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  • CLASSES

    Platinum Compounds

    DEA CLASS

    Rx

    DESCRIPTION

    Non cell-cycle specific, platinum-based alkylating agent
    Used for the treatment of colorectal cancer, in combination with fluorouracil and leucovorin
    Acute or delayed neuropathy can occur; avoid the topical application of ice, as cold temperatures may exacerbate acute neuropathy

    COMMON BRAND NAMES

    Eloxatin

    HOW SUPPLIED

    Eloxatin/Oxaliplatin Intravenous Inj Pwd F/Sol: 50mg, 100mg
    Eloxatin/Oxaliplatin Intravenous Inj Sol: 1mL, 5mg

    DOSAGE & INDICATIONS

    For the treatment of colorectal cancer.
    For adjuvant treatment of patients with stage 3 colorectal cancer who have undergone complete resection of the primary tumor in combination with fluorouracil and leucovorin (FOLFOX4).
    Intravenous dosage
    Adults

    85 mg/m2 IV on day 1, administered concurrently over 2 hours in separate bags via Y-site with leucovorin (200 mg/m2 IV), followed by fluorouracil (400 mg/m2 IV bolus over 2 to 4 minutes, then fluorouracil 600 mg/m2 continuous IV infusion (CIV) over 22 hours). On day 2, give leucovorin (200 mg/m2 IV over 2 hours) followed by fluorouracil (400 mg/m2 IV bolus, then fluorouracil 600 mg/m2 CIV over 22 hours). This 2-day regimen (FOLFOX4) is repeated every 2 weeks for 12 cycles (6 months). Prolongation of the oxaliplatin infusion to 6 hours may mitigate acute toxicities; the infusion time for fluorouracil and leucovorin need not be changed. In a multicenter trial, patients with stage II or III completely resected colon cancer were randomized to either FOLFOX 4 or infusional fluorouracil/leucovorin (De Gramont regimen). At a median follow-up of 81.9 months in the patients with stage 3 disease, there was a significant improvement in 5-year disease-free survival (DFS) in patients receiving FOLFOX4 compared with those receiving infusional fluorouracil/leucovorin (73.3% vs. 67.4%). In a subgroup analysis of patients with stage 3 disease, the 6-year OS rates were also significantly improved with FOLFOX4 (72.9% vs. 68.7%). There was no significant difference observed in DFS or OS in patients with stage 2 disease.

    For the first line treatment of advanced colorectal cancer in combination with irinotecan and 5-fluorouracil-based chemotherapy (FOLFOXIRI)†.
    Intravenous dosage
    Adults

    85 mg/m2 IV, given concurrently via Y-site with levo-leucovorin (200 mg/m2 IV) over 2 hours, preceded by irinotecan (165 mg/m2 IV over 1 hour), on day 1; follow the levo-leucovorin infusion on day 1 with fluorouracil (1,600 mg/m2 per day on days 1 and 2 as a continuous IV infusion (CIV) over 48 hours (total dose 3,200 mg/m2)) (FOLFOXIRI). Repeat every 2 weeks for up to 12 cycles. The order of administration is irinotecan, followed by oxaliplatin plus leucovorin, followed by fluorouracil. Treatment with FOLFOXIRI significantly improved the primary endpoint of overall response rate (ORR) compared with FOLFIRI (60% vs. 34%) in a multicenter, randomized, phase 3 study of patients with unresectable metastatic colorectal cancer (n = 244). In addition, progression-free survival (PFS) (9.8 months vs. 6.9 months) and overall survival (22.6 months vs. 16.7 months) were significantly improved in patients who received FOLFOXIRI. Grade 3 and 4 neutropenia (50% vs. 28%) and grade 2 and 3 peripheral neurotoxicity (19% vs. 0%) were significantly worse in the FOLFOXIRI arm.

    For first- and second-line treatment of advanced colorectal cancer in combination with capecitabine (XELOX or CapeOX)†.
    Intravenous dosage
    Adults

    130 mg/m2 IV over 2 hours on day 1 in combination with capecitabine (1,000 mg/m2 PO twice daily, beginning on the evening of day 1 through the morning of day 15), repeated every 3 weeks. First-line treatment with XELOX was found to be noninferior to FOLFOX4 in a phase 3 clinical trial of patients with metastatic colorectal cancer (n = 2,034), with a median progression-free survival (PFS) of 8 months in patients treated with XELOX compared with 8.5 months for those receiving FOLFOX4; median overall survival (OS) was 19.8 months vs. 19.6 months, respectively. Grade 3 or 4 adverse reactions observed more frequently with XELOX included diarrhea and hand-and-foot syndrome, while FOLFOX4 produced more neutropenia. No difference in PFS or OS was observed between capecitabine/oxaliplatin combinations and fluorouracil/leucovorin/oxaliplatin combinations in patients with metastatic colorectal cancer in a meta-analysis of this trial and 5 additional trials that was performed concurrently with this study. Additional trials have shown efficacy for XELOX in the treatment of both previously treated and previously untreated patients with advanced colorectal cancer.

    For the first line treatment of metastatic colorectal cancer in combination with capecitabine and bevacizumab (XELOX or CapeOx, with bevacizumab)†.
    Intravenous dosage
    Adults

    130 mg/m2 IV over 2 hours on day 1 in combination with capecitabine (1,000 mg/m2 PO twice daily on days 1 to 14), preceded by bevacizumab (7.5 mg/kg IV over 30 to 90 minutes on day 1), repeated every 3 weeks until progressive disease. Treatment with either XELOX or FOLFOX4 plus bevacizumab significantly improved the primary endpoint of median progression-free survival (PFS) compared with either treatment without bevacizumab in a randomized, phase 3, clinical trial (n = 1401) (9.4 months vs. 8 months), with a median duration of response of 8.45 months versus 7.4 months, respectively. An improvement in overall survival in the bevacizumab arms did not reach statistical significance (21.3 vs. 19.9 months). First-line treatment with XELOX was found to be noninferior to FOLFOX4 in a phase 3 clinical trial of patients with metastatic colorectal cancer (n = 2,034).

    For the adjuvant treatment of stage 3 (Dukes C) colon cancer in combination with capecitabine (XELOX or CapeOx)†.
    Intravenous dosage
    Adults

    130 mg/m2 IV on day 1 in combination with capecitabine (1,000 mg/m2 PO twice daily on days 1 to 14), every 3 weeks for a total of 8 cycles. In a phase 3 clinical trial, 1,886 patients with resected stage III colon cancer were randomized to receive oxaliplatin/capecitabine (XELOX) or fluorouracil/leucovorin. After a median follow-up of 57 months, the addition of oxaliplatin to capecitabine significantly improved the primary endpoint of disease-free survival, which at 3 years was 70.9% with XELOX compared with 66.5% with 5-FU/leucovorin. Overall survival was not significantly different between the arms. Grade 3 or 4 neurosensory toxicity, vomiting, hand-foot syndrome, and thrombocytopenia occurred more frequently in the XELOX arm; neutropenia, febrile neutropenia, and stomatitis occurred more frequently with fluorouracil/leucovorin.

    For the first-line treatment of KRAS wild-type metastatic colorectal cancer (mCRC), in combination with cetuximab, leucovorin, and 5-fluorouracil (mFOLFOX6 plus cetuximab)†.
    NOTE: Response rates to cetuximab do not correlate with either the percentage of EGFR-positive cells or the intensity of EGFR expression.
    Intravenous dosage
    Adults

    85 mg/m2 IV concurrently via Y-site with leucovorin (400 mg/m2 IV) over 2 hours on day 1, followed by fluorouracil (400 mg/m2 IV bolus and then 1,200 mg/m2 per day on days 1 and 2 by continuous IV infusion (CIV) [total infusional dose 2,400 mg/m2 given over 46 to 48 hours]), repeated every 14 days (mFOLFOX6). Additionally, give cetuximab 400 mg/m2 IV over 120 minutes (maximum infusion rate, 10 mg/minute) on cycle 1, day 1 followed by weekly infusions of cetuximab 250 mg/m2 IV over 60 minutes (maximum infusion rate, 10 mg/minute); on day 1 of each 2-week cycle, begin oxaliplatin and leucovorin administration 1 hour after completion of cetuximab (order of administration on day 1 is cetuximab, followed by mFOLFOX6). First-line treatment with cetuximab plus modified FOLFOX (mFOLFOX) 4 or 6 significantly improved objective response rates (ORR) in patients with KRAS WT mCRC in two randomized clinical trials. The benefit to progression-free survival (PFS) was small to nonsignificant, and a benefit to overall survival (OS) was not demonstrated. Skin and gastrointestinal toxicities were increased in patients treated with cetuximab. Total exposure (AUC) to fluorouracil was similar when administered as two 22-hour infusions of 600 mg/m2, as in FOLFOX4, or as a single 46-hour infusion of 2,400 mg/m2, as in mFOLFOX6 in a pharmacokinetic study.

    For the adjuvant treatment of colorectal cancer, in combination with leucovorin and fluorouracil (FLOX).
    Intravenous dosage
    Adults

    85 mg/m2 IV concurrently via Y-site with leucovorin (500 mg/m2 IV) over 2 hours, followed 1 hour later by fluorouracil (500 mg/m2 IV bolus) on days 1, 15, and 29. On days 8, 22, and 36, administer leucovorin (500 mg/m2 IV over 2 hours) without oxaliplatin, followed 1 hour later by fluorouracil (500 mg/m2 IV bolus). Repeat every 8 weeks (56 days) for a total of 3 cycles (24 weeks). After a median 8 years of follow-up, patients with stage 2 or 3 colon cancer treated with FLOX (n = 1,247) had significantly improved disease-free survival (DFS) compared with those who received fluorouracil/leucovorin alone (FULV; n = 1,245) in a randomized, phase 3 clinical trial. Overall survival was similar between treatment groups; however, in an unplanned subgroup analysis, age less than 70 years may be associated with improved survival.

    For the adjuvant treatment of colorectal cancer, in combination with leucovorin and fluorouracil (mFOLFOX6).
    Intravenous dosage
    Adults

    85 mg/m2 IV administered concurrently but in separate bags via Y-site over 2 hours with leucovorin (400 mg/m2 IV), followed by fluorouracil (400 mg/m2 IV bolus) on day 1, followed by fluorouracil (1,200 mg/m2 per day on days 1 and 2 by continuous IV infusion (CIV) [total infusional dose, 2,400 mg/m2 over 46 to 48 hours]). This 2-day regimen (mFOLFOX6) is repeated every 2 weeks for 12 cycles (6 months). Prolongation of the oxaliplatin infusion to 6 hours may mitigate acute toxicities; the infusion time for fluorouracil and leucovorin need not be changed. Administering fluorouracil 2,400 mg/m2 over 46 to 48 hours (FOLFOX6) provides similar exposure to the daily bolus plus 22-hour fluorouracil infusion in FOLFOX4, with increased patient convenience and is preferred.[59867] In a multicenter trial, patients with stage II or III completely resected colon cancer were randomized to either FOLFOX4 or infusional fluorouracil/leucovorin (De Gramont regimen). At a median follow-up of 81.9 months in the patients with stage 3 disease, there was a significant improvement in 5-year disease-free survival (DFS) in patients receiving FOLFOX4 compared with infusional fluorouracil/leucovorin (73.3% vs. 67.4%). In a subgroup analysis of patients with stage 3 disease, the 6-year OS rates were also significantly improved with FOLFOX4 (72.9% vs. 68.7%). There was no significant difference observed in DFS or OS in patients with stage 2 disease.[40864] [20587]

    For the treatment of gastric cancer†.
    For the treatment of advanced gastric cancer† in combination with epirubicin and capecitabine or 5-fluorouracil.
    Intravenous dosage
    Adults

    Oxaliplatin 130 mg/m2 IV over 2 hours on day 1 has been given in combination with epirubicin (50 mg/m2 IV on day 1), and capecitabine (625 mg/m2 PO twice daily throughout treatment) or fluorouracil (5-FU) (200 mg/m2/day IV daily throughout treatment); repeat every 3 weeks up to a maximum of 8 cycles. In a phase III trial, 1002 patients with previously untreated esophagogastric cancer were randomized in a 2-by-2 trial design to receive epirubicin and oxaliplatin with either capecitabine or 5-FU (EOX and EOF, respectively), or epirubicin and cisplatin with either capecitabine or 5-FU (ECX and ECF, respectively). The trial was designed to show non-inferiority in overall survival for the treatment arms containing capecitabine as compared to the treatment arms containing fluorouracil. Median overall survival, progression-free survival and overall response rates did not differ significantly between the treatment arms. Grade 3 or 4 neutropenia, nephrotoxicity, thromboembolism, and alopecia occurred less frequently in the oxaliplatin arms compared to the cisplatin arms; grade 3 or 4 peripheral neuropathy and diarrhea occurred more frequently in the oxaliplatin arms.

    For the treatment of advanced gastric cancer† in combination with 5-fluorouracil.
    Intravenous dosage
    Adults

    Oxaliplatin 85 mg/m2 IV over 2 hours on day 1 concurrently with leucovorin (200 mg/m2 IV over 2 hours on day 1) in combination with 5-FU (2600 mg/m2 continuous IV infusion over 24 hours on day 1). Repeat treatment every 2 weeks until disease progression or unacceptable toxicity. In a phase III trial, 220 patients with previously untreated advanced adenocarcinoma of the stomach or gastroesophageal junction were randomized to receive treatment with fluorouracil, leucovorin, and either oxaliplatin or cisplatin (FLO or FLP, respectively). The primary end point, PFS, was not significantly different between the 2 treatment arms (5.8 months vs. 3.9 months, p = 0.077). In a subgroup of 94 patients older than 65 years, FLO had a significantly better overall response rate, and PFS compared to FLP. Leukopenia, anemia, nausea/vomiting, fatigue, nephrotoxicity, hepatotoxicity, and alopecia occurred significantly more often in the FLP arm; neurosensory toxicity occurred significantly more often in the FLO arm.

    For the adjuvant treatment of stage II to IIIB gastric cancer, in combination with capecitabine (XELOX/CapeOx)†.
    Intravenous dosage
    Adults

    130 mg/m2 IV on day 1 in combination with capecitabine 1,000 mg/m2 PO twice daily on days 1 through 14, repeated every 3 weeks for 8 cycles. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In a phase 3 clinical trial, 1,035 patients with stage II to IIIB gastric cancer were randomized to receive adjuvant capecitabine and oxaliplatin or observation after surgical (D2) resection. The primary end point, 3-year disease free survival, was significantly improved with XELOX (74% vs. 60%). At a median follow-up of 34.4 months, the difference in overall survival was not significantly different between the 2 treatment arms.

    For the treatment of advanced or metastatic gastric cancer or gastroesophageal junction cancer (GEJ), in combination with nivolumab, fluorouracil, and leucovorin (mFOLFOX6)†.
    NOTE: Nivolumab is FDA approved in combination with mFOLFOX6 for this indication.
    Intravenous dosage
    Adults

    85 mg/m2 IV on day 1, every 2 weeks until disease progression or unacceptable toxicity. Administer in combination with nivolumab (240 mg IV every 2 weeks until disease progression, unacceptable toxicity, or for up to 2 years in patients without disease progression), leucovorin (400 mg/m2 IV on day 1 infused concurrently with oxaliplatin but in separate bags via Y-site), fluorouracil (400 mg/m2 IV bolus on day 1 following leucovorin, followed by 1,200 mg/m2 per day on days 1 and 2 by continuous IV infusion), every 2 weeks until disease progression or unacceptable toxicity.  Administer nivolumab prior to chemotherapy when given on the same day. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Patients with previously untreated advanced or metastatic gastric cancer, GEJ cancer, and esophageal cancer were randomized to treatment with nivolumab 240 mg IV in combination with mFOLFOX6 every 2 weeks, nivolumab 360 mg IV in combination with CapeOx every 3 weeks, or the same chemotherapy without nivolumab in a multicenter, open-label trial (CHECKMATE-649; n = 1,581). Overall survival was significantly improved with the addition of nivolumab to chemotherapy in the overall patient population (13.8 months vs. 11.6 months); results were consistent in patients with PD-L1 Combined Positive Score (CPS) of 1 or higher and PD-L1 CPS of 5 or higher. The median progression free survival was 7.7 months in patients who received nivolumab compared with 6.9 months in those who did not. The overall response rate was 47% versus 37% respectively (complete response, 10% vs. 7%), for a median duration of 8.5 months versus 6.9 months.

    For the treatment of advanced or metastatic gastric adenocarcinoma or gastroesophageal junction (GEJ) cancer, in combination with capecitabine (XELOX/CapeOx) and nivolumab†.
    NOTE: Nivolumab is FDA approved in combination with XELOX/CapeOx for this indication.
    Intravenous dosage
    Adults

    130 mg/m2 IV on day 1 every 3 weeks until disease progression or unacceptable toxicity. Administer in combination with nivolumab (360 mg IV every 3 weeks until disease progression, unacceptable toxicity, or for up to 2 years in patients without disease progression) and capecitabine (1,000 mg/m2 PO twice daily on days 1 to 14 of each 21 day cycle until disease progression or unacceptable toxicity).   Administer nivolumab prior to chemotherapy when given on the same day. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Patients with previously untreated advanced or metastatic gastric cancer, GEJ cancer, and esophageal cancer were randomized to treatment with nivolumab 240 mg IV in combination with mFOLFOX6 every 2 weeks, nivolumab 360 mg IV in combination with CapeOx every 3 weeks, or the same chemotherapy without nivolumab in a multicenter, open-label trial (CHECKMATE-649; n = 1,581). Overall survival was significantly improved with the addition of nivolumab to chemotherapy in the overall patient population (13.8 months vs. 11.6 months); results were consistent in patients with PD-L1 Combined Positive Score (CPS) of 1 or higher and PD-L1 CPS of 5 or higher. The median progression free survival was 7.7 months in patients who received nivolumab compared with 6.9 months in those who did not. The overall response rate was 47% versus 37% respectively (complete response, 10% vs. 7%), for a median duration of 8.5 months versus 6.9 months.

    For the first-line treatment of HER2-positive locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma, in combination with capecitabine (XELOX; CapeOx), trastuzumab, and pembrolizumab†.
    NOTE: Pembrolizumab is FDA-approved for this indication in combination with trastuzumab, oxaliplatin, and capecitabine.
    Intravenous dosage
    Adults

    130 mg/m2 IV every 3 weeks for up to 6 to 8 cycles. Administer in combination with capecitabine (1,000 mg/m2 PO twice daily on days 1 to 14 every 3 weeks), pembrolizumab (200 mg IV every 3 weeks OR 400 mg IV every 6 weeks until disease progression, unacceptable toxicity, or for up to 24 months in patients without disease progression), and trastuzumab (8 mg/kg IV on day 1 of cycle 1, followed 3 weeks later by 6 mg/kg IV every 3 weeks in subsequent cycles). Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Administer pembrolizumab prior to trastuzumab and chemotherapy when given on the same day. Treatment with pembrolizumab plus trastuzumab and investigator's choice of chemotherapy (cisplatin plus fluorouracil, or capecitabine plus oxaliplatin) significantly improved objective response rate (74% vs. 52%; complete response, 11% vs. 3.1%) compared with placebo plus trastuzumab and chemotherapy in patients with previously untreated HER2-positive advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma at an interim analysis of a multicenter, randomized phase 3 trial (KEYNOTE-811). The median duration of response was 10.6 months in the pembrolizumab arm compared with 9.5 months in the placebo arm; 65% versus 53% of patients, respectively, had a duration of response of at least 6 months. 

    For the treatment of advanced ovarian cancer†.
    Intravenous dosage
    Adults

    As a single agent in previously treated patients (platinum with or without taxane), oxaliplatin 130 mg/m2 IV every 3 weeks demonstrated an overall response rate of 26% (11 of 42 evaluable patients, 2 complete responses), with 10 of 24 (42%) in platinum-sensitive and 1 of 18 (5.6%) in platinum-resistant patients. This lack of benefit in platinum-resistant patients was confirmed in another phase II study of single-agent oxaliplatin in 25 patients; a 4.3% ORR was observed. In a phase II-III trial of chemotherapy naive, advanced ovarian cancer patients, the safety and efficacy of oxaliplatin 130 mg/m2 IV plus cyclophosphamide (1000 mg/m2 IV) every 3 weeks were compared to a standard regimen of cisplatin and cyclophosphamide. Response rates, median progression-free survival, and overall survival were similar between the 2 groups. Myelosuppression and vomiting were significantly less in the oxaliplatin arm. Additional combination regimens studied in phase II trials include gemcitabine/oxaliplatin, paclitaxel/oxaliplatin, docetaxel/oxaliplatin, and pegylated liposomal doxorubicin/oxaliplatin. Overall response rates up to 81% and 37% were observed in platinum-sensitive and platinum-refractory patients, respectively.

    For the treatment of advanced or metastatic breast cancer†.
    Intravenous dosage
    Adults

    In a phase II trial, the safety and efficacy of oxaliplatin 130 mg/m2 IV on day 1 plus 5-fluorouracil (1000 mg/m2/day IV continuous infusion days 1—4) every 3 weeks were evaluated in taxane- and anthracycline-pretreated advanced and metastatic breast cancer patients. Of the 60 evaluable patients, 17 had a partial response, 26 had stable disease, and 17 had disease progression resulting in an overall response rate (ORR) of 26% and 36% in taxane- and anthracycline -resistant populations, respectively. All responders had metastatic liver disease. Median time to progression was 4.8 months, and median survival was 11.9 months. In another phase II clinical trial, 62 patients with pretreated (3 or more prior regimens) stage IV breast cancer were administered oxaliplatin 85 mg/m2 IV on day 1 in combination with leucovorin 200 mg/m2 IV on day 1, 5-fluorouracil 400 mg/m2 IV bolus on day 1, and 5-FU 1200 mg/m2 IV over 44 hours starting on day 1, repeated every 2 weeks. The overall response rate was 18.3%, with no patients achieving a complete response. A numerically higher ORR of 34% was observed in another phase II trial of 50 patients treated with the 3-drug regimen who had received at least 2 prior regimens (including a taxane and an anthracycline).

    For the treatment of relapsed or refractory non-Hodgkin's lymphoma (NHL)† in combination with cytarabine and dexamethasone, with or without rituximab.
    Intravenous dosage
    Adults

    130 mg/m2 IV on day 1 with dexamethasone 40 mg PO days 1, 2, 3 and 4 and cytarabine 2 g/m2 IV every 12 hours for 2 doses on day 2, repeated every 21 days (DHAOx regimen) has been studied. Rituximab 375 mg/m2 IV on day 1 in addition to DHAOx has also been studied. Two small trials (n = 15 and n = 24) examined substituting oxaliplatin for cisplatin in the DHAP regimen (cisplatin, dexamethasone, and cytarabine). The response rate for the DHAOx regimen was 50%—73% in these trials. In a subsequent study, rituximab was given in combination with DHAOx. All 22 patients achieved a response, including a complete response rate of 95%.

    For the treatment of recurrent, advanced head and neck cancer† in combination with 5-fluorouracil-based chemotherapy.
    Intravenous dosage
    Adults

    85 mg/m2 IV on days 1 and 15 with leucovorin (200 mg/m2 IV on days 1, 8, 15, and 22) and 5-FU (2000 mg/m2 IV over 24 hours on days 1, 8, 15, and 22), repeated every 6 weeks (OFF regimen) has been studied. In a phase II trial of 36 patients with recurrent squamous cell carcinoma of the head and neck, OFF produced an overall response rate of 60.6% and an overall survival of 10.8 months.

    For the treatment of pancreatic cancer†.
    For the first-line treatment of metastatic pancreatic cancer, in combination with irinotecan, 5-fluorouracil (5-FU), and leucovorin (FOLFIRINOX)†.
    Intravenous dosage
    Adults

    85 mg/m2 IV over 2 hours on day 1, immediately followed by leucovorin 400 mg/m2 IV over 2 hours; begin irinotecan 180 mg/m2 IV over 90 minutes through a Y-site connector 30 minutes after the leucovorin is started, followed immediately by fluorouracil 400 mg/m2 IV bolus then fluorouracil 2,400 mg/m2 IV over 46 hours. Repeat every 2 weeks for 6 months.[51161]

    For the first-line treatment of locally advanced or metastatic pancreatic cancer, in combination with gemcitabine.
    Intravenous dosage
    Adults

    100 mg/m2 IV on day 2, after administration of gemcitabine (1,000 mg/m2 IV over 100 minutes) on day 1, every 2 weeks until disease progression or unacceptable toxicity. In a phase 3 study (n = 313), the primary endpoint of overall survival was not significantly different between patients treated with oxaliplatin and gemcitabine (GemOx) compared with gemcitabine alone (given over 30 minutes); however, 74% of patients in the gemcitabine arm crossed over to receive gemcitabine and platinum combinations at disease progression, possibly limiting this variable. Response rate (26.8% vs. 17.3%) and progression-free survival (5.8 months vs. 3.7 months) were each significantly better with GemOx. Also, clinical benefit response was significantly greater in patients who received GemOx (38.2% vs. 26.9%).[33970] In another phase 3 trial, 833 patients were randomized to receive GemOx, fixed dose-rate gemcitabine (1,500 mg/m2 IV at a rate of 10 mg/m2/minute on days 1, 8, and 15 of a 28-day cycle), or a 30-minute infusion of gemcitabine (1,000 mg/m2 IV weekly for 7 weeks, followed by 1 week off, and then 1,000 mg/m2 IV on days 2, 8, and 15 every 28 days). Neither GemOx or fixed dose-rate gemcitabine produced a statistically significant difference in overall survival compared with gemcitabine as a 30-minute infusion (5.7 months vs. 6.2 months vs. 4.9 months). Grade 3 or 4 neutropenia and thrombocytopenia occurred more frequently in the gemcitabine fixed dose-rate arm; grade 3 or 4 sensory neuropathy occurred more frequently with GemOx.[35046] [36044]

    For the second-line treatment of gemcitabine-refractory advanced pancreatic cancer, in combination with 5-fluorouracil (5-FU)-based chemotherapy.
    Intravenous dosage
    Adults

    85 mg/m2 IV on days 8 and 22 in combination with fluorouracil (2,000 mg/m2 IV over 24 hours on days 1, 8, 15, and 22) and leucovorin (200 mg/m2 IV over 30 minutes on days 1, 8, 15, and 22), every 42 days until disease progression or unacceptable toxicity. In a phase 3 trial, the primary endpoint of overall survival was significantly longer in patients with pancreatic cancer that progressed on gemcitabine (n = 160) which received fluorouracil, leucovorin, and oxaliplatin (OFF) compared with fluorouracil and leucovorin alone (FF) (26 weeks vs. 13 weeks). Neurologic toxicity and leukopenia occurred more frequently in the oxaliplatin arm.[35050] Initially, this trial randomized patients to receive OFF plus best supportive care (BSC) or BSC alone. Because of the rejection of BSC as an acceptable second-line treatment modality and subsequent poor accrual, the study was amended after the recruitment of 6 patients to OFF versus FF. Final analysis of OFF vs. BSC revealed a significant improvement in overall survival (4.83 months vs. 2.3 months).[45671]

    For the adjuvant treatment of pancreatic cancer, in combination with 5-fluorouracil (5-FU), leucovorin, and irinotecan (mFOLFIRINOX)†.
    Intravenous dosage
    Adults

    85 mg/m2 IV over 2 hours on day 1, immediately followed by leucovorin 400 mg/m2 IV over 2 hours; begin irinotecan 150 mg/m2 IV over 90 minutes 30 minutes after the leucovorin infusion is started, followed by fluorouracil 2,400 mg/m2 IV continuously over 46 hours. Repeat every 14 days for 12 cycles. In a randomized phase 3 trial, adjuvant treatment with mFOLFIRINOX significantly increased both progression-free survival (PFS) and overall survival (OS) compared with gemcitabine monotherapy in patients with pancreatic cancer. In this trial, patients were carefully selected for treatment based on age (younger than 80 years of age), R0 or R1 resection, and a CA 19-9 level of 180 units/mL or less.

    For the treatment of advanced or metastatic biliary tract cancer†.
    Intravenous dosage
    Adults

    Multiple dosage regimens have been studied in phase II trials. Oxaliplatin 100 mg/m2 IV on days 1 and 15 in combination with gemcitabine (1000 mg/m2 IV on days 1, 8, and 15), repeated every 28 days; oxaliplatin 100 mg/m2 IV on day 2 in combination with gemcitabine (1000 mg/m2 IV at a fixed dose rate of 10 mg/m2/min on day 1), repeated every 14 days. All regimens should be given until disease progression or unacceptable toxicity. Response rates of 26%—36% have been achieved.

    For the treatment of cisplatin-refractory or relapsed germ cell cancer (testicular cancer†).
    Intravenous dosage
    Adults

    130 mg/m2 on days 1 and 15 every 4 weeks has been studied. The efficacy and toxicity of oxaliplatin 130 mg/m2 IV on days 1 and 15 every 4 weeks or oxaliplatin 60 mg/m2 IV on days 1, 8, and 15 every 4 weeks were evaluated in 32 patients (16 patients in each dose group) with nonseminomatous cisplatin-refractory germ cell cancer or relapsed disease following high-dose chemotherapy plus autologous stem cell support. Treatment was continued for 2 cycles after achievement of the best response, unless severe toxicity occurred. The response rate in the 130 mg/m2 group was 19%, providing the better dosage option for consideration. Overall, 4 patients achieved a partial response (13%) and 2 additional patients had disease stabilization.

    For the treatment of malignant pleural mesothelioma†.
    Intravenous dosage
    Adults

    80 mg/m2 IV on days 1 and 8 has been given in combination with gemcitabine 1000 mg/m2 IV on days 1 and 8, every 3 weeks for a maximum of 6 cycles. In a clinical trial of 25 patients with previously untreated mesothelioma, an ORR of 40% (0 CR, 10 PR) was observed. In a clinical trial of 29 patients (25 patients oxaliplatin/gemcitabine, 4 patients oxaliplatin monotherapy) with previously treated mesothelioma, a partial response was seen in only 2 patients (ORR 6.9%); both patients received combination chemotherapy.

    For the treatment of esophageal cancer†.
    For the treatment of advanced or metastatic esophageal adenocarcinoma or gastroesophageal junction (GEJ) cancer, in combination with nivolumab, fluorouracil, and leucovorin (mFOLFOX6)†.
    NOTE: Nivolumab is FDA approved in combination with mFOLFOX6 for this indication.
    Intravenous dosage
    Adults

    85 mg/m2 IV on day 1, every 2 weeks until disease progression or unacceptable toxicity. Administer in combination with nivolumab (240 mg IV every 2 weeks until disease progression, unacceptable toxicity, or for up to 2 years in patients without disease progression), leucovorin (400 mg/m2 IV on day 1 infused concurrently with oxaliplatin but in separate bags via Y-site), fluorouracil (400 mg/m2 IV bolus on day 1 following leucovorin, followed by 1,200 mg/m2 per day on days 1 and 2 by continuous IV infusion), every 2 weeks until disease progression or unacceptable toxicity.   Administer nivolumab prior to chemotherapy when given on the same day. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Patients with previously untreated advanced or metastatic gastric cancer, GEJ cancer, and esophageal cancer were randomized to treatment with nivolumab 240 mg IV in combination with mFOLFOX6 every 2 weeks, nivolumab 360 mg IV in combination with CapeOx every 3 weeks, or the same chemotherapy without nivolumab in a multicenter, open-label trial (CHECKMATE-649; n = 1,581). Overall survival was significantly improved with the addition of nivolumab to chemotherapy in the overall patient population (13.8 months vs. 11.6 months); results were consistent in patients with PD-L1 Combined Positive Score (CPS) of 1 or higher and PD-L1 CPS of 5 or higher. The median progression free survival was 7.7 months in patients who received nivolumab compared with 6.9 months in those who did not. The overall response rate was 47% versus 37% respectively (complete response, 10% vs. 7%), for a median duration of 8.5 months versus 6.9 months.

    For the treatment of advanced or metastatic esophageal adenocarcinoma or gastroesophageal junction (GEJ) cancer, in combination with capecitabine (XELOX/CapeOx) and nivolumab†.
    NOTE: Nivolumab is FDA approved in combination with XELOX/CapeOx for this indication.
    Intravenous dosage
    Adults

    130 mg/m2 IV on day 1 every 3 weeks until disease progression or unacceptable toxicity. Administer in combination with nivolumab (360 mg IV every 3 weeks until disease progression, unacceptable toxicity, or for up to 2 years in patients without disease progression) and capecitabine (1,000 mg/m2 PO twice daily on days 1 to 14 of each 21 day cycle until disease progression or unacceptable toxicity).   Administer nivolumab prior to chemotherapy when given on the same day. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Patients with previously untreated advanced or metastatic gastric cancer, GEJ cancer, and esophageal cancer were randomized to treatment with nivolumab 240 mg IV in combination with mFOLFOX6 every 2 weeks, nivolumab 360 mg IV in combination with CapeOx every 3 weeks, or the same chemotherapy without nivolumab in a multicenter, open-label trial (CHECKMATE-649; n = 1,581). Overall survival was significantly improved with the addition of nivolumab to chemotherapy in the overall patient population (13.8 months vs. 11.6 months); results were consistent in patients with PD-L1 Combined Positive Score (CPS) of 1 or higher and PD-L1 CPS of 5 or higher. The median progression free survival was 7.7 months in patients who received nivolumab compared with 6.9 months in those who did not. The overall response rate was 47% versus 37% respectively (complete response, 10% vs. 7%), for a median duration of 8.5 months versus 6.9 months.

    †Indicates off-label use

    MAXIMUM DOSAGE

    The suggested maximum tolerated dose (MTD) for oxaliplatin is dependent on performance status, other chemotherapy agents or radiation given in combination, and disease state. The dosing of oxaliplatin may vary from protocol to protocol. If questions arise, clinicians should consult the appropriate references to verify the dose.

    Adults

    130 mg/m2 IV.

    Elderly

    130 mg/m2 IV.

    Adolescents

    Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    Mild to moderate renal impairment (CrCl 30 mL/min or more): No dosage adjustment necessary.
    Severe renal impairment (CrCl less than 30 mL/min): Reduce the starting dose of oxaliplatin to 65 mg/m2.

    ADMINISTRATION

     
    CAUTION: Observe and exercise appropriate precautions for handling, preparing, and administering cytotoxic drugs.

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Acute hypersensitivity reactions have been reported during or immediately following oxaliplatin administration. Appropriate supportive care equipment and medications should be readily available.
    Do not use aluminum needles or IV sets containing aluminum for the preparation or administration of oxaliplatin. Aluminum has been reported to cause degradation of platinum compounds.
    Do not mix oxaliplatin with or administer simultaneously through the same infusion line as alkaline medications or diluents (such as basic solutions of fluorouracil).
     
    Reconstitution (lyophilized powder):
    50 mg vial: Add 10 mL of Sterile Water for Injection or 5% Dextrose Injection to the vial of lyophilized powder for a final concentration of 5 mg/mL. Do not reconstitute with a sodium chloride solution or other chloride-containing solutions. Further dilution is required prior to administration.
    100 mg vial: Add 20 mL of Sterile Water for Injection or 5% Dextrose Injection to the vial of lyophilized powder for a final concentration of 5 mg/mL. Do not reconstitute with a sodium chloride solution or other chloride-containing solutions. Further dilution is required prior to administration.
    Storage of reconstituted solution: Up to 24 hours under refrigeration (2 to 8 degrees C or 36 to 46 degrees F).
     
    Dilution (aqueous solution and reconstituted lyophilized powder):
    Dilute the appropriate volume of oxaliplatin aqueous solution (5 mg/mL) or reconstituted lyophilized powder (5 mg/mL) in 250 mL to 500 mL of 5% Dextrose Injection. Do not dilute with a sodium chloride solution or other chloride-containing solutions.
    Storage after dilution: Up to 6 hours at room temperature (20 to 25 degrees C or 68 to 77 degrees F) or 24 hours under refrigeration (2 to 8 degrees C or 36 to 46 degrees F). After dilution, protection from light is not required.
     
    Administration:
    Flush the infusion line with 5% Dextrose Injection prior to administration of any concomitant medications.
    Infuse intravenously over 2 hours; prolongation of the infusion to 6 hours may mitigate acute toxicities.
    Avoid extravasation; severe tissue damage and necrosis have been reported.

    STORAGE

    Eloxatin:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Do not freeze
    - Protect from light
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    - Store diluted product in accordance with package insert instructions
    - Store in carton

    CONTRAINDICATIONS / PRECAUTIONS

    Platinum compound hypersensitivity, serious hypersensitivity reactions or anaphylaxis

    Oxaliplatin is contraindicated in patients who have exhibited platinum compound hypersensitivity to oxaliplatin or other platinum compounds. Administration of oxaliplatin is associated with a risk of serious hypersensitivity reactions or anaphylaxis, which may occur during any cycle within minutes of oxaliplatin administration. These reactions are similar in nature and severity to those reported with other platinum-containing compounds, including rash, urticaria, erythema, pruritus, and rarely, bronchospasm and hypotension. Monitor patients for signs and symptoms of hypersensitivity. Discontinue oxaliplatin in patients who develop a hypersensitivity reaction to oxaliplatin, and do not rechallenge.

    Peripheral neuropathy

    Due to dose-limiting neurotoxicity, oxaliplatin should be used cautiously in patients with pre-existing peripheral neuropathy. Instruct patients to avoid the topical application of ice for mucositis prophylaxis or other conditions, as cold temperature can exacerbate acute neurological symptoms. This acute type of neuropathy is usually sensory and peripheral and can occur within hours or up to 2 days after dosing. This type of neuropathy is usually reversible although it frequently recurs with further dosing, and generally resolves within 14 days. Prolongation of the oxaliplatin infusion time from 2 hours to 6 hours may mitigate acute toxicities. A persistent (longer than 14 days), primarily peripheral, sensory neuropathy has also been reported, and may occur without any prior acute neuropathy event; these symptoms may improve in some patients upon discontinuation of oxaliplatin. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for persistent neurosensory reactions based upon severity.

    Myopathy, rhabdomyolysis

    Use oxaliplatin with caution in patients who have a history of myopathy, as symptoms of rhabdomyolysis could be masked. Rhabdomyolysis, including fatal cases, has been reported in patients treated with oxaliplatin. Patients should be instructed to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or pyrexia or elevated body temperature. Discontinue oxaliplatin if signs or symptoms of rhabdomyolysis occur.

    Apheresis, AV block, bradycardia, cardiomyopathy, celiac disease, electrolyte imbalance, females, fever, heart failure, human immunodeficiency virus (HIV) infection, hyperparathyroidism, hypocalcemia, hypokalemia, hypomagnesemia, hypothermia, hypothyroidism, long QT syndrome, myocardial infarction, pheochromocytoma, QT prolongation, rheumatoid arthritis, sickle cell disease, sleep deprivation, stroke, systemic lupus erythematosus (SLE), torsade de pointes

    Avoid the use of oxaliplatin in patients with congenital long QT syndrome. QT prolongation and ventricular arrhythmias, including fatal Torsade de Pointes, have been reported in postmarketing experience with oxaliplatin. Correct hypokalemia or hypomagnesemia before starting therapy and monitor these electrolytes periodically during therapy. Use oxaliplatin with caution in patients with conditions that may increase the risk of QT prolongation including bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, stroke, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalance. Females, people 65 years and older, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation.

    Bone marrow suppression, neutropenia, thrombocytopenia

    Bone marrow suppression including neutropenia and thrombocytopenia has been reported in patients treated with oxaliplatin in clinical trials; neutropenic sepsis including fatal occurrences has also occurred. Monitor complete blood counts at baseline, before each subsequent cycle, and as clinically indicated. Do not administer oxaliplatin until the ANC is 1,500 cells/mm3 or more and platelets are 75,000 cells/mm3 or more. Hold oxaliplatin for sepsis or septic shock. A dose reduction is necessary after recovery from grade 4 neutropenia, neutropenic fever, or grade 3 or 4 thrombocytopenia. Consider discontinuing therapy for patients with a rapid onset of thrombocytopenia or thrombocytopenia that may be immune-mediated.

    Hepatic disease, hepatotoxicity

    Use oxaliplatin with caution in patients with pre-existing hepatic disease, as hepatotoxicity manifested by increased transaminases and alkaline phosphatase has been reported with treatment. Monitor liver function tests at baseline, before each subsequent cycle, and as clinically indicated. Changes noted on liver biopsies have included peliosis, nodular regenerative hyperplasia or sinusoidal alterations, perisinusoidal fibrosis, and veno-occlusive lesions. If abnormal liver function tests or portal hypertension occur which cannot be explained by liver metastases, investigate other hepatic vascular disorders.

    Encephalopathy

    Posterior Reversible Encephalopathy Syndrome (PRES), also known as Reversible Posterior Leukoencephalopathy Syndrome (RPLS), has been reported with oxaliplatin use. Symptoms of PRES include seizures, headache, visual disturbances (e.g., blurry vision or blindness), confusion, and altered mental status. Confirm the diagnosis of PRES with magnetic resonance imaging; permanently discontinue therapy in patients who develop PRES.

    Chronic lung disease (CLD), pneumonitis, pulmonary disease, pulmonary fibrosis

    Use oxaliplatin with caution in patients with pre-existing pulmonary disease or chronic lung disease (CLD), as treatment has been associated with pulmonary fibrosis. Hold oxaliplatin therapy if unexplained respiratory symptoms (e.g., nonproductive cough, dyspnea, crackles, or radiological pulmonary infiltrates) occur, until a diagnosis of interstitial lung disease/pneumonitis or pulmonary fibrosis can be excluded.

    Anticoagulant therapy, bleeding

    Increase the frequency of PT/INR monitoring in patients receiving oral anticoagulant therapy with oxaliplatin. Also, monitor for bleeding in all patients. The incidence of bleeding was higher in patients treated with oxaliplatin plus fluorouracil/leucovorin compared to those receiving fluorouracil/leucovorin without oxaliplatin in clinical trials. Prolonged prothrombin time and INR occasionally associated with hemorrhage have been reported in patients who received oxaliplatin with fluorouracil/leucovorin while on anticoagulants.

    Geriatric

    In randomized clinical trials, the rates of overall adverse events were similar across and between patients younger than 65 years and geriatric patients (65 years and older) treated with oxaliplatin in combination with fluorouracil and leucovorin. The incidence of diarrhea, dehydration, hypokalemia, leukopenia, syncope, and fatigue may be higher in elderly patients. Geriatric patients may also be at increased risk for developing a prolonged QT interval when using oxaliplatin.

    Children

    The safety and effectiveness of oxaliplatin have not been established in children. No responses were observed in pediatric patients with relapsed or refractory malignant solid tumors (primarily neuroblastoma and osteosarcoma) in a multicenter, noncomparative trial (n = 43); the dose-limiting toxicity was sensory neuropathy at a dose of 110 mg/m2. In another noncomparative trial (n = 23), no responses were observed in pediatric patients with metastatic or unresectable solid tumors (primarily neuroblastoma and ganglioneuroblastoma); sensory neuropathy was the dose-limiting toxicity at a dose of 160 mg/m2.

    Pregnancy

    Pregnancy should be avoided by females of reproductive potential during oxaliplatin treatment and for at least 9 months after the last dose. Although there are no adequately controlled studies in pregnant women, oxaliplatin can cause fetal harm or death when administered during pregnancy based on its mechanism of action and animal studies. Women who are pregnant or who become pregnant while receiving oxaliplatin should be apprised of the potential hazard to the fetus. Oxaliplatin caused developmental mortality (increased early resorptions) when administered to pregnant rats on gestational days 6 to 16 and adversely affected fetal growth when given on gestational days 6 to 10 (decreased fetal weight, delayed ossification).

    Contraception requirements, infertility, male-mediated teratogenicity, pregnancy testing, reproductive risk

    Counsel patients about the reproductive risk and contraception requirements during oxaliplatin treatment. Oxaliplatin can be cause fetal harm if taken by the mother during pregnancy. Females of reproductive potential should avoid pregnancy and use effective contraception during and for at least 9 months after treatment with oxaliplatin. Females of reproductive potential should undergo pregnancy testing prior to initiation of regorafenib. Due to the risk of male-mediated teratogenicity, males with female partners of reproductive potential should use effective contraception for 6 months after the last dose of oxaliplatin. Women who become pregnant while receiving oxaliplatin should be apprised of the potential hazard to the fetus. Although there are no data regarding the effect of oxaliplatin on human fertility, male and female infertility has been observed in animal studies.

    Breast-feeding

    Due to the potential for serious adverse reactions in nursing infants from oxaliplatin, advise women to discontinue breast-feeding during treatment and for 3 months after the final dose. It is not known whether oxaliplatin is present in human milk, although many drugs are excreted in human milk.

    ADVERSE REACTIONS

    Severe

    neutropenia / Delayed / 0-53.0
    diarrhea / Early / 4.0-25.0
    leukopenia / Delayed / 0-24.0
    vomiting / Early / 4.0-23.0
    peripheral neuropathy / Delayed / 7.0-19.0
    nausea / Early / 4.0-19.0
    paresthesias / Delayed / 6.0-18.0
    fatigue / Early / 4.0-16.0
    abdominal pain / Early / 1.0-10.0
    thromboembolism / Delayed / 1.0-8.0
    infection / Delayed / 2.0-8.0
    dyspnea / Early / 0-7.0
    dehydration / Delayed / 0-7.0
    thrombosis / Delayed / 0-6.0
    hyperbilirubinemia / Delayed / 1.0-5.0
    thrombocytopenia / Delayed / 2.0-5.0
    GI obstruction / Delayed / 0-5.0
    anorexia / Delayed / 1.0-5.0
    elevated hepatic enzymes / Delayed / 0-4.0
    hypokalemia / Delayed / 0-4.0
    constipation / Delayed / 0-4.0
    weight loss / Delayed / 0-4.0
    injection site reaction / Rapid / 0-3.0
    back pain / Delayed / 0-3.0
    anemia / Delayed / 1.0-3.0
    stomatitis / Delayed / 0-3.0
    hyperglycemia / Delayed / 0-3.0
    hypotension / Rapid / 0-3.0
    myalgia / Early / 0-2.0
    hyponatremia / Delayed / 0-2.0
    lymphopenia / Delayed / 0-2.0
    gastroesophageal reflux / Delayed / 0-2.0
    hiccups / Early / 0-2.0
    rash / Early / 0-1.0
    palmar-plantar erythrodysesthesia (hand and foot syndrome) / Delayed / 0-1.0
    pulmonary fibrosis / Delayed / 0-1.0
    cough / Delayed / 0-1.0
    visual impairment / Early / 0-1.0
    chest pain (unspecified) / Early / 0-1.0
    hypocalcemia / Delayed / 0-1.0
    thrombotic thrombocytopenic purpura (TTP) / Delayed / 0-1.0
    epistaxis / Delayed / 0-1.0
    hematuria / Delayed / 0-1.0
    bleeding / Early / 0-1.0
    dyspepsia / Early / 0-1.0
    dysgeusia / Early / 0-1.0
    flatulence / Early / 0-1.0
    xerostomia / Early / 0-1.0
    flushing / Rapid / 0-1.0
    diaphoresis / Early / 0-1.0
    fever / Early / 0-1.0
    hypoalbuminemia / Delayed / 0-1.0
    increased urinary frequency / Early / 0-1.0
    dysuria / Early / 0-1.0
    peripheral edema / Delayed / 0-1.0
    edema / Delayed / 0-1.0
    dysphagia / Delayed / 0-1.0
    insomnia / Early / 0-1.0
    depression / Delayed / 0-1.0
    anxiety / Delayed / 0-1.0
    GI bleeding / Delayed / 0-0.2
    leukoencephalopathy / Delayed / 0-0.1
    interstitial nephritis / Delayed / Incidence not known
    renal tubular necrosis / Delayed / Incidence not known
    renal failure (unspecified) / Delayed / Incidence not known
    tissue necrosis / Early / Incidence not known
    serious hypersensitivity reactions or anaphylaxis / Rapid / Incidence not known
    angioedema / Rapid / Incidence not known
    anaphylactic shock / Rapid / Incidence not known
    bronchospasm / Rapid / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    veno-occlusive disease (VOD) / Delayed / Incidence not known
    sinusoidal obstruction syndrome (SOS) / Delayed / Incidence not known
    seizures / Delayed / Incidence not known
    cranial nerve palsies / Delayed / Incidence not known
    optic neuritis / Delayed / Incidence not known
    bradycardia / Rapid / Incidence not known
    torsade de pointes / Rapid / Incidence not known
    rhabdomyolysis / Delayed / Incidence not known
    intracranial bleeding / Delayed / Incidence not known
    ileus / Delayed / Incidence not known
    pancreatitis / Delayed / Incidence not known
    hearing loss / Delayed / Incidence not known
    hemolytic-uremic syndrome / Delayed / Incidence not known
    new primary malignancy / Delayed / Incidence not known

    Moderate

    conjunctivitis / Delayed / 2.0-9.0
    ascites / Delayed / 0-5.0
    ataxia / Delayed / 2.0-5.0
    pneumonitis / Delayed / 0-5.0
    hypoxia / Early / 0-5.0
    bone pain / Delayed / 0-5.0
    proctitis / Delayed / 0-5.0
    sinus tachycardia / Rapid / 0-5.0
    melena / Delayed / 0-5.0
    vaginal bleeding / Delayed / 0-5.0
    hemoptysis / Delayed / 0-5.0
    prolonged bleeding time / Delayed / 0-5.0
    hemorrhoids / Delayed / 0-5.0
    hot flashes / Early / 0-5.0
    hypertension / Early / 0-5.0
    urinary incontinence / Early / 0-5.0
    encephalopathy / Delayed / 0-0.1
    dysarthria / Delayed / Incidence not known
    colitis / Delayed / Incidence not known
    erythema / Early / Incidence not known
    peliosis hepatis / Delayed / Incidence not known
    interstitial lung disease / Delayed / Incidence not known
    QT prolongation / Rapid / Incidence not known
    esophagitis / Delayed / Incidence not known

    Mild

    alopecia / Delayed / 3.0-67.0
    headache / Early / 7.0-17.0
    dizziness / Early / 0-13.0
    rhinitis / Early / 0-10.0
    lacrimation / Early / 1.0-9.0
    pharyngitis / Delayed / 0-9.0
    xerosis / Delayed / 0-6.0
    pruritus / Rapid / 0-6.0
    tenesmus / Delayed / 0-5.0
    urticaria / Rapid / 0-5.0
    gingivitis / Delayed / 0-5.0
    weakness / Early / 0-5.0
    purpura / Delayed / 0-5.0
    syncope / Early / 0-5.0
    vertigo / Early / 0-5.0
    arthralgia / Delayed / 0-1.0
    hypoesthesia / Delayed / Incidence not known
    ocular pain / Early / Incidence not known

    DRUG INTERACTIONS

    Aclidinium; Formoterol: (Moderate) Monitor ECGs and electrolytes in patients receiving oxaliplatin concomitantly with long-acting beta-agonists; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Beta-agonists may also be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, fluticasone; vilanterol, umeclidinium; vilanterol) than with short-acting beta-agonists.
    Albuterol: (Minor) Monitor ECGs for QT prolongation and monitor electrolytes if coadministration is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists such as albuterol, levalbuterol, metaproterenol, pirbuterol, and terbutaline.
    Alfuzosin: (Major) Monitor ECGs and electrolytes in patients receiving oxaliplatin and alfuzosin concomitantly; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Based on electrophysiology studies performed by the manufacturer, alfuzosin may also prolong the QT interval in a dose-dependent manner.
    Amiodarone: (Major) Avoid coadministration of amiodarone and oxaliplatin due to the potential for QT prolongation. If coadministration is unavoidable, monitor ECGs and electrolytes periodically during therapy; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes (TdP) have been reported with oxaliplatin use in post-marketing experience. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and TdP. Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Amisulpride: (Major) Monitor ECG and electrolytes if amisulpride is coadministered with oxaliplatin due to the potential for additive QT prolongation and torsade de pointes (TdP). Correct electrolyte abnormalities prior to administration of oxaliplatin. Amisulpride causes dose- and concentration- dependent QT prolongation. QT prolongation and ventricular arrhythmias including fatal TdP have been reported with oxaliplatin use in postmarketing experience.
    Amitriptyline: (Minor) Monitor electrolytes and ECGs for QT prolongation if coadministration of tricyclic antidepressants with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid coadministration of clarithromycin with oxaliplatin due to the risk of QT prolongation. Clarithromycin is associated with an established risk for QT prolongation and torsade de pointes (TdP). QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Anagrelide: (Major) Do not use anagrelide with oxaliplatin due to the risk of QT prolongation. Torsade de pointes (TdP) and ventricular tachycardia have been reported with anagrelide. In addition, dose-related increases in mean QTc and heart rate were observed in healthy subjects. QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Apixaban: (Moderate) Increase the frequency of monitoring in patients who are receiving concomitant therapy with oxaliplatin and apixaban. Prolonged PT/INR occasionally associated with hemorrhage have been reported in patients who received oxaliplatin in combination with fluorouracil/leucovorin while on anticoagulants.
    Apomorphine: (Major) Monitor ECGs and electrolytes in patients receiving oxaliplatin and apomorphine concomitantly; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
    Arformoterol: (Moderate) Monitor ECGs and electrolytes in patients receiving oxaliplatin concomitantly with long-acting beta-agonists; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Beta-agonists may also be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, fluticasone; vilanterol, umeclidinium; vilanterol) than with short-acting beta-agonists.
    Aripiprazole: (Major) Monitor ECGs and electrolytes in patients receiving oxaliplatin and aripiprazole concomitantly; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. QT prolongation has also occurred during therapeutic use of aripiprazole as well as following overdose.
    Arsenic Trioxide: (Major) Avoid concomitant use of arsenic trioxide and oxaliplatin due to the potential for QT prolongation. If concomitant drug use is unavoidable, frequently monitor electrocardiograms and electrolytes; correct electrolyte abnormalities prior to administration. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. QT prolongation and ventricular arrhythmias including fatal TdP have been reported with oxaliplatin use in post-marketing experience.
    Artemether; Lumefantrine: (Major) Avoid coadministration of oxaliplatin and artemether if possible due to the risk of QT prolongation. If unavoidable, monitor ECGs and electrolytes periodically during therapy; correct electrolyte abnormalities prior to administration of oxaliplatin. The administration of artemether; lumefantrine is associated with prolongation of the QT interval. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in post-marketing experience. (Major) Avoid coadministration of oxaliplatin and lumefantrine if possible due to the risk of QT prolongation. If unavoidable, monitor ECGs and electrolytes periodically during therapy; correct electrolyte abnormalities prior to administration of oxaliplatin. The administration of artemether; lumefantrine is associated with prolongation of the QT interval. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in post-marketing experience.
    Asenapine: (Major) Avoid coadministration of asenapine and oxaliplatin due to the risk of QT prolongation. Both asenapine and oxaliplatin have been associated with QT prolongation. Ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in post-marketing experience.
    Atomoxetine: (Major) Monitor ECGs and electrolytes in patients receiving oxaliplatin and atomoxetine concomitantly; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in post-marketing experience. QT prolongation has also occurred during therapeutic use of atomoxetine and following overdose.
    Azithromycin: (Major) Avoid coadministration of azithromycin with oxaliplatin due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. QT prolongation and ventricular arrhythmias including fatal TdP have been reported with oxaliplatin use in postmarketing experience.
    Bedaquiline: (Major) Monitor ECGs and electrolytes in patients receiving oxaliplatin and bedaquiline concomitantly; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Bedaquiline has also been reported to prolong the QT interval; coadministration may result in additive or synergistic prolongation of the QT interval.
    Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Major) Avoid coadministration of oxaliplatin with tenofovir alafenamide due to the risk of increased oxaliplatin-related adverse reactions. Tenofovir alafenamide is known to be potentially nephrotoxic; because platinum-containing drugs like oxaliplatin are eliminated primarily through the kidney, oxaliplatin clearance may be decreased by coadministration with nephrotoxic agents.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and oxaliplatin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and oxaliplatin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Budesonide; Formoterol: (Moderate) Monitor ECGs and electrolytes in patients receiving oxaliplatin concomitantly with long-acting beta-agonists; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Beta-agonists may also be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, fluticasone; vilanterol, umeclidinium; vilanterol) than with short-acting beta-agonists.
    Budesonide; Glycopyrrolate; Formoterol: (Moderate) Monitor ECGs and electrolytes in patients receiving oxaliplatin concomitantly with long-acting beta-agonists; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Beta-agonists may also be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, fluticasone; vilanterol, umeclidinium; vilanterol) than with short-acting beta-agonists.
    Buprenorphine: (Major) Avoid coadministration of buprenorphine with oxaliplatin due to the risk of QT prolongation. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Buprenorphine; Naloxone: (Major) Avoid coadministration of buprenorphine with oxaliplatin due to the risk of QT prolongation. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Cabotegravir; Rilpivirine: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of rilpivirine with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Supratherapeutic doses of rilpivirine (75 to 300 mg per day) have caused QT prolongation. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Ceritinib: (Major) Avoid coadministration of ceritinib with oxaliplatin if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval; QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Chlordiazepoxide; Amitriptyline: (Minor) Monitor electrolytes and ECGs for QT prolongation if coadministration of tricyclic antidepressants with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Chloroquine: (Major) Avoid coadministration of chloroquine with oxaliplatin due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. QT prolongation and ventricular arrhythmias including fatal TdP have been reported with oxaliplatin use in postmarketing experience.
    Chlorpromazine: (Major) Monitor ECGs and electrolytes in patients receiving oxaliplatin and chlorpromazine concomitantly; correct electrolyte abnormalities prior to administration of oxaliplatin. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP). QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience.
    Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
    Cidofovir: (Major) Avoid coadministration of oxaliplatin with cidofovir due to the risk of increased oxaliplatin-related adverse reactions. Cidofovir is known to be potentially nephrotoxic; because platinum-containing drugs like oxaliplatin are eliminated primarily through the kidney, oxaliplatin clearance may be decreased by coadministration with nephrotoxic agents.
    Ciprofloxacin: (Major) Monitor ECGs and electrolytes in patients receiving oxaliplatin and ciprofloxacin concomitantly; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes (TdP) have been reported with oxaliplatin use in postmarketing experience. Rare cases of QT prolongation TdP have also been reported with ciprofloxacin during postmarketing surveillance.
    Cisapride: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of oxaliplatin with cisapride is contraindicated. QT prolongation and ventricular arrhythmias, including fatal TdP and death, have been reported with both cisapride and oxaliplatin.
    Citalopram: (Major) Avoid coadministration of citalopram with oxaliplatin due to the risk of QT prolongation. If concurrent use is considered essential, monitor ECGs and electrolytes; correct electrolyte abnormalities prior to administration of oxaliplatin. Citalopram causes dose-dependent QT interval prolongation. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Clarithromycin: (Major) Avoid coadministration of clarithromycin with oxaliplatin due to the risk of QT prolongation. Clarithromycin is associated with an established risk for QT prolongation and torsade de pointes (TdP). QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Clofazimine: (Major) Monitor ECG and electrolytes if clofazimine is coadministered with oxaliplatin due to the potential for additive QT prolongation and torsade de pointes (TdP). Correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and TdP have been reported in patients receiving clofazimine in combination with QT prolonging medications. QT prolongation and ventricular arrhythmias including fatal TdP have been reported with oxaliplatin use in postmarketing experience.
    Clomipramine: (Minor) Monitor electrolytes and ECGs for QT prolongation if coadministration of tricyclic antidepressants with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Clozapine: (Major) Monitor ECGs and electrolytes in patients receiving oxaliplatin and clozapine concomitantly; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Treatment with clozapine has also been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death.
    Codeine; Phenylephrine; Promethazine: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of promethazine with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Codeine; Promethazine: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of promethazine with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Crizotinib: (Major) Avoid coadministration of crizotinib with oxaliplatin due to the risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct any electrolyte abnormalities. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib if QT prolongation occurs. Crizotinib has been associated with concentration-dependent QT prolongation. Prolongation of the QT interval and ventricular arrhythmias including fatal torsade de pointes (TdP) have been reported with oxaliplatin in postmarketing experience.
    Cyclosporine: (Major) Avoid coadministration of oxaliplatin with cyclosporine due to the risk of increased oxaliplatin-related adverse reactions. Cyclosporine is known to be potentially nephrotoxic; because platinum-containing drugs like oxaliplatin are eliminated primarily through the kidney, oxaliplatin clearance may be decreased by coadministration with nephrotoxic agents.
    Dabigatran: (Major) Increase the frequency of monitoring in patients who are receiving concomitant therapy with oxaliplatin and dabigatran. Prolonged PT/INR occasionally associated with hemorrhage have been reported in patients who received oxaliplatin in combination with fluorouracil/leucovorin while on anticoagulants.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Avoid coadministration of oxaliplatin with tenofovir alafenamide due to the risk of increased oxaliplatin-related adverse reactions. Tenofovir alafenamide is known to be potentially nephrotoxic; because platinum-containing drugs like oxaliplatin are eliminated primarily through the kidney, oxaliplatin clearance may be decreased by coadministration with nephrotoxic agents.
    Dasatinib: (Major) Monitor ECGs and electrolytes in patients receiving oxaliplatin and dasatinib concomitantly; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. In vitro studies have shown that dasatinib also has the potential to prolong the QT interval.
    Degarelix: (Major) Monitor ECGs and electrolytes in patients receiving oxaliplatin and degarelix concomitantly; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Androgen deprivation therapy (i.e., degarelix) may prolong the QT/QTc interval.
    Desflurane: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of halogenated anesthetics with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Halogenated anesthetics can prolong the QT interval; QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Desipramine: (Minor) Monitor electrolytes and ECGs for QT prolongation if coadministration of tricyclic antidepressants with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Deutetrabenazine: (Major) Monitor ECG and electrolytes in patients receiving oxaliplatin concomitantly with deutetrabenazine; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes (TdP) have been reported with oxaliplatin use in postmarketing experience. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range.
    Dextromethorphan; Quinidine: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of quinidine with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Disopyramide: (Major) Monitor ECGs and electrolytes in patients receiving oxaliplatin and disopyramide concomitantly; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes (TdP) have been reported with oxaliplatin use in postmarketing experience. Disopyramide administration is also associated with QT prolongation and TdP.
    Dofetilide: (Major) Coadministration of dofetilide and oxaliplatin is not recommended as concurrent use may increase the risk of QT prolongation. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). QT prolongation and ventricular arrhythmias including fatal TdP have been reported with oxaliplatin use in postmarketing experience.
    Dolasetron: (Major) Monitor ECGs and electrolytes in patients receiving oxaliplatin and dolasetron concomitantly; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Dolasetron has also been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
    Dolutegravir; Rilpivirine: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of rilpivirine with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Supratherapeutic doses of rilpivirine (75 to 300 mg per day) have caused QT prolongation. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Donepezil: (Major) Monitor ECGs and electrolytes in patients receiving oxaliplatin and donepezil concomitantly; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes (TdP) have been reported with oxaliplatin use in postmarketing experience. Case reports indicate that QT prolongation and TdP can also occur during donepezil therapy.
    Donepezil; Memantine: (Major) Monitor ECGs and electrolytes in patients receiving oxaliplatin and donepezil concomitantly; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes (TdP) have been reported with oxaliplatin use in postmarketing experience. Case reports indicate that QT prolongation and TdP can also occur during donepezil therapy.
    Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Major) Avoid coadministration of oxaliplatin with tenofovir disoproxil fumarate due to the risk of increased oxaliplatin-related adverse reactions. Tenofovir disoproxil fumarate is known to be potentially nephrotoxic; because platinum-containing drugs like oxaliplatin are eliminated primarily through the kidney, oxaliplatin clearance may be decreased by coadministration with nephrotoxic agents.
    Doxepin: (Minor) Monitor electrolytes and ECGs for QT prolongation if coadministration of tricyclic antidepressants with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Dronedarone: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of oxaliplatin with dronedarone is contraindicated. Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily. QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in post-marketing experience. Additive QT prolongation is possible.
    Droperidol: (Major) Droperidol should not be used in combination with any drug known to have potential to prolong the QT interval, such as oxaliplatin. If coadministration cannot be avoided, use extreme caution; initiate droperidol at a low dose and increase the dose as needed to achieve the desired effect. Monitor ECGs and electrolytes if coadministration is unavoidable; correct electrolyte abnormalities prior to administration of oxaliplatin. Droperidol administration is associated with an established risk for QT prolongation and torsade de pointes (TdP). Some cases have occurred in patients with no known risk factors for QT prolongation and some cases have been fatal. QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Edoxaban: (Major) Increase the frequency of monitoring in patients who are receiving concomitant therapy with oxaliplatin and edoxaban. Prolonged PT/INR occasionally associated with hemorrhage have been reported in patients who received oxaliplatin in combination with fluorouracil/leucovorin while on anticoagulants.
    Efavirenz: (Major) Consider alternatives to efavirenz when treatment with oxaliplatin is necessary. QTc prolongation has been observed with the use of efavirenz. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Efavirenz; Emtricitabine; Tenofovir: (Major) Avoid coadministration of oxaliplatin with tenofovir disoproxil fumarate due to the risk of increased oxaliplatin-related adverse reactions. Tenofovir disoproxil fumarate is known to be potentially nephrotoxic; because platinum-containing drugs like oxaliplatin are eliminated primarily through the kidney, oxaliplatin clearance may be decreased by coadministration with nephrotoxic agents. (Major) Consider alternatives to efavirenz when treatment with oxaliplatin is necessary. QTc prolongation has been observed with the use of efavirenz. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of oxaliplatin with tenofovir disoproxil fumarate due to the risk of increased oxaliplatin-related adverse reactions. Tenofovir disoproxil fumarate is known to be potentially nephrotoxic; because platinum-containing drugs like oxaliplatin are eliminated primarily through the kidney, oxaliplatin clearance may be decreased by coadministration with nephrotoxic agents. (Major) Consider alternatives to efavirenz when treatment with oxaliplatin is necessary. QTc prolongation has been observed with the use of efavirenz. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Eliglustat: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of eliglustat with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations; QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Avoid coadministration of oxaliplatin with tenofovir alafenamide due to the risk of increased oxaliplatin-related adverse reactions. Tenofovir alafenamide is known to be potentially nephrotoxic; because platinum-containing drugs like oxaliplatin are eliminated primarily through the kidney, oxaliplatin clearance may be decreased by coadministration with nephrotoxic agents.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of oxaliplatin with tenofovir disoproxil fumarate due to the risk of increased oxaliplatin-related adverse reactions. Tenofovir disoproxil fumarate is known to be potentially nephrotoxic; because platinum-containing drugs like oxaliplatin are eliminated primarily through the kidney, oxaliplatin clearance may be decreased by coadministration with nephrotoxic agents.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Avoid coadministration of oxaliplatin with tenofovir alafenamide due to the risk of increased oxaliplatin-related adverse reactions. Tenofovir alafenamide is known to be potentially nephrotoxic; because platinum-containing drugs like oxaliplatin are eliminated primarily through the kidney, oxaliplatin clearance may be decreased by coadministration with nephrotoxic agents. (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of rilpivirine with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Supratherapeutic doses of rilpivirine (75 to 300 mg per day) have caused QT prolongation. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Major) Avoid coadministration of oxaliplatin with tenofovir disoproxil fumarate due to the risk of increased oxaliplatin-related adverse reactions. Tenofovir disoproxil fumarate is known to be potentially nephrotoxic; because platinum-containing drugs like oxaliplatin are eliminated primarily through the kidney, oxaliplatin clearance may be decreased by coadministration with nephrotoxic agents. (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of rilpivirine with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Supratherapeutic doses of rilpivirine (75 to 300 mg per day) have caused QT prolongation. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Emtricitabine; Tenofovir alafenamide: (Major) Avoid coadministration of oxaliplatin with tenofovir alafenamide due to the risk of increased oxaliplatin-related adverse reactions. Tenofovir alafenamide is known to be potentially nephrotoxic; because platinum-containing drugs like oxaliplatin are eliminated primarily through the kidney, oxaliplatin clearance may be decreased by coadministration with nephrotoxic agents.
    Emtricitabine; Tenofovir disoproxil fumarate: (Major) Avoid coadministration of oxaliplatin with tenofovir disoproxil fumarate due to the risk of increased oxaliplatin-related adverse reactions. Tenofovir disoproxil fumarate is known to be potentially nephrotoxic; because platinum-containing drugs like oxaliplatin are eliminated primarily through the kidney, oxaliplatin clearance may be decreased by coadministration with nephrotoxic agents.
    Encorafenib: (Major) Avoid coadministration of encorafenib and oxaliplatin due to the potential for additive QT prolongation. If coadministration is necessary, monitor ECG and electrolytes; correct electrolyte abnormalities prior to treatment. Encorafenib is associated with dose-dependent prolongation of the QT interval. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Enflurane: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of halogenated anesthetics with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Halogenated anesthetics can prolong the QT interval; QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Entrectinib: (Major) Avoid coadministration of entrectinib with oxaliplatin due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Eribulin: (Major) Closely monitor ECGs for QT prolongation and monitor electrolytes if coadministration of eribulin with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Eribulin has been associated with QT prolongation; QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience.
    Erythromycin: (Major) Monitor ECGs for QT prolongation and monitor electrolytes if coadministration of erythromycin with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Erythromycin is associated with QT prolongation and torsade de pointes (TdP); QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Erythromycin; Sulfisoxazole: (Major) Monitor ECGs for QT prolongation and monitor electrolytes if coadministration of erythromycin with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Erythromycin is associated with QT prolongation and torsade de pointes (TdP); QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Escitalopram: (Major) Monitor ECGs for QT prolongation and monitor electrolytes if coadministration of escitalopram with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Escitalopram has been associated with a risk of QT prolongation and torsade de pointes (TdP); QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Ethiodized Oil: (Major) Avoid coadministration of oxaliplatin with non-ionic contrast media due to the risk of increased oxaliplatin-related adverse reactions. Non-ionic contrast media is known to be potentially nephrotoxic; because platinum-containing drugs like oxaliplatin are eliminated primarily through the kidney, oxaliplatin clearance may be decreased by coadministration with nephrotoxic agents.
    Ezogabine: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of ezogabine with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Ezogabine has been associated with QT prolongation; QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Fingolimod: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of fingolimod with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. After the first fingolimod dose, overnight monitoring with continuous ECG in a medical facility is advised for patients taking QT prolonging drugs with a known risk of torsade de pointes (TdP). Fingolimod initiation results in decreased heart rate and may prolong the QT interval. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia.
    Flecainide: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of flecainide with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes (TdP) have been reported with oxaliplatin use in postmarketing experience. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs that have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
    Fluconazole: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of fluconazole with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Fluconazole has been associated with QT prolongation and rare cases of torsade de pointes (TdP). QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Fluoxetine: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of fluoxetine with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and torsade de pointes (TdP) have been reported in patients treated with fluoxetine; QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Fluphenazine: (Minor) Monitor electrolytes and ECGs for QT prolongation if coadministration of fluphenazine with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Fluphenazine is associated with a possible risk for QT prolongation. Theoretically, fluphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
    Fluticasone; Salmeterol: (Moderate) Monitor ECGs and electrolytes in patients receiving oxaliplatin concomitantly with long-acting beta-agonists; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Beta-agonists may also be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, fluticasone; vilanterol, umeclidinium; vilanterol) than with short-acting beta-agonists.
    Fluticasone; Umeclidinium; Vilanterol: (Moderate) Monitor ECGs and electrolytes in patients receiving oxaliplatin concomitantly with long-acting beta-agonists; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Beta-agonists may also be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, fluticasone; vilanterol, umeclidinium; vilanterol) than with short-acting beta-agonists.
    Fluticasone; Vilanterol: (Moderate) Monitor ECGs and electrolytes in patients receiving oxaliplatin concomitantly with long-acting beta-agonists; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Beta-agonists may also be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, fluticasone; vilanterol, umeclidinium; vilanterol) than with short-acting beta-agonists.
    Fluvoxamine: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of fluvoxamine with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with the use of both drugs in postmarketing experience.
    Formoterol: (Moderate) Monitor ECGs and electrolytes in patients receiving oxaliplatin concomitantly with long-acting beta-agonists; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Beta-agonists may also be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, fluticasone; vilanterol, umeclidinium; vilanterol) than with short-acting beta-agonists.
    Formoterol; Mometasone: (Moderate) Monitor ECGs and electrolytes in patients receiving oxaliplatin concomitantly with long-acting beta-agonists; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Beta-agonists may also be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, fluticasone; vilanterol, umeclidinium; vilanterol) than with short-acting beta-agonists.
    Foscarnet: (Major) Avoid use of foscarnet with oxaliplatin due to the potential for QT prolongation; oxaliplatin-related adverse reactions may also increase. Both QT prolongation and torsade de pointes (TdP) have been reported during postmarketing use of foscarnet. QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience. Additionally, foscarnet is known to be potentially nephrotoxic; because platinum-containing drugs like oxaliplatin are eliminated primarily through the kidney, oxaliplatin clearance may be decreased by coadministration with nephrotoxic agents.
    Fostemsavir: (Major) Monitor ECGs and electrolytes in patients receiving oxaliplatin concomitantly with fostemsavir; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Supratherapeutic doses of fostemsavir (2,400 mg twice daily, four times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation.
    Gemifloxacin: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of gemifloxacin with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Do not exceed the recommended dose of gemifloxacin, especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher. Gemifloxacin may prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5 to 10 hours following oral administration of gemifloxacin; the likelihood may increase with increasing doses. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Gemtuzumab Ozogamicin: (Major) Obtain a baseline ECG and electrolyte panel if coadministration of gemtuzumab ozogamicin with oxaliplatin is necessary; monitor ECGs for QT prolongation and monitor electrolytes during therapy. Correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
    Gilteritinib: (Major) Monitor ECGs and electrolytes in patients receiving oxaliplatin concomitantly with gilteritinib; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Gilteritinib has also been associated with QT prolongation.
    Glasdegib: (Major) Avoid coadministration of glasdegib with oxaliplatin due to the potential for additive QT prolongation. If coadministration cannot be avoided, monitor patients for increased risk of QT prolongation with increased frequency of ECG monitoring and monitor electrolytes; correct electrolyte abnormalities prior to administration of oxaliplatin. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience.
    Glycopyrrolate; Formoterol: (Moderate) Monitor ECGs and electrolytes in patients receiving oxaliplatin concomitantly with long-acting beta-agonists; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Beta-agonists may also be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, fluticasone; vilanterol, umeclidinium; vilanterol) than with short-acting beta-agonists.
    Goserelin: (Major) Monitor ECGs for QT prolongation and monitor electrolytes in patients receiving oxaliplatin concomitantly with goserelin; correct electrolyte abnormalities prior to administration of oxaliplatin. Prolongation of the QT interval and ventricular arrhythmias including fatal torsade de pointes (TdP) have been reported with oxaliplatin use in postmarketing experience. Androgen deprivation therapy (i.e., goserelin) may also prolong the QT/QTc interval.
    Granisetron: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of granisetron with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Granisetron has been associated with QT prolongation; QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Halogenated Anesthetics: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of halogenated anesthetics with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Halogenated anesthetics can prolong the QT interval; QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Haloperidol: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of haloperidol with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Halothane: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of halogenated anesthetics with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Halogenated anesthetics can prolong the QT interval; QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Histrelin: (Major) Monitor ECGs for QT prolongation and monitor electrolytes in patients receiving oxaliplatin concomitantly with histrelin; correct electrolyte abnormalities prior to administration of oxaliplatin. Prolongation of the QT interval and ventricular arrhythmias including fatal torsade de pointes (TdP) have been reported with oxaliplatin use in postmarketing experience. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval.
    Hydroxychloroquine: (Major) Avoid coadministration of oxaliplatin and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and ventricular arrhythmias including fatal torsade de pointes (TdP) have been reported with oxaliplatin use in postmarketing experience. Hydroxychloroquine prolongs the QT interval.
    Hydroxyzine: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of hydroxyzine with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with the use of both drugs in postmarketing experience.
    Ibutilide: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of ibutilide with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Ibutilide administration can cause QT prolongation and torsade de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. QT prolongation and ventricular arrhythmias including fatal TdP have been reported with oxaliplatin use in postmarketing experience.
    Iloperidone: (Major) Avoid coadministration of iloperidone and oxaliplatin due to an additive risk of QT prolongation. Iloperidone has been associated with QT prolongation. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Imipramine: (Minor) Monitor electrolytes and ECGs for QT prolongation if coadministration of tricyclic antidepressants with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Indacaterol: (Moderate) Monitor ECGs and electrolytes in patients receiving oxaliplatin concomitantly with long-acting beta-agonists; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Beta-agonists may also be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, fluticasone; vilanterol, umeclidinium; vilanterol) than with short-acting beta-agonists.
    Indacaterol; Glycopyrrolate: (Moderate) Monitor ECGs and electrolytes in patients receiving oxaliplatin concomitantly with long-acting beta-agonists; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Beta-agonists may also be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, fluticasone; vilanterol, umeclidinium; vilanterol) than with short-acting beta-agonists.
    Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with oxaliplatin due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Correct electrolyte abnormalities prior to treatment. Inotuzumab has been associated with QT interval prolongation. QT prolongation and ventricular arrhythmias including, fatal TdP, have been reported with oxaliplatin use in postmarketing experience.
    Iodipamide Meglumine: (Major) Avoid coadministration of oxaliplatin with ionic contrast media due to the risk of increased oxaliplatin-related adverse reactions. Ionic contrast media is known to be potentially nephrotoxic; because platinum-containing drugs like oxaliplatin are eliminated primarily through the kidney, oxaliplatin clearance may be decreased by coadministration with nephrotoxic agents.
    Iodixanol: (Major) Avoid coadministration of oxaliplatin with non-ionic contrast media due to the risk of increased oxaliplatin-related adverse reactions. Non-ionic contrast media is known to be potentially nephrotoxic; because platinum-containing drugs like oxaliplatin are eliminated primarily through the kidney, oxaliplatin clearance may be decreased by coadministration with nephrotoxic agents.
    Iohexol: (Major) Avoid coadministration of oxaliplatin with non-ionic contrast media due to the risk of increased oxaliplatin-related adverse reactions. Non-ionic contrast media is known to be potentially nephrotoxic; because platinum-containing drugs like oxaliplatin are eliminated primarily through the kidney, oxaliplatin clearance may be decreased by coadministration with nephrotoxic agents.
    Ionic Contrast Media: (Major) Avoid coadministration of oxaliplatin with ionic contrast media due to the risk of increased oxaliplatin-related adverse reactions. Ionic contrast media is known to be potentially nephrotoxic; because platinum-containing drugs like oxaliplatin are eliminated primarily through the kidney, oxaliplatin clearance may be decreased by coadministration with nephrotoxic agents.
    Iopamidol: (Major) Avoid coadministration of oxaliplatin with non-ionic contrast media due to the risk of increased oxaliplatin-related adverse reactions. Non-ionic contrast media is known to be potentially nephrotoxic; because platinum-containing drugs like oxaliplatin are eliminated primarily through the kidney, oxaliplatin clearance may be decreased by coadministration with nephrotoxic agents.
    Iopromide: (Major) Avoid coadministration of oxaliplatin with non-ionic contrast media due to the risk of increased oxaliplatin-related adverse reactions. Non-ionic contrast media is known to be potentially nephrotoxic; because platinum-containing drugs like oxaliplatin are eliminated primarily through the kidney, oxaliplatin clearance may be decreased by coadministration with nephrotoxic agents.
    Ioversol: (Major) Avoid coadministration of oxaliplatin with non-ionic contrast media due to the risk of increased oxaliplatin-related adverse reactions. Non-ionic contrast media is known to be potentially nephrotoxic; because platinum-containing drugs like oxaliplatin are eliminated primarily through the kidney, oxaliplatin clearance may be decreased by coadministration with nephrotoxic agents.
    Ioxaglate Meglumine; Ioxaglate Sodium: (Major) Avoid coadministration of oxaliplatin with ionic contrast media due to the risk of increased oxaliplatin-related adverse reactions. Ionic contrast media is known to be potentially nephrotoxic; because platinum-containing drugs like oxaliplatin are eliminated primarily through the kidney, oxaliplatin clearance may be decreased by coadministration with nephrotoxic agents.
    Ipratropium; Albuterol: (Minor) Monitor ECGs for QT prolongation and monitor electrolytes if coadministration is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists such as albuterol, levalbuterol, metaproterenol, pirbuterol, and terbutaline.
    Isoflurane: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of halogenated anesthetics with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Halogenated anesthetics can prolong the QT interval; QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Isosulfan Blue: (Major) Avoid coadministration of oxaliplatin with non-ionic contrast media due to the risk of increased oxaliplatin-related adverse reactions. Non-ionic contrast media is known to be potentially nephrotoxic; because platinum-containing drugs like oxaliplatin are eliminated primarily through the kidney, oxaliplatin clearance may be decreased by coadministration with nephrotoxic agents.
    Itraconazole: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of itraconazole with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Itraconazole has been associated with prolongation of the QT interval. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Ivosidenib: (Major) Avoid coadministration of ivosidenib with oxaliplatin due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. QT prolongation and ventricular arrhythmias, including fatal torsade de pointes, have been reported with oxaliplatin use in postmarketing experience.
    Kanamycin: (Major) Avoid coadministration of oxaliplatin with kanamycin due to the risk of increased oxaliplatin-related adverse reactions. Kanamycin is known to be potentially nephrotoxic; because platinum-containing drugs like oxaliplatin are eliminated primarily through the kidney, oxaliplatin clearance may be decreased by coadministration with nephrotoxic agents.
    Ketoconazole: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of ketoconazole with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Ketoconazole has been associated with prolongation of the QT interval. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of oxaliplatin with tenofovir disoproxil fumarate due to the risk of increased oxaliplatin-related adverse reactions. Tenofovir disoproxil fumarate is known to be potentially nephrotoxic; because platinum-containing drugs like oxaliplatin are eliminated primarily through the kidney, oxaliplatin clearance may be decreased by coadministration with nephrotoxic agents.
    Lansoprazole; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of clarithromycin with oxaliplatin due to the risk of QT prolongation. Clarithromycin is associated with an established risk for QT prolongation and torsade de pointes (TdP). QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Lapatinib: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of lapatinib with oxaliplatin is necessary; correct electrolyte abnormalities prior to treatment. Lapatinib has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience. QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Lefamulin: (Major) Avoid coadministration of lefamulin with oxaliplatin as concurrent use may increase the risk of QT prolongation. If coadministration cannot be avoided, monitor ECGs and electrolytes during treatment; correct electrolyte abnormalities prior to administration of oxaliplatin. Lefamulin has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. QT prolongation and ventricular arrhythmias, including fatal torsade de pointes, have been reported with oxaliplatin use in postmarketing experience.
    Lenvatinib: (Major) Avoid coadministration of lenvatinib with oxaliplatin due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience.
    Leuprolide: (Major) Monitor ECGs for QT prolongation and monitor electrolytes in patients receiving oxaliplatin concomitantly with leuprolide; correct electrolyte abnormalities prior to administration of oxaliplatin. Prolongation of the QT interval and ventricular arrhythmias including fatal torsade de pointes (TdP) have been reported with oxaliplatin use in postmarketing experience. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Leuprolide; Norethindrone: (Major) Monitor ECGs for QT prolongation and monitor electrolytes in patients receiving oxaliplatin concomitantly with leuprolide; correct electrolyte abnormalities prior to administration of oxaliplatin. Prolongation of the QT interval and ventricular arrhythmias including fatal torsade de pointes (TdP) have been reported with oxaliplatin use in postmarketing experience. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Levalbuterol: (Minor) Monitor ECGs for QT prolongation and monitor electrolytes if coadministration is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists such as albuterol, levalbuterol, metaproterenol, pirbuterol, and terbutaline.
    Levofloxacin: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of levofloxacin with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Levofloxacin has been associated with a risk of QT prolongation and, although extremely rare, torsade de pointes (TdP) has been reported during postmarketing surveillance of levofloxacin. QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Lithium: (Major) Avoid coadministration of oxaliplatin with lithium due to the risk of increased oxaliplatin-related adverse reactions; there is also an increased risk of QT prolongation. Lithium is known to be potentially nephrotoxic; because platinum-containing drugs like oxaliplatin are eliminated primarily through the kidney, oxaliplatin clearance may be decreased by coadministration with nephrotoxic agents. Additionally, lithium has been associated with QT prolongation. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Lofexidine: (Major) Monitor ECG and electrolytes if lofexidine is coadministered with oxaliplatin due to the potential for additive QT prolongation and torsade de pointes (TdP). Correct electrolyte abnormalities prior to administration of oxaliplatin. Lofexidine prolongs the QT interval. In addition, there are postmarketing reports of TdP. QT prolongation and ventricular arrhythmias including fatal TdP have been reported with oxaliplatin use in postmarketing experience.
    Long-acting beta-agonists: (Moderate) Monitor ECGs and electrolytes in patients receiving oxaliplatin concomitantly with long-acting beta-agonists; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Beta-agonists may also be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, fluticasone; vilanterol, umeclidinium; vilanterol) than with short-acting beta-agonists.
    Loperamide: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of loperamide with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Loperamide; Simethicone: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of loperamide with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir with oxaliplatin due to the potential for additive QT prolongation. If use together is necessary, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Lopinavir is associated with QT prolongation. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience.
    Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as oxaliplatin. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience.
    Maprotiline: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of maprotiline with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
    Mefloquine: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of mefloquine with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
    Meperidine; Promethazine: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of promethazine with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Metaproterenol: (Minor) Monitor ECGs for QT prolongation and monitor electrolytes if coadministration is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists such as albuterol, levalbuterol, metaproterenol, pirbuterol, and terbutaline.
    Methadone: (Major) The need to coadminister methadone with oxaliplatin should be done with extreme caution and a careful assessment of treatment risks versus benefits. Monitor electrolytes and ECGs for QT prolongation if coadministration of methadone with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes (TdP) have been reported with oxaliplatin use in post-marketing experience. Methadone is also considered to be associated with an increased risk for QT prolongation and TdP, especially at higher doses (greater than 200 mg per day, averaging approximately 400 mg per day in adult patients). Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction. Additive QT prolongation is possible.
    Methotrexate: (Major) Avoid coadministration of oxaliplatin with methotrexate due to the risk of increased oxaliplatin-related adverse reactions. Methotrexate is known to be potentially nephrotoxic; because platinum-containing drugs like oxaliplatin are eliminated primarily through the kidney, oxaliplatin clearance may be decreased by coadministration with nephrotoxic agents.
    Metronidazole: (Major) Concomitant use of metronidazole and oxaliplatin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Midostaurin: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of midostaurin with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation was reported in patients who received midostaurin in clinical trials. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Mifepristone: (Major) Avoid coadministration of mifepristone with oxaliplatin due to the risk of QT prolongation. Mifepristone is associated with dose-related prolongation of the QT interval. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Mirtazapine: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of mirtazapine with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Mirtazapine has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported in postmarketing experience with mirtazapine, primarily in overdose or in patients with other risk factors for QT prolongation. QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Mobocertinib: (Major) Concomitant use of mobocertinib and oxaliplatin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Moxifloxacin: (Major) Avoid coadministration of moxifloxacin with oxaliplatin as concurrent use may increase the risk of QT prolongation and torsade de pointes (TdP). Quinolones have been associated with a risk of QT prolongation. Although extremely rare, TdP has been reported during postmarketing surveillance of moxifloxacin. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory. QT prolongation and ventricular arrhythmias including fatal TdP have been reported with oxaliplatin use in postmarketing experience.
    Nilotinib: (Major) Avoid coadministration of nilotinib with oxaliplatin due to the risk of QT prolongation. Sudden death and QT interval prolongation have occurred in patients who received nilotinib therapy. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Non-Ionic Contrast Media: (Major) Avoid coadministration of oxaliplatin with non-ionic contrast media due to the risk of increased oxaliplatin-related adverse reactions. Non-ionic contrast media is known to be potentially nephrotoxic; because platinum-containing drugs like oxaliplatin are eliminated primarily through the kidney, oxaliplatin clearance may be decreased by coadministration with nephrotoxic agents.
    Norfloxacin: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of norfloxacin with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Quinolones have been associated with a risk of QT prolongation and torsade de pointes (TdP). Although extremely rare, TdP has been reported during postmarketing surveillance of norfloxacin. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory. QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Nortriptyline: (Minor) Monitor electrolytes and ECGs for QT prolongation if coadministration of tricyclic antidepressants with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Octreotide: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of octreotide with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes (TdP) have been reported with oxaliplatin use in postmarketing experience. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Ofloxacin: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of oxaliplatin with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Quinolones have been associated with a risk of QT prolongation and torsade de pointes (TdP). Although extremely rare, TdP has been reported during postmarketing surveillance of ofloxacin. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory. QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Olanzapine: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of olanzapine with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Olanzapine; Fluoxetine: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of fluoxetine with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and torsade de pointes (TdP) have been reported in patients treated with fluoxetine; QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience. (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of olanzapine with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Olanzapine; Samidorphan: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of olanzapine with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Olodaterol: (Moderate) Monitor ECGs and electrolytes in patients receiving oxaliplatin concomitantly with long-acting beta-agonists; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Beta-agonists may also be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, fluticasone; vilanterol, umeclidinium; vilanterol) than with short-acting beta-agonists.
    Ondansetron: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of ondansetron with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Ondansetron has been associated with a dose-related increase in the QT interval and postmarketing reports of torsade de pointes (TdP). QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Osilodrostat: (Major) Monitor ECG and electrolytes if osilodrostat is coadministered with oxaliplatin due to the potential for additive QT prolongation. Correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Osilodrostat is associated with dose-dependent QT prolongation.
    Osimertinib: (Major) Avoid coadministration of oxaliplatin with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, correct electrolyte abnormalities prior to administration of oxaliplatin. Periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. QT prolongation and ventricular arrhythmias including fatal TdP have been reported with oxaliplatin use in postmarketing experience.
    Ozanimod: (Major) In general, do not initiate ozanimod in patients taking oxaliplatin due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If concomitant use is necessary, monitor ECGs and electrolytes; correct electrolyte abnormalities prior to administration of oxaliplatin. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. QT prolongation and ventricular arrhythmias, including fatal TdP, have been reported with oxaliplatin use in postmarketing experience.
    Palifermin: (Moderate) Palifermin should not be administered within 24 hours before, during infusion of, or within 24 hours after administration of antineoplastic agents.
    Paliperidone: (Major) Avoid coadministration of paliperidone with oxaliplatin due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Paliperidone has been associated with QT prolongation; torsade de pointes and ventricular fibrillation have been reported in the setting of overdose. QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Panobinostat: (Major) Concomitant use of panobinostat with oxaliplatin is not recommended due to the risk of QT prolongation. QT prolongation has been reported with panobinostat; QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Pasireotide: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of pasireotide with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Pazopanib: (Major) Concomitant use of pazopanib with oxaliplatin is not advised due to the risk of QT prolongation. If coadministration is unavoidable, closely monitor electrolytes and ECGs for QT prolongation; correct electrolyte abnormalities prior to administration of oxaliplatin. Pazopanib has been associated with QT prolongation; QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Penicillamine: (Major) Do not use penicillamine with antineoplastic agents due to the increased risk of developing severe hematologic and renal toxicity.
    Pentamidine: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of pentamidine with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Systemic pentamidine has been associated with QT prolongation. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Perphenazine: (Minor) Monitor electrolytes and ECGs for QT prolongation if coadministration of perphenazine with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Perphenazine is also associated with a possible risk for QT prolongation. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
    Perphenazine; Amitriptyline: (Minor) Monitor electrolytes and ECGs for QT prolongation if coadministration of perphenazine with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Perphenazine is also associated with a possible risk for QT prolongation. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. (Minor) Monitor electrolytes and ECGs for QT prolongation if coadministration of tricyclic antidepressants with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Pimavanserin: (Major) Avoid coadministration of pimavanserin with oxaliplatin due to additive QT effects and increased risk of cardiac arrhythmia. Pimavanserin prolongs the QT interval. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Pimozide: (Contraindicated) Concomitant use of oxaliplatin and pimozide is contraindicated because there is an increased risk of QT prolongation and torsade de pointes. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). QT prolongation and ventricular arrhythmias including fatal torsade de pointes (TdP) have also been reported with oxaliplatin use in post-marketing experience. Additive QT prolongation is possible.
    Pirbuterol: (Minor) Monitor ECGs for QT prolongation and monitor electrolytes if coadministration is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists such as albuterol, levalbuterol, metaproterenol, pirbuterol, and terbutaline.
    Pitolisant: (Major) Avoid coadministration of pitolisant with oxaliplatin as concurrent use may increase the risk of QT prolongation. Pitolisant prolongs the QT interval. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Ponesimod: (Major) In general, do not initiate ponesimod in patients taking oxaliplatin due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP); additive immunosuppression may also occur which may extend the duration or severity of immune suppression. If concomitant use is unavoidable, monitor ECGs, electrolytes, and for signs and symptoms of infection. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. QT prolongation and ventricular arrhythmias, including fatal TdP, have been reported with oxaliplatin use in postmarketing experience.
    Posaconazole: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of posaconazole with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes (TdP). QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Primaquine: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of primaquine with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Primaquine has been associated with QT prolongation; QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Procainamide: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of procainamide with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Prochlorperazine: (Minor) Monitor electrolytes and ECGs for QT prolongation if coadministration of prochlorperazine with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Prochlorperazine is also associated with a possible risk for QT prolongation. Theoretically, prochlorperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
    Promethazine: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of promethazine with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Promethazine; Dextromethorphan: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of promethazine with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Promethazine; Phenylephrine: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of promethazine with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Propafenone: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of propafenone with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Propafenone is a Class IC antiarrhythmic which increases the QT interval, but largely due to prolongation of the QRS interval. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Protriptyline: (Minor) Monitor electrolytes and ECGs for QT prolongation if coadministration of tricyclic antidepressants with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Quetiapine: (Major) Avoid coadministration of quetiapine with oxaliplatin due to the risk of additive QT prolongation. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Quinidine: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of quinidine with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Quinine: (Major) Avoid coadministration of quinine with oxaliplatin due to the risk of additive QT prolongation and torsade de pointes (TdP). Quinine has been associated with QT prolongation and rare cases of TdP. QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Ranolazine: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of ranolazine with oxaliplatin is necessary as additive QT prolongation is possible; correct electrolyte abnormalities prior to administration of oxaliplatin. Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Relugolix: (Major) Monitor ECGs and electrolytes in patients receiving oxaliplatin concomitantly with relugolix; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
    Relugolix; Estradiol; Norethindrone acetate: (Major) Monitor ECGs and electrolytes in patients receiving oxaliplatin concomitantly with relugolix; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
    Ribociclib: (Major) Avoid coadministration of ribociclib with oxaliplatin due to the risk of additive QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner; these ECG changes typically occurred within the first four weeks of treatment and were reversible with dose interruption. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with oxaliplatin due to the risk of additive QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner; these ECG changes typically occurred within the first four weeks of treatment and were reversible with dose interruption. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Rilpivirine: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of rilpivirine with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Supratherapeutic doses of rilpivirine (75 to 300 mg per day) have caused QT prolongation. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Risperidone: (Major) Closely monitor electrolytes and ECGs for QT prolongation if coadministration of risperidone with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes (TdP), primarily in the overdose setting. QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Rivaroxaban: (Major) Increase the frequency of monitoring in patients who are receiving concomitant therapy with oxaliplatin and rivaroxaban. Prolonged PT/INR occasionally associated with hemorrhage have been reported in patients who received oxaliplatin in combination with fluorouracil/leucovorin while on anticoagulants.
    Romidepsin: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of romidepsin with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Romidepsin has been reported to prolong the QT interval. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Salmeterol: (Moderate) Monitor ECGs and electrolytes in patients receiving oxaliplatin concomitantly with long-acting beta-agonists; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Beta-agonists may also be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, fluticasone; vilanterol, umeclidinium; vilanterol) than with short-acting beta-agonists.
    Saquinavir: (Major) Avoid coadministration of saquinavir with oxaliplatin due to the risk of additive QT prolongation. If concomitant use is unavoidable, perform a baseline ECG, and monitor ECGs and electrolytes during treatment; correct electrolyte abnormalities prior to administration of oxaliplatin. Saquinavir boosted with ritonavir increases the QT interval in a dose-dependent fashion, which may increase the risk for serious arrhythmias such as torsade de pointes (TdP). QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
    Selpercatinib: (Major) Monitor ECGs more frequently for QT prolongation if coadministration of selpercatinib with oxaliplatin is necessary due to the risk of additive QT prolongation. Additionally, monitor electrolytes and correct any abnormalities prior to administration of oxaliplatin. Concentration-dependent QT prolongation has been observed with selpercatinib therapy. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience.
    Sertraline: (Major) Monitor ECGs and electrolytes in patients receiving oxaliplatin concomitantly with sertraline; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes (TdP) have been reported with oxaliplatin use in postmarketing experience. QTc prolongation and TdP have been reported during postmarketing use of sertraline; most cases had confounding risk factors. The risk of sertraline-induced QT prolongation is generally considered to be low in clinical practice. Its effect on QTc interval is minimal (typically less than 5 msec), and the drug has been used safely in patients with cardiac disease (e.g., recent myocardial infarction, unstable angina, chronic heart failure).
    Sevoflurane: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of halogenated anesthetics with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Halogenated anesthetics can prolong the QT interval; QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Short-acting beta-agonists: (Minor) Monitor ECGs for QT prolongation and monitor electrolytes if coadministration is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists such as albuterol, levalbuterol, metaproterenol, pirbuterol, and terbutaline.
    Siponimod: (Major) In general, do not initiate treatment with siponimod in patients receiving oxaliplatin due to the potential for QT prolongation. Consult a cardiologist regarding appropriate monitoring if siponimod use is required. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience.
    Solifenacin: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of solifenacin with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Solifenacin has been associated with dose-dependent prolongation of the QT interval; torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined. QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Sorafenib: (Major) Avoid coadministration of sorafenib with oxaliplatin due to the risk of additive QT prolongation. If concomitant use is unavoidable, monitor electrocardiograms and correct electrolyte abnormalities. An interruption or discontinuation of sorafenib therapy may be necessary if QT prolongation occurs. Sorafenib is associated with QTc prolongation. QT prolongation and ventricular arrhythmias including fatal torsade de pointes (TdP) have been reported with oxaliplatin use in postmarketing experience.
    Sotalol: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of sotalol with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Sotalol administration is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Sunitinib: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of sunitinib with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP). Prolongation of the QT interval and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Tacrolimus: (Major) Avoid coadministration of oxaliplatin with tacrolimus due to the risk of increased oxaliplatin-related adverse reactions; there is also an increased risk of QT prolongation. Tacrolimus is known to be potentially nephrotoxic; because platinum-containing drugs like oxaliplatin are eliminated primarily through the kidney, oxaliplatin clearance may be decreased by coadministration with nephrotoxic agents. Tacrolimus causes QT prolongation. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Tamoxifen: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of tamoxifen with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Tamoxifen has been reported to prolong the QT interval, usually in overdose or when used in high doses; rare case reports of QT prolongation have also been described when tamoxifen is used at lower doses. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience.
    Telavancin: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of telavancin with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Telavancin has been associated with QT prolongation. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Telithromycin: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of telithromycin with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Telithromycin is associated with QT prolongation and torsade de pointes (TdP). QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Tenofovir Alafenamide: (Major) Avoid coadministration of oxaliplatin with tenofovir alafenamide due to the risk of increased oxaliplatin-related adverse reactions. Tenofovir alafenamide is known to be potentially nephrotoxic; because platinum-containing drugs like oxaliplatin are eliminated primarily through the kidney, oxaliplatin clearance may be decreased by coadministration with nephrotoxic agents.
    Tenofovir Alafenamide: (Major) Avoid coadministration of oxaliplatin with tenofovir alafenamide due to the risk of increased oxaliplatin-related adverse reactions. Tenofovir alafenamide is known to be potentially nephrotoxic; because platinum-containing drugs like oxaliplatin are eliminated primarily through the kidney, oxaliplatin clearance may be decreased by coadministration with nephrotoxic agents.
    Tenofovir, PMPA: (Major) Avoid coadministration of oxaliplatin with tenofovir disoproxil fumarate due to the risk of increased oxaliplatin-related adverse reactions. Tenofovir disoproxil fumarate is known to be potentially nephrotoxic; because platinum-containing drugs like oxaliplatin are eliminated primarily through the kidney, oxaliplatin clearance may be decreased by coadministration with nephrotoxic agents.
    Terbutaline: (Minor) Monitor ECGs for QT prolongation and monitor electrolytes if coadministration is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists such as albuterol, levalbuterol, metaproterenol, pirbuterol, and terbutaline.
    Tetrabenazine: (Major) Avoid coadministration of tetrabenazine with oxaliplatin due to the risk of additive QT prolongation. Tetrabenazine causes a small increase in the corrected QT interval (QTc). QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Thioridazine: (Contraindicated) Coadministration of thioridazine with oxaliplatin is contraindicated due to the risk of additive QT prolongation and torsade de pointes (TdP). Thioridazine is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Tiotropium; Olodaterol: (Moderate) Monitor ECGs and electrolytes in patients receiving oxaliplatin concomitantly with long-acting beta-agonists; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Beta-agonists may also be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, fluticasone; vilanterol, umeclidinium; vilanterol) than with short-acting beta-agonists.
    Tolterodine: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of tolterodine with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Toremifene: (Major) Avoid coadministration of oxaliplatin with toremifene if possible due to the risk of additive QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes; correct any electrolyte abnormalities. Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner. Prolongation of the QT interval and ventricular arrhythmias including fatal torsade de pointes (TdP) have been reported with oxaliplatin use in postmarketing experience.
    Trazodone: (Major) Avoid coadministration of trazodone with oxaliplatin due to the additive risk of QT prolongation. Trazodone can prolong the QT/QTc interval at therapeutic doses; in addition, there are postmarketing reports of torsade de pointes (TdP). QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Triclabendazole: (Major) Monitor ECG and electrolytes if triclabendazole is coadministered with oxaliplatin due to the potential for additive QT prolongation. Correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Transient prolongation of the mean QTc interval was noted on the ECG recordings in dogs administered triclabendazole.
    Tricyclic antidepressants: (Minor) Monitor electrolytes and ECGs for QT prolongation if coadministration of tricyclic antidepressants with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Trifluoperazine: (Minor) Monitor electrolytes and ECGs for QT prolongation if coadministration of trifluoperazine with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
    Trimipramine: (Minor) Monitor electrolytes and ECGs for QT prolongation if coadministration of tricyclic antidepressants with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Triptorelin: (Major) Monitor ECGs for QT prolongation and monitor electrolytes in patients receiving oxaliplatin concomitantly with triptorelin; correct electrolyte abnormalities prior to administration of oxaliplatin. Prolongation of the QT interval and ventricular arrhythmias including fatal torsade de pointes (TdP) have been reported with oxaliplatin use in postmarketing experience. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
    Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
    Umeclidinium; Vilanterol: (Moderate) Monitor ECGs and electrolytes in patients receiving oxaliplatin concomitantly with long-acting beta-agonists; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Beta-agonists may also be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, fluticasone; vilanterol, umeclidinium; vilanterol) than with short-acting beta-agonists.
    Valacyclovir: (Major) Avoid coadministration of oxaliplatin with valacyclovir due to the risk of increased oxaliplatin-related adverse reactions. Valacyclovir is known to be potentially nephrotoxic; because platinum-containing drugs like oxaliplatin are eliminated primarily through the kidney, oxaliplatin clearance may be decreased by coadministration with nephrotoxic agents.
    Vancomycin: (Major) Avoid coadministration of oxaliplatin with vancomycin due to the risk of increased oxaliplatin-related adverse reactions. Vancomycin is known to be potentially nephrotoxic; because platinum-containing drugs like oxaliplatin are eliminated primarily through the kidney, oxaliplatin clearance may be decreased by coadministration with nephrotoxic agents.
    Vandetanib: (Major) Avoid coadministration of vandetanib with oxaliplatin due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to treatment. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Prolongation of the QT interval and ventricular arrhythmias including fatal TdP have been reported with oxaliplatin use in postmarketing experience.
    Vardenafil: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of vardenafil with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Vardenafil is associated with QT prolongation at both therapeutic and supratherapeutic doses. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Vemurafenib: (Major) Closely monitor electrolytes and ECGs for QT prolongation if coadministration of vemurafenib with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Vemurafenib has been associated with QT prolongation. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Venlafaxine: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of venlafaxine with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Venlafaxine administration is associated with a possible risk of QT prolongation; torsade de pointes (TdP) has reported with postmarketing use. QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Voclosporin: (Major) Monitor ECGs and electrolytes in patients receiving oxaliplatin concomitantly with voclosporin; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
    Voriconazole: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of voriconazole with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Voriconazole has been associated with QT prolongation and rare cases of torsade de pointes (TdP); QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Vorinostat: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of vorinostat with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Vorinostat therapy is associated with a risk of QT prolongation. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Warfarin: (Moderate) Increase the frequency of PT/INR monitoring in patients who are receiving concomitant therapy with oxaliplatin and warfarin. Prolonged PT/INR occasionally associated with hemorrhage have been reported in patients who received oxaliplatin in combination with fluorouracil/leucovorin while on anticoagulants.
    Ziprasidone: (Major) Concomitant use of ziprasidone and oxaliplatin should be avoided due to the potential for additive QT prolongation. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience.

    PREGNANCY AND LACTATION

    Pregnancy

    Pregnancy should be avoided by females of reproductive potential during oxaliplatin treatment and for at least 9 months after the last dose. Although there are no adequately controlled studies in pregnant women, oxaliplatin can cause fetal harm or death when administered during pregnancy based on its mechanism of action and animal studies. Women who are pregnant or who become pregnant while receiving oxaliplatin should be apprised of the potential hazard to the fetus. Oxaliplatin caused developmental mortality (increased early resorptions) when administered to pregnant rats on gestational days 6 to 16 and adversely affected fetal growth when given on gestational days 6 to 10 (decreased fetal weight, delayed ossification).

    Due to the potential for serious adverse reactions in nursing infants from oxaliplatin, advise women to discontinue breast-feeding during treatment and for 3 months after the final dose. It is not known whether oxaliplatin is present in human milk, although many drugs are excreted in human milk.

    MECHANISM OF ACTION

    Oxaliplatin is a non cell-cycle specific, alkylating agent that inhibits DNA replication and transcription via formation of inter- and intrastrand platinum-DNA crosslinks. It contains a bulky carrier ligand (1,2-diaminocyclohexane [DACH]), which is not present in either cisplatin or carboplatin, that determines the cytotoxicity of oxaliplatin and influences tissue distribution. Oxaliplatin undergoes nonenzymatic conversion to active metabolites via displacement of the labile oxalate ligand, forming several transient reactive species are formed (e.g., monoaquo and diaquo DACH platinum) which covalently bind with macromolecules. The DACH carrier ligand is thought to contribute to the enhanced cytotoxicity and lack of cross-resistance between oxaliplatin and cisplatin. Oxaliplatin produces fewer DNA cross-links compared to cisplatin and is less able to form these cross-links; however, it is more efficient (potent) than cisplatin and thus requires fewer DNA adducts to inhibit DNA chain elongation and produce cytotoxicity. The DACH ligand may also inhibit DNA repair by preventing or reducing the binding of repair proteins (e.g., the mismatch repair enzyme complex). Oxaliplatin showed antitumor activity against colon cancer in vitro. In combination with fluorouracil, oxaliplatin exhibits antiproliferative activity in vitro and in vivo greater than either drug alone in several tumor models.
     
    Tumor cell resistance mechanisms to platinum compounds include reduced accumulation in cells, increased DNA repair mechanisms (e.g., changes in mismatch repair and enhanced replicative bypass), inactivation by conjugation with glutathione or sequestration involving metallothionine, and enhanced tolerance to platinum-DNA adducts. Changes in mismatch repair and enhanced replicative bypass do not appear to contribute to oxaliplatin resistance as compared to cisplatin or carboplatin.

    PHARMACOKINETICS

    Oxaliplatin is administered intravenously. It is highly (greater than 90%) and irreversibly bound to plasma proteins (primarily albumin and gamma-globulins). Platinum also binds irreversibly and accumulates in erythrocytes, where it appears to have no relevant activity. No platinum accumulation was observed in plasma ultrafiltrate following an oxaliplatin dose of 85 mg/m2 every 2 weeks. Oxaliplatin has a large volume of distribution (440 to 582 liters) compared to cisplatin (19.2 liters) and carboplatin (17 liters); this could be due to the 1,2-diaminocyclohexane (DACH) moiety associated with oxaliplatin, which may confer some advantages in terms of enhanced tissue penetration due to altered cell membrane permeability. After a 2-hour oxaliplatin infusion, approximately 15% of the administered platinum is present in the systemic circulation; the remaining 85% is rapidly distributed into tissues or eliminated in the urine. Due to the rapid biotransformation of oxaliplatin, its elimination is described based on platinum levels rather than the parent compound. The decline of ultrafiltrable platinum levels following oxaliplatin administration is triphasic, characterized by 2 relatively short distribution phases (alpha half-life; 0.43 hours; beta half-life, 16.8 hours) and a long terminal elimination phase (half-life 392 hours). Platinum clearance was 10 to 17 liters/hour, exceeding the average human glomerular filtration rate (GFR; 7.5 liters/hour); the renal clearance of ultrafiltrable platinum is significantly correlated with GFR). The major route of platinum elimination is renal excretion, accounting for 54% of a single dose of oxaliplatin after 5 days; fecal excretion accounted for 2% of the dose. However, because tissue distribution is also important for oxaliplatin clearance, renal clearance alone is not a useful predictor of platinum exposure and toxicity after oxaliplatin administration.
     
    Affected cytochrome P450 isoenzymes and drug transporters: None
    Oxaliplatin undergoes rapid and extensive nonenzymatic biotransformation in the blood; there is no evidence of CYP450-mediated metabolism in vitro. Up to 17 platinum-containing derivatives have been observed in plasma ultrafiltrate samples from patients, including several cytotoxic species (monochloro DACH platinum, dichloro DACH platinum, monoaquo DACH platinum, and diaquo DACH platinum) as well as several noncytotoxic, conjugated species. Oxaliplatin does not inhibit human CYP450 isoenzymes in vitro.

    Intravenous Route

    After a single 85 mg/m2 dose of oxaliplatin over 2 hours, the Cmax of the ultrafiltrable platinum was 0.814 mcg/mL. Interpatient and intrapatient variability in ultrafiltrable platinum exposure (AUC0-48) assessed over 3 cycles was 23% and 6%, respectively.