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  • CLASSES

    Platinum Compounds

    DEA CLASS

    Rx

    DESCRIPTION

    Oxaliplatin is a third-generation platinum analog; activity and toxicities differ from both cisplatin and carboplatin; lacks cross-resistance with these compounds. No significant renal or auditory toxicity; hematological toxicity usually mild. Broad spectrum of antineoplastic activity including colorectal CA, ovarian CA, pancreatic CA, non-Hodgkin's lymphoma, breast CA, lung CA, prostate CA, germ-cell carcinomas, and malignant mesothelioma.

    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 5-fluorouracil (5-FU) and leucovorin (LV) (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 5-fluorouracil (5-FU) 400 mg/m2 IV bolus over 2 to 4 minutes, then 5-FU 600 mg/m2 continuous IV infusion (CIV) over 22 hours. On day 2, give leucovorin 200 mg/m2 IV over 2 hours, followed by 5-FU 400 mg/m2 IV bolus, then 5-FU 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 5-FU and leucovorin need not be changed. In a multicenter trial, patients with stage II or III completely resected colon cancer (n = 2,246) were randomized to either FOLFOX 4 or infusional 5-FU/LV (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 5-FU/LV (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 leucovorin infusion on day 1 with 5-fluorouracil (5-FU) 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 5-FU. 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 5-FU/leucovorin. After a median follow-up of 57 months, the addition of oxaliplatin to capecitabine significantly improved the primary end point 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 5-FU/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 5-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 5-FU 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 5-fluorouracil (5-FU) (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 5-FU 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 5-FU 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 5-FU/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 5-fluorouracil (5-FU) (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 5-FU 400 mg/m2 IV bolus on day 1, followed by 5-FU 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 5-FU and leucovorin need not be changed. Administering 5-FU 2,400 mg/m2 over 46 to 48 hours (FOLFOX6) provides similar exposure to the daily bolus plus 22 hour 5-FU 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 (n = 2,246) were randomized to either FOLFOX4 or infusional 5-FU/LV (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 5-FU/LV (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—IIIB gastric cancer† in combination with capecitabine.
    Intravenous dosage
    Adults

    Oxaliplatin 130 mg/m2 IV on day 1 in combination with capecitabine 1000 mg/m2 PO twice daily on days 1—14, repeated every 3 weeks for 8 cycles. In a phase III clinical trial, 1035 patients with stage II—IIIB gastric cancer were randomized to receive adjuvant capecitabine and oxaliplatin (XELOX) or observation after surgical (D2) resection. The primary end point, 3-year disease free survival (DFS), was significantly improved with XELOX (74% vs. 60%, HR 0.56, 95% CI 0.44—0.72, p < 0.0001). At a median follow-up of 34.4 months, the difference in overall survival was not significantly different between the 2 treatment arms (HR 0.74, 95% CI 0.53—1.03, p = 0.0775).

    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 5-FU 400 mg/m2 IV bolus then 5-FU 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 5-FU (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 receved5-FU, leucovorin, and oxaliplatin (OFF) compared with 5-FU 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 5-FU 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.[63750]

    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.

    †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 greater than or equal to 30 mL/min): 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

    Premedication with antiemetics, including 5-HT3 blockers with or without dexamethasone, is recommended. Prehydration is not required.
    Acute hypersensitivity reactions have been reported during or immediately following oxaliplatin administration. Appropriate supportive care equipment and medications should be readily available.

    Intravenous Administration

    Do not use aluminum needles or IV sets containing aluminum for preparation or administration. Aluminum has been reported to cause degradation of platinum compounds.
    Do not mix oxaliplatin with alkaline medications or diluents (such as basic solutions of 5-FU) or administer simultaneously through the same infusion line.
     
    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 prior to administration. 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. If this occurs, the duration of the leucovorin and 5-FU infusions do not need to be adjusted.
    Avoid extravasation; severe tissue damage and necrosis has 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 at 77 degrees F; excursions permitted to 59-86 degrees F
    - Store diluted product in accordance with package insert instructions

    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 is associated with a risk of serious hypersensitivity reactions or anaphylaxis, which may occur during any cycle within minutes of oxaliplatin administration. These a 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 urticaria, pruritus, facial flushing, diarrhea associated with the infusion, shortness of breath, bronchospasm, diaphoresis, chest pain, hypotension, disorientation, and syncope. Epinephrine, corticosteroids, and antihistamines have been utilized to treat these reactions. Discontinue oxaliplatin in patients who develop an anaphylactic/anaphylactoid reaction to oxaliplatin, and do not rechallenge.

    Peripheral neuropathy

    Due to dose-limiting neurotoxicity, oxaliplatin should be used cautiously in patients with preexisting peripheral neuropathy. Acute, reversible, primarily peripheral, sensory neuropathy has been reported with oxaliplatin and can occur within hours to 1 or 2 days after dosing; this acute neuropathy generally resolves within 14 days and frequently recurs with further dosing. This type of neuropathy, usually presenting as transient paresthesia, dysesthesia, and hypoesthesia in the hands, feet, perioral area, or throat, may be exacerbated by exposure to cold temperature or cold objects. Patients should be instructed to avoid cold drinks, use of ice, and should cover exposed skin prior to exposure to cold temperature or cold objects. 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. A dose reduction or interruption / discontinuation of therapy may be necessary for patients who develop grade 2 or higher peripheral neuropathy. Prevention or treatment of the neuropathies have been studied. Administering 1 gm each of calcium gluconate and magnesium sulfate as a 30 minute infusion pre- and post-oxaliplatin was thought to prevent or reduce neurotoxicity; however, this practice was shown to be no more effective than placebo in a phase 3 clinical trial.

    Bone marrow suppression, chemotherapy, herpes infection, infection, neutropenia, radiation therapy, thrombocytopenia, varicella, viral infection

    Patients who have had previous myelosuppressive therapy such as chemotherapy or radiation therapy are at risk of increased bone marrow suppression during oxaliplatin treatment. Do not administer oxaliplatin unless the ANC is 1,500/mm3 or higher and platelets are 75,000/mm3 or higher; if severe neutropenia, thrombocytopenia, or neutropenic fever develops, an interruption of therapy or dose reduction may be necessary. Hold oxaliplatin for sepsis or septic shock. This drug should only be used by clinicians experienced in chemotherapy. Patients with an active infection should be treated prior to receiving oxaliplatin. Opportunistic infections, including fungal infection, may occur in some patients due to severe myelosuppression; sepsis, neutropenic sepsis, and septic shock have been reported with oxaliplatin use, including fatal outcomes. Patients with a history of varicella zoster, other herpes infection (e.g., herpes simplex), or other viral infection are at risk for reactivation of the infection when treated with chemotherapy. Patients should immediately report any symptoms of severe myelosuppression such as fever, sore throat, or abnormal bleeding.

    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. 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.

    Alcoholism, bradycardia, cardiac arrhythmias, cardiac disease, coronary artery disease, diabetes mellitus, electrolyte imbalance, females, heart failure, hypertension, hypocalcemia, hypokalemia, hypomagnesemia, long QT syndrome, malnutrition, myocardial infarction, QT prolongation, thyroid disease, torsade de pointes

    Avoid the use of oxaliplatin in patients with congenital long QT syndrome. Use oxaliplatin with caution and monitor EGCs in patients with cardiac disease or other conditions that may increase the risk of QT prolongation including cardiac arrhythmias, heart failure, bradycardia, myocardial infarction, hypertension, coronary artery disease, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause an electrolyte imbalance. Females, patients with diabetes mellitus, thyroid disease, malnutrition, alcoholism, or hepatic disease may also be at increased risk for QT prolongation. 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 with oxaliplatin and monitor these electrolytes periodically during therapy.

    Encephalopathy

    Reversible Posterior Leukoencephalopathy Syndrome (RPLS), also known as Posterior Reversible Encephalopathy Syndrome (PRES), has been reported with oxaliplatin use. Symptoms of RPLS include seizures, headache, visual disturbances (e.g., blurry vision or blindness), confusion, and altered mental status. This syndrome may be confirmed on magnetic resonance imaging.

    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.

    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 fever. Discontinue oxaliplatin if signs or symptoms of rhabdomyolysis occur.

    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 and infusional fluorouracil and leucovorin. The incidence of diarrhea, dehydration, hypokalemia, leukopenia, syncope, and fatigue were higher in elderly patients.

    Pregnancy

    Pregnancy should be avoided by females of reproductive potential during oxaliplatin treatment (FDA pregnancy risk category D). Although there are no adequately controlled studies in pregnant animals or humans, oxaliplatin can cause fetal harm 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. In animal studies, administration of oxaliplatin during gestation at doses less than one-tenth the recommended human dose based on body surface area caused developmental mortality (increased early resorptions) and adversely affected fetal growth (decreased fetal weight, delayed ossification).

    Contraception requirements, infertility, reproductive risk

    Counsel patients about the reproductive risk and contraception requirements during oxaliplatin treatment. Oxaliplatin can cause fetal harm if taken by the mother during pregnancy. Females and males with female partners of reproductive potential should avoid pregnancy and use effective contraception during treatment with oxaliplatin. Females of reproductive potential should undergo pregnancy testing prior to initiation 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. Administration to both male and female rats prior to mating resulted in 97% post-implantation loss in animals that received approximately one-seventh of the recommended human dose based on body surface area. Testicular damage (e.g., degeneration, hypoplasia, and atrophy) was observed in dogs that received approximately one-sixth of the recommended human dose.

    Breast-feeding

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

    ADVERSE REACTIONS

    Severe

    leukopenia / Delayed / 19.0-20.0
    peripheral neuropathy / Delayed / 7.0-19.0
    paresthesias / Delayed / 6.0-18.0
    neutropenia / Delayed / 12.0-18.0
    thromboembolism / Delayed / 6.0-9.0
    thrombocytopenia / Delayed / 2.0-5.0
    GI obstruction / Delayed / 2.0-4.9
    anemia / Delayed / 1.0-3.0
    hypotension / Rapid / 0-3.0
    back pain / Delayed / 0-3.0
    dysesthesia / Delayed / 1.0-2.0
    myalgia / Early / 0-2.0
    pulmonary fibrosis / Delayed / 0-1.0
    chest pain (unspecified) / Early / 0-1.0
    thrombotic thrombocytopenic purpura (TTP) / Delayed / 0-1.0
    GI bleeding / Delayed / 0.2-0.2
    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
    intracranial bleeding / Delayed / Incidence not known
    hemolytic-uremic syndrome / Delayed / Incidence not known
    ileus / Delayed / Incidence not known
    tissue necrosis / Early / Incidence not known
    angioedema / Rapid / Incidence not known
    anaphylactic shock / Rapid / Incidence not known
    bronchospasm / Rapid / Incidence not known
    hemolytic anemia / Delayed / Incidence not known
    serious hypersensitivity reactions or anaphylaxis / 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
    eosinophilic pneumonia / Delayed / Incidence not known
    hearing loss / Delayed / Incidence not known
    visual impairment / Early / Incidence not known
    optic neuritis / Delayed / Incidence not known
    superinfection / Delayed / Incidence not known
    torsade de pointes / Rapid / Incidence not known
    rhabdomyolysis / Delayed / Incidence not known

    Moderate

    elevated hepatic enzymes / Delayed / 6.0-57.0
    stomatitis / Delayed / 14.0-42.0
    constipation / Delayed / 22.0-32.0
    hyperbilirubinemia / Delayed / 6.0-20.0
    dyspnea / Early / 5.0-20.0
    edema / Delayed / 10.0-15.0
    hyperglycemia / Delayed / 14.0-14.0
    palmar-plantar erythrodysesthesia (hand and foot syndrome) / Delayed / 1.0-11.0
    hypokalemia / Delayed / 3.0-11.0
    peripheral edema / Delayed / 5.0-10.0
    depression / Delayed / 2.0-9.0
    conjunctivitis / Delayed / 2.0-9.0
    dehydration / Delayed / 5.0-9.0
    hypoalbuminemia / Delayed / 8.0-8.0
    hyponatremia / Delayed / 8.0-8.0
    hypocalcemia / Delayed / 7.0-7.0
    dysuria / Early / 2.0-6.0
    hematuria / Delayed / 6.0-6.0
    lymphopenia / Delayed / 6.0-6.0
    ataxia / Delayed / 2.0-5.0
    hypertension / Early / 2.0-5.0
    sinus tachycardia / Rapid / 2.0-5.0
    bone pain / Delayed / 2.0-5.0
    urinary incontinence / Early / 2.0-4.9
    hemoptysis / Delayed / 2.0-4.9
    melena / Delayed / 2.0-4.9
    hot flashes / Early / 2.0-4.9
    hypoxia / Early / 2.0-4.9
    pneumonitis / Delayed / 2.0-4.9
    ascites / Delayed / 2.0-4.9
    hemorrhoids / Delayed / 2.0-4.9
    proctitis / Delayed / 2.0-4.9
    dysphagia / Delayed / Incidence not known
    dysarthria / Delayed / Incidence not known
    pseudomembranous colitis / Delayed / Incidence not known
    colitis / Delayed / Incidence not known
    erythema / Early / Incidence not known
    peliosis hepatis / Delayed / Incidence not known
    QT prolongation / Rapid / Incidence not known
    confusion / Early / Incidence not known

    Mild

    nausea / Early / 64.0-74.0
    fatigue / Early / 44.0-70.0
    diarrhea / Early / 46.0-67.0
    vomiting / Early / 37.0-47.0
    alopecia / Delayed / 3.0-38.0
    anorexia / Delayed / 13.0-35.0
    cough / Delayed / 2.0-35.0
    abdominal pain / Early / 18.0-33.0
    fever / Early / 16.0-29.0
    infection / Delayed / 2.0-25.0
    epistaxis / Delayed / 9.0-16.0
    rhinitis / Early / 6.0-15.0
    dysgeusia / Early / 5.0-14.0
    dyspepsia / Early / 7.0-14.0
    insomnia / Early / 9.0-13.0
    dizziness / Early / 7.0-13.0
    headache / Early / 7.0-13.0
    injection site reaction / Rapid / 6.0-11.0
    rash / Early / 5.0-11.0
    weight loss / Delayed / 2.0-11.0
    flushing / Rapid / 3.0-10.0
    weight gain / Delayed / 10.0-10.0
    arthralgia / Delayed / 5.0-10.0
    flatulence / Early / 3.0-9.0
    pharyngitis / Delayed / 2.0-9.0
    lacrimation / Early / 1.0-9.0
    anxiety / Delayed / 2.0-6.0
    increased urinary frequency / Early / 5.0-5.0
    hiccups / Early / 2.0-5.0
    gastroesophageal reflux / Delayed / 1.0-5.0
    drowsiness / Early / 2.0-5.0
    syncope / Early / 2.0-5.0
    weakness / Early / 2.0-5.0
    gingivitis / Delayed / 2.0-4.9
    xerostomia / Early / 2.0-4.9
    tenesmus / Delayed / 2.0-4.9
    purpura / Delayed / 2.0-4.9
    pruritus / Rapid / 2.0-4.9
    diaphoresis / Early / 2.0-4.9
    xerosis / Delayed / 2.0-4.9
    urticaria / Rapid / 2.0-4.9
    vertigo / Early / 2.0-4.9
    hypoesthesia / Delayed / Incidence not known
    ocular pain / Early / Incidence not known
    musculoskeletal pain / Early / Incidence not known
    urine discoloration / Early / Incidence not known

    DRUG INTERACTIONS

    Albuterol: (Minor) 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. 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. 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.
    Albuterol; Ipratropium: (Minor) 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. 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. 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.
    Amitriptyline: (Major) 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.
    Amitriptyline; Chlordiazepoxide: (Major) 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; Lansoprazole: (Major) Monitor ECGs and electrolytes in patients receiving oxaliplatin and clarithromycin 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. Clarithromycin is also associated with an established risk for QT prolongation and TdP.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Monitor ECGs and electrolytes in patients receiving oxaliplatin and clarithromycin 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. Clarithromycin is also associated with an established risk for QT prolongation and TdP.
    Anagrelide: (Major) Monitor ECGs and electrolytes in patients receiving oxaliplatin and anagrelide 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. Ventricular tachycardia and TdP have also been reported with anagrelide; in addition, dose-related increases in mean QTc and heart rate were observed in healthy subjects who received anagrelide.
    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. Limited data indicate that QT prolongation is also possible with apomorphine administration, although the change in QTc interval is not significant in most patients receiving dosages within the manufacturer's guidelines.
    Arformoterol: (Moderate) Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval, such as oxaliplatin, because the action of beta-agonists on the cardiovascular system may be potentiated. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in post-marketing 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. 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. Coadministration may further increase the risk of QT prolongation and torsade de pointes.
    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) Monitor ECGs and electrolytes in patients receiving oxaliplatin and azithromycin 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. QT prolongation and TdP have also been spontaneously reported during azithromycin postmarketing surveillance.
    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.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of metronidazole 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. Potential QT prolongation has also been reported in limited case reports with metronidazole.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of metronidazole 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. Potential QT prolongation has also been reported in limited case reports with metronidazole.
    Budesonide; Formoterol: (Moderate) Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval, such as oxaliplatin, because the action of beta-agonists on the cardiovascular system may be potentiated. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in post-marketing 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 oxaliplatin with buprenorphine due to the risk of QT prolongation. If coadministration is unavoidable, monitor ECGs and electrolytes periodically during therapy; correct electrolyte abnormalities prior to administration of oxaliplatin. 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. The FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval.
    Buprenorphine; Naloxone: (Major) Avoid coadministration of oxaliplatin with buprenorphine due to the risk of QT prolongation. If coadministration is unavoidable, monitor ECGs and electrolytes periodically during therapy; correct electrolyte abnormalities prior to administration of oxaliplatin. 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. The FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval.
    Ceritinib: (Major) Periodically monitor electrolytes and ECGs in patients receiving concomitant treatment with ceritinib and oxaliplatin; 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.
    Chloroquine: (Major) Avoid coadministration of oxaliplatin with chloroquine if possible due to the risk of additive QT prolongation. If unavoidable, monitor ECGs and electrolytes periodically during therapy; correct electrolyte abnormalities prior to administration of oxaliplatin. Chloroquine administration is associated with an increased risk of QT prolongation and torsades de pointes (TdP). QT prolongation and ventricular arrhythmias including fatal TdP have been reported with oxaliplatin use in post-marketing 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.
    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: (Severe) 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) Coadministration of citalopram with oxaliplatin is not recommended due to an additive risk of QT prolongation. If unavoidable, monitor ECGs and electrolytes periodically during therapy; 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 post-marketing experience.
    Clarithromycin: (Major) Monitor ECGs and electrolytes in patients receiving oxaliplatin and clarithromycin 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. Clarithromycin is also associated with an established risk for QT prolongation and TdP.
    Clomipramine: (Major) 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.
    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. QTc prolongation has also been reported with the use of degarelix.
    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: (Major) 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 other drugs known to prolong the QT interval; correct electrolyte abnormalities prior to administration of oxaliplatin. For patients taking a deutetrabenazine dosage more than 24 mg/day with oxaliplatin, assess the QTc interval before and after increasing the dosage of either medication. Clinically relevant QTc prolongation may occur with deutetrabenazine. QT prolongation and ventricular arrhythmias including fatal torsade de pointes (TdP) have been reported with oxaliplatin use in postmarketing experience.
    Dextromethorphan; 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.
    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: (Severe) Because of the potential for torsade de pointes (TdP), the use of oxaliplatin with dofetilide is contraindicated. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and TdP. QT prolongation and ventricular arrhythmias including fatal TdP have been reported with oxaliplatin use in post-marketing experience. Additive QT prolongation is possible.
    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.
    Doxepin: (Major) 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: (Severe) 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.
    Efavirenz: (Major) Coadministration of efavirenz and oxaliplatin may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. QT prolongation and ventricular arrhythmias including fatal TdP have been reported with oxaliplatin use in post-marketing experience.
    Efavirenz; Emtricitabine; Tenofovir: (Major) Coadministration of efavirenz and oxaliplatin may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. QT prolongation and ventricular arrhythmias including fatal TdP have been reported with oxaliplatin use in post-marketing experience.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Coadministration of efavirenz and oxaliplatin may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. QT prolongation and ventricular arrhythmias including fatal TdP have been reported with oxaliplatin use in post-marketing 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.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (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) 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.
    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 administration of oxaliplatin. Encorafenib is associated with dose-dependent prolongation of the QT interval. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have 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.
    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.
    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.
    Fluoxetine; Olanzapine: (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.
    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) Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval, such as oxaliplatin, because the action of beta-agonists on the cardiovascular system may be potentiated. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in post-marketing 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) Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval, such as oxaliplatin, because the action of beta-agonists on the cardiovascular system may be potentiated. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in post-marketing 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) Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval, such as oxaliplatin, because the action of beta-agonists on the cardiovascular system may be potentiated. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in post-marketing 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 also been reported with the use of both drugs in postmarketing experience.
    Formoterol: (Moderate) Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval, such as oxaliplatin, because the action of beta-agonists on the cardiovascular system may be potentiated. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in post-marketing 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) Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval, such as oxaliplatin, because the action of beta-agonists on the cardiovascular system may be potentiated. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in post-marketing 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) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as oxaliplatin. Foscarnet has been associated with postmarketing reports of both 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. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
    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.
    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. 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) Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval, such as oxaliplatin, because the action of beta-agonists on the cardiovascular system may be potentiated. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in post-marketing 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 electrolytes and ECGs for QT prolongation if coadministration of goserelin with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Androgen deprivation therapy (e.g., goserelin) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience.
    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 EGCs for QT prolongation and monitor electrolytes if coadministration of histrelin and oxaliplatin is necessary; correct any electrolyte abnormalities prior to administration of oxaliplatin. Androgen deprivation therapy (e.g., histrelin) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Prolongation of the QT interval and ventricular arrhythmias including fatal torsade de pointes (TdP) have been reported with oxaliplatin use in postmarketing experience.
    Hydroxychloroquine: (Major) Avoid coadministration of hydroxychloroquine and oxaliplatin. Hydroxychloroquine increases the QT interval and should not be administered with other drugs known to prolong the QT interval. Ventricular arrhythmias and torsade de pointes (TdP) have been reported with the use of hydroxychloroquine. QT prolongation and ventricular arrhythmias including fatal TdP have been reported with oxaliplatin use in postmarketing experience.
    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: (Major) 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) Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval, such as oxaliplatin, because the action of beta-agonists on the cardiovascular system may be potentiated. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in post-marketing 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) Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval, such as oxaliplatin, because the action of beta-agonists on the cardiovascular system may be potentiated. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in post-marketing 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. 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.
    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.
    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.
    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.
    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.
    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 electrolytes and ECGs for QT prolongation if coadministration of leuprolide 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. Androgen deprivation therapy (e.g., leuprolide) also prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval.
    Leuprolide; Norethindrone: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of leuprolide 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. Androgen deprivation therapy (e.g., leuprolide) also prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval.
    Levalbuterol: (Minor) 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. 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. 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) Monitor electrolytes and ECGs for QT prolongation if coadministration of lithium with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. 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) Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval, such as oxaliplatin, because the action of beta-agonists on the cardiovascular system may be potentiated. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in post-marketing 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) Monitor electrolytes and ECGs for QT prolongation if coadministration of lopinavir 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. Lopinavir; ritonavir is also associated with QT prolongation; additive QT prolongation may occur.
    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. Monitor ECGs and electrolytes in patients receiving oxaliplatin; correct electrolyte abnormalities prior to administration of oxaliplatin.
    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) 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. 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. 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.
    Metronidazole: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of metronidazole 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. Potential QT prolongation has also been reported in limited case reports with metronidazole.
    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) Monitor electrolytes and ECGs for QT prolongation if coadministration of mifepristone with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. To minimize the risk of QT prolongation, use the lowest effective dose of mifepristone. Mifepristone has been 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.
    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.
    Moxifloxacin: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of moxifloxacin 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 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 also been reported with oxaliplatin use in postmarketing experience.
    Nilotinib: (Major) Avoid the concomitant use of nilotinib and oxaliplatin; significant prolongation of the QT interval may occur. If concomitant use is unavoidable, closely monitor electrolytes and ECGs for QT prolongation; correct electrolyte abnormalities prior to administration of oxaliplatin. Sudden death and QT prolongation have been reported in patients who received nilotinib therapy. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in post-marketing experience.
    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: (Major) 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.
    Olodaterol: (Moderate) Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval, such as oxaliplatin, because the action of beta-agonists on the cardiovascular system may be potentiated. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in post-marketing 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.
    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.
    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 and oxaliplatin if possible due to the risk of QT prolongation. If concomitant use is unavoidable and the patient has known risk factors for cardiac disease or arrhythmias, closely monitor electrolytes and ECGs; correct electrolyte abnormalities prior to administration of oxaliplatin. Paliperidone has been associated with QT prolongation; torsade de pointes (TdP) and ventricular fibrillation have been reported in the setting of overdose. According to the manufacturer of paliperidone, the drug should be avoided in combination with other agents also known to have this effect. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have 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: (Major) 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. (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.
    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.
    Pimavanserin: (Major) Pimavanserin should be avoided in combination with oxaliplatin. Pimavanserin may cause QT prolongation; QT prolongation and ventricular arrhythmias including fatal torsade de pointes (TdP) have been reported with oxaliplatin use in post-marketing experience. Coadministration may further increase the risk of QT prolongation and TdP.
    Pimozide: (Severe) 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) 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. 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. 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.
    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.
    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: (Major) 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.
    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.
    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) Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval, such as oxaliplatin, because the action of beta-agonists on the cardiovascular system may be potentiated. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in post-marketing 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.
    Sertraline: (Major) There have been postmarketing reports of QT prolongation and torsade de pointes (TdP) during treatment with sertraline and the manufacturer of sertraline recommends avoiding concurrent use with drugs known to prolong the QTc interval. QT prolongation and ventricular arrhythmias including fatal TdP have been reported during postmarketing use of oxaliplatin. Monitor ECGs and electrolytes in patients receiving oxaliplatin concomitantly with other drugs known to prolong the QT interval; correct electrolyte abnormalities prior to administration of oxaliplatin.
    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) 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. 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. 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.
    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 torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Sorafenib: (Major) Monitor ECGs for QT prolongation and monitor electrolytes if coadministration of sorafenib with oxaliplatin is necessary; correct any electrolyte abnormalities. An interruption or discontinuation of sorafenib therapy may be necessary if QT prolongation occurs. Sorafenib has been associated with QT prolongation. Prolongation of the QT interval 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 torsade de pointes 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) Monitor electrolytes and ECGs for QT prolongation if coadministration of tacrolimus with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. 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.
    Terbutaline: (Minor) 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. 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. 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: (Severe) 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) Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval, such as oxaliplatin, because the action of beta-agonists on the cardiovascular system may be potentiated. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in post-marketing 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.
    Tricyclic antidepressants: (Major) 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: (Major) 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 electrolytes and ECGs for QT prolongation if coadministration of triptorelin 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. Androgen deprivation therapy (e.g., triptorelin) also prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT 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) Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval, such as oxaliplatin, because the action of beta-agonists on the cardiovascular system may be potentiated. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in post-marketing 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.
    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.
    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.
    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. Monitor ECGs and electrolytes in patients receiving oxaliplatin concomitantly with other drugs known to prolong the QT interval; correct electrolyte abnormalities prior to administration of oxaliplatin.

    PREGNANCY AND LACTATION

    Pregnancy

    Pregnancy should be avoided by females of reproductive potential during oxaliplatin treatment (FDA pregnancy risk category D). Although there are no adequately controlled studies in pregnant animals or humans, oxaliplatin can cause fetal harm 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. In animal studies, administration of oxaliplatin during gestation at doses less than one-tenth the recommended human dose based on body surface area caused developmental mortality (increased early resorptions) and adversely affected fetal growth (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. It is not known whether oxaliplatin is present in human milk, although many drugs are excreted in human milk.

    MECHANISM OF ACTION

    Mechanism of Action: Oxaliplatin is a non-cell cycle specific, alkylating antineoplastic agent that inhibits DNA synthesis. Oxaliplatin contains a bulky carrier ligand, 1,2-diaminocyclohexane (DACH), not present in either cisplatin or carboplatin. It is the carrier ligand that determines the chemical reactivity and cytotoxicity of the platinum compound and influences the tissue distribution of the molecule. Oxaliplatin undergoes non-enzymatic conversion in blood and plasma to active derivatives via displacement of the labile oxalate ligand. Several transient reactive species are formed, including monoaquo-, monochloro-, dichloro-, and diaquo-DACH platinum, which covalently bind with various blood components or intracellular macromolecules. Potentially lethal bifunctional DNA-protein-Platinum (Pt) cross-links and inter- and intra-strand Pt-DNA cross-links are formed. Crosslinks are formed between the N7 positions of two adjacent guanines (GG), adjacent adenine-gaunines (AG), and guanines separated by an intervening nucleotide (GNG). These crosslinks inhibit DNA replication and transcription. Cytotoxicity is cell-cycle nonspecific. As compared to cisplatin, oxaliplatin produces fewer DNA cross-links and is less able to form these cross-links. However, oxaliplatin is more efficient (potent) than cisplatin and thus requires fewer DNA adducts to inhibit DNA chain elongation and produce cytotoxicity. Despite lower DNA reactivity than cisplatin, oxaliplatin exhibits similar or greater cytotoxicity in several human tumor cell lines. The DACH carrier ligand is thought to contribute to the enhanced cytotoxicity and lack of cross-resistance between oxaliplatin and cisplatin. The DACH ligand may also inhibit DNA repair by preventing or reducing the binding of repair proteins (e.g., the mismatch repair enzyme complex). In addition, oxaliplatin has been shown to affect DNA integrity and induce apoptosis (programmed cell death), which may also contribute to the cytotoxicity of the drug.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. Oxaliplatin undergoes rapid and extensive biotransformation in the blood, which makes pharmacokinetic monitoring of the parent or metabolite compound not feasible. Therefore, platinum pharmacokinetics rather than those of the parent compound or metabolite are discussed. In addition, the antitumor and toxic effects of oxaliplatin are due to the platinum species present in the ultrafiltrable plasma fraction (non-protein-bound drug and biotransformation species); platinum bound to plasma proteins or erythrocytes is considered inactive. The decline of ultrafiltrable platinum levels following oxaliplatin administration is triphasic, characterized by 2 relatively short distribution phases (a-half-life 0.43 hours, ß-half-life 16.8 hours) and a long terminal elimination phase (half-life 391 hours). As compared to cisplatin or carboplatin, oxaliplatin has a very large volume of distribution (582 L vs. 19.2 L and 17 L for cisplatin and carboplatin, respectively). 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. At the end of a 2-hour oxaliplatin infusion, roughly 15% of the administered platinum is present in the systemic circulation. The remaining 85% is rapidly distributed into tissues or is eliminated in the urine. Plasma protein binding of platinum is irreversible and > 90%. The main binding proteins are albumin and gamma-globulins. Platinum also binds irreversibly and accumulates (approximately 2-fold) in erythrocytes, where it appears to have no relevant activity. Intra-erythrocyte platinum does not act as a drug reservoir. Oxaliplatin does not undergo hepatic cytochrome P450 mediated metabolism. No hepatic enzyme-based or protein-binding based drug interactions are predicted. Oxaliplatin appears to be cleared equally by tissue distribution and renal elimination. Renal clearance for oxaliplatin accounts for a little over half the total plasma clearance (54%); 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.