epothilone D

Action and Spectrum

Actions and spectrum: 

• Action: Epothilone D, like other epothilones, acts by binding to the β-tubulin subunit of microtubules in cells. Microtubules are essential components of the cell’s cytoskeleton, and they play a role in cell division. By stabilizing microtubules, epothilone D prevents their disassembly and inhibits the dynamic reorganization required for cell division. The stabilization of microtubules leads to cell cycle arrest in the G2/M phase, preventing cell division and inducing cell death. 
• Anticancer Activity: Epothilone D is primarily used as an anticancer agent in the treatment of various malignancies. It has shown activity against breast cancer, ovarian cancer, and other solid tumors. 
• Clinical Use: Epothilone D has been investigated in clinical trials for its efficacy and safety in cancer treatment. Its potential use in combination with other chemotherapy agents or as a standalone treatment is being explored. 

Drug Interaction

Adverse Reaction

Frequency not defined 

Visual Hallucination 

Diarrhea 

Dehydration 

Nausea 

Black Box Warning

Black Box Warning: 

there was no specific information available regarding a black box warning for epothilone D. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Hypersensitivity: Epothilone D should not be administered to individuals with a known hypersensitivity or allergy to the drug or its components. 
• Preexisting Neuropathy: The use of epothilone D may be contraindicated in individuals with preexisting severe peripheral neuropathy due to the potential for exacerbation. 
• Pregnancy and Lactation: Epothilone D may have potential risks to the fetus, and its use during pregnancy is contraindicated. Breastfeeding should be avoided during treatment. 
• Severe Hepatic Impairment: Epothilone D may undergo hepatic metabolism, and caution is advised in individuals with severe hepatic impairment. 
• Previous Severe Hypersensitivity to Taxanes: Individuals who have experienced severe hypersensitivity reactions to taxanes may be at an increased risk of similar reactions to epothilone D.

Caution: 

• Peripheral Neuropathy: Epothilone D may be associated with peripheral neuropathy. Caution is advised in individuals with a history of neuropathy, and regular monitoring for neuropathic symptoms is recommended. 
• Hematologic Effects: Epothilone D may have effects on blood cell counts. Caution is needed in individuals with preexisting hematologic conditions, and regular blood tests may be necessary. 
• Immunosuppression: Epothilone D may have immunosuppressive effects. Caution is needed in individuals with compromised immune function. 
• History of Hypersensitivity: Individuals with a history of hypersensitivity reactions to other drugs should be monitored closely for potential allergic reactions.

Comorbidities: 

• Peripheral Neuropathy: Patients with peripheral neuropathy may need careful monitoring, as epothilone D may be associated with neuropathic symptoms. 
• Cardiovascular Disease: Individuals with cardiovascular disease may require close monitoring, as some chemotherapy agents, including epothilone D, may have cardiovascular effects. 
• Hepatic Impairment: Patients with preexisting liver conditions may require dosage adjustment or closer monitoring of liver function. 
• Immunosuppression: Patients with compromised immune function with immunosuppressive conditions or treatments, may need careful monitoring due to potential immunosuppressive effects of chemotherapy. 

Pregnancy / Lactation

Pregnancy consideration: pregnancy category: not assigned 

Lactation: excreted into human milk: 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: 

Epothilone D is a microtubule-stabilizing agent with pharmacological properties that make it effective in the treatment of various cancers. Like taxanes, epothilone D works by binding to the β-tubulin subunit of microtubules, thereby stabilizing these crucial cellular structures. By preventing the disassembly of microtubules, epothilone D disrupts the dynamic processes essential for cell division, leading to the cell cycle arrest.

This interference with mitosis results in the inhibition of cell proliferation and induction of apoptosis. Epothilone D exhibits a broad spectrum of activity against various solid tumors, including breast, ovarian, and non-small cell lung cancers. Importantly, it has shown efficacy in taxane-resistant tumors, providing a potential therapeutic option for patients with limited treatment alternatives.

While its pharmacological profile aligns with other microtubule-stabilizing agents, individual variations in drug response and considerations for specific patient populations should be considered for optimal clinical use.  

Pharmacodynamics: 

• Microtubule Stabilization: Epothilone D binds to the β-tubulin subunit of microtubules in cells, stabilizing these dynamic structures. Microtubules are crucial components of the cell’s cytoskeleton and play a fundamental role in mitosis (cell division). 
• Cell Cycle Arrest: By stabilizing microtubules, epothilone D interferes with the normal dynamics of microtubule assembly and disassembly required for proper cell division. This disruption leads to cell cycle arrest, particularly in the G2/M phase of the cell cycle. 
• Inhibition of Cell Proliferation: The primary pharmacodynamic effect of epothilone D is the inhibition of cancer cell proliferation. By preventing proper cell division, the drug impedes the growth of cancer cells. 
• Apoptosis Induction: Epothilone D-induced cell cycle arrest and disruption of microtubule dynamics contribute to the activation of apoptosis, or programmed cell death. Apoptosis is a natural process that eliminates damaged or aberrant cells. 
• Taxane-Resistant Tumors: Notably, epothilone D has shown effectiveness in tumors resistant to taxanes, providing an alternative treatment option for patients with limited responses to taxane therapy.

Pharmacokinetics: 

• Absorption: Epothilone D is typically administered intravenously (IV), allowing for rapid and complete systemic absorption. The intravenous route ensures a more predictable and controlled delivery of the drug into the bloodstream. 
• Distribution: Epothilone D distributes throughout the body via the bloodstream. It can reach various tissues, including tumor sites, due to its systemic circulation. The drug’s distribution properties influence its access to target tissues and organs. 
• Metabolism: Epothilone D undergoes metabolism, primarily in the liver. The liver’s metabolic processes can transform epothilone D into metabolites, which may contribute to its pharmacological effects and elimination. 
• Excretion: The primary route of excretion for epothilone D and its metabolites is through the bile and feces. Renal excretion (via urine) may also play a role, but it is not the predominant route. 

Adminstartion

Administration: 

• Intravenous Infusion: Epothilone D is usually administered as an intravenous infusion over a specified period. The infusion rate and duration are determined based on the specific treatment protocol and the patient’s individual characteristics. 
• Dosage and Schedule: The dosage and administration schedule of epothilone D are determined by the treating oncologist based on the type of cancer, and the specific treatment plan. The drug may be given as part of a combination chemotherapy regimen or as a standalone treatment. 
• Pre-Medication: Patients may receive pre-medications, such as anti-nausea medications or medications to prevent hypersensitivity reactions, prior to the administration of epothilone D. 
• Hydration: Adequate hydration may be recommended to support kidney function and minimize the risk of certain side effects. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: epothilone D 

Pronounced: (ee-POH-thi-loan dee)  

Why do we use epothilone D? 

Epothilone D is an investigational drug that has shown promise in early clinical studies. Its potential uses are primarily being explored in the field of oncology, particularly in the treatment of various types of cancers. Epothilone D has been investigated for its anticancer activity against various solid tumors, including breast, ovarian, and non-small cell lung cancers.

Notably, epothilone D has demonstrated effectiveness in tumors that are resistant to taxane chemotherapy. This makes it a potential option for patients who have limited responses to taxane treatment. Epothilone D may be explored as part of combination chemotherapy regimens, where it is used in conjunction with other anticancer agents to enhance therapeutic outcomes.