docetaxel

docetaxel /do·ce·tax·el/ (do″sĕ-tak´s'l) an antineoplastic agent used particularly in treating carcinoma of the breast and non.

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docetaxel Warning - Hazardous drug!

Taxotere

Pharmacologic class: Mitosis inhibitor

Therapeutic class: Antineoplastic

Pregnancy risk category D

FDA Boxed Warning

• Give under supervision of physician experienced in cancer chemotherapy, in facility with adequate diagnostic and treatment resources.
• Treatment-related death is more likely if patient has abnormal hepatic function, is receiving higher doses, or has non-small-cell lung cancer and history of platinum-based chemotherapy and is receiving drug as a single agent at dosage of 100 mg/m².
• Generally, drug shouldn't be given to patients with bilirubin level above upper limit of normal (ULN) or those with aspartate aminotransferase (AST) or alanine aminotransferase (ALT) above 1.5 x ULN concomitant with alkaline phosphatase (ALP) level above 2.5 x ULN. Bilirubin elevations or transaminase abnormalities concurrent with ALP abnormalities increases patient's risk for grade 4 neutropenia, febrile neutropenia, infections, severe thrombocytopenia, severe stomatitis, severe skin toxicity, and toxic death. Patients with isolated transaminase elevations above 1.5 x ULN have higher rate of grade 4 febrile neutropenia, but without increased incidence of toxic death. Before each cycle, obtain bilirubin, ALT or AST, and ALP values and have physician review them.
• Don't give to patients with neutrophil count below 1,500 cells/mm³. Obtain frequent blood cell counts to monitor for neutropenia (which may be severe and cause infection).
• Severe hypersensitivity reactions and fatal anaphylaxis (rare) have occurred in patients who received recommended 3-day dexamethasone premedication. If hypersensitivity reaction occurs, discontinue docetaxel immediately and give appropriate therapy. Don't give drug to patients with history of severe hypersensitivity reactions to it or other drugs containing polysorbate 80. Severe fluid retention may occur despite dexamethasone premedication regimen.

Action

Inhibits cellular mitosis by disrupting microtubular network

Availability

Injection concentrate: 20 mg, 80 mg

⊘Indications and dosages

➣ Metastatic breast cancer unresponsive to previous regimens

Adults: 60 to 100 mg/m² I.V. over 1 hour q 3 weeks

➣ Metastatic non-small-cell lung cancer; androgen-independent (hormone refractory) metastatic prostate cancer

Adults: 75 mg/m² I.V. over 1 hour q 3 weeks

➣ Gastric adenocarcinoma; head and neck cancer

Adults: 75 mg/m² as a 1-hour infusion, followed by cisplatin as a 1- to 3-hour infusion (both on day 1 only), followed by fluorouracil given as a 24-hour continuous I.V. infusion for 5 days, starting at the end of the cisplatin infusion. Treatment is repeated q 3 weeks.

Dosage adjustment

• Febrile neutropenia

Contraindications

• Hypersensitivity to drug or polysorbate 80
• Hepatic impairment
• Neutrophil count below 1,500 cells/mm³

Precautions

Use cautiously in:
• females of childbearing age
• pregnant or breastfeeding patients.

Administration

• Premedicate patient with oral corticosteroids before docetaxel administration to reduce fluid retention and severity of hypersensitivity reactions.
• Premedicate patient with antiemetics and hydrate with I.V. fluids, as prescribed, before cisplatin administration.
☞ Don't let drug concentrate contact plasticized polyvinyl chloride equipment or devices.
• Know that when used for prostate cancer, drug must be given with prednisone, as prescribed.
• Dilute with accompanying diluent solution; rotate vial gently to mix. Once foam has largely dissipated, withdraw prescribed amount of drug and mix in glass or polypropylene bottle or in plastic bag with 250 ml of normal saline solution or dextrose 5% in water.
• Mix solution thoroughly and infuse over 1 hour, using polyethylene-lined infusion set.

Route	Onset	Peak	Duration
I.V.	Rapid	Unknown	7 days

Adverse reactions

CNS: fatigue, asthenia, neurosensory deficits, peripheral neuropathy

CV: peripheral edema, cardiac tamponade, pericardial effusion

GI: nausea, vomiting, diarrhea, stomatitis, ascites

Hematologic: anemia, thrombocytopenia, leukopenia

Musculoskeletal: myalgia, joint pain

Respiratory: bronchospasm, pulmonary edema

Skin: alopecia, rash, dermatitis, desquamation, erythema, nail disorders

Other: edema, hypersensitivity reactions including anaphylaxis

Interactions

Drug-drug. Antineoplastics: additive bone marrow depression

Cyclosporine, erythromycin, ketoconazole, troleandomycin: significant change in docetaxel effects

Live-virus vaccines: increased risk of infection

Patient monitoring

☞ Watch for signs and symptoms of anaphylaxis or other hypersensitivity reactions, especially with first two doses.
• Monitor vital signs and fluid intake and output. Watch for signs and symptoms of fluid overload and bronchospasm.
• Monitor CBC, and assess for signs and symptoms of blood dyscrasias.
• Closely monitor neutrophil and platelet counts before and during therapy.
• Observe I.V. site frequently for extravasation.
• Assess neurologic status to detect neurosensory deficits and peripheral neuropathy.

Patient teaching

• Instruct patient to weigh himself daily and to immediately report sudden weight gain or difficulty breathing.
☞ Tell patient to report signs and symptoms of blood dyscrasias. Inform him that he'll undergo frequent blood testing to monitor these effects.
☞ Advise patient to immediately report rash or difficulty breathing.
• Inform patient that hair loss is common with docetaxel use, but that hair will grow back after therapy ends.
• Advise female patient of childbearing age to use effective contraception during therapy and to notify prescriber if she suspects pregnancy.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs mentioned above.