oxaliplatin

Action

Unclear. Thought to form reactive platinum complexes that inhibit DNA synthesis through formation of interstrand and intrastrand cross-linking of DNA molecules. Cell-cycle-phase nonspecific.

Availability

Powder for reconstitution for injection, lyophilized: 5 mg/ml in 50-mg and 100-mg single-use vials

Solution for injection: 5 mg/ml in 10-ml, 20-ml, and 40-ml single-use vials

Indications and dosages

➣ Metastatic cancer of colon or rectum, given with 5-fluorouracil (5-FU) and leucovorin

Adults: On day 1, 85 mg/m² oxaliplatin I.V. infusion and 200 mg/m² leucovorin; give both drugs simultaneously over 2 hours, followed by 400 mg/m² I.V. bolus of 5-FU over 2 to 4 minutes, then 600 mg/m² 5-FU I.V. as 22-hour continuous infusion. On day two, 200 mg/m² leucovorin I.V. infusion over 2 hours, followed by 400 mg/m² 5-FU I.V. bolus over 2 to 4 minutes, then 600 mg/m² 5-FU I.V. as 22-hour continuous infusion.

Contraindications

• Hypersensitivity to drug or platinum products

Precautions

Use cautiously in:

• thrombocytopenia

• radiation therapy

• recent pneumococcal or smallpox vaccination

• elderly patients

• pregnant or breastfeeding patients

• children.

Administration

See Follow facility policy for preparing, handling, and administering mutagenic, teratogenic, and carcinogenic drugs.

• Premedicate patient with antiemet-ics, as prescribed.

• Reconstitute with sterile water or dextrose 5% in water (D₅W)-never with normal saline solution or other solutions containing chloride.

• Further dilute reconstituted drug in 250 to 500 ml of D₅W.

• Infuse over 2 hours simultaneously with leucovorin, but in a separate I.V. bag.

• Don't use administration sets or needles that contain aluminum.

See Be aware of importance of using leucovorin rescue with this drug.

See Avoid extravasation, which may cause necrosis and other severe reactions.

• Know that treatment cycles are usually repeated every 2 weeks.

Adverse reactions

CNS: headache, dizziness, fatigue, insomnia, peripheral neuropathy

CV: cardiac abnormalities

EENT: decreased visual acuity, hearing loss, tinnitus, rhinitis, pharyngitis

GI: severe nausea, vomiting, diarrhea, constipation, dyspepsia, gastroesoph-ageal reflux, mucositis, flatulence, stomatitis, anorexia

GU: hematuria, dysuria

Hematologic: anemia, thrombocytopenia, leukopenia, pancytopenia, neutropenia, hemolytic uremic syndrome

Metabolic: hypokalemia

Respiratory: dyspnea, cough, upper respiratory infection, pulmonary fibrosis

Skin: alopecia, rash, flushing, extravasation, redness, swelling, angioedema

Other: weight loss, increased cold sensitivity, pain at injection site, anaphylaxis

Interactions

Drug-drug. Aminoglycosides, loop diuretics: increased risk of nephrotoxicity

Aspirin, nonsteroidal anti-inflammatory drugs: increased risk of bleeding

Live-virus vaccines: decreased antibody response to vaccine

Myelosuppressants: increased bone marrow depression

Drug-diagnostic tests. Alanine aminotransferase, aspartate aminotransferase, bilirubin, creatinine: increased levels

Hemoglobin, neutrophils, platelets, white blood cells: decreased levels

Drug-behaviors. Alcohol use: increased risk of bleeding

Patient monitoring

See Monitor I.V. site frequently to avoid extravasation.

• Monitor CBC, blood chemistry, and kidney and liver function tests before each treatment cycle.

See Watch closely for blood dyscrasias, hemolytic uremic syndrome, serious pulmonary problems, and anaphylaxis.

• Conduct complete neurologic exam before and after each dose.

• Monitor vital signs and ECG. Evaluate cardiovascular and respiratory status closely.

• Assess patient's comfort level. Keep him warm during infusion to minimize neurologic effects.

• Watch for signs and symptoms of toxicity (paresthesia, nausea, vomiting).

Patient teaching

• Inform patient that chemotherapy drugs can cause many adverse effects.

• Tell patient he'll receive drug from trained health care professionals in hospital setting.

See Instruct patient to inform nurse immediately if drug contacts his skin, eyes, or mouth.

• Advise patient to notify nurse if pain or redness occurs at I.V. site.

• Instruct patient to stay warm and avoid iced drinks to minimize neurologic symptoms.

See Tell patient to report itching, hives, swelling of hands or face, chest tightness, difficulty breathing, unsteadiness, severe diarrhea or vomiting, or tingling sensation in hands, arms, legs, or feet.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and behaviors mentioned above.