Medicinal Products

ELOXATINE 5 mg / ml concentrate for solution for infusion box of 1 vial of 10 ml

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

Solution for solution for IV infusion
All forms

Indication

Oxaliplatin in combination with 5-fluorouracil (5FU) and folinic acid (AF) 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 concentrate for solution for infusion box of 1 vial of 10 ml

Oxaliplatin in combination with 5-fluorouracil (5FU) and folinic acid (AF) 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.

Against indications

Oxaliplatin is contraindicated in patients:

· With a known history of hypersensitivity to the active substance or to any of the excipients listed under Composition,

· Who are breastfeeding,

· With bone marrow failure before the first treatment cycle (neutrophils <2x10 9 / L and / or platelets <100x10 9 / L),

· Presenting peripheral sensory neuropathy with functional impairment before the first treatment cycle,

· With severe renal impairment (creatinine clearance <30 ml / min) (see section 5.2 ).

Eloxatin side effects

Tolerance Profile Summary

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 dose-cumulative).

Overall, these adverse events were more frequent and severe with oxaliplatin in combination with 5-FU / AF than with 5-FU / AF alone.

Summary list of adverse reactions

The frequencies presented in the table below are derived from clinical studies in metastatic treatment and adjuvant therapy (including 416 and 1108 patients in the oxaliplatin + 5-FU / AF arm) and experience since the the market.

The frequencies mentioned in the table have been defined using the following criteria: very common (≥ 1/10), common (≥ 1/100, <1/10), uncommon (≥ 1/1000, <1/100), rare (≥ 1/10000, <1/1000), very rare (<1/10000), and of undetermined frequency (can not be estimated from the available data).

Further information is given after the table.

Frequency Class-organ system

Very common

Frequent

Rare

Rare

Infections and infestation *

· Infection

· Rhinitis

· Upper respiratory tract infection

· Sepsis neutropenia

· Sepsis +

Hematological and lymphatic system disorders *

· Anemia

· Neutropenia

· Thrombocytopenia

· Leukopenia

· Lymphopenia

· Febrile neutropenia

· Immune allergic thrombocytopenia

· Hemolytic anemia

Immune system disorders *

· Allergy / allergic reactions ++

Metabolism and nutrition disorders *

· Anorexia

· Hyperglycemia

· Hypokalemia

· Hypernatremia

· Dehydration

· Metabolic acidosis

Psychiatric disorders

· Depression

· Insomnia

· Nervousness

Nervous system disorders *

· Sensory peripheral neuropathy

Sensory disorders

· Alteration of taste

· Headache

· Dizziness

· Motor neuritis

· Meningism

· Dysarthria

· Posterior Reversible Leukoencephalopathy Syndrome (SLPR) (see Warnings and Precautions section )

Eye disorders

· Conjunctivitis

· Visual disturbances

· Transient decrease in visual acuity

· Visual field disorders

· Optic neuritis

· Temporary loss of vision, reversible upon discontinuation of treatment

Affections of the ear and labyrinth

· Ototoxicity

· Deafness

Vascular disorders

· Haemorrhages

· Flushing

· Deep thrombophlebitis

· Hypertension

Respiratory, thoracic and mediastinal disorders

· Dyspnea

· Cough

· Epistaxis

· Hiccup

· Pulmonary embolism

Interstitial pneumonitis, sometimes fatal

· Pulmonary fibrosis **

Gastrointestinal disorders *

· Nausea

· Diarrhea

· Vomiting

· Stomatitis / Mucites

· Abdominal pain

· Constipation

· Dyspepsia

· Gastroesophageal reflux

· Gastrointestinal bleeding

· Rectorragies

· Ileus

· Intestinal obstruction

· Colitis including Clostridium difficile diarrhea

· Pancreatitis

Skin and subcutaneous tissue disorders

· Skin disorders

· Alopecia

· Skin exfoliation (ie hand-foot syndrome)

· Rash erythematosus

· Rash

· Hypersudation

· T roubles of the integuments

Musculoskeletal and systemic disorders

· Back pain

· Arthralgia

· Bone pain

Renal and urinary disorders

· Hematuria

· Dysuria

· Frequent and abnormal urination

General disorders and administration site conditions

· Tired

· Fever +++

· Asthenia

· Pain

· Injection site reaction ++++

investigations

· Elevation of liver enzymes

· Elevation of alkaline phosphatases

· Elevation of bilirubin

· Elevation of LDH

· Weight gain (adjuvant treatment)

· Elevation of creatinine

· Weight loss (metastatic treatment)

* See detailed heading below.

** See section Warnings and precautions for use

+ Frequent neutropenic sepsis, including cases of fatal outcome.

++ Very common allergic / allergic reactions occurring mainly during the infusion, sometimes fatal (frequent allergic reactions such as rash especially urticaria, conjunctivitis, rhinitis). Frequent anaphylactic or anaphylactoid reactions including bronchospasm, angiodemesis, hypotension, chest pain sensation, and anaphylactic shock).

+++ Very frequent fevers, either of infectious origin (with or without febrile neutropenia), or isolated of immunological origin.

++++ Injection site reaction including local pain, redness, swelling and thrombosis. Extravasation may also cause local pain and inflammation, which can be severe and lead to complications including necrosis, particularly when oxaliplatin is perfused via the peripheral venous route (see section 4.4 ). .

Description of some adverse effects

Blood and lymphatic system disorders

Incidence per patient (%), by grade

Oxaliplatin combined with 5-FU / folinic acid 85 mg / m 2 every 2 weeks

Metastatic treatment

Adjuvant treatment

All grades

Grade 3

Grade 4

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

Experience since placing on the market, of undetermined frequency:

Uremic hemolytic syndrome.

Infections and infestations

Incidence per patient (%)

Oxaliplatin associated with

5-FU / folinic acid

85 mg / m²

every 2 weeks

Metastatic treatment

All grades

Adjuvant treatment

All grades

Sepsis (including neutropenic sepsis)

1.5

1.7

Experience since placing on the market of undetermined frequency:

· Septic shock, including cases of fatal outcome

Immune system disorders

Incidence of allergic reactions per patient (%), by grade

Oxaliplatin combined with 5-FU / folinic acid 85 mg / m 2 every 2 weeks

Metastatic treatment

Adjuvant treatment

All grades

Grade 3

Grade 4

All grades

Grade 3

Grade 4

Allergic reactions / allergies

9.1

1

<1

10.3

2.3

0.6

Affection of the 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 section Warnings and precautions for use ).

This functional discomfort, which includes difficulties during the execution of precise gestures, is a possible consequence of the sensory impairment. The risk of persistent symptoms for a cumulative dose of 850 mg / m 2 (10 cycles) is approximately 10% and 20% for a cumulative dose of 1020 mg / m 2 (12 cycles).

In the majority of cases, neurological signs and symptoms improve or resolve completely when treatment is stopped.

In the adjunctive treatment of colon cancer, 6 months after stopping treatment, 87% of patients have no symptoms or moderate symptoms. After more than 3 years of follow-up, approximately 3% of patients presenting with localized persistent paresthesia of moderate intensity (2.3%) are paresthesia that can interfere with functional activities (0.5%).

Acute neurosensory manifestations have been reported (see section 5.3 ). They begin in the hours following administration and often occur during exposure to the cold. They are usually characterized by transient paresthesia, dysesthesia or hypoesthesia. Acute pharyngeal dysesthesia syndrome

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