Tautax^® (Concentrate) Instructions for Use

ATC Code

L01CD02 (Docetaxel)

Active Substance

Docetaxel (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antineoplastic drug

Pharmacotherapeutic Group

Antineoplastic agents; plant alkaloids and other natural substances; taxanes

Pharmacological Action

Antineoplastic agent, a semisynthetic analogue of paclitaxel. The mechanism of action is associated with the accumulation of tubulin in the microtubules of the mitotic spindle, which disrupts the processes of their assembly and disassembly. It disrupts cell division in the G₂ and M phases of the cell cycle.

Docetaxel persists in cells for a long time, where its concentration reaches high values. Furthermore, Docetaxel is active against some, though not all, cells that produce an excessive amount of P-glycoprotein (Pgp), encoded by the multidrug resistance gene.

Pharmacokinetics

After a single intravenous administration at a dose of 100 mg/m², the mean C_max of docetaxel in plasma is 3.7 µg/ml, AUC – 4.6 µg*h/ml. The mean values for total clearance and V_d at steady state were 21 L/h/m² and 113 L, respectively. The values of total docetaxel clearance varied by approximately 50% among different patients.

Docetaxel is more than 95% bound to plasma proteins.

Docetaxel, after oxidation of the tert-butyl ether group by the cytochrome P450 isoenzyme system, is eliminated over 7 days through the kidneys, in urine (6% of the administered dose) and through the gastrointestinal tract, in feces (75% of the administered dose). About 80% of the docetaxel dose is excreted in feces within 48 hours as metabolites (the main inactive metabolite and three less significant inactive metabolites) and a very small amount is excreted unchanged.

Indications

As a first-line treatment for breast cancer, as well as for anthracycline therapy failure; non-small cell lung cancer (including after failure of other antineoplastic agents); malignant tumors of the head and neck; ovarian cancer; prostate cancer; stomach cancer (adenocarcinoma).

ICD codes

Dosage Regimen

Determine the dose and schedule individually based on the specific malignancy, disease stage, and patient’s hematological status.

Calculate the dose based on body surface area (mg/m²). The standard infusion duration is one hour.

For breast cancer, the recommended dose is 60-100 mg/m² administered intravenously every 3 weeks.

For non-small cell lung cancer, use 75 mg/m² intravenously every 3 weeks.

For prostate cancer, administer 75 mg/m² every 3 weeks in combination with prednisone.

For gastric adenocarcinoma, the dose is 75 mg/m² every 3 weeks, combined with cisplatin and fluorouracil.

For head and neck cancer, use 75 mg/m² every 3 weeks as part of a combination regimen with cisplatin and fluorouracil.

Adjust the dose for subsequent cycles based on tolerability and toxicity, particularly the nadir neutrophil count.

Premedicate all patients with oral corticosteroids (e.g., dexamethasone 8 mg twice daily for 3 days) starting one day prior to docetaxel infusion to reduce the incidence and severity of fluid retention and hypersensitivity reactions.

Withhold treatment if the neutrophil count is below 1,500 cells/mm³. Do not administer to patients with a baseline neutrophil count of <1,500 cells/mm³.

Reduce the dose by 25% if patients experience febrile neutropenia, neutropenic infection, or prolonged neutropenia lasting more than seven days.

Reduce the dose by 25% for patients who experience severe or cumulative cutaneous reactions or severe peripheral neuropathy.

Discontinue therapy in case of severe hypersensitivity reactions.

Administer the concentrate only after dilution in a 250 mL infusion bag of 0.9% sodium chloride solution or 5% glucose solution to a final concentration not exceeding 0.9 mg/mL.

Inspect the diluted solution visually for particulate matter and discoloration prior to administration. Do not use if the solution is cloudy or contains precipitate.

Use non-PVC infusion sets and containers. Administer through a peripheral or central venous line.

Adverse Reactions

From the hematopoietic system very often – reversible and non-cumulative (not increasing with repeated administrations) neutropenia; often – bleeding, combined with thrombocytopenia <50,000/µl and anemia (hemoglobin <11 g/dl), including severe anemia (hemoglobin <8 g/dl); infrequently – severe thrombocytopenia.

Infections and parasitic diseases severe infections, combined with a decrease in peripheral blood neutrophil count <500/µl; severe infections including sepsis and pneumonia, including fatal outcomes.

From the immune system very often – allergic reactions (usually occurring within minutes after the start of IV infusion and being mild or moderate) – skin flushing, rash with or without itching; chest tightness, back pain, shortness of breath, drug fever or chills; often – severe allergic reactions characterized by decreased blood pressure and/or bronchospasm or generalized rash/erythema.

From the skin and subcutaneous tissues: very often – reversible skin reactions (usually mild or moderate) – localized rashes, mainly on the hands and feet, as well as on the face and chest, often accompanied by itching; hypo- and hyperpigmentation of nails, pain and onycholysis (loss of the nail plate from the nail bed); alopecia; often – severe skin reactions, such as rashes followed by desquamation, including severe palmar-plantar syndrome; infrequently – severe alopecia.

From the digestive system very often – nausea, vomiting, diarrhea, anorexia, stomatitis; often – severe nausea, severe vomiting, severe diarrhea, constipation, severe stomatitis, esophagitis; abdominal pain, including severe; gastrointestinal bleeding; infrequently – severe gastrointestinal bleeding, severe constipation, severe esophagitis.

From the liver and biliary tract: often – increased activity of AST, ALT, ALP and serum bilirubin concentration, more than 2.5 times the upper limit of normal.

From the nervous system very often – mild or moderate neurosensory reactions (paresthesia, dysesthesia, pain, including burning sensation) and neuromotor reactions, mainly manifested as muscle weakness; taste disturbance; often – severe neurosensory and neuromotor reactions (grade 3-4); rarely – severe taste disturbance.

From the cardiovascular system often – cardiac arrhythmias, increase or decrease in blood pressure, bleeding; infrequently – heart failure.

From the respiratory system: very often – shortness of breath; often – severe shortness of breath.

From the musculoskeletal system: very often – myalgia; often – arthralgia.

From fluid and electrolyte balance very often – peripheral edema; often – pleural and pericardial effusion, ascites.

General reactions: very often – asthenia, including severe asthenia, weight gain; generalized and localized pain syndrome, including non-cardiac chest pain.

Local reactions: very often – hyperpigmentation, inflammation, redness or dryness of the skin, phlebitis, bleeding from the punctured vein or vein swelling.

Contraindications

History of hypersensitivity to docetaxel; neutropenia less than 1500/µl; pregnancy, breastfeeding period; severe hepatic impairment; children and adolescents under 18 years of age.

With caution when used concomitantly with strong inhibitors of the CYP3A4 isoenzyme (e.g., ketoconazole, itraconazole, clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole); when used concomitantly with drugs that induce or inhibit CYP3A isoenzymes, or are metabolized by CYP3A isoenzymes.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and lactation (breastfeeding).

Women of childbearing potential should use reliable methods of contraception during docetaxel therapy.

Use in Hepatic Impairment

Contraindicated in severe hepatic impairment.

Use in Renal Impairment

Should be used with caution in patients with renal impairment.

Pediatric Use

Contraindicated in children and adolescents under 18 years of age.

Geriatric Use

Should be used with caution in elderly patients.

Special Precautions

Treatment with docetaxel should be carried out only under the supervision of a physician experienced in anticancer chemotherapy in a specialized hospital setting.

Docetaxel should not be used if bilirubin is above the upper limit of normal in combination with hepatic transaminase activity exceeding the upper limit of normal by 1.5 times, and ALP exceeding the upper limit of normal by 2.5 times.

Before starting docetaxel therapy, patients should be prescribed oral corticosteroids. The likelihood of developing allergic reactions and edema is significantly increased in patients who have not received such preliminary therapy.

During treatment, systematic monitoring of peripheral blood counts is necessary to detect the degree of myelodepression.

Clinical blood tests should be monitored in patients receiving docetaxel therapy. The maximum decrease in neutrophils occurs by day 7, but in patients who have previously undergone intensive chemotherapy, this interval may be shorter. If severe neutropenia (<500/µl for 7 days) develops during a course of docetaxel, it is recommended to reduce its dose in subsequent cycles or take adequate symptomatic measures. Treatment with docetaxel can be continued after the neutrophil count recovers to > 1500/µl.

Docetaxel should be used with caution in patients with neutropenia, especially if there is a risk of gastrointestinal complications. Enterocolitis can develop throughout the treatment. Enterocolitis can lead to death even on the first day of its development.

To detect the development of hypersensitivity reactions, patients should be carefully monitored, especially during the first and second infusions. Hypersensitivity reactions can develop in the first minutes of docetaxel infusion, so when administering it, it is necessary to have medications and equipment for the treatment of arterial hypotension and bronchospasm.

In patients receiving docetaxel monotherapy at a dose of 100 mg/m² and having elevated hepatic transaminase activity (ALT and/or AST), more than 1.5 times the upper limit of normal, in combination with ALP activity more than 2.5 times above the upper limit of normal, there is an extremely high risk of developing severe side effects such as sepsis, gastrointestinal bleeding, febrile neutropenia, infections, thrombocytopenia, severe toxic skin lesions up to death, as well as stomatitis and asthenia. Liver function tests should be performed before starting treatment and before each subsequent cycle of docetaxel therapy.

Close monitoring is necessary for patients with significant fluid retention: with pleural effusion, pericardial effusion, or ascites. If edema occurs, salt and fluid intake should be restricted and diuretics should be used.

In patients 65 years and older treated with docetaxel every 3 weeks for prostate cancer, the incidence of nail changes, anemia, infections, anorexia, weight loss was >10% greater than in younger patients, and in patients 75 years and older, the incidence of fever, diarrhea, anorexia, and peripheral edema was >10% greater than in younger patients. No differences in treatment efficacy were found when comparing elderly and younger patients.

Men and women of reproductive age should use reliable methods of contraception during docetaxel treatment. Men receiving docetaxel treatment are advised to avoid fathering a child during docetaxel treatment and for at least 6 months after the end of chemotherapy.

Effect on ability to drive and operate machinery

During treatment, patients should avoid driving vehicles and other activities requiring high concentration and speed of psychomotor reactions.

Drug Interactions

It has been shown that the biotransformation of docetaxel can be altered with the concomitant use of substances that induce or inhibit cytochrome CYP3A isoenzymes, or are metabolized (competitive inhibition) by cytochrome CYP3A isoenzymes, such as cyclosporine, terfenadine, erythromycin, and troleandomycin. Therefore, caution should be exercised when co-administering such drugs, considering the possibility of significant interaction.

When docetaxel is used concomitantly with strong inhibitors of the CYP3A4 isoenzyme, the frequency of docetaxel side effects may increase due to decreased metabolism.

The pharmacokinetics of docetaxel in the presence of prednisolone were studied in patients with metastatic prostate cancer. Although Docetaxel is metabolized by the CYP3A4 isoenzyme and prednisolone is an inducer of the CYP3A4 isoenzyme, no statistically significant effect of prednisolone on the pharmacokinetics of docetaxel was observed.

There is evidence of an interaction between docetaxel and carboplatin. When using a combination of carboplatin and docetaxel, the clearance of carboplatin increases by 50% compared to carboplatin monotherapy.

Storage Conditions

Store at 2°C (36°F) to 8°C (46°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.