Paclitax (Concentrate) Instructions for Use

ATC Code

L01CD01 (Paclitaxel)

Active Substance

Paclitaxel (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antineoplastic drug

Pharmacotherapeutic Group

Antineoplastic agent – alkaloid

Pharmacological Action

Antineoplastic agent. It is a mitosis inhibitor. Paclitaxel specifically binds to the beta-tubulin of microtubules, disrupting the process of depolymerization of this key protein, which leads to the suppression of the normal dynamic reorganization of the microtubule network, which plays a crucial role during interphase and without which the implementation of cellular functions in the mitosis phase is impossible.

In addition, Paclitaxel causes the formation of abnormal bundles of microtubules throughout the entire cell cycle and the formation of multiple centrioles during mitosis.

Pharmacokinetics

Plasma protein binding is 89-98%. It is biotransformed mainly in the liver. It is excreted both by the kidneys unchanged and with bile (both unchanged and in the form of metabolites).

Indications

Ovarian cancer (including in cases of resistance to platinum drugs), breast cancer, lung cancer, esophageal cancer, head and neck cancer, bladder cancer.

ICD codes

Dosage Regimen

Administer Paclitax concentrate only as an intravenous infusion after appropriate dilution. Do not administer as an undiluted concentrate or by the intrathecal route, as this will cause death.

Determine the dose based on body surface area (BSA). The standard dose for ovarian and breast cancer is 175 mg/m², infused over 3 hours every 3 weeks. For lung cancer, administer 135 mg/m² over 24 hours every 3 weeks. Adhere strictly to the specific regimen prescribed for the indicated malignancy.

Prior to infusion, all patients must receive premedication to prevent severe hypersensitivity reactions. Premedicate with a corticosteroid (e.g., dexamethasone 20 mg orally approximately 12 and 6 hours before), an H1-antagonist (e.g., diphenhydramine 50 mg IV 30-60 minutes prior), and an H2-antagonist (e.g., ranitidine 50 mg IV 30-60 minutes prior).

Dilute the concentrate only in 0.9% Sodium Chloride Injection, USP, or 5% Dextrose Injection, USP, to a final concentration of 0.3 to 1.2 mg/mL. Prepare the infusion solution in a non-PVC container, such as glass, polypropylene, or polyolefin. Use an in-line filter with a microporous membrane not greater than 0.22 microns during administration.

Withhold therapy if the neutrophil count is below 1,500 cells/mm³ or the platelet count is below 100,000 cells/mm³ prior to a scheduled dose. For severe neutropenia (neutrophils <500 cells/mm³ for 7 days or more) or severe peripheral neuropathy, reduce the dose by 20% for subsequent courses.

For patients with moderate to severe hepatic impairment, significantly reduce the dose. Do not administer to patients with total bilirubin >1.5 times the upper limit of normal (ULN). Monitor patients with hepatic impairment closely for severe myelosuppression and other toxicities.

Adverse Reactions

From the hematopoietic system: leukopenia, thrombocytopenia, anemia.

From the digestive system: nausea, vomiting, diarrhea, mucositis, loss of appetite, constipation (rarely – symptoms of intestinal obstruction), increased activity of liver enzymes and bilirubin levels in the blood.

Allergic reactions: skin rash, angioedema, rarely – bronchospasm.

From the cardiovascular system: arterial hypotension, bradycardia, conduction disorders, peripheral edema.

Other: arthralgia, myalgia, peripheral neuropathy.

Local reactions: thrombophlebitis, with extravasation – necrosis.

Contraindications

Severe neutropenia (less than 1500/µL), pregnancy, hypersensitivity to paclitaxel.

Use in Pregnancy and Lactation

Paclitaxel is contraindicated for use during pregnancy. If it is necessary to use it during lactation, breastfeeding should be discontinued.

Women of childbearing potential should use reliable methods of contraception during the use of paclitaxel.

In experimental studies, it has been established that Paclitaxel has teratogenic and embryotoxic effects.

Use in Hepatic Impairment

For patients with hepatic insufficiency and the associated increased risk of toxicity (in particular, grade III-IV myelosuppression), a dose adjustment of paclitaxel is recommended. Careful monitoring of the patients’ condition is necessary.

Special Precautions

Paclitaxel should be used with caution in patients with angina pectoris, arrhythmias and conduction disorders, chronic heart failure, with chickenpox (including recently contracted or after contact with sick individuals), herpes zoster and other acute infectious diseases, as well as within 6 months after myocardial infarction.

For patients with hepatic insufficiency and the associated increased risk of toxicity (in particular, grade III-IV myelosuppression), a dose adjustment of paclitaxel is recommended. Careful monitoring of the patients’ condition is necessary.

To prevent the occurrence of hypersensitivity reactions, all patients should receive premedication (corticosteroids, histamine H₁– and H₂-receptor blockers).

During treatment, systematic monitoring of the peripheral blood count, blood pressure, and ECG is necessary. The next infusion of paclitaxel should not be administered until the neutrophil count exceeds 1500/µL and the platelet count exceeds 100,000/µL.

Vaccination of patients and their family members is not recommended.

When preparing and administering the paclitaxel solution, infusion systems made of PVC should not be used.

In experimental studies, it has been established that Paclitaxel has a mutagenic effect.

Drug Interactions

Laboratory studies in patients receiving sequential infusions of paclitaxel and cisplatin revealed a more pronounced myelotoxic effect when paclitaxel was administered after cisplatin; in this case, the mean values of the total clearance of paclitaxel decreased by approximately 20%.

Prior administration of cimetidine does not affect the mean values of the total clearance of paclitaxel.

Based on data obtained in vivo and in vitro, it can be assumed that patients receiving ketoconazole experience suppression of paclitaxel metabolism.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°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.