Medicinal Products

DOCETAXEL EBEWE 10 mg / mL

Generic drug of the therapeutic class: Oncology and Hematology
active ingredients: Docetaxel
laboratory: Sandoz

Solution for solution for IV infusion
Box of 1 bottle of 16 ml
All forms

Indication

Breast cancer

DOCETAXEL EBEWE is indicated as monotherapy in the treatment of patients with locally advanced or metastatic breast cancer after failure of cytotoxic chemotherapy, including an anthracycline or alkylating agent.

Non-small cell lung cancer

DOCETAXEL EBEWE is indicated for the treatment of locally advanced or metastatic non-small cell lung cancer after failure of prior chemotherapy.

Prostate cancer

DOCETAXEL EBEWE in combination with prednisone or prednisolone is indicated for the treatment of metastatic hormone-resistant prostate cancer.

Dosage DOCETAXEL EBEWE 10 mg / mL Concentrate for solution for infusion IV Box of 1 vial of 16 ml

The use of docetaxel should be restricted to units specialized in cytotoxic administration and should be administered under the supervision of a physician qualified in the use of anticancer chemotherapy (see section Instructions for use, handling and elimination). ).

Recommended dosage:

In breast, non-small-cell lung and non-contraindicated cancers, premedication with an oral corticosteroid may be used, such as dexamethasone at a dose of 16 mg per day (eg 8 mg twice daily) for 3 days starting the day before the infusion of docetaxel (see Warnings and Precautions ).

In prostate cancer, given the concomitant use of prednisone or prednisolone, the recommended oral premedication of dexamethasone is 8 mg, 12 hours, 3 hours and 1 hour prior to docetaxel infusion (see section 4.4). and precautions for use ).

Docetaxel Ebewe is given as a one-hour infusion every three weeks. See section Instructions for use, handling and disposal for more details on the preparation of the infusion solution.

Precautions should be taken during the infusion to avoid extravasation.

Breast cancer :

For the treatment of patients with locally advanced or metastatic breast cancer, the recommended dose of Docetaxel Ebewe monotherapy is 100 mg / m 2 .

Non-small cell lung cancer:

After failure of platinum-based chemotherapy, the recommended dose is 75 mg / m 2 of docetaxel monotherapy.

Prostate cancer:

The recommended dosage of Docetaxel Ebewe is 75 mg / m 2 . Prednisone or oral prednisolone is administered continuously at a dose of 5 mg twice daily (see section 5.1 Pharmacodynamic properties ).

Dosage adjustment:

Overview

Docetaxel Ebewe should not be administered until the number of neutrophils is less than 1500 / mm 3 .

In patients who during treatment with Docetaxel Ebewe experienced febrile neutropenia, neutrophil count <500 / mm 3 for more than one week, severe or repeated skin reactions, or severe peripheral neuropathy, the dose of Docetaxel Ebewe should be reduced from 100 mg / m 2 to 75 mg / m 2 and / or 75 to 60 mg / m 2 . If these reactions persist at 60 mg / m 2, treatment should be discontinued.

Populations at risk:

Patients with Hepatic Impairment: Based on the pharmacokinetic data for docetaxel 100 mg / m 2 monotherapy, the recommended dose of docetaxel in patients with transaminases (ALT and / or ASAT) greater than 1.5 times the limit normal range (ULN) and alkaline phosphatase greater than 2.5 times the ULN is 75 mg / m 2 (see sections Warnings and Precautions and Pharmacokinetic Properties ). In patients with bilirubinemia> ULN and / or ASAT and ALAT 3.5 times ULN and alkaline phosphatase> 6 x ULN, no dose reduction may be recommended and docetaxel should not be used. administered unless strictly indicated.

There are no data available in patients with hepatic impairment treated with docetaxel in combination with other indications.

This medicine contains 27% ethanol (alcohol). This must be taken into account in at-risk populations such as patients with hepatic impairment.

Patients with renal insufficiency:

There are no data available in patients with severe renal impairment treated with docetaxel.

Children and adolescents:

Docetaxel Ebewe is not recommended for use in children because of lack of sufficient safety data and efficacy.

Elderly: Based on population pharmacokinetic data, no special precautions should be taken in the elderly.

Against indications

Hypersensitivity to the active substance or to any of the excipients.

Docetaxel Ebewe should not be used in patients with an initial neutrophil count <1500 / mm 3 .

Docetaxel Ebewe should not be administered to pregnant or nursing women (see section Pregnancy and breast-feeding ).

In the absence of available data, Docetaxel Ebewe should not be administered to patients with severe hepatic impairment (see sections Posology and method of administration and Warnings and precautions for use ).

Also take into account the contraindications of the specialties associated with Docetaxel Ebewe.

Adverse effects Docetaxel Ebewe

Adverse reactions believed to be possibly or probably related to the administration of docetaxel have been reported in:

· 1312 and 121 patients receiving 100 mg / m 2 and 75 mg / m 2 of docetaxel monotherapy, respectively.

· 332 patients who received docetaxel in combination with prednisone or prednisolone (clinically important and treatment-related adverse events are presented).

These events have been described using the NCI Common Criteria for Toxicity (grade 3 = G3, grade 3-4 = G3 / 4, grade 4 = G4) and COSTART terms. Frequencies are defined as: very common (≥1 / 10), frequent (≥1 / 100, <1/10); uncommon (≥1 / 1000, <1/100); rare (≥1 / 10, 000, <1/1000); very rare (<1/10000).

Within each frequency group, adverse effects are presented in descending order of severity.

The most common adverse events observed with docetaxel monotherapy were: neutropenia (reversible and noncumulative, median nadir onset and median duration of severe neutropenia (<500 / mm 3 ) were 7 days), anemia, alopecia, nausea, vomiting, stomatitis, diarrhea and asthenia.

The severity of the undesirable effects of docetaxel may be increased when combined with other cytotoxics.

The following side effects have been commonly observed with docetaxel:

Nervous system disorders:

The occurrence of severe peripheral neurotoxicity requires a dose reduction (see sections Posology and method of administration and Warnings and precautions for use ).

Mild to moderate neurosensory signs are characterized by paresthesia, dysesthesia or pain-like burning sensations. Neuromotor manifestations are mainly characterized by weakness.

Skin and subcutaneous tissue disorders:

Reversible skin reactions were observed and were generally considered mild to moderate. Reactions were characterized by rash with localized eruptions mainly in the feet and hands (including severe hand-foot syndromes) but also in the arms, face or chest, and frequently associated with pruritus. These eruptions usually occurred in the week following the infusion of docetaxel. Severe symptoms such as eruptions followed by desquamation, rarely leading to temporary or definitive discontinuation of docetaxel, have been reported less frequently (see section 4.2). Posology and method of administration and Warnings and Precautions employment ). Severe nail disorders are characterized by hypo or hyperpigmentation of the nails and sometimes pain and onycholysis.

General disorders and administration site defects:

Injection site reactions were generally minor and manifested by hyperpigmentation, inflammation, redness or dryness of the skin, phlebitis or extravasation, and swelling of the vein.

Fluid retention may result in peripheral edema and, less commonly, pleural effusion, pericardial effusion, ascites, and weight gain. Peripheral edema usually begins in the lower limbs and can be generalized with a weight gain of 3 kg or more. Fluid retention is cumulative in incidence and severity (see Warnings and Precautions section ).

Immune system disorders:

Hypersensitivity reactions usually occurred within minutes of starting a docetaxel infusion and were usually mild to moderate. The most commonly reported symptoms were flushes, rash with or without pruritus, chest tightness, low back pain, dyspnea and fever or chills. Intense reactions were characterized by hypotension and / or bronchospasm or general rash / erythema (see Warnings and Precautions section ).

DOCETAXEL EBEWE 100 mg / m 2 monotherapy

MedDRA system-organ side effects

Very common ≥10% of patients

Frequent ≥1 to <10% of patients

Uncommon ≥0.1 to <1% of patients

investigations

Elevation of bilirubin (G3 / 4 <5%); Elevation of alkaline phosphatases (G3 / 4 <4%); Elevation of ASAT (G3 / 4 <3%); ALT elevation (G3 / 4 <2%)

Heart conditions

Arrhythmia (G3 / 4: 0.7%)

Heart failure

Blood and lymphatic system disorders

Neutropenia (G4: 76.4%); Anemia (G3 / 4: 8.9%); Febrile neutropenia

Thrombocytopenia (G4: 0.2%)

Nervous system disorders

Peripheral sensory neuropathy (G3: 4.1%); Peripheral motor neuropathy (G3 / 4: 4%); Dysgeusia (severe 0.07%)

Respiratory, thoracic and mediastinal disorders

Dyspnoea (severe: 2.7%)

Gastrointestinal disorders

Stomatitis (G3 / 4: 5.3%); Diarrhea (G3 / 4: 4%); Nausea (G3 / 4: 4%); Vomiting (G3 / 4: 3%)

Constipation (severe: 0.2%); Abdominal pain (severe: 1%); Gastrointestinal haemorrhage (severe: 0.3%)

Esophagitis (severe: 0.4%)

Skin and subcutaneous tissue disorders

Alopecia; Cutaneous reactions (G3 / 4: 5.9%); Nail Alteration (severe: 2.6%)

Musculoskeletal and systemic disorders

Myalgia (severe: 1.4%)

arthralgia

Metabolism and nutrition disorders

Anorexia

Infections and infestations

Infections (G3 / 4: 5.7%, including sepsis and pneumonia, fatal in 1.7% of cases)

Infection associated with grade 4 neutropenia (G3 / 4: 4.6%)

Vascular disorders

Hypotension; Hypertension Hemorrhage

General disorders and administration site conditions

Fluid retention (severe: 6.5%); Asthenia (severe: 11.2%); pains

Reaction at the injection site; Chest pain of non-cardiac origin (severe: 0.4%)

Immune system disorders

Hypersensitivity (G3 / 4: 5.3%)

Hematological and lymphatic system disorders:

Rare: bleeding episodes associated with grade 3/4 thrombocytopenia.

Nervous system disorders:

Reversibility data are available for 35.3% of patients with neurotoxic manifestations following docetaxel monotherapy at 100 mg / m 2 . These effects were spontaneously reversible within 3 months.

Skin and subcutaneous tissue disorders:

Very rare: 1 case of non-reversible alopecia at the end of the study. 73% of the skin reactions were reversible within 21 days.

General disorders and administration site defects:

For fluid retention, the median cumulative dose at discontinuation was greater than 1000 mg / m 2 and the median reversal time was 16.4 weeks (range 0 to 42 weeks).

The occurrence of moderate to severe fluid retention is delayed (median cumulative dose: 818.9 mg / m 2 ) in premedicated patients compared to patients who did not receive premedication (median cumulative dose: 489, 7 mg / m 2 ); however, this event has been reported in some patients during the first cycles of treatment.

DOCETAXEL 75 mg / m 2 monotherapy

MedDRA system-organ side effects

Very common ≥10% of patients

Frequent ≥1 to <10% of patients

investigations

Elevation of bilirubin (G3 / 4 <2%)

Heart conditions

Arrhythmia (never severe)

Blood and lymphatic system disorders

Neutropenia (G4: 54.2%);

Anemia (G3 / 4: 10.8%);
Thrombocytopenia (G4: 1.7%)

Febrile neutropenia

Nervous system disorders

Peripheral sensory neuropathy (G3 / 4: 0.8%)

Peripheral motor neuropathy (G3 / 4: 2.5%)

Gastrointestinal disorders

Nausea (G3 / 4: 3.3%);
Stomatitis (G3 / 4: 1.7%);
Vomiting (G3 / 4: 0.8%);
Diarrhea (G3 / 4: 1.7%)

Constipation

Skin and subcutaneous tissue disorders

Alopecia; Cutaneous reactions (G3 / 4: 0.8%)

Nail alteration (severe: 0.8%)

Musculoskeletal and systemic disorders

myalgia

Metabolism and nutrition disorders

Anorexia

Infections and infestations

Infections (G3 / 4: 5%)

Vascular disorders

hypotension

General disorders and administration site conditions

Asthenia (severe: 12.4%); Fluid retention (severe: 0.8%;

Immune system disorders

Hypersensitivity (never severe)

DOCETAXEL 75 mg / m 2 in combination with prednisone or prednisolone

MedDRA system-organ side effects

Very common ≥10% of patients

Frequent ≥1 to <10% of patients

Heart conditions

Decrease in left ventricular ejection fraction (G3 / 4: 0.3%)

Blood and lymphatic system disorders

Neutropenia (G3 / 4: 32%);
Anemia (G3 / 4: 4.9%)

Thrombocytopenia; (G3 / 4: 0.6%); Febrile neutropenia

Nervous system disorders

Sensory neuropathy
peripheral (G3 / 4: 1.2%);
Dysgeusia (G3 / 4: 0%)

Peripheral motor neuropathy (G3 / 4: 0%)

Eye disorders

Increased tearing (G3 / 4: 0.6%)

Respiratory, thoracic and mediastinal disorders

Epistaxis (G3 / 4: 0%);
Dyspnoea (G3 / 4: 0.6%); Cough (G3 / 4: 0%)

Gastrointestinal disorders

Nausea (G3 / 4: 2.4%);
Diarrhea (G3 / 4: 1.2%);
Stomatitis / Pharyngitis (G3 / 4: 0.9%);
Vomiting (G3 / 4: 1.2%)

Skin and subcutaneous tissue disorders

Alopecia; Nail Alteration (never severe)

Eruption with desquamation (G3 / 4: 0.3%)

Musculoskeletal and systemic disorders

Arthralgia (G3 / 4: 0.3%); Myalgia (G3 / 4: 0.3%)

Metabolism and nutrition disorders

Anorexia (G3 / 4: 0.6%)

Infections and infestations

Infection (G3 / 4: 3.3%)

General disorders and administration site conditions

Fatigue (G3 / 4: 3.9%); Fluid retention (severe: 0.6%)

Immune system disorders

Hypersensitivity (G3 / 4: 0.6%)

Other adverse effects observed after the placing on the market:

Heart conditions:

Rare cases of myocardial infarction have been reported.

Hematological and lymphatic system disorders:

Myelosuppression and other hematologic adverse events have been reported. Cases of disseminated intravascular coagulation (DIC), often associated with sepsis or multiple organ failure, have been reported.

Nervous system disorders:

Rare cases of convulsion or transient loss of consciousness have been observed following administration of docetaxel. These reactions sometimes appear during the infusion of the drug.

Eye disorders:

Very rare cases of transient visual disturbances (flashes, flickers, scotomas) have been reported to occur typically during infusion of the product and in association with hypersensitivity reactions. These effects are reversible when the infusion is stopped. Rare cases of tearing, with or without conjunctivitis, and lacrimal duct obstruction with inadvertent tearing have been reported.

Affections of the ear and labyrinth:

Rare cases of ototoxicity, hearing impairment and / or hearing loss have been reported.

Respiratory, thoracic and mediastinal disorders:

Rare cases of acute respiratory distress syndrome, interstitial lung disease and pulmonary fibrosis have been reported. Rare cases of radiation pneumonitis have been reported in patients receiving concomitant radiotherapy.

Gastrointestinal disorders:

Rare cases of dehydration due to gastrointestinal events, intestinal perforations, ischemic colitis, colitis and enterocolitis during neutropenia have been reported. Rare cases of ileus and intestinal obstruction have been reported.

Skin and subcutaneous tissue disorders:

Very rare cases of cutaneous lupus erythematosus and bullous eruptions such as erythema multiforme, Stevens-Johnson syndrome, Lyell syndrome, have been reported with docetaxel. In some cases, other concomitant factors may have contributed to the development of these effects. Cutaneous changes of the scleroderma type usually preceded by peripheral lymphoedema have been reported with docetaxel.

Vascular disorders:

Venous thromboembolic effects have been reported rarely.

General disorders and administration site defects:

Radiation reaction reactivation phenomena have rarely been reported.

Cases of fluid retention were not accompanied by acute episodes of oliguria or hypotension. Dehydration and pulmonary edema have been reported rarely.

Immune system disorders:

Some cases of sometimes fatal anaphylactic shocks have been reported.

Hepatobiliary disorders:

Very rare cases of sometimes fatal hepatitis have been reported, mainly in patients with pre-existing liver damage.

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