Oxitan Adverse Reactions

The following serious adverse reactions are discussed in greater detail in other sections of the monograph: Hypersensitivity reactions; Peripheral Sensory Neuropathy; Severe Myelosuppression; Reversible Posterior Leukoencephalopathy Syndrome; Pulmonary Toxicities; Hepatotoxicity; QT Interval Prolongation and Ventricular Arrhythmias; Rhabdomyolysis; Hemorrhage.
The most common adverse reactions in patients with stage II or III colon cancer receiving adjuvant therapy 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 were peripheral sensory neuropathies, fatigue, neutropenia, nausea, emesis, and diarrhea.
Thrombocytopenia and bleeding: Thrombocytopenia was frequently reported with the combination of oxaliplatin and infusional 5-FU/LV. The incidence of all hemorrhagic events in the adjuvant and previously treated patients was higher on the oxaliplatin combination arm compared to the infusional 5-FU/LV arm. These events included gastrointestinal bleeding, hematuria, and epistaxis. In the adjuvant trial, two patients died from intracerebral hemorrhages.
Neutropenia: Neutropenia was frequently observed with the combination of oxaliplatin and 5-FU/LV in patients with colon cancer.
Gastrointestinal: Grade 3 and 4 nausea, vomiting, diarrhea, and mucositis/stomatitis were reported.
Dermatologic: Oxaliplatin did not increase the incidence of alopecia compared to 5-FU/LV alone. No complete alopecia was reported.
Intravenous Site Reactions: Extravasation, in some cases including necrosis, has been reported.
Injection site reaction, including redness, swelling, and pain, has been reported.
Anticoagulation and Hemorrhage: There have been reports of prolonged prothrombin time and INR occasionally associated with hemorrhage in patients who received Oxaliplatin plus 5-fluorouracil/leucovorin while on anticoagulants. Patients receiving Oxaliplatin plus 5-fluorouracil/leucovorin and requiring oral anticoagulants may require closer monitoring.
Renal: About 5-10% of patients in all groups had some degree of elevation of serum creatinine. The incidence of grade 3/4 elevations in serum creatinine in the oxaliplatin and 5-FU/LV combination arm was 1% in the previously treated patients.
Hepatic: Hepatotoxicity (defined as elevation of liver enzymes) appears to be related to oxaliplatin combination therapy.
Thromboembolism: The incidence of thromboembolic events in adjuvant patients with colon cancer was 6% (1.8% grade 3/4) in the infusional 5-FU/LV arm and 6% (1.2% grade 3/4) in the oxaliplatin and infusional 5-FU/LV combined arm, respectively. The incidence was 6 and 9% of the patients previously untreated for advanced colorectal cancer and previously treated patients in the oxaliplatin and 5-FU/LV combination arm, respectively.
Other Adverse Reactions: Body as a whole: Angioedema, anaphylactic shock.
Cardiovascular disorders: QT prolongation leading to ventricular arrhythmias including fatal Torsade de Pointes; bradyarrhythmia.
Central and peripheral nervous system disorders: Loss of deep tendon reflexes, dysarthria, Lhermitte's sign, cranial nerve palsies, fasciculations, convulsions.
Hearing and vestibular system disorders: Deafness.
Infections: Septic shock, including fatal outcomes.
Infusion reactions/hypersensitivity: Laryngospasm.
Liver and gastrointestinal system disorders: Severe diarrhea/vomiting resulting in hypokalemia, colitis (including Clostridium difficile diarrhea), metabolic acidosis; ileus; intestinal obstruction, pancreatitis; veno-occlusive disease of liver also known as sinusoidal obstruction syndrome, and perisinusoidal fibrosis, which rarely may progress, focal nodular hyperplasia, esophagitis.
Musculoskeletal and connective tissue disorders: Rhabdomyolysis, including fatal outcomes.
Platelet, bleeding, and clotting disorders: Immuno-allergic thrombocytopenia.
Prolongation of prothrombin time and of INR in patients receiving anticoagulants.
Blood disorders: Secondary leukemia.
Red Blood Cell disorders: Hemolytic uremic syndrome, immuno-allergic hemolytic anemia.
Renal disorders: Acute tubular necrosis, Acute interstitial nephritis and acute renal failure.
Respiratory system disorders: interstitial lung diseases (sometimes fatal) and pneumonia (including fatal outcomes).
Vision disorders: Decrease of visual acuity, visual field disturbance, optic neuritis and transient vision loss (reversible following therapy discontinuation).
Injury, poisoning, and procedural complications: fall-related injuries.