Version July 2025
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.
Dosage guidance:
Safety: Correct hypokalemia and hypomagnesemia prior to and during oxaliplatin treatment. Avoid oxaliplatin in patients with congenital long QT syndrome.
Clinical considerations: 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). Refer to the protocol or institutional guidance for additional details of off-label dosing.
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 six phase 3 studies demonstrated similar 5-year overall 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 six phase 3 studies, a favorable 5-year overall survival was 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, 5-year overall survival was marginally higher (although not statistically significant) in patients treated for 6 months compared to 3 months in the subgroup of patients with T4 and/or N2 stage III colon cancer (Ref).
Esophageal cancer (off-label use):
CAPOX + nivolumab regimen (advanced or metastatic esophageal or gastroesophageal junction adenocarcinoma): IV: 130 mg/m2 on day 1 of a 21-day treatment cycle (in combination with capecitabine and nivolumab); continue until disease progression or unacceptable toxicity (in patients without disease progression, nivolumab was administered for a maximum of 2 years) (Ref).
CAPOX + tislelizumab regimen (unresectable or metastatic esophageal squamous cell carcinoma): IV: 130 mg/m2 on day 1 of a 21-day treatment cycle (in combination with capecitabine and tislelizumab; may limit oxaliplatin to 6 cycles per local guidelines or provider discretion); continue treatment until disease progression or unacceptable toxicity (in patients without disease progression, tislelizumab could be discontinued after 2 years of treatment per provider discretion) (Ref).
FLOT regimen (advanced, resectable gastroesophageal junction adenocarcinoma): IV: 85 mg/m2 on day 1 of a 14-day treatment cycle (in combination with fluorouracil, leucovorin, and docetaxel) for 4 preoperative and 4 postoperative cycles (Ref).
Fluorouracil/oxaliplatin/tislelizumab regimen (unresectable or metastatic esophageal squamous cell carcinoma): IV: 130 mg/m2 on day 1 of a 21-day treatment cycle (in combination with fluorouracil and tislelizumab; may limit oxaliplatin to 6 cycles per local guidelines or provider discretion); continue treatment until disease progression or unacceptable toxicity (in patients without disease progression, tislelizumab could be discontinued after 2 years of treatment per provider discretion) (Ref).
FOLFOX4 regimen (chemoradiotherapy for locally advanced, recurrent, or metastatic disease ): IV: 85 mg/m2 on day 1 of a 14-day treatment cycle, in combination with fluorouracil and leucovorin and radiation for 3 cycles, then without radiation for an additional 3 cycles (Ref).
mFOLFOX + nivolumab regimen (advanced or metastatic esophageal or gastroesophageal junction adenocarcinoma): IV: 85 mg/m2 on day 1 of a 14-day treatment cycle (in combination with fluorouracil, leucovorin, and nivolumab); continue until disease progression or unacceptable toxicity (in patients without disease progression, nivolumab was administered for a maximum of 2 years) (Ref).
FLOT regimen (locally advanced, recurrent, or metastatic disease): IV: 85 mg/m2 on day 1 of a 14-day treatment cycle (in combination with fluorouracil, leucovorin, and docetaxel) for up to 8 cycles (Ref).
Paclitaxel/oxaliplatin/tislelizumab regimen (unresectable or metastatic esophageal squamous cell carcinoma): IV: 130 mg/m2 on day 1 of a 21-day treatment cycle (in combination with paclitaxel and tislelizumab; may limit oxaliplatin to 6 cycles per local guidelines or provider discretion); continue treatment until disease progression or unacceptable toxicity (in patients without disease progression, tislelizumab could be discontinued after 2 years of treatment per provider discretion) (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 of a 21-day treatment cycle (in combination with capecitabine) for 8 cycles following D2 gastrectomy in patients who did not receive preoperative therapy (Ref).
CAPOX/nivolumab regimen (advanced or metastatic gastric or gastroesophageal junction adenocarcinoma): IV: 130 mg/m2 on day 1 of a 21-day treatment cycle (in combination with capecitabine and nivolumab); continue until disease progression or unacceptable toxicity (in patients without disease progression, nivolumab was administered for a maximum of 2 years) (Ref).
CAPOX/pembrolizumab regimen (HER2-negative locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma): IV: 130 mg/m2 on day 1 of a 21-day treatment cycle (in combination with capecitabine and pembrolizumab; may limit oxaliplatin to 6 cycles per local guidelines or provider discretion); continue capecitabine and pembrolizumab until disease progression or unacceptable toxicity or (in patients without disease progression) for up to 24 months (Ref).
CAPOX/pembrolizumab/trastuzumab regimen (HER2-positive unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma): IV: 130 mg/m2 on day 1 of a 21-day treatment cycle (in combination with capecitabine, pembrolizumab, and trastuzumab); continue until disease progression or unacceptable toxicity or (in patients without disease progression) for up to 24 months (Ref).
CAPOX/tislelizumab regimen (HER2-negative unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma): IV: 130 mg/m2 on day 1 of a 21-day treatment cycle (in combination with capecitabine and tislelizumab for up to 6 cycles); continue tislelizumab ± optional capecitabine maintenance until disease progression or unacceptable toxicity (in patients without disease progression, tislelizumab could be discontinued after 2 years of treatment per provider discretion) (Ref).
CAPOX/zolbetuximab regimen (claudin 18.2 positive, HER2-negative, locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma): IV: 130 mg/m2 on day 1 of a 21-day treatment cycle (in combination with capecitabine and zolbetuximab for 8 cycles); continue zolbetuximab ± optional capecitabine maintenance until disease progression or unacceptable toxicity (Ref).
FLOT regimen (locally advanced, resectable disease): IV: 85 mg/m2 on day 1 of a 14-day treatment cycle (in combination with fluorouracil, leucovorin, and docetaxel) for 4 preoperative and 4 postoperative cycles (Ref).
mFOLFOX/nivolumab regimen (advanced or metastatic disease): IV: 85 mg/m2 on day 1 of a 14-day treatment cycle (in combination with fluorouracil, leucovorin, and nivolumab); continue until disease progression or unacceptable toxicity (in patients without disease progression, nivolumab was administered for a maximum of 2 years) (Ref).
mFOLFOX/zolbetuximab regimen (claudin 18.2 positive, HER2-negative, gastric or gastroesophageal junction cancer): IV: 85 mg/m2 on days 1, 15, and 29 of a 42-day treatment cycle (in combination with fluorouracil, leucovorin, and zolbetuximab for 4 cycles); continue zolbetuximab ± optional fluorouracil/leucovorin maintenance until disease progression or unacceptable toxicity (Ref).
FLOT regimen (locally advanced, recurrent, or metastatic disease ): IV: 85 mg/m2 on day 1 of a 14-day treatment cycle (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 or 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).
NALIRIFOX regimen: IV: 60 mg/m2 on day 1 and 15 of a 28-day treatment cycle (in combination with irinotecan [liposomal], leucovorin, and fluorouracil); continue until disease progression or unacceptable toxicity (Ref).
FOLFOX regimen (second-line therapy): IV: 85 mg/m2 on day 1 every 2 weeks (in combination with fluorouracil and leucovorin); continue 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); continue 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); continue 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. Other concomitant anticancer therapies may also require treatment interruption, dosage reduction, and/or discontinuation.
|
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).
Oxaliplatin is a DNA-alkylating platinum compound known to cause myelosuppression. Treatment with oxaliplatin has resulted in neutropenia, which is typically mild and uncomplicated, but has led to febrile neutropenia, neutropenic sepsis, and septic shock. Some cases of severe neutropenia have been fatal (Ref). Thrombocytopenia can occur with or without splenomegaly and may be associated with hemorrhage. Anemia is uncommon, but has been observed, with oxaliplatin treatment (Ref). Decreased neutrophil and platelet counts generally occur between administrations and recover by the next cycle but may be cause for delay if not recovered.
Mechanism: Dose-related; progenitor cells within the bone marrow are particularly susceptible to cellular cytotoxicity from chemotherapy agents due to the near constant DNA synthesis and replication required for hematopoiesis. Neutropenia and thrombocytopenia were the most common hematologic toxicities observed after single doses in early phase trials (Ref).
Risk factors:
• Higher doses (Ref)
• Concurrent or prior chemotherapy (Ref)
• Females (Ref)
• Older age (≥70 years) (Ref)
Prolonged QT interval on ECG (acquired long QT syndrome) has been reported with oxaliplatin. Symptoms preceding discovery of QT prolongation typically include episodes of angina, bradycardia, hypotension, and/or syncope (Ref). Ventricular arrhythmia, including fatal cases of torsades de pointes, have been reported (Ref). Other cardiac toxicities, including atrioventricular block and takotsubo cardiomyopathy, have also been reported (Ref).
Mechanism: Not clearly established; most likely related to oxaliplatin-induced changes in cardiac sodium channels leading to altered repolarization and prolonged action potentials (Ref). Other proposed mechanisms include inflammatory mediators secondary to drug allergy or changes in cardiac myocyte energy metabolism (Ref).
Onset: Varied; symptom presentation is acute, generally during the infusion of oxaliplatin, but there has not been a clearly established timeline for development of toxicity after initiation of treatment. In case reports, cardiotoxicity presented as early as the first cycle of chemotherapy and as late as the 21st cycle (Ref).
Risk factors:
• Concurrent chemotherapy (fluoropyrimidine) (Ref)
• Concurrent use of other QT-prolonging medications (Ref)
• Electrolyte abnormalities (hypomagnesemia or hypokalemia) (Ref)
• Females (Ref)
• Ischemic heart disease or cardiomyopathy (Ref)
Clinical trials and case reports have both documented a risk of hemorrhage, sometimes fatal, related to oxaliplatin. The severity and location of bleeding varies, but may include epistaxis, gingival bleeding, petechial hemorrhage, gastrointestinal hemorrhage, hematuria, and/or intracranial hemorrhage (Ref). Prolonged prothrombin time and INR may be associated with oxaliplatin and fluoropyrimidine treatment and can contribute to hemorrhagic symptoms. Oxaliplatin is also known to cause thrombocytopenia through myelosuppression, splenic sequestration, and immune-mediated mechanisms, the latter of which is associated with a rapid and precipitous drop in serum platelet count and increased bleeding risk (Ref). Hemolysis may also occur and exacerbate anemia associated with bleeding (Ref).
Mechanism: Non–dose related; most cases of hemorrhage occur in the setting of thrombocytopenia. Multiple cases of immune thrombocytopenia, with or without the presence of antidrug antibodies, have been reported (Ref). Decreased platelets due to myelosuppression and/or splenic sequestration may also contribute to bleeding, although thrombocytopenia associated with these mechanisms is typically less severe than immune-mediated cases (Ref).
Onset: Varied; hemorrhagic symptoms may occur at any time. Immune thrombocytopenia occurs rapidly, within hours to days of the inciting dose, but requires prior exposure to the drug to prime the immune system, and most cases describe bleeding events occurring after months of treatment (Ref).
Risk factors:
• Concurrent chemotherapy (Ref)
• Concurrent use of bevacizumab (Ref)
• Concurrent use of anticoagulants
• Platelet count <10 × 109/L (Ref)
• Increasing number of previous oxaliplatin doses (Ref)
Oxaliplatin treatment is associated with a range of presentations of drug-induced liver injury. Mild increases in serum transaminases (including increased serum alanine aminotransferase, increased serum alkaline phosphatase, increased serum aspartate aminotransferase, increased serum alkaline phosphatase, and increased serum bilirubin) are relatively common and reversible. Rarely, overt hepatic failure may occur. Ongoing use of oxaliplatin results in hepatic sinusoidal injury with common findings of steatosis, hepatic vascular injury, nodular regenerative hyperplasia, and secondary sequelae such as splenomegaly, portal hypertension, esophageal varices, and thrombocytopenia (Ref). While most patients experience recovery of hepatic injury after cessation of oxaliplatin, hepatotoxicity may adversely affect curative resection of liver metastases (Ref)
Mechanism: Dose- and time-related; although some reports conflict, it seems that the risk of hepatotoxicity, particularly sinusoidal injury and splenic sequelae, increases with cumulative dose (Ref). The cellular cause of oxaliplatin-induced liver damage is not completely elucidated, but generally believed to be a result of oxidative stress at the level of the sinusoidal epithelium leading to cell death and lysis, and congestion of the hepatic sinusoids (Ref).
Onset: Varied; elevation of transaminases and/or alkaline phosphatase may occur at any point during therapy. Most cases with sinusoidal injury described have been surgical, with preoperative treatment with oxaliplatin ranging from 8 to 54 weeks in duration (Ref).
Risk factors:
• Cumulative doses >1,000 mg/m2 (sinusoidal injury) (Ref)
• Concurrent chemotherapy (fluoropyrimidine or irinotecan) (Ref)
• No concurrent use of bevacizumab (Ref)
Flushing, pruritus, urticaria, angioedema, and skin manifestations that may progress to generalized erythema are the most common symptoms of an oxaliplatin immediate hypersensitivity reaction. Dizziness, diarrhea, bronchospasm, tachycardia, and blood pressure changes may also occur; cardiovascular collapse and death have also been reported (Ref). Reactions have been reported after IV and hepatic arterial infusion (Ref). Delayed oxaliplatin hypersensitivity reactions are rare and include thrombocytopenia, hemolytic anemia, and/or kidney failure (Ref); this has been described as oxaliplatin immune-induced syndrome (Ref).
Mechanism:
• Immediate hypersensitivity reactions: Non–dose-related, IgE-mediated (Ref).
• Delayed hypersensitivity reactions: Non–dose-related, unknown; may involve IgG or IgM (Ref).
Onset:
• Immediate hypersensitivity reactions: Rapid; often occur within the first hour of infusion (Ref). Most reactions occur after multiple infusions, ranging from 5 to 7 cycles (Ref).
• Delayed hypersensitivity reactions: Varied; oxaliplatin immune-induced syndrome may occur within 24 hours from administration, usually after multiple cycles of oxaliplatin-based regimens (average: 17 cycles) (Ref).
Risk factors:
• Infusion time: Increased duration of infusion may decrease risk of reaction (Ref)
• Previous oxaliplatin exposure (Ref)
• Longer oxaliplatin-free interval (>36 months) (Ref)
• Higher baseline eosinophil counts (Ref)
• Low doses of dexamethasone n(<20 mg) when used as premedication (Ref)
• Cross-reactivity may occur between platinum derivatives, although not in all patients (Ref)
Oxaliplatin use is associated with two separate, but related, forms of neuropathy. Acute neuropathy, which occurs in up to 90% of patients and typically resolves prior to the next infusion, is classically exacerbated by exposure to cold temperatures and manifests as transient paresthesia, dysesthesia, or hypoesthesia in the hands, feet, perioral area, or throat. Other symptoms may include jaw pain (particularly upon chewing), abnormal sensation in the tongue, dysarthria, a feeling of chest pressure, pharyngolaryngeal dysesthesia, and eye pain or visual symptoms. The cumulative dose-limiting toxicity of oxaliplatin is a delayed, progressive peripheral neuropathy characterized by paresthesias, dysesthesias, and hypoesthesias. Deficits in proprioception, limiting activities of daily living (eg, writing, buttoning, swallowing, walking) may also occur. Oxaliplatin-induced neuropathy typically improves over a period of months after drug discontinuation but may not fully resolve (Ref).
Mechanism: Not clearly established; acute neuropathy is commonly thought to be related to chelation of calcium by oxaliplatin metabolites (oxalate) leading to transient activation of peripheral nerve voltage-gated channels manifesting as nerve hyperexcitability (Ref). The underlying cause of delayed neuropathy is less clear but hypothesized to be direct neuronal cell death from heavy metal accumulation (ie, platinum) and/or DNA adducts and crosslinks (Ref).
Onset: Acute neuropathy: Rapid; often within hours of infusion, and sometimes during the infusion (Ref). Delayed neuropathy: Varied; typically presents >14 days after initiation; more prevalent with longer courses of therapy (eg, ≥6 months vs 3 months) (Ref).
Risk factors:
• Exposure to cold temperatures (acute neuropathy)
• Hyperoxaluria (acute neuropathy) (Ref)
• Shorter infusion duration (≤2 hours) (Ref)
• Higher doses (individual doses >130 mg/m2 or cumulative doses ≥500 mg/m2) (Ref)
• Longer continuous treatment duration (≥4 months) (delayed neuropathy) (Ref)
• More severe or multiple symptoms of acute neuropathy (delayed neuropathy) (Ref)
• Diabetes (delayed neuropathy) (Ref)
• Increased BMI (≥25) (delayed neuropathy) (Ref)
Posterior reversible encephalopathy syndrome (PRES) has been associated with oxaliplatin-based treatment. Patients may present with hypertension and/or various neurological problems including headache, visual disturbances, altered mental status, lethargy, or seizure. Diagnosis is confirmed radiologically via magnetic resonance imaging, wherein posterior cerebral white matter edema is typical (Ref).
Mechanism: Not clearly established; believed to be related to direct cellular damage to the vasculature of the blood brain barrier and endothelial damage. This results in capillary leakage, failure of cerebral autoregulation, and vasogenic edema (Ref). Oxaliplatin specifically may also induce hypersecretion of arginine vasopressin and other vasoactive compounds (Ref). The hallmark cerebral edema may be exacerbated by hypertension, particularly rapidly increasing or fluctuating blood pressure, and/or fluid overload (Ref).
Onset: Varied; case reports describe an acute onset of symptoms beginning days after initiation (Ref). Other cases occurred weeks after initiating oxaliplatin-based chemotherapy (Ref).
Risk factors:
• Concurrent chemotherapy (taxanes, fluoropyrimidines, gemcitabine) (Ref)
• Concurrent bevacizumab (Ref)
• Increased blood pressure (Ref)
• Sepsis (Ref)
• Females (Ref)
• Immunosuppression (calcineurin inhibitors) (Ref)
Oxaliplatin treatment has been associated with a range of pulmonary toxicities, including severe drug-induced lung injury. Cough, dyspnea, and hypoxia may occur, particularly in patients with pulmonary metastases, but severe pulmonary toxicity is rare. Reported patterns of severe oxaliplatin-induced lung injury include pulmonary fibrosis, interstitial lung disease (including exacerbation of preexisting interstitial lung disease), cryptogenic organizing pneumonia, eosinophilic pneumonitis, and diffuse alveolar damage (Ref). Despite drug discontinuation and treatment with corticosteroids, lung injury may progress to fatal respiratory failure (Ref).
Mechanism: Not clearly established; multiple potential causes of pulmonary toxicity related to oxaliplatin have been proposed. Inflammation of the lungs and alveolar damage are common underlying features; thus, an immune-mediated hypersensitivity reaction has been suggested (Ref). Oxidative cellular injury, either through glutathione depletion or another mechanism, is another commonly cited underlying cause (Ref).
Onset: Varied; usually delayed, with initial presentation of symptoms weeks to months after initiation (Ref). However, cases of rapid onset after the first or second dose have also been reported (Ref).
Risk factors:
• Baseline lung disease (interstitial) (Ref)
• Lung metastases (Ref)
• History of smoking (Ref)
• Prior or concurrent chemotherapy (bleomycin, fluoropyrimidine) (Ref)
• Concurrent immunotherapy (Ref)
Although extremely rare, cases of rhabdomyolysis, with or without acute kidney injury, have been reported with oxaliplatin (Ref). These cases may be related to other cases of intravascular hemolysis and drug-induced thrombotic microangiopathy (Ref). Presenting signs and symptoms may include fatigue, weakness, muscular pain, elevated creatinine kinase, and acute kidney injury (Ref).
Mechanism: Unknown; may be caused by direct cellular toxicity at a cellular level similar to other organ toxicities (Ref), tissue breakdown similar to cases of extravasation (Ref), or an immune-mediated toxicity similar to drug-induced thrombotic microangiopathy (Ref).
Onset: Varied; one case report describes an acute onset of symptoms of ~4 weeks from the start of oxaliplatin treatment (Ref).
Risk factors: Not clearly established; most published cases have included Asian patients and males, but it is unclear if there are true regional or genetic variations in this toxicity or simply a publication bias effect (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%) (table 1), leukopenia (13%), thrombocytopenia (30%; grades 3/4: 3%) (table 2)
|
Drug (Oxaliplatin) |
Comparator (Fluorouracil/Leucovorin) |
Indication |
Number of Patients (Oxaliplatin) |
Number of Patients (Fluorouracil/Leucovorin) |
|---|---|---|---|---|
|
64% |
68% |
Previously treated advanced colorectal cancer |
153 |
142 |
|
Grades 3/4: 1% |
Grades 3/4: 2% |
Previously treated advanced colorectal cancer |
153 |
142 |
|
Drug (Oxaliplatin) |
Comparator (Fluorouracil/Leucovorin) |
Indication |
Number of Patients (Oxaliplatin) |
Number of Patients (Fluorouracil/Leucovorin) |
|---|---|---|---|---|
|
30% |
20% |
Previously treated advanced colorectal cancer |
153 |
142 |
|
Grades 3/4: 3% |
Grades 3/4: 0% |
Previously treated advanced colorectal cancer |
153 |
142 |
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%) (table 3)
|
Drug (Oxaliplatin) |
Comparator (Fluorouracil/Leucovorin) |
Indication |
Number of Patients (Oxaliplatin) |
Number of Patients (Fluorouracil/Leucovorin) |
|---|---|---|---|---|
|
76% |
17% |
Previously treated advanced colorectal cancer |
153 |
142 |
|
Acute: 65% |
10% |
Previously treated advanced colorectal cancer |
153 |
142 |
|
Delayed (persistent): 43% |
9% |
Previously treated advanced colorectal cancer |
153 |
142 |
|
Grades 3/4: 7% |
Grades 3/4: 0% |
Previously treated advanced colorectal cancer |
153 |
142 |
|
Grades 3/4 (acute): 5% |
Grades 3/4 (acute): 0% |
Previously treated advanced colorectal cancer |
153 |
142 |
|
Grades 3/4 (delayed [persistent]): 3% |
Grades 3/4 (delayed [persistent]): 0% |
Previously treated advanced colorectal cancer |
153 |
142 |
Neuromuscular & skeletal: Back pain (11%)
Respiratory: Cough (11%) (table 4), dyspnea (13%) (table 5)
|
Drug (Oxaliplatin) |
Comparator (Fluorouracil/Leucovorin) |
Indication |
Number of Patients (Oxaliplatin) |
Number of Patients (Fluorouracil/Leucovorin) |
|---|---|---|---|---|
|
11% |
9% |
Previously treated advanced colorectal cancer |
153 |
142 |
|
Drug (Oxaliplatin) |
Comparator (Fluorouracil/Leucovorin) |
Indication |
Number of Patients (Oxaliplatin) |
Number of Patients (Fluorouracil/Leucovorin) |
|---|---|---|---|---|
|
13% |
11% |
Previously treated advanced colorectal cancer |
153 |
142 |
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%) (table 6)
|
Drug (Oxaliplatin) |
Comparator (Fluorouracil/Leucovorin) |
Indication |
Number of Patients (Oxaliplatin) |
Number of Patients (Fluorouracil/Leucovorin) |
|---|---|---|---|---|
|
7% |
25% |
Previously treated advanced colorectal cancer |
153 |
142 |
|
Grades 3/4: 0% |
Grades 3/4: 5% |
Previously treated advanced colorectal cancer |
153 |
142 |
Hypersensitivity: Hypersensitivity reaction (3%; including anaphylaxis, nonimmune anaphylaxis) (table 7)
|
Drug (Oxaliplatin) |
Comparator (Fluorouracil/Leucovorin) |
Indication |
Number of Patients (Oxaliplatin) |
Number of Patients (Fluorouracil/Leucovorin) |
|---|---|---|---|---|
|
3% |
1% |
Previously treated advanced colorectal cancer |
153 |
142 |
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: Posterior reversible encephalopathy syndrome
Respiratory: Pulmonary fibrosis
Frequency not defined:
Gastrointestinal: Dysphagia
Hematologic & oncologic: Hemorrhage (including gastrointestinal hemorrhage, hematuria)
Postmarketing:
Cardiovascular: Atrioventricular block (Ref), bradycardia, cardiomyopathy (takotsubo) (Ref), portal hypertension (Ref), prolonged QT interval on ECG (Ref), torsades de pointes (Ref), ventricular arrhythmia
Dermatologic: Pruritus (Ref), urticaria (Ref)
Endocrine & metabolic: Lactic acidosis (Ref), metabolic acidosis
Gastrointestinal: Colitis (including Clostridioides difficile-associated diarrhea), esophageal varices (Ref), esophagitis, intestinal obstruction, pancreatitis
Hematologic & oncologic: Febrile neutropenia (Ref), hemolytic anemia (immuno-allergic; including Evan syndrome (Ref), hemolytic-uremic syndrome (Ref), immune thrombocytopenia (Ref), leukemia (Ref), thrombotic microangiopathy (Ref)
Hepatic: Hepatic fibrosis (Ref), hepatic focal nodular hyperplasia, hepatic sinusoidal obstruction syndrome (veno-occlusive disease of liver) (Ref)
Hypersensitivity: Anaphylactic shock, angioedema (Ref), hypersensitivity angiitis (Ref)
Immunologic: Splenomegaly (Ref)
Infection: Neutropenic sepsis (Ref), sepsis (Ref), septic shock (Ref)
Nervous system: Cranial nerve palsy, decreased deep tendon reflex, dysarthria, Lhermitte sign (Ref), seizure
Neuromuscular & skeletal: Fasciculations, laryngospasm, rhabdomyolysis (Ref)
Ophthalmic: Decreased visual acuity (Ref), optic neuritis, temporary vision loss (Ref), visual field loss (Ref)
Otic: Deafness, hearing loss (can be irreversible) (Ref)
Renal: Acute interstitial nephritis (Ref), acute kidney injury (Ref), renal tubular necrosis (Ref)
Respiratory: Cryptogenic organizing pneumonia (Ref), eosinophilic pneumonitis (Ref), interstitial lung disease (including exacerbation of preexisting interstitial lung disease) (Ref), pneumonia (including interstitial pneumonia (Ref)
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 kidney 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. 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. [DSC] = Discontinued product
Solution, Intravenous:
Generic: 50 mg/10 mL (10 mL); 100 mg/20 mL (20 mL [DSC])
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): $1,162.55
100 mg (per each): $2,325.14 - $2,325.15
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
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 2024 [table 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 2023; NIOSH 2024; 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
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
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 drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Antithyroid Agents: Myelosuppressive Agents may increase neutropenic effects of Antithyroid Agents. Risk C: Monitor
BCG (Intravesical): Myelosuppressive Agents may decrease therapeutic effects of BCG (Intravesical). Myelosuppressive Agents may increase adverse/toxic effects of BCG (Intravesical). Risk X: Avoid
Capecitabine: Oxaliplatin may increase QTc-prolonging effects of Capecitabine. Oxaliplatin may increase nephrotoxic effects of Capecitabine. Oxaliplatin may increase neurotoxic (peripheral) effects of Capecitabine. Risk C: Monitor
Chloramphenicol (Ophthalmic): May increase adverse/toxic effects of Myelosuppressive Agents. Risk C: Monitor
Chloramphenicol (Systemic): Myelosuppressive Agents may increase myelosuppressive effects of Chloramphenicol (Systemic). Risk X: Avoid
Cladribine: May increase myelosuppressive effects of Myelosuppressive Agents. Risk X: Avoid
CloZAPine: Myelosuppressive Agents may increase adverse/toxic effects of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor
Deferiprone: Myelosuppressive Agents may increase neutropenic effects 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
Fexinidazole: Myelosuppressive Agents may increase myelosuppressive effects of Fexinidazole. Risk X: Avoid
Fosphenytoin-Phenytoin: Platinum Derivatives may decrease serum concentration of Fosphenytoin-Phenytoin. Risk C: Monitor
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Avoid) may increase QTc-prolonging effects of Haloperidol. Risk C: Monitor
Lenograstim: Antineoplastic Agents may decrease therapeutic effects 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 increase QTc-prolonging effects 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
Linezolid: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Lipegfilgrastim: Antineoplastic Agents may decrease therapeutic effects 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 increase myelosuppressive effects of Olaparib. Risk C: Monitor
Palifermin: May increase adverse/toxic effects 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
Piperacillin: May increase hypokalemic effects of Antineoplastic Agents. Risk C: Monitor
Promazine: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Avoid) may increase QTc-prolonging effects 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
Ropeginterferon Alfa-2b: Myelosuppressive Agents may increase myelosuppressive effects 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 increase myelosuppressive effects 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 increase adverse/toxic effects 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 could 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 kidney 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) kidney impairment compared with patients with normal kidney function. The mean Cmax was 38% higher in patients with severe impairment compared with patients with normal kidney function.
