Docetaxel Adco 20 mg/1 ml/80 mg/4 ml/140 mg/7 ml Solution

DOCETAXEL ADCO is indicated for the following:

1. Breast Cancer: DOCETAXEL ADCO, in combination with doxorubicin and cyclophosphamide is indicated for the adjuvant treatment of patients with operable node-positive breast cancer. DOCETAXEL ADCO, in combination with doxorubicin, is indicated for the treatment of patients with locally advanced or metastatic breast cancer who have not previously received cytotoxic therapy for his condition. DOCETAXEL ADCO monotherapy is indicated for the treatment of patients with locally advanced or metastatic breast cancer, after failure of cytotoxic therapy. DOCETAXEL ADCO, in combination with capecitabine, is indicated for the treatment of patients with locally advanced or metastatic breast after failure of cytotoxic chemotherapy. Previous therapy should have included an anthracycline.
2. Non-small Cell Lung Cancer (NSCLC): DOCETAXEL ADCO, in combination with cisplatin, is indicated for the treatment of patients with unresectable, locally advanced or metastatic non-small cell lung cancer, who have not previously received chemotherapy for this condition. DOCETAXEL ADCO is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer breast cancer, even after failure of platinum-based chemotherapy.
3. Ovarian Cancer: DOCETAXEL ADCO is indicated, after failure of first-line or subsequent chemotherapy, for treatment of metastatic carcinoma of the ovary.
4. Prostate Cancer: DOCETAXEL ADCO in combination with prednisone or prednisolone is indicated for the treatment of patients with androgen independent (hormone refractory) metastatic prostate cancer.
5. Head and neck Cancer: DOCETAXEL ADCO in combination with cisplatin and 5-flurouracil is indicated for treatment of patients with inoperable locally advanced squamous cell carcinoma of the head and neck.

A premedication consisting of a corticosteroid (see below for prostate cancer), such as oral dexamethasone 16 mg per day (e.g. 8 mg twice daily) for 3 days starting one day prior to docetaxel administration, unless contraindicated, can be used. 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 ADCO infusion. Prophylactic G-CSF may be used to mitigate the risk of haematological toxicities. Docetaxel is administered as a one-hour infusion every three weeks.

1. Breast cancer: In the adjuvant treatment of operable node-positive breast cancer, the recommended dose of DOCETAXEL ADCO is 75 mg/m2 administered 1-hour after doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 every 3 weeks for 6 cycles (see also u201cDosage adjustments during treatmentu201d). In first-line treatment, DOCETAXEL ADCO 75 mg/m2 is given in combination therapy with doxorubicin (50 mg/m2). For the second line treatment of breast cancer the recommended dosage of DOCETAXEL ADCO therapy is 100 mg/m2 is given in monotherapy. In combination with capecitabine, the recommended dose of DOCETAXEL ADCO is 75 mg/m2 every three weeks, combined with capecitabine at 1 250 mg/m2 twice daily (within 30 minutes after a meal) for 2 weeks followed by 1-week rest period. For capecitabine dose calculation according to body surface area, see capecitabine package insert.
2. Non-small cell lung cancer: In combination therapy (chemotherapy nau00efve patients): The recommended dose regimen is DOCETAXEL ADCO 75 mg/m2 immediately followed by cisplatin 75 mg/m2 over 30-60 minutes. In monotherapy (for previously treated patients): The recommended dosage of DOCETAXEL ADCO therapy is 100 mg/m2 as a single medicine.
3. Ovarian Cancer: The recommended dosage of DOCETAXEL ADCO therapy is 100 mg/m2.
4. Prostate cancer: The recommended dose of DOCETAXEL ADCO is 75 mg/m2. Prednisone or prednisolone 5 mg orally twice daily is administered continuously. Patients should be observed closely especially during the first and second infusion of DOCETAXEL ADCO, because of risk of hypersensitivity reactions.
5. Head and neck cancer: For the induction treatment of locally advanced inoperable squamous cell carcinoma of the head and neck (SCCHN), the recommended dose of DOCETAXEL ADCO is 75 mg/m2 as a 1-hour infusion followed by cisplatin 75 mg/m2 over 1 hour, on day one, followed by 5-fluorouracil as a continuous infusion at 750 mg/m2 per day for five days. This regimen is administered every 3 weeks for 4 cycles. Following chemotherapy, patients should receive radiotherapy. Patients must receive premedication with antiemetics and appropriate hydration (prior to and after cisplatin administration). Prophylaxis for neutropenic infections should be administered. For cisplatin and 5-fluorouracil dose modifications, see local package insert.

Dosage adjustments during treatment

General: ONLY the medical practitioner can modify the schedule of administration. DOCETAXEL ADCO should be administered when the neutrophil count is > 1 500 cells/mm3. Patients who experienced either febrile neutropenia, neutrophil count < 500 cells/mm3 for more than one week, severe or cumulative cutaneous reactions or severe neurosensory signs and/or symptoms, during DOCETAXEL ADCO therapy, should have the dosage of DOCETAXEL ADCO reduced, during the subsequent cycle, from 100 mg/m2 to 75 mg/m2 and/or from 75 to 60 mg/m2. If the patient continues to experience these reactions at 60 mg/m2, the treatment should be discontinued.

DOCETAXEL ADCO is contra-indicated in patients who have a history of severe hypersensitivity reactions to docetaxel or polysorbate 80 or any of the other inactive ingredients contained in DOCETAXEL ADCO. DOCETAXEL ADCO should not be used in patients with baseline neutrophil count of < 1 500 cells/mm3. DOCETAXEL ADCO should not be used in pregnancy and lactation. The safe use of DOCETAXEL ADCO in children has not been established. DOCETAXEL ADCO should not be used in patients with severe liver impairment since there are no data available (see section 4.4 and 4.2).

DOCETAXEL ADCO (docetaxel) concentrate for infusion should be administered under the supervision of a qualified physician experienced in the use of antineoplastic agents. Appropriate management of complications is possible only when adequate diagnostic and treatment facilities are readily available.

The incidence of treatment-related mortality associated with DOCETAXEL ADCO therapy is increased in patients with abnormal liver function and in patients receiving higher doses. DOCETAXEL ADCO should generally not be given to patients with serum bilirubin > upper limit of normal (ULN), or to patients with AST and/or ALT > 1,5 x ULN concomitant with alkaline phosphatase > 2,5 x ULN. Patients with elevations of bilirubin or abnormalities of transaminase concurrent with alkaline phosphatase are at increased risk for the development of grade 4 neutropenia, febrile neutropenia, infections, severe thrombocytopenia, severe stomatitis, severe skin toxicity and toxic death. Patients with isolated elevations of transaminase > 1,5 x ULN may have a higher rate of febrile neutropenia grade 4, but may not have an increased incidence of toxic death. Bilirubin, AST or ALT and alkaline phosphatase values should be obtained prior to each cycle of DOCETAXEL ADCO therapy and reviewed by the treating medical doctor. DOCETAXEL ADCO therapy should not be given to patients with neutrophil counts of < 1 500 cells/mm3. In order to monitor the occurrence of neutropenia, which may be severe and result in infection, frequent blood cell counts should be performed on all patients receiving DOCETAXEL ADCO.

Severe hypersensitivity reactions characterised by hypotension and/or bronchospasm, or generalised rash/erythema may occur in 2,2 % (2/92) of patients who received the recommended 3-day dexamethasone premedication. Hypersensitivity reactions requiring discontinuation of the DOCETAXEL ADCO infusion may occur in patients who did not receive premedication. These reactions may resolve after discontinuation of the infusion and the administration of appropriate therapy.

DOCETAXEL ADCO must not be given to patients who have a history of severe hypersensitivity reactions to docetaxel or to other medicines formulated with polysorbate 80. Severe fluid retention may occur in 6,5 % (6/92) of patients despite use of a 3-day dexamethasone premedication regimen. This is characterised by one or more of the following events: poorly tolerated peripheral oedema, generalised oedema, pleural effusion requiring urgent drainage, dyspnoea at rest, cardiac tamponade or pronounced abdominal distention (due to ascites). The use of DOCETAXEL ADCO should be confined to units specialised in the administration of cytotoxic chemotherapy and it should only be administered under the supervision of a qualified oncologist. Since significant hypersensitivity reactions may occur, appropriate supportive equipment should be available. During the infusion, it is recommended that vital functions should be closely monitored.

Premedication consisting of an oral corticosteroid such as dexamethasone 16 mg per day (e.g. 8 mg twice daily) for 3 days, starting one day prior to DOCETAXEL ADCO administration, unless contra-indicated, may reduce the incidence and severity of fluid retention as well as the severity of hypersensitivity reactions.

Haematology: Neutropenia is the most frequent adverse reaction of DOCETAXEL ADCO and occurs in almost all patients. Severe neutropenia (grade 3-4) occurs in 99 % of patients on combination therapy with doxorubicin. Neutrophil nadirs may occur at approximately 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 ADCO. Patients should be re-treated with DOCETAXEL ADCO only after neutrophils recover to a level > 1 500 cells/mm3 (see section 4.2). In the case of severe neutropenia (< 500 cells/mm3 for seven days or more) during a course of DOCETAXEL ADCO therapy, a reduction in dose for subsequent courses of therapy and the use of appropriate symptomatic measures are recommended.

In vitro studies have shown that the metabolism of DOCETAXEL ADCO may be modified by the concomitant administration of medicines which induce, inhibit or are metabolised by (and thus may inhibit the enzyme competitively) cytochrome P450-3A such as ciclosporin, ketoconazole, erythromycin and troleandomycin. As a result, caution should be exercised when treating patients with these medicines as concomitant therapy, since there is a potential for a significant interaction. DOCETAXEL ADCO is highly protein bound (> 95 %). Although the possible in vivo interaction of DOCETAXEL ADCO with concomitantly administered medicines 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 does not affect protein binding of docetaxel. DOCETAXEL ADCO does not influence the binding of digoxin. In the doxorubicin/docetaxel combination, the clearance of docetaxel is increased. Dexamethasone did not affect protein binding of DOCETAXEL ADCO.

Pregnancy and lactation are contraindicated as DOCETAXEL ADCO is teratogenic in animals. Contraceptive measures must be taken during and for at least three months after cessation of therapy.

DOCETAXEL ADCO contains ethanol and this may impair the ability to drive or use machinery.

a. Summary of the safety profile Not Applicable

b. Tabulated summary of adverse reactions DOCETAXEL 100 mg/m2 single agent:

In case of overdose, the patient should be kept in a specialised unit and vital functions monitored. The anticipated complications of overdosage would consist of neutropenia, mucositis, cutaneous reactions and paraesthesia. Treatment of overdose: There is no known antidote for DOCETAXEL ADCO overdosage. Patients should receive therapeutic G-CSF as soon as possible after discovery of overdose. Other appropriate symptomatic measures should be taken as needed.