paclitaxel protein-bound

Action and Spectrum

Actions and Spectrum: 

• paclitaxel protein-bound (also known as nab-paclitaxel) is a chemotherapy drug used to treat several types of cancer, including breast cancer, non-small cell lung cancer, and pancreatic cancer. 
• The mechanism of action of paclitaxel protein-bound is like that of paclitaxel. It binds to microtubules, structures within cells that help them divide and grow. By binding to microtubules, paclitaxel protein-bound disrupts the normal process of cell division, ultimately leading to the death of cancer cells. 
• However, unlike traditional paclitaxel, paclitaxel protein-bound is formulated with albumin protein, which allows it to be more easily absorbed by cancer cells. This means that paclitaxel protein-bound can be given at a higher dose and with less frequent dosing than traditional paclitaxel while maintaining its effectiveness. 
• The spectrum of activity of paclitaxel protein-bound is broad, as it is used to treat several types of cancer. It effectively treats metastatic breast cancer, non-small cell lung cancer, and pancreatic cancer, among others. However, its use is generally limited to cases where other treatments have failed or are inappropriate. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Neutropenia (<2 x 10^9/L) (80%) 

Abnormal EKG, all patients (60%) 

Myalgia/arthralgia (44%) 

Abnormal EKG, patients normal at baseline (35%) 

Diarrhea (27%) 

Vomiting (18%) 

Dyspnea (12%) 

Alopecia (90%) 

Sensory neuropathy, any (71%) 

Asthenia (47%) 

Alkaline phosphatase increased (36%) 

AST increased (39%) 

Nausea (30%) 

Infections (24%) 

Anemia (<11 g/dL) (33%)  

Neutropenia (grade 3-4) 

Pancreatic cancer (38%) 

NSCLC (47%) 

Metastatic breast cancer (34%) 

1-10% 

Edema (10%) 

Cough (7%) 

Bilirubin increased (7%) 

Hypersensitivity reactions (4%) 

Febrile neutropenia (2%) 

Bleeding (2%) 

Anemia (<8 g/dL) (1%) 

Sensory neuropathy, severe (10%) 

Neutropenia (<0.5 x 10^9/L) (9%) 

Mucositis (7%) 

Hypotension during infusion (5%) 

Thrombocytopenia (2%) 

Post-marketing reports 

Congestive heart failure 

Atrioventricular block 

Reduced visual acuity due to cystoid macular edema 

Intestinal perforation 

Ischemic colitis 

Tumor lysis syndrome 

Pulmonary embolism 

Left ventricular dysfunction 

Persistent optic nerve damage 

Intestinal obstruction 

Pancreatitis 

Neutropenic enterocolitis (typhlitis) 

Interstitial pneumonia 

Lung fibrosis 

Black Box Warning

Black box warning: 

Patients with initial neutrophil numbers below 1,500 cells/mm should not receive treatment. 

Neutropenia, which may be severe and lead to infection or sepsis, should be monitored closely. 

Frequently check the whole blood levels of all people taking this medicine. 

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

• Hypersensitivity: Patients with a severe allergic reaction to paclitaxel protein-bound or other drugs containing paclitaxel should not receive this medication. 
• Neutrophil count: Patients with low neutrophil counts (less than 1500 cells/mm3) should not receive paclitaxel protein-bound, as it can further decrease their white blood cell count and increase the risk of infections. 
• Hepatic impairment: Patients with severe liver dysfunction should not receive paclitaxel protein-bound, as it can further damage the liver and lead to liver failure. 
• Pregnancy and breast-feeding: paclitaxel protein-bound can harm a developing fetus, and its use is not recommended during pregnancy or while breast-feeding. 
• Heart disease: Patients with a history of heart diseases, such as heart failure or arrhythmia, should use paclitaxel protein-bound with caution, as it can cause cardiac toxicity and worsen these conditions. 
• Infection: Patients with active infections should receive paclitaxel protein-bound once the infection has been treated and resolved. 

Caution: 

• Neurotoxicity: paclitaxel protein-bound can cause peripheral neuropathy, which is nerve damage that causes tingling, numbness, and pain in the hands and feet. Patients should be monitored for signs of neuropathy, and the dose may need to be adjusted if symptoms become severe. 
• Myelosuppression: paclitaxel protein-bound can cause myelosuppression, which decreases blood cell production. This can lead to anemia, thrombocytopenia, and neutropenia. Patients should monitor their blood counts regularly during treatment; the dose may need to be adjusted if blood counts become too low. 
• Hypersensitivity reactions: While rare, some patients may develop hypersensitivity reactions to paclitaxel protein-bound, ranging from mild to severe. Patients should be monitored closely during the first few doses, and appropriate precautions should be taken to manage any possible allergic reactions. 
• Infections: Patients taking paclitaxel protein-bound may have an increased risk of infections due to myelosuppression. Patients should be advised to avoid crowds and individuals who are sick and to report any signs of infection to their healthcare provider. 
• Hepatic dysfunction: Patients with mild to moderate liver dysfunction should use paclitaxel protein-bound cautiously, as it can further damage the liver. Liver function should be monitored regularly during treatment. 
• Renal dysfunction: Patients with renal dysfunction may experience an increased risk of side effects from paclitaxel protein-bound, and the dose may need to be adjusted accordingly. Renal function should be monitored regularly during treatment. 

Pregnancy / Lactation

Pregnancy consideration: paclitaxel protein-bound can harm a developing fetus, and its use is not recommended during pregnancy 

Lactation: Excretion of the drug in human breast milk is unknown 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester.   

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

paclitaxel protein-bound, also known as nab-paclitaxel, is a chemotherapy drug used to treat various types of cancer, including breast, lung, and pancreatic cancer. It works by inhibiting the growth of cancer cells by preventing them from dividing and multiplying.  

The protein-bound form of paclitaxel is created by combining the drug with a protein called albumin. This protein helps deliver the drug more effectively to cancer cells, as it binds to a protein called SPARC (secreted protein acidic and rich in cysteine) in many cancer cells. This targeted delivery allows a higher drug concentration to reach the tumor while minimizing its exposure to healthy tissue.  

Once inside the cancer cell, paclitaxel protein-bound works by binding to a protein called tubulin, which forms the cell’s internal structure, called the cytoskeleton. By binding to tubulin, paclitaxel protein-bound prevents the cell from dividing and multiplying, ultimately leading to the cancer cell’s death. 

Pharmacodynamics: 

The pharmacodynamics of paclitaxel protein-bound involves interacting with the target protein tubulin, which forms the cell’s cytoskeleton. Paclitaxel protein-bound binds to tubulin and promotes the formation of stable microtubules, which are essential for cell division.  

The drug prevents the depolymerization of microtubules by binding to and stabilizing them, which leads to the arrest of the cell cycle at the G2/M phase. This results in the inhibition of cell division and leads to the death of cancer cells.  

paclitaxel protein-bound also affects the immune system. It has been shown to stimulate dendritic cells, essential cells in the immune system that present antigens to T cells, activating the immune response against cancer cells.  

The protein-bound formulation of paclitaxel has been designed to enhance its solubility and uptake by cancer cells, leading to higher concentrations of the drug in the tumor. This results in a more effective and targeted cancer treatment while reducing the side effects associated with the drug. 

Pharmacokinetics: 

Absorption 

paclitaxel protein-bound is administered intravenously, and its absorption is immediate after infusion.  

Distribution 

paclitaxel protein-bound is highly protein-bound, with 89-98% of the drug bound to plasma proteins. The volume of distribution of paclitaxel protein-bound is 632 L/m², indicating extensive tissue distribution.  

Metabolism 

The liver primarily metabolizes paclitaxel protein-bound through the CYP2C8 and CYP3A4 enzymes. The major metabolite is 6-alpha hydroxy paclitaxel, while two minor metabolites are 3’-p-hydroxypaclitaxel and 6-alpha, 3’-p-dihydroxypaclitaxel.  

Elimination and Excretion 

The elimination half-life of paclitaxel protein-bound is 27 hours, and its total body clearance is 15 L/hr/m². paclitaxel protein-bound is excreted mainly in the feces (20%) and, to a lesser extent, in the urine (4%) as an unchanged drug. 

Adminstartion

Administration: 

• paclitaxel protein-bound is administered as an intravenous infusion. The recommended dose and schedule may vary depending on the type of cancer being treated, the patient’s medical history, and other factors. A trained healthcare professional should give the infusion in a clinical setting. 
• The infusion is usually given over 30 minutes, and patients are monitored closely for adverse reactions during and after the infusion. The frequency and duration of treatment may also depend on the patient’s response to the treatment and any side effects experienced. 
• Before administering paclitaxel protein-bound, healthcare professionals should ensure that patients do not have any contraindications or pre-existing conditions that may make the drug unsafe or increase the risk of adverse reactions. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: paclitaxel protein-bound 

Why do we use paclitaxel protein-bound? 

paclitaxel protein-bound is used in the treatment of various types of cancer, including: 

• Breast cancer: paclitaxel protein-bound is used to treat metastatic breast cancer in patients who have not responded to other treatments. 
• Non-Small Cell Lung Cancer (NSCLC): paclitaxel protein-bound is combined with carboplatin to treat locally advanced or metastatic NSCLC. 
• Pancreatic cancer: paclitaxel protein-bound is used in combination with gemcitabine for the treatment of metastatic pancreatic cancer. 
• Ovarian cancer: paclitaxel protein-bound treats advanced ovarian cancer after failed initial chemotherapy. 
• Gastric cancer: paclitaxel protein-bound is combined with ramucirumab to treat advanced gastric or gastroesophageal junction adenocarcinoma.