Taxotere

Taxotere - General Information

Taxotere is a clinically well established anti-mitotic chemotherapy medication used mainly for the treatment of breast, ovarian, and non-small cell lung cancer. Taxotere binds to microtubules reversibly with high affinity and has a maximum stoichiometry of 1 mole docetaxel per mole tubulin in microtubules.

 

Pharmacology of Taxotere

Taxotere is a taxoid antineoplastic agent. It 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, docetaxel induces abnormal arrays or "bundles" of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis.

 

Taxotere for patients

Questions and Answers About Taxotere® Injection Concentrate

(generic name = docetaxel) (pronounced as TAX-O-TEER)

What is Taxotere?

Taxotere is a medication to treat breast cancer, non-small cell lung cancer and prostate cancer. It has severe side effects in some patients. This leaflet is designed to help you understand how to use Taxotere and avoid its side effects to the fullest extent possible. The more you understand your treatment, the better you will be able to participate in your care. If you have questions or concerns, be sure to ask your doctor or nurse. They are always your best source of information about your condition and treatment.

What is the most important information about Taxotere?

•Since this drug, like many other cancer drugs, affects your blood cells, your doctor will ask for routine blood tests. These will include regular checks of your white blood cell counts. People with low blood counts can develop life-threatening infections. The earliest sign of infection may be fever, so if you experience a fever, tell your doctor right away.

•Occasionally, serious allergic reactions have occurred with this medicine. If you have any allergies, tell your doctor before receiving this medicine.

• A small number of people who take Taxotere have severe fluid retention, which can be life-threatening. To help avoid this problem, you must take another medication such as dexamethasone (DECKS-A-METH-A-SONE) prior to each Taxotere treatment. You must follow the schedule and take the exact dose of dexamethasone prescribed. If you forget to take a dose or do not take it on schedule you must tell the doctor or nurse prior to your Taxotere treatment.

• If you are using any other medicines, tell your doctor before receiving your infusions of Taxotere.

How does Taxotere work?

Taxotere works by attacking cancer cells in your body. Different cancer medications attack cancer cells in different ways.

Here's how Taxotere works: Every cell in your body contains a supporting structure (like a skeleton). Damage to this "skeleton" can stop cell growth or reproduction. Taxotere makes the "skeleton" in some cancer cells very stiff, so that the cells can no longer grow.

How will I receive Taxotere?

Taxotere is given by an infusion directly into your vein. Your treatment will take about 1 hour. Generally, people receive Taxotere every 3 weeks. The amount of Taxotere and the frequency of your infusions will be determined by your doctor.

As part of your treatment, to reduce side effects your doctor will prescribe another medicine called dexamethasone. Your doctor will tell you how and when to take this medicine. It is important that you take the dexamethasone on the schedule set by your doctor. If you forget to take your medication, or do not take it on schedule, make sure to tell your doctor or nurse BEFORE you receive your Taxotere treatment.

Included with this information leaflet is a chart to help you remember when to take your dexamethasone.

What should be avoided while receiving Taxotere?

Taxotere can interact with other medicines. Use only medicines that are prescribed for you by your doctor and be sure to tell your doctor all the medicines that you use, including nonprescription drugs.

What are the possible side effects of Taxotere?

Low Blood Cell Count - Many cancer medications, including Taxotere, cause a temporary drop in the number of white blood cells. These cells help protect your body from infection. Your doctor will routinely check your blood count and tell you if it is too low. Although most people receiving Taxotere do not have an infection even if they have a low white blood cell count, the risk of infection is increased.

Fever is often one of the most common and earliest signs of infection. Your doctor will recommend that you take your temperature frequently, especially during the days after treatment with Taxotere. If you have a fever, tell your doctor or nurse immediately.

Allergic Reactions - This type of reaction, which occurs during the infusion of Taxotere, is infrequent. If you feel a warm sensation, a tightness in your chest, or itching during or shortly after your treatment, tell your doctor or nurse immediately.

Fluid Retention - This means that your body is holding extra water. If this fluid retention is in the chest or around the heart it can be life-threatening. If you notice swelling in the feet and legs or a slight weight gain, this may be the first warning sign. Fluid retention usually does not start immediately; but, if it occurs, it may start around your 5th treatment. Generally, fluid retention will go away within weeks or months after your treatments are completed.

Dexamethasone Since this drug, like many other cancer drugs, affects your blood cells, tablets may protect patients from significant fluid retention. It is important that you take this medicine on schedule. If you have not taken dexamethasone on schedule, you must tell your doctor or nurse before receiving your next Taxotere treatment.

Gastrointestinal - Diarrhea has been associated with TAXOTERE use and can be severe in some patients. Nausea and/or vomiting are common in patients receiving TAXOTERE. Severe inflammation of the bowel can also occur in some patients and may be life threatening.

Hair Loss - Loss of hair occurs in most patients taking Taxotere (including the hair on your head, underarm hair, pubic hair, eyebrows, and eyelashes). Hair loss will begin after the first few treatments and varies from patient to patient. Once you have completed all your treatments, hair generally grows back.

Your doctor or nurse can refer you to a store that carries wigs, hairpieces, and turbans for patients with cancer.

Fatigue - A number of patients (about 10%) receiving Taxotere feel very tired following their treatments. If you feel tired or weak, allow yourself If you are using any other medicines, tell your doctor before receiving extra rest before your next treatment. If it is bothersome or lasts for longer than 1 week, inform your doctor or nurse.

Muscle Pain - This happens about 20% of the time, but is rarely severe. You may feel pain in your muscles or joints. Tell your doctor or nurse if howthis happens. They may suggest ways to make you more comfortable.

Rash- This side effect occurs commonly but is severe in about 5%. You may develop a rash that looks like a blotchy, hive-like reaction. This usually occurs on the hands and feet but may also appear on the arms, face, or body. Generally, it will appear between treatments and will go away before the next treatment. Inform your doctor or nurse if you experience a rash. They can help you avoid discomfort.

Odd Sensations - About half of patients getting Taxotere will feel numbness, tingling, or burning sensations in their hands and feet. If you do experience this, tell your doctor or nurse. Generally, these go away within a few weeks or months after your treatments are completed. About 14% of patients may also develop weakness in their hands and feet.

Nail Changes- Color changes to your fingernails or toenails may occur while taking Taxotere. In extreme, but rare, cases nails may fall off. After you have finished Taxotere treatments, your nails will generally grow back.

Eye Changes - Excessive tearing, which can be related to conjunctivitis or blockage of the tear ducts, may occur.

If you are interested in learning more about this drug, ask your doctor for a copy of the package insert.

Aventis Pharmaceuticals Inc.

Bridgewater, NJ08807 USA www.aventis-us.com
Rev. January 2005 TAX-AUG04-PIL-A

Every three-week injection of TAXOTERE for breast and non-small cell lung cancers Take dexamethasone tablets, 8 mg twice daily.
Dexamethasone dosing:
Day 1 Date:___________	Time: ______	AM ______PM
Day 2 Date: ___________	Time: ______	AM______PM
(Taxotere Treatment Day)
Day 3 Date: ___________	Time: ______	AM______PM

Every three-week injection of TAXOTERE for prostate cancer Take dexamethasone 8 mg, at 12 hours, 3 hours and 1 hour before TAXOTERE infusion.
Dexamethasone dosing:
Date: ___________	Time: ___________
Date: ___________	Time: ___________
(Taxotere Treatment Day)
	Time: ___________

 

Taxotere Interactions

There have been no formal clinical studies to evaluate the drug interactions of TAXOTERE with other medications. In vitro studies have shown that the metabolism of docetaxel may be modified by the concomitant administration of compounds that induce, inhibit, or are metabolized by cytochrome P450 3A4, such as cyclosporine, terfenadine, ketoconazole, erythromycin, and troleandomycin. Caution should be exercised with these drugs when treating patients receiving TAXOTERE as there is a potential for a significant interaction.

 

Taxotere Contraindications

TAXOTERE is contraindicated in patients who have a history of severe hypersensitivity reactions to docetaxel or to other drugs formulated with polysorbate 80.

TAXOTERE should not be used in patients with neutrophil counts of <1500 cells/mm³.

 

Additional information about Taxotere

Taxotere Indication: For the treatment of patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy. Also used as a single agent in the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of prior platinum-based chemotherapy. Lastly, for use, in combination with prednisone, in the treatment of patients with androgen independent (hormone refractory) metastatic prostate cancer.
Mechanism Of Action: Taxotere interferes with the normal function of microtubule growth. Whereas drugs like colchicine cause the depolymerization of microtubules in vivo, docetaxel 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, docetaxel binds to the β-subunit of tubulin. Tubulin is the "building block" of mictotubules, and the binding of docetaxel locks these building blocks in place. The resulting microtubule/docetaxel 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 docetaxel 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
Erythromycin The agent increases the serum levels and toxicity of docetaxel
Josamycin The agent increases the serum levels and toxicity of docetaxel
Ketoconazole The agent increases the serum levels and toxicity of docetaxel
Midazolam The agent increases the serum levels and toxicity of docetaxel
Orphenadrine The agent increases the serum levels and toxicity of docetaxel
Quinupristin This combination presents an increased risk of toxicity
Testosterone The agent increases the serum levels and toxicity of docetaxel
Testosterone Propionate The agent increases the serum levels and toxicity of docetaxel
Food Interactions: Not Available
Generic Name: Docetaxel
Synonyms: Docetaxel anhydrous; Docetaxel, Trihydrate; TXL
Drug Category: Antimalarials; Antineoplastic Agents, Phytogenic; Radiation-Sensitizing Agents
Drug Type: Small Molecule; Approved

Other Brand Names containing Docetaxel: Taxotere;
Absorption: Not Available
Toxicity (Overdose): Oral LD₅₀ in rat is >2000 mg/kg. Anticipated complications of overdosage include: bone marrow suppression, peripheral neurotoxicity, and mucositis. In two reports of overdose, one patient received 150 mg/m² and the other received 200 mg/m² as 1-hour infusions. Both patients experienced severe neutropenia, mild asthenia, cutaneous reactions, and mild paresthesia, and recovered without incident.
Protein Binding: About 94% protein bound, mainly to a1-acid glycoprotein, albumin, and lipoproteins.
Biotransformation: Hepatic. In vitro drug interaction studies revealed that docetaxel is metabolized by the CYP3A4 isoenzyme (1 major, 3 minor metabolites).
Half Life: Dose-dependent. Doses of 70 mg per square meter of body surface area (mg/m 2 ) or higher produce a triphasic elimination profile. With lower doses, assay limitations precluded detection of the terminal elimination phase. Alpha (distribution) 4 minutes. Beta 36 minutes. Gamma (terminal) 11.1 hours.
Dosage Forms of Taxotere: Solution Intravenous
Chemical IUPAC Name: Not Available
Chemical Formula: C43H53NO14
Docetaxel on Wikipedia: https://en.wikipedia.org/wiki/Docetaxel
Organisms Affected: Humans and other mammals