What Is Docetaxel?

Docetaxel injection, the indication is 1. Docetaxel is suitable for the treatment of advanced or metastatic breast cancer that failed early chemotherapy. Unless it is clinically contraindicated, prior treatment should include anthracycline anticancer drugs. 2. Docetaxel is suitable for the treatment of advanced or metastatic non-small cell lung cancer with cisplatin-based chemotherapy failure.

Drug Name: Docetaxel injection

Drug type: Prescription drugs, medicines for medical workers' injuries
Use classification: Cytotoxic drugs

Ingredients of docetaxel injection

The chemical composition of this product is docetaxel, and the special solvent is a sterile aqueous solution of ethanol.
Chemical name: [2aR- (2a, 4, 4a, 6, 9, (aR *, S *), 11, 12, 12a, 12b)]--[[(1,1-dimethylethoxy ) Carbonyl] amino] --hydroxyphenylpropionic acid [12b-acetyloxy-12-benzoyloxy-2a, 3,4,4a, 5,6,9,10,11,12,12a, 12b-ten Dihydro-4,6,11-trihydroxy-4a, 8,13,13-tetramethyl-5-oxo-7,11-methylene-1H-cyclodecpentaeno- [3,4] Benzo [1,2-b] oxetan-9-yl] ester.
Chemical Structure:

Molecular formula: C ₄₃ H ₅₃ NO ₁₄
Molecular weight: 807.89
Excipients: 20% citric acid solution and polysorbate 80.

Traits of docetaxel injection

This product is a light yellow to yellow brown clear viscous liquid.

Indications for docetaxel injection

1. Docetaxel is suitable for the treatment of advanced or metastatic breast cancer in which early chemotherapy has failed. Unless it is clinically contraindicated, prior treatment should include anthracycline anticancer drugs.
2. Docetaxel is suitable for the treatment of advanced or metastatic non-small cell lung cancer with cisplatin-based chemotherapy failure.

Docetaxel injection specifications

(1) Docetaxel injection: 0.5ml: 20mg, Docetaxel injection solvent: 1.5ml
(2) Docetaxel injection: 1.5ml: 60mg, Docetaxel injection solvent: 4.5ml
(3) Docetaxel injection: 2.0ml: 80mg, Docetaxel injection solvent: 6.0ml

Docetaxel injection dosage

Docetaxel can only be used for intravenous drip. All patients must take oral glucocorticoids, such as dexamethasone, before taking the docetaxel treatment period, taking one day before docetaxel infusion, 16 mg daily for at least 3 days to prevent allergic reactions and fluid retention .
Immediately before use, inhale the corresponding solvent of docetaxel into the corresponding solution, gently shake and mix well, place the mixed medicine bottle at room temperature for 5 minutes, and then check whether the solution is uniform and clear. , Inhale the mixed solution with a syringe, and inject it into the injection bottle or injection bag of 5% glucose injection or 0.9% sodium chloride injection, shake it gently and mix well, and the final concentration should not exceed 0.9mg / ml. The recommended dose of docetaxel is 75 mg / m ^{2 for} one hour, every three weeks.

Adverse effects of docetaxel injection

1. Myelosuppression: neutropenia is the most common side effect and is usually more severe (less than 500 cells / mm ³ ), reversible and non-accumulating.
2. Allergic reactions: Severe allergic reactions can occur in some cases, which are characterized by hypotension and bronchospasm, and need to be discontinued. The patient can return to normal after stopping the instillation and immediate treatment. Some cases may also have mild allergic reactions. Such as blushing, with or without itchy erythema, chest tightness, back pain, dyspnea, drug fever or chills.
3. Skin reactions are often manifested as erythema, which are mainly seen in the hands and feet, but can also occur on the arms, face and chest with local rashes, sometimes accompanied by itching. The rash may usually occur within a week after the infusion of docetaxel, but can recover before the next infusion. Severe symptoms, such as peeling after a rash, rarely occur. Finger (toe) nail lesions may occur. It is characterized by hyperpigmentation or lightening, and sometimes pain and shedding of nails.
4. Fluid retention includes edema. There are also very few cases of pleural effusion, ascites, pericardial effusion, increased capillary permeability, and weight gain. After 4 cycles of treatment or a cumulative dose of 400 mg / m ² , fluid retention in the lower extremities may occur and may develop into systemic edema with a weight gain of 3 kg or more. After stopping docetaxel treatment, fluid retention gradually disappeared. To reduce fluid retention, patients should be given prophylactic corticosteroids.
5. Gastrointestinal reactions such as nausea, vomiting or diarrhea may occur.
6. There have been reports of neurotoxicity in clinical trials.
7. Cardiovascular side effects such as hypotension, sinus tachycardia, palpitations, pulmonary edema, and hypertension may occur.
8. Other side effects include: hair loss, weakness, mucositis, joint and muscle pain, hypotension and injection site reactions.
9. Patients with normal liver function also had elevated transaminase and bilirubin during treatment. The relationship with docetaxel was not clear.

Docetaxel injection contraindications

The following patients are disabled:
1. Patients with a history of severe allergies to docetaxel or Tween-80;
2. Patients with white blood cell count less than 1500 cells / mm3;
3. Patients with severely impaired liver function.

Precautions for docetaxel injection

1. Docetaxel must be used under the guidance of a doctor who has experience in applying cancer chemotherapy drugs. Due to the possibility of more severe allergic reactions, corresponding first aid facilities should be available. It is recommended that the main functional indicators be closely monitored during the injection.
2. Treatment-related deaths occur in patients with abnormal liver function, patients treated with high doses of this product, and patients with non-small cell lung cancer who are receiving platinum therapy at the time, when the dose of docetaxel reaches 100 mg / m ² The rate will increase.
3. All patients need to take pre-drugs to reduce fluid retention before receiving docetaxel. The pre-drugs only include glucocorticoids, such as dexamethasone, which are taken on the first day of docetaxel injection. 16 mg daily for 4 to 5 days.
4. Neutropenia is the most common side effect. Blood cell numbers are often monitored during docetaxel treatment. Docetaxel treatment is only available when the patient's neutrophil count has recovered to> 1500 cells / mm ³ or more. If severe neutropenia occurs during docetaxel treatment (<500 cells / mm ³ and persists) 7 days or more), it is recommended to reduce the dose in the next course of treatment. If the same problem still occurs, it is recommended to reduce or stop the treatment.
5. An allergic reaction is highly likely to occur within the first few minutes of the infusion of docetaxel. There is no need to discontinue treatment if symptoms of an allergic reaction are mild, such as flushing or local skin reactions. If a severe allergic reaction occurs, such as a drop in blood pressure of more than 20mmHg, bronchospasm, or systemic rash / erythema, the infusion should be stopped immediately and treated symptomatically. Docetaxel should not be reapplied to patients who have had serious adverse reactions.
6. Peripheral neurotoxicity may occur during docetaxel treatment. If the response is severe, it is recommended to reduce the dose during the next course of treatment.
7. If the skin reactions have been observed with localized erythema with edema, exfoliation, etc. Such toxicity may cause discontinuation or discontinuation of treatment.
8. Patients with impaired liver function: If serum transaminase (ALT and / or AST) exceeds the upper limit of normal values by 1.5 times and accompanied by alkaline phosphatase exceeds the upper limit of normal values by 2.5 times, there is a high risk of serious adverse reactions, such as Toxic deaths include fatal sepsis, gastrointestinal bleeding, and febrile neutropenia, infections, thrombocytopenia, stomatitis, and fatigue. Therefore, these patients should not be used and liver function should be measured before baseline and before each chemotherapy cycle.

Docetaxel injection for pregnant and lactating women

There are no adequate and strictly controlled clinical studies of pregnant women. If patients use this product during pregnancy, or if they become pregnant while using this product, they should be informed about the potential harm to the fetus and the potential danger of miscarriage. Women with childbearing potential should avoid pregnancy during treatment with this product.
It is unclear whether docetaxel is excreted from human milk. Given that many drugs can be excreted from human milk, and docetaxel may cause serious adverse reactions in nursing infants, mothers should stop breastfeeding before using this product.

Docetaxel injection for children

The effectiveness and safety of docetaxel in children has not been determined.

Docetaxel injection for the elderly

Not clear yet.

Docetaxel injection drug interactions

In vitro studies have shown that CYP3A4 inhibitors may interfere with the metabolism of this product, so extra care should be taken when used with such drugs (such as ketoconazole, erythromycin, cyclosporine, etc.).

Docetaxel injection overdose

Once overdose occurs, the patient should be moved to a special care unit to closely monitor vital organ functions. When docetaxel is overdose, no antidote is available. The major predictable complications of overdose include neutropenia, skin reactions and paresthesias.

Pharmacology and Toxicology of Docetaxel Injection

Pharmacological effects Docetaxel is a paclitaxel-based antitumor drug, which plays an antitumor role by interfering with the microtubule network necessary for cell mitosis and interphase cell function. Docetaxel can whiten with free tubulin, promote the assembly of tubulin into stable microtubules, and inhibit its disaggregation, leading to the production of microtubule bundles that have lost their normal functions and the fixation of microtubules, thereby inhibiting cells Mitosis. The combination of docetaxel and microtubules does not change the number of protofilaments, which is different from most spindle toxic drugs currently in clinical use.
Toxicological studies for genotoxicity:
In the CHO-K1 cell chromosome aberration test and mouse bone marrow micronucleus test, docetaxel showed a disruptive effect, but no mutation effect was seen in the Ames test and the CHO / HGDRT gene mutation test.
Reproductive toxicity:
Intravenous injection of 0.3 mg / kg of docetaxel in rats (calculated based on body surface area, about 1/50 of the clinically recommended dose), no damage to fertility was seen, but testicular weight could be reduced. The results are correlated with the results of repeated dosing tests in rats and dogs for 10 cycles (once every 21 days for 6 consecutive months); the intravenous injection doses for rats and dogs are 5 mg / kg and 0.375 mg / At kg (converted according to body surface area, approximately equivalent to 1/3 and 1/15 of the clinically recommended dose, respectively), testicular atrophy and degeneration can be seen, and rats at low doses also showed similar effects by increasing the number of doses.
Use of docetaxel during pregnancy can cause fetal damage. Rats and rabbits were given docetaxel 0.3 mg / kg / day and 0.03 mg / kg / day during organogenesis (based on body surface area, equivalent to 1/50 and 1/300 of the recommended daily dose). ), Embryo toxicity and fetal toxicity (manifested as intrauterine death, increased absorption of fetus, fetal weight loss and delayed ossification). The above doses can also cause maternal toxicity. There are no adequate and strictly controlled clinical studies of pregnant women. If patients use this product during pregnancy, or if they become pregnant while using this product, they should be informed about the potential harm to the fetus and the potential danger of miscarriage. Women with childbearing potential should avoid pregnancy during treatment with this product.
It is unclear whether docetaxel is excreted from human milk. Given that many drugs can be excreted from human milk, and docetaxel may cause serious adverse reactions in nursing infants, mothers should stop breastfeeding before using this product.

Pharmacokinetics of docetaxel injection

In phase I clinical studies, pharmacokinetic studies of cancer patients at doses of 20-115 mg / m ² were performed. When the dose was 75 to 115 mg / m ² and the intravenous infusion was 1 to 2 hours, the AUC was dose-dependent. The pharmacokinetic characteristics of this product are in line with the three-compartment pharmacokinetic model. The alpha, beta, and gamma half-life are 4 minutes, 36 minutes, and 11.1 hours, respectively. The rapid decrease in concentration at the initial stage indicates that the drug is distributed to the peripheral compartment, and the latter phase is due in part to the relatively slow elimination of the drug from the peripheral compartment. Docetaxel was given intravenously at a dose of 100 mg / m ² within 1 hour, with an average peak concentration of 3.7 g / ml and an AUC of 4.6 g / ml · h. The overall clearance and steady state distribution was ²¹ L / h / m ² 113L. Docetaxel and its metabolites are mainly excreted from feces. Fecal and urinary excretion account for approximately 75% and 6% of the given dose, respectively, with only a small portion excreted as prototypes. In vitro studies have shown that the plasma protein binding rate of docetaxel exceeds approximately 94-97%, and dexamethasone does not affect the binding of docetaxel to proteins. In vitro studies have shown that docetaxel is metabolized by CYP3A4 isoenzymes, and this metabolism can be suppressed by CYP3A4 inhibitors.

Storage of docetaxel injection

Store at 2-8 ° C in a sealed, light-proof container.

Docetaxel injection packaging

The vial. (1) Each box contains a bottle of 1 docetaxel injection: 0.5ml: 20mg and a bottle of solvent 1.5ml
(2) Each box contains a bottle of docetaxel injection: 1.5ml: 60mg and a bottle of solvent 4.5ml (3) Each box contains a bottle of docetaxel injection: 2.0ml: 80mg and a bottle of solvent 6.0ml

Validity of Docetaxel Injection

(1) 0.5ml: 20mg tentative 24 months (2) 1.5ml: 60mg tentative 18 months (3) 2.0ml: 80mg tentative 12 months

Docetaxel injection standard

YBH02032007 ^[1]