Docehope (Docetaxel) 80 mg/2 ml concentrate and solvent for solution for infusion
- NAME OF THE MEDICINAL PRODUCT
Docehope (Docetaxel) 80 mg/2 ml concentrate and solvent for solution for infusion
- QUALITATIVE AND QUANTITATIVE COMPOSITION
Docetaxel for Injection 80 mg
Each vial of concentrate contains
Docetaxel anhydrous 80 mg
Polysorbate 80 2000 mg
Each vial of diluent contains
Water for injection 5.220 ml
95% Ethyl alcohol 0.780 ml
For the full list of excipients, see section 5.1.
- PHARMACEUTICAL FORM
Concentrate and solvent for solution for infusion.
Clear yellow solution.
The solvent is a colourless solution free from foreign particles.
- CLINICAL PARTICULARS
4.1 Therapeutic indication
Breast cancer
Docetaxel in combination with doxorubicin and cyclophosphamide is indicated for the adjuvant treatment of patients with :
- Operable node-positive breast cancer
- Operable node-negative breast cancer
For patients with operable node-negative breast cancer, adjuvant treatment should be restricted to patients eligible to receive chemotherapy according to internationally established criteria for primary therapy of early breast cancer.
Docetaxel 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 this condition.
Docetaxel monotherapy is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of cytotoxic therapy. Previous chemotherapy should have included and anthracycline or an alkylating agent.
Docetaxel in combination with trastuzumab is indicated for the treatment of patients with metastatic breast cancer whose tumors over express HER2 and who previously have not received chemotherapy for metastatic disease.
Docetaxel in combination with capecitabine is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of cytotoxic chemotherapy.
Previous therapy shoul have included an anthracycline.
Non-small cell lung cancer
Docetaxel is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of prior chemotherapy.
Docetaxel in combination with cisplatin is indicated for the treatment of patients with unresectable, locally advanced or metastatic non-small cell lung cancer, in patients who have not previously received chemotherapy for this condition.
Docetaxel in combination with carboplatin represents a treatment option to Cisplatin based therapy.
Prostate cancer
Docetaxel in combination with prednisone or prednisolone is indicated for the treatment of patients with hormone refractory metastatic prostate cancer.
Gastric adenocarcinoma
Docetaxel in combination with cisplatin and 5-fluorouracil is indicated for the treatment of patients with metastatic gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, who have not received prior chemotherapy for metastatic disease.
Head and neck cancer
Docetaxel in combination with cisplatin and 5-fluorouracil is indicated for the induction treatment of patients with locally advanced squamous cell carcinoma of the head and neck.
Ovarium cancer
Docetaxel is indicated for the treatment of patients with metastatic carcinoma of the ovary after failure offirst-line or subsequent chemotherapy.
4.2 Posology and Method of Administration
The use of docetaxel should be confined to units specialised in the administration of cytotoxic chemotherapy and it should only be administered under the supervision of a physician in the use of anticancer chemotherapy.
Recomended dose
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 maybe 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 linfusion.
Docetaxel is administered as a one-hour infusion every three weeks.
Breast cancer
In the adjuvant treatment of operable node-positive and node-negative breast cancer, the recommended dose of Docetaxel is 75 mg/m2 administered 1-hour after doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 every 3 weeks for 6 cycles (TAC regimen) (see olso Dose adjustments during treatment).
For the treatment of patients with locally advanced or metastatic breast cancer, the recommended dose of docetaxel is 100 mg/m2 in monotherapy. In first-line treatment, docetaxel 75 mg/m2 is given in combination therapy with doxorubicin (50 mg/m2).
In combination with trastuzumab the recommended dose of docetaxel is 100 mg/m2 every three weeks, with trastuzumab administered weekly. In the pivotal study the initial docetaxel infusion was started the day following the first dose of trastuzumab. The subsequent docetaxel doses were administered immediately after completion of the Trastuzumab infusion, if the preceding dose of Trastuzumab was well tolerated. For trastuzumab dose and administration, see trastuzumab summary of product characteristics.
In combination with capecitabine, the recommended dose of docetaxel is 75 mg/m2 every 3 weeks, combined with capecitabine at 1,250 mg/m2 twice daily (within 30 minutes after a meal) for 2 weeks followed by a 1-week rest period. For capecitabine dose calculation according to body surface area, see capecitabine summary of product characteristics.
Non-small cel lung cancer
In chemotherapy naïve patients treated for non-small cell lung cancer, the recommended dose regimen is docetaxel 75 mg/m2 immediately followed by cisplatin 75 mg/m2 over 30 – 60 minutes. For treatment after failure of prior platinum-based chemotherapy, the recommended dose is 75mg/m² as a single agent.
Prostate cancer
The recommended dose of docetaxel is 75 mg/m2. Prednisone or prednisolone 5 mg orally twice daily is administered continuously.
Gastric adenocarcinoma
The recommended dose of docetaxel is 75 mg/m2 as a 1-hour infusion, followed by cisplatin 75 mg/m2, as a 1- to 3-hour infusion (both on day 1 only), followed by 5-fluorouracil 750 mg/m2 per day given as a 24-hour continuous infusion for 5 days, starting at the end of the cisplatin infusion. Treatment is repeated every three weeks. Patients must receive premedication with antiemetics and appropriate hydration for cisplatin administration. Prophylactic G-CSF should be used to mitigate the risk of haematological toxicities.
Head and neck cancer
Patients must receive premedication with antiemetics and appropriate hydration (prior to and after cisplatin administration). Prophylactic G-CSF may be used to mitigate the risk of haematological toxicities. All patients on the docetaxel-containing arm of the studies, received prophylactic antibiotics.
- Induction chemotherapy followed by radiotherapy
For the induction treatment of inoperable locally advanced squamous cell carcinoma of the head and neck (SCCHN), the recommended dose of docetaxel 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.
- Induction chemotherapy followed by chemoradiotherapy
For the induction treatment of patients with locally advanced (technically unresectable, low probability of surgical cure, and aiming at organ preservation) squamous cell carcinoma of the head and neck (SCCHN) ,the recommended dose of docetaxel is 75 mg/m2 as a 1 hour intravenous infusion on day 1, followed by cisplatin 100 mg/m2 administered as a 30-minute to 3-hour infusion, followed by 5 fluorouracil 1000 mg/m2/day as a continuous infusion from day 1 to day 4. This regimen is administered every 3 weeks for 3 cycles. Following chemotherapy, patients should receive chemo radiotherapy.
For cisplatin and 5-fluorouracil dose modifications, see the corresponding summary of product characteristics.
Ovarian cancer
The recommended dose of docetaxel is 75 to 100 mg/m2 administered as one hour infusion every three weeks. A dose of 100 mg/m2 has been show to result in a moderate increase in response rates compared with 75 mg/m2 but is associated with greater toxicity.
Dose adjustment during treatment
General
Docetaxel should be administered when the neutrophil count is ≥ 1,500 cells/mm3.
In patients who experienced either febrile neutropenia, neutrophil count < 500 cells/mm3 for more than one week, severe or cumulative cutaneous reactions or severe peripheral neuropathy during docetaxel therapy, the dose of docetaxel should be reduced 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.
Adjuvant therapy for breast cancer
Primary G-CSF prophylaxis should be considered in patients who receive docetaxel, doxorubicin and cyclophosphamide (TAC) adjuvant therapy for breast cancer. Patients who experience febrile neutropenia and/or neutropenic infection should have their docetaxel dose reduced to 60 mg/m² in all subsequent cycles. Patients who experience Grade 3 or 4 stomatitis should have their dose decreased to 60 mg/m². However, in clinical practice neutropenia could occur earlier.Thus the use of G-CSF should be considered function of the neutropenic risk of the patient and current recommendations. Patients who experience Grade 3 or 4 stomatitis should have their dose decreased to 60 mg/m².
In combination with Cisplatin
For patients who are dosed initially at docetaxel 75 mg/m2 in combination with Cisplatin and whose nadir of platelet count during the previous course of therapy is < 25,000 cells/mm3, or in patients who experience febrile neutropenia, or in patients with serious non-haematologic toxicities, the docetaxel dose in subsequent cycles should be reduced to 65 mg/m2. For cisplatin dose adjustments, see the corresponding summary of product characteristics.
In combination with Capecitabine
- For capecitabine dose modifications, see capecitabine summary of product characteristics.
- For patients developing the first appearance of Grade 2 toxicity, which persists at the time of the next docetaxel/capecitabine treatment, delay treatment until resolved to Grade 0-1, and resume at 100% of the original dose.
- For patients developing the second appearance of Grade 2 toxicity, or the first appearance of Grade 3 toxicity, at any time during the treatment cycle, delay treatment until resolved to Grade 0-1 and then resume treatment with docetaxel 55 mg/m².
- For any subsequent appearances of toxicities, or any Grade 4 toxicities, discontinue the docetaxel dose.
For trastuzumab dose modifications, see trastuzumab summary of product characteristic.
In combination with Cisplatin and 5-fluorouracil
If an episode of febrile neutropenia, prolonged neutropenia or neutropenic infection occurs despite G-CSF use, the docetaxel dose should be reduced from 75 to 60 mg/m2. If subsequent episodes of complicated neutropenia occur the docetaxel dose should be reduced from 60 to 45 mg/m2. In case of Grade 4 thrombocytopenia the docetaxel dose should be reduced from 75 to 60 mg/m2. Patients should not be retreated with subsequent cycles of docetaxel until neutrophils recover to a level > 1,500 cells/mm3 and platelets recover to a level > 100,000 cells/mm3. Discontinue treatment if these toxicities persist. Recommended dose modifications for toxicities in patients treated with Docetaxel in combination with Cisplatin and 5-fluorouracil (5-FU) :
| Toxicity | Dose adjustment |
| Diarrhoea grade 3 | First episode : reduce 5-FU dose by 20%.
Second episode : then reduce docetaxel dose by 20 %. |
| Diarrhoea grade 4 | First episode : reduce docetazel and 5-FU doses by 20%.
Second episode : discontinue treatment. |
| Stomatitis/mucositis grade 3 | First episode : reduce 5-FU dose by 20%.
Second episode : stop 5-FU only, at all subsequent cycles. Third episode : reduce docetaxel dose by 20%. |
| Stomatitis/mucositis grade 4 | First episode : stop 5-FU only, at all subsequent cycles.
Second episode : reduce docetaxel dose by 20%. |
For Cisplatin and 5-fluorouracil dose adjustments, see the corresponding summary of product characteristics.
Patients who experienced complicated neutropenia (including prolonged neutropenia, febrile neutropenia, or infection), it was recommended to use G-CSF to provide prophylactic coverage (e.g., day 6-15) in all subsequent cycles.
Special populations:
Patients with hepatic impairement
Docetaxel at 100 mg/m² as single agent, patients who have both elevations of transaminase (ALT and/or AST) greater than 1.5 times the upper limit of the normal range (ULN) and alkaline phosphatase greater than 2.5 times the ULN, the recommended dose of docetaxel is 75 mg/m2. For those patients with serum bilirubin > ULN and/or ALT and AST > 3.5 times the ULN associated with alkaline phosphatase > 6 times the ULN, no dose reduction can be recommended and docetaxel should not be used unless strictly indicated.
In combination with Cisplatin and 5-fluorouracil for the treatment of patients with gastric adenocarcinoma, the pivotal clinical study excluded patients with ALT and/or AST > 1.5 × ULN associated with alkaline phosphatase > 2.5 × ULN, and bilirubin > 1 x ULN; for these patients, no dose-reductions can be recommended and docetaxel should not be used unless strictly indicated. No data are available in patients with hepatic impairment treated by Docetaxel in combination in the other indications.
Pediatric population
Docetaxel is not recommended for children.
Elderly
Based on a population pharmacokinetic analysis, there are no special instructions for use in the elderly.
In combination with Capecitabine, for patients 60 years of age or more, a starting dose reduction of capecitabine to 75% is recommended (see capecitabine summary of product characteristics).
Administration precautions
Docetaxel must be administered intravenously it is extremely important that the intravenous people or catheter be properly positioned before any docetaxel is injected. Leakage into surrounding tissue during intravenous administration of Docetaxel may cause considerable irritation, local tissue necrosis and/or thrembophlebitis. If extravasation occurs, the injection should be discontinued immediately and any remaining portion of the dose should be introduced into another vein.
4.3 Contraindications
Hypersensitivity reactions to the active substance or to any of the excipients listed in section 6.1.
Patients with baseline neutrophil count of < 1,500 cells/mm3.
Patients with severe liver impairment.
Contraindications for other medicinal products also apply, when combined with docetaxel.
4.4 Special Warnings and Precautions for Use
For breast and non-small cell lung cancers, premedication consisting of an oral corticosteroid, such as dexamethasone 16 mg per day (e.g. 9 mg BID) for 3 days starting 1 day prior to docetaxel admnistration, unless contraindicated, can reduce the incidence and severity of fluid retention as well as the severity of hypersensitivity reactions. For prostate cancer, the premedication is oral dexamethasone 8 mg, 12 hours, 3 hours and 1 hour before the docetaxel infusion.
Hematology
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 ≥ 1,500 cells/mm3.
In the case of severe neutropenia (< 500 cells/mm3 for seven days or more) during a course of docetaxel therapy, a reduction in dose for subsequent courses of therapy or the use of appropriate symptomatic measures are recommended.
In patients treated with docetaxel in combination with cisplatin and 5-fluorouracil (TCF), febrile neutropenia and neutropenic infection occurred at lower rates when patients received prophylactic G-CSF. Patients treated with TCF should receive prophylactic G-CSF to mitigate the risk of complicated neutropenia (febrile neutropenia, prolonged neutropenia or neutropenic infection). Patients receiving TCF should be closely monitored.
In patients treated with docetaxel in combination with doxorubicin and cyclophosphamide (TAC), febrile neutropenia and/or neutropenic infection occurred at lower rates when patients received primary G-CSF prophylaxis. Primary G-CSF prophylaxis should be considered in patients who receive adjuvant therapy with TAC for breast cancer to mitigate the risk of complicated neutropenia (febrile neutropenia, prolonged neutropenia or neutropenic infection). Patients receiving TAC should be closely monitored.
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 rechallenged with docetaxel.
Cutaneous reactions
Localized skin ertythema of the extremities (palms of the hands and soles of the feet) with oedema followed by desquamation has been observed. Severe symptomps such as eruptions followed by desquamation which lead to interruption or discontinuation of docetaxel treatment were reported.
Fluid retention
Patients with severe fluidretention such as pleural effusion, pericardial effusion and ascites should be monitored closely.
Patient with liver impairement
In patients treated with docetaxel at 100 mg/m2 as single agent who have serum transaminase levels (ALT and/or AST) greater than 1.5 times the ULN concurrent with serum alkaline phosphatase levels greater than 2.5 times the ULN, 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.
For patients with serum bilirubin levels > ULN and/or ALT and AST > 3.5 times the ULN concurrent with serum alkaline phosphatase levels > 6 times the ULN, no dose-reduction can be recommended and docetaxel should not be use dunless strictly indicated.
In combination with cisplatin and 5-fluorouracil for the treatment of patients with gastric adenocarcinoma, the pivotal clinical study excluded patients with ALT and/or AST > 1.5 × ULN associated with alkaline phosphatase > 2.5 × ULN, and bilirubin > 1 x ULN; for these patients, no dose-reductions can be recommended and docetaxel should not be used unless strictly indicated. No data are available in patients with hepatic impairment treated by docetaxel in combination in the other indications.
Patients with renal impairment
There are no data available in patients with severly impaired renal function treated with docetaxel.
Nervous system
The development of severe peripheral neurotoxicity requires are duction 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.
When patients 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. For more details see summary of product characteristics of trastuzumab.
Other
Contraceptive measures must be taken by both men and women during treatment and for men at least 6 months after cessation of therapy.
Additional cautions for use in adjuvant for use in adjuvant treatment of breast cancer
Compilicated neutropenia
For patients who experience complicated neutropenia (prolonged neutropenia, febrile neutropenia or infecton), G-CSF and dose reduction should be considered.
Gastrointestinal reactions
Symptoms such as early abdominal pain and tenderness, fever, diarrhoea, with or without neutropenia, may be early manifestations of serious gastrointestinal toxicity and should be evaluated and treated promptly.
Congestive heart failure (CHF)
Patients should be monitored for symptoms of congestive heart failure during therapy and during the follow up period.
Leukaemia
In the docetaxel, doxorubicin and cyclophosphamide (TAC) treated patients, the risk of delayed myelodysplasia or myeloid leukaemia requires haematological follow-up.
Patients with 4+ nodes
The benefit/risk ratio for TAC in patients with 4+ nodes was not defined fully at the interim analysis.
Elderly
There are limited data available in patients > 70 years of age on docetaxel use in combination with doxorubicin and cyclophosphamide. Elderly patients treated with TCF should be closely monitored.
Docetaxel 20 mg/0.5 ml concentrate and solvent for solution for infusion
This medicinal product contains 10.505% (w/w) ethanol 95% v/v (alcohol), i.e. up to 156 mg ethanol 95% v/v per solvent vial.
Docetaxel 80 mg/2 ml concentrate and solvent for solution for infusion
This medicinal product contains 10.505% (w/w) ethanol 95% v/v (alcohol), i.e. up to 624 mg ethanol 95% v/v per solvent vial.
Harmful for those suffering from alcoholism.
To be taken into account in pregnant or breast-feeding women, in children and in high-risk groups such as patients with liver disease or epilepsy.
Consideration should be given to possible effects on the central nervous system.
The amount of alcohol in this medicinal product may alter the effects of other medicinal products.
The amount of alcohol in this medicinal product may impair the patients ability to drive or use machines.
4.5 Interaction with other medicinal products and other forms of interaction
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 ciclosporine, terfenadine, ketoconazole, erythromycin and troleandomycin. As a result, caution should be exercised when treating patients with these medicinal products as concomitant therapy since there is a potential for a significant interaction.
Docetaxel is highly protein bound (> 95%). Although the possible interaction of docetaxel with concomitantly administered medicinal product has not been investigated formally, interactions with tightly protein-bound agents 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 co-administration. When combined to docetaxel, the clearance of carboplatin was about 50% higher than values previously reported for carboplatin monotherapy.
Docetaxel is metabolised by CYP3A4 and prednisone is known to induce CYP3A4. No significant effect of prednisone on the pharmacokinetics of docetaxel was observed.
Increase in docetaxel toxicity were reported when it was combined with ritonavir. The mechanism behind this interaction is a CYP3A4 inhibition, the main isoenzyme involved in docetaxel metabolism by ritonavir. 50% docetaxel dose reduction if patients require coadministration of a strong CYP3A4 inhibitor such as azole antifungals, ritonavir and some macrolides (clarithromycin, telithromycin).
4.6 Fertility, Pregnancy and lactation
Pregnancy
There is no information on the use of Docetaxel in pregnant women. As with other cytotoxic medicinal 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 potential/contraception
Women of childbearing age receiving Docetaxel should be advised to avoid becoming pregnant, and to inform the treating physician immediately should this occur.
An effective method ofc ontraception should be used during treatment.
In non-clinical studies, Docetaxel has genotoxic effects and may alter male fertility. Therefore, men being treated with Docetaxel are advised not to father a child during and up to 6 months after treatment and to seek advice on conservation of sperm prior to treatment.
Lactation
Docetaxel is alipophilic 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.
4.7 Effects on ability to drive and use machines
No studies on the effects on the ability to drive and use machines have been performed.
The amount of ethanol in doxcetaxel may impair the ability to drive or use machines.
4.8 Undesirable effects
The most commonly reported adverse reactions of Docetaxel alone are : neutropenia (which was reversible and not cumulative; the median day to nadir was 7 days and the median duration of severe neutropenia (< 500 cells/mm3) was 7 days), anaemia, alopecia, nausea, vomiting, stomatitis, diarrhea and asthenia. The severity of adverse events of Docetaxel may be increased when Docetaxel is given in combination with other chemotherapeutic agents.
Immune system disorders
Hypersensitivity reactions have generally occurred within a few minutes following the start of the infusion of Docetaxel and were usually mild to moderate. The most frequently reported symptoms were flushing, rash with or without pruritus, chest tightness, back pain, dyspnoea and fever or chills. Severe reactions were characterised by hypotension and/or bronchospasm or generalized rash/erythema.
Skin and suvcutaneous tissue disorder
Reversible cutaneous reactions have been observed and were generally considered as mild to moderate. Reactions were characterised by a rash including localised eruptions mainly on the feet and hands (including severe hand and foot syndrome),but also on the arms, face or thorax and frequently associated with pruritus. Eruptions generally occurred within one week after the Docetaxel infusion. Less frequently, severe symptoms such as eruptions followed by desquamation which rarely lead to interruption or discontinuation of Docetaxel treatment were reported. Severe nail disorders are characterised by hypo- or hyper pigmentation and sometimes pain and onycholysis.
General disorders and administration site conditions
Infusion site reactions were generally mild and consisted of hyperpigmentation, inflammation, redness or dryness of the skin, phlebitis or extravasation and swelling of the vein. Fluid retention includes events such as peripheral oedema and less frequently pleural effusion, pericardial effusion, ascites and weight gain. The peripheral oedema usually starts at the lower extremities and may become generalised with a weight gain of 3 kg or more. Fluid retention is cumulative in incidence and severity.
4.9 Overdose
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.
- PHARMACEUTICAL PARTICULARS
5.1 List of excipients
Docetaxel 20 mg/0.5 ml concentrate and solvent for solution for infusion
Concentrate vial:
Polysorbate 80
Solvent vial:
Ethanol 95%
Water for injection
Docetaxel 80mg/2 ml concentrate and solvent for solution for infusion
Concentrate vial:
Polysorbate 80
Solvent vial:
Ethanol 95%
Water for injection
5.2 Incompatibilities
This medicinal product must not be mixed with other medicinal products except 5 glucose solution or sodium chloride 9 mg/ml (0.9%) solution for infusion.
5.3 Shelf life
24 months
5.4 Special precautions for storage
Store between 2 – 8ºC. Protect from bright light.
5.5 Nature and contents of container
Docetaxel 20 mg vial size is 15 ml
Docetaxel 80 mg vial size is 15 ml
Diluent vial size for both the strength is 15 ml
5.6 Special precautions for disposal and other handling
Docetaxel is an antineoplastic agent and, as with other potentially toxic compounds, caution should be exercised when handling it and preparing docetaxel solutions. The use of gloves is recommended.
If docetaxel concentrate, premix solution or infusion solution should come into contact with skin, wash immediately and thoroughly with soap and water. If docetaxel concentrate, premix solution or infusion solution should come into contact with mucous membranes, wash immediately and thoroughly with water.
Preparation for the intravenous administration
a) Preparation of the docetaxel premix solution (10 mg docetaxel/ml)
If the vials are stored under refrigeration, allow the required number of docetaxel boxes to stand at room temperature (below 25°C) for 5 minutes.
Using a syringe fitted with a needle, aseptically withdraw the entire contents of the solvent for docetaxel vial by partially inverting the vial.
Inject the entire contents of the syringe into the corresponding docetaxel vial.
Remove the syringe and needle and mix manually by repeated inversions for at least 45 seconds. Do not shake.
Allow the premix vial to stand for 5 minutes at room temperature (below 25°C) and then check that the solution is homogenous and clear (foaming is normal even after 5 minutes due to the presence of polysorbate 80 in the formulation).
The premix solution contains 10 mg/ml docetaxel and should be used immediately after preparation. However the chemical and physical stability of the premix solution has been demonstrated for 8 hours when stored either between 2°C and 8°C or at room temperature (below 25°C).
b) Preparation of the infusion solution
More than one premix vial may be necessary to obtain the required dose for the patient. Based on the required dose for the patient expressed in mg, aseptically withdraw the corresponding premix volume containing 10 mg/ml docetaxel from the appropriate number of premix vials using graduated syringes fitted with a needle. For example, a dose of 140 mg docetaxel would require 14 ml docetaxel premix solution.
Inject the required premix volume into a 250 ml infusion bag or bottle containing either 5% glucose solution or sodium chloride 9 mg/ml (0.9%) solution for infusion.
If a dose greater than 200 mg of docetaxel is required, use a larger volume of the infusion vehicle so that a concentration of 0.74 mg/ml docetaxel is not exceeded.
Mix the infusion bag or bottle manually using a rocking motion.
The docetaxel infusion solution should be used within 4 hours and should be aseptically administered as a 1-hour infusion under room temperature (below 25°C) and normal lighting conditions.
As with all parenteral products, docetaxel premix solution and infusion solution should be visually inspected prior to use, solutions containing a precipitate should be discarded. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
- MARKETING AUTHORISATION HOLDER
PT Graha Farma
Solo-Indonesia
- MARKETING AUTHORISATION NUMBER(S)
Reg No.DKI2055000349A1
- DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
–
- DATE OF REVISION OF THE TEXT
April 2020
ON MEDICAL PRESCRIPTION ONLY
Manufactured by :
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Imported by:
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Solo-Indonesia
