Paclikal^® (Lyophilisate) 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 depolymerization process 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.

Furthermore, 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 metabolized primarily 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-based drugs), breast cancer, lung cancer, esophageal cancer, head and neck cancer, bladder cancer.

ICD codes

Dosage Regimen

Determine the dosage individually based on the specific malignancy, disease stage, and the chosen chemotherapy regimen.

Administer the reconstituted solution as an intravenous infusion over 3 hours. Do not administer as a bolus intravenous injection or undiluted solution.

Premedicate all patients approximately 30-60 minutes prior to the paclitaxel infusion to prevent severe hypersensitivity reactions. The standard premedication regimen includes a corticosteroid (e.g., dexamethasone), and H1 and H2 receptor antagonists.

For ovarian cancer, a common dose is 175 mg/m² administered over 3 hours every 3 weeks. For breast cancer, a dose of 175 mg/m² over 3 hours every 3 weeks is also frequently used.

Adjust the dose for patients with hepatic impairment. For patients with moderate to severe hepatic impairment, significantly reduce the dose.

Monitor the complete blood count (CBC) frequently. Do not administer a subsequent cycle until the neutrophil count recovers to at least 1,500 cells/mm³ and the platelet count recovers to at least 100,000 cells/mm³.

In cases of severe neutropenia (neutrophils < 500 cells/mm³ for a week or longer) or severe peripheral neuropathy, reduce the dose for subsequent courses of therapy by 20%.

Use only non-PVC infusion sets and containers (e.g., glass, polypropylene, or polyolefin) for preparation and administration. Filter the solution through a 0.22-micron in-line filter during infusion.

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/mcL), pregnancy, hypersensitivity to paclitaxel.

Use in Pregnancy and Lactation

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

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

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 a 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/mcL and the platelet count exceeds 100,000/mcL.

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 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.