Professional Information
Oxaliplatin (Systemic)
VA CLASSIFICATION
Primary: AN900
Commonly used brand name(s): Eloxatin™.
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).
†Not commercially available in Canada.
Category:
Antineoplastic—
Indications
Accepted
Carcinoma, colorectal (treatment adjunct)—Oxaliplatin is indicated for use in combination with infusional 5-fluorouracil/leucovorin (5-FU/LV) as second-line treatment of metastatic colon or rectum carcinoma after the disease has recurred or progressed during or within 6 months of completion of first line therapy with the combination of bolus 5-FU/LV and irinotecan. {01}
Pharmacology/Pharmacokinetics
Physicochemical characteristics:
Molecular weight—
397.3 {01}
Solubility
Oxaliplatin is slightly soluble in water at 6 milligrams per milliliter, very slightly soluble in methanol, and practically insoluble in ethanol and acetone. {01}
Mechanism of action/Effect:
Oxaliplatin undergoes nonenzymatic conversion in physiologic solutions to active derivatives via displacement of the labile oxalate ligand. Several transient reactive species are formed, including monoaquo and diaquo diaminocyclohexane (DACH) platinum, which covalently bind with macromolecules. Both inter- and intra-strand Pt-DNA crosslinks are formed. Crosslinks are formed between the N7 positions of two adjacent guanines (GG), adjacent adenine-guanines (AG), and guanines separated by an intervening nucleotide (GNG). These crosslinks inhibit DNA replication and transcription. Cytotoxicity is cell-cycle nonspecific{01}
Other actions/effects:
In vivo studies have shown antitumor activity of oxaliplatin against colon carcinoma. In combination with 5-fluorouracil (5-FU), oxaliplatin exhibits in vitro and in vivo antiproliferative activity greater than either compound alone in several tumor models [HT29 (colon), GR (mammary), and L1210 (leukemia)]. {01}
Absorption:
Interpatient and intrapatient variability in ultrafilterable platinum exposure (AUC0-48) assessed over 3 cycles was moderate to low (23% to 6%, respectively). {01}
Note: AUC0-48hr of platinum in the plasma ultrafiltrate increases as renal function decreases. The AUC0-48hr of platinum in patients with mild (creatine clearance, CL cr 50 to 80 milliliters per minute), moderate (CL cr 30 to <50 milliliters per minute) and severe renal (CL cr <30 milliliters per minute) impairment is increased by about 60, 140 and 190%, respectively, compared to patients with normal renal function (CLcr >80 milliliters per minute).{01}
Distribution:
Volume of distribution (Vol D)—440 liters, following 2-hour intravenous infusion of oxaliplatin; approximately 15% of platinum is present in the systemic circulation; remaining 85% is rapidly distributed into tissues or eliminated in the urine.{01}
Protein binding:
Very high (greater than 90% ), plasma protein binding, primarily to albumin and gamma-globulins; binding is irreversible and accumulates (approximately 2-fold) in erythrocytes.{01}
Biotransformation:
Oxaliplatin undergoes rapid and extensive nonenzymatic biotransformation. The reactive oxaliplatin derivatives are present as a fraction of the unbound platinum in plasma ultrafiltrate. Up to 17 platinum containing derivatives have been observed in plasma ultrafiltrate including several cytotoxic species and a number of noncytotoxic conjugated species. There is no evidence of cytochrome P450-mediated metabolism in vitro. {01}
Half-life:
Following oxaliplatin administration the decline of ultrafilterable platinum levels is triphasic.{01}
Alpha phase (distribution)—0.43 hours {01}.
Beta phase (distribution)—16.8 hours {01}.
Lambda phase (terminal)—391 hours{01}.
Peak plasma concentration
Ultrafilterable platinum Cmaxwas 0.814 micrograms per milliliter following a single 2-hour intravenous infusion dose of 85 milligrams per square meter.{01}
Elimination:
Renal (after 5 days)—major route; approximately 54%.{01}
Fecal (after 5 days)—approximately 2%.{01}
Clearance— 10 to 17 liters per hour; similar to or exceeded the average human glomerular filtration rate (GFR; 7.5 liters per hour).
Note: Renal clearance of ultrafilterable platinum is significantly correlated with GFR.
{01}
Precautions to Consider
Cross-sensitivity and/or related problems
Contraindicated in patients with a history of known allergy to oxaliplatin or other platinum compounds. Allergic reactions can occur within minutes of administration. Drug related deaths associated with platinum compounds from this reaction have been reported.{01}
Carcinogenicity
Long-term animal studies have not been performed to evaluate the carcinogenic potential of oxaliplatin.{01}
Mutagenicity
Oxaliplatin was not mutagenic to bacteria (Ames test) but was mutagenic to mammalian cells in vitro (L5178Y mouse lymphoma assay). It was clastogenic both in vitro (chromosome aberration in human lymphocytes) and in vivo (mouse bone marrow micronucleus assay).{01}
Pregnancy/Reproduction
Fertility—
In dogs, testicular damage, characterized by degeneration, hypoplasia, and atrophy has been observed after administration of 0.75 mg per kg per day for 5 days every 28 days for three cycles (canine dose represents one-sixth the recommended human dose on a body surface area basis).{01}
Pregnancy—
Oxaliplatin may cause fetal harm when administered to a pregnant women. Women of child bearing potential should be advised to avoid becoming pregnant while receiving treatment with oxaliplatin. {01}
In rats, a dose of 2 mg per kg per day of oxaliplatin (less than one-seventh the recommended human dose based on body surface area) increased early resorptions, decreased live fetuses, decreased live births, delayed fetal growth and decreased fetal weight. When administered a dose of 1 mg per kg of body weight per day (less than one-tenth the human dose based on body surface area basis) during pre implantation or organogenesis, oxaliplatin caused increased early resorptions, decreased fetal weight and delayed ossification.{01}.
FDA Pregnancy Category D{01}
Breast-feeding
It is not known if oxaliplatin or its derivatives are excreted in human milk. However, due to the potential serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or delay the use of the drug, taking into account the importance of the drug to the mother.{01}
Pediatrics
No information is available on the relationship of age to the effects of oxaliplatin in the pediatric population. Safety and efficacy have not been established.{01}
Geriatrics
Appropriate studies on the relationship of age to the effects of oxaliplatin have been performed in the geriatric population. The rates of overall adverse events, were similar to different age groups. The incidence of diarrhea, dehydration, hypokalemia, and fatigue were higher in patients 65 years of age and older. No dose modifications are recommended.{01}
Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):
5-Fluorouracil (5-FU) (5-FU plasma concentrations are increased approximately 20% with concomitant oxaliplatin doses of 130 mg per m2 body surface area administered every 3 weeks. No pharmacokinetic interaction is seen with concomitant doses of 85 mg per m2 body surface area of oxaliplatin administered every 2 weeks. Concomitant administration also results in increased incidences of gastrointestinal and hematologic adverse events or neuropathies{01})
Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):
With physiologic/laboratory test values
Alanine aminotransferase (ALT [SGPT]) or
Aspartate aminotransferase (AST [SGOT]) or
Bilirubin (Altered values occured in ³ 5% of patients based on laboratory values and NCI CTC grade.{01})
» Serum creatinine (elevations in serum creatinine occurred in 10% of patients in clinical trials{01})
Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).
Except under special circumstances, this medication should not be used when the following medical problem exists:
» Hypersensitivity to oxaliplatin or other platinum compounds{01} (drug related deaths associated with platinum compounds from allergic reactions have been reported.)
Risk-benefit should be considered when the following medical problems exist
» Renal function impairment (use with caution; platinum is primarily eliminated renally)
Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):
» Laboratory testing such as:
Alanine aminotransferase (ALT [SGPT]) and
Aspartate aminotransferase (AST [SGOT]) and
Bilirubin and
Creatinine and
Hemoglobin and
Platelet and
White blood cell count with differential (standard monitoring is recommended before each oxaliplatin cycle; patients should be monitored for signs of low blood cell counts and should report fever, persistent diarrhea or evidence of infection.{01})
» Neuropathy and neurotoxicity testing (patients should be evaluated for neuropathy neurotoxicity prior to subsequent oxaliplatin therapy cycles{01})
» Pulmonary toxicity (patients should be monitored for unexplained respiratory symptoms such as nonproductive cough, dyspnea, crackles, or radiological pulmonary infiltrates; oxaliplatin should be discontinued until interstitial lung disease or pulmonary fibrosis can be excluded.{01})
Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Note: Concomitant administration with 5-Fluorouracil may alter the frequency of occurrence of the following side effects.
Those indicating need for medical attention
Incidence more frequent
Anemia{01} (pale skin; troubled breathing with exertion; unusual bleeding or bruising; unusual tiredness or weakness)
arthralgia{01} (pain in joints; muscle pain or stiffness; difficulty in moving)
chest pain
cough, persistent
dehydration (confusion; decreased urination; dizziness; dry mouth; fainting; increase in heart rate; lightheadedness; rapid breathing; sunken eyes; thirst; unusual tiredness or weakness; wrinkled skin)
dyspnea ( difficult breathing)
edema{01} (swelling)
hand-foot syndrome{01} (blistering, peeling, redness, and/or swelling of palms of hands or bottoms of feet; numbness, pain, tingling, or unusual sensations in palms of hands or bottoms of feet)
injection site reaction{01} (bleeding, blistering, burning, coldness, discoloration of skin; feeling of pressure; hives; infection; inflammation; itching; lumps; numbness; pain; rash; redness; scarring; soreness; stinging; swelling; tenderness; tingling; ulceration; warmth)
leukopenia or neutropenia{01} (black, tarry stools; chest pain; chills; cough; fever; painful or difficult urination; shortness of breath; sore throat; sores, ulcers, or white spots on lips or in mouth; swollen glands; unusual bleeding or bruising; unusual tiredness or weakness)
neuropathy{01} (abnormal tongue sensation; burning, prickling, itching, or tingling of skin; difficulty in articulating words; difficulty breathing; difficulty performing daily activities such as writing, buttoning, swallowing or walking; difficulty swallowing; eye pain; jaw spasm; numbness, decreased feeling, or pain in the hands, feet, around mouth, or throat; pressure in chest; sensation of pins and needles, stabbing pain)
stomatitis{01} (swelling or inflammation of the mouth)
thrombocytopenia{01} (black, tarry stools; bleeding gums; blood in urine or stools; pinpoint red spots on skin; unusual bleeding or bruising)
thromboembolism{01} (pain in chest, groin, or legs, especially the calves; difficulty breathing; severe, sudden headache; slurred speech; sudden, unexplained shortness of breath; sudden loss of coordination; sudden, severe weakness or numbness in arm or leg; vision changes)
{01}
Incidence less frequent
Allergic reaction{01} (cough; difficulty swallowing; dizziness; fast heartbeat; hives; itching; puffiness or swelling of the eyelids or around the eyes, face, lips or tongue; shortness of breath; skin rash; tightness in chest; unusual tiredness or weakness; wheezing)
hypokalemia{01} (convulsions; decreased urine; dry mouth; irregular heartbeat; increased thirst; loss of appetite; mood changes; muscle pain or cramps; nausea or vomiting; numbness or tingling in hands, feet, or lips; shortness of breath; unusual tiredness or weakness)
Incidence rare
pulmonary fibrosis{01} (fever; cough; shortness of breath)
{01}
Incidence not determined
—Observed during clinical; estimates of frequency can not be determined{01}
Anaphylactic shock{01} (cough; difficulty swallowing; dizziness; fast heartbeat; hives; itching; puffiness or swelling of the eyelids or around the eyes, face, lips or tongue; shortness of breath; skin rash; tightness in chest; unusual tiredness or weakness; wheezing)
angioedema{01} (large, hive-like swelling on face, eyelids, lips, tongue, throat, hands, legs, feet, sex organs )
cranial nerve palsies (weakness of the muscles in your face)
deafness{01}
Decreased visual acuity{01} ( decrease in vision)
diarrhea, severe{01}
dysarthria{01} (trouble in speaking; slurred speech; changes in patterns and rhythms of speech)
fasciculations (twitches of the muscle visible under the skin )
hemolytic uremic syndrome{01} (black, tarry, stools; stomach pain; blood in urine; fever; increased or decreased urination; pinpoint red spots on skin; swelling of face, fingers, feet, or lower legs; unusual bleeding or bruising; unusual tiredness or weakness; yellow eyes or skin)
ileus (abdominal pain; severe constipation; severe vomiting)
immuno-allergic thrombocytopenia{01} (black, tarry stools; bleeding gums; blood in urine or stools; pinpoint red spots on skin; unusual bleeding or bruising)
intestinal obstruction{01} (abdominal pain; severe constipation; nausea; vomiting)
Lhermittes' sign (an electric shock-like sensation that moves down the back and into the legs following a bending movement of the neck)
loss of deep tendon reflexes{01}
metabolic acidosis{01} (confusion; drowsiness; muscle tremors; nausea; rapid, deep breathing; restlessness; stomach cramps; unusual tiredness or weakness)
optic neuritis{01} (blindness; blue-yellow color blindness; blurred vision; decreased vision; eye pain)
pancreatitis{01} (bloating; chills; constipation; darkened urine; fast heartbeat; fever; indigestion; loss of appetite; nausea; pains in stomach, side, or abdomen, possibly radiating to the back; vomiting; yellow eyes or skin)
visual field disturbance{01} (blurred vision; decrease or change in vision)
Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
Abdominal pain{01}
anorexia{01} (loss of appetite; weight loss)
back pain{01}
constipation{01}
diarrhea{01}
dizziness{01}
dyspepsia{01} (acid or sour stomach; belching; heartburn; indigestion ; stomach discomfort, upset or pain)
fatigue{01} (unusual tiredness or weakness)
fever{01}
headache{01}
insomnia{01} ( sleeplessness; trouble sleeping; unable to sleep)
nausea{01}
rhinitis{01} (stuffy nose; runny nose; sneezing)
rigors{01} (feeling unusually cold shivering)
upper respiratory infection{01} ( ear congestion; nasal congestion; chills; cough; fever; sneezing, or sore throat; body aches or pain; headache; loss of voice; runny nose; unusual tiredness or weakness; difficulty in breathing)
vomiting{01}
{01}
Incidence less frequent
dysuria{01} (difficult or painful urination; burning while urinating)
epistaxis{01} (bloody nose)
flatulence{01} (bloated, full feeling; excess air or gas in stomach or intestines; passing gas)
flushing{01} (feeling of warmth; redness of the face, neck, arms and occasionally, upper chest)
gastroesophageal reflux{01} (heartburn; vomiting)
hiccup{01}
lacrimation, abnormal{01} (unusual tearing of eyes)
mucositis{01} (cracked lips; diarrhea; difficulty in swallowing; sores, ulcers, or white spots on lips, tongue, or inside mouth)
peripheral edema{01} (bloating or swelling of face, arms, hands, lower legs, or feet; rapid weight gain; tingling of hands or feet unusual; weight gain or loss)
pharyngitis{01} (body aches or pain; congestion; cough; dryness or soreness of throat; fever; hoarseness; runny nose; tender, swollen glands in neck; trouble in swallowing; voice changes )
rash{01}
taste perversion{01} (change in taste; bad, unusual or unpleasant (after) taste)
Those not indicating need for medical attention
Incidence less frequent
Alopecia{01} (hair loss; thinning of hair)
Overdose
For more information on the management of overdose or unintentional ingestion, contact a poison control center (see Poison Control Center Listing).
Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Chest pain
bradycardia (chest pain or discomfort; dizziness or fainting; lightheadedness; shortness of breath; slow or irregular heartbeat; unusual tiredness)
diarrhea
dyspnea (difficulty breathing)
dysesthesia (lack of sensation)
myelosuppression (black, tarry stools; blood in urine or stools; cough or hoarseness; difficult urination; fever or chills; lower back or side pain painful; pinpoint red spots on skin; unusual bleeding or bruising)
neurotoxicity ( agitation; coma; confusion; disorientation; dizziness; involuntary, rapid, rhythmic movement of the eyes; lack of coordination; lethargy; muscle twitching; paralysis; severe weakness; seizures; slurred speech; tremors)
paresthesia (burning, prickling, itching, or tingling of skin)
respiratory failure
thrombocytopenia (black, tarry stools; bleeding gums; blood in urine or stools; pinpoint red spots on skin; unusual bleeding or bruising)
vomiting, profuse
wheezing
{01}
Treatment of overdose
Specific treatment:
There is no known antidote for oxaliplatin{01}
See the package insert or Parenteral dosage forms, Oxaliplatin (Systemic) for specific dosing guidelines for use of this product.
Supportive care:
Inpatient supportive care should be given, including hydration, electrolyte support, and platelet transfusion{01}
Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric consultation.
Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Oxaliplatin (Systemic).
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):
Before using this medication
» Conditions affecting use, especially:
Hypersensitivity to oxaliplatin or other platinum compounds
Pregnancy—Use not recommended during pregnancy because it may cause fetal harm; advising woman of childbearing potential to avoid becoming pregnant while receiving treatment with oxaliplatin; apprising patient of potential hazard to the fetus; reporting suspected pregnancy to the physician immediately
Breast-feeding—Use of oxaliplatin has potential serious adverse reactions in nursing infants; decision should be made whether to discontinue nursing or delay the use of the drug, taking into account the importance of oxaliplatin to the mother
Use in the elderly—The incidence of some adverse effects are higher patients ³ 65. No dose modifications recommended.
Other medical problems, especially renal function impairment
Proper use of this medication
Frequency of severe nausea and vomiting; importance of continuing treatment regimen as directed by physician despite stomach upset
Monitoring patient for signs of neuropathy or pulmonary toxicity; performing standard laboratory monitoring.
» Proper dosing, especially dose modifications for neurotoxicity, gastrointestinal or hematologic toxicity.
Proper storage
Precautions while using this medication
» Importance of close monitoring by a qualified physician experienced in the use of cancer chemotherapeutic agents
» Avoiding immunizations unless approved by physician; other persons in patient's household should avoid immunizations with oral poliovirus vaccine; avoiding persons who have taken oral poliovirus vaccine or wearing a protective mask that covers nose and mouth
Caution if bone marrow depression occurs
» Avoiding exposure to persons with infections, especially during periods of low blood counts; checking with physician immediately if fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination occurs
» Checking with physician immediately if unusual bleeding or bruising; black, tarry stools; blood in urine or stools; or pinpoint red spots on skin occur
Caution in use of regular toothbrush, dental floss, or toothpick; physician, dentist, or nurse may suggest alternatives; checking with physician before having dental work done
Not touching eyes or inside of nose unless hands washed immediately before
Using caution to avoid accidental cuts with use of sharp objects such as safety razor or fingernail or toenail cutters
Avoiding contact sports or other situations where bruising or injury could occur
» Possibility of local tissue injury and scarring if infiltration of intravenous solution occurs; telling doctor or nurse right away about redness, pain, or swelling at injection site
Side/adverse effects
Importance of discussing expected side effects of oxaliplatin, especially its neurologic effects, with physician. Avoiding cold drinks, the use of ice, and covering skin before going out in cold temperatures to lessen neurologic effects.
Signs of potential side effects, especially anemia, arthralgia, chest pain, dehydration, dyspnea, edema, hand-foot syndrome, hypokalemia, injection site reaction, leukopenia, neutropenia, neuropathy, persistent cough, pulmonary fibrosis, stomatitis, thrombocytopenia, thromboembolism.
Signs of potential side effects observed during clinical practice, especially anaphylactic shock, angioedema, cranial nerve palsies, deafness, severe diarrhea, decreased visual acuity, dysarthria, fasciculations, hemolytic uremic syndrome, ileus, immuno-allergic, intestinal obstruction, Lhermittes' sign, loss of deep tendon reflexes, metabolic acidosis, optic neuritis, pancreatitis, or visual field disturbance.
General Dosing Information
Oxaliplatin should be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents. Appropriate management of therapy and complications is possible only when adequate diagnostic and treatment facilities are readily available. {01}
The administration of oxaliplatin dose not require prehydration. {01}
Premedication with antiemetics, including 5-HT3 blockers with or without dexamethasone, is recommended. {01}
Prolongation of infusion time for oxaliplatin from 2 hours to 6 hours decreases the Cmax by an estimated 32% and may mitigate acute toxicities. The infusion time for infusional 5-FU and leucovorin do not need to be changed. {01}
The oxaliplatin infusion line should be flushed with 5% dextrose injection prior to administration of any concomitant medication. {01}
Diet/Nutrition
The use of ice, cold drinks, cold objects and the exposure of skin to the cold should be avoided during the infusion of oxaliplatin because cold temperature can exacerbate acute neurological symptoms. {01}
Care should be exercised in the handling and preparation of infusion solutions prepared from oxaliplatin including: the use of gloves, washing the skin immediately and thoroughly with soap and water if a solution of oxaliplatin contacts the skin, and flushing the mucous membranes thoroughly with water if contact with oxaliplatin occurs. {01}
There is limited but increasing evidence and concern that personnel involved in preparation and administration of parenteral antineoplastics may be at some risk because of the potential mutagenicity, teratogenicity, and/or carcinogenicity of these agents, although the actual risk is unknown. USP advisory panels recommend cautious handling both in preparation and disposal of antineoplastic agents. Precautions that have been suggested include: • Use of a biological containment cabinet during reconstitution and dilution of parenteral medications and wearing of disposable surgical gloves and masks.
• Use of proper technique to prevent contamination of the medication, work area, and operator during transfer between containers (including proper training of personnel in this technique).
• Cautious and proper disposal of needles, syringes, vials, ampuls, and unused medication.
A number of medical centers have developed detailed guidelines for handling of antineoplastic agents.
Oxaliplatin is used as part of a treatment regimen that also includes 5-fluorouracil and leucovorin. As a result, incidence and/or severity of side effects may be altered by the use of 5-fluorouracil and leucovorin as part of the regimen. {01}
For treatment of adverse effects
In patients with anaphylactic-like reactions to oxaliplatin, the use of epinephrine, corticosteroids, and antihistamines have been employed to alleviate symptoms. {01}
For patients with persistent Grade 3 neurosensory events, discontinuing therapy should be considered. {01}
Parenteral Dosage Forms
OXALIPLATIN FOR INJECTION
Usual Adult Dose
Carcinoma, colorectal
The recommended dose schedule for oxaliplatin given every two weeks is as follows: • Day 1: Intravenous, 85 mg per m2 in 250 to 500 ml 5% dextrose and leucovorin 200 mg per m 22 in 5% dextrose both given over 120 minutes at the same time in separate bags using a Y-line, followed by 5-fluorouracil 400 mg per m2 IV bolus given over 2 to 4 minutes, followed by 5-fluorouracil 600 mg per m2 IV infusion in 500 ml 5% dextrose (recommended) as a 22-hour continuous infusion. {01}
• Day 2: Intravenous, leucovorin 200 mg per m 2 given over 120 minutes followed by 5-fluorouracil 400 mg per m2 IV bolus given over 2 to 4 minutes, followed by 5-fluorouracil 600 mg per m2 IV infusion in 500 ml 5% dextrose (recommended) as a 22-hour continuous infusion. {01}
For 5-fluorouracil dosing information, see Fluorouracil (Systemic) and for leucovorin dosing information, see Leucovorin (Systemic).
Note: For patients who experience persistent Grade 2 neurosensory events that do not resolve, a dose reduction of oxaliplatin to 65 mg per m 2 should be considered. The infusional 5-FU/LV part of the regimen does not need to be altered. {01}
For patients following recovery from grade 3/4 gastrointestinal (despite prophylactic treatment) or grade 3/4 hematologic toxicity (neutrophils < 1.5 x 109 per L, platelets < 100 x 109 per L), a dose reduction of oxaliplatin to 65 mg per m2 and infusional 5-FU by 20% (300 mg per m2 bolus and 500 mg per m 2 22 hour infusion) is recommended. {01}
Usual Pediatric Dose
Carcinoma, colorectal
Safety and efficacy have not been established{01}
Usual Geriatric Dose
See Usual adult dose.
Size(s) usually available:
U.S.—
50 mg single-use vial (sterile, preservative-free, lyophilized powder for reconstitution) (Rx) [Eloxatin™ ( lactose monohydrate)]{01}
100 mg single-use vial (sterile, preservative-free, lyophilized powder for reconstitution) (Rx) [Eloxatin™ ( lactose monohydrate)]{01}
Canada—
Not commercially available
Packaging and storage:
Store at 25°C (77°F), excursions permitted to 15 to 30°C (59 to 86°F), unless otherwise specified by manufacturer. Store under normal lighting conditions.{01}
Preparation of dosage form:
Note: Reconstitution or final dilution must never be performed with a sodium chloride solution or other chloride-containing solutions {01}
The oxaliplatin lyophilized powder is reconstituted by adding 10 mL (for the 50-mg vial) or 20 mL (for the 100-mg vial) of Water for Injection, USP or 5% Dextrose Injection, USP. Do not administer the reconstituted solution without further dilution. The reconstituted solution must be further diluted in an infustion solution of 250 to 500 mL of 5% Dextrose Injection, USP.{01} See the manufacturer's package insert for instructions.
Stability:
After reconstitution in the original vial, the solution may be stored up to 24 hours under refrigeration at 2 to 8°C (36 to 46°F). After final dilution with 250 to 500 mL of 5% dextrose injection, the shelf life is 6 hours at room temperature [20 to 25°C (68 to 77°F)] or up to 24 hours under refrigeration at 2 to 8°C (36 to 46°F). Oxaliplatin is not light sensitive. {01}
Incompatibilities:
Oxaliplatin is incompatible in solution with alkaline medications or media (such as basic solutions of 5-fluorouracil) and must not be mixed with these or administered simultaneously through the same infusion line. {01}
Not using needles or intravenous administration sets containing aluminum parts that may come in contact with oxaliplatin to prepare or mix the drug. Aluminum has been reported to cause degradation of platinum compounds. {01}
Auxiliary labeling:
• This product should be visually inspected for particulate matter prior to administration. Samples containing visible particulates should not be used.
• Caution: Chemotherapy. Handle and dispose of properly
Developed: 1/30/2003
References
- Product Information: Eloxatin™, oxaliplatin. Sanofi-Synthelabo, New York, NY, (PI revised 8/2002) reviewed 01/2003.
| Link to this page |  |
Printable Version |  |
Email Page |
