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Oxaliplatin

FDA Drug Information • Also known as: Oxaliplatin

Brand Names
Oxaliplatin
Drug Class
Platinum-based Drug [EPC]
Route
INTRAVENOUS
Dosage Form
INJECTION, SOLUTION
Product Type
HUMAN PRESCRIPTION DRUG

⚠ Boxed Warning (Black Box)

WARNING: HYPERSENSITIVITY REACTIONS, INCLUDING ANAPHYLAXIS Serious and fatal hypersensitivity adverse reactions, including anaphylaxis, can occur with oxaliplatin within minutes of administration and during any cycle. Oxaliplatin is contraindicated in patients with hypersensitivity reactions to oxaliplatin and other platinum-based drugs [see Contraindications ( 4 )]. Immediately and permanently discontinue oxaliplatin for hypersensitivity reactions and administer appropriate treatment for management of the hypersensitivity reaction [see Warnings and Precautions ( 5.1 )]. WARNING: HYPERSENSITIVITY REACTIONS, INCLUDING ANAPHYLAXIS See full prescribing information for complete boxed warning. Serious and fatal hypersensitivity adverse reactions, including anaphylaxis, can occur with oxaliplatin within minutes of administration and during any cycle. Oxaliplatin is contraindicated in patients with hypersensitivity reactions to oxaliplatin and other platinum-based drugs. Immediately and permanently discontinue oxaliplatin for hypersensitivity reactions and administer appropriate treatment. ( 4 , 5.1 )

Description

11 DESCRIPTION Oxaliplatin, USP is a platinum-based drug with the molecular formula C 8 H 14 N 2 O 4 Pt and the chemical name of cis -[(1 R ,2 R)-1,2-cyclohexanediamine- N,N′ ] [oxalato(2-)- O,O′ ] platinum. Oxaliplatin is an organoplatinum complex in which the platinum atom is complexed with 1,2-diaminocyclohexane (DACH) and with an oxalate ligand as a leaving group. Oxaliplatin, USP is white to off-white crystalline powder. The molecular weight is 397.29. Oxaliplatin is slightly soluble in water, very slightly soluble in methanol and practically insoluble in alcohol. Oxaliplatin injection, USP for intravenous use is supplied in vials containing 50 mg/10 mL or 100 mg/20 mL of oxaliplatin as a sterile, preservative-free, aqueous solution at a concentration of 5 mg/mL. Water for Injection, USP is present as an inactive ingredient. oxaliplatinstructure

What Is Oxaliplatin Used For?

1 INDICATIONS AND USAGE Oxaliplatin injection, in combination with infusional fluorouracil and leucovorin, is indicated for:

  • adjuvant treatment of stage III colon cancer in patients who have undergone complete resection of the primary tumor.
  • treatment of advanced colorectal cancer. Oxaliplatin injection is a platinum-based drug used in combination with infusional fluorouracil and leucovorin, which is indicated for:
  • adjuvant treatment of stage III colon cancer in patients who have undergone complete resection of the primary tumor. ( 1 )
  • treatment of advanced colorectal cancer. ( 1 )

    • Dosage and Administration

    2 DOSAGE AND ADMINISTRATION

  • Administer oxaliplatin injection 85 mg/m 2 as an intravenous infusion over 120 minutes concurrently with leucovorin over 120 minutes in separate bags, followed by fluorouracil on Day 1 of each 14-day cycle. Administer fluorouracil and leucovorin on Day 2 as recommended. ( 2.1 )
  • Adjuvant Treatment: Continue treatment for up to 12 cycles or unacceptable toxicity. ( 2.1 )
  • Advanced Colorectal Cancer: Continue treatment until disease progression or unacceptable toxicity. ( 2.1 ) 2.1 Recommended Dosage Administer oxaliplatin injection in combination with fluorouracil and leucovorin every 2 weeks.
  • For adjuvant treatment, continue treatment for up to 12 cycles or unacceptable toxicity.
  • For advanced colorectal cancer, continue treatment until disease progression or unacceptable toxicity. Day 1 Administer oxaliplatin injection 85 mg/m 2 as an intravenous infusion over 120 minutes and leucovorin 200 mg/m 2 as an intravenous infusion over 120 minutes at the same time in separate bags, followed by fluorouracil 400 mg/m 2 as intravenous bolus over 2-4 minutes, followed by fluorouracil 600 mg/m 2 as a 22-hour continuous infusion. Day 2 Administer leucovorin 200 mg/m 2 as an intravenous infusion over 120 minutes, followed by fluorouracil 400 mg/m 2 as intravenous bolus over 2-4 minutes, followed by fluorouracil 600 mg/m 2 as a 22-hour continuous infusion. Refer to the prescribing information for fluorouracil and leucovorin for additional information. 2.2 Dose Modifications for Adverse Reactions Prolongation of infusion time for oxaliplatin injection from 2 hours to 6 hours may mitigate acute toxicities, such as non-life-threatening infusion-related reactions. Permanently discontinue oxaliplatin injection for any of the following:
  • Hypersensitivity Reactions [see Warnings and Precautions ( 5.1 )]
  • Posterior reversible encephalopathy syndrome (PRES) [see Warnings and Precautions ( 5.4 )]
  • Confirmed interstitial lung disease or pulmonary fibrosis [see Warnings and Precautions ( 5.5 )]
  • Rhabdomyolysis [see Warnings and Precautions ( 5.8 )] Refer to the fluorouracil and leucovorin prescribing information for dosage modifications for adverse reactions. Dosage Modifications for Adjuvant Treatment Dosage modifications for adverse reactions for adjuvant treatment are presented in Table 1. Table 1: Dosage Modifications for Adjuvant Treatment in Patients with Stage III Colon Cancer Adverse Reactions Severity Oxaliplatin Injection Dosage Modifications Peripheral Sensory Neuropathy [see Warnings and Precautions (5.2)] Persistent Grade 2 Consider reducing oxaliplatin injection dose to 75 mg/m 2 . Persistent Grade 3 Consider discontinuing oxaliplatin injection. Grade 4 Discontinue oxaliplatin injection. Myelosuppression [see Warnings and Precautions (5.3), Adverse Reactions (6.1)]. Grade 4 neutropenia or febrile neutropenia Delay the next dose until neutrophils greater than or equal to 1.5 × 10 9 /L and platelets greater than or equal...

    • Side Effects (Adverse Reactions)

    6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in labeling:

  • Hypersensitivity Reactions [see Warnings and Precautions ( 5.1 )]
  • Peripheral Sensory Neuropathy [see Warnings and Precautions ( 5.2 )]
  • Severe Myelosuppression [see Warnings and Precautions ( 5.3 )]
  • Reversible Posterior Leukoencephalopathy Syndrome [see Warnings and Precautions ( 5.4 )]
  • Pulmonary Toxicity [see Warnings and Precautions ( 5.5 )]
  • Hepatotoxicity [see Warnings and Precautions ( 5.6 )]
  • QT Interval Prolongation and Ventricular Arrhythmias [see Warnings and Precautions ( 5.7 )]
  • Rhabdomyolysis [see Warnings and Precautions ( 5.8 )]
  • Hemorrhage [see Warnings and Precautions ( 5.9 )] Most common adverse reactions (incidence greater than or equal to 40%) were peripheral sensory neuropathy, neutropenia, thrombocytopenia, anemia, nausea, increase in transaminases and alkaline phosphatase, diarrhea, emesis, fatigue, and stomatitis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Hetero Labs Limited at 1-866-495-1995 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. More than 1100 patients with stage II or III colon cancer and more than 4,000 patients with advanced colorectal cancer were treated in trials with oxaliplatin. The most common adverse reactions in patients with stage II or III colon cancer receiving adjuvant treatment were peripheral sensory neuropathy, neutropenia, thrombocytopenia, anemia, nausea, increase in transaminases and alkaline phosphatase, diarrhea, emesis, fatigue and stomatitis. The most common adverse reactions in previously untreated and treated patients with advanced colorectal cancer were peripheral sensory neuropathies, fatigue, neutropenia, nausea, emesis, and diarrhea. Adjuvant Treatment The safety of oxaliplatin in combination with fluorouracil (FU)/leucovorin (LV) was evaluated in patients with stage II or III colon cancer, who had undergone complete resection of the primary tumor in the adjuvant treatment trial [see Clinical Studies ( 14.1 )]. Fatal adverse reactions in patients who received oxaliplatin in the combination arm included sepsis/neutropenic sepsis (n=3), intracerebral hemorrhage (n=2), and eosinophilic pneumonia (n=1). Thromboembolic events occurred in 6% (grade 3-4, 1.2%) of patients in the oxaliplatin arm. Grade 3 or 4 adverse reactions occurred in 70% of patients in the oxaliplatin arm. Grade 3-4 gastrointestinal bleeding occurred in 0.2% of patients. Febrile neutropenia occurred in 0.7% and documented infection with concomitant grade 3-4 neutropenia occurred in 1.1%. Discontinuation due to an adverse reaction occurred in 15% of the patients in the oxaliplatin arm. Tables 5, 6, and 7 summarize the adverse reactions reported in patients with colon cancer receiving adjuvant treatment. Table 5: Adverse Reactions Reported in Patients with Colon Cancer Receiving Adjuvant Treatment (greater than or equal to 5% of all patients and with greater than or equal to 1% grade 3-4) Adverse Reaction* Oxaliplatin + FU/LV N=1108 FU/LV N=1111 All Grades (%) Grade 3-4 (%) All Grades (%) Grade 3-4 (%) Neurology Peripheral Sensory Neuropathy 92 12 16 <1 Gastrointestinal Nausea 74 5 61 2 Diarrhea 56 11 48 7 Vomiting 47 6 24 1 Stomatitis 42 3 40 2 Anorexia 13 1 8 <1 Constitutional Symptoms/Pain Fatigue 44 4 38 1 Abdominal Pain 18 1 17 2 Dermatology/Skin Skin Disorder 32 2 36 2 Injection Site Reaction † 11 3 10 3 Fever/Infection Fever 27 1 12 1 Infection 25 4 25 3 Allergy/Immunology Allergic Reaction 10 3 2 <1 * Event coded in WHO-ART dictionary † Includes thrombosis related to the catheter Table 6: Adverse Reactions Reported in Patients with Colon Cancer Receiving Adjuvant...

    • Drug Interactions

    7 DRUG INTERACTIONS 7.1 Drugs that Prolong the QT Interval QT interval prolongation and ventricular arrhythmias can occur with oxaliplatin [see Warnings and Precautions ( 5.7 )]. Avoid coadministration of oxaliplatin with medicinal products with a known potential to prolong the QT interval. 7.2 Use with Nephrotoxic Products Because platinum-containing species are eliminated primarily through the kidney, clearance of these products may be decreased by coadministration of potentially nephrotoxic compounds [see Clinical Pharmacology ( 12.3 )]. Avoid coadministration of oxaliplatin with medicinal products known to cause nephrotoxicity. 7.3 Use with Anticoagulants Prolonged prothrombin time and INR occasionally associated with hemorrhage have been reported in patients who received oxaliplatin with fluorouracil/leucovorin while on anticoagulants [see Warnings and Precautions ( 5.9 ), Adverse Reactions ( 6.2 )]. Increase frequency of monitoring in patients who are receiving oxaliplatin with fluorouracil/leucovorin and oral anticoagulants.

    Contraindications

    4 CONTRAINDICATIONS Oxaliplatin is contraindicated in patients with a history of a hypersensitivity reaction to oxaliplatin or other platinum-based drugs. Reactions have included anaphylaxis [see Warnings and Precautions ( 5.1 )].

  • History of hypersensitivity reaction to oxaliplatin or other platinum-based drugs. ( 4 , 5.1 )

    • Pregnancy and Breastfeeding

    8.1 Pregnancy Risk Summary Based on its direct interaction with DNA, oxaliplatin can cause fetal harm when administered to a pregnant woman. The available human data do not establish the presence or absence of major birth defects or miscarriage related to the use of oxaliplatin. Reproductive toxicity studies demonstrated adverse effects on embryo-fetal development in rats at maternal doses that were below the recommended human dose based on body surface area (see Data). Advise a pregnant woman of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal data Pregnant rats were administered oxaliplatin at less than one-tenth the recommended human dose based on body surface area during gestation days (GD)1-5 (preimplantation), GD 6-10, or GD 11-16 (during organogenesis). Oxaliplatin caused developmental mortality (increased early resorptions) when administered on days GD 6-10 and GD 11-16 and adversely affected fetal growth (decreased fetal weight, delayed ossification) when administered on days GD 6-10.

    Overdosage

    10 OVERDOSAGE The maximum dose of oxaliplatin that has been administered in a single infusion is 825 mg. Several cases of overdoses have been reported with oxaliplatin. Adverse reactions observed following an overdosage were grade 4 thrombocytopenia (less than 25,000/mm 3 ) without bleeding, anemia, sensory neuropathy (including paresthesia, dysesthesia, laryngospasm and facial muscle spasms), gastrointestinal disorders (including nausea, vomiting, stomatitis, flatulence, abdomen enlarged and grade 4 intestinal obstruction), grade 4 dehydration, dyspnea, wheezing, chest pain, respiratory failure, severe bradycardia and death. Closely monitor patients suspected of receiving an overdose, including for the adverse reactions described above and administer appropriate supportive treatment.

    How Supplied

    16 HOW SUPPLIED/STORAGE AND HANDLING Oxaliplatin injection, USP is supplied in clear, glass, single-dose vials with red elastomeric stoppers and aluminum flip-off seals containing 50 mg/10 mL or 100 mg/20 mL of oxaliplatin as a clear, colorless, sterile, preservative-free, aqueous solution at a concentration of 5 mg/mL. NDC 31722-357-10: 50 mg/10 mL (5 mg/mL) single-dose vial with red color flip-off seal individually packaged in a carton. NDC 31722-358-20: 100 mg/20 mL (5 mg/mL) single-dose vial with red color flip-off seal individually packaged in a carton. Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Do not freeze and protect from light (keep in original outer carton). Discard unused portion. Oxaliplatin injection, USP is a cytotoxic drug. Follow applicable special handling and disposal procedures. 1 The use of gloves is recommended. If a solution of oxaliplatin injection contacts the skin, wash the skin immediately and thoroughly with soap and water. If oxaliplatin injection contacts the mucous membranes, flush thoroughly with water.

    About This Information

    This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

    What are side effects?

    Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

    What are drug interactions?

    Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.