(doe se TAKS el)
US labeling:
Docefrez:
Breast cancer: Treatment of breast cancer (locally advanced/metastatic) after prior chemotherapy failure
Non-small cell lung cancer: Treatment of locally advanced or metastatic non " “small cell lung cancer (NSCLC) after prior platinum-based chemotherapy failure; treatment of previously untreated unresectable locally advanced or metastatic NSCLC (in combination with cisplatin)
Prostate cancer: Treatment of hormone-refractory metastatic prostate cancer (in combination with prednisone)
Taxotere (and various generic brands):
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)
NSCLC: Treatment of locally advanced or metastatic 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 androgen-independent (hormone refractory) metastatic prostate cancer (in combination with prednisone)
Canadian labeling:
Breast cancer: Treatment of breast cancer (locally advanced/metastatic [in combination with doxorubicin]; adjuvant treatment of operable node-positive [in combination with doxorubicin and cyclophosphamide]; advanced or metastatic [in combination with capecitabine] after failure of anthracycline-containing chemotherapy)
Head and neck cancer: Treatment (monotherapy) of recurrent and/or metastatic squamous cell head and neck cancer after failure of a prior chemotherapy regimen
NSCLC: Treatment of locally advanced or metastatic NSCLC (as a single-agent or in combination with platinum derivatives)
Ovarian cancer: Treatment of metastatic ovarian cancer following failure of first-line or subsequent chemotherapy
Prostate cancer: Treatment of hormone refractory, metastatic prostate cancer (in combination with prednisone or prednisolone)
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 US labeling): Severe hepatic impairment; pregnancy; breast-feeding
The incidence of treatment-related mortality associated with docetaxel is increased in patients with abnormal liver function, patients receiving higher doses, and patients with non " “small cell lung cancer and a history of prior treatment with platinum-based chemotherapy who receive docetaxel as a single agent at a dose of 100 mg/m2.
Hepatic function impairment:Do not give docetaxel to patients with bilirubin above the upper limit of normal (ULN), or patients with AST and/or ALT above 1.5 times the ULN concomitant with alkaline phosphatase above 2.5 times the ULN. Patients with elevations of bilirubin or abnormalities of transaminase concurrent with alkaline phosphatase are at increased risk for the development of grade 4 neutropenia, febrile neutropenia, infections, severe thrombocytopenia, severe stomatitis, severe skin toxicity, and toxic death. Patients with isolated elevations of transaminase above 1.5 times the ULN also had a higher rate of febrile grade 4 neutropenia but did not have an increased incidence of toxic death. Obtain bilirubin, AST or ALT, and alkaline phosphatase values prior to each cycle of docetaxel therapy.
Neutropenia:Do not give docetaxel therapy to patients with neutrophil counts below 1,500 cells/mm3. In order to monitor the occurrence of neutropenia, which may be severe and result in infection, perform frequent blood cell counts on all patients receiving docetaxel.
Hypersensitivity:Severe hypersensitivity reactions, characterized by general rash/erythema, hypotension, and/or bronchospasm, or, very rarely, fatal anaphylaxis, have been reported in patients who received a 3-day dexamethasone premedication. Hypersensitivity reactions require immediate discontinuation of the docetaxel infusion and administration of appropriate therapy. Do not give docetaxel to patients who have a history of severe hypersensitivity reactions to docetaxel or to other drugs formulated with polysorbate 80.
Fluid retention:Severe fluid retention occurred in 6.5% of patients despite the use of a 3-day dexamethasone premedication regimen. It was characterized by 1 or more of the following events: poorly tolerated peripheral edema, generalized edema, pleural effusion requiring urgent drainage, dyspnea at rest, cardiac tamponade, or pronounced abdominal distention (due to ascites).
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.
US labeling:
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)
Non-small cell lung cancer: IV: 75 mg/m2 every 3 weeks (as a single agent or in combination with cisplatin)
Prostate cancer: IV: 75 mg/m2 every 3 weeks (in combination with prednisone)
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
Canadian labeling:
Breast cancer: IV:
Locally advanced or metastatic: 75 mg/m2 (as combination therapy) or 100 mg/m2 (as a single agent) every 3 weeks
Operable, node-positive (adjuvant treatment): 75 mg/m2 every 3 weeks for 6 courses (in combination with doxorubicin and cyclophosphamide)
Non-small cell lung cancer (locally advanced or metastatic), ovarian cancer (metastatic), head and neck cancer (recurrent and/or metastatic): IV: 75 mg/m2 (as combination therapy) or 100 mg/m2 (as a single agent) every 3 weeks
Prostate cancer (hormone-refractory, metastatic): IV: 75 mg/m2 every 3 weeks (in combination with prednisone or prednisolone)
Off-label uses:
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)
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, osteosarcoma (recurrent or progressive; off-label uses): IV: 100 mg/m2 on day 8 of a 21-day cycle (in combination with gemcitabine) (Navid 2008)
Ovarian cancer (off-label use in US): 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, metastatic, hormone-sensitive (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).
Refer to adult dosing.
Note: Premedicate with corticosteroids for 3 days, beginning one day prior to docetaxel administration, to reduce the severity of hypersensitivity reactions and fluid retention. Dexamethasone (dose not specified) was administered for 3 to 4 days, starting the day before or the day of docetaxel administration and continuing for 2 days afterward in the bone sarcoma study (Navid 2008).
Ewing sarcoma, osteosarcoma (recurrent or progressive; off-label uses): Children ≥8 years and Adolescents: IV: 100 mg/m2 on day 8 of a 21-day cycle (in combination with gemcitabine) (Navid 2008)
Renal excretion is minimal (~6%), therefore, the need for dosage adjustments for renal dysfunction is unlikely (Janus 2010; Li 2007). Not removed by hemodialysis, may be administered before or after hemodialysis (Janus 2010).
US labeling:
Total bilirubin greater than the ULN, or AST and/or ALT >1.5 times ULN concomitant with alkaline phosphatase >2.5 times ULN: Use is not recommended.
Hepatic impairment dosing adjustment specific for gastric or head and neck cancer:
AST/ALT >2.5 to ≤5 times ULN and alkaline phosphatase ≤2.5 times ULN: Administer 80% of dose
AST/ALT >1.5 to ≤5 times ULN and alkaline phosphatase >2.5 to ≤5 times ULN: Administer 80% of dose
AST/ALT >5 times ULN and /or alkaline phosphatase >5 times ULN: Discontinue docetaxel
Canadian labeling:
Serum bilirubin >ULN or AST and/or ALT > 1.5 times ULN associated with alkaline phosphatase >2.5 times ULN: Avoid use.
Severe hepatic impairment: Use is contraindicated.
The following adjustments have also been used (Floyd 2006):
Transaminases 1.6 to 6 times ULN: Administer 75% of dose.
Transaminases >6 times ULN: Use clinical judgment.
Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]).
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.
Administer IV infusion 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).
Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]).
Storage and stability may vary by manufacturer, refer to specific prescribing information.
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. Multi-use vials (80 mg/8 mL and 160 mg/16 mL) 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 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 at 25 ‚ °C (77 ‚ °F); excursions permitted between 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F). Protect from light. Solutions diluted for infusion in D5W or NS should be used within 4 hours of preparation, including infusion time.
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
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); 20 mg/0.5 mL (0.5 mL); 80 mg/2 mL (2 mL)
Concentrate, Intravenous [preservative free]:
Generic: 20 mg/mL (1 mL); 80 mg/4 mL (4 mL); 140 mg/7 mL (7 mL); 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); 20 mg/mL (1 mL); 80 mg/4 mL (4 mL); 160 mg/8 mL (8 mL)
Solution Reconstituted, Intravenous:
Docefrez: 20 mg (1 ea); 80 mg (1 ea) [contains alcohol, usp, polysorbate 80]
Stable in D5W, LR, NS.
Y-site administration: Incompatible with amphotericin B, doxorubicin liposome, methylprednisolone sodium succinate, nalbuphine.
Antifungal Agents (Azole Derivatives, Systemic): May decrease the metabolism of DOCEtaxel. Fluconazole and isavuconazonium considerations are addressed in separate monographs. Exceptions: Fluconazole; Isavuconazonium Sulfate. Consider therapy modification
Antineoplastic Agents (Anthracycline, Systemic): Taxane Derivatives may enhance the adverse/toxic effect of Antineoplastic Agents (Anthracycline, Systemic). Taxane Derivatives may increase the serum concentration of Antineoplastic Agents (Anthracycline, Systemic). Taxane Derivatives may also increase the formation of toxic anthracycline metabolites in heart tissue. 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. 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. Avoid combination
CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. 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. Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Consider therapy modification
Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. 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
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Avoid combination
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
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification
Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates. 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
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
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
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. Consider therapy modification
Luliconazole: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates. 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. 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. Monitor therapy
Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification
Osimertinib: May increase the serum concentration of CYP3A4 Substrates. Osimertinib may decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
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
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
Ranolazine: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy
Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Simeprevir: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy
SORAfenib: May increase the serum concentration of DOCEtaxel. Monitor therapy
St Johns Wort: May decrease the serum concentration of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
Stiripentol: May increase the serum concentration of CYP3A4 Substrates. 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. 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. Avoid combination
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy
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. Avoid combination
CBC with differential, liver function tests, bilirubin, alkaline phosphatase, renal function; monitor for hypersensitivity reactions, neurosensory symptoms, gastrointestinal toxicity (eg, diarrhea, stomatitis), cutaneous reactions, visual impairment, fluid retention, epiphora, and canalicular stenosis
Percentages reported for docetaxel monotherapy; frequency may vary depending on diagnosis, dose, liver function, prior treatment, and premedication.
>10%:
Central nervous system: Central nervous system toxicity (20% to 58%; severe: ≤6%; including neuropathy)
Dermatologic: Alopecia (56% to 76%), dermatological reaction (20% to 48%; severe: ≤5%), nail disease (11% to 41%)
Endocrine & metabolic: Fluid retention (includes edema and effusion; 13% to 60%; severe: 7% to 9%; dose dependent)
Gastrointestinal: Stomatitis (19% to 53%; severe 1% to 8%), diarrhea (23% to 43%; severe: 5% to 6%), nausea (34% to 42%), vomiting (22% to 23%)
Hematologic & oncologic: Neutropenia (84% to 99%; grade 4: 75% to 86%; nadir [median]: 7 days, duration [severe neutropenia]: 7 days; dose dependent), leukopenia (84% to 99%; grade 4: 32% to 44%), anemia (65% to 97%; dose dependent; grades 3/4: 8% to 9%), thrombocytopenia (8% to 14%; grade 4: 1%; dose dependent), febrile neutropenia ( ≤14%; dose dependent)
Hepatic: Increased serum transaminases (4% to 19%)
Hypersensitivity: Hypersensitivity (1% to 21%; with premedication 15%)
Infection: Infection (1% to 34%; dose dependent)
Neuromuscular & skeletal: Weakness (53% to 66%; severe: ≤18%), myalgia (3% to 23%), neuromuscular reaction (16%)
Respiratory: Pulmonary reaction (41%)
Miscellaneous: Fever (31% to 35%)
1% to 10%:
Cardiovascular: Decreased left ventricular ejection fraction (8%), hypotension (3%)
Central nervous system: Peripheral motor neuropathy (4%; severe; mainly distal extremity weakness)
Gastrointestinal: Dysgeusia (6%)
Hepatic: Increased serum bilirubin (9%), increased serum alkaline phosphatase (4% to 7%)
Infection: Severe infection (6%)
Local: Infusion site reactions (4%, including hyperpigmentation, inflammation, redness, dryness, phlebitis, extravasation, swelling of the vein)
Neuromuscular and skeletal: Arthralgia (3% to 9%)
<1% (Limited to important or life-threatening): Acute myelocytic leukemia, acute respiratory distress, alopecia (permanent), anaphylactic shock, anorexia, ascites, atrial fibrillation, atrial flutter, back pain, bronchospasm, cardiac arrhythmia, cardiac tamponade, chest pain, chest tightness, chills, colitis, confusion, conjunctivitis, constipation, cystoid macular edema, deep vein thrombosis, dehydration, disease of the lacrimal apparatus (duct obstruction), disseminated intravascular coagulation, drug fever, duodenal ulcer, dyspnea, ECG abnormality, epiphora (more common with weekly administration [Kintzel 2006]), erythema multiforme, esophagitis, flushing, gastrointestinal hemorrhage, gastrointestinal obstruction, gastrointestinal perforation, hearing loss, hemorrhagic diathesis, hepatitis, hypertension, hyponatremia, intestinal obstruction, interstitial pulmonary disease, ischemic colitis, localized erythema of the extremities, loss of consciousness (transient), lymphedema (peripheral), multiorgan failure, myelodysplastic syndrome, myocardial infarction, neutropenic enterocolitis, ototoxicity, palmar-plantar erythrodysesthesia, pneumonia, pneumonitis, pruritus, pulmonary edema, pulmonary embolism, pulmonary fibrosis, radiation pneumonitis, radiation recall phenomenon, renal failure, renal insufficiency, respiratory failure, seizure, sepsis, sinus tachycardia, skin changes (scleroderma-like), skin rash, Stevens-Johnson syndrome, subacute cutaneous lupus erythematosus, syncope, tachycardia, thrombophlebitis, toxic epidermal necrolysis, unstable angina pectoris, visual disturbance (transient)
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 ƒ — ULN concomitant with alkaline phosphatase more than 2.5 ƒ —ULN).
Concerns related to adverse effects:
- Bone marrow suppression: [US Boxed Warning]: Patients with an absolute neutrophil count <1,500/mm3 should not receive docetaxel. Monitor blood counts frequently to monitor for neutropenia (which may be severe and result in infection). The dose-limiting toxicity is neutropenia. Platelets should recover to >100,000/mm3 prior to treatment. 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.
- 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, generalized edema, and weight gain, has been reported (despite the use of premedication with 3 days of 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.
- Hypersensitivity reactions: [US Boxed Warning]: Severe hypersensitivity reactions, characterized by generalized rash/erythema, hypotension, bronchospasms, or rare anaphylaxis may occur (may be fatal; has occurred in patients receiving a 3-day corticosteroid premedication). Hypersensitivity reactions require immediate discontinuation of the docetaxel infusion and administration of appropriate therapy. Do not administer to patients with a history of severe hypersensitivity to docetaxel or polysorbate 80. 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: Treatment-related acute myeloid leukemia or myelodysplasia occurred in patients receiving docetaxel in combination with anthracyclines and/or cyclophosphamide.
- Treatment-related mortality: [US Boxed Warning]: 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 are at higher risk for treatment-related mortality.
- 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:
- Hepatic impairment: [US Boxed Warning]: Avoid use in patients with bilirubin exceeding upper limit of normal (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 grade 4 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 grade 4 neutropenic fever, although no increased incidence of toxic death. Monitor bilirubin, AST or ALT, and alkaline phosphatase prior to each docetaxel cycle. The alcohol content of the docetaxel formulation should be taken into account when administering to patients with hepatic impairment. Canadian labeling contraindicates use in severe 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.
Special handling:
- Hazardous agent: Use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]).
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.
D
Adverse events have been observed in animal reproduction studies. 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). Some pharmacokinetic properties of docetaxel may be altered in pregnant women (van Hasselt 2014). Women of childbearing potential should avoid becoming pregnant during therapy. A pregnancy registry is available for all cancers diagnosed during pregnancy at Cooper Health (877-635-4499).
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.
Extensive extravascular distribution and/or tissue binding; Vdss: 113 L (mean steady state)
Hepatic; oxidation via CYP3A4 to metabolites
Feces (~75%, <8% as unchanged drug); urine (~6%)
Terminal: ~11 hours
~94% to 97%, primarily to alpha1-acid glycoprotein, albumin, and lipoproteins
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience diarrhea, mouth sores, alopecia, nail changes, change in taste, constipation, lack of appetite, joint pain, eye redness, or tearing. Have patient report immediately to prescriber signs of infection, signs of bleeding (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 bleeding that is very bad or that will not stop), signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), shortness of breath, excessive weight gain, swelling of arm or leg, severe dizziness, passing out, severe nausea, vomiting, burning or numbness feeling, loss of strength and energy, angina, tachycardia, arrhythmia, severe headache, muscle pain, injection site irritation, or signs of cystoid macular edema (vision changes, vision loss) (HCAHPS).
- Educate patient about signs of a significant reaction (eg, 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. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.