oxaliplatin

ox-A-li-pla-tin

Therapeutic Classification: antineoplastics

Pharmacologic Classification: alkylating agents

High Alert

Adjuvant treatment of stage III colon cancer in patients who have undergone complete resection of the primary tumor (in combination with 5-fluorouracil and leucovorin).
Advanced colorectal cancer (in combination with 5-fluorouracil and leucovorin)

Unlabeled Use:

Ovarian cancer that has progressed despite treatment with other agents.

Inhibits DNA replication and transcription by incorporating platinum into normal cross-linking (cell-cycle nonspecific).

Therapeutic effects:

Death of rapidly replicating cells, particularly malignant ones.

Absorption: IV administration results in complete bioavailability.

Distribution: Extensive tissue distribution.

Protein Binding: >90% (platinum).

Metabolism/Excretion: Undergoes rapid and extensive nonenzymatic biotransformation; excreted mostly by the kidneys.

Half-Life: 391 hrs.

ROUTE	ONSET	PEAK	DURATION
IV	unknown	unknown	unknown

Contraindicated in:

Hypersensitivity;
Hypersensitivity to other platinum compounds;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Renal impairment;
HF, bradycardia, concomitant use of QT interval prolonging medications, hypokalemia, and hypomagnesemia;
Rep: Women of reproductive potential and men with female partners of reproductive potential;
Pedi: Safety and effectiveness not established in children;
Geri: risk of adverse reactions in older adults.

Adverse reactions are noted for the combination of oxaliplatin, 5-fluorouracil and leucovorin

CV: chest pain, edema, QT interval prolongation, thromboembolism, TORSADES DE POINTES

EENT: visual abnormalities

F and E: dehydration, hypokalemia

GI: diarrhea, nausea, vomiting, abdominal pain, anorexia, gastroesophageal reflux, stomatitis

Hemat: anemia, neutropenia, thrombocytopenia, leukopenia

Local: injection site reactions

MS: rhabdomyolysis, back pain

Neuro: fatigue, neurotoxicity, REVERSIBLE POSTERIOR LEUKOENCEPHALOPATHY SYNDROME

Resp: cough, dyspnea, PULMONARY FIBROSIS

Misc: ANAPHYLAXIS/ANAPHYLACTOID REACTIONS, fever

Drug-drug:

Concurrent use of nephrotoxic agents may ↑ toxicity.
Concurrent use of QT interval prolonging medications, including Class Ia antiarrhythmics and Class III antiarrhythimics may ↑ risk of torsades de pointes.

IV (Adults ): Day 1: 85 mg/m² with leucovorin 200 mg/m² at the same time over 2 hr, followed by 5-fluorouracil 400 mg/m² bolus over 2–4 min, then 5-fluorouracil 600 mg/m² as a 22-hr infusion. Day 2: leucovorin 200 mg/m² over 2 hr, followed by 5-fluorouracil 400 mg/m² bolus over 2–4 min, then 5-fluorouracil 600 mg/m² as a 22-hr infusion. Cycle is repeated every 2 wk. Dosage reduction/alteration may be required for neurotoxicity or other serious adverse effects.

Renal Impairment

IV (Adults ): CCr <30 mL/min:↓ dose on Day 1 to 65 mg/m².

(Generic available)

Lyophilized powder for injection: 50 mg/vial; 100 mg/vial
Solution for injection: 5 mg/mL

Assess for peripheral sensory neuropathy. Acute onset occurs within hr to 1–2 days of dosing, resolves within 14 days, and frequently recurs with further dosing (transient paresthesia, dysesthesia, and hypoesthesia of hands, feet, perioral area, or throat). Symptoms may be precipitated or exacerbated by exposure to cold or cold objects; avoid ice during symptoms. May also cause jaw spasm, abnormal tongue sensation, dysarthria, eye pain, and a feeling of chest pressure. Persistent (>14 days) causes paresthesias, dysethesias, and hypoesthesias, but may also include deficits in proprioception that may interfere with daily activities (walking, writing, swallowing). Persistent neuropathy may occur without prior acute neuropathy and may improve upon discontinuation of oxaliplatin. Adjuvant Therapy:For persistent Grade 2 neurosensory events that do not resolve, reduce dose of oxaliplatin to 75 mg/m². For patients with persistent Grade 3 neurosensory events, consider discontinuing therapy. Do not alter infusional 5-fluorouracil/leucovorin regimen. For Grade 4 neuropathy, discontinue oxaliplatin. Advanced Colorectal Cancer: For persistent Grade 2 neurosensory events that do not resolve, reduce dose to 65 mg/m². For patients with persistent Grade 3 neurosensory events, consider discontinuing therapy. Do not alter infusional 5-fluorouracil/leucovorin regimen. For Grade 4 neuropathy, discontinue oxaliplatin.
Assess for signs of pulmonary fibrosis (nonproductive cough, dyspnea, crackles, radiological; infiltrates). May be fatal. Discontinue oxaliplatin if pulmonary fibrosis occurs.
Monitor for signs of anaphylaxis (rash, hives, swelling of lips or tongue, sudden cough). Epinephrine, corticosteroids, and antihistamines should be readily available.
Monitor for signs and symptoms of reversible posterior leukoencephalopathy syndrome (headache, altered mental functioning, seizures, abnormal vision from blurriness to blindness, associated or not with hypertension).
Monitor ECG in patients with HF, bradyarrhythmias, and electrolyte abnormalities and in patients taking drugs known to prolong the QT interval, including Class Ia and III antiarrhythmics.
Monitor for signs and symptoms of GI adverse reactions (nausea, vomiting, diarrhea) during therapy. If Grade 3 or 4 GI adverse reactions occur, after recovery, reduce oxaliplatin dose to 75 mg/m² along with dose reduction of fluorouracil to 300 mg/m² as an IV bolus and 500 mg/m² as a 22-hr continuous infusion.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.Monitor WBC with differential, hemoglobin, platelet count, and blood chemistries (ALT, AST, bilirubin, and serum creatinine) at baseline and before each oxaliplatin cycle. Adjuvant Therapy:For Grade 4 neutropenia or febrile neutropenia, or Grade 3 or 4 thrombocytopenia, hold next dose until neutrophils ≥1.5 × 10⁹/L and platelets ≥75 × 10⁹/L. Reduce dose of oxaliplatin to 75 mg/m² and infusional 5-fluorouracil to 300 mg/m² bolus and 500 mg/m² 22-hr infusion. Advanced Colorectal Cancer:After recovery from grade 3/4 gastrointestinal (despite prophylactic treatment), or grade 4 neutropenia, or febrile neutropenia, or grade 3/4 thrombocytopenia: reduce dose of oxaliplatin to 65 mg/m² and 5-fluorouracil by 20% (300 mg/m² bolus and 500 mg/m² 22-hr infusion). Delay next dose until neutrophils ≥1.5 × 10⁹/L and platelets ≥75 × 10⁹/L.Monitor and correct electrolytes before starting therapy and periodically during therapy.

Monitor IV site frequently. Extravasation may result in local pain and inflammation that may be severe and lead to necrosis. If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do not flush the line); remove needle/cannula; elevate extremity. Anti-inflammatory medication, such as high-dose oral dexamethasone, may reduce severity of the inflammatory reaction.
- Correct hypokalemia and hypermagnesemia before starting therapy.
- Premedicate patient with antiemetics with or without dexamethasone. Prehydration is not required.

IV Administration:

Reconstitution: Use only sterile water for injection or D5W to reconstitute powder.Concentration: To obtain final concentration of 5 mg/mL add 10 mL of diluent to 50-mg vial or 20 mL diluent to 100-mg vial. Gently swirl vial to dissolve powder. Diluent: Dilution with D5W (250 or 500 mL) is required prior to administration. Discard unused portion of vial. Solutions diluted in D5W are stable up to 6 hrs at room temperature or up to 24 hr under refrigeration. Solutions diluted for infusion do not require protection from light.
Intermittent Infusion: Protect concentrated solution from light; do not freeze. Diluent: Must be further diluted with 250–500 mL of D5W. Do not use 0.9% NaCl or any other chloride-containing solution for final solution. Do not use aluminum needles or administration sets containing aluminum parts; aluminum may cause degradation of platinum compounds. May be stored in refrigerator for 24 hr or 6 hr at room temperature. Diluted solution is not light-sensitive. Do not administer solutions that are discolored or contain particulate matter.Concentration: 0.2–0.6 mg/mL.
Rate: Administer oxaliplatin simultaneously with leucovorin in separate bags via Y-line over 120 min. Prolonging infusion time to 6 hr may decrease acute toxicities. Infusion times for fluorouracil and leucovorin do not need to change.

Explain purpose of oxaliplatin to patient. Advise patient to read Patient Information before starting therapy and periodically during therapy in case of changes.
Inform patients and caregivers of potential for peripheral neuropathy and potentiation by exposure to cold or cold objects. Advise patient to avoid cold drinks, use of ice in drinks or as ice packs, and to cover exposed skin prior to exposure to cold temperature or cold objects. Caution patients to cover themselves with a blanket during infusion, do not breathe deeply when exposed to cold air, wear warm clothing, and cover mouth and nose with a scarf or pull-down ski cap to warm the air that goes to their lungs, do not take things from the freezer or refrigerator without wearing gloves, drink fluids warm or at room temperature, always drink through a straw, do not use ice chips for nausea, be aware that most metals (car doors, mailbox) are cold; wear gloves to touch, do not run air conditioning at high levels in house or car, if hands get cold wash them with warm water. Advise health care professional of how you did since last treatment before next infusion.
Instruct patient to notify health care professional immediately if signs of reversible posterior leukoencephalopathy syndrome, low blood cell counts (fever, persistent diarrhea, infection) or if persistent vomiting, signs of dehydration, cough or breathing difficulty, thirst, dry mouth, dizziness, decreased urination, signs of infection (fever, temperature of ≥100.5° F, cough that brings up mucus, chills or shivering, burning or pain on urination, pain on swallowing, sore throat, redness or swelling at intravenous site) or signs of allergic reactions occur.
Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception during therapy and for at least 9 mo after final dose and to avoid breastfeeding during and for 3 mo after final dose. Advise males with female partners of reproductive potential to use effective contraception for 6 mo after final dose. May impair female and male fertility.

Decrease in size and spread of malignancies.

~~Eloxatin~~

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Assessment ⬆ ⬇

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US Brand Names ⬆