oxaliplatin

ROUTE	ONSET	PEAK	DURATION
IV	unknown	unknown	unknown

Adverse reactions are noted for the combination of oxaliplatin, 5-fluorouracil, and leucovorin.

CV: chest pain, edema, QT interval prolongation, thromboembolism, TORSADES DE POINTES

EENT: visual abnormalities

F and E: dehydration, hypokalemia

GI: diarrhea, nausea, vomiting, abdominal pain, anorexia, gastroesophageal reflux, stomatitis

Hemat: anemia, neutropenia, thrombocytopenia, leukopenia

Local: injection site reactions

MS: rhabdomyolysis, back pain

Neuro: fatigue, neurotoxicity, POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME (PRES)

Resp: cough, dyspnea, INTERSTITIAL LUNG DISEASE (ILD), PULMONARY FIBROSIS

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS), fever

Interactions ⬆ ⬇

Drug-drug:

Nephrotoxic agents may ↑ risk of nephrotoxicity.
QT interval prolonging medications, including Class Ia antiarrhythmics and Class III antiarrhythmics, may ↑ risk of torsades de pointes.

Route/Dosage ⬆ ⬇

IV (Adults ): Day 1: 85 mg/m² with leucovorin 200 mg/m² at the same time over 2 hr, followed by 5-fluorouracil 400 mg/m² bolus over 2–4 min, then 5-fluorouracil 600 mg/m² as a 22-hr infusion. Day 2: Leucovorin 200 mg/m² over 2 hr, followed by 5-fluorouracil 400 mg/m² bolus over 2–4 min, then 5-fluorouracil 600 mg/m² as a 22-hr infusion. Cycle is repeated every 2 wk. Dosage ↓/alteration may be required for neurotoxicity or other serious adverse effects.

Renal Impairment

IV (Adults ): CCr <30 mL/min:↓ dose on Day 1 to 65 mg/m².

Availability ⬆ ⬇

(Generic available)

Lyophilized powder for injection: 50 mg/vial; 100 mg/vial
Solution for injection: 5 mg/mL

Assessment ⬆ ⬇

Assess for acute or delayed peripheral sensory neuropathy. Acute onset occurs within hr to 1–2 days of dosing, resolves within 14 days, and frequently recurs with further dosing (transient paresthesia, dysesthesia, and hypoesthesia of hands, feet, perioral area, or throat). Symptoms may be precipitated or exacerbated by exposure to cold or cold objects; avoid ice during symptoms. May also cause jaw spasm, abnormal tongue sensation, dysarthria, eye pain, and a feeling of chest pressure. Persistent (>14 days) causes paresthesias, dysesthesias, and hypoesthesias, but may also include deficits in proprioception that may interfere with daily activities (walking, writing, swallowing). Persistent neuropathy may occur without prior acute neuropathy and may improve upon discontinuation of oxaliplatin. Adjuvant Therapy:For persistent Grade 2 neurosensory events that do not resolve,↓ dose to 75 mg/m². For persistent Grade 3 neurosensory events, consider discontinuing therapy. Do not alter 5-fluorouracil/leucovorin regimen. For Grade 4 neuropathy, discontinue oxaliplatin. Advanced Colorectal Cancer: For persistent Grade 2 neurosensory events that do not resolve, ↓dose to 65 mg/m². For persistent Grade 3 neurosensory events, consider discontinuing therapy. Do not alter 5-fluorouracil/leucovorin regimen. For Grade 4 neuropathy, discontinue oxaliplatin.
Monitor for signs/symptoms of anaphylaxis (rash, hives, swelling of lips or tongue, sudden cough). If hypersensitivity reaction occurs, permanently discontinue oxaliplatin and treat as indicated. Epinephrine, corticosteroids, and antihistamines should be readily available during therapy.
Assess for signs/symptoms of pulmonary toxicity (nonproductive cough, dyspnea, crackles, radiological infiltrates). If signs or symptoms occur, hold and evaluate. If pulmonary fibrosis or ILD confirmed,permanently discontinue oxaliplatin.
Monitor for signs/symptoms of PRES (headache, altered mental functioning, seizure, vision changes, with or without hypertension). If PRES confirmed by MRI, permanently discontinue oxaliplatin.
Monitor ECG in patients with HF, bradyarrhythmias, and electrolyte abnormalities and in patients taking drugs known to prolong the QT interval.
Monitor for signs/symptoms of rhabdomyolysis (muscle pain or weakness, dark, red-brown urine). If rhabdomyolysis occurs, permanently discontinue oxaliplatin.
Monitor for signs/symptoms of GI adverse reactions (nausea, vomiting, diarrhea) during therapy. If Grade 3 or 4 GI adverse reactions occur, after recovery, ↓ oxaliplatin dose to 75 mg/m² and ↓ fluorouracil dose to 300 mg/m² as IV bolus and 500 mg/m² as 22-hr continuous infusion.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy. Monitor WBC with differential, ALT, AST, bilirubin, and serum creatinine at baseline, before each oxaliplatin cycle and as indicated. Adjuvant Therapy:For Grade 4 neutropenia or febrile neutropenia, or Grade 3 or 4 thrombocytopenia, hold next dose until neutrophils ≥1.5 × 10⁹/L and platelets ≥75 × 10⁹/L; then ↓ oxaliplatin dose to 75 mg/m² and ↓ 5-fluorouracil dose to 300 mg/m² as IV bolus and 500 mg/m² as 22-hr infusion. Advanced Colorectal Cancer:After recovery from grade 3–4 GI reactions (despite prophylactic treatment), grade 4 neutropenia, febrile neutropenia, or grade 3–4 thrombocytopenia:↓ oxaliplatin dose to 65 mg/m² and ↓ 5-fluorouracil dose by 20% (300 mg/m² as IV bolus and 500 mg/m² as 22-hr infusion). Delay next dose until neutrophils ≥1.5 × 10⁹/L and platelets ≥75 × 10⁹/L. Monitor and correct electrolytes before starting therapy and periodically during therapy.

Implementation ⬆ ⬇

Correct hypokalemia and hypermagnesemia before starting therapy.
Premedicate with antiemetic with or without dexamethasone. Prehydration is not required.

IV Administration:

Oxaliplatin is a vesicant. If extravasation occurs, immediately stop infusion. Leave needle/cannula in place temporarily but do not flush the line. Gently aspirate extravasated solution; then remove needle/cannula. Elevate patient's extremity. Apply dry warm (if concerned for oxaliplatin-induced cold neuropathy) or dry cold compresses for 20 min 4 times day for 1–2 days. If extravasation of >40 mg of oxaliplatin occurs, consider high-dose oral dexamethasone to ↓ severity of resulting inflammatory reaction.
Reconstitution: Reconstitute lyophilized powder with sterile water for injection or D5W by adding 10 mL to 50-mg vial or 20 mL to 100-mg vial. Gently swirl to dissolve. Concentration: 5 mg/mL. Diluent: Further dilute reconstituted solution in 250–500 mL of D5W. Diluted solution is stable for up to 6 hr at room temperature or up to 24 hr under refrigeration.
Intermittent Infusion: Protect concentrated solution from light; do not freeze. Diluent: Must be further diluted with 250–500 mL of D5W. Do not use 0.9% NaCl or any other chloride-containing solution for final solution. Do not use aluminum needles or administration sets containing aluminum parts; aluminum may cause degradation of platinum compounds. May be stored in refrigerator for 24 hr or at room temperature for 6 hr. Diluted solution is not light-sensitive. Do not administer solutions that are discolored or contain particulates.Concentration: 0.2–0.6 mg/mL.
Rate: Administer oxaliplatin simultaneously with leucovorin in separate bags via Y-line over 120 min. Prolonging infusion time to 6 hr may ↓ acute toxicities. Infusion times for fluorouracil and leucovorin do not need to change.
Infusion line should be flushed with D5W prior to administration of other solutions or medications.
Y-Site Compatibility:
- alemtuzumab
- allopurinol
- amikacin
- aminocaproic acid
- aminophylline
- amiodarone
- amphotericin B deoxycholate
- amphotericin B liposomal
- ampicillin
- ampicillin/sulbactam
- anidulafungin
- argatroban
- atracurium
- azithromycin
- aztreonam
- bivalirudin
- bleomycin
- bumetanide
- buprenorphine
- butorphanol
- calcium gluconate
- carboplatin
- caspofungin
- cefazolin
- cefotaxime
- cefotetan
- cefoxitin
- ceftazidime
- ceftriaxone
- cefuroxime
- chloramphenicol
- chlorpromazine
- ciprofloxacin
- cisatracurium
- cisplatin
- clindamycin
- cyclophosphamide
- cyclosporine
- cytarabine
- dacarbazine
- dactinomycin
- daptomycin
- daunorubicin
- dexamethasone
- dexmedetomidine
- dexrazoxane
- digoxin
- diltiazem
- diphenhydramine
- dobutamine
- docetaxel
- dopamine
- doxorubicin hydrochloride
- doxorubicin liposomal
- doxycycline
- droperidol
- enalaprilat
- ephedrine
- epinephrine
- epirubicin
- ertapenem
- erythromycin
- esmolol
- etoposide
- etoposide phosphate
- famotidine
- fentanyl
- fluconazole
- fludarabine
- foscarnet
- fosphenytoin
- furosemide
- gemcitabine
- gemtuzumab ozogamicin
- gentamicin
- glycopyrrolate
- granisetron
- haloperidol
- heparin
- hetastarch
- hydralazine
- hydrocortisone
- hydromorphone
- idarubicin
- ifosfamide
- imipenem/cilastatin
- insulin regular
- irinotecan
- isoproterenol
- ketorolac
- labetalol
- leucovorin
- levofloxacin
- levoleucovorin calcium
- lidocaine
- linezolid
- lorazepam
- magnesium sulfate
- mannitol
- meperidine
- meropenem
- mesna
- methadone
- methylprednisolone
- metoclopramide
- metoprolol
- metronidazole
- midazolam
- milrinone
- minocycline
- mitomycin
- mitoxantrone
- morphine
- moxifloxacin
- nafcillin
- nalbuphine
- naloxone
- nicardipine
- nitroglycerin
- nitroprusside
- norepinephrine
- octreotide
- ondansetron
- paclitaxel
- palonosetron
- pemetrexed
- pentamidine
- phentolamine
- phenylephrine
- potassium acetate
- potassium chloride
- potassium phosphates
- procainamide
- prochlorperazine
- promethazine
- propranolol
- rocuronium
- sodium acetate
- sodium bicarbonate
- sodium phosphates
- succinylcholine
- sufentanil
- tacrolimus
- theophylline
- thiotepa
- tigecycline
- tirofiban
- tobramycin
- topotecan
- trimethoprim/sulfamethoxazole
- vancomycin
- vasopressin
- vecuronium
- verapamil
- vinblastine
- vincristine
- vinorelbine
- voriconazole
- zidovudine
- zoledronic acid
Y-Site Incompatibility:
- calcium chloride
- cefepime
- dantrolene
- diazepam
- sodium chloride

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication. Advise patient to read Patient Information before starting therapy.
Inform patient of potential for peripheral neuropathy and potentiation by exposure to cold or cold objects. Advise patient to avoid cold drinks, use of ice in drinks or as ice packs, and to cover exposed skin prior to exposure to cold temperatures or cold objects. Caution patients to cover themselves with a blanket during infusion, avoid breathing deeply when exposed to cold air, wear warm clothing, cover mouth and nose with a scarf or pull-down ski cap to warm the air that goes to their lungs, avoid taking things from the freezer or refrigerator without wearing gloves, drink fluids warm or at room temperature, always drink through a straw, avoid using ice chips for nausea, avoid running air conditioning at high levels in house or car, wash hands with warm water. Notify health care provider of response since last treatment before next infusion.
Instruct patient to notify health care provider immediately if signs of allergic reactions occur.
Instruct patient to notify health care provider immediately if signs of PRES, low blood cell counts (fever, persistent diarrhea, infection), persistent vomiting, signs of dehydration, cough or breathing difficulty, thirst, dry mouth, dizziness, ↓ urination, or signs of infection (fever, temperature of ≥100.5° F, cough that brings up mucus, chills or shivering, burning or pain on urination, pain on swallowing, sore throat, redness or swelling at IV site) occur.
Rep: May cause fetal harm. Advise women of reproductive potential to use effective contraception during therapy and for ≥9 mo after final dose and to avoid breastfeeding during and for 3 mo after final dose. Advise men with female partners of reproductive potential to use effective contraception for 6 mo after final dose. May impair female and male fertility.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇