Taxotere

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Taxotere: instructions for use and reviews

1. Release form and composition
2. Pharmacological properties
3. Indications for use
4. Contraindications
5. Method of application and dosage
6. Side effects
7. Overdose
8. Special instructions
9. Application during pregnancy and lactation
10. Use in the elderly
11. Drug interactions
12. Analogs
13. Terms and conditions of storage
14. Terms of dispensing from pharmacies
15. Reviews
16. Price in pharmacies

Latin name: Taxotere

ATX code: L01CD02

Active ingredient: Docetaxel (Docetaxel)

Producer: Aventis Pharma (Dagenham) (Great Britain), Sanofi-Aventis Deutschland GmbH (Germany)

Description and photo update: 2019-07-08

Prices in pharmacies: from 17600 rubles.

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Concentrate for preparation of solution for infusion Taxotere

Taxotere is an anticancer agent of plant origin, belongs to the group of taxoids.

Release form and composition

Dosage form Taxotere - concentrate for preparation of solution for infusion: clear oily liquid from brownish-yellow to yellow [0.61 ml or 2.36 ml each in glass vials without color with a green or red plastic cap (respectively), in a contour cell packaging 1 bottle complete with a solvent (bottle of colorless glass, 1.98 ml or 7.33 ml), in a cardboard box 1 package].

1 bottle of concentrate contains:

active substance: docetaxel trihydrate, corresponding to 20 mg or 80 mg of anhydrous docetaxel;
auxiliary component: polysorbate 80.

The composition of the solvent: 13% solution - water for injection and 95% ethanol (V / V).

Pharmacological properties

Pharmacodynamics

The active component of Taxotere, docetaxel, is a plant-derived antineoplastic substance belonging to the taxoid group. It accumulates tubulin in microtubules and prevents their breakdown, which leads to disturbances in the process of tumor cell division. Docetaxel persists for a long time in cells, where its level remains high enough. Also, the compound is characterized by activity against some cells that synthesize an excessive amount of P-glycoprotein, which contains a gene for multiple resistance to chemotherapeutic drugs. In vivo, docetaxel has a broad spectrum of activity against transplanted human tumor cells and inhibits tumor growth in mice.

Taxotere has been proven to be effective in head and neck cancer, stomach cancer, breast cancer, hormone-resistant prostate cancer, ovarian cancer, and non-small cell lung cancer.

Pharmacokinetics

There is no dependence of the pharmacokinetics of docetaxel on the dose taken. Taxotere is characterized by a three-phase pharmacokinetic model, where the half-lives for the α, β and γ-phases are 4 minutes, 36 minutes and 11.1 hours, respectively.

When docetaxel was infused at a dose of 100 mg / m ² for 1 hour, the average maximum concentration of the substance in the blood plasma was 3.7 μg / ml with the corresponding area under the concentration-time curve equal to 4.6 μg · h / ml. The average indicators of the volume of distribution and total clearance in equilibrium are 113 l and 21 l / h / m ². In different patients, the spread in the values of the total clearance of docetaxel was up to 50%.

Docetaxel is more than 95% bound to plasma proteins. The tert-butyl ester group of this compound undergoes oxidation with the participation of cytochrome P ₄₅₀ isoenzymes, after which docetaxel is excreted for 7 days via the kidneys in the urine (6% of the administered dose) and through the gastrointestinal tract with feces (75% of the administered dose). Approximately 80% of the active substance of Taxotera is excreted in the feces within 2 days in the form of metabolites (the main inactive metabolite and 3 inactive metabolites, which are of lesser importance), and only a small part of docetaxel is unchanged.

The pharmacokinetics of the drug is not determined by the sex and age of the patient.

With mild and moderate liver dysfunctions [the activity of aspartate aminotransferase and alanine aminotransferase is 1.5 times (or more) higher than their upper limits of the norm, while the activity of alkaline phosphatase is 2.5 times (or more) higher than the upper limits of the normal], the total clearance of the active component of Taxotere decreases by about 27%.

With mild to moderate fluid retention, no significant changes in the clearance of docetaxel are observed, and there is no information on its clearance with severe fluid retention.

When Taxotera is combined with other drugs, docetaxel does not affect the clearance of doxorubicin and the content of doxorubicinol (a metabolite of doxorubicin) in blood plasma. With the simultaneous use of the drug with doxorubicin and cyclophosphamide, their pharmacokinetic parameters remained stable. Capecitabine has no effect on the pharmacokinetics of docetaxel, and the latter also does not alter the pharmacokinetics of capecitabine and its most significant metabolite, 5'-DFUR. The clearance of docetaxel both with monotherapy and when used as an element of combination therapy with cisplatin remains the same. Prednisone has no effect on the pharmacokinetics of docetaxel when infused after standard dexamethasone premedication. Pharmacokinetic parameters of fluorouracil and docetaxel remain unchanged when used in combination.

In children with monotherapy with docetaxel and a course of treatment with Taxotere in combination with fluorouracil and cisplatin, the pharmacokinetic parameters were identical to those in adult patients.

Indications for use

adjuvant therapy of operable breast cancer (BC) with lesions of regional lymph nodes in combination with cyclophosphamide and doxorubicin;
metastatic or locally advanced breast cancer: the first line of chemotherapy treatment - in combination with doxorubicin; second line: monotherapy - in the absence of effect from previous treatment in combination with anthracyclines or alkylating agents, or combination therapy with capecitabine after previous treatment, including anthracyclines;
metastatic breast cancer with tumor expression of HER2 - simultaneously with trastuzumab (without previous chemotherapy);
locally advanced or metastatic non-small cell lung cancer in an inoperable form: first-line therapy - in combination with carboplatin or cisplatin; second-line monotherapy - in the absence of the effect of chemotherapy with platinum drugs;
hormone-resistant, metastatic prostate cancer - while using prednisone or prednisolone;
metastatic ovarian cancer: second-line therapy - in the absence of effect after first-line therapy;
metastatic gastric and cardiac cancer: first-line therapy in combination with 5-fluorouracil (5-FU) and cisplatin;
locally advanced squamous cell carcinoma of the head and neck in an inoperable form - first-line therapy in combination with 5-FU and cisplatin;
metastatic squamous cell carcinoma of the head and neck - second-line therapy in the absence of effect from previous treatment.

Contraindications

severe liver dysfunction;
the number of neutrophils in the patient's blood is less than 1500 / μl;
the period of pregnancy and breastfeeding;
individual hypersensitivity to the components of Taxotere.

Instructions for the use of Taxotere: method and dosage

In order to reduce fluid retention and the risk of developing hypersensitivity reactions, it is advisable to administer Taxotere against the background of premedication with glucocorticosteroids. The patient is prescribed dexamethasone 8 mg 2 times a day, its ingestion begins on the first day of therapy (the day before the infusion) and continues for 3 days. In prostate cancer with concomitant therapy with prednisone or prednisolone, premedication is performed with dexamethasone at a dose of 8 mg 12, 3 and 1 hour before the start of the infusion.

For the prevention of hematological complications, preliminary administration of granulocyte colony-stimulating factor (G-CSF) preparations is necessary.

The ready-made solution of Taxotere concentrate is intended for intravenous (i / v) infusion over one hour. For the treatment of all pathologies from the clinical indications for the use of the drug, the procedure is carried out 1 time in 3 weeks.

A solution for intravenous administration is prepared immediately before the procedure.

The vials with the preparation and the solvent should stand at room temperature for 5 minutes before dilution. Then, holding the solvent bottle at an angle, the contents are drawn into a syringe and injected into the drug bottle. The mixture should be turned over within ¾ minutes without shaking. After settling for 5 minutes (the presence of foam is normal), the solution should be visually examined for homogeneity and transparency. If there is a precipitate in the solution, the solution must be destroyed.

Then the required dose of the premixed solution is diluted in 250 ml of 0.9% sodium chloride solution or 5% dextrose solution and mixed. The volume of solutions for infusion should provide a concentration level of docetaxel not exceeding 0.74 mg per ml.

The actual content of the drug and solvent in the vials is calculated for natural losses (foaming, adhesion to the walls of the vial) during the preparation process and guarantees that after mixing them, 2 ml or 8 ml of solution, with 20 mg or 80 mg of docetaxel.

The premixed solution is suitable for use within 8 hours when stored in a refrigerator (2 to 8 ° C) or at room temperature.

The prepared solution must be used within 4 hours from the moment of preparation.

Recommended dosage:

breast cancer: monotherapy - at the rate of 100 mg per 1 m ² of body surface every 3 weeks; adjuvant therapy for patients with resectable breast cancer - at the rate of 75 mg per 1 m ² of body surface 1 hour after administration of doxorubicin at a dose of 50 mg per 1 m ² and cyclophosphamide - 500 mg per 1 m ². The procedure is carried out once every three weeks, in total - 6 procedures; combination therapy - 75 mg per 1 m ² with concomitant treatment with doxorubicin at a dose of 50 mg per 1 m ² or capecitabine - 1250 mg per 1 m ² orally 2 times a day for 2 weeks, followed by a weekly break, or 100 mg per 1 m ² when combining Taxotera with trastuzumab (the dose of trastuzumab is determined according to the instructions for its use);
non-small cell lung cancer: at a dose of 75 mg per 1 m ² both in monotherapy and in combination with platinum preparations;
metastatic ovarian cancer: 100 mg per 1 m ² of body surface;
locally advanced squamous cell carcinoma of the head and neck: at a dose of 75 mg per 1 m ²; on the same day, after the Taxotere infusion, it is necessary to infuse cisplatin at a dose of 75 mg per 1 m ² within one hour, then an infusion of 5-FU at a dose of 750 mg per 1 m ² per day. Duration of 5-FU infusion is 24 hours, duration of treatment is 5 days. The listed procedures are prescribed once every three weeks and are 1 cycle. In total, up to 4 cycles are carried out, then radiation therapy is prescribed;
metastatic squamous cell carcinoma of the head and neck: at a dose of 100 mg per 1 m ²;
metastatic hormone-resistant prostate cancer: 75 mg per 1 m ² in combination with oral prednisone or prednisolone 5 mg twice a day during the entire period of course therapy;
metastatic gastric cancer (including the cardiac section): at a dose of 75 mg per 1 m ²; on the same day, after infusion of docetaxel, intravenous drip of cisplatin at a dose of 75 mg per 1 m ^{2 is} carried out for 1-3 hours, followed by a 24-hour infusion of 5-FU at a dose of 750 mg per 1 m ² per day within 5 days. The listed procedures are prescribed once every three weeks.

Indications for Docetaxel Dose Adjustment:

a drop in the number of neutrophils below 500 / μl, lasting more than a week;
the appearance of pronounced skin reactions;
development of febrile neutropenia;
the development of severe peripheral neuropathy during the treatment period.

In the presence of one of these violations, the dose of docetaxel for the next cycle should be reduced to 75 mg per 1 m ² with the initial appointment of 100 mg per 1 m ² and / or to 60 mg per 1 m ² from 75 mg per 1 m ². If complications arise with the use of docetaxel at a dose of 60 mg per 1 m ², treatment should be canceled.

With the development of febrile neutropenia during adjuvant therapy in patients with resectable breast cancer, G-CSF should be taken in each subsequent cycle. If febrile neutropenia is stored, it is necessary to continue receiving G-CSF and reduce the dose of docetaxel and 60 mg per 1 m ². For stomatitis of grade 3 or 4, the dose should be no more than 60 mg per 1 m ².

In the treatment of non-small cell lung cancer, in the case of a decrease in the number of platelets in the previous cycle to 25,000 / μl when combined with cisplatin and up to 75,000 / μl with carboplatin, or with the development of febrile neutropenia, or with serious manifestations of nonhematological toxicity, an initial dose of docetaxel of 75 mg per 1 m ² in the next cycle, it is necessary to reduce to 65 mg per 1 m ².

Correction of the dosage regimen with the development of complications during combination therapy:

combination with capecitabine: in case of grade 2 toxicity, which appeared for the first time and persists until the next cycle, further therapy should be postponed until the toxicity decreases to grade 0-1. The next cycle is performed at the initial dose of Taxotere. In case of repeated development of grade 2 toxicity or the first development of grade 3 toxicity during the treatment cycle, it is necessary to postpone the continuation of the drug until the toxicity decreases to 0–1 degrees. The therapy should be resumed with a dose of 55 mg per 1 m ². If any type of toxicity of grade 4 or subsequent manifestations of toxicity appears, the drug must be discontinued;
combination with 5-FU and cisplatin: if infection or febrile neutropenia develops while taking G-CSF, the dose of the drug should be reduced to 60 mg per 1 m ². If the appearance of episodes of complicated neutropenia does not stop, the dose is reduced to 45 mg per 1 m ². In case of grade 4 thrombocytopenia, the dose of Taxotere is reduced from 75 mg to 60 mg per 1 m ²… Conducting subsequent cycles is possible when the number of neutrophils is above 1500 / μl and platelets are above 100,000 / μl. Persistence of toxicity is the basis for discontinuation of treatment. For grade 3 diarrhea: the first episode - the 5-FU dose should be reduced by 1/5, with a second episode - the Taxotere dose should be reduced by 1/5. For grade 4 diarrhea: first episode - the dose of docetaxel and 5-FU should be reduced by 1/5, with repeated episodes, treatment should be discontinued. For grade 3 stomatitis: the first episode - the dose of 5-FU should be reduced by 1/5, with a second episode, 5-FU should be canceled in the following cycles, for the third episode - the dose of docetaxel should be reduced by 1/5. For grade 4 stomatitis: first episode - 5-FU should be discontinued in the next cycles, with a second episode - reduce the dose of docetaxel by 1/5.

In patients with severe hepatic dysfunction [ALT and AST activity is more than 3.5 times the upper limit of normal (ULN) in combination with more than 6 times higher alkaline phosphatase or increased bilirubin] Taxotere is not recommended. With a moderate degree of impairment, the drug is prescribed at a dose of 75 mg per 1 m ².

The experience of using the drug in children is limited, so the safety and effectiveness of therapy have not been established.

There are no specific instructions for the use of docetaxel in elderly patients. In combination therapy of patients over 60 years of age with capecitabine, it is recommended to reduce the starting dose of capecitabine.

Side effects

hematopoietic organs: often - (in patients who have not received G-CSF enzymes) reversible neutropenia (may be accompanied by the addition of infections, fever, development of pneumonia and sepsis); possibly - thrombocytopenia, anemia; rarely - bleeding (more often caused by thrombocytopenia);
allergic reactions: mild to moderate severity - in the form of hot flashes, rash, skin itching, chest tightness, back pain, shortness of breath, fever or chills; severe reactions - bronchospasm, decreased blood pressure (BP), generalized rash or erythema;
dermatological reactions: alopecia, skin reactions of mild to moderate severity; infrequently - severe reactions in the form of a skin rash with itching, limited erythema of the skin of the hands, face, chest and extremities (including severe syndrome of damage to the palms and feet) with edema and desquamation of the extremities; rarely - hypo- or hyperpigmentation of nails, onycholysis; extremely rarely - bullous rash (Stevens-Johnson syndrome, Lyell's syndrome), fluid retention (peripheral edema, ascites, pleural and pericardial effusion, weight gain, in rare cases - dehydration, pulmonary edema);
gastrointestinal tract: taste disturbance, nausea, vomiting, pain in the stomach, diarrhea, constipation, anorexia, stomatitis, colitis (including ischemic), esophagitis, enterocolitis, intestinal and / or stomach perforation; rarely - intestinal obstruction, gastrointestinal bleeding;
nervous system: peripheral neuropathy (mild or moderate degree of hyperesthesia, paresthesia, dysesthesia, pain, burning), motor weakness; very rarely - convulsions, transient loss of consciousness;
cardiovascular system: atrial fibrillation, sinus tachycardia, heart failure, decrease or increase in blood pressure; rarely - venous thromboembolism, myocardial infarction;
hepatobiliary system: possible (with monotherapy at a dose of 100 mg per 1 m ² of body surface) - an increase in the serum activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, an increase in the level of bilirubin concentration in the blood serum (more than 2.5 times from the upper limit of the norm); extremely rare - hepatitis, including fatal in patients with a history of liver disease;
respiratory system: very rarely - interstitial pneumonia, acute respiratory distress syndrome, increased response to radiation, pulmonary fibrosis;
musculoskeletal system: arthralgia, myalgia, muscle weakness;
organ of vision: rarely - transient visual disorders (with the introduction of the drug - the appearance of flashes of light in the eyes, cattle), lacrimation, conjunctivitis; very rarely (more often with the simultaneous use of other antineoplastic agents) - occlusion of the lacrimal canal;
local reactions: hyperpigmentation, inflammation, redness or dryness of the skin at the injection site, phlebitis, hemorrhage or vein edema;
others: shortness of breath, asthenia, local or generalized pain, chest pain (not associated with pathologies of the heart and lungs).

Overdose

Overdose cases of Taxotere are relatively rare. Symptoms include mucositis (an inflammatory process in the mucous membranes), peripheral neurotoxicity, and bone marrow suppression.

There is currently no specific antidote for docetaxel. In case of an overdose, urgent hospitalization is required and careful monitoring of the functioning of vital organs. It is necessary to prescribe G-CSF as soon as possible and, if necessary, carry out symptomatic therapy.

special instructions

The use of Taxotere is indicated in a specialized hospital under the supervision of a physician with experience in anticancer chemotherapy.

Treatment should be accompanied by careful monitoring of the clinical blood test. If severe neutropenia develops and persists for 7 days (less than 500 / μl), the dose of the drug in the following courses should be reduced or appropriate symptomatic measures should be taken. You can start the next cycle of therapy only after increasing the number of neutrophils to 1500 / μl.

The development of hypersensitivity reactions is possible from the first minutes of infusion, therefore, when the drug is administered, the patient should be carefully monitored. In case of reddening of the patient's face or the appearance of localized skin reactions, the infusion should not be interrupted. If the drug causes a decrease in blood pressure, generalized rash or erythema, bronchospasm, immediate discontinuation of the drug is required and measures to be taken to stop these complications. Further therapy with Taxotere is not permitted in this category of patients.

Due to the risk of fluid retention, it is recommended to carefully monitor patients with ascites, pleural effusion or pericardial effusion. To relieve edema, salt and drinking regimes should be limited, and diuretics should be prescribed.

When combined with capecitabine, disorders of the gastrointestinal tract, palmar-foot syndrome, dehydration, lacrimation, arthralgia, severe hyperbilirubinemia, thrombocytopenia and anemia develop more often, in elderly patients - the development of toxicity of 3-4 degrees. This combination more rarely causes severe neutropenia, alopecia, asthenia, myalgia, disorders of the nails, edema of the lower extremities.

Compared with monotherapy, when combined with trastuzumab, the incidence of adverse events, the development of grade 4 toxicity, and cases of heart failure increases, especially when supplemented with doxorubicin or epirubicin therapy.

Patients of childbearing age, regardless of gender, need to use reliable methods of contraception both during the entire course of treatment and for at least three months after the end of therapy.

Since the concentrate is a toxic substance, it is necessary to observe safety measures during the preparation of the solution and its application. If the drug gets on the skin or mucous membranes, they should be immediately washed thoroughly with water.

Influence on the ability to drive vehicles and complex mechanisms

Special studies of the effect of Taxotere on the ability to drive vehicles and complex mechanisms have not been conducted. However, the occurrence of adverse reactions from the gastrointestinal tract, the organ of vision, the central nervous system, as well as the presence of ethanol in the composition of the drug, can lead to a dissipation of attention and a decrease in the speed of psychomotor reactions. Therefore, during the course of therapy, it is recommended to refuse to drive a car and perform other potentially dangerous work.

Application during pregnancy and lactation

According to the instructions, Taxotere is strictly prohibited during pregnancy and breastfeeding. Women and men of reproductive age should avoid conception, using reliable contraception, during the course of treatment with the drug and for at least 3 months after its cancellation.

Women who become pregnant during the course of therapy should immediately inform their doctor about this.

Since preclinical studies have shown that docetaxel is genotoxic and can lead to impaired male fertility (fertility), men using Taxotere are strongly advised to refrain from conceiving a child during drug treatment and for at least 6 months after discontinuation. Preservation of sperm is possible before starting therapy.

Use in the elderly

Compared with patients under 60 years of age, patients aged 60 years or older who receive combination chemotherapy with Taxotere and capecitabine have an increased incidence of treatment-related grade 3 and 4 side effects associated with the treatment of severe side effects, and also more often there is a cancellation of treatment at the initial stage due to the occurrence of adverse reactions.

Limited information is available on the combination of docetaxel with cyclophosphamide and doxorubicin in patients over 70 years of age.

Patients aged 65 and older, who were treated with Taxotere for prostate cancer every 3 weeks, experienced changes in the nail plates 10% (or more) more often than patients of younger age. In patients 75 years and older, anorexia, fever, diarrhea, and peripheral edema occurred 10% (or more) more often than in younger patients.

The combination of docetaxel with fluorouracil and cisplatin in patients over 65 years old increases the incidence of adverse reactions of all severity [these include lethargic state (drowsiness, numbness, lethargy), neutropenic infection, stomatitis] by 10% (or more) compared with patients more young age. Therefore, elderly patients who have been prescribed a similar treatment regimen require more close medical supervision.

Drug interactions

The simultaneous use of cyclosporine, terfenadine, ketoconazole, erythromycin and troleandomycin, drugs that inhibit or induce the cytochrome CYP3A4 system, or are metabolized by the cytochrome CYP3A4 system, can cause docetaxel biotransformation and a pronounced interaction.

The following drugs do not affect the binding of the drug to proteins: propafenone, phenytoin, erythromycin, propranolol, diphenhydramine, salicylates, sodium valproate, dexamethasone, sulfamethoxazole.

Docetaxel does not affect the binding of digitoxin to the protein.

When combined therapy with doxorubicin, the clearance of docetaxel increases, while its effectiveness remains. Docetaxel does not affect the clearance of doxorubicin and its level in blood plasma.

Taxotere increases the clearance of carboplatin by 1/2 of the level of this indicator in monotherapy.

A negative interaction of Taxotere with capecitabine has not been established.

Analogs

Taxotere analogs are: Taxolik, Taxol, Paclitaxel, Docet, Docetactin, Docetaxel, Docetax.

Terms and conditions of storage

Keep out of the reach of children.

Store in a dark place at temperatures up to 2-25 ° C.

Shelf life: 20 mg vials - 2 years, 80 mg vials - 3 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Taxotere

Taxotere is a relatively new and highly effective drug used in the treatment of various cancers. It is prescribed as monotherapy or in combination with other drugs. However, according to reviews, Taxotere increases the risk of developing infectious diseases and other serious complications. Many patients are also confused by its high cost.

Price for Taxotere in pharmacies

The price of Taxotere per vial containing 20 mg of docetaxel is approximately 11,200-12,500 rubles, depending on the region of sale. You can order the drug, which contains 80 mg of the active substance, for 33,500–35,000 rubles.

Taxotere: prices in online pharmacies

Drug name

Price

Pharmacy

Taxotere 80 mg concentrate for preparation of solution for infusion 2 ml 1 pc.

RUB 17600

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Anna Kozlova Medical journalist About the author

Education: Rostov State Medical University, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!