PDR MEMBER LOGIN:
  • PDR Search

    Required field
  • Advertisement
  • CLASSES

    Taxanes

    BOXED WARNING

    Infection, neutropenia, thrombocytopenia

    Docetaxel is contraindicated in patients with neutropenia (ANC less than 1,500 cells/mm3); patients with thrombocytopenia (platelets less than 100,000 cells/mm3) also should not receive docetaxel therapy. Neutropenia occurs in most patients treated with docetaxel; it may be severe and result in infection. Frequently monitor complete blood counts in all patients. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for patients with severe and prolonged neutropenia, febrile neutropenia, or severe infection.[60484]

    Biliary tract disease, hepatic disease

    Use of docetaxel in patients with biliary tract disease or hepatic disease may increase the risk of grade 4 neutropenia, febrile neutropenia, infections, severe thrombocytopenia, severe stomatitis, severe skin toxicity, or toxic death. Monitor bilirubin, AST/ALT, and alkaline phosphatase levels prior to each cycle of docetaxel. Avoid use in patients with a bilirubin level greater than the upper limit of normal (ULN) or with combined transaminase (AST and/or ALT level greater than 1.5 times the ULN) and alkaline phosphatase (AP) elevations (AP level greater than 2.5 times the ULN). Consider a docetaxel dose reduction in patients with isolated transaminase elevations (AST and/or ALT level greater than 1.5 times the ULN).[60484]

    Ascites, cardiac tamponade, edema, fluid retention, peripheral edema, pleural effusion

    Severe fluid retention (e.g., poorly tolerated peripheral edema, generalized edema, pleural effusion requiring urgent drainage, dyspnea at rest, cardiac tamponade, and/or pronounced abdominal distention due to ascites) has occurred in patients treated with docetaxel despite premedication with 3 days of corticosteroids. Premedicate patients with oral corticosteroids prior to each docetaxel administration to reduce the incidence and severity of fluid retention. Closely monitor patients with pre-existing effusions for signs of a possible exacerbation. Docetaxel-related fluid retention was completely, but sometimes slowly, reversible with a median of 16 weeks from the last infusion of docetaxel to resolution (range, 0 to 42 weeks). Treat peripheral edema with standard measures (e.g., salt restriction, oral diuretics).

    Mortality

    Docetaxel at a dose of 100 mg/m2 in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) and a history of prior platinum-based chemotherapy was associated with increased treatment-related mortality (14% and 5% in two randomized, controlled studies). There were 2.8% treatment-related deaths among the 176 patients treated at the 75 mg/m2 dose in randomized trials; 3 of these 5 patients had an ECOG performance status of 2 at study entry. The 100 mg/m2 dose was also associated with deaths possibly or probably related to treatment in 2% of metastatic breast cancer patients with normal baseline liver function (n = 965), both previously treated and untreated, and in 11.5% of patients with various tumor types who had abnormal baseline liver function (n = 61). Among patients dosed at 60 mg/m2, treatment-related mortality occurred in 0.6% of patients with normal liver function (n = 481) and in 3 of 7 patients with abnormal liver function. Approximately half of these deaths occurred during the first cycle; sepsis accounted for the majority of deaths.[60484]

    DEA CLASS

    Rx

    DESCRIPTION

    A taxane microtubule inhibitor
    Used for certain types of breast cancer, non-small cell lung cancer, gastric cancer, prostate cancer, and head and neck cancer
    Oral corticosteroid premedication required prior to each dose to reduce the incidence and severity of hypersensitivity, fluid retention, and skin toxicity

    COMMON BRAND NAMES

    Taxotere

    HOW SUPPLIED

    Docetaxel Intravenous Inj Sol: 1mL, 10mg, 20mg
    Docetaxel/Taxotere Intravenous Inj Sol Conc: 1mL, 20mg

    DOSAGE & INDICATIONS

    For the treatment of breast cancer.
    For locally advanced or metastatic breast cancer after failure of previous chemotherapy.
    Intravenous dosage
    Adults

    60 to 100 mg/m2 IV over 1 hour, administered once every 3 weeks. Premedicate with dexamethasone 8 mg by mouth twice daily for 3 days, beginning 1 day prior to docetaxel administration, to reduce the incidence and severity of fluid retention and hypersensitivity reactions. A phase 3 study compared docetaxel 100 mg/m2 IV to the combination of mitomycin and vinblastine (MV) in patients with metastatic breast cancer resistant to anthracyclines. Docetaxel produced significantly higher overall responses rates than MV (30% vs. 11.6%, respectively), median time to progression, and overall survival. Patients who are initially dosed at 60 mg/m2 and do not experience febrile neutropenia, neutrophils less than 500 cells/mm3 for more than 1 week, severe or cumulative cutaneous reactions, or severe peripheral neuropathy may tolerate higher doses.

    For the treatment of metastatic breast cancer after failure of prior anthracycline-containing chemotherapy, in combination with capecitabine†.
    NOTE: Capecitabine is FDA approved for use in combination with docetaxel for this indication.
    Intravenous dosage
    Adults

    75 mg/m2 IV over 1 hour on day 1, in combination with capecitabine (1,250 mg/m2 PO twice daily within 30 minutes after a meal on days 1 to 14, followed by 1 week of rest). Repeat every 3 weeks. Premedicate with dexamethasone 8 mg by mouth twice daily for 3 days, beginning 1 day prior to docetaxel administration, to reduce the incidence and severity of fluid retention and hypersensitivity reactions. Capecitabine doses should be adjusted based on toxicity during treatment cycle; once a dosage is reduced, it should not be increased at a later time. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In a multicenter, randomized, open-label, phase 3 trial (n = 511), treatment with capecitabine plus docetaxel significantly improved the time to disease progression (6.2 months vs. 4.3 months), overall survival (14.7 months vs. 11.7 months), and objective response rate (32% vs. 22%) compared to monotherapy with docetaxel in patients with metastatic breast cancer resistant to or recurring during/after anthracycline-based chemotherapy. Docetaxel/capecitabine patients experienced more hand-foot syndrome, diarrhea, stomatitis, nausea, and vomiting. Neutropenic fever, myalgia, arthralgia, and fatigue occurred more frequently with single-agent docetaxel.

    For adjuvant treatment of operable node-positive breast cancer in combination with cyclophosphamide and doxorubicin.
    Intravenous dosage (TAC regimen)
    Adults

    75 mg/m2 IV administered 1 hour after doxorubicin (50 mg/m2 IV) and cyclophosphamide (500 mg/m2 IV) every 3 weeks for 6 courses. Premedicate with dexamethasone 8 mg by mouth twice daily for 3 days, beginning 1 day prior to docetaxel administration, to reduce the incidence and severity of fluid retention and hypersensitivity reactions. Prophylactic colony stimulating factor support has been recommended to mitigate the risk of hematologic toxicities. Dosages should be adjusted based on toxicity. In an open-label randomized trial, 1,491 patients (stratified based on number of positive lymph nodes) were randomized to receive either docetaxel, doxorubicin, and cyclophosphamide (TAC regimen) or doxorubicin, fluorouracil, and cyclophosphamide (FAC regimen) every 3 weeks for 6 cycles. Results from the second interim analysis (median follow-up, 55 months) indicated that the disease-free survival was significantly longer for the TAC regimen versus the FAC regimen (HR, 0.74; 2-sided 95% CI, 0.6 to 0.92; p = 0.0047). The primary endpoint, disease-free survival, included local and distant recurrences, contralateral breast cancer, and death from any cause. The overall reduction in risk of relapse was 25.7% for TAC-treated patients.

    For adjuvant treatment of operable stage I to III invasive breast cancer in combination with cyclophosphamide†.
    Intravenous dosage
    Adults

    75 mg/m2 IV on day 1 and cyclophosphamide 600 mg/m2 IV on day 1, given every 21 days for 4 cycles (TC regimen). Premedicate with dexamethasone 8 mg by mouth twice daily for 3 days, beginning 1 day prior to docetaxel administration, to reduce the incidence and severity of fluid retention and hypersensitivity reactions. In a phase 3 trial comparing TC to doxorubicin and cyclophosphamide (AC regimen), the primary endpoint of 5-year disease-free survival (DFS) was significantly improved with TC (86% vs. 80%). Extended follow-up after 7 years showed a significant benefit for TC in 7-year DFS (81% vs. 75%) and showed a benefit for TC in 7-year overall survival (87% vs. 82%). Edema, myalgia and arthralgia were seen more frequently with the TC regimen and nausea and vomiting were seen more frequently with the AC regimen. No formal cardiac function comparison was performed.

    For adjuvant treatment of operable node-positive or high-risk node-negative (tumor greater than 2 cm) breast cancer administered sequentially to standard doxorubicin-containing combination chemotherapy†.
    Intravenous dosage
    Adults

    100 mg/m2 IV over 1 hour given every 3 weeks for 4 courses following completion of standard doxorubicin-based combination chemotherapy. Premedicate with dexamethasone 8 mg by mouth twice daily for 3 days, beginning 1 day prior to docetaxel administration, to reduce the incidence and severity of fluid retention and hypersensitivity reactions. In a study of 4,950 patients, either docetaxel or paclitaxel were administered after completion of doxorubicin/cyclophosphamide chemotherapy (AC). At a median follow-up of 63.8 months, disease-free survival at 5 years was significantly improved with docetaxel compared to paclitaxel (81.2% vs. 76.9%). No difference in overall survival at 5 years was observed (87.3% vs. 86.5%).

    For adjuvant treatment of HER2 overexpressing, node-positive or node negative (ER/PR negative or with one high-risk feature) breast cancer, in combination with trastuzumab and carboplatin (TCH regimen)†.
    NOTE: Trastuzumab is FDA approved for the adjuvant treatment of HER2 overexpressing, node-positive or node negative (ER/PR negative or with one high-risk feature) breast cancer, in combination with docetaxel and carboplatin.
    Intravenous dosage
    Adults

    75 mg/m2 IV on day 1 with carboplatin (AUC 6 IV on day 1), repeated every 3 weeks for a total of 6 cycles given concurrently with trastuzumab (4 mg/kg IV on week 1, then 2 mg/kg IV weekly for 18 total weekly doses, then 6 mg/kg IV every 3 weeks for the balance of 52 weeks total) (TCH regimen). Premedicate with dexamethasone 8 mg by mouth twice daily for 3 days, beginning 1 day prior to docetaxel administration, to reduce the incidence and severity of fluid retention and hypersensitivity reactions. In a phase 3 trial of 3,222 patients with node-positive or high-risk node-negative breast cancer, patients were randomized to receive TCH, doxorubicin/cyclophosphamide followed by docetaxel/trastuzumab (AC-TH), or the control arm, doxorubicin/cyclophosphamide followed by docetaxel (AC-T). At a median follow-up of 65 months, 5-year disease-free survival (81% vs. 75%) and 5-year overall survival (91% vs. 87%) were significantly improved by TCH compared to AC-T.

    For adjuvant treatment of node-positive breast cancer in sequence with fluorouracil, epirubicin, and cyclophosphamide (FEC-D regimen)†.
    Intravenous dosage
    Adults

    100 mg/m2 IV on day 1 repeated every 21 days is administered for 3 cycles beginning 21 days after the completion of 3 cycles of fluorouracil (500 mg/m2 IV), epirubicin (100 mg/m2 IV), and cyclophosphamide (500 mg/m2 IV). Premedicate with dexamethasone 8 mg by mouth twice daily for 3 days, beginning 1 day prior to docetaxel administration, to reduce the incidence and severity of fluid retention and hypersensitivity reactions. A phase 3 trial of 1,999 patients with node-positive breast cancer compared adjuvant fluorouracil, epirubicin, and cyclophosphamide for 3 cycles then docetaxel for 3 cycles (FEC-D) versus fluorouracil, epirubicin, and cyclophosphamide (FEC) for 6 cycles. The primary endpoint, 5-year disease-free survival, was significantly longer in the FEC-D arm (78.4% vs. 73.2 %). Overall survival at 5 years was also increased by FEC-D (90.7% vs. 86.7%). Grade 3 and 4 neutropenia and the incidence of nausea/vomiting were higher with FEC, while stomatitis, edema and nail changes were more common with FEC-D.

    For first-line treatment of metastatic breast cancer†.
    Intravenous dosage
    Adults

    100 mg/m2 IV on day 1, repeated every 3 weeks until disease progression or unacceptable toxicity. Premedicate with dexamethasone 8 mg by mouth twice daily for 3 days, beginning 1 day prior to docetaxel administration, to reduce the incidence and severity of fluid retention and hypersensitivity reactions. In a phase 3 trial, 449 patients with locally advanced or metastatic breast cancer that progressed on anthracycline-containing chemotherapy, or disease that progressed during or within 12 months of anthracycline-containing adjuvant or neoadjuvant chemotherapy were randomized to receive docetaxel or paclitaxel (175 mg/m2 IV on day 1 every 3 weeks). Overall response rate was not significantly different in the intent-to-treat population (32% vs. 25%), but time-to-progression (5.7 months vs. 3.6 months) and overall survival (15.4 months vs. 12.7 months) were significantly prolonged in the docetaxel arm.

    For HER2-positive metastatic breast cancer in combination with trastuzumab†.
    NOTE: Trastuzumab is FDA approved for use in combination with docetaxel for the treatment of metastatic HER-2 positive breast cancer
    Intravenous dosage
    Adults

    100 mg/m2 IV on day 1repeated every 21 days for 6 to 8 cycles, in combination with trastuzumab (4 mg/kg IV on day 1 of first cycle only, then 2 mg/kg IV weekly). Premedicate with dexamethasone 8 mg by mouth twice daily for 3 days, beginning 1 day prior to docetaxel administration, to reduce the incidence and severity of fluid retention and hypersensitivity reactions. Trastuzumab should be continued until disease progression or unacceptable toxicity. Docetaxel in combination with trastuzumab was studied in a phase 2 trial of 186 patients with previously untreated HER2-positive metastatic breast cancer. In this trial, docetaxel/trastuzumab was compared to docetaxel alone. Overall response rate (ORR) (61% vs. 34%), time-to-progression (TTP) (11.7 months vs. 6.1 months), and overall survival (OS) (31.2 months vs. 22.7 months) were all significantly improved in the docetaxel/trastuzumab arm. This benefit has been confirmed in other clinical trials, including a phase 3 trial of 263 patients where it was shown to produce a similar TTP and OS to docetaxel/carboplatin/trastuzumab, a regimen with known activity against breast cancer in the adjuvant setting. In a phase 2 trial of 30 women with HER2-overexpressed metastatic breast cancer, docetaxel 35 mg/m2 IV on days 1, 8, and 15 in combination with trastuzumab on days 1, 8, and 15, every 28 days was studied, and treatment was continued until disease progression or unacceptable toxicity; ORR was 63%.

    For patients who have not previously received chemotherapy for metastatic or inoperable locally recurrent HER2-negative breast cancer, in combination with bevacizumab†.
    Intravenous dosage
    Adults

    100 mg/m2 IV on day 1 in combination with bevacizumab (15 mg/kg IV) on day 1, repeated every 3 weeks. Combination treatment has been administered up to a maximum of 9 cycles, at which point bevacizumab monotherapy was continued until disease progression or unacceptable toxicity. Premedicate with dexamethasone 8 mg by mouth twice daily for 3 days, beginning 1 day prior to docetaxel administration, to reduce the incidence and severity of fluid retention and hypersensitivity reactions. In a phase 3 trial of 736 patients with metastatic or inoperable locally recurrent breast cancer, docetaxel was compared with docetaxel plus bevacizumab 7.5 mg/kg IV or 15 mg/kg IV. After a median follow-up of 25 months, the primary endpoint of progression-free survival (PFS) was significantly increased in the bevacizumab 15 mg/kg arm compared to docetaxel monotherapy (10 months vs. 8.1 months). The overall response rate (ORR) was also significantly improved with bevacizumab 15 mg/kg versus docetaxel monotherapy (64.1% vs. 46.4%). Grade 3 or 4 neutropenia (19.8% vs. 17.3%), febrile neutropenia (16.2% vs. 11.3%), and hypertension (4.5% vs. 1.3%) occurred more frequently in the bevacizumab 15 mg/kg arm. The bevacizumab 7.5 mg/kg arm did not reach a statistically significant improvement in PFS or ORR compared to placebo. Trial design precluded a direct comparison between the bevacizumab arms. Overall survival was not significantly different between any of the treatment arms.

    For first-line treatment of HER2-positive metastatic breast cancer in combination with pertuzumab and trastuzumab†.
    NOTE: Pertuzumab is FDA approved in combination with trastuzumab and docetaxel for the first-line treatment of HER2-positive metastatic breast cancer.
    Intravenous dosage
    Adults

    75 mg/m2 IV every 3 weeks; dose may be escalated to 100 mg/m2 if initial dose is well tolerated. Premedicate with dexamethasone 8 mg by mouth twice daily for 3 days, beginning 1 day prior to docetaxel administration, to reduce the incidence and severity of fluid retention and hypersensitivity reactions. Docetaxel is administered in combination with trastuzumab (8 mg/kg IV over 90 minutes, followed 3 weeks later by trastuzumab 6 mg/kg IV over 30 to 90 minutes repeated every 3 weeks) and pertuzumab (840 mg IV over 60 minutes initially, followed 3 weeks later by pertuzumab 420 mg IV over 30 to 60 minutes repeated every 3 weeks). Pertuzumab and trastuzumab can be given in any order; however, both agents should precede docetaxel. Observe for infusion-related reactions for 30 to 60 minutes after the pertuzumab infusion; do not start trastuzumab or docetaxel therapy until after this observation period. Patients with HER2-positive metastatic breast cancer received pertuzumab and trastuzumab until disease progression or unacceptable toxicity and docetaxel for at least 6 cycles (median of 8 cycles) in a multicenter, double-blind, placebo-controlled trial. In this study (the CLEOPATRA study), the primary endpoint of progression-free survival time (reviewed by an independent review facility) was significantly improved in the pertuzumab plus trastuzumab and docetaxel arm compared with the placebo plus trastuzumab and docetaxel arm (18.5 months vs. 12.4 months). In a second interim analysis, overall survival (OS) was significantly improved in the pertuzumab-containing arm (median OS time not reached vs. 37.6 months).

    For the treatment of non-small cell lung cancer (NSCLC).
    For advanced or metastatic non-small cell lung cancer (NSCLC) after the failure of prior platinum containing chemotherapy.
    Intravenous dosage
    Adults

    75 mg/m2 IV over 1 hour every 3 weeks. A dose of docetaxel 100 mg/m2 in patients previously treated with chemotherapy was associated with increased hematologic toxicity, infection, and treatment-related mortality. Premedicate with dexamethasone 8 mg by mouth twice daily for 3 days, beginning 1 day prior to docetaxel administration, to reduce the incidence and severity of fluid retention and hypersensitivity reactions. In a phase II trial, the combination of docetaxel 100 mg/m2 IV over 1 hour on day 8 and gemcitabine (900 mg/m2 IV, days 1, 8) with G-CSF support, was evaluated in previously untreated patients with stage IIIB or IV NSCLC. A partial response was seen in 37.5% of patients with an actuarial 1-year survival of 50.7%. The combination of docetaxel (75 to 100 mg/m2 IV over 1 hour on day 1) and vinorelbine (20 to 25 mg/m2 IV on days 1 and 5) has shown response rates of 27% to 36%. Severe neutropenia and febrile neutropenia are associated with this regimen despite colony-stimulating factor support and may limit the effectiveness of the combination.

    For first-line treatment of unresectable, locally advanced or metastatic non-small cell lung cancer (NSCLC) in combination with cisplatin in patients who have not received prior chemotherapy.
    Intravenous dosage
    Adults

    75 mg/m2 IV over 1 hour immediately followed by cisplatin (75 mg/m2 IV) every 3 weeks. Premedicate with dexamethasone 8 mg by mouth twice daily for 3 days, beginning 1 day prior to docetaxel administration, to reduce the incidence and severity of fluid retention and hypersensitivity reactions. In a clinical trial comparing docetaxel plus cisplatin or carboplatin to a standard regimen of vinorelbine plus cisplatin, patients in the docetaxel plus cisplatin group had a median survival time of 10.9 months vs 10 months for patients treated with vinorelbine plus cisplatin. The overall response rates were 31.6% for docetaxel plus cisplatin vs 24.4% for vinorelbine plus cisplatin. Additional analysis demonstrated that benefits were maintained in patients >= 65 years. In a Japanese phase III trial, previously untreated patients with stage IV NSCLC were randomized to receive docetaxel 60 mg/m2 IV on day 1 plus cisplatin (80 mg/m2 IV day 1) every 3 to 4 weeks or vindesine (3 mg/m2 IV on days 1, 8, and 15) plus cisplatin (80 mg/m2 IV on day 1) every 4 weeks. Of the 302 patients eligible for evaluation, patients randomized to the docetaxel arm demonstrated significant improvements as compared to those in the vindesine arm for response rates (37% vs. 21%, respectively) and median survival times (11.3 vs. 9.6 months, respectively). In addition, quality of life measures also were favored in the docetaxel arm.

    For first-line treatment of unresectable, locally advanced or metastatic non-small cell lung cancer (NSCLC) in combination with carboplatin†.
    Intravenous dosage
    Adults

    75 mg/m2 IV, followed by carboplatin (AUC 6 IV) on day 1, given every 21 days for 4 to 6 cycles. Premedicate with dexamethasone 8 mg by mouth twice daily for 3 days, beginning 1 day prior to docetaxel administration, to reduce the incidence and severity of fluid retention and hypersensitivity reactions. In a phase III trial of 1,203 patients with unresectable locally advanced or metastatic NSCLC, docetaxel and platinum combinations (cisplatin or carboplatin) were compared with cisplatin/vinorelbine. No difference was observed between docetaxel/carboplatin and cisplatin/vinorelbine in overall survival, the primary endpoint. Grade 3 and 4 anemia and nausea/vomiting were significantly lower in both docetaxel containing arms. In addition, hospitalizations and treatment discontinuation secondary to toxicity were higher with cisplatin/vinorelbine. A separate phase III trial conducted in 422 patients with inoperable, locally advanced or metastatic NSCLC compared docetaxel/carboplatin to mitomycin C/cisplatin plus either ifosfamide or vinblastine. The primary endpoint, 1-year overall survival, was not significantly different between the treatment arms. Grade 3 and 4 neutropenia, infection, and mucositis were all significantly higher with docetaxel/carboplatin, while quality of life scores were significantly better.

    For first-line treatment of unresectable, locally advanced or metastatic non-small cell lung cancer (NSCLC) in combination with gemcitabine†.
    Intravenous dosage
    Adults

    Multiple dosage regimens have been evaluated. Docetaxel 75, 85 or 100 mg/m2 IV on day 8 in combination with gemcitabine days 1 and 8 repeated every 21 days (GD regimen) has been studied. Premedicate with dexamethasone 8 mg by mouth twice daily for 3 days, beginning 1 day prior to docetaxel administration, to reduce the incidence and severity of fluid retention and hypersensitivity reactions. In a phase III trial of 311 patients with Stage IIIB or IV NSCLC, GD (docetaxel dose 85 mg/m2) was compared to cisplatin/vinorelbine (CV). Progression-free survival (4.2 months vs. 4 months) and overall survival (11.1 months vs. 9.6 months) were not significantly different between the two arms. Grade 3 and 4 febrile neutropenia, anemia and gastrointestinal toxicities were all significantly higher with CV, while fluid retention and grade 3 or 4 pulmonary events were greater with GD. In another phase III trial of 413 patients comparing GD (docetaxel dose 100 mg/m2) to CV, no difference in overall survival, the primary endpoint, was observed (9 months vs. 9.7 months). Grade 3 and 4 neutropenia and nausea/vomiting occurred more frequently with CV. In a phase III trial of 312 patients, GD (docetaxel dose 75 mg/m2) was compared to single-agent docetaxel. Overall survival, the primary endpoint, was significantly improved in the combination arm (9.4 months vs. 8.3 months, p = 0.037).

    For the treatment of metastatic prostate cancer.
    For the treatment of hormone-refractory, metastatic prostate cancer in combination with prednisone.
    Intravenous dosage
    Adult males

    75 mg/m2 IV over 1 hour every 21 days plus prednisone (5 mg orally twice daily) for 10 cycles. All patients should be pre-medicated with corticosteroids prior to docetaxel infusion to reduce the incidence and severity of fluid retention as well as the severity of hypersensitivity reactions. In a multinational, multicenter randomized clinical trial (n = 1,006), patients treated with every-3-week docetaxel plus prednisone had a statistically significant survival advantage over those who received mitoxantrone plus prednisone (18.9 months vs. 16.5 months; HR 0.761; p = 0.0094). The administration of weekly docetaxel plus prednisone did not show a survival advantage over mitoxantrone plus prednisone.

    For the treatment of hormone-refractory, metastatic prostate cancer in combination with estramustine†.
    Intravenous dosage
    Adult males

    60 mg/m2 IV on day 2, plus estramustine (280 mg orally three times daily on days 1, 2, 3, 4, and 5) every 21 days until disease progression or unacceptable toxicity. The night before docetaxel administration (day 1), begin administration of dexamethasone 60 mg orally in 3 divided doses (i.e., 20 mg PO every 12 hours for 3 doses). In a randomized, phase 3 clinical trial in patients with androgen-independent prostate cancer (n = 674), administration of docetaxel/estramustine/dexamethasone significantly improved overall survival compared with mitoxantrone/prednisone (17.5 vs. 15.6 months; p = 0.02). In addition, the median time to progression was improved in the docetaxel/estramustine/dexamethasone arm (6.3 vs. 3.2 months; p < 0.001).

    For the first-line treatment of metastatic, hormone-sensitive prostate cancer in selected patients, in combination with androgen-deprivation therapy†.
    Intravenous dosage
    Adult males

    75 mg/m2 IV over 1 hour on day 1, every 21 days, in combination with androgen deprivation therapy for 6 to 9 cycles, or until progressive disease or unacceptable toxicity. Premedicate with dexamethasone 8 mg orally twice daily for 3 days, starting 1 day prior to docetaxel administration in order to reduce the incidence and severity of fluid retention as well as the severity of hypersensitivity reactions. The use of docetaxel in men with hormone sensitive advanced or metastatic prostate cancer was evaluated in 3 randomized clinical trials. Two of the 3 trials showed improvement in both overall survival (OS) and progression-free survival (PFS). Differences in patient populations may account for the lack of OS seen in the GETUG-AFU 15 trial.

    For the treatment of gastric cancer.
    For advanced gastric cancer, including adenocarcinoma of the gastroesophageal junction, in combination with cisplatin and 5-fluorouracil in patients who have not received prior chemotherapy for advanced disease.
    Intravenous dosage
    Adults

    75 mg/m2 IV over 1 hour followed by cisplatin (75 mg/m2 IV over 1 to 3 hours) on day 1, followed by 5-fluorouracil (750 mg/m2 IV as a 24 hour continuous infusion on days 1, 2, 3, 4, and 5, starting at the end of the cisplatin infusion). Repeat every 3 weeks until disease progression or unacceptable toxicity. Appropriate pre-medications (e.g., antiemetics and hydration) should be given prior to treatment, including dexamethasone 8 mg by mouth twice daily for 3 days, beginning 1 day prior to docetaxel administration, to reduce the incidence and severity of fluid retention and hypersensitivity reactions. During the clinical trial, colony-stimulating factors were recommended for the second and/or subsequent cycles for prophylaxis of febrile neutropenia, documented infections with neutropenia, or neutropenia lasting more than 7 days. The pivotal phase III trial compared docetaxel, cisplatin, and 5-FU (TCF) (n = 221), in FDA-approved dosages, to cisplatin and 5-FU (CF) (n = 224) for the treatment of metastatic gastric cancer or gastroesophageal junction cancer (22% of patients). The time to progression was significantly higher for patients treated with TCF compared with CF (5.6 vs. 3.7 months), with a 32.1% reduction in risk of progression (p = 0.0004). The median duration of response was 6.1 months (range, 5 to 8.3 months) for the TCF arm and 5.6 months (range, 4.2 to 6.4 months) for the CF arm; a response duration of more than 9 months was reported in 25.9% and 14% of responders for TCF and CF, respectively. After a median follow-up of 23 months, the median overall survival was significantly longer for the TCF arm (9.2 months) compared with the CF arm (8.6 months) with a 22.7% risk reduction (p = 0.0201). Phase III trials are underway comparing docetaxel-cisplatin-fluorouracil with epirubicin-cisplatin-fluorouracil.

    For the treatment of advanced gastric cancer as a single agent†.
    Intravenous dosage
    Adults

    100 mg/m2 IV has been administered on day 1 every 3 weeks, until disease progression. Premedicate with dexamethasone 8 mg by mouth twice daily for 3 days, beginning 1 day prior to docetaxel administration, to reduce the incidence and severity of fluid retention and hypersensitivity reactions. In a phase II trial of 37 patients with previously untreated advanced gastric cancer, docetaxel produced an overall response rate (ORR) of 22%. Docetaxel 75 mg/m2 IV day 1 every 3 weeks was administered to 40 patients with recurrent or metastatic gastric cancer in another phase II trial and produced an ORR of 15.9%. The use of weekly docetaxel showed minimal activity in the salvage treatment of patients with relapsed or metastatic gastric cancer.

    For the treatment of head and neck cancer.
    For induction treatment of locally advanced inoperable squamous cell head and neck cancer in combination with cisplatin and 5-fluorouracil (5-FU).
    Intravenous dosage
    Adults

    75 mg/m2 IV over 1 hour followed by cisplatin (75 mg/m2 IV over 1 hour) on day 1, followed by 5-FU continuous IV infusion (750 mg/m2/day continuous infusion on days 1, 2, 3, 4, and 5); this regimen is given every 3 weeks for 4 cycles. Premedicate with dexamethasone 8 mg by mouth twice daily for 3 days, beginning 1 day prior to docetaxel administration, to reduce the incidence and severity of fluid retention and hypersensitivity reactions. After completion of chemotherapy, patients should receive radiation therapy. All patients must receive prophylaxis for neutropenic infections, premedication with antiemetics, and appropriate hydration (before and after cisplatin administration). During clinical trials, colony-stimulating factors were recommended during the second and/or subsequent cycles for prophylaxis of febrile neutropenia, documented infections with neutropenia, or neutropenia lasting longer than 7 days. In a randomized trial of 358 patients with inoperable, locally advanced squamous head and neck cancer, patients were treated with the FDA-approved regimen of docetaxel/cisplatin/5-FU or cisplatin (100 mg/m2 IV day 1) and 5-FU (1,000 mg/m2/day continuous IV infusion for 5 days) every 3 weeks for 4 cycles. Progression-free survival (PFS), the primary end-point of the study, was significantly longer in the docetaxel/cisplatin/5-FU arm as compared to the cisplatin/5-FU (median PFS, 11.4 months vs. 8.3 months, respectively) with a median follow-up of 33.7 months. With a follow-up of 51.2 months, the median overall survival also favored patients treated docetaxel/cisplatin/5-FU as compared to those treated with cisplatin/5-FU (18.6 months vs. 14.2 months, respectively).

    For induction treatment of locally advanced (unresectable disease, low surgical cure, or organ preservation) squamous cell head and neck cancer in combination with cisplatin and 5-fluorouracil (5-FU).
    NOTE: Survival was significantly improved among patients who got the 3 drugs (see Dosage below) as compared with receipt of only cisplatin 100 mg/m2 IV on day 1 and 5- fluorouracil 1000 mg/m2/day by continuous IV infusion for 5 days. Specifically, the relative risk of death was 30% lower. Also, the median overall survival was 70.6 months as compared with 30.1 months for patients receiving only cisplatin and 5-fluorouracil. Three to 8 weeks after the start of the last cycle, all patients in both treatment arms who did not have progressive disease got carboplatin (AUC 1.5 weekly for 7 doses) and radiation therapy (2 Gy per day, 5 days per week for 7 weeks) followed by surgery, if appropriate.
    Intravenous dosage
    Adults

    75 mg/m2 IV over 1 hour followed by cisplatin (100 mg/m2 IV over 30 minutes to 3 hours) on day 1, followed by 5-FU continuous IV infusion (1,000 mg/m2/day continuous infusion on days 1, 2, 3, and 4); this regimen is given every 3 weeks for 3 cycles. Premedicate with dexamethasone 8 mg by mouth twice daily for 3 days, beginning 1 day prior to docetaxel administration, to reduce the incidence and severity of fluid retention and hypersensitivity reactions. After completion of chemotherapy, patients should receive chemoradiotherapy. All patients must receive prophylaxis for neutropenic infections, premedication with antiemetics, and appropriate hydration (before and after cisplatin administration).

    For the treatment of ovarian cancer†.
    For refractory advanced ovarian cancer†.
    Intravenous dosage
    Adults

    100 mg/m2 IV over 1 hour every 3 weeks has produced an overall response rate of 20% to 35% in patients with paclitaxel- and/or platinum-resistant ovarian or peritoneal carcinoma in phase II studies. Premedicate with dexamethasone 8 mg by mouth twice daily for 3 days, beginning 1 day prior to docetaxel administration, to reduce the incidence and severity of fluid retention and hypersensitivity reactions.

    For the first-line adjuvant treatment of Stage Ic through IV ovarian cancer and peritoneal cancers in combination with carboplatin†.
    Intravenous dosage
    Adults

    75 mg/m2 IV over 1 hour followed by carboplatin (AUC 5 IV on day 1), repeated every 3 weeks for 6 cycles. Premedicate with dexamethasone 8 mg by mouth twice daily for 3 days, beginning 1 day prior to docetaxel administration, to reduce the incidence and severity of fluid retention and hypersensitivity reactions. In a phase III trial of 1,077 patients, docetaxel-carboplatin was compared to paclitaxel-carboplatin. No significant differences in response rate, progression-free survival, or overall survival were observed between the two groups. Grade 2 to 4 neurosensory toxicity was significantly greater in the paclitaxel containing regimen (30% vs. 11%, p < 0.001) and grade 3 or 4 neutropenia was significantly higher in the docetaxel containing regimen (94% vs. 84%, p < 0.001).

    For the treatment of metastatic malignant melanoma†.
    Intravenous dosage
    Adults

    Multiple regimens containing docetaxel have been studied yielding low-level to moderate activity. Regimens include docetaxel 100 mg/m2 IV over 1 hour every 3 weeks as a single-agent; docetaxel 80 mg/m2 IV on day 1 in combination with temozolomide (150 mg/m2/day PO on days 1, 2, 3, 4, and 5) every 4 weeks for 6 cycles; docetaxel 80 mg/m2 IV on day 1 in combination with dacarbazine (400 mg/m2/day IV on days 1 and 2) every 3 weeks for 6 cycles. Single-agent docetaxel produced an overall response rate of 12.5% in a phase II trial of 40 patients. Combination therapy with temozolomide produced an objective response in 27% of patients; combination therapy with dacarbazine produced an objective response in 24% of patients. Premedicate with dexamethasone 8 mg by mouth twice daily for 3 days, beginning 1 day prior to docetaxel administration, to reduce the incidence and severity of fluid retention and hypersensitivity reactions.

    †Indicates off-label use

    MAXIMUM DOSAGE

    The suggested maximum tolerated dose (MTD) for docetaxel is dependent on performance status, other chemotherapy agents or radiation given in combination, and disease state. The optimal dose or infusion duration of docetaxel has not been determined. Therefore, dosing may vary from protocol to protocol. If questions arise, clinicians should consult the appropriate references to verify the dose.

    Adults

    100 mg/m2 IV over 1 hour every 3 weeks as a single agent; doses of 100 mg/m2 IV have been associated with toxic deaths in patients with breast and lung cancer (see Adverse Reactions). Doses up to 40 mg/m2 have been given on a weekly basis. The recommended dose of intraperitoneal docetaxel is 100 mg/m2 IP every 3 weeks.

    Elderly

    100 mg/m2 IV over 1 hour every 3 weeks as a single agent; doses of 100 mg/m2 IV have been associated with toxic deaths in patients with breast and lung cancer (see Adverse Reactions). Doses up to 40 mg/m2 have been given on a weekly basis. The recommended dose of intraperitoneal docetaxel is 100 mg/m2 IP every 3 weeks.

    Adolescents

    In a phase I study of children with refractory solid tumors, the MTD for heavily pretreated patients was 65 mg/m2 IV every 3 weeks and 125 mg/m2 IV over 1 hour in less heavily pretreated patients.

    Children

    In a phase I study of children with refractory solid tumors, the MTD for heavily pretreated patients was 65 mg/m2 IV every 3 weeks and 125 mg/m2 IV over 1 hour in less heavily pretreated patients.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Baseline Hepatic Impairment
    Bilirubin level greater than the upper limit of normal (ULN): Avoid use.AST/ALT level greater than 1.5 times the ULN with concurrent alkaline phosphatase (AP) level greater than 2.5 times the ULN: Avoid use.Isolated AST/ALT level greater than 1.5 times the ULN without concurrent AP level elevation: Consider a dose reduction.
    Treatment-Related Hepatotoxicity
    Gastric or Head and Neck Cancer, in combination with cisplatin and fluorouracil:
    AST/ALT level of 2.6 to 5 times the ULN and AP level less than or equal to 2.5 times the ULN, OR AST/ALT level 1.6 to 5 times the ULN and AP level 2.6 to 5 times the ULN: Reduce docetaxel dose by 20%.AST/ALT level greater than 5 times the ULN and/or AP level greater than 5 times the ULN: Discontinue docetaxel.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

    ADMINISTRATION

    Hazardous Drugs Classification
    NIOSH 2016 List: Group 1
    NIOSH (Draft) 2020 List: Table 1
    Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
    Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.
    Emetic Risk
    Low
    Administer routine antiemetic prophylaxis prior to treatment.
    Extravasation Risk
    Vesicant
    Administer drug through a central venous line.
    If docetaxel comes into contact with the skin, wash thoroughly with soap and water; wash/flush area with water if docetaxel comes into contact with mucosa.

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Docetaxel is available as 10 mg/mL or 20 mg/mL vials from multiple manufacturers; check the concentration prior to calculating the volume of drug needed.
    Further dilution is required prior to administration.
    Recommended vial dilutions (1 or 2 vial formulation), size of needle for vial content withdrawal (18- to 21-gauge needle), multi-dose vial storage, and storage following dilution differ among products; refer to the manufacturer package insert for specific instructions.
    Do NOT mix the contents of the 2-vial formulation with the 1-vial formulation.
    Do not use plasticized PVC equipment or devices to prepare or infuse docetaxel; di-2-ethylhexyl phthalate (DEHP) may leach from PVC infusion bags or sets.
    Premedication with oral dexamethasone should be administered starting the day before docetaxel to reduce the incidence and severity of fluid retention and hypersensitivity reactions.
    Dilution:
    If applicable, allow docetaxel solution vials to stand at room temperature for approximately 5 minutes before use.
    Prepare and store diluted docetaxel admixtures in bottles (glass, polypropylene) or plastic (non-PVC) bags (polypropylene, polyolefin).
    Aseptically withdraw the calculated amount of docetaxel with a calibrated syringe and inject into a 250 mL infusion bag or bottle of 0.9% sodium chloride or 5% dextrose to a final concentration of 0.3 to 0.74 mg/mL; dilute in a larger volume for docetaxel doses greater than 200 mg.
    Thoroughly mix the infusion by gentle manual rotation.
    Storage after dilution (Taxotere and the following generics: Accord, Actavis, Armas, Dr. Reddy's, Hikma, Sagent, Sun Pharma, Winthrop): After dilution, docetaxel may be stored at 2 to 25 degrees C (36 to 77 degrees F) for up to 6 hours (including the 1 hour for IV administration). Physical and chemical in-use stability of the infusion solution has also been demonstrated in non-PVC bags for up to 48 hours when stored between 2 and 8 degrees C (36 and 46 degrees F).
    Storage after dilution (generics including Baxter, Gland Pharma, Hospira, Ingenus, Mylan, Sandoz): After dilution, docetaxel may be stored at 2 to 25 degrees C (36 to 77 degrees F) for up to 4 hours (including the 1 hour for IV administration).
    Intravenous (IV) Infusion:
    Administer IV over 1 hour using a polyethylene-lined administration set.
    Monitor patients closely for hypersensitivity reactions, especially during the first and second infusions. Discontinue the docetaxel infusion and administer supportive therapy in patients who develop a severe hypersensitivity reaction.[60484]

    STORAGE

    Generic:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Flammable, keep away from heat and flame
    - Product is stable for 28 days after initial use when stored under refrigeration (36 to 46 degrees F)
    - Store at controlled room temperature (between 68 and 77 degrees F)
    - Store diluted product in accordance with package insert instructions
    - Store in the original carton to protect from light
    Docefrez :
    - Discard unused portion. Do not store for later use.
    - Protect from light
    - Store between 36 to 46 degrees F
    - Store in original package until time of use
    Taxotere:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Protect from direct sunlight
    - Store between 36 to 77 degrees F
    - Store in a cool, well ventilated, dry place
    - Store in the original carton to protect from light
    - Store upright

    CONTRAINDICATIONS / PRECAUTIONS

    Infection, neutropenia, thrombocytopenia

    Docetaxel is contraindicated in patients with neutropenia (ANC less than 1,500 cells/mm3); patients with thrombocytopenia (platelets less than 100,000 cells/mm3) also should not receive docetaxel therapy. Neutropenia occurs in most patients treated with docetaxel; it may be severe and result in infection. Frequently monitor complete blood counts in all patients. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for patients with severe and prolonged neutropenia, febrile neutropenia, or severe infection.[60484]

    New primary malignancy

    A new primary malignancy has occurred in patients treated with docetaxel-containing regimens, including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), non-Hodgkin's lymphoma (NHL), and renal cell cancer. Treatment-related AML or MDS has occurred in patients given anthracyclines and/or cyclophosphamide. These cancers may occur several months or years after docetaxel-containing therapy. In the adjuvant breast cancer trial (TAX316), AML occurred in 3 of 744 patients (0.4%) who received docetaxel, doxorubicin, and cyclophosphamide (TAC) and in 1 of 736 patients who received 5-fluorouracil, doxorubicin, and cyclophosphamide (0.1%). In TAC-treated patients, the risk of delayed myelodysplasia or myeloid leukemia requires hematologic follow-up. Monitor patients for new primary malignancies.

    Biliary tract disease, hepatic disease

    Use of docetaxel in patients with biliary tract disease or hepatic disease may increase the risk of grade 4 neutropenia, febrile neutropenia, infections, severe thrombocytopenia, severe stomatitis, severe skin toxicity, or toxic death. Monitor bilirubin, AST/ALT, and alkaline phosphatase levels prior to each cycle of docetaxel. Avoid use in patients with a bilirubin level greater than the upper limit of normal (ULN) or with combined transaminase (AST and/or ALT level greater than 1.5 times the ULN) and alkaline phosphatase (AP) elevations (AP level greater than 2.5 times the ULN). Consider a docetaxel dose reduction in patients with isolated transaminase elevations (AST and/or ALT level greater than 1.5 times the ULN).[60484]

    Acute bronchospasm, hypotension, polysorbate 80 hypersensitivity, serious hypersensitivity reactions or anaphylaxis, taxane hypersensitivity

    Docetaxel is contraindicated in patients who have a history of severe docetaxel hypersensitivity or other drugs formulated with polysorbate 80 (polysorbate 80 hypersensitivity). Use docetaxel with caution in patients with a history of other taxane hypersensitivity; patients who have previously experienced a hypersensitivity reaction to paclitaxel may develop serious hypersensitivity reactions or anaphylaxis to docetaxel that may be fatal. Severe hypersensitivity reactions characterized by generalized rash/erythema, hypotension and/or acute bronchospasm, or very rarely fatal anaphylaxis, have been reported in patients despite receiving 3 days of dexamethasone premedication. Premedicate all patients with an oral corticosteroid prior to initiation of a docetaxel infusion. Observe patients closely, especially during the first and second infusions; reactions may occur within a few minutes following initiation of an infusion. If minor reactions such as flushing or localized skin reactions occur, interruption of therapy is not required. Severe reactions require immediate discontinuation of docetaxel infusion and aggressive therapy. Do not rechallenge patients with a history of severe hypersensitivity to docetaxel.[60484]

    Ascites, cardiac tamponade, edema, fluid retention, peripheral edema, pleural effusion

    Severe fluid retention (e.g., poorly tolerated peripheral edema, generalized edema, pleural effusion requiring urgent drainage, dyspnea at rest, cardiac tamponade, and/or pronounced abdominal distention due to ascites) has occurred in patients treated with docetaxel despite premedication with 3 days of corticosteroids. Premedicate patients with oral corticosteroids prior to each docetaxel administration to reduce the incidence and severity of fluid retention. Closely monitor patients with pre-existing effusions for signs of a possible exacerbation. Docetaxel-related fluid retention was completely, but sometimes slowly, reversible with a median of 16 weeks from the last infusion of docetaxel to resolution (range, 0 to 42 weeks). Treat peripheral edema with standard measures (e.g., salt restriction, oral diuretics).

    Ocular disease

    Use docetaxel with caution in patients with pre-existing ocular disease; cystoid macular edema (CME) has been reported in patients treated with docetaxel. If a patient experiences impaired vision, perform a prompt and comprehensive eye examination. If CME is diagnosed, discontinue docetaxel and initiate appropriate treatment; alternative non-taxane treatment for cancer should be considered.[60484]

    Colitis

    Enterocolitis and neutropenic colitis (typhlitis) have occurred with docetaxel treatment, despite administration of growth factors. Use docetaxel with caution in patients who are neutropenic, as they are particularly at risk for developing gastrointestinal (GI) complications. Enterocolitis and typhlitis can develop at any time and could lead to death. Monitor patients closely from the onset of any gastrointestinal symptoms. Inform patients to contact their healthcare provider for any new or worsening GI symptoms.

    Alcoholism, driving or operating machinery, ethanol ingestion, ethanol intoxication

    Most docetaxel injection formulations contain ethanol to dissolve the active ingredients; take this into account for patients in whom ethanol ingestion should be avoided or minimized, including patients with alcoholism or hepatic disease. The amount of alcohol varies between products; consult individual product labeling for alcohol content. Dosing has resulted in reports of ethanol intoxication or feeling drunk during and after treatment. Slowing the rate of infusion may help to resolve symptoms of alcohol intoxication. Patients should give consideration to the effect of the alcohol content in docetaxel on driving or operating machinery immediately after the infusion.[60484] An alcohol-free docetaxel formulation is available.

    Mortality

    Docetaxel at a dose of 100 mg/m2 in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) and a history of prior platinum-based chemotherapy was associated with increased treatment-related mortality (14% and 5% in two randomized, controlled studies). There were 2.8% treatment-related deaths among the 176 patients treated at the 75 mg/m2 dose in randomized trials; 3 of these 5 patients had an ECOG performance status of 2 at study entry. The 100 mg/m2 dose was also associated with deaths possibly or probably related to treatment in 2% of metastatic breast cancer patients with normal baseline liver function (n = 965), both previously treated and untreated, and in 11.5% of patients with various tumor types who had abnormal baseline liver function (n = 61). Among patients dosed at 60 mg/m2, treatment-related mortality occurred in 0.6% of patients with normal liver function (n = 481) and in 3 of 7 patients with abnormal liver function. Approximately half of these deaths occurred during the first cycle; sepsis accounted for the majority of deaths.[60484]

    Serious rash

    Serious rash has been reported with docetaxel therapy. Severe cutaneous adverse reactions (SCARs) that were associated with docetaxel therapy include Stevens-Johnson syndrome, toxic epidermal necrolysis, and acute generalized exanthematous pustulosis. Monitor patients for the development of skin toxicity. If severe rash occurs, a docetaxel dose adjustment may be necessary; consider treatment discontinuation in patients who experience SCARs.

    Neurotoxicity

    Severe neurotoxicity has been reported in patients treated with docetaxel; a dose adjustment of docetaxel is necessary if these symptoms occur (e.g., paresthesia, dysesthesia, pain). Discontinue docetaxel for persistent neurosensory symptoms. In clinical trials, spontaneous reversal of symptoms occurred with a median of 9 weeks from the onset, but ranged up to 106 weeks.[60484]

    Hyperuricemia, renal impairment, tumor lysis syndrome (TLS)

    Cases of tumor lysis syndrome (TLS) have been reported in postmarketing experience in patients treated with docetaxel; patients with a significant tumor burden may be at higher risk. Correct dehydration and treat high uric acid levels prior to initiation of treatment. Closely monitor patients at risk (e.g., renal impairment, hyperuricemia, bulky tumor) prior to initiating therapy and periodically during treatment.

    Children, infants

    The alcohol content of docetaxel injection should be taken into account when administered to infants and children; an alcohol-free formulation of docetaxel is available. The efficacy of docetaxel in pediatric patients as monotherapy or in combination with other agents has not been established. The overall safety profile of docetaxel in pediatric patients was consistent with the known safety profile in adults. In a dose-finding phase 1 trial (n = 61), the primary dose-limiting toxicity was neutropenia.

    Geriatric

    In general, dose selection for a geriatric patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy in the elderly. The incidence of adverse reactions is higher in elderly patients treated with docetaxel (alone or in combination with other agents) as compared to patients younger than 65 years of age.[60484]

    Pregnancy

    Pregnancy should be avoided by females of reproductive potential during docetaxel treatment and for at least 6 months after the last dose. Although there are no adequately controlled studies in pregnant women, docetaxel can cause fetal harm or death when administered during pregnancy based on its mechanism of action and animal studies. Women who are pregnant or who become pregnant while receiving docetaxel should be apprised of the potential hazard to the fetus. An increased incidence of embryofetal toxicities (e.g., intrauterine mortality, resorptions, reduced fetal weights, and fetal ossification delays) occurred when docetaxel was administered to pregnant rats and rabbits during organogenesis at doses 0.02 and 0.003 times the recommended human dose based on body surface area, respectively; maternal toxicity was also observed at these doses. Additionally, docetaxel injection is formulated with alcohol, which has been independently associated with fetal harm including central nervous system abnormalities, behavioral disorders, and impaired intellectual development.

    Contraception requirements, infertility, male-mediated teratogenicity, pregnancy testing, reproductive risk

    Counsel patients about the reproductive risk and contraception requirements during docetaxel treatment. Docetaxel can be teratogenic if taken by the mother during pregnancy. Females of reproductive potential should avoid pregnancy and use effective contraception during and for at least 6 months after treatment with docetaxel. Females of reproductive potential should undergo pregnancy testing prior to initiation of docetaxel. Due to the risk of male-mediated teratogenicity, males with female partners of reproductive potential should avoid pregnancy and use effective contraception during and for at least 3 months after treatment with docetaxel. Women who become pregnant while receiving docetaxel should be apprised of the potential hazard to the fetus. Although there are no data regarding the effect of docetaxel on human fertility, male infertility has been observed in animal studies.

    Breast-feeding

    Due to the potential for serious adverse reactions in nursing infants from docetaxel, advise women to discontinue breast-feeding during treatment and for 1 week after the final dose; recommendations differ among products. Refer to the manufacturer package insert for specific instructions. It is not known whether docetaxel is present in human milk, although many drugs are excreted in human milk.[60484]

    ADVERSE REACTIONS

    Severe

    neutropenia / Delayed / 65.0-94.0
    leukopenia / Delayed / 32.0-49.0
    stomatitis / Delayed / 1.0-39.0
    infection / Delayed / 0-33.0
    anemia / Delayed / 4.0-31.0
    asthenia / Delayed / 13.0-25.0
    diarrhea / Early / 2.0-20.0
    thrombocytopenia / Delayed / 0-17.0
    nausea / Early / 0-14.0
    dysphagia / Delayed / 0-13.0
    odynophagia / Delayed / 0-13.0
    esophagitis / Delayed / 0-13.0
    anorexia / Delayed / 1.0-12.0
    alopecia / Delayed / 0-11.0
    serious hypersensitivity reactions or anaphylaxis / Rapid / 1.0-10.0
    heart failure / Delayed / 0-8.1
    fever / Early / 0-8.0
    vomiting / Early / 0-8.0
    fluid retention / Delayed / 0-6.5
    GI bleeding / Delayed / 0-6.0
    dizziness / Early / 0-5.0
    abdominal pain / Early / 0-5.0
    lethargy / Early / 0-5.0
    fatigue / Early / 0-5.0
    myocardial infarction / Delayed / 0-2.0
    dyspepsia / Early / 0-2.0
    myalgia / Early / 0-2.0
    weight loss / Delayed / 0-2.0
    rash / Early / 0-1.0
    exfoliative dermatitis / Delayed / 0-1.0
    acute respiratory distress syndrome (ARDS) / Early / 0-1.0
    pulmonary fibrosis / Delayed / 0-1.0
    peripheral vasodilation / Rapid / 0-1.0
    syncope / Early / 0-1.0
    dysgeusia / Early / 0-1.0
    constipation / Delayed / 0-1.0
    arthralgia / Delayed / 0-1.0
    leukemia / Delayed / 0-0.4
    disseminated intravascular coagulation (DIC) / Delayed / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known
    erythema multiforme / Delayed / Incidence not known
    cardiac tamponade / Delayed / Incidence not known
    pleural effusion / Delayed / Incidence not known
    atrial flutter / Early / Incidence not known
    atrial fibrillation / Early / Incidence not known
    ventricular tachycardia / Early / Incidence not known
    bronchospasm / Rapid / Incidence not known
    anaphylactic shock / Rapid / Incidence not known
    seizures / Delayed / Incidence not known
    ileus / Delayed / Incidence not known
    GI obstruction / Delayed / Incidence not known
    peptic ulcer / Delayed / Incidence not known
    GI perforation / Delayed / Incidence not known
    ischemic colitis / Early / Incidence not known
    typhlitis / Delayed / Incidence not known
    enterocolitis / Delayed / Incidence not known
    hepatotoxicity / Delayed / Incidence not known
    new primary malignancy / Delayed / Incidence not known
    lymphoma / Delayed / Incidence not known
    renal failure (unspecified) / Delayed / Incidence not known
    pulmonary embolism / Delayed / Incidence not known
    thrombosis / Delayed / Incidence not known
    ototoxicity / Delayed / Incidence not known
    hearing loss / Delayed / Incidence not known
    tumor lysis syndrome (TLS) / Delayed / Incidence not known

    Moderate

    edema / Delayed / 13.0-67.0
    elevated hepatic enzymes / Delayed / 0-18.9
    hyperbilirubinemia / Delayed / 0-8.9
    dyspnea / Early / 0-3.0
    hypotension / Rapid / 1.9-2.8
    phlebitis / Rapid / 0-1.0
    pneumonitis / Delayed / 0-1.0
    bone marrow suppression / Delayed / Incidence not known
    bleeding / Early / Incidence not known
    bullous rash / Early / Incidence not known
    erythema / Early / Incidence not known
    palmar-plantar erythrodysesthesia (hand and foot syndrome) / Delayed / Incidence not known
    radiation recall reaction / Delayed / Incidence not known
    ascites / Delayed / Incidence not known
    peripheral edema / Delayed / Incidence not known
    sinus tachycardia / Rapid / Incidence not known
    angina / Early / Incidence not known
    hypertension / Early / Incidence not known
    neurotoxicity / Early / Incidence not known
    peripheral neuropathy / Delayed / Incidence not known
    confusion / Early / Incidence not known
    colitis / Delayed / Incidence not known
    dehydration / Delayed / Incidence not known
    hepatitis / Delayed / Incidence not known
    hypocalcemia / Delayed / Incidence not known
    hypomagnesemia / Delayed / Incidence not known
    hyponatremia / Delayed / Incidence not known
    hypokalemia / Delayed / Incidence not known
    ethanol intoxication / Early / Incidence not known
    chest pain (unspecified) / Early / Incidence not known

    Mild

    amenorrhea / Delayed / 0-62.0
    dysosmia / Delayed / 0-20.0
    cough / Delayed / 0-12.0
    lacrimation / Early / 2.0-11.0
    epistaxis / Delayed / 0-6.0
    xerosis / Delayed / 0-6.0
    injection site reaction / Rapid / 3.0-4.0
    onycholysis / Delayed / 0.8-0.8
    pruritus / Rapid / Incidence not known
    nail discoloration / Delayed / Incidence not known
    skin hyperpigmentation / Delayed / Incidence not known
    weight gain / Delayed / Incidence not known
    back pain / Delayed / Incidence not known
    flushing / Rapid / Incidence not known
    chills / Rapid / Incidence not known
    paresthesias / Delayed / Incidence not known
    dysesthesia / Delayed / Incidence not known

    DRUG INTERACTIONS

    Amlodipine; Celecoxib: (Major) Due to the thrombocytopenic effects of docetaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid coadministration of docetaxel with clarithromycin if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
    Amprenavir: (Minor) Amprenavir may inhibit the metabolism of other medications that are metabolized via cytochrome P450 3A4, such as docetaxel. Although drug interaction studies have not been conducted, the serum concentrations of docetaxel may be increased with concomitant administration of amprenavir
    Apalutamide: (Major) Avoid coadministration of docetaxel with apalutamide due to decreased plasma concentrations of docetaxel. Docetaxel is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. Concomitant use with other strong CYP3A4 inducers increased docetaxel metabolism by 2.6-fold to 32-fold.
    Aprepitant, Fosaprepitant: (Moderate) Aprepitant, fosaprepitant is indicated for the prophylaxis of chemotherapy-induced nausea/vomiting and is often used in combination with docetaxel. However, use caution and monitor for a possible increase in non-emetogenic docetaxel-related adverse effects for several days after administration of a multi-day aprepitant regimen. Docetaxel is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and theoretically may increase plasma concentrations of docetaxel. The AUC of another CYP3A4 substrate, midazolam, was increased when coadministered with aprepitant; however, in a pharmacokinetic study, oral aprepitant (125 mg/80 mg) did not influence the pharmacokinetics of docetaxel. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction.
    Atazanavir: (Major) Avoid coadministration of docetaxel with atazanavir if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
    Atazanavir; Cobicistat: (Major) Avoid coadministration of docetaxel with atazanavir if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold. (Major) Avoid coadministration of docetaxel with cobicistat if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Major) Avoid coadministration of docetaxel with phenobarbital due to decreased plasma concentrations of docetaxel. Docetaxel is a CYP3A4 substrate and phenobarbital is a strong CYP3A4 inducer. Concomitant use with other strong CYP3A4 inducers increased docetaxel metabolism by 2.6-fold to 32-fold.
    Boceprevir: (Moderate) Close clinical monitoring is advised when administering docetaxel with boceprevir due to an increased potential for docetaxel-related adverse events. If docetaxel dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of docetaxel. Docetaxel is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; boceprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated docetaxel plasma concentrations.
    Bortezomib: (Minor) Monitor patients for the development of peripheral neuropathy when receiving bortezomib in combination with other drugs that can cause peripheral neuropathy like docetaxel; the risk of peripheral neuropathy may be additive.
    Bosentan: (Minor) Bosentan is an inducer of cytochrome P450 enzymes, specifically the CYP2C9 and CYP3A4 isoenzymes, and may decrease concentrations of drugs metabolized by these enzymes, such as docetaxel.
    Brigatinib: (Moderate) Monitor for decreased efficacy of docetaxel if coadministration with brigatinib is necessary. Docetaxel is a CYP3A substrate and brigatinib induces CYP3A in vitro; plasma concentrations of docetaxel may decrease.
    Bupivacaine; Meloxicam: (Major) Due to the thrombocytopenic effects of docetaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Cabozantinib: (Minor) Monitor for an increase in docetaxel-related adverse reactions if coadministration with cabozantinib is necessary. Docetaxel is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
    Carbamazepine: (Major) Avoid coadministration of docetaxel with carbamazepine due to decreased plasma concentrations of docetaxel. Docetaxel is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Concomitant use with other strong CYP3A4 inducers increased docetaxel metabolism by 2.6-fold to 32-fold.
    Carvedilol: (Major) Increased concentrations of docetaxel may occur if it is coadministered with carvedilol; exercise caution. Carvedilol is a P-glycoprotein (P-gp) inhibitor and docetaxel is a P-gp substrate.
    Celecoxib: (Major) Due to the thrombocytopenic effects of docetaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Celecoxib; Tramadol: (Major) Due to the thrombocytopenic effects of docetaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Ceritinib: (Major) Avoid coadministration of docetaxel with ceritinib if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
    Chloramphenicol: (Major) Avoid coadministration of docetaxel with chloramphenicol if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
    Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) Due to the thrombocytopenic effects of docetaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
    Ciprofloxacin: (Moderate) The plasma concentrations of docetaxel may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as myelosuppression and neurologic toxicity, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor, while docetaxel is a CYP3A4 substrate.
    Clarithromycin: (Major) Avoid coadministration of docetaxel with clarithromycin if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
    Cobicistat: (Major) Avoid coadministration of docetaxel with cobicistat if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
    Cyclosporine: (Major) Cyclosporine is a substrate and inhibitor of P-glycoprotein, an energy-dependent drug efflux pump encoded for by the multidrug resistance gene-1 (MDR1). Overexpression of this protein has been described as a mechanism of resistance to naturally-occurring (non-synthetic) chemotherapy agents. Cyclosporine may enhance the efficacy of the certain chemotherapy agents including docetaxel, paclitaxel, and vinca alkaloids by inhibiting this protein. Cyclosporine can block MDR1-mediated resistance when given at much higher doses than those used in transplantation. The addition of cyclosporine may also enhance the efficacy and/or toxicity of these chemotherapy regimens by other mechanisms. The addition of cyclosporine may increase the AUC values of these chemotherapy agents due to a decrease in either chemotherapy metabolism or clearance, or due to an increase in the intracellular concentrations of the chemotherapy agent.
    Daclatasvir: (Moderate) Systemic exposure of docetaxel, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of docetaxel; monitor patients for potential adverse effects.
    Dalfopristin; Quinupristin: (Moderate) Caution is warranted during coadministration of docetaxel and dalfopristin; quinupristin, as the systemic exposure of docetaxel may be increased resulting in increased treatment-related adverse reactions. Docetaxel is a CYP3A4 substrate; dalfopristin; quinupristin is a weak CYP3A4 inhibitor.
    Darunavir: (Major) Avoid coadministration of docetaxel with darunavir if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and darunavir is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
    Darunavir; Cobicistat: (Major) Avoid coadministration of docetaxel with cobicistat if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold. (Major) Avoid coadministration of docetaxel with darunavir if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and darunavir is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Avoid coadministration of docetaxel with cobicistat if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold. (Major) Avoid coadministration of docetaxel with darunavir if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and darunavir is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) Avoid coadministration of docetaxel with ritonavir if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and ritonavir is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
    Delavirdine: (Major) Avoid coadministration of docetaxel with delavirdine if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and delavirdine is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
    Diclofenac: (Major) Due to the thrombocytopenic effects of docetaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Diclofenac; Misoprostol: (Major) Due to the thrombocytopenic effects of docetaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Diflunisal: (Major) Due to the thrombocytopenic effects of docetaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Diphenhydramine; Ibuprofen: (Major) Due to the thrombocytopenic effects of docetaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Diphenhydramine; Naproxen: (Major) Due to the thrombocytopenic effects of docetaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Doxorubicin Liposomal: (Minor) Docetaxel appears to cause sequence-related drug interactions with doxorubicin. Antagonism may occur if docetaxel and doxorubicin are administered simultaneously, and when doxorubicin was added prior to docetaxel.
    Doxorubicin: (Minor) Docetaxel appears to cause sequence-related drug interactions with doxorubicin. Antagonism may occur if docetaxel and doxorubicin are administered simultaneously, and when doxorubicin was added prior to docetaxel.
    Dronedarone: (Major) Docetaxel is a substrate for CYP3A4 and P-gp and dronedarone is metabolized by and is an inhibitor of CYP3A; dronedarone also inhibits P-gp. The concomitant administration of dronedarone with CYP3A4 and P-gp substrates may result in increased exposure of the substrate; concomitant use of these agents should be used with extreme caution and possibly avoided in elderly patients. Fatal pan mucositis was reported in an elderly patient who was receiving docetaxel for metastatic prostate cancer and dronedarone to control atrial fibrillation in a case report. This 79-year-old man presented to the hospital with grade 4 mucositis and febrile neutropenia following his third cycle of docetaxel after receiving dronedarone for appoximately 6 weeks. Despite neutrophil recovery, he experienced skin and cutaneous lesion deterioration, grade 4 stomatitis, necrotic conjunctivitis, and grade 4 keratitis; no infectious etiology for mucositis was identified. A docetaxel level of 2.4 ng/ml was detected 14 days after the last infusion; this detectable docetaxel level was unexpected. The patient subsequently died of ICU-acquired sepsis. Consider using an alternate antiarrhythmic agent in patients receiving docetaxel. Following a risk/benefit analysis, if docetaxel is administered in a patient who also requires dronedarone, monitor patient for signs of severe stomatitis/mucositis or cutaneous reactions and other serious side effects associated with docetaxel (eg, paresthesias/dysesthesias, asthenia, febrile neutropenia, infection).
    Efavirenz: (Moderate) Efavirenz induces CYP3A4 and may decrease serum concentrations of drugs metabolized by this enzyme, such as docetaxel.
    Efavirenz; Emtricitabine; Tenofovir: (Moderate) Efavirenz induces CYP3A4 and may decrease serum concentrations of drugs metabolized by this enzyme, such as docetaxel.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Efavirenz induces CYP3A4 and may decrease serum concentrations of drugs metabolized by this enzyme, such as docetaxel.
    Elagolix: (Moderate) Monitor for decreased docetaxel efficacy when coadministration with elagolix is necessary. Docetaxel exposure may be decreased during concurrent use. Elagolix is a weak to moderate CYP3A4 inducer and docetaxel is a CYP3A4 substrate.
    Elagolix; Estradiol; Norethindrone acetate: (Moderate) Monitor for decreased docetaxel efficacy when coadministration with elagolix is necessary. Docetaxel exposure may be decreased during concurrent use. Elagolix is a weak to moderate CYP3A4 inducer and docetaxel is a CYP3A4 substrate.
    Elbasvir; Grazoprevir: (Moderate) Administering docetaxel with elbasvir; grazoprevir may result in elevated docetaxel plasma concentrations. Docetaxel is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
    Elexacaftor; tezacaftor; ivacaftor: (Moderate) Monitor for docetaxel-related adverse reactions during coadministration of elexacaftor; tezacaftor; ivacaftor as concurrent use may increase exposure of docetaxel. Docetaxel is a substrate for the transporters OATP1B1 and OATP1B3; elexacaftor; tezacaftor; ivacaftor may inhibit uptake of OATP1B1 and OATP1B3.
    Eliglustat: (Major) Coadministration of docetaxel and eliglustat may result in increased plasma concentrations of docetaxel. If coadministration is necessary, use caution and monitor closely. Docetaxel is a P-glycoprotein (P-gp) substrate; eliglustat is a P-gp inhibitor.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Avoid coadministration of docetaxel with cobicistat if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of docetaxel with cobicistat if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
    Enzalutamide: (Major) Avoid coadministration of docetaxel with enzalutamide due to decreased plasma concentrations of docetaxel. Docetaxel is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer. Concomitant use with other strong CYP3A4 inducers increased docetaxel metabolism by 2.6-fold to 32-fold.
    Epirubicin: (Moderate) Monitor for an increase in epirubicin-related adverse reactions, including hematologic and gastrointestinal toxicities, if coadministration with docetaxel is necessary. Coadministration of docetaxel immediately before or after epirubicin had no effect on the systemic exposure of epirubicin. However, the mean AUC of epirubicinol and 7-deoxy-aglycone (inactive metabolites) increased by 22.5% and 95%, respectively, when docetaxel was administered immediately after epirubicin. Epirubicin had no effect on the exposure of docetaxel.
    Erlotinib: (Moderate) The use of taxane-based chemotherapy with erlotinib appears to be one of the risk factors for gastrointestinal (GI) perforation with erlotinib. Monitor for symptoms of GI perforation (e.g., severe abdominal pain, fever, nausea, and vomiting) if coadministration of erlotinib with a taxane chemotherapy agent is necessary.
    Erythromycin: (Minor) Docetaxel is metabolized by cytochrome P450 3A (CYP3A4 and CYP3A5) enzymes. Erythromycin is a CYP3A4 inhibitor. In vitro studies have shown drugs that inhibit, induce, or are also metabolized by CYP3A enzymes can significantly affect the metabolism of docetaxel. In a small pharmacokinetic study, 7 patients received 2 courses of docetaxel, one with concurrent ketoconazole (docetaxel 10 mg/m2) and one without ketoconazole (docetaxel 100mg/m2). The ketoconazole dosage was 200 mg once daily for 3 days. Concurrent administration of ketoconazole decreased the clearance of docetaxel by 49% as compared to giving docetaxel alone. However, there was large interpatient variability in the reduction in clearance. Use docetaxel cautiously when administered concurrently with inducers or inhibitors of CYP3A enzymes.
    Erythromycin; Sulfisoxazole: (Minor) Docetaxel is metabolized by cytochrome P450 3A (CYP3A4 and CYP3A5) enzymes. Erythromycin is a CYP3A4 inhibitor. In vitro studies have shown drugs that inhibit, induce, or are also metabolized by CYP3A enzymes can significantly affect the metabolism of docetaxel. In a small pharmacokinetic study, 7 patients received 2 courses of docetaxel, one with concurrent ketoconazole (docetaxel 10 mg/m2) and one without ketoconazole (docetaxel 100mg/m2). The ketoconazole dosage was 200 mg once daily for 3 days. Concurrent administration of ketoconazole decreased the clearance of docetaxel by 49% as compared to giving docetaxel alone. However, there was large interpatient variability in the reduction in clearance. Use docetaxel cautiously when administered concurrently with inducers or inhibitors of CYP3A enzymes.
    Etodolac: (Major) Due to the thrombocytopenic effects of docetaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Etravirine: (Moderate) Etravirine is a CYP3A4 inducer/substrate and a P-glycoprotein (PGP) inhibitor and docetaxel is a CYP3A4 and PGP substrate. Caution is warranted if these drugs are coadministered.
    Famotidine; Ibuprofen: (Major) Due to the thrombocytopenic effects of docetaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Fenoprofen: (Major) Due to the thrombocytopenic effects of docetaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Filgrastim, G-CSF: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert their toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
    Fluconazole: (Minor) Docetaxel is metabolized by cytochrome P450 3A enzymes. Drugs that inhibit the CYP3A enzymes, such as fluconazole, can significantly reduce the metabolism of docetaxel. Use docetaxel cautiously when administered concurrently with inhibitors of CYP3A enzymes.
    Fluoxetine: (Minor) Docetaxel is metabolized by cytochrome P450 3A enzymes. Drugs that inhibit the CYP3A enzymes, such as fluoxetine, can significantly reduce the metabolism of docetaxel.
    Flurbiprofen: (Major) Due to the thrombocytopenic effects of docetaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Fluvoxamine: (Minor) Docetaxel is metabolized by cytochrome P450 3A enzymes. Drugs that inhibit CYP3A enzymes, such as fluvoxamine, can significantly reduce the metabolism of docetaxel. Use docetaxel cautiously when administered concurrently with inhibitors of CYP3A enzymes.
    Fosamprenavir: (Major) Avoid coadministration of docetaxel with fosamprenavir if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and fosamprenavir is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
    Fosphenytoin: (Major) Avoid coadministration of docetaxel with fosphenytoin due to decreased plasma concentrations of docetaxel. Docetaxel is a CYP3A4 substrate and fosphenytoin is a strong CYP3A4 inducer. Concomitant use with other strong CYP3A4 inducers increased docetaxel metabolism by 2.6-fold to 32-fold.
    Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with the coadministration of glecaprevir and docetaxel as coadministration may increase serum concentrations of docetaxel and increase the risk of adverse effects. Docetaxel is a substrate of P-glycoprotein (P-gp); glecaprevir is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and docetaxel as coadministration may increase serum concentrations of docetaxel and increase the risk of adverse effects. Docetaxel is a substrate of P-glycoprotein (P-gp); pibrentasvir is an inhibitor of P-gp.
    Grapefruit juice: (Major) Advise patients to avoid grapefruit juice while on docetaxel due to increased plasma concentrations of docetaxel. Docetaxel is a CYP3A4 substrate and grapefruit juice is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
    Hydrocodone; Ibuprofen: (Major) Due to the thrombocytopenic effects of docetaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Ibuprofen: (Major) Due to the thrombocytopenic effects of docetaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Ibuprofen; Oxycodone: (Major) Due to the thrombocytopenic effects of docetaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Ibuprofen; Pseudoephedrine: (Major) Due to the thrombocytopenic effects of docetaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Idelalisib: (Major) Avoid coadministration of docetaxel with idelalisib if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
    Ifosfamide: (Minor) When docetaxel and ifosfamide are given concurrently or in sequence, an apparent decrease in the AUC of ifosfamide is observed due to an increased ifosfamide clearance when docetaxel (over 1 hour) is followed by ifosfamide (over 24 hours). The reverse sequence (ifosfamide over 24 hours followed by docetaxel over 1 hour) does not cause an AUC alteration. The pharmacokinetics of docetaxel were unchanged in either case.
    Imatinib: (Moderate) Imatinib is a potent inhibitor of cytochrome P450 3A4 and may increase concentrations of other drugs metabolized by this enzyme including docetaxel.
    Indinavir: (Major) Avoid coadministration of docetaxel with indinavir if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and indinavir is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
    Indomethacin: (Major) Due to the thrombocytopenic effects of docetaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with docetaxel may result in increased serum concentrations of docetaxel. Docetaxel is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Caution and close monitoring are advised if these drugs are used together.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid coadministration of docetaxel with rifampin due to decreased plasma concentrations of docetaxel. Docetaxel is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Concomitant use with other strong CYP3A4 inducers increased docetaxel metabolism by 2.6-fold to 32-fold.
    Isoniazid, INH; Rifampin: (Major) Avoid coadministration of docetaxel with rifampin due to decreased plasma concentrations of docetaxel. Docetaxel is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Concomitant use with other strong CYP3A4 inducers increased docetaxel metabolism by 2.6-fold to 32-fold.
    Itraconazole: (Major) Administration of docetaxel is not recommended during or for 2 weeks after discontinuation of itraconazole treatment due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and itraconazole is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
    Ixabepilone: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp). Docetaxel is a Pgp substrate, and concomitant use of ixabepilone with a Pgp substrate may cause an increase in docetaxel concentrations. Use caution if ixabepilone is coadministered with a Pgp substrate.
    Ketoconazole: (Major) Avoid coadministration of docetaxel with ketoconazole if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and ketoconazole is a strong CYP3A4 inhibitor. Concomitant use with ketoconazole increased docetaxel exposure by 2.2-fold.
    Ketoprofen: (Major) Due to the thrombocytopenic effects of docetaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Ketorolac: (Major) Due to the thrombocytopenic effects of docetaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Lansoprazole; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of docetaxel with clarithromycin if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
    Lansoprazole; Naproxen: (Major) Due to the thrombocytopenic effects of docetaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Ledipasvir; Sofosbuvir: (Minor) Caution and close monitoring of docetaxel-associated adverse reactions is advised with concomitant administration of ledipasvir. Docetaxel is a substrate of the drug transporter P-glycoprotein (P-gp); ledipasvir is a P-gp inhibitor. Taking these drugs together may increase docetaxel plasma concentrations.
    Letermovir: (Moderate) Administering letermovir with docetaxel may increase docetaxel concentration and risk for adverse events. Avoid coadministration if the patient is also receiving cyclosporine, because the magnitude of this interaction may be increased. Consider a 50% dose reduction of docetaxel if all 3 drugs must be administered concurrently. Docetaxel is a substrate of CYP3A4. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor. Concurrent administration with a strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold and reduced drug clearance by 49%.
    Levoketoconazole: (Major) Avoid coadministration of docetaxel with ketoconazole if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and ketoconazole is a strong CYP3A4 inhibitor. Concomitant use with ketoconazole increased docetaxel exposure by 2.2-fold.
    Live Vaccines: (Contraindicated) Do not administer live vaccines to docetaxel recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving docetaxel. At least 2 weeks before initiation of docetaxel therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Docetaxel recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
    Lonafarnib: (Major) Avoid coadministration of docetaxel with lonafarnib if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and lonafarnib is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
    Lopinavir; Ritonavir: (Major) Avoid coadministration of docetaxel with ritonavir if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and ritonavir is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold. (Moderate) Monitor for docetaxel-related adverse reactions during coadministration with lopinavir as concurrent use may increase exposure of docetaxel. Docetaxel is a substrate of the drug transporter organic anion transporting polypeptide (OATP1B1); lopinavir is an OATP1B1 inhibitor.
    Lumacaftor; Ivacaftor: (Major) Avoid coadministration of docetaxel with lumacaftor; ivacaftor due to decreased plasma concentrations of docetaxel. Docetaxel is a CYP3A4 substrate and lumacaftor is a strong CYP3A4 inducer. Concomitant use with other strong CYP3A4 inducers increased docetaxel metabolism by 2.6-fold to 32-fold.
    Lumacaftor; Ivacaftor: (Major) Avoid coadministration of docetaxel with lumacaftor; ivacaftor due to decreased plasma concentrations of docetaxel. Docetaxel is a CYP3A4 substrate and lumacaftor is a strong CYP3A4 inducer. Concomitant use with other strong CYP3A4 inducers increased docetaxel metabolism by 2.6-fold to 32-fold.
    Meclofenamate Sodium: (Major) Due to the thrombocytopenic effects of docetaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Mefenamic Acid: (Major) Due to the thrombocytopenic effects of docetaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Meloxicam: (Major) Due to the thrombocytopenic effects of docetaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Mephobarbital: (Major) Avoid coadministration of docetaxel with mephobarbital due to decreased plasma concentrations of docetaxel. Docetaxel is a CYP3A4 substrate and mephobarbital is a strong CYP3A4 inducer. Concomitant use with other strong CYP3A4 inducers increased docetaxel metabolism by 2.6-fold to 32-fold.
    Mifepristone: (Major) Avoid coadministration of docetaxel with mifepristone if possible due to increased plasma concentrations of docetaxel. If concomitant use of docetaxel with chronic mifepristone is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown. Docetaxel is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
    Mitotane: (Major) Avoid coadministration of docetaxel with mitotane due to decreased plasma concentrations of docetaxel. Docetaxel is a CYP3A4 substrate and mitotane is a strong CYP3A4 inducer. Concomitant use with other strong CYP3A4 inducers increased docetaxel metabolism by 2.6-fold to 32-fold.
    Nabumetone: (Major) Due to the thrombocytopenic effects of docetaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Naproxen: (Major) Due to the thrombocytopenic effects of docetaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Naproxen; Esomeprazole: (Major) Due to the thrombocytopenic effects of docetaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Naproxen; Pseudoephedrine: (Major) Due to the thrombocytopenic effects of docetaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Nefazodone: (Major) Avoid coadministration of docetaxel with nefazodone if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and nefazodone is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
    Nelfinavir: (Major) Avoid coadministration of docetaxel with nelfinavir if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and nelfinavir is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
    Netupitant, Fosnetupitant; Palonosetron: (Major) Netupitant; palonosetron is indicated for the prophylaxis of chemotherapy-induced nausea/vomiting; however, docetaxel-related adverse events may be increased. Netupitant is a moderate CYP3A4 inhibitor and docetaxel is a CYP3A4 substrate; the inhibitory effect of netupitant on CYP3A4 can last for multiple days. When coadministered with netupitant, palonosetron, the mean Cmax and AUC of docetaxel were increased by 49% and 35%, respectively, compared to when coadministered with palonosetron alone. The mean AUC of palonosetron was approximately 65% higher when netupitant; palonosetron was coadministered with docetaxel than with etoposide or cyclophosphamide, while the AUC of netupitant was similar among groups.
    Nevirapine: (Minor) Docetaxel is metabolized by cytochrome P450 3A (CYP3A4 and CYP3A5) enzymes. In vitro studies have shown drugs that induce CYP3A enzymes, like nevirapine, can significantly affect the metabolism of docetaxel.
    Nilotinib: (Major) Concomitant use of nilotinib, a moderate CYP3A4 inhibitor, and docetaxel, a CYP3A4 substrate, may result in increased docetaxel levels. A docetaxel dose reduction may be necessary if these drugs are used together.
    Nirmatrelvir; Ritonavir: (Major) Avoid coadministration of docetaxel with ritonavir if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and ritonavir is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
    Nonsteroidal antiinflammatory drugs: (Major) Due to the thrombocytopenic effects of docetaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Olanzapine; Fluoxetine: (Minor) Docetaxel is metabolized by cytochrome P450 3A enzymes. Drugs that inhibit the CYP3A enzymes, such as fluoxetine, can significantly reduce the metabolism of docetaxel.
    Ombitasvir; Paritaprevir; Ritonavir: (Major) Avoid coadministration of docetaxel with ritonavir if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and ritonavir is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
    Oritavancin: (Moderate) Docetaxel is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of docetaxel may be reduced if these drugs are administered concurrently.
    Oxaprozin: (Major) Due to the thrombocytopenic effects of docetaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Palifermin: (Moderate) Palifermin should not be administered within 24 hours before, during infusion of, or within 24 hours after administration of antineoplastic agents.
    Pazopanib: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and docetaxel, a CYP3A4 substrate, may cause an increase in systemic concentrations of docetaxel. Use caution when administering these drugs concomitantly.
    Penicillamine: (Major) Do not use penicillamine with antineoplastic agents due to the increased risk of developing severe hematologic and renal toxicity.
    Phenobarbital: (Major) Avoid coadministration of docetaxel with phenobarbital due to decreased plasma concentrations of docetaxel. Docetaxel is a CYP3A4 substrate and phenobarbital is a strong CYP3A4 inducer. Concomitant use with other strong CYP3A4 inducers increased docetaxel metabolism by 2.6-fold to 32-fold.
    Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Avoid coadministration of docetaxel with phenobarbital due to decreased plasma concentrations of docetaxel. Docetaxel is a CYP3A4 substrate and phenobarbital is a strong CYP3A4 inducer. Concomitant use with other strong CYP3A4 inducers increased docetaxel metabolism by 2.6-fold to 32-fold.
    Phenytoin: (Major) Avoid coadministration of docetaxel with phenytoin due to decreased plasma concentrations of docetaxel. Docetaxel is a CYP3A4 substrate and phenytoin is a strong CYP3A4 inducer. Concomitant use with other strong CYP3A4 inducers increased docetaxel metabolism by 2.6-fold to 32-fold.
    Piroxicam: (Major) Due to the thrombocytopenic effects of docetaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Posaconazole: (Major) Avoid coadministration of docetaxel with posaconazole if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
    Primidone: (Major) Avoid coadministration of docetaxel with primidone due to decreased plasma concentrations of docetaxel. Docetaxel is a CYP3A4 substrate and primidone is a strong CYP3A4 inducer. Concomitant use with other strong CYP3A4 inducers increased docetaxel metabolism by 2.6-fold to 32-fold.
    Ribociclib: (Major) Avoid coadministration of docetaxel with ribociclib if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
    Ribociclib; Letrozole: (Major) Avoid coadministration of docetaxel with ribociclib if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
    Rifampin: (Major) Avoid coadministration of docetaxel with rifampin due to decreased plasma concentrations of docetaxel. Docetaxel is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Concomitant use with other strong CYP3A4 inducers increased docetaxel metabolism by 2.6-fold to 32-fold.
    Rifapentine: (Major) Avoid coadministration of docetaxel with rifapentine due to decreased plasma concentrations of docetaxel. Docetaxel is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Concomitant use with other strong CYP3A4 inducers increased docetaxel metabolism by 2.6-fold to 32-fold.
    Ritonavir: (Major) Avoid coadministration of docetaxel with ritonavir if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and ritonavir is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
    Rofecoxib: (Major) Due to the thrombocytopenic effects of docetaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Rolapitant: (Moderate) Use caution if docetaxel and rolapitant are used concurrently, and monitor for docetaxel-related adverse effects. Docetaxel is a P-glycoprotein (P-gp) substrate, where an increase in exposure may significantly increase adverse effects; rolapitant is a P-gp inhibitor. When rolapitant was administered with another P-gp substrate, digoxin, the day 1 Cmax and AUC were increased by 70% and 30%, respectively; the Cmax and AUC on day 8 were not studied.
    Rufinamide: (Minor) Rufinamide is not metabolized through hepatic CYP isozymes; however, it is a weak inducer of CYP3A4. In theory, decreased exposure of drugs that are extensively metabolized by CYP3A4, such as docetaxel, may occur during concurrent use with rufinamide.
    Saquinavir: (Major) Avoid coadministration of docetaxel with saquinavir if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and saquinavir is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
    SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
    Simeprevir: (Moderate) Simeprevir, a P-glycoprotein (P-gp) inhibitor and a mild intestinal CYP3A4 inhibitor, may increase the side effects of docetaxel, which is a P-gp and CYP3A4 substrate. Monitor patients for adverse effects of docetaxel, such as myelosuppression and cutaneous reactions.
    Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Plasma concentrations of docetaxel, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with voxilaprevir, a P-gp inhibitor. Monitor patients for increased side effects if these drugs are administered concurrently.
    St. John's Wort, Hypericum perforatum: (Major) Avoid coadministration of docetaxel with St. John's Wort due to decreased plasma concentrations of docetaxel. Docetaxel is a CYP3A4 substrate and St. John's Wort is a strong CYP3A4 inducer. Concomitant use with St. John's Wort increased docetaxel metabolism by 2.6-fold to 32-fold.
    Streptogramins: (Moderate) Caution is warranted during coadministration of docetaxel and dalfopristin; quinupristin, as the systemic exposure of docetaxel may be increased resulting in increased treatment-related adverse reactions. Docetaxel is a CYP3A4 substrate; dalfopristin; quinupristin is a weak CYP3A4 inhibitor.
    Sulindac: (Major) Due to the thrombocytopenic effects of docetaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Sumatriptan; Naproxen: (Major) Due to the thrombocytopenic effects of docetaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Tbo-Filgrastim: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert their toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
    Telaprevir: (Moderate) Close clinical monitoring is advised when administering docetaxel with telaprevir due to an increased potential for docetaxel-related adverse events. If docetaxel dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of docetaxel. Docetaxel is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; telaprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated docetaxel plasma concentrations.
    Telithromycin: (Major) Avoid coadministration of docetaxel with telithromycin if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
    Thalidomide: (Moderate) Thalidomide and other agents that cause peripheral neuropathy such as docetaxel should be used cautiously due to the potential for additive effects.
    Tipranavir: (Major) Avoid coadministration of docetaxel with tipranavir if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and tipranavir is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
    Tolmetin: (Major) Due to the thrombocytopenic effects of docetaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
    Tucatinib: (Major) Avoid coadministration of docetaxel with tucatinib if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and tucatinib is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
    Valdecoxib: (Major) Due to the thrombocytopenic effects of docetaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Vemurafenib: (Moderate) Concomitant use of vemurafenib and docetaxel may result in altered concentrations of docetaxel. Vemurafenib is an inhibitor of P-glycoprotein (PGP) and an inducer of CYP3A4. Docetaxel is a substrate of PGP and CYP3A4. Use caution and monitor patients for toxicity and efficacy.
    Voriconazole: (Major) Avoid coadministration of docetaxel with voriconazole if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and voriconazole is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
    Zonisamide: (Minor) Zonisamide is a weak inhibitor of P-glycoprotein (P-gp), and docetaxel is a substrate of P-gp. There is theoretical potential for zonisamide to affect the pharmacokinetics of drugs that are P-gp substrates. Use caution when starting or stopping zonisamide or changing the zonisamide dosage in patients also receiving drugs which are P-gp substrates.

    PREGNANCY AND LACTATION

    Pregnancy

    Pregnancy should be avoided by females of reproductive potential during docetaxel treatment and for at least 6 months after the last dose. Although there are no adequately controlled studies in pregnant women, docetaxel can cause fetal harm or death when administered during pregnancy based on its mechanism of action and animal studies. Women who are pregnant or who become pregnant while receiving docetaxel should be apprised of the potential hazard to the fetus. An increased incidence of embryofetal toxicities (e.g., intrauterine mortality, resorptions, reduced fetal weights, and fetal ossification delays) occurred when docetaxel was administered to pregnant rats and rabbits during organogenesis at doses 0.02 and 0.003 times the recommended human dose based on body surface area, respectively; maternal toxicity was also observed at these doses. Additionally, docetaxel injection is formulated with alcohol, which has been independently associated with fetal harm including central nervous system abnormalities, behavioral disorders, and impaired intellectual development.

    Due to the potential for serious adverse reactions in nursing infants from docetaxel, advise women to discontinue breast-feeding during treatment and for 1 week after the final dose; recommendations differ among products. Refer to the manufacturer package insert for specific instructions. It is not known whether docetaxel is present in human milk, although many drugs are excreted in human milk.[60484]

    MECHANISM OF ACTION

    Similar to paclitaxel, docetaxel is an antimicrotubule chemotherapy agent. The mechanism of action of the taxanes differs from the vinca alkaloids, although both bind to tubulin. Docetaxel promotes the assembly of microtubules and stabilizes their formation by inhibiting depolymerization. These microtubules are extremely stable and nonfunctional. In addition to functioning as components of the spindle apparatus within the cell, normal microtubules also maintain cell shape, assist in cellular motility, attachment, and intracellular transport, and modulate interactions with growth factors. Microtubules are in equilibrium with tubulin heterodimers, the building blocks of microtubules, which consist of alpha- and beta-subunits. Microtubule-assembly proteins (MAPs) control the equilibrium between the tubulin heterodimers and microtubules. Docetaxel and paclitaxel have different effects on MAPs, which may explain differences in activity and resistance. Docetaxel binds to microtubules at a site that is different from the binding site of colchicine, epipodophyllotoxins, and vinblastine. In contrast to other tubulin toxins, including paclitaxel, the binding of docetaxel does not alter the number of tubulin heterodimers in the microtubules. Docetaxel also promotes tubulin stabilization in conditions where polymerization would not normally occur and stabilizes microtubules in the presence of cold temperatures. Cell death results from inhibition of normal microtubule processes. In vitro studies show that docetaxel is approximately twice as potent as paclitaxel as an inhibitor of microtubule depolymerization, more active as a promoter of tubulin assembly, and twice as efficient as paclitaxel in stabilizing microtubules against cold-induced depolymerization.[25784] The cytotoxic effect of docetaxel is the prevention of effective cell division. Docetaxel specifically blocks critical components in S-phase that are essential for mitosis. Gross damage is detectable after mitosis, with dysfunction in cytokinesis and accumulation of multinucleated non-viable cells. Docetaxel affects centrosome organization in S-phase, resulting in incomplete mitosis and cell death. It is only partially toxic against cells in mitosis and has minimal toxicity against cells in G1. This leads to an accumulation of cells at the G2/M phase. This differs from paclitaxel, which causes cell damage by affecting the mitotic spindle.[25785]
     
    Docetaxel has 1.3 to 12 times more cytotoxic activity in vitro as compared to paclitaxel. This is due to a three-fold decrease in efflux of docetaxel out of cell that results in a higher intracellular concentration of docetaxel. In addition, docetaxel has a higher affinity for microtubules than paclitaxel. There is also evidence that docetaxel and paclitaxel are not completely cross-resistant. Docetaxel cytotoxicity correlates with total dosage as opposed to prolonged exposure. Thus, docetaxel activity is mostly schedule-independent. In vitro concentrations required to reduce murine and human cell line survival by 50% range from 4 to 35 ng/mL, with greater effects on proliferating versus non-proliferating cells.[25784]

    PHARMACOKINETICS

    Docetaxel is administered by intravenous infusion. Docetaxel is 94% to 97% protein bound, primarily to alpha1-acid glycoprotein, albumin, and lipoproteins. A three-compartment model best describes docetaxel elimination, with half-lives of 4 minutes, 36 minutes and 11.1 hours for the alpha, beta and gamma phases, respectively. The initial rapid decline represents rapid distribution to the peripheral compartments and the extended terminal half-life is due, in part, to a relatively slow efflux of docetaxel from the peripheral compartment. The mean total body clearance of docetaxel in cancer patients was 21 liters/hour/m2 and the mean steady-state volume of distribution (Vd) was 113 liters. Docetaxel is eliminated in both the urine and the feces after oxidative metabolism of the tert-butyl ester group. Within 7 days of administration of radiolabeled docetaxel to 3 cancer patients, urinary excretion accounted for 6% and fecal excretion 75% of the administered radioactivity. Approximately 80% of the radioactivity recovered in feces is excreted during the first 48 hours as one major and 3 minor metabolites; less than 8% was recovered as unchanged drug.[60484]
     
    Affected cytochrome (CYP) 450 isoenzymes and drug transporters: CYP3A4
    Docetaxel is metabolized by CYP3A4 in vitro.[60484] All 4 principle metabolites of docetaxel have greatly reduced cytotoxic activity against cancer cell lines in vitro and in vivo.[63757]

    Oral Route

    Although IV and intraperitoneal administration of docetaxel to mice with B16 melanoma xenografts resulted in considerable activity, oral administration was associated with a total lack of activity, possibly due to intragastric degradation by P-glycoprotein (P-gp).

    Intravenous Route

    The AUC of docetaxel was dose proportional following doses of 70 mg/m2 to 115 mg/m2 with infusion times of 1 to 2 hours.