Medicinal Products

DOCETAXEL INTAS PHARMA 20 mg / 0.5 mL

Generic drug of Taxotere
Therapeutic class: Oncology and hematology
active ingredients: Docetaxel
laboratory: Intas Pharmaceuticals Ltd

Solution for solution and solvent for IV infusion
Box of 1 vial of 0.5 ml + vial of solvent of 1.5 ml
All forms

Indication

Breast cancer

DOCETAXEL INTAS PHARMACEUTICALS in combination with doxorubicin and cyclophosphamide is indicated for the adjuvant treatment of operable breast cancer in patients with lymph node involvement.

DOCETAXEL INTAS PHARMACEUTICALS in combination with doxorubicin is indicated for the treatment of locally advanced or metastatic breast cancer in patients who have not received prior cytotoxic chemotherapy for this condition.

DOCETAXEL INTAS PHARMACEUTICALS 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.

DOCETAXEL INTAS PHARMACEUTICALS in combination with trastuzumab is indicated for the treatment of metastatic breast cancer with over-expression of HER2 tumors in patients who have not been pre-treated with chemotherapy for metastatic disease.

DOCETAXEL INTAS PHARMACEUTICALS in combination with capecitabine is indicated for the treatment of locally advanced or metastatic breast cancer after failure of cytotoxic chemotherapy with an anthracycline.

Non-small cell lung cancer

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

DOCETAXEL INTAS PHARMACEUTICALS in combination with cisplatin is indicated for the treatment of unresectable, locally advanced or metastatic non-small cell lung cancer in patients who have not received prior chemotherapy for this indication.

Prostate cancer

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

Gastric cancer

DOCETAXEL INTAS PHARMACEUTICALS in combination with cisplatin and 5-fluorouracil is indicated for the treatment of patients with metastatic gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, in patients who have not received chemotherapy for metastatic disease.

Cancer of the upper aero-digestive tract

DOCETAXEL INTAS PHARMACEUTICALS in combination with cisplatin and 5-fluorouracil is indicated for the induction therapy of locally advanced squamous cell carcinoma of the upper aerodigestive tract.

Dosage DOCETAXEL INTAS PHARMA 20 mg / 0.5 mL Concentrate for solution and solvent for IV infusion Box of 1 vial of 0.5 ml + vial of solvent of 1.5 ml

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

Recommended dosage:

In breast, non-small-cell lung, gastric and upper aero-digestive tract cancers, and unless contraindicated, premedication with an oral corticosteroid may be used, such as dexamethasone at a dose of 16 mg per day ( for example: 8 mg twice daily) for 3 days starting the day before the infusion of docetaxel (see Warnings and Precautions ). Prophylaxis with G CSF can be used to reduce the risk of hematologic toxicity.

In prostate cancer, given the concomitant use of prednisone or

prednisolone, the recommended oral dexamethasone premedication is 8 mg, 12 hours, 3 hours and 1 hour prior to docetaxel infusion (see Warnings and Precautions section ).

Docetaxel is given as a one-hour infusion every three weeks.

Breast cancer :

In the adjuvant treatment of operable, node-positive breast cancer, the recommended dose of docetaxel is 75 mg / m 2 given 1 hour after 50 mg / m 2 of doxorubicin and 500 mg / m 2 of cyclophosphamide every 3 weeks. for 6 cycles (see Dosage Adjustment).

For the treatment of patients with locally advanced or metastatic breast cancer, the recommended dose of docetaxel monotherapy is 100 mg / m 2 . In the first line, docetaxel at the recommended dose of 75 mg / m² is associated with doxorubicin (50 mg / m²).

In combination with trastuzumab, the recommended dose of docetaxel is 100 mg / m 2 every 3 weeks, in combination with trastuzumab administered weekly. In the pivotal study, the first docetaxel infusion was performed the day after the first administration of trastuzumab. The following courses of docetaxel were given immediately after the completion of the trastuzumab infusion if the previous dose of trastuzumab had been well tolerated. For the dosage and method of administration of trastuzumab, see the summary of product characteristics of trastuzumab.

In combination with capecitabine, the recommended dose of docetaxel is 75 mg / m 2 every three weeks, combined with 1250 mg / m 2 of capecitabine twice daily (within 30 minutes after a meal) for two weeks followed by a period without treatment of one week. For capecitabine dose calculations based on body surface area, see capecitabine summary of product characteristics.

Non-small cell lung cancer:

In patients treated for non-small cell lung cancer who received no prior chemotherapy, the recommended doses are 75 mg / m² docetaxel followed immediately by 75 mg / m² cisplatin in 30-60 minutes. After failure of platinum-based chemotherapy, the recommended dose is 75 mg / m² of docetaxel monotherapy.

Prostate cancer :

The recommended dosage of docetaxel 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 ).

Gastric cancer:

The recommended dose of docetaxel is 75 mg / m 2 followed on the same day by a 1 to 3 hour infusion of cisplatin at a dose of 75 mg / m 2. Immediately after the end of the cisplatin infusion, the continuous 5-day infusion of fluorouracil is begun at a dosage of 750 mg / m² / day. The treatment is repeated every 3 weeks. Premedication with antiemetics and adequate hydration prior to cisplatin administration should be performed.

Prophylaxis with G CSF should be used to reduce the risk of hematologic toxicity (see also dose adjustments during treatment).

Cancer of the upper aero-digestive tract:

Patients should be premedicated with anti-emetics and adequate hydration (before and after administration of cisplatin). G-CSF prophylaxis can be used to reduce the risk of haematological toxicity. All docetaxel arm patients in TAX323 and TAX324 were given antibiotic prophylaxis.

· Induction chemotherapy followed by radiotherapy (TAX323)

In the induction treatment of locally advanced and inoperable squamous cell carcinoma of the upper aero-digestive tract, the recommended dose of docetaxel is 75 mg / m² infused over one hour, followed by cisplatin at a dosage of 75 mg / m² infusion. from 1 hour to D1, followed by 5 fluorouracil at a dosage of 750 mg / m² / day in continuous infusion over 5 days. This pattern is repeated every 3 weeks for 4 cycles. After chemotherapy, patients should be treated with radiotherapy.

· Induction chemotherapy followed by chemoradiotherapy (TAX324)

In the induction treatment of patients with locally advanced squamous cell carcinoma of the upper aerodigestive tract (VADS) (unresectable technically, low probability of surgical curability or organ preservation), the recommended dose of docetaxel is 75 mg / day. m 2 intravenous infusion for 1 hour on D1, followed by cisplatin at the dosage of 100 mg / m 2 infusion 30 minutes to 3 hours, followed by 5-fluorouracil 1000 mg / m 2 / day continuous infusion from D1 to J4. This schedule is administered every 3 weeks at 3 cycles. After chemotherapy, patients should be treated with chemoradiotherapy.

For dosage adjustments of cisplatin and 5-fluorouracil, refer to the summary of the corresponding product characteristics.

Dosage adjustment:

Overview

Docetaxel should not be administered until the number of neutrophils is less than 1500 / mm 3 . In patients who during treatment with docetaxel experienced febrile neutropenia, neutrophils <500 / mm 3 for more than 1 week, severe or repeated skin reactions or severe peripheral neuropathy, docetaxel must be reduced from 100 mg / m 2 to 75 mg / m 2 and / or from 75 to 60 mg / m 2 . If these reactions persist at 60 mg / m², treatment should be discontinued.

Adjuvant treatment of breast cancer

In the pivotal study, in patients who received adjuvant treatment for breast cancer and who had complicated neutropenia (including prolonged neutropenia, febrile neutropenia, or infection), it was recommended that G -CSF prophylactically (ex: from 4th to 11th day) for all subsequent cycles. Patients who continued to have this effect should remain on G-CSF and the docetaxel dose should be decreased to 60 mg / m 2 . However, in clinical practice, neutropenia may occur sooner. Therefore, the use of G-CSF should be considered according to the neutropenic risk of the patient and the recommendations in force.

For patients with grade 3 or 4 stomatitis, the dose of docetaxel should be decreased to 60 mg / m 2 .

In combination with cisplatin

In patients who received an initial dose of docetaxel 75 mg / m 2 in combination with cisplatin, for whom nadir platelet count at the previous course of treatment was <25, 000 / mm 3, or with febrile neutropenia, or severe non-haematological toxicities, the dose of docetaxel should be reduced to 65 mg / m² in subsequent cycles. For dosage adjustment of cisplatin, refer to the Summary of Product Characteristics.

In combination with capecitabine

• For dosage adjustment of capecitabine, see its summary of product characteristics.

• In patients with a first appearance of Grade 2 toxicity, which persists until the next dose of docetaxel / capecitabine, delay treatment until returning to Grade 0-1, then continue at 100% initial dosages. .

• In patients with 2nd Grade 2 toxicity or Grade 3 toxicity, regardless of the stage of the treatment cycle, delay treatment until returning to Grade 0-1, then resume treatment with 55 mg / m 2 of docetaxel.

• For any subsequent appearance of toxicity, or any Grade 4 toxicity, discontinue docetaxel therapy.

For dosage modifications of trastuzumab, see the Summary of Product Characteristics.

In combination with cisplatin and 5 fluorouracil

If an episode of complicated neutropenia (febrile, prolonged, or neutropenic) occurs despite the use of G-CSF, the dosage of docetaxel should be reduced from 75 to 60 mg / m².

If other episodes of complicated neutropenia occur, the dosage of docetaxel should be reduced from 60 to 45 mg / m².

In Grade 4 thrombocytopenia, the dose of docetaxel should be reduced from 75 to 60 mg / m².

The following administrations of docetaxel should be resumed only if the number of neutrophils is> 1500 / mm 3 and the number of platelets is> 100 000 / mm 3 . If these haematological toxicities persist treatment should be stopped (see Warnings and precautions for use ).

In case of toxicities, the dose adjustments of patients receiving docetaxel in combination with cisplatin and 5-fluorouracil (5-FU) are as follows:

Toxicity - grade

Dosage adjustments

Diarrhea - grade 3

1st episode: 20% reduction in the dose of 5-FU.

2nd episode: 20% reduction in the dose of docetaxel.

Diarrhea - grade 4

1st episode: 20% reduction in the dose of docetaxel and 5-FU.

2nd episode: discontinuation of treatment.

Stomatitis / mucositis - grade 3

1st episode: 20% reduction in the dose of 5-FU.

2nd episode: definitive cessation of 5-FU only.

3rd episode: 20% reduction of the dose of docetaxel.

Stomatitis / mucositis - grade 4

1st episode: final stop of 5-FU only.

2nd episode: 20% reduction in the dose of docetaxel.

For dosage adjustments for 5-fluorouracil and cisplatin, refer to the summary of product characteristics.

In pivotal studies in patients treated with induction chemotherapy for squamous cell carcinoma of the upper aero-digestive tract, and with complicated neutropenia (including prolonged neutropenia, febrile neutropenia, or infection), G-CSF prophylaxis (ex 6th to 15th day) was recommended for subsequent cycles.

Populations at risk :

Patients with Hepatic Impairment : Based on the pharmacokinetics of 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 ULN as well as alkaline phosphatase greater than 2.5 times the ULN, is 75 mg / m 2 (see Warnings and Precautions and Pharmacokinetic Properties sections). In patients with bilirubinemia> ULN and / or ASAT and ALT 3.5 times ULN and alkaline phosphatase> 6x ULN, no dose reduction may be recommended and docetaxel should not be used. administered unless strictly indicated.

In the treatment of gastric adenocarcinoma, in combination with cisplatin and 5-fluorouracil, the pivotal study excluded patients with transaminase levels (ASAT and / or ALT)> 1.5 times the ULN associated with alkaline phosphatase> 2.5 times ULN and bilirubin> 1 times ULN: therefore, for these patients, no dose reduction may be recommended and docetaxel should not be administered unless strictly indicated. There is no data on hepatic impairment treated with docetaxel in combination with other indications.

Children and adolescents: Use in children is rare.

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

In combination with capecitabine, it is recommended that the initial dose of capecitabine be reduced to 75% in subjects 60 years of age or older (see summary of capecitabine product characteristics).

Against indications

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

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

In the absence of available data, docetaxel 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.

Adverse effects Docetaxel Intas Pharma

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 / m² and 75 mg / m² of docetaxel monotherapy, respectively.

• 258 patients who received docetaxel in combination with doxorubicin.

• 406 patients who received docetaxel in combination with cisplatin.

• 92 patients who received docetaxel in combination with trastuzumab.

• 255 patients who received docetaxel in combination with capecitabine.

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

• 744 patients who received docetaxel in combination with doxorubicin and cyclophosphamide (clinically relevant and treatment-related adverse events are presented below).

• 300 patients with gastric adenocarcinoma (221 patients in phase III and 79 patients in phase II) who received docetaxel in combination with cisplatin and 5-fluorouracil (clinically relevant and treatment-related adverse events are presented below).

• 174 and 251 patients with upper aerodigestive tract cancer treated with docetaxel in combination with cisplatin and 5-fluorouracil (clinically relevant and treatment-related adverse events are presented below).

These events have been described using 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 / 10, 000).

Within each frequency group, adverse effects should be presented in order of decreasing severity.

The most commonly observed adverse events when using docetaxel monotherapy are: neutropenia (reversible and non-cumulative, 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.

For association with trastuzumab, adverse effects (all grades) reported in at least 10% of cases are presented. An increase in the incidence of serious adverse events (40% vs. 31%) and Grade 4 adverse events (34% vs. 23%) was observed for the combination with trastuzumab compared with docetaxel monotherapy.

For the combination with capecitabine, the most commonly reported adverse events (≥5%) in a phase III trial in patients treated for breast cancer after failure of treatment with anthracycline are presented (see summary of characteristics of capecitabine).

The following side effects have been commonly observed with docetaxel:

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 ).

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

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 frequently,

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 ).

DOCETAXEL INTAS PHARMACEUTICALS 100 mg / m² monotherapy

Side effects by system class-organ

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 phosphatase

(G3 / 4 <4%);

elevation of ASAT

(G3 / 4 <3%);

ALT elevation

(G3 / 4 <2%)

Heart conditions

Arrhythmia (G3 / 4: 0.7%)

Heart failure

affections

hematological and

lymphatic system

Neutropenia (G4:

76.4%);

anemia (G3 / 4: 8.9%);

febrile neutropenia

Thrombocytopenia (G4:

0.2%)

Nervous system disorders

Sensory neuropathy

peripheral

(G3: 4.1%);

motor neuropathy

peripheral (G3 / 4:

4%);

dysgeusia (severe:

0.07%)

Respiratory, thoracic and

mediastinal

Dyspnoea (severe:

2.7%)

Gastrointestinal disorders

intestinal

Stomatitis (G3 / 4: 5.3%);

diarrhea (G3 / 4: 4%);

nausea (G3 / 4: 4%);

vomiting (G3 / 4: 3%)

Constipation (severe:

0.2%); pain

abdominal (severe: 1%);

gastrointestinal haemorrhages

intestinal (severe: 0.3%)

Esophagitis (severe:

0.4%)

Skin and subcutaneous tissue disorders

Alopecia;

skin reactions

(G3 / 4: 5.9%); nail alteration (severe: 2.6%)

Musculoskeletal disorders

skeletal and

systemic

Myalgia (severe: 1.4%)

arthralgia

Metabolism disorders and

nutrition

Anorexia

Infections and infestations

Infections (G3 / 4: 5.7%, including sepsis and

pneumonia, fatal evolution 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%); pain

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 / m². 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 / m² and the median reversal time was 16.4 weeks (range 0 to 42 weeks).

The onset of moderate to severe fluid retention is delayed (median cumulative dose:

818.9 mg / m²) in patients who received premedication compared to patients who did not receive premedication (median cumulative dose: 489.7 mg / m²); however, this event has been reported in some patients during the first cycles of treatment.

DOCETAXEL INTAS PHARMACEUTICALS 75 mg / m² monotherapy

Side effects by system class-organ

Very common10% of patients

Frequent1 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

Sensory neuropathy

Peripheral (G3 / 4: 0.8%)

Motor neuropathy

Peripheral (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; skin reactions (G3 / 4: 0.8%)

Nail alteration (severe: 0.8%)

Musculoskeletal disorders

skeletal and systemic

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%); pain

System conditions

immune

Hypersensitivity (never severe)

DOCETAXEL INTAS PHARMACEUTICALS 75 mg / m² in combination with doxorubicin

Side effects by system class-organ

Very common

10% of patients

Frequent1 to <10% of patients

Uncommon0.1 to <1% of patients

investigations

Increase of the

bilirubin G3 / 4 <2.5%);

increase

alkaline phosphatase

(G3 / 4 <2.5%)

Increase in

ASAT (G3 / 4 <1%);

increase

ALAT (G3 / 4 <1%)

Heart conditions

Heart failure ;

arrhythmia (never

severe)

affections

hematological and

lymphatic system

Neutropenia (G4:

91.7%); anemia (G3 / 4: 9.4%);

febrile neutropenia; thrombocytopenia (G4: 0.8%)

Nervous system disorders

Sensory neuropathy

Peripheral (G3: 0.4%)

Motor neuropathy

peripheral (G3 / 4:

0.4%)

Gastrointestinal disorders

intestinal

Nausea (G3 / 4: 5%); stomatitis (G3 / 4: 7.8%);

diarrhea (G3 / 4: 6.2%); vomiting (G3 / 4: 5%); constipation

Skin and subcutaneous tissue disorders

Alopecia;

nail alteration (severe: 0.4%); skin reactions

(never severe)

Musculoskeletal disorders

skeletal and

systemic

myalgia

Disorders of

metabolism and the

nutrition

Anorexia

Infections and infestations

Infection (G3 / 4: 7.8%)

Vascular disorders

hypotension

General disorders and

site anomalies

administration

Asthenia (severe:

8.1%); fluid retention (severe: 1.2%); pain

Feedback to the site

injection

Immune system disorders

Hypersensitivity (G3 / 4: 1.2%)

DOCETAXEL INTAS PHARMACEUTICALS 75 mg / m² in combination with cisplatin

Side effects by system class-organ

Very common

10% of patients

Frequent1 to <10% of patients

Uncommon0.1 to <1% of patients

investigations

Increase of the

bilirubin

(G3 / 4: 2.1%); increase of ALAT

(G3 / 4: 1.3%)

Increase in

AST

(G3 / 4: 0.5%);

increase

alkaline phosphatase

(G3 / 4: 0.3%)

Heart conditions

Arrhythmia (G3 / 4: 0.7%)

Heart failure

affections

hematologic and lymphatic system

Neutropenia (G4: 51.5%);

anemia (G3 / 4: 6.9%); thrombocytopenia (G4: 0.5%)

Febrile neutropenia

Nervous system disorders

Sensory neuropathy

peripheral (G3:

3.7%); peripheral motor neuropathy (G3 / 4: 2%)

Gastrointestinal disorders

intestinal

Nausea (G3 / 4: 9.6%);

vomiting (G3 / 4: 7.6%); diarrhea (G3 / 4: 6.4%);

stomatitis (G3 / 4: 2%)

Constipation

Skin and subcutaneous tissue disorders

Alopecia; nail alteration (severe: 0.7%); skin reactions (G3 / 4: 0.2%)

Musculoskeletal disorders

skeletal and systemic

Myalgia (severe: 0.5%)

Disorders of

metabolism and the

nutrition

Anorexia

Infections and infestations

Infection (G3 / 4: 5.7%)

Vascular disorders

Hypotension (G3 / 4: 0.7%)

General disorders and site abnormalities

administration

Asthenia (severe: 9.9%);

fluid retention

(severe: 0.7%);

fever (G3 / 4: 1.2%)

Feedback to the site

injection;

pain

Immune system disorders

Hypersensitivity (G3 / 4: 2.5%)

DOCETAXEL INTAS PHARMACEUTICALS 100 mg / m² in combination with trastuzumab

Side effects by system class-organ

Very common10% of patients

Frequent1 to <10% of patients

investigations

Increase in weight

Heart conditions

Heart failure

Blood and lymphatic system disorders

Neutropenia (G3 / 4: 32%);

febrile neutropenia (including neutropenia associated with fever and use

of antibiotics) or neutropenia with sepsis

Nervous system disorders

Paresthesia headache;

Dysgeusia; hypoaesthesia

Eye disorders

Increased tearing conjunctivitis

Respiratory disorders,

thoracic and mediastinal

Epistaxis; pharyngolaryngeal pain; nasopharyngitis; dyspnea; cough; rhinorrhea

Gastrointestinal disorders

Nausea; diarrhea;

vomiting; constipation;

stomatitis; dyspepsia; abdominal pain

Skin and subcutaneous tissue disorders

Alopecia; erythema; rash;

nail alteration

Musculoskeletal disorders

skeletal and systemic

Myalgia; arthralgia; pains of extremities; bone pain; back pain

Metabolism and nutrition disorders

Anorexia

Vascular disorders

lymphedema

General disorders and administration site conditions

Asthenia; peripheral edema; fever; tired ; inflammation of the mucous membranes; pains;

flu-like syndrome;

chest pain ; chills

Lethargy

Psychiatric disorders

Insomnia

Heart conditions:

Symptomatic heart failure was reported in 2.2% of patients receiving docetaxel plus trastuzumab, compared to 0% of patients receiving docetaxel alone. In the docetaxel arm associated with trastuzumab, 64% of patients had previously received anthracycline as adjunctive therapy, compared to 55% in the docetaxel arm alone.

Hematological and lymphatic system disorders:

Very common: Hematologic toxicity was higher in patients receiving trastuzumab and docetaxel than in those receiving docetaxel alone (G 3/4 neutropenia: 32% vs. 22%, based on NCI-CTC criteria). It is possible that these figures are underestimated since according to the nadir blood count, docetaxel monotherapy at the dose of 100 mg / m² is known to cause neutropenia in 97% of patients, 76% of grade 4. The The incidence of febrile neutropenia / neutropenia with sepsis was also increased in patients treated with trastuzumab in combination with docetaxel compared to those treated with docetaxel alone (23% vs. 17%).

DOCETAXEL INTAS PHARMACEUTICALS 75 mg / m² in combination with capecitabine

Side effects by system class-organ

Very common10% of patients

Frequent1 to <10% of patients

investigations

Decrease in weight

increased bilirubin (G3 / 4: 9%)

Blood and lymphatic system disorders

Neutropenia (G3 / 4: 63%);

anemia (G3 / 4: 10%)

Thrombocytopenia (G3 / 4: 3%)

Nervous system disorders

Dysgeusia (G3 / 4: <1%);

paresthesia (G3 / 4: <1%)

Dizziness; headache (G3 / 4: <1%); peripheral neuropathy

Eye disorders

Increased tearing

Respiratory disorders,

thoracic and mediastinal

Pharyngolaryngeal pain

(G3 / 4: 2%)

Dyspnoea (G3 / 4: 1%); cough (G3 / 4: <1%); epistaxis (G3 / 4: <1%)

Gastrointestinal disorders

Stomatitis (G3 / 4: 18%);

diarrhea (G3 / 4: 14%);

nausea (G3 / 4: 6%);

vomiting (G3 / 4: 4%);

constipation (G3 / 4: 1%);

abdominal pain (G3 / 4:

2%); dyspepsia

Epigastric pain;

dryness of the mouth

Skin and subcutaneous tissue disorders

Hand-foot syndrome (G3 / 4: 24%); alopecia (G3 / 4: 6%); nail alteration (G3 / 4: 2%)

Dermatitis; erythematous rash (G3 / 4: <1%);

discoloration of the nails;

onycholysis (G3 / 4: 1%)

Musculoskeletal disorders

skeletal and systemic

Myalgia (G3 / 4: 2%);

Arthralgia (G3 / 4: 1%)

Extremity pain (G3 / 4: <1%); back pain (G3 / 4: 1%);

Metabolism and nutrition disorders

Anorexia (G3 / 4: 1%);

decreased appetite

Dehydration (G3 / 4: 2%)

Infections and infestations

Oral candidiasis (G3 / 4:

<1%)

General disorders and administration site conditions

Asthenia (G3 / 4: 3%);

fever (G3 / 4: 1%);

Fatigue / weakness (G3 / 4: 5%); peripheral edema (G3 / 4: 1%)

Lethargy; pain

DOCETAXEL INTAS PHARMACEUTICALS 75 mg / m² in combination with prednisone or prednisolone

Side effects by system class-organ

Very common10% of patients

Frequent1 to <10% of patients

Heart conditions

Decrease of the fraction

left ventricular ejection (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%)

Motor neuropathy

Peripheral (G3 / 4: 0%)

Eye disorders

Increased tearing (G3 / 4: 0.6%)

Respiratory disorders,

thoracic and mediastinal

Epistaxis (G3 / 4: 0%);

dyspnea (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 disorders

skeletal and systemic

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%)

System conditions

immune

Hypersensitivity (G3 / 4: 0.6%)

DOCETAXEL INTAS PHARMACEUTICALS 75 mg / m² in combination with doxorubicin and cyclophosphamide

Side effects by system class-organ

Very common10% of patients

Frequent1 to <10% of patients

Uncommon0.1 to <1% of patients

investigations

Loss or weight gain (G3 / 4: 0.3%)

Heart conditions

Arrhythmia (G3 / 4: 0.1%);

Congestive heart failure

Blood and lymphatic system disorders

Anemia (G3 / 4: 4.3%); neutropenia (G3 / 4: 65.5%); thrombocytopenia (G3 / 4: 2.0%); febrile neutropenia

Nervous system disorders

Dysgeusia (G3 / 4: 0.7%); Peripheral sensory neuropathy (G3 / 4: 0%)

Peripheral motor neuropathy (G3 / 4: 0%); neurocortical disorders (G3 / 4: 0.3%); neurocerebellar disorders (G3 / 4: 0.1%)

Syncope (G3 / 4: 0%)

Eye disorders

Lachrymation (G3 / 4: 0.1%); conjunctivitis (G3 / 4: 0.3%)

Respiratory, thoracic and mediastinal disorders

Cough (G3 / 4: 0%)

Gastrointestinal disorders

Nausea (G3 / 4: 5.1%); stomatitis (G3 / 4: 7.1%); vomiting (G3 / 4: 4.3%); diarrhea (G3 / 4: 3.2%); constipation (G3 / 4: 0.4%)

Abdominal pain (G3 / 4: 0.5%)

Colitis / enteritis / extensive intestinal perforation

Skin and subcutaneous tissue disorders

Alopecia; skin toxicity (G3 / 4: 0.7%); nail alteration (G3 / 4: 0.4%)

Musculoskeletal and systemic disorders

Myalgia (G3 / 4: 0.8%); arthralgia (G3 / 4: 0.4%)

Metabolism and nutrition disorders

Anorexia (G3 / 4: 2.2%)

Infections and infestations

Infection (G3 / 4: 3.2%); neutropenic infection. There was no septic death.

Vascular disorders

Vasodilatation (G3 / 4: 0.9%)

Hypotension (G3 / 4: 0%)

Phlebitis (G3 / 4: 0%); lymphoedema (G3 / 4: 0%)

General disorders and

site anomalies

administration

Asthenia (G3 / 4: 11%); fever (G3 / 4: 1.2%); peripheral edema

(G3 / 4: 0.4%)

System conditions

immune

Hypersensitivity (G3 / 4: 1.1%)

Organ disorders

reproduction and

breast

Amenorrhea

Heart conditions:

Congestive heart failure (2.3% with a median follow-up of 70 months) was also reported. One patient in each arm died of heart failure.

Nervous system disorders:

In 73 patients with peripheral sensory neuropathy at the end of chemotherapy, neurosensory disorders persisted in 9 patients after a median follow-up of 55 months.

Skin and subcutaneous tissue disorders:

Of the 687 patients who had alopecia at the end of chemotherapy, alopecia persisted in 22 patients after a median follow-up of 55 months.

General disorders and administration site defects:

Of the 112 patients who experienced peripheral edema at the end of chemotherapy, peripheral edema persisted in 18 patients after a median follow-up of 55 months.

Disorders of the reproductive organs and the breast:

Of the 233 patients who had amenorrhea at the end of chemotherapy, amenorrhea persisted in 133 patients after a median follow-up of 55 months.

DOCETAXEL INTAS PHARMACEUTICALS 75 mg / m² in combination with cisplatin and 5-fluorouracil in gastric adenocarcinoma

Side effects by system class-organ

Very common10% of patients

Frequent1 to <10% of patients

Heart conditions

Arrhythmia (G3 / 4: 1.0%)

Blood and lymphatic system disorders

Anemia (G3 / 4: 20.9%);

neutropenia (G3 / 4: 83.2%);

thrombocytopenia (G3 / 4: 8.8%);

febrile neutropenia

Nervous system disorders

Sensory neuropathy

peripheral (G3 / 4: 8.7%)

Dizziness (G3 / 4: 2.3%);

motor neuropathy

peripheral (G3 / 4: 1.3%)

Eye disorders

Increased tearing (G3 / 4: 0%)

Affections of the ear and

labyrinth

Hearing disorders (G3 / 4: 0%)

Gastrointestinal disorders

Diarrhea (G3 / 4: 19.7%);

nausea (G3 / 4: 16%);

stomatitis (G3 / 4: 23.7%);

vomiting (G3 / 4: 14.3%)

Constipation (G3 / 4: 1.0%);

gastrointestinal pain

(G3 / 4: 1.0%); esophagitis / dysphagia /

odynophagy (G3 / 4: 0.7%)

Skin and subcutaneous tissue disorders

Alopecia (G3 / 4: 4.0%)

Rash, itching (G3 / 4:

0.7%); nail discoloration (G3 / 4: 0.7%);

desquamation (G3 / 4: 0%)

Metabolism and nutrition disorders

Anorexia (G3 / 4: 11.7%)

Infections and infestations

Neutropenic infection;

infection (G3 / 4: 11.7%)

General disorders and administration site conditions

Lethargy (G3 / 4: 19.0%);

fever (G3 / 4: 2.3%);

fluid retention

(severe / life-threatening: 1%)

System conditions

immune

Hypersensitivity (G3 / 4: 1.7%)

Hematological and lymphatic system disorders:

Febrile neutropenia and neutropenic infection occurred in 17.2% and 13.5%, respectively, regardless of the use of G-CSF. G-CSF was used for secondary prophylaxis in 19.3% of patients (10.7% of chemotherapy cycles). Febrile neutropenia and neutropenic infection occurred in 12.1% and 3.4%, respectively, of patients who received G-CSF prophylaxis and 15.6% and 12.9% of patients who did not receive G-CSF. -CSF (see section Dosage and method of administration ).

DOCETAXEL INTAS PHARMACEUTICALS 75 mg / m² in combination with cisplatin and 5-fluorouracil in cancers of the upper aero-digestive tract

· Induction chemotherapy followed by radiotherapy (TAX323)

Side effects by system class-organ

Very common

10% of patients

Frequent

1 to <10% of patients

Rare

0.1 to <1% of

patients

investigations

Increase in weight

Heart conditions

Myocardial ischemia

(G3 / 4: 1.7%)

Arrhythmia (G3 / 4:

0.6%)

affections

hematological and

lymphatic system

Neutropenia (G3 / 4:

76.3%); anemia (G3 / 4: 9.2%);

thrombocytopenia (G3 / 4:

5.2%)

Febrile neutropenia

Affection of the system

nervous

Dysgeusia / parosmia;

sensitive neuropathy

peripheral (G3 / 4:

0.6%)

Fear of heights

Eye disorders

Increased tearing conjunctivitis

Affections of the ear and labyrinth

Hearing disorders

Gastrointestinal disorders

intestinal

Nausea (G3 / 4: 0.6%); stomatitis (G3 / 4: 4.0%);

diarrhea (G3 / 4: 2.9%); vomiting (G3 / 4: 0.6%)

Constipation; oesophagitis / dysphagia / odynophagia (G3 / 4:

0.6%); abdominal pain ; dyspepsia; gastrointestinal bleeding (G3 / 4: 0.6%)

Skin disorders and

subcutaneous tissue

Alopecia (G3 / 4: 10.9%)

Rash with pruritus; dry skin ; desquamation (G3 / 4: 0.6%)

Musculoskeletal disorders

skeletal and

systemic

Myalgia (G3 / 4: 0.6%)

Disorders of

metabolism and the

nutrition

Anorexia (G3 / 4: 0.6%)

Infections and infestations

Infections (G3 / 4: 6.3%); infections

neutropenic

Benign tumors and

malignant (including

cysts and polyps)

Cancerous pain

(G3 / 4: 0.6%)

Vascular disorders

Venous disorders (G3 / 4: 0.6%)

General disorders and

site anomalies

administration

Lethargy (G3 / 4: 3.4%); fever (G3 / 4: 0.6%); fluid retention; edema

System conditions

immune

Hypersensitivity (never

severe)

· Induction chemotherapy followed by chemoradiotherapy (TAX324)

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Side effects

by class system

organ

Very common

10% of patients

Frequent

1 to <10% of

patients

Rare

0.1 to <1% of

patients

investigations

Weightloss

Increase in weight

Heart conditions

Arrhythmia (G3 / 4: 2.0%)

Myocardial ischemia