Paclitaxel

Paclitaxel is an antineoplastic agent belonging to the pharmacological class of taxanes or microtubule damaging agents.

It is a taxane derivative, derived initially from the Pacific yew tree, Taxus brevifolia, and currently obtained semisynthetically from the needles of European yew, Taxus baccata.

Paclitaxel is FDA-approved for the treatment of various cancers, including breast cancer, ovarian cancer, lung cancer, and Kaposi's sarcoma.

Paclitaxel swiftly enters circulation post-parenteral administration and widely distributes across tissues and fluids, including breast milk. With minimal urinary elimination, liver enzymes create metabolites like 6α-hydroxy Paclitaxel, mainly excreted via faeces.

The most common side effects of Paclitaxel include nausea, vomiting, and weakness.

Paclitaxel is available as an injectable solution.

The molecule is available in India, the United States, Canada, countries within the European Union, Australia, Japan and South Korea.

Paclitaxel is an antineoplastic agent belonging to the pharmacological class of taxanes or microtubule damaging agents.

Paclitaxel disrupts microtubule growth's regular process. In contrast to colchicine, which depolymerizes microtubules in vivo, Paclitaxel hyper-stabilizes microtubule structure instead of depolymerizing it. This eliminates the cell's capacity to make flexible use of its cytoskeleton. Paclitaxel specifically binds to tubulin's β subunit. Microtubules' "building block" is tubulin, and Paclitaxel binding secures these building blocks. The resulting microtubule/paclitaxel complex cannot disassemble. Because microtubules' role as the cell's transportation network depends on their ability to shorten and lengthen (a process known as dynamic instability), this harms cell function. During mitosis, for instance, chromosomes depend on this microtubule characteristic. According to additional research, Paclitaxel causes cancer cells to undergo programmed cell death, or apoptosis, by attaching to and inhibiting the activity of the apoptosis-inducing protein Bcl-2 (B-cell leukaemia 2).

Paclitaxel is available as an injectable solution.

Injectable solution: To be administered by healthcare professionals through intravenous infusion after appropriate dilution.

Parenterally: Paclitaxel is administered parenterally intravenously through a diluted infusion, following specific instructions. The duration, typically lasting one to several hours, depends on the prescribed dose and the patient's tolerance. Use sterile equipment to minimize infection risks during administration. Monitor the Paclitaxel infusion closely to manage potential adverse reactions promptly. Ensure strict adherence to the specified infusion rate to reduce the risk of adverse effects, maintaining intravenous injection as the preferred route of administration.

The dosage and duration of treatment should be as per the treating physician's clinical judgment.

Paclitaxel is available as an injectable solution.

Previous failure to receive treatment: 175 mg/m² IV over three hours every three weeks (cisplatin to follow), OR

IV 135 mg/m² every three weeks for twenty-four hours (followed by cisplatin)

Previously treated: There are several regimens available: every three weeks at a dose of 135–175 mg/m² IV.

Adjuvant chemotherapy for breast cancer node-positive patients: 175 mg/m² IV over three hours every three weeks for four weeks (using a regimen that includes doxorubicin).

The recommended dose for metastatic disease (175 mg/m² IV over 3 hours q3 weeks) is as follows: failure of the initial chemotherapy or relapse within six months after adjuvant chemotherapy.

IV 135 mg/m² every three weeks for twenty-four hours (followed by cisplatin)

Second-line treatment for AIDS-related Kaposi's sarcoma

every three weeks at a dose of 135 mg/m² IV; OR

Q2Weeks, 100 mg/m² IV over 3 hours

Gemcitabine 125 mg/m² IV is being investigated for pancreatic cancer (off-label).

While taking Paclitaxel, follow dietary restrictions for optimal safety. Consume leafy vegetables, citrus fruits, fatty fish, berries, yoghurt, apples, peaches, cauliflower, cabbage, broccoli, beans, herbs, and spices. Avoid fast food, fried food, processed meats, refined carbs, and added sugar to optimize your diet's effectiveness.

The dietary restriction should be individualized as per patient requirements.

It is unsafe to consume paclitaxel with alcohol.

The adverse reactions related to Paclitaxel can be categorized as:

The clinically relevant drug interactions of Paclitaxel are briefly summarized here.

The common side effects of Paclitaxel include:

Pregnancy Category D (FDA): Use in situations where there is no safer medication available and life is in danger. Evidence that human fetal risk exists.

When given to a pregnant woman, Paclitaxel may harm the fetus due to its mode of action and research on animals. There is no human data on the use of Paclitaxel in pregnancy that can be used to determine the risk associated with the drug.

When administered as albumin-bound particles to pregnant rats during the organogenesis phase in animal reproduction studies, Paclitaxel caused embryo-fetal toxicity at doses roughly 2% of the recommended maximum daily human dose on a mg/m2 basis. Inform women who are capable of bearing children about the possible harm to an unborn child.

Data regarding the presence of Paclitaxel in human milk, its impact on the child being breastfed, or its effect on milk production are lacking. In animal studies, Paclitaxel and/or its metabolites were excreted into lactating rats' milk (see Data). It is advised that nursing women refrain from breastfeeding while taking Paclitaxel and for two weeks following the last dose due to the possibility of severe adverse reactions in a breastfed child.

Rats were given radiolabeled Paclitaxel intravenously on days 9 and 10 postpartum. The radioactivity levels in the milk were higher than those in the plasma, and they decreased concurrently with the plasma levels.

As per FDA, the safety and efficacy of Paclitaxel in Pediatric patients have not been established.

Paclitaxel use in older people requires careful monitoring because of age-related vulnerabilities. Appropriate dosage adjustments and assessments are necessary to manage potential risks and ensure that Paclitaxel is suitable for treating specific cancers in older adults.

Renal impairment: No dosage adjustment is required

Mild hepatic impairment (total bilirubin > ULN and ≤ 1.5 x ULN and aspartate aminotransferase [AST] ≤ 10 x ULN) do not need to have their starting paclitaxel dose adjusted.

Lower the initial dosage of Paclitaxel in individuals with moderate to severe liver impairment. Patients with total bilirubin > 5 x ULN or AST > 10 x ULN should not use Paclitaxel.

Patients with moderate to severe hepatic impairment who have metastatic pancreatic adenocarcinoma are not advised to use Paclitaxel.

The physician should be vigilant about the knowledge pertaining to the identification and treatment of overdosage of Paclitaxel.

Overconsumption of Paclitaxel could lead to marrow suppression, sensory neurotoxicity, and mucositis.

There is no specific antidote or treatment for overdosage of Paclitaxel, so treatment typically involves symptomatic and supportive measures, closely monitoring vital signs, frequent assessment of blood counts, and appropriate management of potential complications such as infections or myelosuppression. Consideration of dose reduction or discontinuation might be necessary based on the severity of symptoms. Hemodialysis is not practical due to the high degree of Paclitaxel protein binding. Administering granulocyte colony-stimulating factor (G-CSF) may help with neutropenia. Timely medical intervention plays a crucial role in managing Paclitaxel overdose, ensuring careful monitoring and proper care to address symptoms and prevent complications.

As first-line and subsequent therapy for advanced ovarian carcinoma and other cancers, including breast cancer, Paclitaxel is a taxoid antineoplastic agent. With its ability to prevent depolymerization and promote the formation of microtubules from tubulin dimers, Paclitaxel is a potent antimicrotubule agent. The microtubule network's normal dynamic reorganization, which is necessary for critical interphase and mitotic cellular functions, is inhibited due to this stability. Additionally, Paclitaxel causes aberrant microtubule arrays or "bundles" and multiple microtubule asters throughout the cell cycle during mitosis.