docetaxel
Taxotere

Available forms
Available by prescription only
Injection: 20 mg, 80 mg

Indications and dosages
  Consult current literature for additional dosages and unlabeled uses.
 Treatment of patients with locally advanced or metastatic breast cancer who have progressed during anthracycline-based therapy or have relapsed during anthracycline-based adjuvant therapy. Adults: 60 to 100 mg/m² I.V. over 1 hour q 3 weeks. All patients should be premedicated with dexamethasone 16 mg daily in divided doses for 3 days, starting 1 day before docetaxel therapy.
≡ Dosage adjustment. Patients who initially receive 100 mg/m² and who experience febrile neutropenia, a neutrophil count less than 500 cells/mm³ for longer than 1 week, severe or cumulative cutaneous reactions, or severe peripheral neuropathy during docetaxel therapy should have dosage reduced from 100 to 75 mg/m². If patients continue to experience these reactions, either dosage should be decreased from 75 to 55 mg/m² or drug should be discontinued. Patients who initially receive 60 mg/m² and who don’t experience febrile neutropenia, a neutrophil count less than 500 cells/mm³ for longer than 1 week, severe or cumulative cutaneous reactions, or severe peripheral neuropathy during docetaxel therapy may tolerate higher doses. For patients who develop grade 3 or higher peripheral neuropathy, discontinue docetaxel entirely.
 Locally advanced or metastatic non-small-cell lung cancer after failure of platinum-based chemotherapy. Adults: 75 mg/m² I.V. over 1 hour every 3 weeks.
 All patients should be premedicated with dexamethasone 16 mg daily in divided doses for 3 days, starting 1 day before docetaxel therapy.
≡ Dosage adjustment. For patients with febrile neutropenia, neutrophils less than 500 cells/mm³ for longer than 1 week, severe or cumulative cutaneous reactions, or other grade 3 or 4 nonhematologic toxicities during therapy, discontinue docetaxel until toxicity is resolved, then restart at 55 mg/m². For patients who develop grade 3 or higher peripheral neuropathy, discontinue docetaxel entirely.

Pharmacodynamics
Antineoplastic action: Docetaxel acts by disrupting the microtubular network in cells that’s essential for mitotic and interphase cellular functions. This results in inhibition of mitosis.

Pharmacokinetics
Absorption: Administered I.V.
Distribution: About 94% protein-bound.
Metabolism: Undergoes oxidative metabolism. Metabolized by the CYP3A4 isoenzyme.
Excretion: Eliminated primarily in feces with a small amount eliminated in urine.

Contraindications and precautions
Contraindicated in patients with history of severe hypersensitivity to drug or other drugs formulated with polysorbate 80. Don’t give docetaxel to patients with neutrophil counts below 1,500 cells/mm³.

Interactions
Drug-drug. Compounds that induce, inhibit, or are metabolized by cytochrome P-450 3A4, such as cyclosporine, erythromycin, ketoconazole, and troleandomycin: May modify metabolism of docetaxel. Use together cautiously.

Adverse reactions
CNS: paresthesia, dysesthesia, pain (including burning sensation), weakness.
CV: flushing, fluid retention, hypotension, chest tightness.
GI: stomatitis, nausea, vomiting, diarrhea.
Hematologic: anemia, NEUTROPENIA, FEBRILE NEUTROPENIA, myelosuppression (dose-limiting), LEUKOPENIA, thrombocytopenia.
Musculoskeletal: myalgia, arthralgia, back pain.
Respiratory: dyspnea.
Skin: alopecia, maculopapular eruptions, desquamation, nail pigmentation alteration, onycholysis, nail pain, rash.
Other: hypersensitivity reactions, infections, drug fever, chills, TOXIC DEATH

Effects on lab test results
• May increase ALT, AST, bilirubin, and alkaline phosphatase levels.
• May decrease hemoglobin and WBC and platelet counts.

Overdose and treatment
Signs and symptoms of overdose may include bone marrow suppression, peripheral neurotoxicity, and mucositis.
 There’s no known antidote for docetaxel. Closely monitor patient’s vital functions. Administer G-CSF as soon as possible to prevent neutropenia.

Special considerations
• Patients with bilirubin values above the upper limit of normal usually shouldn’t receive docetaxel. Also, patients with ALT or AST levels more than 1.5 times the upper limit of normal and alkaline phosphatase levels more than 2.5 times the upper limit of normal usually shouldn’t receive drug.
• Premedicate patient with oral corticosteroids such as dexamethasone 16 mg daily for 3 days starting 1 day before docetaxel administration, to reduce fluid retention and hypersensitivity reactions.
• Dilute docetaxel before administration using the diluent supplied with drug. Allow drug and diluent to stand at room temperature for about 5 minutes before mixing. After adding the entire contents of diluent to the vial of docetaxel, gently rotate the vial for about 15 seconds. Then allow solution to stand for a few minutes to allow any foam to dissipate.
• To prepare docetaxel infusion solution, aseptically withdraw the required amount of premix solution from the vial and inject into a 250-ml infusion bag or bottle of normal saline solution or D₅W solution to produce a final concentration of 0.3 to 0.9 mg/ml. Doses exceeding 240 mg require a larger volume of infusion solution so a concentration of 0.9 mg/ml of docetaxel isn’t exceeded. Thoroughly mix the infusion by manual rotation.
• Use caution during preparation and administration of docetaxel. Use of gloves is recommended. If solution contacts skin, wash skin immediately and thoroughly with soap and water. If docetaxel contacts mucous membranes, flush membranes thoroughly with water. Mark all waste materials with chemotherapy hazard labels.
• Contact of the undiluted concentrate with plasticized polyvinyl chloride equipment or devices used to prepare solutions for infusion isn’t recommended. Prepare and store infusion solutions in bottles (glass, polypropylene) or plastic bags (polypropylene, polyolefin) and administer through polyethylene-lined administration sets.
 ALERT Don’t confuse Taxotere and Taxol. Potential errors include look-alike and sound-alike names, packaging and labeling similarity, and errors in reconstitution of Taxotere because of overfill in the vial.
• Monitor patient closely for hypersensitivity reactions, especially during the first and second infusions. If minor reactions, such as flushing or localized skin reactions occur, interruption of therapy isn’t required. More severe reactions require the immediate discontinuation of docetaxel and aggressive treatment.
• Bone marrow toxicity is the most frequent and dose-limiting toxicity. Frequent blood count monitoring is needed during therapy.
• Advise patient that hypo- or hyperpigmentation of the nails may occur, which may be accompanied by pain or onycholysis.
• Localized skin eruptions may form on the arms, face, or thorax. Lesions are often pruritic, but are reversible and will recover by the next infusion.
Pregnant patients
• Advise patient of childbearing age to avoid becoming pregnant during therapy because of potential harm to fetus.
Breast-feeding patients
• Because of risk of serious adverse reactions in breast-fed infants, it’s recommended that breast-feeding be discontinued during docetaxel therapy.
Pediatric patients
• Safety and effectiveness in children younger than age 16 haven’t been established.

Patient education
• Explain that alopecia occurs in almost 80% of patients.
• Explain to patient that localized skin eruptions, often pruritic, may form on the arms, face, or thorax, but are reversible and will recover by the next infusion.
• Tell patient to promptly report sore throat, fever, unusual bruising, or bleeding.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use