+, N++, P+, R++,

Central nervous system depression, convulsions, coma seen at high doses.

An++, G+, M+

Hemolysis in G6PD-deficient patients. Methemoglobinemia reported.

G+, H+, M+, R+

Reversible myelosuppression after oral dose of 35 mg/kg. Peak level 8 hours after oral dose. Hemodialysis probably ineffective owing to rapid intracellular incorporation.

DNA demethylation agents

En+, G++, H+, M++, N+, R+

Neuromuscular toxicity (eg, weakness, muscle tenderness, lethargy, coma) seen. Watch for fluid, electrolyte abnormalities.

D+, En+, G+, M++

Hyperglycemia and electrolyte abnormalities common.

G+, M+, N++, P+

Paralysis, seizures, coma, Guillain-Barre–like symptoms reported during treatment.