Tevataxel (Lyophilisate) Instructions for Use

Marketing Authorization Holder

Teva Pharmaceutical Industries, Ltd. (Israel)

Manufactured By

Pharmachemie, B.V. (Netherlands)

ATC Code

L01CD01 (Paclitaxel)

Active Substance

Paclitaxel (Rec.INN registered by WHO)

Dosage Form

Tevataxel

Lyophilisate for the preparation of suspension for infusion 100 mg: fl. 1 pc.

Dosage Form, Packaging, and Composition

Lyophilisate for the preparation of a suspension for infusion in the form of a lyophilized mass from white to light yellow in color; the prepared suspension is homogeneous, opaque, from white to light yellow in color.

Excipients: human albumin (in a solution containing sodium, sodium caprylate, and N-acetyl-DL-tryptophan).

Colorless glass vials with a capacity of 50 ml (1) – cardboard boxes^×.

^× protective stickers may be additionally applied.

Clinical-Pharmacological Group

Antineoplastic drug

Pharmacotherapeutic Group

Antineoplastic agents; plant alkaloids and other natural substances; taxanes

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

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

Administer the reconstituted suspension only as an intravenous infusion over 30 minutes. Do not administer as a bolus injection.

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

Premedicate all patients approximately 30-60 minutes prior to the paclitaxel infusion to prevent severe hypersensitivity reactions. Premedication typically includes a corticosteroid (e.g., dexamethasone), and H1 and H2 antagonists (e.g., diphenhydramine and cimetidine/famotidine).

Monitor complete blood counts frequently. Do not administer if the neutrophil count is below 1500 cells/µL or the platelet count is below 100,000 cells/µL.

Substantial dose reduction is required for patients with severe hepatic impairment. For patients with significant liver dysfunction, reduce the dose by 50% or more.

Manage severe peripheral neuropathy by delaying treatment and/or subsequent dose reduction.

Use only non-PVC infusion sets and containers (e.g., glass, polypropylene, polyolefin) for preparation and administration. Filter the reconstituted suspension 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, in case of 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 was found that Paclitaxel has a teratogenic and embryotoxic effect.

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.

It is necessary to establish careful monitoring of the patients’ condition.

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. It is necessary to establish careful monitoring of the patients’ condition.

To prevent the occurrence of hypersensitivity reactions, all patients should receive premedication (glucocorticosteroids, 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 was found that Paclitaxel has a mutagenic effect.

Drug Interactions

During laboratory studies in patients receiving sequential infusions of paclitaxel and cisplatin, a more pronounced myelotoxic effect was detected 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.