DAXOTEL INJECTION

Indications

• Breast cancer
• Non-small cell lung cancer
• Prostate cancer
• Ovarian cancer

Dosage

Children: Not established; refer to specialist guidelines for paediatric use.

Adults: Dacetaxel dosing varies based on the specific cancer type and treatment regimen; consult relevant clinical guidelines for appropriate dosing.

Mechanism of action

Dacetaxel works by binding to the beta subunit of tubulin, leading to the stabilization of microtubules and preventing their depolymerization. This results in the inhibition of mitotic spindle formation, effectively blocking cell division and triggering apoptosis in rapidly dividing cancer cells.

Pharmacodynamics

The pharmacodynamics of dacetaxel involve its interaction with the cell cycle, specifically the M phase, where it exerts its cytotoxic effects. The drug is known to be more effective against tumors that have a high growth fraction, as these cells are more sensitive to microtubule disruption. Dacetaxel may also induce changes in gene expression related to apoptosis and cell survival pathways, enhancing its anticancer effects.

Pharmacokinetics

Dacetaxel exhibits variable pharmacokinetics, with absorption occurring primarily through intravenous administration. The drug is extensively metabolized in the liver, primarily by cytochrome P450 enzymes. It has a relatively long half-life, allowing for prolonged exposure to cancer cells. Renal excretion is a minor pathway for elimination, with most of the drug being excreted as metabolites.

Contra-indications

• Hypersensitivity to dacetaxel or any component of the formulation
• Severe liver impairment
• Pregnancy

Adverse effects

• Nausea and vomiting
• Diarrhea
• Fatigue
• Neutropenia
• Peripheral neuropathy
• Alopecia
• Mucositis
• Hypersensitivity reactions

Interactions

• CYP3A4 inhibitors may increase dacetaxel levels, leading to increased toxicity
• CYP3A4 inducers may decrease dacetaxel levels, reducing efficacy
• Concomitant use with other myelosuppressive agents may increase the risk of neutropenia

Precautions

• Monitor blood counts regularly due to the risk of myelosuppression
• Caution in patients with hepatic impairment, as dose adjustment may be necessary
• Avoid use in patients with active infections or severe dehydration

Pregnancy

Dacetaxel is contraindicated in pregnancy due to potential harm to the fetus.

Breast-feeding

It is not known if dacetaxel is excreted in human milk. Caution is advised.

Storage

Store at 2 to 8 degrees Celsius. Protect from light and keep out of reach of children.

Formulations

• Injection solution for intravenous use