Epitaxol
Epitaxol - General Information
A cyclodecane isolated from the bark of the Pacific yew tree, TAXUS brevifolia. It stabilizes microtubules in their polymerized form leading to cell death. [PubChem]
Pharmacology of Epitaxol
Epitaxol is a taxoid antineoplastic agent indicated as first-line and subsequent therapy for the treatment of advanced carcinoma of the ovary, and other various cancers including breast cancer. Epitaxol is a novel antimicrotubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. In addition, paclitaxel induces abnormal arrays or "bundles" of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis.
Epitaxol for patients
TAXOL INJECTION
(generic name = paclitaxel)
WHAT IS TAXOL?
TAXOL is a prescription cancer medicine. It is injected into a vein and it is used to treat different types of tumors. The tumors include advanced ovary and breast cancer. The tumors also include certain lung cancers (non-small cell) in people who cannot have surgery or radiation therapy. TAXOL may also be used to treat AIDS-related Kaposi’s sarcoma.
WHAT IS CANCER?
Under normal conditions, the cells in your body divide and grow in an orderly, controlled way. Cell division and growth are necessary for the human body to perform its functions and to repair itself, when necessary. Cancer cells are different from normal cells because they are not able to control their own growth. The reasons for this abnormal growth are not yet fully understood.
A tumor is a mass of unhealthy cells that are dividing and growing fast and in an uncontrolled way. When a tumor invades surrounding healthy body tissue it is known as a malignant tumor. A malignant tumor can spread (metastasize) from its original site to other parts of the body if not found and treated early.
HOW DOES TAXOL WORK?
TAXOL is a type of medical treatment called chemotherapy. The purpose of chemotherapy is to kill cancer cells or prevent their growth.
All cells, whether they are healthy cells or cancer cells, go through several stages of growth. During one of the stages, the cell starts to divide. TAXOL may stop the cells from dividing and growing, so they eventually die. In addition, normal cells may also be affected by TAXOL causing some of the side effects.
WHO SHOULD NOT TAKE TAXOL?
Patients who have a history of hypersensitivity (allergic reactions) to TAXOL or other drugs containing Cremophor EL* (polyoxyethylated castor oil), like cyclosporine or teniposide, should not be given TAXOL. In addition, TAXOL should not be given to patients with dangerously low white blood cell counts.
HOW IS TAXOL (PACLITAXEL) INJECTION GIVEN?
TAXOL is injected into a vein [intravenous (I.V.) infusion]. Before you are given TAXOL, you will have to take certain medicines (premedications) to prevent or reduce the chance you will have a serious allergic reaction. Such reactions have occurred in a small number of patients while receiving TAXOL and have been rarely fatal..
WHAT ARE THE POSSIBLE SIDE EFFECTS OF TAXOL?
Most patients taking TAXOL will experience side effects, although it is not always possible to tell whether such effects are caused by TAXOL, another medicine they may be taking, or the cancer itself. Important side effects are described below; however, some patients may experience other side effects that are less common. Report any unusual symptoms to your doctor.
Important side effects observed in studies of patients taking TAXOL were as follows:
– Allergic reactions. Allergic reactions can vary in degrees of severity. They may cause death in rare cases. When a severe allergic reaction develops, it usually occurs at the time the medicine is entering the body (during TAXOL infusion). Allergic reactions may cause trouble breathing, very low blood pressure, sudden swelling, and/or hives or rash. The likelihood of a serious allergic reaction is lowered by the use of several kinds of medicines that are given to you before the TAXOL (paclitaxel) Injection infusion.
– Heart and blood vessel (cardiovascular) effects. TAXOL may cause a drop in heart rate (bradycardia) and low blood pressure (hypotension). The patient usually does not notice these changes. These changes usually do not require treatment. Your heart function, including blood pressure and pulse, will be monitored while you are receiving the medicine. You should notify your doctor if you have a history of heart disease.
– Infections due to low white blood cell count. Among the body’s defenses against bacterial infections are white blood cells. Between your TAXOL treatment cycles, you will often have blood tests to check your white blood cell counts. TAXOL usually causes a brief drop in white blood cells. If you have a fever (temperature above 100.4° F) or other sign of infection, tell your doctor right away. Sometimes serious infections develop that require treatment in the hospital with antibiotics. Serious illness or death could result if such infections are not treated when white blood cell counts are low.
– Hair loss. Complete hair loss, or alopecia, almost always occurs with TAXOL. This usually involves the loss of eyebrows, eyelashes, and pubic hair, as well as scalp hair. It can occur suddenly after treatment has begun, but usually happens 14 to 21 days after treatment. Hair generally grows back after you’ve finished your TAXOL treatment.
– Joint and muscle pain. You may get joint and muscle pain a few days after your TAXOL treatment. These symptoms usually disappear in a few days. Although pain medicine may not be necessary, tell your doctor if you are uncomfortable.
– Irritation at the injection site. TAXOL sometimes causes irritation at the site where it enters the vein. Reactions may include discomfort, redness, swelling, inflammation (of the surrounding skin or of the vein itself), and ulceration (open sores). These reactions are usually caused by the I.V. (intravenous) fluid leaking into the surrounding area. If you notice anything unusual at the site of the injection (needle), either during or after treatment, tell your doctor right away.
– Low red blood cell count. Red blood cells deliver oxygen to tissues throughout all parts of the body and take carbon dioxide from the tissues by using a protein called hemoglobin. A lowering of the volume of red blood cells may occur following TAXOL treatment causing anemia. Some patients may need a blood transfusion to treat the anemia. Patients can feel tired, tire easily, appear pale, and become short of breath. Contact your doctor if you experience any of these symptoms following TAXOL treatment.
– Mouth or lip sores (mucositis). Some patients develop redness and/or sores in the mouth or on the lips. These symptoms might occur a few days after the TAXOL treatment and usually decrease or disappear within one week. Talk with your doctor about proper mouth care and other ways to prevent or reduce your chances of developing mucositis.
– Numbness, tingling, or burning in the hands and/or feet (neuropathy).
These symptoms occur often with TAXOL and usually get better or go away without medication within several months of completing treatment. However, if you are uncomfortable, tell your doctor so that he/she can decide the best approach for relief of your symptoms.
– Stomach upset and diarrhea. Some patients experience nausea, vomiting, and/or diarrhea following TAXOL use. If you experience nausea or stomach upset, tell your doctor. Diarrhea will usually disappear without treatment; however, if you experience severe abdominal or stomach area pain and/or severe diarrhea, tell your doctor right away.
Talk with your doctor or other healthcare professional to discuss ways to prevent or reduce some of these side effects. Because this leaflet does not include all possible side effects that can occur with TAXOL, it is important to talk with your doctor about other possible side effects.
CAN I TAKE TAXOL IF I AM PREGNANT OR NURSING A BABY?
TAXOLcould harm the fetus when given to a pregnant woman. Women should avoid becoming pregnant while they are undergoing treatment with TAXOL.
Tell your doctor if you become pregnant or plan to become pregnant while taking TAXOL.
Because studies have shown TAXOL to be present in the breast milk of animals receiving the drug, it may be present in human breast milk as well. Therefore, nursing a baby while taking TAXOL is NOT recommended.
This medicine was prescribed for your particular condition. This summary does not include everything there is to know about TAXOL. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information Leaflet. If you have questions or concerns, or want more information about TAXOL, your doctor and pharmacist have the complete prescribing information upon which this guide is based. You may want to read it and discuss it with your doctor. Remember, no written summary can replace careful discussion with your doctor.
* Cremophor EL is the registered trademark of BASF Aktiengesellschaft., Cremophor EL is further purified by a Bristol-Myers Squibb Company proprietary process before use.
This Patient Information Leaflet has been approved by the U.S. Food and Drug Administration. 1109663B1, 347630DIM-16 K4-B001-04-03 Based on package insert dated March 2003
Epitaxol Interactions
In a Phase I trial using escalating doses of TAXOL (110-200 mg/m2) and cisplatin (50 or 75 mg/m2) given as sequential infusions, myelosuppression was more profound when TAXOL was given after cisplatin than with the alternate sequence (ie, TAXOL before cisplatin). Pharmacokinetic data from these patients demonstrated a decrease in paclitaxel clearance of approximately 33% when TAXOL was administered following cisplatin.
The metabolism of TAXOL is catalyzed by cytochrome P450 isoen-zymes CYP2C8 and CYP3A4. In the absence of formal clinical drug interaction studies, caution should be exercised when administering TAXOL concomitantly with known substrates or inhibitors of the cytochrome P450 isoenzymes CYP2C8 and CYP3A4.
Potential interactions between TAXOL, a substrate of CYP3A4, and protease inhibitors (ritonavir, saquinavir, indinavir, and nelfinavir), which are substrates and/or inhibitors of CYP3A4, have not been evaluated in clinical trials.
Reports in the literature suggest that plasma levels of doxorubicin (and its active metabolite doxorubicinol) may be increased when paclitaxel and doxorubicin are used in combination.
Hematology: TAXOL therapy should not be administered to patients with baseline neutrophil counts of less than 1,500 cells/mm3. In order to monitor the occurrence of myelotoxicity, it is recommended that frequent peripheral blood cell counts be performed on all patients receiving TAXOL. Patients should not be re-treated with subsequent cycles of TAXOL until neutrophils recover to a level >1500 cells/mm3 and platelets recover to a level >100,000 cells/mm3. In the case of severe neutropenia (<500 cells/mm3 for seven days or more) during a course of TAXOL therapy, a 20% reduction in dose for subsequent courses of therapy is recommended.
For patients with advanced HIV disease and poor-risk AIDS-related Kaposi’s sarcoma, TAXOL, at the recommended dose for this disease, can be initiated and repeated if the neutrophil count is at least 1000 cells/mm3.
Hypersensitivity Reactions: Patients with a history of severe hypersensitivity reactions to products containing Cremophor EL (eg, cyclosporin for injection concentrate and teniposide for injection concentrate) should not be treated with TAXOL. In order to avoid the occurrence of severe hypersensitivity reactions, all patients treated with TAXOL should be premedicated with corticosteroids (such as dexamethasone), diphen-hydramine and H2 antagonists (such as cimetidine or ranitidine). Minor symptoms such as flushing, skin reactions, dyspnea, hypotension, or tachycardia do not require interruption of therapy. However, severe reactions, such as hypotension requiring treatment, dyspnea requiring bronchodilators, angioedema, or generalized urticaria require immediate discontinuation of TAXOL and aggressive symptomatic therapy. Patients who have developed severe hypersensitivity reactions should not be rechallenged with TAXOL.
Cardiovascular: Hypotension, bradycardia, and hypertension have been observed during administration of TAXOL, but generally do not require treatment. Occasionally TAXOL infusions must be interrupted or discontinued because of initial or recurrent hypertension. Frequent vital sign monitoring, particularly during the first hour of TAXOL infusion, is recommended. Continuous cardiac monitoring is not required except for patients with serious conduction abnormalities.
Nervous System: Although the occurrence of peripheral neuropathy is frequent, the development of severe symptomatology is unusual and requires a dose reduction of 20% for all subsequentcourses of TAXOL.
TAXOL contains dehydrated alcohol USP, 396 mg/mL; consideration should be given to possible CNS and other effects of alcohol.
Hepatic: There is limited evidence that the myelotoxicity of TAXOL may be exacerbated in patients with serum total bilirubin >2 times ULN. Extreme caution should be exercised when administering TAXOL to such patients, with dose reduction as recommended in DOSAGE AND ADMINISTRATION, Table 17.
InjectionSite Reaction: Injection site reactions, including reactions secondary to extravasation, were usually mild and consisted of erythema, tenderness, skin discoloration, or swelling at the injection site. These reactions have been observed more frequently with the 24-hour infusion than with the 3-hour infusion. Recurrence of skin reactions at a site of previous extravasation following administration of TAXOL at a different site, ie, "recall", has been reported rarely.
Rare reports of more severe events such as phlebitis, cellulitis, induration, skin exfoliation, necrosis, and fibrosis have been received as part of the continuing surveillance of TAXOL safety. In some cases the onset of the injection site reaction either occurred during a prolonged infusion or was delayed by a week to ten days.
A specific treatment for extravasation reactions is unknown at this time. Given the possibility of extravasation, it is advisable to closely monitor the infusion site for possible infiltration during drug administration.
Epitaxol Contraindications
TAXOL is contraindicated in patients who have a history of hypersensitivity reactions to TAXOL or other drugs formulated in Cremophor EL (polyoxyethylated castor oil).
TAXOL should not be used in patients with solid tumors who have baseline neutrophil counts of <1500 cells/mm3 or in patients with AIDS-related Kaposi’s sarcoma with baseline neutrophil counts of <1000 cells/mm3.
Additional information about Epitaxol
Epitaxol Indication: Used in the treatment of Kaposi's sarcoma and cancer of the lung, ovarian, and breast.
Mechanism Of Action: Epitaxol interferes with the normal function of microtubule growth. Whereas drugs like colchicine cause the depolymerization of microtubules in vivo, paclitaxel arrests their function by having the opposite effect; it hyper-stabilizes their structure. This destroys the cell's ability to use its cytoskeleton in a flexible manner. Specifically, paclitaxel binds to the β subunit of tubulin. Tubulin is the "building block" of mictotubules, and the binding of paclitaxel locks these building blocks in place. The resulting microtubule/paclitaxel complex does not have the ability to disassemble. This adversely affects cell function because the shortening and lengthening of microtubules (termed dynamic instability) is necessary for their function as a transportation highway for the cell. Chromosomes, for example, rely upon this property of microtubules during mitosis. Further research has indicated that paclitaxel induces programmed cell death (apoptosis) in cancer cells by binding to an apoptosis stopping protein called Bcl-2 (B-cell leukemia 2) and thus arresting its function.
Drug Interactions: Aprepitant Aprepitant may change levels of chemotherapy agent
Cisplatin Cisplatin increases the effect and toxicity of paclitaxel
Gemcitabine Epitaxol increases the effect/toxicity of gemcitabine
Quinupristin This combination presents an increased risk of toxicity
Food Interactions: Not Available
Generic Name: Paclitaxel
Synonyms: 7-epi-Paclitaxel; 7-epi-Taxol; 7-Epipaclitaxel; 7-Epitaxol
Drug Category: Antineoplastic Agents
Drug Type: Small Molecule; Approved; Investigational
Other Brand Names containing Paclitaxel: Epitaxol; LipoPac; Onxol; Paxceed; Paxene; Taxol; Taxol A;
Absorption: I.V injected
Toxicity (Overdose): Rat (ipr) LD50=32530 µg/kg. Symptoms of overdose include bone marrow suppression, peripheral neurotoxicity, and mucositis. Overdoses in pediatric patients may be associated with acute ethanol toxicity.
Protein Binding: 89%-98%
Biotransformation: Hepatic. In vitro studies with human liver microsomes and tissue slices showed that paclitaxel was metabolized primarily to 6a-hydrox-ypaclitaxel by the cytochrome P450 isozyme CYP2C8; and to two minor metabolites, 3’-p-hydroxypaclitaxel and 6a, 3’-p-dihydroxypaclitaxel, by CYP3A4.
Half Life: Average distribution half-life of 0.34 hours and an average elimination half-life of 5.8 hours.
Dosage Forms of Epitaxol: Solution Intravenous
Powder, for suspension Intravenous
Chemical IUPAC Name: 5 beta,20-Epoxy-1,2a,4,7 beta,10 beta,13 alpha-hexahydroxytax-11-en-9-one 4,10-diacetate 2-benzoate 13-ester with (2 R,3S)-N-benzoyl-3-phenylisoserine
Chemical Formula: C47H51NO14
Paclitaxel on Wikipedia: https://en.wikipedia.org/wiki/Paclitaxel
Organisms Affected: Humans and other mammals
