Paclitaxel

BRAND NAMES:

Taxol – It contains the active ingredients of paclitaxel. It is available in the form of an IV formulation used to treat cancer by stopping cell division.

Abraxane – It contains the active ingredients of paclitaxel. It is available in the form of an IV formulation used to treat various types of cancers.

MECHANISM OF ACTION:

Paclitaxel binds to microtubules' inner surface, near the nucleotide binding site on β-tubulin. This interaction supports the assembly of tubulin subunits into stable non-dynamic microtubules, preventing their typical disintegration or depolymerization.

PHARMACOKINETICS:

Absorption: After administration of paclitaxel, the absorption phase is bypassed through direct administration into the bloodstream. The IV infusion ensures rapid and complete distribution of paclitaxel into the systemic circulation.

Distribution: The volume of distribution of paclitaxel is 182L/m2 

Metabolism: The cytochrome P450 enzyme system, particularly the CYP2C8 and CYP3A4 isoenzymes, metabolizes over 90% of paclitaxel in the liver. The main metabolic process involves hydroxylation of the side chain at the C13 position, resulting in various metabolites such as 6α-hydroxyl paclitaxel and 3'-ρ-hydroxy paclitaxel. These metabolites have less pharmacological activity than the parent medication.

Excretion: Paclitaxel is eliminated through the feces in 120 hours, with 14% recovered in the urine. 

PHARMACODYNAMICS:

Paclitaxel is a new antimicrotubule drug that promotes microtubule formation from tubulin dimers and keeps microtubules stable by inhibiting depolymerization. This stability inhibits the usual dynamic reorganization of the microtubule network, which is required for important interphase and mitotic cellular processes.

DOSAGE AND ADMINISTRATION:

Paclitaxel injection is a liquid that is administered intravenously over three or twenty-four hours by a physician or nurse at a clinic. Paclitaxel is often administered once every week to patients with breast cancer, ovarian cancer, or non-small cell lung cancer. Paclitaxel can be used once every two or three weeks to treat Kaposi's sarcoma. 

It is available as an injectable solution at a concentration of 6mg/mL. 

DRUG INTERACTIONS:

Drug interactions with paclitaxel may include

• Antibiotics – rifampicin, erythromycin
• Anti-fungal – ketoconazole
• Anti-depressant – fluoxetine
• Anti-epileptic – carbamazepine, phenytoin
• Lipid regulating agent – gemfibrozil
• Antacid – cimetidine
• HIV-AIDS – ritonavir, nelfinavir, efavirenz and nevirapine
• Anti-platelet - clopidogrel 

CONTRAINDICATIONS:

Patients with a severe allergic reaction to paclitaxel or any of its excipients should not be given this medication. Paclitaxel dose determines bone marrow suppression, which is a dosing constraint owing to toxicity. Paclitaxel should not be used on individuals with solid tumors if their baseline neutrophil count is less than 1500 cells/mm3. 

SIDE EFFECTS:

Side effects of paclitaxel may include

• Muscle pain
• Pain, swelling, and redness in the place at the site of injection
• Diarrhea
• Nausea
• Hair loss
• Vomiting
• Pale skin
• Shortness of breath
• Excessive tiredness
• Chest pain
• Pale skin 

OVERDOSE:

Symptoms of an overdose of paclitaxel may include

• Numbness, burning, or tingling of the hands and feet
• Pale skin
• Excessive tiredness
• Unusual bleeding
• Shortness of breath
• Sores in the mouth

TOXICITY:

There is no treatment for paclitaxel overdose. Overdosage's principal predicted consequences include bone marrow suppression, peripheral neurotoxicity, and mucositis. It is worth noting that hyaluronidase is frequently used as an antidote to prevent paclitaxel extravasation. Overdose in pediatric patients may cause acute ethanol poisoning.