Docetaxel Hospira

/ Pfizer

Recommended dosage: For breast, non-small cell lung, gastric, and head and neck cancers, premedication consisting of an oral corticosteroid, such as dexamethasone 16 mg per day (e.g., 8 mg BID) for 3 days starting 1 day prior to docetaxel administration, unless contraindicated, can be used. Prophylactic G-CSF may be used to mitigate the risk of haematological toxicities.
For prostate cancer, given the concurrent use of prednisone or prednisolone the recommended premedication regimen is oral dexamethasone 8 mg 12 hours, 3 hours and 1 hour before the docetaxel infusion. Docetaxel is administered as a one-hour infusion every three weeks.
See prescribing information for full details.

Breast cancer: In combination with doxorubicin and cyclophosphamide for the adjuvant treatment of patients with operable node-positive breast cancer. In combination with doxorubicin for the treatment of patients with locally advanced or metastatic breast cancer who have not previously received cytotoxic therapy for this condition. Monotherapy for the treatment of patients with metastatic breast cancer after failure of cytotoxic therapy. Previous chemotherapy should have included an anthracycline or an alkylating agent. In combination with trastuzumab for the treatment of patients with metastatic breast cancer whose tumors overexpress HER2 and who previously have not received chemotherapy for metastatic disease. In combination with capecitabine for the treatment of patients with metastatic breast cancer after failure of cytotoxic chemotherapy. Previous therapy should have included an anthracycline. Doxorubicin and cyclophosphamide followed by docetaxel in combination with trastuzumab (AC-TH) for the adjuvant treatment of patients with HER2 overexpressing, node-positive or high risk node-negative, breast cancer. In combination with trastuzumab, and carboplatin (TCH) for the adjuvant treatment of patients with HER2 over-expressing, node-positive or high risk node-negative, breast cancer.
Non-small cell lung cancer: Treatment of patients with advanced non-small cell lung carcinoma.
Ovarian cancer: Treatment of metastatic carcinoma of the ovary after failure of first line or subsequent chemotherapy.
Prostate cancer: In combination with prednisone or prednisolone for the treatment of patients with hormone refractory metastatic prostate cancer. Esophageal cancer: Treatment of esophageal cancer.
Gastric cancer: Treatment of advanced gastric cancer.
Head and neck (SCCHN): Monotherapy in the treatment of patients with recurrent and/or metastasis squamous cell carcinoma of the head and neck after failure of a previous chemotherapy regimen. In combination with cisplatin and 5 fluorouracil for the induction treatment of patients with locally advanced squamous cell carcinoma of the head and neck.

– Hypersensitivity to the active substance or to any of the excipients, or to other drugs formulated with polysorbate 80. Severe reactions, including
anaphylaxis, have occurred.
– Patients with baseline neutrophil count of <1,500 cells/mm³
– Severe liver impairment since there is no data available.
Contraindications for other medicinal products also apply when combined with docetaxel.

Haematology
Neutropenia is the most frequent adverse reaction of docetaxel. Neutrophil nadirs occurred at a median of 7 days but this interval may be shorter in heavily pre-treated patients. Frequent monitoring of complete blood counts should be conducted on all patients receiving docetaxel. Patients should be retreated with docetaxel when neutrophils recover to a level of ≥ 1500 cells/mm3.
Gastrointestinal reactions
Caution is recommended for patients with neutropenia, particularly at risk for developing gastrointestinal complications. Although majority of cases occurred during the first or second cycle of docetaxel containing regimen, enterocolitis could develop at any time, and could lead to death as early as on the first day of onset. Patients should be closely monitored for early manifestations of serious gastrointestinal toxicity.
Hypersensitivity reactions
Patients should be observed closely for hypersensitivity reactions especially during the first and second infusions. Hypersensitivity reactions may occur within a few minutes following the initiation of the infusion of docetaxel, thus facilities for the treatment of hypotension and bronchospasm should be available. If hypersensitivity reactions occur, minor symptoms such as flushing or localised cutaneous reactions do not require interruption of therapy. However, severe reactions, such as severe hypotension, bronchospasm or generalised rash/erythema require immediate discontinuation of docetaxel and appropriate therapy. Patients who have developed severe hypersensitivity reactions should not be re-challenged with docetaxel. Patients who have previously experienced a hypersensitivity reaction to paclitaxel may be at risk to develop hypersensitivity reaction to docetaxel, including more severe hypersensitivity reaction. These patients should be closely monitored during initiation of docetaxel therapy.
Cutaneous reactions
Localised skin erythema of the extremities (palms of the hands and soles of the feet) with oedema followed by desquamation has been observed. Severe symptoms such as eruptions followed by desquamation which lead to interruption or discontinuation of docetaxel treatment were reported. Severe Cutaneous Adverse Reactions (SCARs) such as Stevens – Johnson syndrome (SJS), Toxic Epidermal Necrolysis (TEN) and Acute Generalized Exanthematous Pustulosis (AGEP) have been reported with docetaxel treatment. Patients should be informed about the signs and symptoms of serious skin manifestations and closely monitored. If signs and symptoms suggestive of these reactions appear discontinuation of docetaxel should be considered.
Fluid retention
Patients with severe fluid retention such as pleural effusion, pericardial effusion and ascites should be monitored closely.
Respiratory disorders
Acute respiratory distress syndrome, interstitial pneumonia/pneumonitis, interstitial lung disease, pulmonary fibrosis and respiratory failure have been reported and may be associated with fatal outcome. Cases of radiation pneumonitis have been reported in patients receiving concomitant radiotherapy.
If new or worsening pulmonary symptoms develop, patients should be closely monitored, promptly investigated, and appropriately treated. Interruption of docetaxel therapy is recommended until diagnosis is available. Early use of supportive care measures may help improve the condition. The benefit of resuming docetaxel treatment must be carefully evaluated.
Patients with liver impairment
In patients treated with docetaxel there is a higher risk of developing severe adverse reactions such as toxic deaths including sepsis and gastrointestinal haemorrhage which can be fatal, febrile neutropenia, infections, thrombocytopenia, stomatitis and asthenia. Therefore, the recommended dose of docetaxel in those patients with elevated liver function test (LFTs) is 75 mg/m2 and LFTs should be measured at baseline and before each cycle
Patients with renal impairment
This medicinal product contains Macrogol 300 which may increase the risk of nephrotoxicity in patients with renal impairment.
Nervous system
The development of severe peripheral neurotoxicity requires a reduction of dose.
Cardiac toxicity
Heart failure has been observed in patients receiving docetaxel in combination with trastuzumab, particularly following anthracycline (doxorubicin or epirubicin)-containing chemotherapy. This may be moderate to severe and has been associated with death. Patients who are candidates for treatment with docetaxel in combination with Trastuzumab, they should undergo baseline cardiac assessment. Cardiac function should be further monitored during treatment (e.g. every three months) to help identify patients who may develop cardiac dysfunction.
Ventricular arrhythmia including ventricular tachycardia (sometimes fatal) has been reported in patients treated with docetaxel in combination regimens including doxorubicin, 5-fluorouracil and/or cyclophosphamide
Eye disorders
Cystoid macular oedema (CMO) has been reported in patients treated with docetaxel. Patients with impaired vision should undergo a prompt and complete ophthalmologic examination. In case CMO is diagnosed, docetaxel treatment should be discontinued and appropriate treatment initiated
Second primary malignancies
Second primary malignancies have been reported when docetaxel was given in combination with anticancer treatments known to be associated with second primary malignancies. Second primary malignancies (including acute myeloid leukaemia, myelodysplastic syndrome and non-Hodgkin lymphoma) may occur several months or years after docetaxel-containing therapy. Patients should be monitored for second primary malignancies.
Tumor lysis syndrome
Tumour lysis syndrome has been reported after the first or the second cycle. Patients at risk of tumour lysis syndrome (e.g. with renal impairment, hyperuricemia, bulky tumour, rapid progression) should be closely monitored. Correction of dehydration and treatment of high uric acid levels are recommended prior to initiation of treatment.
See prescribing information for full details.

The most commonly reported adverse reactions of docetaxel alone are: neutropenia, anaemia, alopecia, nausea, vomiting, stomatitis, diarrhoea and asthenia. The severity of adverse events of docetaxel may be increased when docetaxel is given in combination with other chemotherapeutic agents.
See prescribing information for full details.

In vitro studies have shown that the metabolism of docetaxel may be modified by the concomitant administration of compounds which induce, inhibit or are metabolised by (and thus may inhibit the enzyme competitively) cytochrome P450-3A such as ciclosporin, terfenadine, ketoconazole, erythromycin and troleandomycin. As a result, caution should be exercised when treating patients with these drugs as concomitant therapy since there is a potential for a significant interaction.
In case of combination with CYP3A4 inhibitors, the occurrence of docetaxel adverse reactions may increase, as a result of reduced metabolism. If the concomitant use of a strong CYP3A4 inhibitor (e.g., ketoconazole, itraconazole, clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin and voriconazole) cannot be avoided, a close clinical surveillance is warranted and a dose-adjustment of docetaxel may be suitable during the treatment with the strong CYP3A4 inhibitor. In a pharmacokinetic study with 7 patients, the co-administration of docetaxel with the strong CYP3A4 inhibitor ketoconazole leads to a significant decrease in docetaxel clearance by 49%.
Docetaxel is highly protein-bound (>95%). Although the possible in vivo interaction of docetaxel with concomitantly administered medication has not been investigated formally, in vitro interactions with tightly protein-bound drugs such as erythromycin, diphenhydramine, propranolol, propafenone, phenytoin, salicylate, sulfamethoxazole and sodium valproate did not affect protein binding of docetaxel. In addition, dexamethasone did not affect protein binding of docetaxel. Docetaxel did not influence the binding of digitoxin.
The pharmacokinetics of docetaxel, doxorubicin and cyclophosphamide were not influenced by their coadministration. Limited data from a single uncontrolled study were suggestive of an interaction between docetaxel and carboplatin. When combined to docetaxel, the clearance of carboplatin was about 50% higher than values previously reported for carboplatin monotherapy.
Docetaxel pharmacokinetics in the presence of prednisone has been studied in patients with metastatic prostate cancer. Docetaxel is metabolised by CYP3A4 and prednisone is known to induce CYP3A4. No statistically significant effect of prednisone on the pharmacokinetics of docetaxel was observed.

Women of childbearing potential/Contraception in males and females
Women of childbearing potential and men receiving docetaxel should be advised to avoid becoming pregnant. Due to the genotoxic risk of docetaxel, women of childbearing potential must use effective method of contraception during treatment and for 2 months after cessation of treatment with docetaxel. Men must use effective contraception during treatment and for 4 months after cessation of treatment with docetaxel.
Pregnancy: There is no information on the use of docetaxel in pregnant women. Docetaxel has been shown docetaxel to be both embryotoxic and foetotoxic in rabbits and rats, and to reduce fertility in rats. As with other cytotoxic medical products docetaxel may cause foetal harm when administered to pregnant women. Therefore, docetaxel must not be used during pregnancy unless clearly indicated.
Women of childbearing age receiving docetaxel should be advised to avoid becoming pregnant, and to inform the treating physician immediately should this occur.
Breast -feeding: Docetaxel is a lipophilic substance but it is not known whether it is excreted in human milk. Consequently, because of the potential for adverse reactions in nursing infants, breast-feeding must be discontinued for the duration of docetaxel therapy.

There were a few reports of overdose. There is no known antidote for docetaxel overdose.
In case of overdose, the patient should be kept in a specialised unit and vital functions closely monitored. In cases of overdose, exacerbation of adverse events may be expected.
The primary anticipated complications of overdose would consist of bone marrow suppression, peripheral neurotoxicity and mucositis. Patients should receive therapeutic G-CSF as soon as possible after discovery of overdose. Other appropriate symptomatic measures should be taken, as needed.