Serious and fatal hypersensitivity adverse reactions, including anaphylaxis, can occur with oxaliplatin within minutes of administration and during any cycle. Oxaliplatin is contraindicated in patients with hypersensitivity reactions to oxaliplatin and other platinum-based drugs. Immediately and permanently discontinue oxaliplatin for hypersensitivity reactions and administer appropriate treatment for management of the hypersensitivity reaction.
Note: Oxaliplatin is associated with a moderate emetic potential and is known to cause delayed nausea and vomiting; antiemetics are recommended to prevent nausea and vomiting (Ref). Avoid oxaliplatin in patients with congenital long QT syndrome. Correct hypokalemia and hypomagnesemia prior to and during oxaliplatin treatment.
Biliary tract cancer, advanced (off-label use):
GEMOX regimen: IV: 100 mg/m2 on day 2 every 2 weeks (in combination with gemcitabine) until disease progression or unacceptable toxicity (Ref).
Modified GEMOX regimen: IV: 80 mg/m2 on days 1 and 8 every 3 weeks (in combination with gemcitabine) for up to 6 cycles (Ref).
CAPOX regimen: IV: 130 mg/m2 on day 1 every 3 weeks (in combination with capecitabine) until disease progression or unacceptable toxicity (Ref).
FOLFOX regimen: IV: 85 mg/m2 on day 1 every 2 weeks (in combination with fluorouracil and leucovorin) for up to 12 cycles (Ref) or until disease progression or unacceptable toxicity (Ref).
Chronic lymphocytic leukemia, fludarabine refractory (off-label use): OFAR regimen: IV: 25 mg/m2 on days 1 to 4 every 4 weeks (in combination with fludarabine, cytarabine, and rituximab) for up to 6 cycles (Ref).
Colorectal cancer, advanced: IV: 85 mg/m2 on day 1 every 2 weeks (in combination with infusional fluorouracil/leucovorin) until disease progression or unacceptable toxicity.
Colorectal cancer, advanced (off-label dosing/combinations):
FOLFOX regimens: IV: 85 mg/m2 on day 1 every 2 weeks (in combination with fluorouracil/leucovorin and bevacizumab) until disease progression or unacceptable toxicity (Ref) or 85 mg/m2 on day 1 every 2 weeks (in combination with fluorouracil/leucovorin and cetuximab) until disease progression or unacceptable toxicity (Ref) or 85 mg/m2 on day 1 every 2 weeks (in combination with fluorouracil/leucovorin and panitumumab) until disease progression or unacceptable toxicity (Ref).
FOLFOXIRI regimens: IV: 85 mg/m2 on day 1 every 2 weeks (in combination with fluorouracil/leucovorin/irinotecan) until disease progression or unacceptable toxicity (Ref) or 85 mg/m2 on day 1 every 2 weeks (in combination with fluorouracil/leucovorin/irinotecan and bevacizumab) for up to 12 cycles, followed by fluorouracil/leucovorin and bevacizumab maintenance (Ref).
CAPOX regimens: IV: 130 mg/m2 on day 1 every 3 weeks (in combination with capecitabine) until disease progression or unacceptable toxicity (Ref) or 130 mg/m2 on day 1 every 3 weeks in combination with capecitabine and bevacizumab until disease progression or unacceptable toxicity (Ref) or 130 mg/m2 on day 1 every 3 weeks (in combination with capecitabine and panitumumab) for at least 6 cycles or until disease progression or unacceptable toxicity (Ref).
Colon cancer, stage III, adjuvant therapy: IV: 85 mg/m2 on day 1 every 2 weeks (in combination with infusional fluorouracil/leucovorin) for up to 12 cycles.
Colon cancer, adjuvant therapy (off-label dosing/combinations):
FLOX regimen: IV: 85 mg/m2 on days 1, 15, and 29 of an 8-week treatment cycle (in combination with fluorouracil/leucovorin) for 3 cycles (Ref).
CAPOX regimen: IV: 130 mg/m2 on day 1 every 3 weeks (in combination with capecitabine) for 8 cycles (Ref).
Adjuvant therapy duration; completely resected stage III colon cancer (off label):
Low risk (T1, T2, or T3 and N1): A duration of therapy of 3 or 6 months of oxaliplatin (when used in combination with fluoropyrimidine-based therapy) may be offered (Ref). A pooled analysis of 6 phase III studies demonstrated non-inferiority (based on 3-year disease-free survival) with a 3-month (compared to a 6-month) adjuvant oxaliplatin-capecitabine (CAPOX) treatment duration in the subgroup of patients with T1, T2, or T3 and N1 stage III colon cancer (Ref).
High risk (T4 and/or N2): A duration of therapy of 6 months of oxaliplatin (when used in combination with fluoropyrimidine-based therapy) should be offered (Ref). In a pooled analysis of 6 phase III studies, superior disease-free survival has been demonstrated with 6 months (compared to 3 months) of adjuvant FOLFOX therapy in the subgroup of patients with T4 and/or N2 stage III colon cancer. Among patients treated with CAPOX, disease-free survival was similar between patients treated for 3 months compared to 6 months in the subgroup of patients with T4 and/or N2 stage III colon cancer, although statistical noninferiority was not proven (Ref).
Esophageal cancer (off-label use):
CAPOX regimen (advanced or metastatic esophageal or gastroesophageal junction adenocarcinoma): IV: 130 mg/m2 on day 1 every 3 weeks (in combination with capecitabine and nivolumab) until disease progression or unacceptable toxicity (Ref).
FLOT regimen (advanced, resectable gastroesophageal junction adenocarcinoma): IV: 85 mg/m2 on day 1 every 2 weeks (in combination with fluorouracil, leucovorin, and docetaxel) for 4 preoperative and 4 postoperative cycles (Ref).
FOLFOX4 regimen (chemoradiotherapy for locally advanced, recurrent, or metastatic disease ): IV: 85 mg/m2 on day 1 every 2 weeks, in combination with fluorouracil and leucovorin and radiation for 3 cycles, then without radiation for 3 more cycles (Ref).
mFOLFOX regimen (advanced or metastatic esophageal or gastroesophageal junction adenocarcinoma): IV: 85 mg/m2 on day 1 every 2 weeks (in combination with fluorouracil, leucovorin, and nivolumab) until disease progression or unacceptable toxicity (Ref).
FLOT regimen (locally advanced, recurrent, or metastatic disease): IV: 85 mg/m2 on day 1 every 2 weeks (in combination with fluorouracil, leucovorin, and docetaxel) for up to 8 cycles (Ref).
Dose optimization for advanced, palliative treatment in frail and/or elderly patients: A dose optimization study that examined 60%, 80%, or 100% of a 130 mg/m2 dose once every 21 days (in combination with capecitabine) found that the 60% dose was not inferior (for progression-free survival) and had less toxicity compared to the full dose (Ref).
Treatment of advanced or metastatic disease: Treatment with doublet, rather than triplet, chemotherapy may be preferred in the palliative setting due to increased toxicity (without clear benefit) with triplet regimens (Ref).
Gastric cancer (off-label use):
Adjuvant therapy: IV: 130 mg/m2 on day 1 every 3 weeks (in combination with capecitabine) for 8 cycles following D2 gastrectomy in patients who did not receive preoperative therapy (Ref).
CAPOX regimen (locally advanced, unresectable disease, or advanced or metastatic disease): IV: 130 mg/m2 on day 1 every 3 weeks (in combination with capecitabine, pembrolizumab, and trastuzumab for HER2-positive gastric or gastroesophageal adenocarcinoma) until disease progression or unacceptable toxicity or (in patients without disease progression) for up to 24 months (Ref) or 130 mg/m2 on day 1 every 3 weeks (in combination with capecitabine and nivolumab) until disease progression or unacceptable toxicity (Ref).
FLOT regimen (locally advanced, resectable disease): IV: 85 mg/m2 on day 1 every 2 weeks (in combination with fluorouracil, leucovorin, and docetaxel) for 4 preoperative and 4 postoperative cycles (Ref).
mFOLFOX regimen (advanced or metastatic disease): IV: 85 mg/m2 on day 1 every 2 weeks (in combination with fluorouracil, leucovorin, and nivolumab) until disease progression or unacceptable toxicity (Ref).
FLOT regimen (locally advanced, recurrent, or metastatic disease ): IV: 85 mg/m2 on day 1 every 2 weeks (in combination with fluorouracil, leucovorin, and docetaxel) for up to 8 cycles (Ref).
Dose optimization for advanced, palliative treatment in frail and/or elderly patients: A dose optimization study that examined 60%, 80%, or 100% of a 130 mg/m2 dose once every 21 days (in combination with capecitabine) found that the 60% dose was not inferior (for progression-free survival) and had less toxicity compared to the full dose (Ref).
Treatment of advanced or metastatic disease: Treatment with doublet, rather than triplet, chemotherapy is preferred in the palliative setting due to increased toxicity (without clear benefit) with triplet regimens (Ref).
Neuroendocrine tumors: GI/carcinoid, refractory (off-label use): IV: 130 mg/m2 on day 1 every 3 weeks (in combination with capecitabine) for up to 6 cycles (Ref).
Non-Hodgkin lymphomas, relapsed/refractory (off-label use): IV: 100 mg/m2 on day 1 every 3 weeks (in combination with gemcitabine and rituximab) (Ref).
Ovarian cancer, advanced (off-label use): IV: 130 mg/m2 once every 3 weeks (as a single agent) until disease progression or unacceptable toxicity (Ref).
Pancreatic cancer, advanced or metastatic (off-label use):
FOLFIRINOX regimen: IV: 85 mg/m2 every 2 weeks (in combination with fluorouracil, leucovorin, and irinotecan) for up to 6 months (Ref).
FOLFOX regimen (second-line therapy): IV: 85 mg/m2 on day 1 every 2 weeks (in combination with fluorouracil and leucovorin) until disease progression or unacceptable toxicity (Ref).
OFF regimen (second-line therapy): IV: 85 mg/m2 on days 8 and 22 every 6 weeks (in combination with fluorouracil and leucovorin) until disease progression or unacceptable toxicity (Ref).
CAPOX regimen: IV: 110 to 130 mg/m2 on day 1 every 3 weeks (in combination with capecitabine) until disease progression or unacceptable toxicity (Ref).
Pancreatic cancer, potentially curable, adjuvant therapy (off-label use): Note: American Society of Clinical Oncology (ASCO) guidelines recommend 6 months of adjuvant therapy if recovery is complete; if preoperative chemotherapy therapy was received, a total of 6 months of adjuvant therapy (including the preoperative regimen) is recommended (Ref).
mFOLFIRINOX regimen: IV: 85 mg/m2 every 2 weeks (in combination with fluorouracil, leucovorin, and irinotecan; modified FOLFIRINOX regimen) for 24 weeks (Ref). According to ASCO guidelines, mFOLFIRINOX is the preferred first-line adjuvant regimen for potentially curable disease (Ref).
Small bowel adenocarcinoma, advanced unresectable or metastatic (off-label use): Note: Ampullary adenocarcinomas were excluded from some studies (Ref).
CAPOX regimen: IV: 130 mg/m2 on day 1 every 3 weeks (in combination with capecitabine) until disease progression or unacceptable toxicity (Ref).
mFOLFOX or FOLFOX regimen: IV: 85 mg/m2 on day 1 every 2 weeks (in combination with fluorouracil and leucovorin) until disease progression or unacceptable toxicity (Ref).
Unknown primary cancer, recurrent or refractory (off-label use): IV: 130 mg/m2 on day 1 of a 21-day cycle (in combination with capecitabine) for 6 cycles or may continue until clinical benefit no longer realized (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS; Kenar D. Jhaveri , MD.
Note: CrCl may be calculated using the Cockroft-Gault equation (Ref).
Altered kidney function: IV:
CrCl ≥30 mL/minute: No dosage adjustment necessary (Ref).
CrCl 20 to <30 mL/minute: Administer 75% to 100% of the usual indication-specific dose (Ref). For example, the manufacturer’s labeling suggests reducing the dose from 85 to 65 mg/m2 in patients with colorectal cancer. Alternatively, the increased exposure to oxaliplatin has not been associated with increased drug-related toxicity in patients with CrCl >20 mL/minute; therefore, administration of 100% of the usual indication-specific dose may also be considered (Ref).
CrCl <20 mL/minute: Administer 75% of the usual indication-specific dose (Ref). For example, the manufacturer's labeling suggests reducing the dose from 85 to 65 mg/m2 in patients with colorectal cancer.
Hemodialysis, intermittent (thrice weekly): Partially dialyzable (56% of free platinum (Ref)):
IV: Avoid use when possible due to limited data. Multiple case reports have described various dosing and timing strategies (Ref). If necessary, a reasonable approach would be to begin with 75% of the usual recommended dose and make subsequent adjustments based on efficacy and toxicity (Ref). Can consider dialyzing after the infusion to decrease risk of toxicity; allow the infusion to be completed at least 1.5 to 2 hours before dialysis to allow for oxaliplatin to distribute into the tissue (Ref).
Peritoneal dialysis: Dialyzability unknown:
IV: Avoid use when possible due to lack of data (has not been studied). If necessary, dose as for patients with CrCl <20 mL/minute. If patient has significant residual kidney function, then dosing should be individualized (Ref).
CRRT:
Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) and minimal residual kidney function unless otherwise noted. Appropriate dosing requires consideration of adequate drug concentrations. Close monitoring of response and adverse reactions (eg, neurotoxicity) due to drug accumulation is important.
IV: There are no data available in patients on CRRT (has not been studied). If necessary, administer 100% of the usual indication-specific dose (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration):
Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Appropriate dosing requires consideration of adequate drug concentrations. Close monitoring of response and adverse reactions (eg, neurotoxicity) due to drug accumulation is important.
IV: There are no data available in patients on PIRRT (has not been studied). If necessary, administer 100% of the usual indication-specific dose. Can consider dialyzing after the infusion to decrease risk of toxicity; allow the infusion to be completed at least 1.5 to 2 hours before dialysis to allow for oxaliplatin to distribute into the tissue (Ref).
Hepatic impairment prior to treatment initiation :
Mild, moderate, or severe impairment: No dosage adjustment necessary (Ref).
Hepatotoxicity during treatment:
Portal hypertension or increased LFTs that cannot be explained by liver metastases: Consider evaluating for hepatic vascular disorders.
American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2: Utilize patient's actual body weight for calculation of BSA- or weight-based dosing; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m2; if a dose reduction is utilized due to toxicity, may consider resumption of full, weight-based dosing (or previously tolerated dose level) with subsequent cycles only if dose escalations are allowed in the prescribing information, if contributing underlying factors (eg, hepatic or kidney impairment) are sufficiently resolved, AND if performance status has markedly improved or is considered adequate (Ref).
Note: Dose reduction recommendations in the following tables are considered applicable to patients with CrCl ≥30 mL/minute. For patients with CrCl <30 mL/minute or on renal replacement therapy, further dose reductions may be necessary for patients experiencing oxaliplatin-associated toxicities; dose should be individualized.
Adverse reaction |
Severity |
Oxaliplatin dose modification |
---|---|---|
a Avoid mucositis prophylaxis with ice chips, exposure to cold temperatures, or consumption of cold food/beverages during or within hours after oxaliplatin infusion (may exacerbate symptoms). | ||
GI toxicity |
Grades 3 or 4 |
After recovery, reduce oxaliplatin dose to 75 mg/m2 (also reduce fluorouracil doses). |
Hematologic toxicity |
Grade 4 neutropenia or neutropenic fever |
Delay next dose until neutrophils recover to ≥1,500/mm3, then reduce oxaliplatin dose to 75 mg/m2. |
Grade 3 or 4 thrombocytopenia |
Delay next dose until platelets recover to ≥75,000/mm3, then reduce oxaliplatin dose to 75 mg/m2. | |
Peripheral sensory neuropathya |
Persistent grade 2 |
Consider reducing oxaliplatin dose to 75 mg/m2. |
Persistent grade 3 |
Consider discontinuing oxaliplatin. | |
Grade 4 |
Discontinue oxaliplatin. |
Adverse reaction |
Severity |
Oxaliplatin dose modification |
---|---|---|
a Avoid mucositis prophylaxis with ice chips, exposure to cold temperatures, or consumption of cold food/beverages during or within hours after oxaliplatin infusion (may exacerbate symptoms). | ||
GI toxicity |
Grades 3 or 4 |
After recovery, reduce oxaliplatin dose to 65 mg/m2 (also reduce fluorouracil doses). |
Hematologic toxicity |
Grade 4 neutropenia or neutropenic fever |
Delay next dose until neutrophils recover to ≥1,500/mm3, then reduce oxaliplatin dose to 65 mg/m2. |
Grade 3 or 4 thrombocytopenia |
Delay next dose until platelets recover to ≥75,000/mm3, then reduce oxaliplatin dose to 65 mg/m2. | |
Neuropathya |
Persistent grade 2 |
Consider reducing oxaliplatin dose to 65 mg/m2. |
Persistent grade 3 |
Consider discontinuing oxaliplatin. | |
Grade 4 |
Discontinue oxaliplatin. |
Adverse reaction |
Oxaliplatin dose modification |
---|---|
Acute toxicities (including non–life-threatening infusion reaction) |
Longer infusion time (increasing infusion duration from 2 hours to 6 hours) may mitigate acute toxicities. |
Hypersensitivity |
Immediately and permanently discontinue oxaliplatin (and administer appropriate management for hypersensitivity). Oxygen and bronchodilators have also been used for hypersensitivity management (Kim 2009). |
Immune-mediated thrombocytopenia |
Consider discontinuing oxaliplatin. |
Posterior reversible encephalopathy syndrome |
Permanently discontinue oxaliplatin. |
Pulmonary symptoms (unexplained pulmonary symptoms such as crackles, dyspnea, nonproductive cough, pulmonary infiltrates) |
Withhold oxaliplatin until interstitial lung disease or pulmonary fibrosis are excluded. |
Pulmonary toxicity (confirmed interstitial lung disease or pulmonary fibrosis) |
Permanently discontinue oxaliplatin. |
Rhabdomyolysis (signs or symptoms) |
Permanently discontinue oxaliplatin. |
Sepsis or septic shock |
Withhold oxaliplatin treatment. |
No dosage adjustment necessary. Refer to adult dosing.
(For additional information see "Oxaliplatin: Pediatric drug information")
Refer to individual protocols; details concerning dosing in combination regimens should also be consulted. Oxaliplatin is associated with moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (Ref).
Solid tumors, relapsed/refractory: Limited data available; several regimens reported; efficacy results highly variable; has shown limited activity in pediatric patients (primarily some delayed tumor progression reported) and an acceptable safety profile; should not be used first-line; reserved for refractory cases; patients should be hydrated prior to and during administration (eg, 3 L/m2/day) (Ref).
Lam 2015; McGregor 2009: Children and Adolescents: IV: 130 mg/m2 over 2 hours on day 1 in combination with etoposide with/without ifosfamide every 21 days.
Geoerger 2011; Macy 2013: Children and Adolescents: IV: 100 mg/m2 over 2 hours on day 1 of a 14-day cycle in combination with gemcitabine or fluorouracil/leucovorin.
Hartmann 2011: Children and Adolescents: IV: 85 mg/m2 over 2 hours on day 1 in combination with irinotecan (day 1) and gemcitabine (day 1 and 8).
Neuroblastoma, relapsed or refractory: Limited data available; efficacy results highly variable; should not be used first-line; reserved for refractory case. Children ≥2 years and Adolescents: IV: 105 mg/m2 on day 1 in combination with doxorubicin on a 21-day cycle (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing adjustments for toxicity: The presented dosing adjustments are based on experience in adult patients. Refer to specific protocol management in pediatric patients if available.
Adult:
Acute toxicities: Longer infusion time (6 hours) may mitigate acute toxicities (eg, pharyngolaryngeal dysesthesia).
Neurosensory events:
Persistent (>7 days) grade 2 neurosensory events:
Adjuvant treatment of stage III colon cancer: Reduce dose to 75 mg/m2.
Advanced colorectal cancer: Reduce dose to 65 mg/m2.
Consider withholding oxaliplatin for grade 2 neuropathy lasting >7 days despite dose reduction.
Persistent (>7 days) grade 3 neurosensory events: Consider discontinuing oxaliplatin.
Gastrointestinal toxicity (grade 3/4) occurring despite prophylactic treatment:
Adjuvant treatment of stage III colon cancer: Delay next dose until recovery from toxicity, then reduce dose to 75 mg/m2.
Advanced colorectal cancer: Delay next dose until recovery from toxicity, then reduce dose to 65 mg/m2.
Hematologic toxicity (grade 4 neutropenia, febrile neutropenia, or grade 3/4 thrombocytopenia):
Adjuvant treatment of stage III colon cancer: Delay next dose until neutrophils recover to ≥1,500/mm3 and platelets recover to ≥75,000/mm3, then reduce dose to 75 mg/m2.
Advanced colorectal cancer: Delay next dose until neutrophils recover to ≥1,500/mm3 and platelets recover to ≥75,000/mm3, then reduce dose to 65 mg/m2.
Pulmonary toxicity (unexplained respiratory symptoms, including nonproductive cough, dyspnea, crackles, pulmonary infiltrates): Discontinue until interstitial lung disease or pulmonary fibrosis have been excluded.
Rhabdomyolysis: Discontinue for signs/symptoms of rhabdomyolysis.
Sepsis or septic shock: Withhold treatment.
There are no pediatric specific recommendations; refer to individual protocols; based on experience in adult patients, dosing adjustment suggested.
There are no pediatric specific recommendations; refer to individual protocols; based on experience in adult patients, some have suggested that dosage adjustment is not necessary (Ref).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Percentages reported with monotherapy.
>10%:
Gastrointestinal: Abdominal pain (31%), anorexia (20%), constipation (31%), diarrhea (46%; grades 3/4: 4%), nausea (64%; grades 3/4: 4%), stomatitis (2% to 14%), vomiting (37%; grades 3/4: 4%)
Hematologic & oncologic: Anemia (64%; grades 3/4: 1%), leukopenia (13%), thrombocytopenia (30%; grades 3/4: 3%)
Hepatic: Increased serum alanine aminotransferase (36%), increased serum alkaline phosphatase (42%), increased serum aspartate aminotransferase (54%), increased serum bilirubin (13%)
Nervous system: Fatigue (61%), headache (13%), insomnia (11%), pain (14%), peripheral neuropathy (76%, grades 3/4: 7%; acute: 65%, grades 3/4: 5%; delayed [persistent]: 43%, grades 3/4: 3%)
Neuromuscular & skeletal: Back pain (11%)
Respiratory: Cough (11%), dyspnea (13%)
Miscellaneous: Fever (25%)
1% to 10%:
Cardiovascular: Chest pain (5%), edema (10%), flushing (3%), peripheral edema (5%), thromboembolism (2%)
Dermatologic: Alopecia (3%), palmar-plantar erythrodysesthesia (1%), skin rash (5%)
Endocrine & metabolic: Dehydration (5%), hypokalemia (3%)
Gastrointestinal: Dysgeusia (5%), dyspepsia (7%), flatulence (3%), gastroesophageal reflux disease (1%), hiccups (2%)
Genitourinary: Dysuria (1%)
Hematologic & oncologic: Neutropenia (7%)
Hypersensitivity: Hypersensitivity reaction (3%; including anaphylaxis, nonimmune anaphylaxis)
Local: Injection-site reaction (9%, including erythema at injection site, pain at injection site, swelling at injection site)
Nervous system: Dizziness (7%), rigors (9%)
Neuromuscular & skeletal: Arthralgia (7%)
Ophthalmic: Abnormal lacrimation (1%)
Renal: Increased serum creatinine (5% to 10%)
Respiratory: Epistaxis (2%), pharyngitis (2%), pharyngolaryngeal dysesthesia (grades 3/4: 1% to 2%), rhinitis (6%), upper respiratory tract infection (7%)
<1%:
Nervous system: Reversible posterior leukoencephalopathy syndrome
Respiratory: Pulmonary fibrosis
Frequency not defined:
Gastrointestinal: Dysphagia, gastrointestinal hemorrhage
Genitourinary: Hematuria
Hematologic & oncologic: Hemorrhage
Postmarketing:
Cardiovascular: Bradycardia, prolonged QT interval on ECG (Hancox 2016), septic shock, torsades de pointes (Hancox 2016), ventricular arrhythmia
Endocrine & metabolic: Lactic acidosis (Smith 2019), metabolic acidosis
Gastrointestinal: Colitis (including Clostridioides difficile-associated diarrhea), esophagitis, intestinal obstruction, pancreatitis
Hematologic & oncologic: Hemolytic anemia (immuno-allergic; including Evan syndrome [Earle 2001]), hemolytic-uremic syndrome (Saad 2022), immune thrombocytopenia (Woo 2015), leukemia (Carneiro 2006), thrombotic microangiopathy (Saad 2022)
Hepatic: Hepatic fibrosis (Kang 2013), hepatic focal nodular hyperplasia, hepatic sinusoidal obstruction syndrome (veno-occlusive disease of liver) (Seo 2014)
Hypersensitivity: Anaphylactic shock, angioedema, hypersensitivity angiitis (Quack 2013)
Infection: Neutropenic sepsis, sepsis
Nervous system: Cranial nerve palsy, decreased deep tendon reflex, dysarthria, Lhermitte sign (Okamoto 2020), seizure
Neuromuscular & skeletal: Fasciculations, laryngospasm, rhabdomyolysis (Pissarra 2019)
Ophthalmic: Decreased visual acuity (Mesquida 2010), optic neuritis, temporary vision loss (Ah-Thiane 2021), visual field loss (Mesquida 2010)
Otic: Deafness, hearing loss (can be irreversible) (Kim 2020; Oh 2013)
Renal: Acute interstitial nephritis (Yamada 2019), acute kidney injury (Yamada 2019), renal tubular necrosis (Jain 2015)
Respiratory: Interstitial lung disease (including exacerbation of preexisting interstitial lung disease) (Ryu 2011; Wilcox 2008), pneumonia (including interstitial pneumonia [Taooka 2021])
Hypersensitivity to oxaliplatin, other platinum-containing compounds, or any component of the formulation.
Canadian labeling: Additional contraindications (not in the US labeling): Preexisting peripheral sensitive neuropathy with functional impairment; pregnancy; breastfeeding; severe renal impairment (CrCl <30 mL/minute).
Concerns related to adverse effects:
• Bone marrow suppression: Grade 3 and 4 neutropenia occurs commonly with oxaliplatin in combination with fluorouracil and leucovorin; sepsis, neutropenic sepsis, and septic shock have been reported with oxaliplatin (some fatal). Grade 3 and 4 thrombocytopenia has also occurred.
• Cardiotoxicity: QT prolongation and ventricular arrhythmias, including fatal torsades de pointes, have been reported with oxaliplatin.
• Extravasation: Oxaliplatin is an irritant with vesicant-like properties; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation.
• Hemorrhage: GI bleeding, hematuria, and epistaxis have been reported with oxaliplatin; there have been case reports of death due to intracerebral hemorrhage. Prolonged PT and INR occasionally associated with hemorrhage have been reported in patients also receiving anticoagulants while on oxaliplatin. Thrombocytopenia and immune-mediated thrombocytopenia have been observed with oxaliplatin; immune-mediated thrombocytopenia has been associated with a rapid thrombocytopenia onset along with a greater risk of bleeding.
• Hepatotoxicity: Elevated transaminases and alkaline phosphatase have occurred with oxaliplatin. Liver biopsy has revealed peliosis, nodular regenerative hyperplasia or sinusoidal alterations, perisinusoidal fibrosis, and veno-occlusive lesions. Consider evaluating for hepatic vascular disorders in patients who develop portal hypertension or increased LFTs that cannot be explained by liver metastases.
• Hypersensitivity: Serious and fatal hypersensitivity reactions (including anaphylaxis) may occur within minutes of oxaliplatin administration and during any cycle. Grade 3 or 4 hypersensitivity has been observed (rare). Allergic reactions are similar to reactions reported with other platinum analogs and may occur with any cycle. Reactions typically occur after multiple cycles; in retrospective reviews, reaction occurred at a median of 7 to 9 cycles, with an onset of 5 to 70 minutes (Kim 2009; Polyzos 2009). Symptoms may include bronchospasm (rare), erythema, hypotension (rare), pruritus, rash, and/or urticaria; previously untreated patients have also experienced flushing, diaphoresis, diarrhea, shortness of breath, chest pain, hypotension, syncope, and disorientation. According to the manufacturer, rechallenge is contraindicated (deaths due to anaphylaxis have been associated with platinum derivatives). In patients rechallenged after mild hypersensitivity, reaction recurred at a higher level of severity; for patients with severe hypersensitivity, rechallenge (with 2 to 3 days of antihistamine and corticosteroid premedication, and prolongation of infusion time) allowed for 2 to 4 additional oxaliplatin cycles; however, rechallenge was not feasible in nearly two-thirds of patients due to the severity of the initial reaction (Polyzos 2009).
• Neuropathy: Two types of peripheral sensory neuropathy may occur: The first type of neuropathy is an acute presentation (within hours to 2 days), reversible (resolves within 14 days), with primarily peripheral symptoms that are often exacerbated by cold. Symptoms may include transient paresthesia, dysesthesia, and hypoesthesia in the hands, feet, perioral area, or throat; jaw spasm, abnormal tongue sensation, pharyngolaryngeal dysesthesia, dysarthria, eye pain, and a feeling of chest pressure have also been observed. Avoid mucositis prophylaxis with ice chips, exposure to cold temperatures, or consumption of cold food/beverages during or within hours after oxaliplatin infusion (may exacerbate symptoms). Acute neuropathy commonly recurs with subsequent doses. Cold-triggered neuropathy may last up to 7 days after oxaliplatin administration (Grothey 2011). The second type of neuropathy is a more persistent (>14 days) presentation that usually is characterized by paresthesia, dysesthesias, and hypoesthesias and may interfere with daily activities (eg, writing, buttoning, swallowing, difficulty walking). These symptoms may improve in some patients upon discontinuing treatment. In a retrospective evaluation of patients treated with oxaliplatin for colorectal cancer, the incidence of peripheral sensory neuropathy was similar between diabetic and nondiabetic patients (Ramanathan 2010). Several retrospective studies (as well as a small, underpowered randomized trial) have suggested calcium and magnesium infusions before and after oxaliplatin administration may reduce incidence of cumulative sensory neuropathy; however, a randomized, placebo-controlled, double-blind study in patients with colorectal cancer suggests there is no benefit of calcium and magnesium in preventing sensory neuropathy or in decreasing oxaliplatin discontinuation rates (Loprinzi 2014).
• Posterior reversible encephalopathy syndrome: Cases of posterior reversible encephalopathy syndrome have been reported (rare). Signs/symptoms include headache, mental status changes, seizure, blurred vision, blindness, and/or other vision changes; may be associated with hypertension.
• Pulmonary toxicity: Oxaliplatin is associated with pulmonary fibrosis (rare), which may be fatal. Pulmonary toxicity may present with dyspnea, cough, and/or hypoxia; grade 3 and 4 events have occurred. Eosinophilic pneumonia has been reported rarely.
• Rhabdomyolysis: Rhabdomyolysis (including fatal cases) has been reported with oxaliplatin.
Special populations:
• Older adult: Patients ≥65 years of age experienced a higher incidence of diarrhea and grade 3 or 4 neutropenia and may be more susceptible to dehydration, hypokalemia, leukopenia, fatigue, and syncope.
Other warnings/precautions:
• Administration: Oxaliplatin is for IV administration. Administration via the intraperitoneal route (not an approved administration route) is associated with peritoneal hemorrhage and hemorrhagic complications (Charrier 2016).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Generic: 50 mg/10 mL (10 mL); 100 mg/20 mL (20 mL)
Solution, Intravenous [preservative free]:
Generic: 50 mg/10 mL (10 mL); 100 mg/20 mL (20 mL); 200 mg/40 mL (40 mL)
Solution Reconstituted, Intravenous [preservative free]:
Generic: 50 mg (1 ea); 100 mg (1 ea)
Yes
Solution (Oxaliplatin Intravenous)
50 mg/10 mL (per mL): $0.86 - $21.22
100 mg/20 mL (per mL): $0.74 - $21.22
200 mg/40 mL (per mL): $6.00
Solution (reconstituted) (Oxaliplatin Intravenous)
50 mg (per each): $120.00 - $1,162.55
100 mg (per each): $240.00 - $2,325.15
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Generic: 5 mg/mL (10 mL, 20 mL, 30 mL, 40 mL)
IV: Administer as IV infusion over 2 hours; extend infusion time to 6 hours for acute toxicities.
Off-label rate: A fixed infusion rate of 1 mg/m2/minute (eg, an 85 mg/m2 dose infused over 85 minutes) has been used and did not show a statistically significant difference in the rate of hypersensitivity reactions (Ref).
Flush infusion line with D5W prior to administration of any concomitant medication. Avoid mucositis prophylaxis with ice chips, exposure to cold temperatures, or consumption of cold food/beverages during or within hours after oxaliplatin infusion (may exacerbate acute neurological symptoms). Do not use needles or administration sets containing aluminum. When used in combination with a fluoropyrimidine (eg, 5-FU), infuse oxaliplatin first.
Oxaliplatin is associated with a moderate emetic potential and is known to cause delayed nausea and vomiting; antiemetics are recommended to prevent nausea and vomiting (Ref).
Irritant with vesicant-like properties; ensure proper needle or catheter placement prior to and during infusion. Avoid extravasation; monitor IV site for redness, swelling, or pain.
Extravasation management: 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.
Information conflicts regarding use of warm or cold compresses. Cold compresses may cause local vasoconstriction and reduce cellular injury; however, may cause or exacerbate peripheral neuropathy; warm compresses may increase local drug removal, although may also increase cellular uptake and injury (Ref).
Extravasation of moderate to large oxaliplatin doses (>40 mg) can result in pronounced tissue inflammation resembling erysipelas. Anti-inflammatory medication, such as high-dose oral dexamethasone, may reduce the severity of the inflammatory reaction (Ref).
Oxaliplatin is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (Ref).
IV: Administer as IV infusion over 2 to 6 hours. Flush infusion line with D5W prior to and following administration of oxaliplatin. Do not use IV administration sets containing aluminum. When used in combination with a fluoropyrimidine (eg, 5-FU), infuse oxaliplatin first.
Irritant with vesicant-like properties; ensure proper needle or catheter placement prior to and during infusion. Avoid extravasation; monitor IV site for redness, swelling, or pain. 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. Information conflicts regarding use of warm or cold compresses. Cold compresses could potentially precipitate or exacerbate peripheral neuropathy (Ref).
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and <USP 800> recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Colon cancer, stage III (adjuvant therapy): Adjuvant treatment of stage III colon cancer (in combination with infusional fluorouracil and leucovorin) after complete resection of primary tumor.
Colorectal cancer, advanced: Treatment of advanced colorectal cancer (in combination with infusional fluorouracil and leucovorin).
Biliary tract cancer, advanced; Chronic lymphocytic leukemia, refractory; Esophageal cancer; Gastric cancer; Neuroendocrine tumors: GI/carcinoid, refractory; Non-Hodgkin lymphomas, relapsed/refractory; Ovarian cancer, advanced; Pancreatic cancer, advanced or metastatic; Pancreatic cancer, potentially curable, adjuvant therapy; Small bowel adenocarcinoma, advanced or metastatic; Testicular cancer, refractory; Unknown primary cancer, recurrent or refractory
Oxaliplatin may be confused with Aloxi, carboplatin, cisplatin
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
Substrate of OCT2
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
Capecitabine: Oxaliplatin may enhance the nephrotoxic effect of Capecitabine. Oxaliplatin may enhance the neurotoxic (peripheral) effect of Capecitabine. Oxaliplatin may enhance the QTc-prolonging effect of Capecitabine. Risk C: Monitor therapy
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Fosphenytoin-Phenytoin: Platinum Derivatives may decrease the serum concentration of Fosphenytoin-Phenytoin. Risk C: Monitor therapy
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy
Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification
Levoketoconazole: QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of Levoketoconazole. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy
Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D: Consider therapy modification
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Taxane Derivatives: Platinum Derivatives may enhance the myelosuppressive effect of Taxane Derivatives. Administer Taxane derivative before Platinum derivative when given as sequential infusions to limit toxicity. Management: Administer paclitaxel before cisplatin, when given as sequential infusions, to limit toxicity. Problems associated with other taxane/platinum combinations are possible, although unsubstantiated. Administering the taxane before platinum is likely warranted Risk D: Consider therapy modification
Topotecan: Platinum Derivatives may enhance the adverse/toxic effect of Topotecan. Management: Consider administering platinum derivatives after topotecan when possible to minimize toxicity or using lower doses if administering platinum derivatives prior to topotecan. Monitor for hematologic toxicity (eg, neutropenia, thrombocytopenia). Risk D: Consider therapy modification
Verify pregnancy status prior to treatment initiation in patients who could become pregnant. Patients who could become pregnant should use effective contraception during treatment and for at least 9 months after the last oxaliplatin dose. Patients with partners who can become pregnant should use effective contraception during treatment and for 6 months after the last oxaliplatin dose.
Oxaliplatin may adversely affect female fertility and have an intermediate risk of treatment-related azoospermia and male infertility (ESMO [Lambertini 2020]; Levi 2015). Recommendations are available for fertility preservation of male and female patients to be treated with anticancer agents (ASCO [Oktay 2018]; Klipstein 2020).
Based on the mechanism of action and data from animal reproduction studies, in utero exposure to oxaliplatin may cause fetal harm.
Outcome data following maternal use of oxaliplatin during pregnancy are available (Frydenberg 2020; Kozai 2022; NTP 2013; Petruzzelli 2020).
The European Society for Medical Oncology has published guidelines for diagnosis, treatment, and follow-up of cancer during pregnancy. The guidelines recommend referral to a facility with expertise in cancer during pregnancy and encourage a multidisciplinary team (obstetrician, neonatologist, oncology team) approach. In general, if chemotherapy is indicated, it should be avoided in the first trimester, there should be a 3-week time period between the last chemotherapy dose and anticipated delivery, and chemotherapy should not be administered beyond week 33 of gestation (ESMO [Peccatori 2013]).
A long-term observational research study is collecting information about the diagnosis and treatment of cancer during pregnancy. For additional information about the pregnancy and cancer registry or to become a participant, contact Cooper Health (877-635-4499).
Oxaliplatin is present in breast milk.
Data related to the presence of oxaliplatin in breast milk are available from a lactating patient treated for colorectal cancer 7 months postpartum. Oxaliplatin 200 mg was infused every 3 weeks for 4 doses. The patient continued to express breast milk, but infant feeds were replaced with formula. Breast milk was sampled 34 and 65 days following the last oxaliplatin dose; platinum breast concentrations were 7.8 ng/mL and 10.3 ng/mL, respectively. The breast milk supply significantly decreased over time during chemotherapy and radiation treatments (Krutsch 2023).
Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer recommends discontinuing breastfeeding during oxaliplatin treatment and for 3 months after the last oxaliplatin dose.
CBC with differential, blood chemistries, including serum creatinine, ALT, AST, and bilirubin (baseline, prior to each cycle, and as clinically indicated), electrolytes, including potassium and magnesium (prior to and periodically during treatment); INR and PT (in patients on oral anticoagulant therapy; increase the frequency of monitoring in patients who receive oxaliplatin and oral anticoagulants). Evaluate pregnancy status prior to treatment initiation in females of reproductive potential. ECG monitoring is recommended in patients at risk for QT prolongation, heart failure, bradyarrhythmias, and electrolyte abnormalities and in patients taking concomitant medications known to cause QT prolongation (including class Ia and III antiarrhythmics). Perform neurologic evaluation prior to each dose and periodically thereafter. Monitor for signs/symptoms of hypersensitivity, pulmonary toxicity, posterior reversible encephalopathy syndrome (diagnosis is confirmed with MRI), neuropathy, bleeding, and GI toxicity.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Oxaliplatin, a platinum derivative, is an alkylating agent. Following intracellular hydrolysis, the platinum compound binds to DNA forming cross-links which inhibit DNA replication and transcription, resulting in cell death. Cytotoxicity is cell-cycle nonspecific.
Distribution: Vd: 440 L.
Protein binding: >90% primarily albumin and gamma globulin (irreversible binding to platinum).
Metabolism: Nonenzymatic (rapid and extensive), forms active and inactive derivatives.
Half-life elimination:
Children: Oxaliplatin ultrafilterable platinum (terminal): Median: 293 hours; range: 187 to 662 hours (Beaty 2010).
Adults: Oxaliplatin ultrafilterable platinum: Distribution: Alpha phase: 0.43 hours; Beta phase: 16.8 hours; Terminal: 392 hours.
Excretion: Urine (~54%); feces (~2%).
Altered kidney function: The mean AUC of unbound platinum increases as renal function decreases: 40% increase with mild (CrCl 50 to 80 mL/minute), 95% increase with moderate (CrCl 30 to 49 mL/minute), and 342% increase with severe (CrCl <30 mL/minute) renal impairment compared with patients with normal renal function. The mean Cmax was 38% higher in patients with severe impairment compared with patients with normal renal function.
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