Chetax-20/Chetax-80

Docetaxel 20 mg: A pale yellow or brownish yellow viscous solution filled in 5 mL clear moulded glass vial USP Type I with 20 mm bromobutyl rubber stopper & sealed with 20 mm grey colour flip off seal.
Each vial contains: Docetaxel Trihydrate USP eq. to Docetaxel anhydrous 20 mg.
Docetaxel 80 mg: A pale yellow or brownish yellow viscous solution filled in 10 mL clear moulded glass vial USP Type I with 20 mm bromobutyl rubber plug & sealed with 20 mm yellow colour flip off aluminum seal.
Each vial contains: Docetaxel Trihydrate USP eq. to Docetaxel anhydrous 80 mg.

Pharmacotherapeutic group: Taxanes.
Pharmacology: Pharmacodynamics: Mechanism of action: Docetaxel is an antineoplastic agent which acts by promoting the assembly of tubulin into stable microtubules and inhibits their disassembly which leads to a marked decrease of free tubulin. The binding of docetaxel to microtubules does not alter the number of protofilaments.
Docetaxel has been shown in vitro to disrupt the microtubular network in cells which is essential for vital mitotic and interphase cellular functions.
Pharmacodynamic effects: Docetaxel was found to be cytotoxic in vitro against various murine and human tumour cell lines and against freshly excised human tumour cells in clonogenic assays. Docetaxel achieves high intracellular concentrations with a long cell residence time. In addition, docetaxel was found to be active on some but not all cell lines over expressing the p glycoprotein which is encoded by the multidrug resistance gene. In vivo, docetaxel is schedule independent and has a broad spectrum of experimental antitumour activity against advanced murine and human grafted tumours.
Pharmacokinetics: Absorption: The pharmacokinetics of docetaxel have been evaluated in cancer patients after administration of 20-115 mg/m² in phase I studies. The kinetic profile of docetaxel is dose independent and consistent with a three-compartment pharmacokinetic model with half lives for the α, β and γ phases of 4 min, 36 min and 11.1 h, respectively. The late phase is due, in part, to a relatively slow efflux of docetaxel from the peripheral compartment.
Distribution: Following the administration of a 100 mg/m² dose given as a one-hour infusion a mean peak plasma level of 3.7 μg/mL was obtained with a corresponding AUC of 4.6 h.μg/mL. Mean values for total body clearance and steady-state volume of distribution were 21 L/h/m² and 113 L, respectively. Inter individual variation in total body clearance was approximately 50%. Docetaxel is more than 95% bound to plasma proteins.
Elimination: A study of 14C docetaxel has been conducted in three cancer patients. Docetaxel was eliminated in both the urine and faeces following cytochrome P450 mediated oxidative metabolism of the tert-butyl ester group, within seven days, the urinary and faecal excretion accounted for about 6% and 75% of the administered radioactivity, respectively. About 80% of the radioactivity recovered in faeces is excreted during the first 48 hours as one major inactive metabolite and 3 minor inactive metabolites and very low amounts of unchanged medicinal product.
Special populations: Age and gender: A population pharmacokinetic analysis has been performed with docetaxel in 577 patients. Pharmacokinetic parameters estimated by the model were very close to those estimated from phase I studies. The pharmacokinetics of docetaxel were not altered by the age or sex of the patient.
Hepatic impairment: In a small number of patients (n=23) with clinical chemistry data suggestive of mild to moderate liver function impairment (ALT, AST ≥1.5 times the ULN associated with alkaline phosphatase ≥2.5 times the ULN), total clearance was lowered by 27% on average.
Fluid retention: Docetaxel clearance was not modified in patients with mild to moderate fluid retention and there are no data available in patients with severe fluid retention.
Combination therapy: Doxorubicin: When used in combination, docetaxel does not influence the clearance of doxorubicin and the plasma levels of doxorubicinol (a doxorubicin metabolite). The pharmacokinetics of docetaxel, doxorubicin and cyclophosphamide were not influenced by their co-administration.
Capecitabine: Phase I study evaluating the effect of capecitabine on the pharmacokinetics of docetaxel and vice versa showed no effect by capecitabine on the pharmacokinetics of docetaxel (Cmax and AUC) and no effect by docetaxel on the pharmacokinetics of a relevant capecitabine metabolite 5'-DFUR.
Cisplatin: Clearance of docetaxel in combination therapy with cisplatin was similar to that observed following monotherapy. The pharmacokinetic profile of cisplatin administered shortly after docetaxel infusion is similar to that observed with cisplatin alone.
Cisplatin and 5-fluorouracil: The combined administration of docetaxel, cisplatin and 5-fluorouracil in 12 patients with solid tumours had no influence on the pharmacokinetics of each individual medicinal product.
Prednisone and dexamethasone: The effect of prednisone on the pharmacokinetics of docetaxel administered with standard dexamethasone premedication has been studied in 42 patients.
Prednisone: No effect of prednisone on the pharmacokinetics of docetaxel was observed.

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 an anthracycline or an alkylating agent.
Docetaxel in combination with trastuzumab is indicated for the treatment of patients with metastatic breast cancer whose tumours 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 should 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.
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.

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.
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 also 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 three weeks, combined with capecitabine at 1250 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 cell 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 75 mg/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 (see also Dose adjustments during treatment).
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 TAX 323 and TAX 324 studies, received prophylactic antibiotics.
Induction chemotherapy followed by radiotherapy (TAX 323): 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 (TAX 324): 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 chemoradiotherapy.
Dose adjustments 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.
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.

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.

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

For breast and non-small cell lung 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 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.
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 ≥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. 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.
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.
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.
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.
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.
Baseline cardiac assessment is recommended.
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.
Others: Contraceptive measures must be taken by both men and women during treatment and for men at least 6 months after cessation of therapy.
The concomitant use of docetaxel with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin and voriconazole) should be avoided.
Additional cautions for use in adjuvant treatment of breast cancer.
Complicated neutropenia: For patients who experience complicated neutropenia (prolonged neutropenia, febrile neutropenia or infection), 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. In patients treated with the TAC regimen for node positive breast cancer, the risk of CHF has been shown to be higher during the first year after treatment.
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: As the benefit observed in patient with 4+ nodes was not statistically significant on disease-free survival (DFS) and overall survival (OS), the positive benefit/risk ratio for TAC in patients with 4+ nodes was not fully demonstrated at the final analysis.
Excipients: This medicinal product contains 50 vol% ethanol (alcohol), i.e. 395 mg (0.5 mL) ethanol anhydrous per 1 mL vial, equivalent to 10 mL of beer or 4 mL wine per 1 mL vial, 1.58 g (2 mL) ethanol anhydrous per 4 mL vial, equivalent to 40 mL of beer or 17 mL wine per 4 mL vial, or 3.16 g (4 mL) ethanol anhydrous per vial of 8 mL fill volume, equivalent to 80 mL beer or 33 mL wine per 8 mL vial. Harmful for those suffering from alcoholism.
To be taken into account in pregnant or breast-feeding women, children and high-risk groups such as patients with liver disease, or epilepsy.
Patients with liver impairment: 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 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 × 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 severely impaired renal function treated with docetaxel.
Use in the Elderly: There are limited data available in patients >70 years of age on docetaxel use in combination with doxorubicin and cyclophosphamide.
Of the 333 patients treated with docetaxel every three weeks in a prostate cancer study, 209 patients were 65 years of age or greater and 68 patients were older than 75 years. In patients treated with docetaxel every three weeks, the incidence of related nail changes occurred at a rate ≥10% higher in patients who were 65 years of age or greater compared to younger patients. The incidence of related fever, diarrhoea, anorexia, and peripheral oedema occurred at rates ≥10% higher in patients who were 75 years of age or greater versus less than 65 years.
Among the 300 (221 patients in the phase III part of the study and 79 patients in the phase II part) patients treated with docetaxel in combination with cisplatin and 5 fluorouracil in the gastric cancer study, 74 were 65 years of age or older and 4 patients were 75 years of age or older. The incidence of serious adverse events was higher in the elderly patients compared to younger patients. The incidence of the following adverse events (all grades): lethargy, stomatitis, neutropenic infection occurred at rates ≥10% higher in patients who were 65 years of age or older compared to younger patients.
Elderly patients treated with TCF should be closely monitored.

Pregnancy: There is no information on the use of docetaxel in pregnant women. Docetaxel has been shown to be both embryotoxic and foetotoxic in rabbits and rats, and to reduce fertility in rats. 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 age receiving docetaxel should be advised to avoid becoming pregnant, and to inform the treating physician immediately should this occur.
Lactation: 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.

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.
Nervous system disorders: The development of severe peripheral neurotoxicity requires a reduction of dose. Mild to moderate neuro-sensory signs are characterised by paresthesia, dysesthesia or pain including burning. Neuro-motor events are mainly characterised by weakness.
Skin and subcutaneous tissue disorders: 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 hyperpigmentation and sometimes pain and onycholysis.
General disorders and administration site conditions: Infusion site reactions were generally mild and consisted of hyper pigmentation, 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.

The amount of alcohol in this medicinal product may alter the effects of other medicinal products.
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 ciclosporine, ketoconazole and erythromycin. 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.
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 pharmacokinetics in the presence of prednisone was 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.
Docetaxel is highly protein bound (>95%). Although the possible in vivo interaction of docetaxel with concomitantly administered medicinal product has not been investigated formally, in vitro 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. 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.

Direction for Reconstitution: Reconstitute using entire contents of Solvent for Docetaxel 80 mg/2 mL Concentrate Solution for IV Infusion to get a premix solution of 8 mL (approx. 10 mg/mL). Rotate the vial gently and allow the premix to stand for 5 minutes. Use this premix for further dilution. Use immediately after reconstitution.

Store between 2°C to 8°C. Protect from light.

Cytotoxic Chemotherapy

L01CD02 - docetaxel ; Belongs to the class of taxanes from plant alkaloids and other natural products. Used in the treatment of cancer.

Rx