A-Z Drug Facts > Oxaliplatin

Oxaliplatin

Pronouncation: (ocks-AL-ih-pla-tin)
Class: Platinum coordination complex, Antineoplastic agent

Trade Names:
Eloxatin
- Injection 50 mg
- Injection 100 mg

Pharmacology

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The cytotoxic effect of oxaliplatin has been correlated with formation of inter- and intrastrand DNA crosslinks that inhibit DNA replication and transcription. Cytotoxicity is cell-cycle nonspecific.

Pharmacokinetics

Absorption

Following a 2-h infusion, C _max was 0.814 mcg/mL and Vd was 440 L.

Distribution

Following a 2‐h infusion, about 15% of administered platinum is present in the systemic circulation; the remaining 85% is rapidly distributed into tissues and eliminated in the urine. Plasma protein binding (albumin and gamma globulins) is irreversible and greater than 90%. Platinum also binds irreversibly and accumulates about 2‐fold in erythrocytes.

Metabolism

Rapid and extensive nonenzymatic biotransformation.

Elimination

Renal excretion is major route of platinum elimination (54% of platinum eliminated in urine; about 2% excreted in feces). Plasma Cl is 10 to 17 L/h and correlates with glomerular-filtration rate.

Special Populations

Renal Function Impairment

AUC of platinum increases as renal function decreases: 60% increase with mild (CrCl 50 to 80 mL/min), 140% increase with moderate (CrCl 30 to less than 50 mL/min), and 190% increase with severe (CrCl less than 30 mL/min) renal impairment.

Indications and Usage

Adjuvant treatment of stage ΙΙΙ colon cancer in combination with infusional 5‐fluorouracil/leucovorin in patients who have undergone complete resection of the primary tumor; in combination with infusional 5‐fluorouracil/leucovorin for the treatment of advanced carcinoma of the colon or rectum.

Unlabeled Uses

Treatment of relapsed non-Hodgkin lymphoma; treatment of advanced ovarian cancer.

Contraindications

Standard considerations.

Dosage and Administration

Adjuvant Therapy for Stage ΙΙΙ Colon Cancer
Adults

IV Recommended dose schedule given every 2 wk for 12 cycles (6 mo) according to the dose schedule for previously treated patients with advanced colorectal cancer.

Previously Untreated and Previously Treated Advanced Colorectal Cancer
Adults

IV Recommended dose schedule given every 2 wk: Day 1 : Oxaliplatin 85 mg/m ² IV infusion and leucovorin 200 mg/m ² IV infusion, both given over 120 min at the same time in separate bags using a Y‐line, followed by 5‐fluorouracil 400 mg/m ² IV bolus given over 2 to 4 min, followed by 5‐fluorouracil 600 mg/m ² IV infusion as a 22‐h continuous infusion. Day 2 : Leucovorin 200 mg/m ² IV infusion over 120 min, followed by 5‐fluorouracil 400 mg/m ² IV bolus given over 2 to 4 min, followed by 5‐fluorouracil 600 mg/m ² IV infusion as a 22‐h continuous infusion.

Dose modification

Prior to subsequent therapy cycles, evaluate patients for clinical toxicities and laboratory tests. Prolongation of infusion time for oxaliplatin from 2 to 6 h decreases C _max about 32% and may mitigate acute toxicities. The infusion times for infusional 5‐fluorouracil and leucovorin do not need to be changed.

Dose Modification Recommendations in Patients With Stage ΙΙΙ Colon Cancer
Adults

IV Reduce oxaliplatin dose to 75 mg/m ² in patients who experience persistent grade 2 neurosensory events that do not resolve. Discontinue oxaliplatin in patients who experience persistent grade 3 neurosensory events. The infusional 5‐fluorouracil/leucovorin regimen need not be altered. Reduce oxaliplatin dose to 75 mg/m ² and infusional 5‐fluorouracil to 300 mg/m ² bolus and 500 mg/m ² 22‐h infusion for patients after recovery from grade 3/4 GI, grade 4 neutropenia, or grade 3/4 thrombocytopenia. Delay next dose until neutrophils are 1,500/mm ³ or more and platelets are at least 75,000/mm ³ .

Dose Modification Recommendations in Previously Untreated and Previously Treated Patients With Advanced Colorectal Cancer
Adults

IV Reduce oxaliplatin dose to 65 mg/m ² in patients who experience persistent grade 2 neurosensory events that do not resolve. Discontinue oxaliplatin in patients who experience persistent grade 3 neurosensory events. The infusional 5‐fluorouracil/leucovorin regimen need not be altered. Reduce oxaliplatin dose to 65 mg/m ² and infusional 5‐fluorouracil to 300 mg/m ² bolus and 500 mg/m ² 22‐h infusion for patients after recovery from grade 3/4 GI or grade 4 neutropenia or grade 3/4 thrombocytopenia. Delay next dose until neutrophils are 1,500/mm ³ or greater and platelets are 75,000/mm ³ or greater.

General Advice

• For IV infusion only. Not for intradermal, subcutaneous, IM, IV bolus, or intra‐arterial administration.
• Follow institutional and National Institute of Health procedures for handling, administration, and disposal of anticancer drugs. Wear appropriate protective equipment when preparing and administering oxaliplatin.
• If oxaliplatin solution comes in contact with the skin, wash the skin immediately with soap and water. If oxaliplatin solution contacts a mucus membrane, flush thoroughly with water.
• Dilute prescribed dose of oxaliplatin in 250 to 500 mL 5% dextrose injection.
• Do not use needles or IV administration sets containing aluminum parts that could come in contact with oxaliplatin during preparation or administration. Aluminum can cause degradation of platinum compounds.
• Do not dilute with sodium chloride injection or other chloride‐containing solutions.
• Do not mix with alkaline medications or media (eg, basic solutions of 5‐fluorouracil), or administer simultaneously through same infusion line. Flush infusion line with D5W prior to administration of any concomitant medications.
• Do not administer if solution is discolored, cloudy, or contains particulate matter.
• Premedicate with antiemetics (eg, 5‐HT ₃ blockers with or without dexamethasone) as ordered.

Storage/Stability

Store vials at controlled room temperature (59° to 86°F). Do not freeze; protect from light (keep in original outer carton). Solution diluted in D5W is stable for up to 6 h at controlled room temperature (68° to 77°F) or up to 24 h under refrigeration (36° to 46°F). Protection from light is not required after final dilution.

Drug Interactions

Anticoagulants

Prolongation of PT and INR has been reported.

5‐Fluorouracil

Increased 5‐fluorouracil plasma concentrations may occur.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Thromboembolism (9%); chest pain (8%); thrombosis (6%); hypotension (5%); hypertension, tachycardia (2% to 5%).

CNS

Overall peripheral sensory neuropathy (92%); neuropathy (82%); paresthesias (77%); fatigue (70%); headache (17%); dizziness, insomnia (13%); depression (9%); anxiety (6%); dysphasia, neuralgia (5%); hot flashes, nervousness, somnolence, syncope, vertigo (2% to 5%); cranial nerve palsies, dysarthria, fasciculations, Lhermittes sign, loss of deep tendon reflexes (postmarketing).

Dermatologic

Alopecia (67%); skin disorder (32%); sweating (12%); rash (11%); flushing (10%); dry skin, pruritus (6%); pigmentation changes, purpura, urticaria (2% to 5%).

EENT

Pharyngolaryngeal dysesthesias (38%); epistaxis (16%); rhinitis (15%); conjunctivitis, pharyngitis, tearing (9%); abnormal lacrimation (7%); deafness, decreased visual acuity, optic neuritis, visual field disturbances (postmarketing).

GI

Nausea (83%); diarrhea (76%); vomiting (64%); stomatitis (42%); abdominal pain (39%); anorexia (35%); constipation (32%); dyspepsia, taste perversion (14%); flatulence (9%); mucositis (7%); dry mouth, gastroesophageal reflux, hiccups (5%); ascites, enlarged abdomen, gingivitis, hemorrhoids, intestinal obstruction, melena, rectal bleeding, rectal pain (2% to 5%); severe vomiting/diarrhea resulting in hypokalemia, colitis, ileus, intestinal obstruction, pancreatitis, perisinusoidal fibrosis (postmarketing).

Genitourinary

Dysuria, hematuria (6%); urinary frequency (5%); abnormal micturition frequency, catheter infection, urinary incontinence, vaginal hemorrhage (2% to 5%).

Hematologic-Lymphatic

Leukopenia (85%); anemia, neutropenia (81%); thrombocytopenia (77%); febrile neutropenia (12%); lymphopenia (6%); hemolytic uremic syndrome, immuno-allergic hemolytic anemia, immuno-allergic thrombocytopenia, prolongation of PT and INR in patients receiving anticoagulants (postmarketing).

Hepatic

Veno-occlusive disease of the liver (postmarketing).

Hypersensitivity

Allergic reactions (10%); anaphylactic shock, angioedema (postmarketing).

Lab Tests

Increased transaminases (57%); increased alkaline phosphatase (42%); bilirubinemia (20%); elevated creatine (5%).

Local

Injection-site reaction (11%).

Metabolic-Nutritional

Increased alkaline phosphate (42%); dehydration, hyperglycemia (14%); hypokalemia, weight loss (11%); weight increase (10%); hypoalbuminemia (9%); hyponatremia (8%); hypocalcemia (7%); metabolic acidosis (postmarketing).

Musculoskeletal

Back pain (19%); myalgia (14%); arthralgia (10%); rigors (9%); ataxia, bone pain, involuntary muscle contractions, muscle weakness (2% to 5%).

Respiratory

Cough (35%); dyspnea (19%); upper respiratory tract infection (10%); hemoptysis, hypoxia, pneumonia, pneumonitis (2% to 5%); interstitial lung disease, pulmonary fibrosis (postmarketing).

Miscellaneous

Fever (29%); infection (25%); edema, pain (15%); hand-foot syndrome (11%); peripheral edema (10%); sensory disturbance (8%); nail changes (2% to 5%).

Precautions

Warnings Administer only under supervision of qualified physician experienced in use of cancer chemotherapeutic agents. Appropriate management of therapy and complications is possible only when adequate diagnostic and treatment facilities are readily available. Anaphylactic-like reactions have been reported and may occur within minutes of administration.

Monitor Monitor WBC with differential, Hgb, platelet count, and blood chemistries (ALT, AST, bilirubin, and creatinine) before each cycle.

Pregnancy

Category D .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Renal Function

Use with caution in patients with renal function impairment.

Hepatotoxicity

Elevated transaminases and alkaline phosphatase occurs. Consider hepatic vascular disorders in case of abnormal LFT results or portal hypertension, which cannot be explained by liver metastases.

Neuropathy

May occur in patients previously untreated or previously treated with oxaliplatin.

Pulmonary toxicity

Pulmonary fibrosis, which may be fatal, may occur. Discontinue use in case of unexplained pulmonary symptoms (eg, crackles, dyspnea, nonproductive cough, pulmonary infiltrates) until further pulmonary investigation excludes interstitial lung disease or pulmonary fibrosis.

Overdosage

Symptoms

Chest pain, diarrhea, dysesthesia, dyspnea, laryngospasm, myelosuppression, nausea, neurotoxicity, paresthesia, profuse vomiting, respiratory failure, severe bradycardia, thrombocytopenia, wheezing.

Patient Information

• Explain name, action, potential benefits, and potential side effects of drug, particularly the neurologic effects, both the acute, reversible effects and the persistent neurosensory toxicity. Review the treatment regimen including dosing schedule, duration of treatment, and monitoring that will be required.
• Advise patient or caregiver to read patient information leaflet before starting therapy.
• Advise patient or caregiver that medication will be prepared and administered by health care professionals in a health care setting.
• Instruct patient to avoid cold drinks, use of ice, and to cover exposed skin prior to exposure to cold or cold objects.
• Instruct patient to immediately notify health care provider if any of the following occur: bleeding; chest pressure; chills, fever, or other signs of infection; difficulty breathing or unexplained shortness of breath; nonproductive cough; odd feelings in tongue; pain, tingling, burning, numbness in hands, feet, or around the mouth or throat; rash, hives, or any other sign of allergic reaction; severe or persistent diarrhea or vomiting; signs of dehydration; sores in mouth; trouble swallowing or saying words; unusual bruising.
• Advise patient or caregiver that hair loss is a common adverse reaction of therapy, but that this is usually reversible after therapy has been completed.
• Caution women of childbearing potential to avoid becoming pregnant during therapy.

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