Medicinal Products

ELOXATINE 5 mg / ml Powder for solution for infusion Box of 1 vial of 100 mg

Generic drug of the therapeutic class: Oncology and Hematology
active ingredients: Oxaliplatin
laboratory: Sanofi Synthelabo France

Powder for IV infusion solution
All forms

Indication

Oxaliplatin in combination with 5-fluorouracil and folinic acid is indicated in:
- adjuvant treatment of stage III colon cancer (stage C Dukes) after complete resection of the initial tumor,
- the treatment of metastatic colorectal cancers.

Dosage ELOXATINE 5 mg / ml Powder for solution for infusion Box of 1 vial of 100 mg

Dosage:
RESERVED FOR THE ADULT.
- The recommended dose of oxaliplatin as adjunctive therapy is 85 mg / m² intravenously repeated every two weeks for 12 cycles (6 months).
- The recommended dose of oxaliplatin for the treatment of metastatic colorectal cancer is 85 mg / m² intravenously repeated every two weeks.
- The dose will be adjusted according to the tolerance (see warnings and precautions for use).
- The administration of oxaliplatin must always precede that of fluoropyrimidines .
Oxaliplatin is administered as an IV infusion for 2 to 6 hours in 250 to 500 ml of a 5% glucose solution in order to obtain a concentration greater than 0.2 mg / ml.
Oxaliplatin was most often administered in combination with 5-fluorouracil as a continuous infusion. For repeated treatment every 2 weeks, a regimen containing 5-fluorouracil bolus and continuous infusion was used.
- Populations at risk:
. Renal insufficiency :
Oxaliplatin has not been studied in patients with severe renal impairment (see contraindications).
In patients with moderate impairment of renal function, treatment may be initiated at the recommended dose (see warnings and precautions for use). It is not necessary to adjust the dose in patients with mild impairment of renal function.
. Hepatic insufficiency :
Oxaliplatin has not been studied in patients with severe hepatic impairment. The acute toxicity of oxaliplatin was not observed in the subgroup of patients with liver function abnormalities. During clinical development, no dose adjustment was performed in patients with liver function abnormalities.
. Elderly
There was no evidence of worsening of the severe toxicity of oxaliplatin alone or in combination with 5-fluorouracil in subjects over 65 years of age. As a result, no adjustment of the dose is necessary in the elderly.
Administration mode :
- Oxaliplatin is administered as an intravenous infusion.
- Administration of oxaliplatin does not require hyperhydration.
- Oxaliplatin diluted in 250-500 ml of 5% glucose solution, in order to obtain a concentration greater than 0.2 mg / ml, must be perfused by the central venous or peripheral venous route over a period of 2 at 6 o'clock and always before 5-fluorouracil.
- In case of extravasation, the administration will be interrupted immediately.
How to handle:
Oxaliplatin should be reconstituted and diluted before administration. Only recommended solvents should be used for reconstitution and dilution of the powder (see instructions for use, handling and disposal).

Against indications

CONTRAINDICATED:
Oxaliplatin is contraindicated in patients:
- having a history of hypersensitivity to oxaliplatin,
- who are breastfeeding: the passage into breast milk has not been studied. Breast-feeding is contraindicated during treatment with oxaliplatin,
- carriers of bone marrow failure (neutrophils <2 x 10 9 / L and / or platelets <100 x 10 9 / L) before the first treatment cycle,
- carriers of peripheral sensory neuropathy with functional discomfort before the first treatment cycle,
- with severe renal impairment (creatinine clearance <30 ml / min).
NOT RECOMMENDED :
Pregnancy: No information on the safety of use of oxaliplatin is currently available in pregnant women. Based on preclinical data, oxaliplatin, probably lethal and / or teratogenic to the fetus at the recommended therapeutic dose, is therefore not recommended during pregnancy and should only be considered after specifically informing the patient of the risk to the fetus. and with his consent.

Eloxatin side effects

- The most common adverse events in the combination of oxaliplatin with 5-fluorouracil / folinic acid (5-FU / AF) are gastrointestinal (diarrhea, nausea, vomiting and mucositis), hematologic (neutropenia, thrombocytopenia) and neurological (acute sensory peripheral neuropathy and cumulative dose). Overall, these adverse events were more frequent and severe with oxaliplatin in combination with 5-FU / AF than with 5-FU / AF alone.
- The frequencies presented below are derived from clinical studies in metastatic treatment and adjuvant therapy (including respectively 416 and 1108 patients in the oxaliplatin + 5-FU / AF arm) and experience since marketing. .
- The mentioned frequencies have been defined using the following criteria: very frequent (> 1/10), frequent (> 1/100, 1/1000, 1/10000, <= 1/1000) and very rare (<= 1) / 10000) including isolated cases.
Further information is given later.
UNDESIRABLE EVENTS BY CLASS-ORGAN SYSTEM :
- Disorders related to the administration site:
Very common : Reaction at the injection site ( extravasation may cause local pain and inflammation, which can be severe and lead to complications particularly when oxaliplatin is perfused via the peripheral venous route ) (see warnings and precautions job).
- autonomic nervous system disorders:
Frequent : Flushing.
- General disorders *:
. Very common : fever ++, fatigue, allergy / allergic reactions +, asthenia, pain, weight gain (adjuvant treatment).
. Common : chest pain, weight loss (metastatic treatment).
. Rare : immunoallergic thrombocytopenia, hemolytic anemia.
+ Frequent allergic reactions such as rash (especially urticaria), conjunctivitis, rhinitis. Frequent anaphylactic reactions including bronchospasm, angioedema, hypotension, and anaphylactic shock.
++ Very frequent fevers, either of infectious origin (with or without febrile neutropenia) or isolated of immunological origin.
- Central and Peripheral Nervous System Disorders *:
. Very common : sensitive peripheral neuropathy, headache, sensory disturbances.
. Common : dizziness, motor neuritis, meningism
. Rare : dysarthria.
- Gastrointestinal disorders:
. Very common : diarrhea, nausea, vomiting, stomatitis / mucitis, abdominal pain, constipation.
. Frequent : dyspepsia, gastroesophageal reflux, hiccups.
. Uncommon : ileus, intestinal obstruction.
. Rare : colitis including Clostridium difficile diarrhea.
- Metabolism and nutrition disorders:
. Very common : anorexia.
. Frequent : dehydration.
. Uncommon : metabolic acidosis.
- Musculoskeletal problems :
. Very common : back pain.
. Common : arthralgia, bone pain
- Platelet disorders, bleeding and coagulation:
. Very common : epistaxis.
. Frequent : haemorrhage, hematuria, deep thrombophlebitis, pulmonary embolism, rectorrhagia.
- Psychiatric disorders:
. Frequent : depression, insomnia.
. Uncommon : nervousness
- Disorders of the defense mechanisms:
Very common : infection.
- Respiratory disorders:
. Very common : dyspnea, cough.
. Common : rhinitis, infection of the upper respiratory tract.
. Rare : interstitial lung disease, pulmonary fibrosis **.
- Skin and subcutaneous tissue disorders:
. Very common : skin disorders, alopecia.
. Frequent : skin exfoliation (ex-hand-foot syndrome), erythematous rash, rash, sweating, dandruff disorders.
- Disorders of other sense organs:
. Very common : taste alteration.
. Uncommon : ototoxicity.
. Rare : deafness.
- Renal and urinary disorders:
Common : dysuria, frequent and abnormal urination
- Vision disorders:
. Uncommon : conjunctivitis, visual disturbances.
. Rare : transient drop in visual acuity, visual field disorder, optic neuritis.
- Disturbance of laboratory parameters:
Hematologic *:
. Very common : Anemia, neutropenia, thrombocytopenia, leukopenia, lymphopenia.
. Common : Febrile neutropenia / septic neutropenia (eg neutropenia grade 3, 4 and proven infections).
Biochemistry:
. Very common : increased alkaline phosphatase, increased bilirubin, abnormal blood glucose levels, elevated LDH, hypokalaemia, hepatic enzyme elevations (SGPT / ALAT, SGOT / AST), abnormalities of serum sodium.
. Frequent : elevation of creatinine.
* see detailed section below.
** see section warnings and precautions for use.
HEMATOLOGICAL TOXICITY :
Oxaliplatin combined with 5-FU / folinic acid 85 mg / m² every 2 weeks.
Incidence per patient, by grade.
Metastatic treatment: All grades / Grade 3 / Grade 4 // Adjuvant therapy: All grades / Grade 3 / Grade 4.
- Anemia: 82.2% / 3% / <1% // 75.6% / 0.7% / 0.1%.
- Neutropenia: 71.4% / 28% / 14% // 78.9% / 28.8% / 12.3%.
Thrombocytopenia: 71.6% / 4% / <1% // 77.4% / 1.5% / 0.2%.
Febrile neutropenia: 5.0% / 3.6% / 1.4% // 0.7% / 0.7% / 0.0%.
- Septic neutropenia: 1.1% / 0.7% / 0.4% // 1.1% / 0.6% / 0.4%.
DIGESTIVE TOXICITY :
Oxaliplatin combined with 5-FU / folinic acid 85 mg / m² every 2 weeks.
Incidence per patient, by grade.
Metastatic treatment: All grades / Grade 3 / Grade 4 // Adjuvant therapy: All grades / Grade 3 / Grade 4.
- Nausea: 69.9% / 8% / <1% // 73.7% / 4.8% / 0.3%.
- Diarrhea: 60.8% / 9% / 2% // 56.3% / 8.3% / 2.5%.
- Vomiting: 49.0% / 6% / 1% // 47.2% / 5.3% / 0.5%.
- Mucites / stomatitis: 39.9% / 4% / <1% // 42.1% / 2.8% / 0.1%.
Preventive and / or curative treatment with strong anti-emetic agents is indicated.
Dehydration, paralytic ileus, intestinal obstruction, hypokalemia, metabolic acidosis, and impaired renal function may be caused by severe diarrhea and / or vomiting, particularly when oxaliplatin is combined with 5-fluorouracil (see warnings and precautions for use).
NERVOUS SYSTEM :
- The limiting toxicity of oxaliplatin is neurological. It is essentially a sensitive peripheral neuropathy characterized by dysaesthesia and / or paresthesia of extremities accompanied or not by cramps, often triggered by cold. These symptoms occur in up to 95% of treated patients. The duration of these symptoms, generally regressive between the cycles of treatment, increases with the repetition of these.
- The occurrence of pain and / or functional discomfort requires, depending on the duration of the symptoms, the adjustment of the dose or even the cessation of treatment (see warnings and precautions for use).
- This functional discomfort, which includes difficulties during the execution of the fine gestures, is a possible consequence of the sensory impairment. The risk of persistent symptoms for a cumulative dose of 850 mg / m² (10 cycles) is about 10%, 20% for a cumulative dose of 1000 mg / m² (12 cycles). The neurological symptomatology improves most often at the end of the treatment.
- In the majority of cases, neurological signs and symptoms improve or resolve completely when treatment is stopped.
- In the adjuvant treatment of colon cancer, 6 months after stopping treatment, 87% of patients have no more symptoms or moderate symptoms. After more than 3 years of follow-up, approximately 3% of patients presented with localized persistent paresthesia of moderate intensity (2.3%) or paresthesia that could interfere with functional activities (0.5%).
- Acute neurosensory manifestations have been reported (see preclinical safety data). They begin in the hours following administration and often occur during exposure to the cold. They are characterized by transient paresthesia, dysesthesia or hypoesthesia or even an acute syndrome of pharyngolaryngeal dysaesthesia. This acute syndrome, whose incidence is estimated between 1% and 2%, is characterized by subjective feelings of dysphagia or dyspnea without objective signs of respiratory distress (without cyanosis or hypoxia) or by laryngospasm or bronchospasm (without stridor or hissing); jaw contracture, lingual dysesthesia, dysarthria and chest tightness were also observed.
Although antihistamines and bronchodilators have been administered in these situations, this symptomatology is rapidly reversible even in the absence of any treatment. The lengthening of the duration of the infusion in the following cycles favors the reduction of the incidence of this syndrome (see warnings and precautions for use).
- Other neurological symptoms such as dysarthria, disappearance of osteotendinous reflexes and a sign of Lhermitte have been reported during treatment with oxaliplatin.
Isolated cases of optic neuritis have been reported.
ALLERGIC REACTIONS :
Oxaliplatin combined with 5-FU / folinic acid 85 mg / m² every 2 weeks.
Incidence per patient, by grade.
Metastatic treatment: All grades / Grade 3 / Grade 4 // Adjuvant therapy: All grades / Grade 3 / Grade 4.
Allergic reactions / allergies: 9.1% / 1% / <1% // 10.3% / 2.3% / 0.6%.

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