Docetax® (Docetaxel INN), is an antineoplastic agent belonging to the taxane family. It is prepared by semisynthesis beginning with a precursor extracted from the renewable needle biomass of yew plants. The chemical name for docetaxel is (2R,3S)-N-carboxy-3-
phenylisoserine,N-tert-butyl ester, 13-ester with 5β-20-epoxy-l,2 α,4,7β,10β,13α-hexahydroxytax-ll-en-9-one 4-acetate 2-benzoate, trihydrate. Docetax is a white to almost-white powder with an empirical formula of C43H53NO14•3H2O and a molecular weight of 861.9. It is highly lipophilic and practically insoluble in water.
Docetax® has the following structural formula:
Docetax® injection contains the concentrate of Docetaxel INN as a sterile, non-pyrogenic, pale yellow solution at 20 mg/0.5 mL and 80 mg/2 mL concentration.
Mechanism of action
The cytotoxic activity of Docetax® is exerted by promoting and stabilising microtubule assembly, while preventing physiological microtubule depolymerisation/disassembly in the absence of GTP. This leads to a significant decrease in free tubulin, needed for
Cytotoxic antibiotic (Taxane group) Inj. microtubule formation and results in inhibition of mitotic cell division between metaphase and anaphase, preventing further cancer cell
progeny. Because microtubules do not disassemble in the presence of Docetax®, they accumulate inside the cell and cause initiation of apoptosis.
Protein binding >98%
Half-life 86 hours
Breast cancer: for the treatment of patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy. In combination with doxorubicin and cyclophosphamide it is indicated for the adjuvant treatment of patients with operable node-positive breast cancer. Non-small cell lung cancer: as a single agent is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of prior platinum-based chemotherapy. Prostate cancer: in combination with prednisone is indicated for the treatment of patients with androgen independent (hormone
refractory) metastatic prostate cancer. Gastric adenocarcinoma: in combination with cisplatin and fluorouracil is indicated for the treatment of patients with advanced gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, who have not received prior chemotherapy for advanced disease. Head and neck cancer: in combination with cisplatin and fluorouracil is indicated for the induction treatment of patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN).
Dosage and administration
Breast cancer: For locally advanced or metastatic breast cancer after failure of prior chemotherapy, the recommended dose is 60 mg/m2 to 100 mg/m2 administered intravenously over 1 hour every 3 weeks. For the adjuvant treatment of operable node-positive breast cancer, the recommended dose is 75 mg/m2 administered 1 hour after doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 every 3 weeks for 6 courses. Prophylactic G-CSF may be used to mitigate the risk of hematological toxicities.
Non-small cell lung cancer: For treatment after failure of prior platinum-based chemotherapy the recommended dose is 75 mg/m2 administered intravenously over 1 hour every 3 weeks. Drug Interacting with Docetaxel Adverse Effects from Interaction
Cisplatin increased risk of delayed neuropathy Cyclosporine, Dalfopristin, Erythromycin,
Itraconazole, Ketoconazole, Quinupristin, Terfenadine, Troleandomycin increased risk of docetaxel toxicity including some or all of; anaemia, leucopoenia, thrombocytopenia, fever,
diarrhoea Doxorubicin Hydrochloride cholestatic jaundice and pseudomembranous colitis
Doxorubicin Hydrochloride Liposome increased doxorubicin exposure Vaccinations for; Bacillus of Calmette and Guerin, Measles, Mumps, Poliovirus, Rotavirus, Rubella, Smallpox, Typhoid, Varicella, YellowFever increased risk of infection by live vaccine
Thalidomide increased risk of venous thromboembolism
Prostate cancer: For hormone-refractory metastatic prostate cancer, the recommended dose is 75 mg/m2 every 3 weeks as a 1 hour intravenous infusion.
Gastric adenocarcinoma: For gastric adenocarcinoma, the recommended dose is 75 mg/m2 as a 1 hour intravenous infusion, followed by cisplatin 75 mg/m2 , as a 1 to 3 hour intravenous infusion (both on day 1 only), followed by fluorouracil 750 mg/m2 per day given as a 24-hour continuous intravenous infusion for 5 days, starting at the end of the cisplatin infusion. Treatment is repeated every three weeks.
Head and neck cancer: For the induction treatment of locally advanced inoperable SCCHN, the recommended dose is 75 mg/m2 as a 1 hour intravenous infusion followed by cisplatin 75 mg/m2 intravenously over 1 hour, on day one, followed by fluorouracil as a
continuous intravenous infusion at 750 mg/m2 per day for five days.
Possible side effects
Common chemotherapy side effects such as alopecia, pain/redness at location of injection, nausea, stomach pain, vomiting, lowered blood cell count, numbness, headache, constipation, nervous system problems such as neuropathy or sensory impairment, blurred vision, overall weakness and hematological adverse effects include
neutropenia, anaemia,febrile neutropenia, thrombocytopenia.
Docetaxel is contraindicated in pregnant and lactating women.
Special precautions Docetaxel should be used with caution in patients with bilirubin above upper limit of normal or other abnormal liver function tests (greater than 1.5 times the upper limit of normal) because of more profound neutropenia.
How to use
Docetax® injection (20 mg/0.5 mL & 80 mg/2 mL) is to be diluted by supplied diluent prior to infusion and should be used 21 gauge needle to withdraw Docetax from the vial because larger bore needles (e.g., 18 and 19 gauge) may result in stopper coring and
Docetax® final dilution for infusion, if stored between 2°C to 25°C is stable for 4 hours. Docetax® final dilution for infusion (in either 0.9% sodium chloride solution or 5% Dextrose solution) should be used within 4 hours (including the 1 hour intravenous administration).
Product should be stored between 2°C to 25°C and retained in the original package to protect from bright light.
Docetax® 20 mg injection: Each box contains 1 vial of 0.5 mL solution containing Docetaxel INN 20 mg along with 1 vial of diluent (Ethanol in WFI).