oxaliplatin (Rx)

>10%

Peripheral neuropathy (76%)

Anemia (64%)

Nausea (64%)

Fatigue (61%)

Diarrhea (46%)

Vomiting (37%)

Abdominal pain (31%)

Constipation (31%)

Thrombocytopenia (30%)

Fever (25%)

Anorexia (20%)

Leukopenia (13%)

Dyspnea (13%)

Cough (11%)

1-10%

Edema (10%)

Neutropenia (7%)

Pharyngolaryngeal dysesthesia (1-2%)

<1%

Pulmonary fibrosis

Posterior leukoencephalopathy syndrome

Frequency Not Defined

Anaphylactic-like reaction (uncommon)

Pulmonary fibrosis (uncommon)

Postmarketing Reports

Body as a whole: Angioedema, anaphylactic shock

Central and peripheral nervous system disorders: Loss of deep tendon reflexes, dysarthria, Lhermitte’s sign, cranial nerve palsies, fasciculations, convulsion, RPLS

Hearing and vestibular system disorders: Deafness

Infusion reactions/hypersensitivity: Laryngospasm

Liver and gastrointestinal system disorders: Severe diarrhea/vomiting resulting in hypokalemia, colitis (including Clostridium difficile diarrhea), metabolic acidosis; ileus; intestinal obstruction, pancreatitis; veno-occlusive disease of liver (ie, sinusoidal obstruction syndrome), perisinusoidal fibrosis which rarely may progress

Platelet, bleeding, and clotting disorders: immuno-allergic thrombocytopenia prolongation of prothrombin time and of INR in patients receiving anticoagulants

Red blood cell disorders: Hemolytic uremic syndrome, immuno-allergic hemolytic anemia

Renal disorders: Acute tubular necrosis, acute interstitial nephritis, acute renal failure

Respiratory system disorders: Pulmonary fibrosis, and other interstitial lung diseases (sometimes fatal)

Cardiovascular toxicity

Rhabdomyolysis

Septic shock

Contraindications

Hypersensitivity to oxaliplatin, other platinum compounds

Pregnancy

Cautions

Caution in renal impairment, elderly, neuropathy, neurotoxic agents

For 3-4 days, avoid contact with ice/cold food/objects, avoid breathing cold air

Avoid contact with aluminum needles or equipment

Avoid pregnancy

Pulmonary fibrosis may occur

Concomitant use with fluorouracil may increase gastrointestinal effects

Grade 3 or 4 neutropenia reported in patients with colorectal cancer treated in combination with 5-flurouracil (5-FU) and leucovorin; delay oxaliplatin therapy until neutrophils are at 1.5 x 10^9/L; withhold oxaliplatin for sepsis or septic shock; reduce dose after recovery from Grade 4 neutropenia or febrile neutropenia

Cardiovascular toxicity reported; ECG monitoring recommended if therapy initiated in patients with congestive heart failure, bradyarrhythmias, drugs known to prolong the QT interval, including Class Ia and III antiarrhythmics, and electrolyte abnormalities; correct hypokalemia or hypomagnesemia prior to initiating oxaliplatin and monitor these electrolytes periodically during therapy; avoid oxaliplatin in patients with congenital long QT syndrome

Reversible posterior leukoencephalopathy syndrome (RPLS, also known as PRES, Posterior Reversible Encephalopathy Syndrome) reported in clinical trials and postmarketing experience

Rhabdomyolysis, including fatal cases reported; discontinue oxaliplatin if any signs or symptoms of rhabdomyolysis occur

Pregnancy

Based on direct interaction with DNA, therapy can cause fetal harm when administered to a pregnant woman; available human data do not establish presence or absence of major birth defects or miscarriage related to use of drug; advise a pregnant woman of potential hazard to fetus

Verify pregnancy status in females of reproductive potential prior to initiating therapy

Therapy can cause embryo-fetal harm when administered to a pregnant woman

Advise females of reproductive potential to use effective contraception while receiving therapy and for 9 months after final dose

Based on mechanism action as a genotoxic drug, advise males with female partners of reproductive potential to use effective contraception while receiving drug and for 6 months after final dose

Based on animal studies, therapy may impair fertility in males and females

Animal data

• Reproductive toxicity studies demonstrated adverse effects on embryo-fetal development in rats at maternal doses that were below the recommended human dose based on body surface area

Lactation

There are no data on presence of drug or its metabolites in human or animal milk, effects on breastfed infant or on milk production; because of potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment and for 3 months after final dose

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Platinum coordination compound that inhibits DNA synthesis; cross-links and denatures strands of DNA; disrupts DNA function by covalently binding to DNA bases

Pharmacokinetics

Peak plasma time: 2 hr

Concentration: 1.21 mcg/mL

Protein bound: >90%; platinum accumulates in RBCs

Vd: 440 L

Half-life: 391 hr

Clearance: 10.1 L/hr

Excretion: Urine (54%); feces (2%)

Dialyzable: no

IV Incompatibilities

Alkaline medications or media (eg, basic solutions of 5-FU)

IV Preparation

Reconstitute by adding 10 mL (for 50 mg vial) or 20 mL (for 100 mg vial) of SWI or D5W. Dilute required amount of reconstituted solution in an infusion solution of 250-500 mL of D5W. Do NOT use NS or chloride-containing solutions

Reconstituted solution may be refrigerated up to 24 hr at 2-8°C (36-46°F). After final dilution with 250-500 mL D5W, the shelf life is 6 hr at room temp [20-25°C (68-77°F)] or up to 24 hr under refrigeration at 2-8°C (36-46°F)

Eloxatin is not light sensitive

Do not use aluminum-containing needles or IV administration sets that may come in contact with carboplatin (aluminum can react causing precipitate formation and loss of potency)

IV Administration

Flush infusion line with D5W prior to administration of oxaliplatin or any concomitant drug

Inspect visually for particulate matter and discoloration prior to administration and discard if present

Use separate bags for oxaliplatin and leucovorin (administered through Y-site)

See adult dosing for infusion and bolus rate