DOCEtaxel

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Concentrate, Intravenous:

Taxotere: 20 mg/mL (1 mL); 80 mg/4 mL (4 mL) [contains alcohol, usp, polysorbate 80]

Generic: 20 mg/mL (1 mL); 80 mg/4 mL (4 mL); 160 mg/8 mL (8 mL); 200 mg/10 mL (10 mL); 20 mg/0.5 mL (0.5 mL [DSC]); 80 mg/2 mL (2 mL [DSC])

Concentrate, Intravenous [preservative free]:

Generic: 20 mg/mL (1 mL [DSC]); 80 mg/4 mL (4 mL [DSC]); 140 mg/7 mL (7 mL [DSC]); 160 mg/8 mL (8 mL)

Solution, Intravenous:

Generic: 20 mg/2 mL (2 mL); 80 mg/8 mL (8 mL); 160 mg/16 mL (16 mL); 200 mg/20 mL (20 mL [DSC]); 20 mg/mL (1 mL [DSC]); 80 mg/4 mL (4 mL [DSC]); 160 mg/8 mL (8 mL [DSC])

Solution Reconstituted, Intravenous:

Docefrez: 20 mg (1 ea [DSC]) [contains alcohol, usp, polysorbate 80]

Pharmacology

Mechanism of Action

Docetaxel promotes the assembly of microtubules from tubulin dimers, and inhibits the depolymerization of tubulin which stabilizes microtubules in the cell. This results in inhibition of DNA, RNA, and protein synthesis. Most activity occurs during the M phase of the cell cycle.

Pharmacokinetics/Pharmacodynamics

Distribution

Extensive extravascular distribution and/or tissue binding; V_dss: 113 L (mean steady state)

Metabolism

Hepatic; oxidation via CYP3A4 to metabolites

Excretion

Feces (~75%, <8% as unchanged drug); urine (~6%)

Half-Life Elimination

Terminal: ~11 hours

Protein Binding

~94% to 97%, primarily to alpha₁-acid glycoprotein, albumin, and lipoproteins

Use in Specific Populations

Special Populations: Hepatic Function Impairment

Total body clearance is reduced by average of 27% and AUC increased 38% in patients with mild to moderate hepatic function impairment (ALT and/or AST more than 1.5 × ULN concomitant with alkaline phosphatase more than 2.5 × ULN).

Use: Labeled Indications

Breast cancer: Treatment of breast cancer (locally advanced/metastatic) after prior chemotherapy failure; adjuvant treatment (in combination with doxorubicin and cyclophosphamide) of operable node-positive breast cancer

Gastric cancer: Treatment of advanced gastric adenocarcinoma, including gastroesophageal junction adenocarcinoma (in combination with cisplatin and fluorouracil) in patients who have not received prior chemotherapy for advanced disease

Head and neck cancer: Treatment (induction) of locally advanced squamous cell head and neck cancer (in combination with cisplatin and fluorouracil)

Non-small cell lung cancer: Treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of prior platinum-based chemotherapy; treatment of previously untreated unresectable locally advanced or metastatic NSCLC (in combination with cisplatin)

Prostate cancer: Treatment of metastatic castration-resistant prostate cancer (in combination with prednisone)

Use: Off Label

Bladder cancer, metastatic (single-agent)b

Data from a small phase II study supports the use of docetaxel as a single agent in the management of previously treated advanced or metastatic bladder cancer McCaffrey 1997. Data from an additional small phase II study supports the use of docetaxel (in combination with gemcitabine and cisplatin) in the treatment of advanced bladder cancer Pectasides 2002.

Esophageal cancer, chemoradiationb

Data from a phase II study supports the use of docetaxel (in combination with cisplatin/radiation) as sequential chemotherapy and chemoradiation in the treatment of esophageal cancer Ruhstaller 2009. Data from a single-center study supports the use of docetaxel (in combination with cisplatin/radiation) as definitive chemoradiation in the treatment of esophageal cancer Li 2010.

Esophageal cancer, locally-advanced or metastatic diseasea

Data from two large phase III studies supports the use of docetaxel (in combination with cisplatin and fluorouracil) in the management of locally recurrent or metastatic esophageal cancer Ajani 2007, Van Cutsem 2006. Data from a small phase II study supports the use of docetaxel (in combination with fluorouracil, leucovorin, and oxaliplatin) in the management of metastatic esophageal cancer Al-Batran 2008. Data from a phase II study supports the use of docetaxel (in combination with cisplatin, fluorouracil and radiotherapy) for the neoadjuvant management of locally advanced esophageal cancer Pasini 2013.

Ewing sarcoma, osteosarcoma (recurrent or progressive)c

Data from a limited number of patients studied suggest that docetaxel (in combination with gemcitabine) may be beneficial for the treatment of recurrent or progressive osteosarcoma or Ewing sarcoma Navid 2008.

Ovarian cancera

Data from a large phase III study supports the use of docetaxel (in combination with carboplatin) as first-line treatment of ovarian cancer Vasey 2004. Data from two phase II studies also support the use of docetaxel (in combination with carboplatin) for the treatment of ovarian cancer Markman 2001, Kushner 2007.

Prostate cancer, metastatic, hormone-sensitivea

Data from 2 large randomized studies support the use of docetaxel (in combination with androgen-deprivation therapy) as first-line treatment of metastatic hormone-sensitive prostate cancer James 2016, Sweeney 2015.

Small cell lung cancer, relapsedb

Data from a small phase II study supports the use of docetaxel as a single agent in the management of previously treated locally advanced or metastatic small cell lung cancer Smyth 1994.

Soft tissue sarcomab

Data from a phase II study supports the use of docetaxel (in combination with gemcitabine) in the management of metastatic soft tissue sarcoma Maki 2007. A retrospective review also suggest that docetaxel (in combination with gemcitabine) may be beneficial for the treatment of soft tissue sarcoma Leu 2004.

Unknown-primary, adenocarcinomab

Data from small phase II studies support the use of docetaxel (either in combination with carboplatin, cisplatin, or gemcitabine) in the management of unknown primary adenocarcinoma Greco 2000, Mukai 2010, Pouessel 2004.

Contraindications

Severe hypersensitivity to docetaxel or any component of the formulation; severe hypersensitivity to other medications containing polysorbate 80; neutrophil count <1,500/mm³

Canadian labeling: Additional contraindications (not in the US labeling): Severe hepatic impairment; pregnancy; breastfeeding

Dosage and Administration

Dosing: Adult

Note: Docefrez has been discontinued in the US for more than 1 year.

Note: Premedicate with corticosteroids for 3 days, beginning one day prior to docetaxel administration, to reduce the severity of hypersensitivity reactions and fluid retention. Patients being treated for prostate cancer with concurrent prednisone should be premedicated with oral dexamethasone at 12 hours, 3 hours, and 1 hour prior to docetaxel administration.

Bladder cancer, metastatic (off-label use): IV: 100 mg/m² every 3 weeks (as a single agent) (McCaffrey 1997) or 35 mg/m² on days 1 and 8 of a 21-day cycle (in combination with gemcitabine and cisplatin) for at least 6 cycles or until disease progression or unacceptable toxicity (Pectasides 2002).

Breast cancer: IV:

Locally advanced or metastatic: 60 to 100 mg/m² every 3 weeks (as a single agent).

Operable, node-positive (adjuvant treatment): TAC regimen: 75 mg/m² every 3 weeks for 6 courses (in combination with doxorubicin and cyclophosphamide) (Mackey 2013; Martin 2005).

Adjuvant treatment (off-label dosing): 75 mg/m² every 21 days (in combination with cyclophosphamide) for 4 cycles (Jones 2006) or 75 mg/m² every 21 days (in combination with carboplatin and trastuzumab) for 6 cycles (Slamon 2011).

Neoadjuvant treatment (off-label dosing): 75 mg/m² (cycle 1; if tolerated, may increase to 100 mg/m² in subsequent cycles) every 21 days for a total of 4 cycles (in combination with trastuzumab and pertuzumab) (Gianni 2012).

Metastatic treatment (off-label dosing):

Every-3-week administration: 75 mg/m² (cycle 1; may increase to 100 mg/m² in subsequent cycles) every 21 days for at least 6 cycles (in combination with trastuzumab and pertuzumab) (Baselga 2012; Swain 2013) or 100 mg/m² every 21 days (in combination with trastuzumab) for at least 6 cycles (Marty 2005) or 75 mg/m² every 21 days (in combination with capecitabine) until disease progression or unacceptable toxicity (O’Shaughnessy 2002) or 60 mg/m², 75 mg/m², or 100 mg/m² every 21 days for at least 6 cycles until disease progression, unacceptable toxicity, or discontinuation (Harvey 2006).

Weekly administration: 40 mg/m²/dose once a week (as a single agent) for 6 weeks followed by a 2-week rest, repeat until disease progression or unacceptable toxicity (Burstein 2000) or 35 mg/m²/dose once weekly for 3 weeks, followed by a 1-week rest, may increase to 40 mg/m² once weekly for 3 weeks followed by a 1-week rest with cycle 2 (Rivera 2008) or 35 mg/m²/dose once weekly (in combination with trastuzumab) for 3 weeks followed by a 1-week rest; repeat until disease progression or unacceptable toxicity (Esteva 2002).

Esophageal cancer (off-label use): IV:

Sequential chemotherapy and chemoradiation: Induction: 75 mg/m² on days 1 and 22 (in combination with cisplatin) for 2 cycles, followed by chemoradiation: 20 mg/m² weekly for 5 weeks (in combination with cisplatin and radiation) (Ruhstaller 2009).

Definitive chemoradiation: 60 mg/m² on days 1 and 22 (in combination with cisplatin and radiation) for 1 cycle (Li 2010).

Locally advanced or metastatic disease: 75 mg/m² on day 1 every 3 weeks (in combination with cisplatin and fluorouracil) (Ajani 2007; Van Cutsem 2006) or 50 mg/m² on day 1 every 2 weeks (in combination with fluorouracil, leucovorin, and oxaliplatin) until disease progression or unacceptable toxicity up to a maximum of 8 cycles (Al-Batran 2008) or 35 mg/m² on days 1, 8, 15, 29, 36, 43, 50, and 57 (in combination with cisplatin, fluorouracil, and radiotherapy; neoadjuvant setting) (Pasini 2013).

Ewing sarcoma or osteosarcoma, recurrent or progressive (off-label uses; based on limited data): Adults ≤23 years of age: IV: 100 mg/m² on day 8 of a 21-day cycle (in combination with gemcitabine) (Navid 2008).

Gastric adenocarcinoma: IV: 75 mg/m² every 3 weeks (in combination with cisplatin and fluorouracil).

Sequential chemotherapy and chemoradiation (off-label dosing): Induction: 75 mg/m² on days 1 and 22 (in combination with cisplatin) for 2 cycles, followed by chemoradiation: 20 mg/m² weekly for 5 weeks (in combination with cisplatin and radiation) (Ruhstaller 2009).

Locally advanced or metastatic disease (off-label dosing): 50 mg/m² on day 1 every 2 weeks (in combination with fluorouracil, leucovorin, and oxaliplatin) until disease progression or unacceptable toxicity up to a maximum of 8 cycles (Al-Batran 2008).

Head and neck cancer: IV: 75 mg/m² every 3 weeks (in combination with cisplatin and fluorouracil) for 3 or 4 cycles, followed by radiation therapy.

Non-small cell lung cancer: IV: 75 mg/m² every 3 weeks (as a single agent or in combination with cisplatin).

Ovarian cancer (off-label use): IV: 60 mg/m² every 3 weeks (in combination with carboplatin) for up to 6 cycles (Markman 2001) or 75 mg/m² every 3 weeks (in combination with carboplatin) for 6 cycles (Vasey 2004) or 35 mg/m² (maximum dose: 70 mg) weekly for 3 weeks followed by a 1-week rest (in combination with carboplatin) (Kushner 2007).

Prostate cancer, castration-resistant, metastatic: IV: 75 mg/m² every 3 weeks (in combination with prednisone).

Prostate cancer, hormone-sensitive, metastatic (off-label use): 75 mg/m² on day 1 every 3 weeks (in combination with androgen deprivation therapy and prednisolone) for 6 cycles (James 2016) or 75 mg/m² on day 1 every 3 weeks (in combination with androgen deprivation therapy; daily prednisone not required) for 6 cycles (Sweeney 2015).

Small cell lung cancer, relapsed (off-label use): IV: 100 mg/m² every 3 weeks (Smyth 1994).

Soft tissue sarcoma (off-label use): IV: 100 mg/m² on day 8 of a 3-week treatment cycle (in combination with gemcitabine and filgrastim or pegfilgrastim) (Leu 2004; Maki 2007).

Unknown-primary, adenocarcinoma (off-label use): IV: 65 mg/m² every 3 weeks (in combination with carboplatin) (Greco 2000) or 75 mg/m² on day 8 of a 3-week treatment cycle (in combination with gemcitabine) for up to 6 cycles (Pouessel 2004) or 60 mg/m² on day 1 of a 3-week treatment cycle (in combination with cisplatin) (Mukai 2010).

Dosing adjustment for concomitant CYP3A4 inhibitors: Avoid the concomitant use of strong CYP3A4 inhibitors with docetaxel. If concomitant use of a strong CYP3A4 inhibitor cannot be avoided, consider reducing the docetaxel dose by 50% (based on limited pharmacokinetic data).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Docefrez has been discontinued in the US for more than 1 year. Dose, frequency, number of doses, and start date may vary by protocol and treatment phase. Refer to individual protocols: Premedicate with corticosteroids, beginning the day before docetaxel administration (administer corticosteroids for 1 to 3 days), to reduce the severity of hypersensitivity reactions and pulmonary/peripheral edema. Docetaxel is associated with a low emetic potential (Dupuis 2011); antiemetics are recommended to prevent nausea and vomiting (Dupuis 2013)

Sarcomas, Ewing Sarcoma; osteosarcoma (recurrent or progressive): Limited data available:

Mora 2009: G + D regimen: Children and Adolescents: IV: 100 mg/m² over 2 to 4 hours on Day 8 of a 21-day cycle in combination with gemcitabine

Rapkin 2012: GEMDOX regimen:

Infants: IV: 2.5 mg/kg over 1 hour on Day 8 of a 21-day cycle in combination with gemcitabine

Children and Adolescents: IV: 75 mg/m² over 1 hour on Day 8 of a 21-day cycle in combination with gemcitabine

Hepatoblastoma (refractory or relapsed): Limited data available, case-series reports (George 2012): Infants and Children:

Patient weight <10 kg: IV: 3.3 mg/kg as a 1-hour infusion every 21 days

Patient weight >10 kg: IV: 100 mg/m² given as a 1-hour infusion every 21 days

Dosing adjustment for concomitant CYP3A4 inhibitors: Specific pediatric recommendations are lacking; based on experience in adult patients: Avoid the concomitant use of strong CYP3A4 inhibitors with docetaxel. If concomitant use of a strong CYP3A4 inhibitor cannot be avoided, consider reducing the docetaxel dose.

Dosing adjustment for toxicity: The presented dosing adjustments are based on experience in adult patients; specific recommendations for pediatric patients are limited. Refer to specific protocol for management in pediatric patients if available.

Adult: Note: Toxicity includes febrile neutropenia, neutrophils ≤500/mm³ for >1 week, severe or cumulative cutaneous reactions; in non-small cell lung cancer, this may also include platelets <25,000/mm³ and other grade 3/4 nonhematologic toxicities.

Breast cancer (single agent): Patients dosed initially at 100 mg/m² (adult); reduce dose to 75 mg/m² (adult); Note: If the patient continues to experience these adverse reactions, the dosage should be reduced to 55 mg/m² (adult) or therapy should be discontinued; discontinue for peripheral neuropathy ≥ grade 3. Patients initiated at 60 mg/m² (adult) who do not develop toxicity may tolerate higher doses.

Breast cancer, adjuvant treatment (combination chemotherapy): TAC regimen should be administered when neutrophils are ≥1,500/mm³. Patients experiencing febrile neutropenia should receive G-CSF in all subsequent cycles. Patients with persistent febrile neutropenia (while on G-CSF), patients experiencing severe/cumulative cutaneous reactions, moderate neurosensory effects (signs/symptoms) or grade 3 or 4 stomatitis should receive a reduced dose (60 mg/m² in adults) of docetaxel. Discontinue therapy with persistent toxicities after dosage reduction.

Non-small cell lung cancer:

Monotherapy: Patients dosed initially at 75 mg/m² (adult) should have dose held until toxicity is resolved, then resume at 55 mg/m² (adult); discontinue for peripheral neuropathy ≥ grade 3

Combination therapy (with cisplatin): Patients dosed initially at 75 mg/m² (adult) should have the docetaxel dosage reduced to 65 mg/m² (adult) in subsequent cycles; if further adjustment is required, dosage may be reduced to 50 mg/m² (adult)

Prostate cancer: Reduce dose to 60 mg/m² (adult); discontinue therapy if toxicities persist at lower dose.

Gastric cancer, head and neck cancer: Note: Cisplatin may require dose reductions/therapy delays for peripheral neuropathy, ototoxicity, and/or nephrotoxicity. Patients experiencing febrile neutropenia, documented infection with neutropenia or neutropenia >7 days should receive G-CSF in all subsequent cycles. For neutropenic complications despite G-CSF use, further reduce dose to 60 mg/m² (adult). Dosing with neutropenic complications in subsequent cycles should be further reduced to 45 mg/m² (adult). Patients who experience grade 4 thrombocytopenia should receive a dose reduction from 75 mg/m² to 60 mg/m² (adult dosing). Discontinue therapy for persistent toxicities.

Gastrointestinal toxicity for docetaxel in combination with cisplatin and fluorouracil for treatment of gastric cancer or head and neck cancer:

Diarrhea, grade 3:

First episode: Reduce fluorouracil dose by 20%

Second episode: Reduce docetaxel dose by 20%

Diarrhea, grade 4:

First episode: Reduce fluorouracil and docetaxel doses by 20%

Second episode: Discontinue treatment

Stomatitis, grade 3:

First episode: Reduce fluorouracil dose by 20%

Second episode: Discontinue fluorouracil for all subsequent cycles

Third episode: Reduce docetaxel dose by 20%

Stomatitis, grade 4:

First episode: Discontinue fluorouracil for all subsequent cycles

Second episode: Reduce docetaxel dose by 20%

Dosing: Adjustment for Toxicity

Note: Toxicity includes febrile neutropenia, neutrophils <500/mm³ for >1 week, severe or cumulative cutaneous reactions; in non-small cell lung cancer, this may also include platelet nadir <25,000/mm³ and other grade 3/4 nonhematologic toxicities.

Dermatologic toxicity: Consider permanent docetaxel discontinuation in patients who develop severe cutaneous adverse reactions.

Hypersensitivity: Immediately discontinue docetaxel for severe hypersensitivity reaction.

Neurosensory symptoms (eg, paresthesia, dysesthesia, pain): Adjust docetaxel dose for severe neurosensory symptoms; discontinue docetaxel for persistent symptoms.

Ocular disorders: Discontinue docetaxel if cystoid macular edema is diagnosed.

Also refer to specific reference/protocol for dosage adjustments for off-label uses or combinations.

Breast cancer (single agent): Patients dosed initially at 100 mg/m²; reduce dose to 75 mg/m²; Note: If the patient continues to experience these adverse reactions, the dosage should be reduced to 55 mg/m² or therapy should be discontinued; discontinue for peripheral neuropathy ≥ grade 3. Patients initiated at 60 mg/m² who do not develop toxicity may tolerate higher doses.

Breast cancer, adjuvant treatment (combination chemotherapy): TAC regimen should be administered when neutrophils are ≥1,500/mm³. Patients experiencing febrile neutropenia should receive G-CSF in all subsequent cycles. Patients with persistent febrile neutropenia (while on G-CSF), patients experiencing severe/cumulative cutaneous reactions, moderate neurosensory effects (signs/symptoms) or grade 3 or 4 stomatitis should receive a reduced dose (60 mg/m²) of docetaxel. Discontinue therapy with persistent toxicities after dosage reduction.

Non-small cell lung cancer:

Monotherapy: Patients dosed initially at 75 mg/m² should have dose held until toxicity is resolved, then resume at 55 mg/m²; discontinue for peripheral neuropathy ≥ grade 3.

Combination therapy (with cisplatin): Patients dosed initially at 75 mg/m² should have the docetaxel dosage reduced to 65 mg/m² in subsequent cycles; if further adjustment is required, dosage may be reduced to 50 mg/m².

Prostate cancer: Reduce dose to 60 mg/m²; discontinue therapy if toxicities persist at lower dose.

Gastric cancer, head and neck cancer: Note: Cisplatin may require dose reductions/therapy delays for peripheral neuropathy, ototoxicity, and/or nephrotoxicity. Patients experiencing febrile neutropenia, documented infection with neutropenia or neutropenia >7 days should receive G-CSF in all subsequent cycles. For neutropenic complications despite G-CSF use, reduce dose to 60 mg/m². Dosing with neutropenic complications in subsequent cycles should be further reduced (following neutrophil recovery to ≥1,500/mm³) to 45 mg/m². Patients who experience grade 4 thrombocytopenia should receive a dose reduction from 75 mg/m² to 60 mg/m² (following platelet recovery to >100,000/mm³). Discontinue therapy for persistent toxicities.

Gastrointestinal toxicity for docetaxel in combination with cisplatin and fluorouracil for treatment of gastric cancer or head and neck cancer:

Diarrhea, grade 3:

First episode: Reduce fluorouracil dose by 20%.

Second episode: Reduce docetaxel dose by 20%.

Diarrhea, grade 4:

First episode: Reduce fluorouracil and docetaxel doses by 20%.

Second episode: Discontinue treatment.

Stomatitis, grade 3:

First episode: Reduce fluorouracil dose by 20%.

Second episode: Discontinue fluorouracil for all subsequent cycles.

Third episode: Reduce docetaxel dose by 20%.

Stomatitis, grade 4:

First episode: Discontinue fluorouracil for all subsequent cycles.

Second episode: Reduce docetaxel dose by 20%.

Dosing: Obesity

ASCO Guidelines for appropriate chemotherapy dosing in obese adults with cancer: Utilize patient’s actual body weight (full weight) for calculation of body surface area- or weight-based dosing, particularly when the intent of therapy is curative; manage regimen-related toxicities in the same manner as for nonobese patients; if a dose reduction is utilized due to toxicity, consider resumption of full weight-based dosing with subsequent cycles, especially if cause of toxicity (eg, hepatic or renal impairment) is resolved (Griggs 2012).

Reconstitution

Preparation instructions may vary by manufacturer, refer to specific prescribing information. Note: Some formulations contain overfill.

Note: Multiple concentrations: Docetaxel is available as a one-vial formulation at concentrations of 10 mg/mL (generic formulation) and 20 mg/mL (concentrate/solution; Taxotere, generic [including a non-alcohol generic formulation]), and as a lyophilized powder (Docefrez) which is reconstituted (with provided diluent) to 20 mg/0.8 mL (20 mg vial) or 24 mg/mL (80 mg vial). Admixture errors have occurred due to the availability of various concentrations. Docetaxel was previously available as a two-vial formulation which included two vials (a concentrated docetaxel vial and a diluent vial), resulting in a reconstituted concentration of 10 mg/mL; the two-vial formulation has been discontinued by the Taxotere manufacturer (available generically).

One-vial formulations: Further dilute for infusion in 250 to 500 mL of NS or D5W in a non-DEHP container (eg, glass, polypropylene, polyolefin) to a final concentration of 0.3 to 0.74 mg/mL. Gently rotate and invert manually to mix thoroughly; avoid shaking or vigorous agitation.

Non-alcohol formulation: Use a 20 gauge needle to withdraw docetaxel from the vial; dilute in 250 mL of NS or D5W to a final concentration of 0.3 to 0.74 mg/mL. If docetaxel dose is >200 mg, use a larger volume of infusion fluid to maintain a final concentration of 0.3 to 0.74 mg/mL. Mix by gentle manual rotation.

Taxotere: Use only a 21 gauge needle to withdraw docetaxel from the vial (larger bore needles, such as 18 gauge or 19 gauge needles, may cause stopper coring and rubber precipitates). If intact vials were stored refrigerated, allow to stand at room temperature for 5 minutes prior to dilution. Inspect vials prior to dilution; solution is supersaturated and may crystalize over time; do not use if crystalized.

Lyophilized powder: Dilute with the provided diluent (contains ethanol in polysorbate 80); add 1 mL to each 20 mg vial (resulting concentration is 20 mg/0.8 mL) and 4 mL to each 80 mg vial (resulting concentration is 24 mg/mL). Shake well to dissolve completely. Reconstituted solution is supersaturated and could crystallize over time; if crystals appear, discard the solution (should no longer be used). If air bubbles are present, allow to stand for a few minutes while air bubbles dissipate. Further dilute in 250 mL of NS or D5W in a non-DEHP container (eg, glass, polypropylene, polyolefin) to a final concentration of 0.3 to 0.74 mg/mL (for doses >200 mg, use a larger volume of NS or D5W, not to exceed a final concentration of 0.74 mg/mL). Mix thoroughly by manual agitation.

Two-vial formulation (generic; concentrate plus diluent formulation): Vials should be diluted with 13% (w/w) polyethylene glycol 400/water (provided with the drug) to a final concentration of 10 mg/mL. Do not shake. Further dilute for infusion in 250 to 500 mL of NS or D5W in a non-DEHP container (eg, glass, polypropylene, polyolefin) to a final concentration of 0.3 to 0.74 mg/mL. Gently rotate to mix thoroughly. Do not use the two-vial formulation with the one-vial formulation for the same admixture product.

Administration

IV: Infuse over 1 hour through nonsorbing polyethylene lined (non-DEHP) tubing. Note: Premedication with corticosteroids for 3 days, beginning the day before docetaxel administration, is recommended to reduce the incidence and severity of hypersensitivity reactions and fluid retention. Some docetaxel formulations contain alcohol (content varies by formulation); use with caution in patients for whom alcohol intake should be avoided or minimized (a non-alcohol generic formulation [20 mg/mL] is also available).

The use of an in-line filter is not necessary during Taxotere administration; according to the manufacturer, studies have not been performed to determine the compatibility of IV filters for administration and filters are not recommended for use with docetaxel (data on file [Sanofi Aventis 2016]). The use of an inline filter is also not recommended for administration of the non-alcohol docetaxel formulation (data on file [Eagle Pharmaceuticals 2016]).

Irritant with vesicant-like properties; avoid extravasation. Assure proper needle or catheter position prior to administration.

Extravasation management: If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); remove needle/cannula; elevate extremity. Information conflicts regarding the use of warm or cold compresses (Perez Fidalgo 2012; Polovich 2009).

Storage

Storage and stability may vary by manufacturer, refer to specific prescribing information. Follow USP 797 recommendations for beyond use dates based on the level of risk for preparation.

Docetaxel 10 mg/mL: Store intact vials between 2°C to 25°C (36°F to 77°F) (actual recommendations may vary by generic manufacturer; consult manufacturer's labeling). Protect from bright light. Freezing does not adversely affect the product. Multidose vials are stable for up to 28 days after first entry when stored between 2°C to 8°C (36°F to 46°F) and protected from light (actual recommendations may vary by generic manufacturer; consult manufacturer's labeling). Solutions diluted for infusion should be used within 4 hours of preparation, including infusion time.

Docetaxel 20 mg/mL concentrate/solution:

Taxotere: Store intact vials between 2°C to 25°C (36°F to 77°F). Protect from bright light. Freezing does not adversely affect the product. Solutions diluted for infusion in D5W or NS in non-PVC containers should be used within 6 hours of preparation, including infusion time, when stored between 2°C to 25°C (36°F to 77°F) or within 48 hours when stored between 2°C to 8°C (36°F to 46°F).

Generic formulations: Store intact vials between 2°C to 25°C (36°F to 77°F). Protect from light. Freezing does not adversely affect the product. Multi-use vials are stable for up to 28 days after first entry when stored between 2°C to 8°C (36°F to 46°F) and protected from light. Solutions diluted for infusion in D5W or NS should be used within 6 hours of preparation, including infusion time. Actual recommendations may vary by generic manufacturer; consult manufacturer's labeling.

Non-alcohol formulation: Store intact vials at 20°C to 25°C (68°F to 77°F). Protect from light. After the first use and following multiple needle entries and withdrawals, multi-use vials (80 mg/4 mL and 160 mg/8 mL) are stable for up to 28 days when stored between 2°C to 8°C (36°F to 46°F) and protected from light. Solutions diluted for infusion in NS or D5W are stable for 24 hours when stored between 2°C to 8°C (36°F to 46°F).

Docetaxel lyophilized powder (Docefrez): Store intact vials between 2°C to 8°C (36°F to 46°F). Protect from light. Allow vials (and provided diluent) to stand at room temperature for 5 minutes prior to reconstitution. After reconstitution, may be stored refrigerated or at room temperature for up to 8 hours. Solutions diluted for infusion in D5W or NS should be used within 6 hours of preparation, including infusion time. According to the manufacturer, physical and chemical in-use stability of the infusion solution (prepared as recommended) has been demonstrated in non-PVC bags up to 48 hours when stored between 2°C and 8°C (36°F and 46°F).

Two-vial formulation (generic; concentrate plus diluent formulation): Reconstituted solutions of the two-vial formulation are stable in the vial for 8 hours at room temperature or under refrigeration. Solutions diluted for infusion in NS or D5W in polyolefin containers should be used within 4 hours of preparation, including infusion time.

Drug Interactions

Anthracyclines: Taxane Derivatives may enhance the adverse/toxic effect of Anthracyclines. Taxane Derivatives may increase the serum concentration of Anthracyclines. Taxane Derivatives may also increase the formation of toxic anthracycline metabolites in heart tissue. Consider therapy modification

Baricitinib: Immunosuppressants may enhance the immunosuppressive effect of Baricitinib. Management: Use of baricitinib in combination with potent immunosuppressants such as azathioprine or cyclosporine is not recommended. Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted. Consider therapy modification

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Monitor therapy

Cladribine: May enhance the immunosuppressive effect of Immunosuppressants. Avoid combination

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Avoid combination

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of DOCEtaxel. Management: Avoid the concomitant use of docetaxel and strong CYP3A4 inhibitors when possible. If combined use is unavoidable, consider a 50% docetaxel dose reduction and monitor for increased docetaxel toxicities. Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Consider therapy modification

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination

Dronedarone: May increase the serum concentration of DOCEtaxel. Management: Avoid this combination whenever possible. If this combination must be used, consider using a reduced docetaxel dose, and/or increase monitoring for evidence of serious docetaxel toxicity (e.g., neutropenia, mucositis, etc.). Consider therapy modification

Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Erdafitinib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Lasmiditan: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Avoid combination

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification

Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Consider therapy modification

Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Consider therapy modification

Lorlatinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. Consider therapy modification

Mesalamine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification

Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification

Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Consider therapy modification

P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

Pidotimod: Immunosuppressants may diminish the therapeutic effect of Pidotimod. Monitor therapy

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Platinum Derivatives: May enhance the myelosuppressive effect of Taxane Derivatives. Administer Taxane derivative before Platinum derivative when given as sequential infusions to limit toxicity. Consider therapy modification

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Ranolazine: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Siponimod: Immunosuppressants may enhance the immunosuppressive effect of Siponimod. Monitor therapy

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy. Consider therapy modification

Smallpox and Monkeypox Vaccine (Live): Immunosuppressants may diminish the therapeutic effect of Smallpox and Monkeypox Vaccine (Live). Monitor therapy

SORAfenib: May increase the serum concentration of DOCEtaxel. Monitor therapy

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Consider therapy modification

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy

Upadacitinib: Immunosuppressants may enhance the immunosuppressive effect of Upadacitinib. Avoid combination

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Exceptions: Smallpox and Monkeypox Vaccine (Live). Avoid combination

Adverse Reactions

Percentages reported for docetaxel monotherapy; frequency may vary depending on diagnosis, dose, liver function, prior treatment, and premedication.

>10%:

Dermatologic: Alopecia (56% to 76%), dermatological reaction (20% to 48%), nail disease (11% to 41%)

Endocrine & metabolic: Fluid retention (26% to 60%)

Gastrointestinal: Stomatitis (26% to 53%; grades 3/4: 2%), diarrhea (23% to 43%), nausea (34% to 42%), vomiting (22% to 23%)

Hematologic & oncologic: Neutropenia (84% to 99%; grade 4: 75% to 86%; grades 3/4: 65%; nadir [median]: 7 days, duration [severe neutropenia]: 7 days), leukopenia (84% to 99%; grades 3/4: 49%; grade 4: 32% to 44%), anemia (87% to 97%; grades 3/4: 8% to 9%), thrombocytopenia (7% to 12% ; grades 3/4: 3%; grade 4: 1%), febrile neutropenia (5% to 14%)

Hepatic: Increased serum transaminases (4% to 19%)

Hypersensitivity: Hypersensitivity reaction (6% to 21%)

Infection: Infection (22% to 34%; severe: 6%)

Neuromuscular & skeletal: Asthenia (53% to 66%), myalgia (6% to 23%), neuromuscular reaction (16%)

Respiratory: Pulmonary disorder (41%)

Miscellaneous: Fever (31% to 35%)

1% to 10%:

Cardiovascular: Hypotension (3%)

Gastrointestinal: Dysgeusia (6%)

Hepatic: Increased serum bilirubin (9%), increased serum alkaline phosphatase (7%)

Infection: Severe infection (2% to 6%)

Local: Infusion site reaction (4%)

Nervous system: Neurotoxicity (grades 3/4: 2% to 6%), peripheral motor neuropathy (4%; severe; mainly distal extremity weakness)

Neuromuscular and skeletal: Arthralgia (3% to 9%)

Frequency not defined:

Cardiovascular: Cardiac tamponade, decreased left ventricular ejection fraction, localized phlebitis, peripheral edema

Dermatologic: Exfoliation of skin, local dryness of skin, localized erythema of the extremities, nail depigmentation, nail hyperpigmentation, skin discoloration at injection site

Hepatic: Ascites

Local: Erythema at injection site, inflammation at injection site

Nervous system: Fatigue

Respiratory: Pleural effusion

<1%, postmarketing, and/or case reports: Abdominal pain, acute hepatic failure (Morgan 2011), acute myelocytic leukemia, acute myocardial infarction, acute respiratory distress, alcohol intoxication, alopecia (permanent), anaphylactic shock, anorexia, atrial fibrillation, atrial flutter, back pain, bleeding tendency disorder, bronchospasm, cardiac arrhythmia, cardiac failure, chest pain, chest tightness, chills, colitis, confusion, conjunctivitis, constipation, cutaneous lupus erythematosus, cystoid macular edema, deafness, deep vein thrombosis, dehydration, dermatological reaction (injection site recall at previous site of extravasation), disease of the lacrimal apparatus (duct obstruction), disseminated intravascular coagulation, drug fever, duodenal ulcer, dyspnea, ECG abnormality, electrolyte disorder, enterocolitis, epiphora (more common with weekly administration [Kintzel 2006]), erythema multiforme, esophagitis, flushing, gastrointestinal hemorrhage, gastrointestinal perforation, hearing loss, hepatitis, hypertension, hypocalcemia, hypokalemia, hypomagnesemia, hyponatremia, intestinal obstruction, interstitial pulmonary disease, ischemic colitis, lacrimation, loss of consciousness (transient), lymphedema (peripheral), multiorgan failure, myelodysplastic syndrome, neutropenic enterocolitis, onycholysis, ototoxicity, pain, palmar-plantar erythrodysesthesia, pneumonia (interstitial), pneumonitis, pruritus, pulmonary edema, pulmonary embolism, pulmonary fibrosis, radiation pneumonitis, radiation recall phenomenon, renal failure syndrome, renal insufficiency, respiratory failure, skin changes (scleroderma-like), seizure, sepsis, sinus tachycardia, skin rash, Stevens-Johnson syndrome, syncope, tachycardia, thrombophlebitis, toxic epidermal necrolysis, unstable angina pectoris, ventricular arrhythmia, ventricular tachycardia, visual disturbance (transient)

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: [US Boxed Warning]: Do not administer docetaxel to patients with an absolute neutrophil count <1,500/mm³. Monitor blood counts frequently to monitor for neutropenia (which may be severe and result in infection). The dose-limiting toxicity is neutropenia. Neutrophils should recover to >1,500/mm³ and platelets should recover to >100,000/mm³ prior to treatment with subsequent cycles. Patients with increased liver function tests experienced more episodes of neutropenia with a greater number of severe infections; monitor liver function tests frequently. Hematologic toxicity may require dose reduction or therapy discontinuation.
• Cutaneous reactions: Cutaneous reactions, including erythema (with edema) and desquamation, have been reported; may require dose reduction. Severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome, toxic epidermal necrolysis, and acute generalized exanthematous pustulosis have been reported and may be associated with docetaxel. Monitor closely for signs/symptoms of serious skin toxicity; consider permanent discontinuation if SCARs develop.
• Extravasation: Docetaxel is an irritant with vesicant-like properties; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation.
• Fluid retention: [US Boxed Warning]: Severe fluid retention, characterized by pleural effusion (requiring immediate drainage), ascites with pronounced abdominal distention, peripheral edema (poorly tolerated), dyspnea at rest, cardiac tamponade, and/or generalized edema, has been reported (despite the use of premedication with dexamethasone). Fluid retention may begin as lower extremity peripheral edema and become generalized with a median weight gain of 2 kg. In patients with breast cancer, the median cumulative dose to onset of moderate or severe fluid retention was 819 mg/m²; fluid retention resolves in a median of 16 weeks after discontinuation. Patients should be premedicated with a corticosteroid (starting 1 day prior to administration) to reduce the incidence and severity of fluid retention. Closely monitor patients with existing effusions.
• GI toxicity: Enterocolitis and neutropenic colitis (typhlitis) have occurred with docetaxel (either as a single agent or in combination with other chemotherapy) and despite administration of filgrastim; may occur at any time and could be fatal on the first day of symptom onset. Use with caution in patients with neutropenia, particularly those at increased risk for developing GI complications. Inform patients to report new-onset or worsening symptoms of GI toxicity; monitor closely from onset of any GI toxicity symptoms.
• Hypersensitivity: [US Boxed Warning]: Severe hypersensitivity reactions have been reported despite dexamethasone premedication. Hypersensitivity reactions require immediate discontinuation of the docetaxel infusion and administration of appropriate therapy. Do not administer docetaxel to patients with a history of severe hypersensitivity to docetaxel or other drugs formulated with polysorbate 80. Severe hypersensitivity reactions have been characterized by generalized rash/erythema, hypotension, bronchospasm, and/or fatal anaphylaxis. Patients with a history of hypersensitivity reaction to paclitaxel may develop hypersensitivity to docetaxel; may be severe or fatal (including anaphylaxis); monitor patients with paclitaxel hypersensitivity closely during initiation of docetaxel therapy. Minor reactions including flushing or localized skin reactions may also occur. Observe for hypersensitivity, especially with the first 2 infusions. Discontinue for severe reactions; do not rechallenge if severe. Patients should be premedicated with a corticosteroid (starting 1 day prior to administration) to prevent or reduce the severity of hypersensitivity reactions.
• Neurosensory symptoms: Dosage adjustment is recommended with severe neurosensory symptoms (paresthesia, dysesthesia, pain); persistent symptoms may require discontinuation. Reversal of symptoms may be delayed after discontinuation.
• Ocular adverse effects: Cystoid macular edema (CME) has been reported; if vision impairment occurs, a prompt comprehensive ophthalmic exam is recommended. If CME is diagnosed, initiate appropriate CME management and discontinue docetaxel (consider non-taxane treatments). In a study of patients receiving docetaxel for the adjuvant treatment of breast cancer, a majority of patients experienced tearing, which occurred in patients with and without lacrimal duct obstruction at baseline. Onset was generally after cycle 1, but subsided in most patients within 4 months after therapy completion (Chan 2013).
• Secondary malignancies: Second primary malignancies, including acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), non-Hodgkin lymphoma, and renal cancer have occurred in patients several months or years after receiving docetaxel-containing regimens. Treatment-related AML or MDS has occurred in patients receiving docetaxel in combination with anthracyclines and/or cyclophosphamide (with or without fluorouracil), including patients who received docetaxel-containing regimens as adjuvant therapy. Monitor for second primary malignancies.
• Treatment-related mortality: [US Boxed Warning]: Treatment-related mortality associated with docetaxel is increased in patients with abnormal liver function, those receiving higher doses, and patients with non-small cell lung cancer and a history of prior treatment with platinum derivatives who receive single-agent docetaxel at a dose of 100 mg/m².
• Weakness: Fatigue and weakness (may be severe) have been reported; symptoms may last a few days up to several weeks. In patients with progressive disease, weakness may be associated with a decrease in performance status.

Disease-related concerns:

• Heart failure: In a scientific statement from the American Heart Association, docetaxel has been determined to be an agent that may either cause direct myocardial toxicity or exacerbate underlying myocardial dysfunction (magnitude: moderate) (AHA [Page 2016]).
• Hepatic impairment: [US Boxed Warning]: Avoid the use of docetaxel in patients with bilirubin > ULN or AST and/or ALT >1.5 times ULN in conjunction with alkaline phosphatase >2.5 times ULN. Patients with bilirubin elevations or abnormal transaminases (with concurrent abnormal alkaline phosphatase) are at increased risk for severe neutropenia, neutropenic fever, infections, severe thrombocytopenia, severe stomatitis, severe skin toxicity, and toxic death. Patients with isolated transaminase elevations >1.5 times ULN also had a higher rate of neutropenic fever. Monitor bilirubin, AST or ALT, and alkaline phosphatase prior to each docetaxel cycle. Consider docetaxel dose modification in patients with isolated transaminase elevations >1.5 times ULN. The alcohol content of the docetaxel formulation should be taken into account when administering to patients with hepatic impairment.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Dosage form specific issues:

• Alcohol content: Some docetaxel formulations contain alcohol (content varies by formulation), which may affect the central nervous system and cause symptoms of alcohol intoxication. Consider alcohol content and use with caution in patients for whom alcohol intake should be avoided or minimized. Patients should avoid driving or operating machinery immediately after the infusion. An FDA-approved non-alcohol generic formulation (20 mg/mL) is available.
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.

Other warnings/precautions:

• Premedication: Premedication with oral corticosteroids is recommended to decrease the incidence and severity of fluid retention and severity of hypersensitivity reactions. The manufacturer recommends dexamethasone 16 mg/day (8 mg twice daily) orally for 3 days, starting the day before docetaxel administration; for prostate cancer, when prednisone is part of the antineoplastic regimen, dexamethasone 8 mg orally is administered at 12 hours, 3 hours, and 1 hour prior to docetaxel.

Monitoring Parameters

CBC with differential (prior to each cycle), LFTs (bilirubin, ALT, AST, alkaline phosphatase; prior to each cycle), renal function. Evaluate pregnancy status prior to use in females of reproductive potential. Monitor for hypersensitivity reactions (patients with a history of paclitaxel hypersensitivity require close monitoring during initiation), neurosensory symptoms, GI toxicity (eg, diarrhea, stomatitis, enterocolitis, neutropenic colitis), cutaneous reactions or severe skin toxicity, visual impairment, fluid retention, epiphora, canalicular stenosis, and second primary malignancies.

Pregnancy

Pregnancy Considerations

An ex vivo human placenta perfusion model illustrated that docetaxel crossed the placenta at term. Placental transfer was low and affected by the presence of albumin; higher albumin concentrations resulted in lower docetaxel placental transfer (Berveiller 2012).

Based on the mechanism of action and data from animal reproduction studies, in utero exposure to docetaxel may cause fetal harm. Formulations may contain alcohol, which is also associated with adverse fetal effects.

Some pharmacokinetic properties of docetaxel may be altered in pregnant women (van Hasselt 2014). Data related to the use of docetaxel for the treatment of breast cancer in pregnancy is limited. Use should be restricted for clinically urgent situations; use of other agents is preferred. The European Society for Medical Oncology has published guidelines for diagnosis, treatment, and follow-up of cancer during pregnancy; the guidelines recommend referral to a facility with expertise in cancer during pregnancy and encourage a multidisciplinary team (obstetrician, neonatologist, oncology team). In general, if chemotherapy is indicated, it should be avoided in the first trimester and there should be a 3-week time period between the last chemotherapy dose and anticipated delivery, and chemotherapy should not be administered beyond week 33 of gestation (Peccatori 2013).

Evaluate pregnancy status prior to use in females of reproductive potential. Females of reproductive potential should use effective contraceptive measures before beginning treatment, during therapy, and for 6 months after the last docetaxel dose. Males with female partners of reproductive potential should use effective contraceptive measures during therapy and for 3 months after the last docetaxel dose.

A pregnancy registry is available for all cancers diagnosed during pregnancy at Cooper Health (877-635-4499).

Patient Education

What is this drug used for?

• It is used to treat cancer.

Frequently reported side effects of this drug

• Nausea
• Vomiting
• Mouth sores
• Hair loss
• Nail changes
• Change in taste
• Constipation
• Lack of appetite
• Muscle pain
• Joint pain
• Flushing
• Weight loss
• Eye redness
• Tearing

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Infection
• Bleeding like vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding
• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin.
• Fast heartbeat
• Abnormal heartbeat
• Muscle weakness
• Skin reaction
• Difficulty breathing
• Shortness of breath
• Cough
• Abdominal pain
• Tender stomach
• Diarrhea
• Dizziness
• Passing out
• Burning or numbness feeling
• Severe loss of strength and energy
• Confusion
• Drunk feeling
• Stumbling
• Severe fatigue
• Cystoid macular edema like vision changes, blindness
• Severe injection site redness, edema, pain, or irritation
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.