Brand names: Docefrez, Taxotere
Drug class: Antineoplastic Agents
- Antimitotic Agents
- Antimicrotubule Agents
VA class: AN900
Chemical name: [2aR-[2aα,4β,4aβ,6β,9α(αR*,βS*),11α,12α,12aα,12bα]]-12b-(acetyloxy)-12-(benzoyloxy)-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-4,6,11-trihydroxy-4a,8,13,13-tetramethyl-5-oxo-7,11-methano-1H-cyclodeca[3,4]benz[1,2-b]oxet-9-yl ester β-[[(1,1-dimethylethoxy)carbonyl]amino]-α-hydroxybenzenepropanoic acid
Molecular formula: C₄₃H₅₃NO₁₄
CAS number: 114977-28-5

Medically reviewed by Drugs.com on Jun 14, 2024. Written by ASHP.

Introduction

Semisynthetic taxoid; an antineoplastic agent.^{1 2 3 4 5 6 7 8}

Uses for Docetaxel

Breast Cancer

In combination with doxorubicin and cyclophosphamide as adjuvant treatment for operable node-positive breast cancer.^{1 65 68 84 86}

Other docetaxel-containing regimens under investigation as adjuvant therapy for early-stage breast cancer, including nonanthracycline-containing regimens^{† [off-label]}.⁸⁰

In combination with doxorubicin for the initial treatment of metastatic breast cancer^{† [off-label]}.^{65 67 74}

In combination with capecitabine for the treatment of metastatic breast cancer in patients with disease that has failed anthracycline-containing chemotherapy.^{64 65 66}

Monotherapy for the second-line treatment of locally advanced or metastatic breast cancer after failure of prior chemotherapy.^{1 13 14 15 16 17 41 42 54 63 65 84 85 86}

Non-small Cell Lung Cancer

In combination with cisplatin as first-line therapy for unresectable, locally advanced or metastatic NSCLC.^{1 52 54 69 84 85 86}

Monotherapy for second-line treatment of locally advanced or metastatic NSCLC in patients with disease that has recurred or progressed following prior treatment with platinum-based chemotherapy.^{1 52 54 59 84 85 86}

Prostate Cancer

In combination with prednisone for the treatment of androgen-independent (hormone-refractory) metastatic prostate cancer.^{1 70 84 85 86}

Gastric Cancer

In combination with cisplatin and fluorouracil for the initial treatment of advanced gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction.^{1 71 84 86}

Head and Neck Cancer

In combination with cisplatin and fluorouracil as induction chemotherapy for locally advanced squamous cell carcinoma of the head and neck.^{1 72 73 84 86}

Ovarian Cancer

In combination with carboplatin as an alternative regimen for the first-line treatment of ovarian epithelial cancer^{† [off-label]}.^{54 82 83}

Treatment of recurrent or persistent ovarian epithelial cancer that is platinum-resistant or platinum-refractory^{† [off-label]}.^{54 82}

Docetaxel Dosage and Administration

General

• Consult specialized references for procedures for proper handling and disposal of antineoplastics.^{1 84 85 86}

Premedication

• Premedicate all patients with oral corticosteroids to prevent severe hypersensitivity reactions and to reduce the incidence and severity of fluid retention.^{1 84 85 86} Patients with hormone-refractory prostate cancer may receive dexamethasone 8 mg orally at 1, 3, and 12 hours prior to docetaxel administration.^{1 84 85 86} Patients with other cancers may receive dexamethasone 8 mg orally twice daily for 3 days, starting 1 day prior to docetaxel administration.^{1 84 85 86}

• Patients with gastric cancer or head and neck cancer: Administer appropriate antiemetic premedication and hydration before and after cisplatin administration in the docetaxel/cisplatin/fluorouracil regimen.^{1 84 86}

Administration

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by IV infusion.^{1 84 85 86}

Handle cautiously; use protective equipment (e.g., gloves).^{1 84 85 86}

Immediately treat accidental contact with skin by thoroughly washing with soap and water; immediately treat accidental contact with mucous membranes by thoroughly washing with water.^{1 84 85 86}

Contact of docetaxel injection concentrate or reconstituted solution with PVC equipment or devices used to prepare solutions for infusion is not recommended.^{1 36 84 85 86} (See Storage under Stability.)

Administer through polyethylene-lined administration sets.^{1 36 84 85 86} Use of inline filters is neither required nor recommended.³⁷

Commercially available as injection concentrate and lyophilized powder.^{1 84 85 86} Lyophilized powder must be reconstituted and then diluted to prepare final infusion solution.⁸⁵ Injection concentrate must be diluted prior to IV administration.^{1 84 86}

Precautions for Use of Injection Concentrate

Procedure for preparing a final docetaxel infusion solution from an injection concentrate may vary by manufacturer (i.e., some preparations may require 1 dilution step; others may require 2 dilution steps).^{1 84 86} Taxotere injection concentrate has been reformulated to require 1 dilution step rather than 2 dilution steps.⁸⁸

Injection concentrates available from various manufacturers may contain different concentrations of the drug.^{1 84 86}

Consult manufacturer’s instructions for the specific formulation being used to ensure that the correct preparation procedure is followed.^{1 84 85 86 87}

Do not use formulations requiring 2 dilution steps with formulations requiring 1 dilution step.^{1 86}

Dilution of Injection Concentrate Requiring One Dilution Step

If vial was refrigerated, allow to stand at room temperature for approximately 5 minutes prior to dilution.¹

Inject required amount of docetaxel injection concentrate into a 250-mL infusion bag or bottle containing 0.9% sodium chloride injection or 5% dextrose injection (using a 21-gauge needle) to produce a final solution with docetaxel concentration of 0.3–0.74 mg/mL.^{1 84 86} If required dose is >200 mg, increase solution volume accordingly so that docetaxel concentration does not exceed 0.74 mg/mL.^{1 84 86}

Mix docetaxel infusion solution thoroughly by gentle manual rotation.^{1 84 86}

Dilution of Injection Concentrate Requiring Two Dilution Steps

First dilution step: Add entire contents of the vial of diluent supplied by the manufacturer (13% w/v polyethylene glycol 400 in water for injection; approximately 1.95 mL of diluent for docetaxel 20 mg and approximately 7.2 mL of diluent for docetaxel 80 mg) to the appropriate vial of docetaxel injection concentrate to create an initial diluted solution of docetaxel 10 mg/mL.⁸⁶

Invert vial repeatedly for ≥45 seconds to fully mix the concentrate and diluent; do not shake the vial.⁸⁶ Allow solution to stand for a few minutes to let any foam on top dissipate; then preparation may continue even if some foam remains.⁸⁶ Initial diluted solution should be clear.⁸⁶

Use initial diluted solution immediately to prepare final diluted solution for infusion or store in refrigerator or at room temperature for up to 8 hours.⁸⁶

Second dilution step: Inject required amount of the initial diluted solution (docetaxel 10 mg/mL) into a 250-mL infusion bag or bottle containing 0.9% sodium chloride injection or 5% dextrose injection to produce a final solution with docetaxel concentration of 0.3–0.74 mg/mL.⁸⁶ If required dose is >200 mg, increase solution volume accordingly so that docetaxel concentration does not exceed 0.74 mg/mL.⁸⁶

Mix docetaxel infusion solution thoroughly by manual rotation.⁸⁶

Reconstitution and Dilution (Lyophilized Powder for Injection)

Remove appropriate number of vials of diluent (ethanol 35.4% w/w and polysorbate 80) and docetaxel lyophilized powder from the refrigerator; allow to stand at room temperature for approximately 5 minutes prior to reconstitution.⁸⁵

Withdraw 1 mL of diluent using a 1-mL syringe with an 18- or 21-gauge needle and add to a vial containing docetaxel 20 mg to provide a solution containing 20 mg in 0.8 mL or withdraw 4 mL of diluent using a 4-mL syringe with an 18- or 21-gauge needle and add to a vial containing docetaxel 80 mg to provide a solution containing 24 mg/mL.⁸⁵

Shake vial well to ensure complete dissolution.⁸⁵ Allow solution to stand for a few minutes to let any air bubbles dissipate.⁸⁵ Solution should be clear.⁸⁵

Use reconstituted solution immediately to prepare final diluted docetaxel solution for infusion or store in refrigerator or at room temperature for up to 8 hours.⁸⁵

To prepare final diluted docetaxel solution for infusion, inject required amount of reconstituted docetaxel solution into a 250-mL infusion bag or bottle containing 0.9% sodium chloride injection or 5% dextrose injection to produce a final solution with docetaxel concentration of 0.3–0.74 mg/mL.⁸⁵ If required dose is >200 mg, increase solution volume accordingly so that docetaxel concentration does not exceed 0.74 mg/mL. ⁸⁵

Mix docetaxel infusion solution thoroughly by manual rotation.⁸⁵

Rate of Administration

Administer over 1 hour.^{1 84 85 86}

Dosage

Adults

If concomitant use with a potent CYP3A4 inhibitor cannot be avoided, consider reducing docetaxel dosage by 50%.^{1 84 85 86} (See Interactions.)

If neutropenia or thrombocytopenia occurs, do not administer subsequent cycle until neutrophil count is >1500/mm³ and platelet count is >100,000/mm³.^{1 84 85 86}

If severe neutropenia (neutrophil count <500/mm³) lasting more than 1 week, febrile neutropenia, or grade 4 infection occurs during a cycle of therapy, reduce dose by 25% for subsequent cycles.^{1 84 85 86}

Breast Cancer (Adjuvant Therapy)

IV

75 mg/m² administered 1 hour following doxorubicin 50 mg/m² IV and cyclophosphamide 500 mg/m² IV in repeated 3-week cycles for up to 6 cycles.^{1 84 86}

Prophylactic granulocyte colony-stimulating factor (G-CSF) may be used. ^{1 76 77 78 84 86}

Dosage Modification for Toxicity

IV

If febrile neutropenia occurs, initiate G-CSF for all subsequent cycles.^{1 84 86} If patient continues to experience febrile neutropenia, continue G-CSF and reduce docetaxel dose to 60 mg/m².^{1 84 86}

If severe or cumulative cutaneous reactions, moderate neurosensory manifestations, or grade 3 or 4 stomatitis occurs, reduce docetaxel dose to 60 mg/m².^{1 84 86} If patient continues to experience severe or cumulative cutaneous reactions or moderate neurosensory manifestations, discontinue treatment.^{1 84 86}

If cystoid macular edema develops, discontinue docetaxel and initiate appropriate treatment.^{1 84 85 86} Consider alternative therapy with a nontaxane antineoplastic agent.^{1 84 85 86}

Breast Cancer (Advanced Disease)

IV

60–100 mg/m² in repeated 3-week cycles.^{1 84 85 86}

Higher doses may be tolerated by patients who are dosed initially at 60 mg/m² and who do not experience febrile neutropenia, neutrophil count <500/mm³ for more than 1 week, severe or cumulative cutaneous reactions, or severe peripheral neuropathy.^{1 84 85 86}

Dosage Modification for Toxicity

IV

In patients initially dosed at 100 mg/m² who experience febrile neutropenia, neutrophil count <500/mm³ for more than 1 week, or severe or cumulative cutaneous reactions, reduce dose to 75 mg/m² for subsequent courses of therapy.^{1 37 84 85 86} If the patient continues to experience these reactions, further reduce dose to 55 mg/m² or discontinue treatment.¹

If grade 3 or greater peripheral neuropathy develops, discontinue treatment.^{1 84 85 86}

If cystoid macular edema develops, discontinue docetaxel and initiate appropriate treatment.^{1 84 85 86} Consider alternative therapy with a nontaxane antineoplastic agent.^{1 84 85 86}

NSCLC (First-line Therapy for Advanced Disease)

IV

Docetaxel 75 mg/m² immediately followed by cisplatin 75 mg/m² IV in repeated 3-week cycles.^{1 84 85 86}

Dosage Modification for Toxicity

IV

If nadir platelet count is <25,000/mm³ or febrile neutropenia or serious nonhematologic toxicity occurs, reduce docetaxel dose to 65 mg/m² for subsequent cycles.^{1 84 85 86} If further dose reduction is required, 50 mg/m² is recommended.^{1 84 85 86}

Cisplatin dosage adjustments may be necessary; consult manufacturer's labeling.^{1 84 85 86}

If cystoid macular edema develops, discontinue docetaxel and initiate appropriate treatment.^{1 84 85 86} Consider alternative therapy with a nontaxane antineoplastic agent.^{1 84 85 86}

NSCLC (Second-line Therapy for Advanced Disease)

IV

75 mg/m² in repeated 3-week cycles; higher doses are associated with increased hematologic toxicity, infection, and treatment-related mortality and are not recommended.^{1 59 60 84 85 86}

Dosage Modification for Toxicity

IV

If febrile neutropenia, neutrophil count <500/mm³ for more than 1 week, severe or cumulative cutaneous reactions, or other grade 3/4 nonhematologic toxicity occurs, withhold drug until toxicity resolves and then resume at 55 mg/m².^{1 84 85 86}

If grade 3 or greater peripheral neuropathy develops, discontinue treatment.^{1 84 85 86}

If cystoid macular edema develops, discontinue docetaxel and initiate appropriate treatment.^{1 84 85 86} Consider alternative therapy with a nontaxane antineoplastic agent.^{1 84 85 86}

Prostate Cancer

IV

75 mg/m² in repeated 3-week cycles; given in combination with prednisone 5 mg orally twice daily continuously.^{1 84 85 86}

Dosage Modification for Toxicity

IV

If febrile neutropenia, neutrophil count <500/mm³ for more than 1 week, severe or cumulative cutaneous reactions, or moderate neurosensory manifestations occur, reduce dose to 60 mg/m².^{1 84 85 86} If patient continues to experience these reactions, discontinue treatment.^{1 84 85 86}

If cystoid macular edema develops, discontinue docetaxel and initiate appropriate treatment.^{1 84 85 86} Consider alternative therapy with a nontaxane antineoplastic agent.^{1 84 85 86}

Gastric Cancer

IV

Docetaxel 75 mg/m² followed by cisplatin 75 mg/m² on day 1, then fluorouracil 750 mg/m² per day as a 24-hour continuous IV infusion for 5 days (days 1–5) initiated upon completion of cisplatin infusion; regimen repeated in 3-week cycles.^{1 84 86}

Consider primary prophylaxis with G-CSF.⁷¹

Dosage Modification for Hematologic Toxicity

IV

If febrile neutropenia, documented infection with neutropenia, or neutropenia lasting more than 1 week occurs, administer G-CSF during the second and/or subsequent cycles; if such toxicity occurs despite use of G-CSF, reduce docetaxel dose to 60 mg/m².^{1 84 86} If subsequent episodes of complicated neutropenia occur, further reduce dose to 45 mg/m².^{1 84 86} If these reactions persist, discontinue treatment.^{1 84 86}

If grade 4 thrombocytopenia occurs, reduce docetaxel dose to 60 mg/m².^{1 84 86} If reaction persists, discontinue treatment.^{1 84 86}

Dosage Modification for Hepatotoxicity

IV

See Table 1 for docetaxel dosage modifications for hepatotoxicity.^{1 84 86 89}

Dosage Modification for GI Toxicity

IV

See Table 2 for docetaxel and fluorouracil dosage modifications for GI toxicity.^{1 84 86}

Other Dosage Modifications

IV

Dosage adjustments for cisplatin and fluorouracil may be necessary; consult manufacturers' labelings in addition to the dosage adjustments described here.^{1 84 86}

If grade 2 peripheral neuropathy occurs, reduce cisplatin dose by 20%; discontinue treatment if grade 3 peripheral neuropathy occurs.^{1 84 86}

If grade 2 or greater palmar-plantar erythrodysesthesia (hand-foot syndrome) occurs, withhold fluorouracil until resolution and then resume fluorouracil with a 20% dose reduction.^{1 84 86}

If grade 3 ototoxicity occurs, discontinue treatment.^{1 84 86}

If other grade 3 toxicities occur (except alopecia and anemia), delay chemotherapy for a maximum of 2 weeks until resolution to grade 1 or less, and then resume therapy if medically appropriate.^{1 84 86}

If cystoid macular edema develops, discontinue docetaxel and initiate appropriate treatment.^{1 84 85 86} Consider alternative therapy with a nontaxane antineoplastic agent.^{1 84 85 86}

See Table 3 for cisplatin dosage modifications for nephrotoxicity.^{1 84 86}

Head and Neck Cancer

IV

Induction treatment followed by radiotherapy: Docetaxel 75 mg/m² followed by cisplatin 75 mg/m² on day 1, then fluorouracil 750 mg/m² per day as a 24-hour continuous IV infusion for 5 days (days 1–5) initiated upon completion of cisplatin infusion; regimen repeated in 3-week cycles for up to 4 cycles.^{1 84 86} Following completion of chemotherapy, administer radiotherapy.^{1 84 86}

Induction treatment followed by chemoradiotherapy: Docetaxel 75 mg/m² followed by cisplatin 100 mg/m² on day 1, then fluorouracil 1 g/m² per day as a 24-hour continuous IV infusion for 4 days (days 1–4); regimen repeated in 3-week cycles for up to 3 cycles.^{1 84 86} Following completion of chemotherapy, administer chemoradiotherapy.^{1 84 86}

Administer prophylaxis for neutropenic infection; in clinical trials, patients received prophylactic antibiotic treatment.^{1 84 86}

Dosage Modification for Hematologic Toxicity

IV

If febrile neutropenia, documented infection with neutropenia, or neutropenia lasting more than 1 week occurs, administer G-CSF during the second and/or subsequent cycles; if such toxicity occurs despite use of G-CSF, reduce docetaxel dose to 60 mg/m².^{1 84 86} If subsequent episodes of complicated neutropenia occur, further reduce dose to 45 mg/m².^{1 84 86} If these reactions persist, discontinue treatment.^{1 84 86}

If grade 4 thrombocytopenia occurs, reduce docetaxel dose to 60 mg/m².^{1 84 86} If reaction persists, discontinue treatment.^{1 84 86}

Dosage Modification for Hepatotoxicity

IV

See Table 1 for docetaxel dosage modifications for hepatotoxicity.^{1 84 86 89}

Dosage Modification for GI Toxicity

IV

See Table 2 for docetaxel and fluorouracil dosage modifications for GI toxicity.^{1 84 86}

Other Dosage Modifications

IV

Dosage adjustments for cisplatin and fluorouracil may be necessary during treatment; consult manufacturer's labelings in addition to the dosage adjustments described here.^{1 84 86}

If grade 2 peripheral neuropathy occurs, reduce cisplatin dose by 20%.¹ If grade 3 peripheral neuropathy occurs, discontinue treatment.^{1 84 86}

If grade 2 or greater palmar-plantar erythrodysesthesia (hand-foot syndrome) occurs, withhold fluorouracil until resolution, and then resume fluorouracil with a 20% dose reduction.^{1 84 86}

If grade 3 ototoxicity occurs, discontinue treatment.^{1 84 86}

If other grade 3 toxicities occur (except alopecia and anemia), delay chemotherapy for a maximum of 2 weeks until resolution to grade 1 or less, and then resume therapy if medically appropriate.^{1 84 86}

If cystoid macular edema develops, discontinue docetaxel and initiate appropriate treatment.^{1 84 85 86} Consider alternative therapy with a nontaxane antineoplastic agent.^{1 84 86}

See Table 3 for cisplatin dosage modifications for nephrotoxicity.^{1 84 86}

Prescribing Limits

Adults

Treatment-related mortality is increased at higher dosages.^{1 84 85 86} (See Treatment-related Mortality under Cautions.)

NSCLC (Second-line Therapy for Advanced Disease)

IV

Maximum 75 mg/m² in repeated 3-week cycles; higher doses associated with increased hematologic toxicity, infection, and treatment-related mortality.^{1 59 60 84 85 86}

Special Populations

Hepatic Impairment

Do not use in patients with serum total bilirubin >ULN or in patients with serum AST and/or ALT >1.5 times ULN concurrent with alkaline phosphatase >2.5 times ULN.^{1 84 85 86} (See Hepatic Impairment in Boxed Warning.)

Renal Impairment

Dosage adjustment does not appear to be necessary.³⁷

Geriatric Patients

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.^{1 84 85 86}

Cautions for Docetaxel

Contraindications

• History of severe hypersensitivity to docetaxel or polysorbate 80.^{1 84 85 86}

• Baseline neutrophil count <1500/mm³.^{1 84 85 86}

Warnings/Precautions

Warnings

Adequate Patient Evaluation and Monitoring

Prior to each cycle, assess serum bilirubin, AST and/or ALT, and alkaline phosphatase concentrations.^{1 84 85 86} Frequent monitoring of blood cell counts also recommended.^{1 84 85 86}

Do not administer docetaxel in patients with serum total bilirubin >ULN or patients with serum AST and/or ALT >1.5 times ULN with concomitant alkaline phosphatase >2.5 times ULN.^{1 84 85 86}

Do not administer subsequent cycles until neutrophil count recovers to >1500/mm³ and platelet count recovers to >100,000/mm³.^{1 84 85 86}

Patients who respond to docetaxel may not experience an improvement and/or may experience worsening in performance status.^{1 84 85 86} The relationship between changes in performance status, response to therapy, and treatment-related adverse effects not established.^{1 84 85 86}

Treatment-related Mortality

Increased incidence of treatment-related mortality in patients with abnormal hepatic function, patients receiving higher doses, and patients with NSCLC previously treated with platinum-based chemotherapy who received docetaxel 100 mg/m².^{1 84 85 86}

Death possibly or probably related to treatment reported in 11.5% of patients with hepatic dysfunction receiving docetaxel 100 mg/m² for various tumors; 3 of 7 patients with hepatic dysfunction receiving docetaxel 60 mg/m² for metastatic breast cancer; and 0.6 or 2% of patients with normal hepatic function receiving docetaxel 60 or 100 mg/m², respectively, for metastatic breast cancer.^{1 84 85 86} Approximately half of deaths occurred during the first cycle; most deaths due to sepsis.^{1 84 85 86}

In patients with advanced NSCLC who received prior platinum-based therapy, treatment-related death occurred in 5 or 14% of those receiving docetaxel 100 mg/m² and 2.8% of those receiving 75 mg/m².^{1 84 85 86}

Hematologic Effects

Bone marrow suppression is major dose-limiting toxicity.^{1 3 7 8 84 85 86}

Frequency and severity of hematologic toxicity, febrile reactions and infections, and rates of septic death increase with dose and presence of hepatic dysfunction.^{1 7 22 84 85 86} (See Hepatic Impairment in Boxed Warning.)

Neutropenia (i.e., neutrophils <2000/mm³) occurs in essentially all patients receiving doses of 60–100 mg/m² and is dose related; grade 4 neutropenia (<500/mm³) reported in >75% of patients.^{1 84 85 86} Neutrophil nadir at day 7–8;^{1 8 13 14 19 20 84 85 86} the median duration of grade 4 neutropenia is about 7 days.^{1 5 7 13 84 85 86}

Febrile neutropenia reported in about 12% of patients receiving docetaxel 100 mg/m²; uncommon in patients receiving 60 mg/m².^{1 84 85 86} Febrile neutropenia and/or neutropenic infection occurred in 28% of gastric cancer patients receiving docetaxel/cisplatin/fluorouracil regimen without G-CSF compared with 12% of those receiving G-CSF concomitantly; monitor closely during first and subsequent cycles.^{1 84 86}

Fatal GI bleeding associated with severe thrombocytopenia reported in several breast cancer patients with severe hepatic dysfunction (bilirubin >1.7 times ULN).^{1 84 85 86}

Monitor blood counts frequently and adjust dosage accordingly.^{1 84 85 86} (See Dosage under Dosage and Administration.)

Patients must have recovered from acute toxicities (e.g., neutrophils recovered to >1500/mm³, platelets to >100,000/mm³) of previous cytotoxic therapy before each cycle.^{1 84 85 86}

Cardiovascular Toxicity

Severe fluid retention reported, sometimes despite dexamethasone premedication.^{1 3 84 85 86} (See Fluid Retention in Boxed Warning.)

Peripheral edema usually begins in lower extremities and appears to be completely (although sometimes slowly) reversible;^{1 3 84 85 86} generally responds to standard measures, including sodium restriction and oral diuretics.^{1 3 13 25 84 85 86}

Premedicate with oral corticosteroids to reduce the incidence and severity of fluid retention.^{1 84 85 86} (See Premedication under Dosage and Administration.)

Monitor patients with preexisting effusions beginning with the first dose.^{1 84 85 86}

Sensitivity Reactions

Hypersensitivity Reactions

Severe reactions (hypotension and/or bronchospasm, generalized rash/erythema, and, rarely, fatal anaphylaxis) reported in some patients despite receiving recommended 3 days of dexamethasone premedication.^{1 84 85 86}

Premedicate with oral corticosteroids to reduce the severity of hypersensitivity reactions.^{1 84 85 86} (See Premedication under Dosage and Administration.)

Closely observe for hypersensitivity reactions, especially during the first and second infusions.^{1 84 85 86}

Reactions may occur within a few minutes following initiation of the infusion.^{1 9 25 84 85 86} Interruption of therapy generally is not needed for mild reactions (e.g., flushing, localized skin reactions);^{1 13 15 18 19 20 23 84 85 86} consider decreasing the infusion rate until symptoms resolve.³⁷

Discontinue immediately and treat if severe reaction occurs.^{1 84 85 86}

Do not administer to any patient who experienced a severe hypersensitivity reaction during a previous course.^{1 84 85 86}

Other Warnings and Precautions

Myelodysplastic Syndrome and Secondary Leukemia

Treatment-related myelodysplasia or acute myeloid leukemia (AML) reported in patients who received docetaxel in combination with other antineoplastic agents with or without radiation therapy.^{1 84 85 86}

Patients receiving docetaxel with cyclophosphamide and doxorubicin as adjuvant therapy for breast cancer require continued hematologic monitoring.^{1 84 85 86}

Dermatologic Effects

Localized erythema of the extremities with edema followed by desquamation reported.^{1 84 85 86}

Reversible cutaneous reactions characterized by rash (e.g., localized eruptions on the feet, hands, arms, face, or thorax) and pruritus reported; generally occur within 1 week of administration, resolve before the next infusion, and are not disabling.^{1 84 85 86}

Adjust dosage if severe skin toxicity occurs.^{1 84 85 86} (See Dosage under Dosage and Administration.)

Nervous System Effects

Severe neurosensory symptoms (paresthesia, dysesthesia, pain) reported; spontaneous reversal reported in a median of 9 weeks from onset.^{1 84 85 86} Neuromotor toxicity reported less frequently.^{1 27 28 29 84 85 86} Dosage reduction or drug discontinuance may be required (see Dosage under Dosage and Administration).^{1 84 85 86}

Severe asthenia reported; fatigue and weakness may last a few days to several weeks and may be associated with deterioration of performance status in patients with progressive disease.^{1 84 85 86}

Intoxication related to alcohol content of the docetaxel formulation can occur.^{1 84 85 86 90 91} (See Alcohol Content under Cautions.)

Ocular Effects

Cystoid macular edema reported.^{1 84 85 86} If impaired vision occurs, patients should promptly receive a comprehensive ophthalmologic examination.^{1 84 85 86} Discontinue docetaxel therapy if cystoid macular edema occurs and consider alternative therapy with a nontaxane antineoplastic agent.^{1 84 85 86}

Alcohol Content

Alcohol intoxication reported during or within 24 hours after docetaxel administration.^{1 84 85 86 90 91} In 3 such cases identified from case reports or the FDA Adverse Event Reporting System (AERS) database, symptoms were transient or subsided and the docetaxel infusion was completed at a slower infusion rate.⁹⁰

Formulations of docetaxel available from various manufacturers may contain different amounts of alcohol.^{1 84 85 86 90} Consult manufacturer's labeling for alcohol content of the specific formulation used.^{1 84 85 86 90}

Consider alcohol content of docetaxel formulations available from various manufacturers, especially for patients with hepatic impairment, patients in whom alcohol should be avoided or minimized, patients who experienced alcohol intoxication with a previous docetaxel infusion, and those receiving concomitant therapy with drugs with CNS depressant effects (see Specific Drugs under Interactions).^{1 84 85 86 90 91}

Monitor for symptoms of alcohol intoxication during and after administration; if such symptoms occur, consider reducing the infusion rate and using a formulation with the least amount of alcohol for subsequent infusions.⁹⁰

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; embryotoxic and fetotoxic in animals.^{1 84 85 86} Avoid pregnancy during therapy.^{1 84 85 86} If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.^{1 84 85 86}

Prescribing and Dispensing Precautions

Ensure accuracy of prescription; similarity of spelling of Taxotere (docetaxel) and Taxol (paclitaxel) may result in errors.⁶²

Specific Populations

Pregnancy

Category D.^{1 84 85 86} (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Not known whether distributed into milk; discontinue nursing or drug.^{1 84 85 86}

Pediatric Use

Consider alcohol content of docetaxel formulations available from various manufacturers.^{1 84 85 86} (See Alcohol Content under Cautions.)

Has been studied in patients 1–26 years of age with various recurrent or refractory solid tumors;^{1 84 85} however, efficacy in pediatric patients not established.^{1 84 85 86} Safety and pharmacokinetic (i.e., clearance) data appeared similar to data for adults.^{1 84 85} Primary dose-limiting toxicity was neutropenia.^{1 84 85}

Geriatric Use

Certain toxicities associated with docetaxel therapy may occur more frequently and with greater severity in geriatric patients ≥65 years of age; select dose with caution because of age-related decreases in hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy.^{1 84 85 86}

Docetaxel with cisplatin as first-line therapy for advanced NSCLC: Similar survival but increased incidence of diarrhea, infections, peripheral edema, and stomatitis in patients ≥65 years of age compared with younger adults.^{1 81 84 85 86}

Docetaxel with prednisone for treatment of advanced prostate cancer: Increased incidence of anemia, infection, nail changes, anorexia, and weight loss in patients ≥65 years of age compared with younger adults.^{1 84 85 86}

Docetaxel with cisplatin and fluorouracil for treatment of advanced gastric cancer: Increased incidence of lethargy, stomatitis, diarrhea, dizziness, edema, febrile neutropenia, and neutropenic infection in patients ≥65 years of age compared with younger adults; insufficient experience to determine whether geriatric patients respond differently than younger adults.^{1 84 86}

Docetaxel with cisplatin and fluorouracil as induction therapy for advanced head and neck cancer: Insufficient experience to determine whether geriatric patients respond differently than younger adults.^{1 84 86}

Docetaxel with doxorubicin and cyclophosphamide as adjuvant therapy for breast cancer: Insufficient experience to determine age-related differences in response or tolerance.^{1 84 86}

Hepatic Impairment

Consider alcohol content of docetaxel formulations available from various manufacturers.^{1 84 85 86} (See Alcohol Content under Cautions.)

Increased incidence of treatment-related mortality in patients with abnormal liver function.^{1 84 85 86} (See Hepatic Impairment in Boxed Warning.)

Common Adverse Effects

Alopecia, neutropenia, anemia, febrile neutropenia, hypersensitivity, thrombocytopenia, fluid retention, neuropathy, dysgeusia, dyspnea, constipation, anorexia, nail disorders, asthenia, pain, nausea, diarrhea, vomiting, infections, mucositis, skin reactions, myalgia.^{1 84 85 86}

Drug Interactions

Metabolized by CYP3A4.^{1 84 85 86}

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interactions likely with drugs that are inhibitors, inducers, or substrates of CYP3A.^{1 84 85 86}

Potent CYP3A4 inhibitors: Possible pharmacokinetic interaction (increased exposure to docetaxel).^{1 84 85 86} Avoid concomitant use; if concomitant use cannot be avoided, consider reducing docetaxel dosage and carefully monitor for toxicity.^{1 84 85 86} Manufacturer recommends considering a 50% reduction in docetaxel dosage based on limited pharmacokinetic data for ketoconazole; however, clinical data not available for use of this adjusted dosage in patients receiving potent CYP3A4 inhibitors.^{1 84 85 86} (See Specific Drugs under Interactions.)

Specific Drugs

Docetaxel Pharmacokinetics

Distribution

Extent

Not known whether docetaxel is distributed into milk.^{1 84 85 86}

Plasma Protein Binding

94–97%.^{1 84 85 86}

Elimination

Metabolism

Metabolized by CYP3A4.^{1 84 85 86}

Elimination Route

Eliminated in feces (75%) and in urine (6%), mainly as metabolites; <8% recovered in feces as unchanged drug within 48 hours.^{1 84 85 86}

Half-life

Half-lives for the α, β, and γ phases are about 4 minutes, 36 minutes, and 11.1 hours, respectively.^{1 84 85 86}

Special Populations

Clearance reduced and systemic exposure increased in patients with mild to moderate hepatic impairment (serum AST and/or ALT >1.5 times ULN concurrent with alkaline phosphatase >2.5 times ULN).^{1 84 85 86} Wide interindividual variation; insufficient data for dosage recommendation.^{1 84 85 86}

Stability

Storage

Parenteral

Polysorbate 80 (in docetaxel injection) can cause leaching of diethylhexyl phthalate (DEHP) from PVC containers.³⁶ Do not permit contact of docetaxel injection concentrate or reconstituted docetaxel solution with plasticized PVC equipment or devices.^{1 36 84 85 86} Store final diluted docetaxel solutions for infusion in glass or polypropylene containers or in plastic (polypropylene or polyolefin) bags and administer through polyethylene-lined administration sets.^{1 36 84 85 86}

Injection Concentrate Requiring One Dilution Step

Taxotere: Store unopened vials at 2–25°C in original package to protect from light.¹

Docetaxel injection concentrate (Hospira): Store unopened vials at 20–25°C in original package to protect from light.⁸⁴ Store multiple-dose vials at 2–8°C between uses, protected from light, for up to 28 days.⁸⁴

Docetaxel injection concentrate (Accord): Store unopened vials at 15–25°C in original package to protect from light.⁸⁶ Store multiple-dose vials at room temperature between uses, protected from light, for up to 28 days.⁸⁶

Freezing does not adversely affect injection concentrate.^{1 84 86}

Docetaxel infusion solution (prepared by mixing Taxotere injection concentrate with 0.9% sodium chloride injection or 5% dextrose injection): Store for up to 5 hours at 2–25°C before initiating the 1-hour IV infusion.¹ When prepared as directed and stored in non-PVC bags at 2–8°C, stable for up to 48 hours.¹

Docetaxel infusion solution (prepared by mixing injection concentrate [Hospira or Accord] with 0.9% sodium chloride injection or 5% dextrose injection): Store for up to 3 hours at 2–25°C before initiating the 1-hour IV infusion.^{84 86}

Injection Concentrate Requiring Two Dilution Steps

Docetaxel injection concentrate (Accord): Store unopened vials at 25°C (may be exposed to 15–30°C); protect from light.⁸⁶

Initial diluted solution (prepared by mixing contents of diluent vial with docetaxel injection concentrate): Store in refrigerator or at room temperature for up to 8 hours.⁸⁶

Final diluted solution for infusion (prepared by mixing initial diluted solution with 0.9% sodium chloride injection or 5% dextrose injection): Store for up to 3 hours at 2–25°C before initiating the 1-hour IV infusion.⁸⁶

Powder for Injection

Docefrez: 2–8°C in original package to protect from bright light.⁸⁵

Reconstituted solution: Store in refrigerator or at room temperature for up to 8 hours.⁸⁵

Docetaxel infusion solution (prepared by mixing reconstituted solution with 0.9% sodium chloride injection or 5% dextrose injection): Store for up to 5 hours at 2–25°C before initiating the 1-hour IV infusion.⁸⁵ When prepared as directed and stored in non-PVC bags at 2–8°C, stable for up to 48 hours.⁸⁵

Compatibility

Parenteral

Reconstituted and diluted docetaxel solutions are supersaturated; crystallization may occur over time.^{1 85}

Solution Compatibility1 HID

Drug Compatibility

Actions

• A semisynthetic taxoid produced from the needles of the European yew (Taxus baccata) tree.^{1 2 3 4 5 6} Structurally and pharmacologically similar to paclitaxel.^{2 4 5 7 8}

• Disrupts the microtubular network in cells that is essential for mitotic and interphase cellular function.¹

Advice to Patients

• Importance of recognizing and reporting adverse effects including myalgia, neurologic effects, and cutaneous reactions.^{1 84 85 86}

• Importance of reading the patient information leaflet.^{1 84 85 86}

• Importance of recognizing and reporting signs of alcohol intoxication (e.g., confusion, stumbling, drowsiness).^{1 84 85 86 90} Advise patients to avoid driving, operating machinery, or performing other dangerous activities for 1–2 hours following administration of the drug.⁹⁰

• Risk of cystoid macular edema.^{1 84 85 86}

• Importance of recognizing and immediately reporting manifestations of a hypersensitivity reaction (e.g., difficulty breathing or swallowing, facial swelling, rash).^{1 84 85 86}

• Importance of taking the oral corticosteroid premedication as directed to prevent severe hypersensitivity reactions and minimize incidence and severity of fluid retention; importance of patients informing clinicians of noncompliance.^{1 84 85 86}

• Importance of recognizing and reporting signs of fluid retention (e.g., peripheral edema in lower extremities, weight gain, dyspnea).^{1 84 85 86}

• Importance of obtaining routine blood cell counts; inform patients to monitor temperature frequently and immediately inform clinician of fever.^{1 84 85 86}

• Risk of nausea, vomiting, diarrhea, constipation, fatigue, excessive tearing, infusion site reactions, and alopecia.^{1 84 85 86}

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed; necessity for clinicians to advise women to avoid pregnancy and to use an effective method of contraception during therapy.^{1 84 85 86} Advise pregnant women of risk to fetus.^{1 84 85 86}

• Importance of patients informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illness.^{1 84 85 86}

• Importance of informing patients of other important precautionary information.^{1 84 85 86} (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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