Docivyx
docetaxel · Injection, Solution · Intravenous
Uses
1 INDICATIONS AND USAGE DOCIVYX is a microtubule inhibitor indicated for: Breast Cancer (BC) : single agent for locally advanced or metastatic BC after chemotherapy failure; and with doxorubicin and cyclophosphamide as adjuvant treatment of operable node-positive BC ( 1.1 ) Non-small Cell Lung Cancer (NSCLC): single agent for locally advanced or metastatic NSCLC after platinum therapy failure; and with cisplatin for unresectable, locally advanced or metastatic untreated NSCLC ( 1.2 ) Castration- Resistant Prostate Cancer (CRPC) : with prednisone in metastatic CRPC ( 1.3 ) Gastric Adenocarcinoma (GC): with cisplatin and fluorouracil for untreated, advanced GC, including the gastroesophageal junction ( 1.4 ) Squamous Cell Carcinoma of the Head and Neck (SCCHN): with cisplatin and fluorouracil for induction treatment of locally advanced SCCHN ( 1.5 ) 1.1 Breast Cancer DOCIVYX is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy. DOCIVYX in combination with doxorubicin and cyclophosphamide is indicated for the adjuvant treatment of patients with operable node-positive breast cancer. 1.2 Non-small Cell Lung Cancer DOCIVYX as a single agent is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of prior platinum-based chemotherapy. DOCIVYX in combination with cisplatin is indicated for the treatment of patients with unresectable, locally advanced or metastatic non-small cell lung cancer who have not previously received chemotherapy for this condition. 1.3 Prostate Cancer DOCIVYX in combination with prednisone is indicated for the treatment of patients with metastatic CRPC. 1.4 Gastric Adenocarcinoma DOCIVYX in combination with cisplatin and fluorouracil is indicated for the treatment of patients with advanced gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, who have not received prior chemotherapy for advanced disease. 1.5 Head and Neck Cancer DOCIVYX in combination with cisplatin and fluorouracil is indicated for the induction treatment of patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN).
Dosage and administration
For all indications, toxicities may warrant dosage adjustments [see Dosage and Administration (2.7) ] . Administer in a facility equipped to manage possible complications (e.g., anaphylaxis). Administer in a facility equipped to manage possible complications (e.g., anaphylaxis). Administer intravenously (IV) over 1 hr every 3 weeks. PVC equipment is not recommended. Use only a 21-gauge needle to withdraw DOCIVYX from the vial. BC locally advanced or metastatic: 60 mg/m 2 to 100 mg/m 2 single agent ( 2.1 ) BC adjuvant: 75 mg/m 2 administered 1 hour after doxorubicin 50 mg/m 2 and cyclophosphamide 500 mg/m 2 every 3 weeks for 6 cycles ( 2.1 ) NSCLC: after platinum therapy failure: 75 mg/m 2 single agent ( 2.2 ) NSCLC: chemotherapy naive: 75 mg/m 2 followed by cisplatin 75 mg/m 2 ( 2.2 ) CRPC: 75 mg/m 2 with 5 mg prednisone twice a day continuously ( 2.3 ) GC: 75 mg/m 2 followed by cisplatin 75 mg/m 2 (both on day 1 only) followed by fluorouracil 750 mg/m 2 per day as a 24-hour IV (days 1-5), starting at end of cisplatin infusion ( 2.4 ) SCCHN: 75 mg/m 2 followed by cisplatin 75 mg/m 2 IV (day 1), followed by fluorouracil 750 mg/m 2 per day as a 24-hr IV (days 1–5), starting at end of cisplatin infusion; for 4 cycles ( 2.5 ) SCCHN: 75 mg/m 2 followed by cisplatin 100 mg/m 2 IV (day 1), followed by fluorouracil 1000 mg/m 2 per day as a 24-hr IV (days 1–4); for 3 cycles ( 2.5 ) For all patients: Premedicate with oral corticosteroids ( 2.6 ) Adjust dose as needed ( 2.7 ) 2.1 Breast Cancer For locally advanced or metastatic breast cancer after failure of prior chemotherapy, the recommended dose of DOCIVYX is 60 mg/m 2 to 100 mg/m 2 administered intravenously over 1 hour every 3 weeks. For the adjuvant treatment of operable node-positive breast cancer, the recommended DOCIVYX dose is 75 mg/m 2 administered 1 hour after doxorubicin 50 mg/m 2 and cyclophosphamide 500 mg/m 2 every 3 weeks for 6 courses. Prophylactic G-CSF may be used to mitigate the risk of hematological toxicities [see Dosage and Administration (2.7) ] . 2.2 Non-small Cell Lung Cancer For treatment after failure of prior platinum-based chemotherapy, DOCIVYX was evaluated as monotherapy, and the recommended dose is 75 mg/m 2 administered intravenously over 1 hour every 3 weeks. A dose of 100 mg/m 2 in patients previously treated with chemotherapy was associated with increased hematologic toxicity, infection, and treatment-related mortality in randomized controlled trials [see Boxed Warning , Dosage and Administration (2.7), Warnings and Precautions (5), Clinical Studies (14) ] . For chemotherapy-naive patients, DOCIVYX was evaluated in combination with cisplatin. The recommended dose of DOCIVYX is 75 mg/m 2 administered intravenously over 1 hour immediately followed by cisplatin 75 mg/m 2 over 30–60 minutes every 3 weeks [see Dosage and Administration (2.7) ] . 2.3 Prostate Cancer For metastatic CRPC, the recommended dose of DOCIVYX is 75 mg/m 2 every 3 weeks as a 1-hour intravenous infusion. Prednisone 5 mg orally twice daily is administered continuously [see Dosage and Administration (2.7) ] . 2.4 Gastric Adenocarcinoma For gastric adenocarcinoma, the recommended dose of DOCIVYX is 75 mg/m 2 as a 1-hour intravenous infusion, followed by cisplatin 75 mg/m 2 , as a 1 to 3 hour intravenous infusion (both on day 1 only), followed by fluorouracil 750 mg/m 2 per day given as a 24-hour continuous intravenous infusion for 5 days, starting at the end of the cisplatin infusion. Treatment is repeated every three weeks. Patients must receive premedication with antiemetics and appropriate hydration for cisplatin administration [see Dosage and Administration (2.7) ] . 2.5 Head and Neck Cancer Patients must receive premedication with antiemetics, and appropriate hydration (prior to and after cisplatin administration). Prophylaxis for neutropenic infections should be administered. All patients treated on the DOCIVYX containing arms of the TAX323 and TAX324 studies received prophylactic antibiotics. Induction Chemotherapy Followed by Radiotherapy (TAX323) For the induction treatment of locally advanced inoperable SCCHN, the recommended dose of DOCIVYX is 75 mg/m 2 as a 1-hour intravenous infusion followed by cisplatin 75 mg/m 2 intravenously over 1 hour, on day one, followed by fluorouracil as a continuous intravenous infusion at 750 mg/m 2 per day for five days. This regimen is administered every 3 weeks for 4 cycles. Following chemotherapy, patients should receive radiotherapy [see Dosage and Administration (2.7) ] . Induction Chemotherapy Followed by Chemoradiotherapy (TAX324) For the induction treatment of patients with locally advanced (unresectable, low surgical cure, or organ preservation) SCCHN, the recommended dose of DOCIVYX is 75 mg/m 2 as a 1-hour intravenous infusion on day 1, followed by cisplatin 100 mg/m 2 administered as a 30-minute to 3 hour infusion, followed by fluorouracil 1000 mg/m 2 /day as a continuous infusion from day 1 to day 4. This regimen is administered every 3 weeks for 3 cycles. Following chemotherapy, patients should receive chemoradiotherapy [see Dosage and Administration (2.7) ] . 2.6 Premedication Regimen All patients should be premedicated with oral corticosteroids (see below for CRPC) such as dexamethasone 16 mg per day (e.g., 8 mg twice daily) for 3 days starting 1 day prior to DOCIVYX administration in order to reduce the incidence and severity of fluid retention as well as the severity of hypersensitivity reactions [see Boxed Warning , Warnings and Precautions (5.5) ] . For metastatic CRPC, given the concurrent use of prednisone, the recommended premedication regimen is oral dexamethasone 8 mg at 12 hours, 3 hours, and 1 hour before the DOCIVYX infusion [see Warnings and Precautions (5.5) ] .
Dosage forms and strengths
(docetaxel) Injection, is a sterile, non-pyrogenic, pale-yellow to brownish-yellow solution available in the following strengths: 20 mg/2 mL, 80 mg/8 mL and 160 mg/16 mL in single-dose vials. Injection: Single-dose vials 20 mg/2 mL, 80 mg/8 mL and 160 mg/16 mL ( 3 )
Contraindications
4 CONTRAINDICATIONS DOCIVYX is contraindicated in patients with: neutrophil counts of <1500 cells/mm3 [see Warnings and Precautions (5.3) ]. a history of severe hypersensitivity reactions to docetaxel. Severe reactions, including anaphylaxis, have occurred [see Warnings and Precautions (5.5) ] . Hypersensitivity to docetaxel ( 4 ) Neutrophil counts of <1500 cells/mm 3 ( 4 )
Warnings and precautions
Second primary malignancies: In patients treated with DOCIVYX-containing regimens, monitor for delayed AML, MDS, NHL, and renal cancer. ( 5.7 ) Cutaneous reactions: Reactions including erythema of the extremities with edema followed by desquamation may occur. Severe cutaneous adverse reactions have been reported. Severe skin toxicity may require dose adjustment or permanent treatment discontinuation. ( 5.8 ) Neurologic reactions: Reactions including paresthesia, dysesthesia, and pain may occur. Severe neurosensory symptoms require dose adjustment or discontinuation if persistent. ( 5.9 ) Eye disorders: Cystoid macular edema (CME) has been reported and requires treatment discontinuation. ( 5.10 ) Asthenia: Severe asthenia may occur and may require treatment discontinuation. ( 5.11 ) Embryo-fetal toxicity: Can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception. ( 5.12, 8.1, 8.3 ) Alcohol content: The alcohol content in a dose of DOCIVYX may affect the central nervous system. This may include impairment of a patient's ability to drive or use machines immediately after infusion. ( 5.13 ) Tumor lysis syndrome: Tumor lysis syndrome has been reported. Patients at risk should be well hydrated and closely monitored during treatment. ( 5.14 ) 5.1 Toxic Deaths Breast Cancer DOCIVYX administered at 100 mg/m 2 was associated with deaths considered possibly or probably related to treatment in 2.0% (19/965) of metastatic breast cancer patients, both previously treated and untreated, with normal baseline liver function and in 11.5% (7/61) of patients with various tumor types who had abnormal baseline liver function (AST and/or ALT >1.5 times ULN together with AP >2.5 times ULN). Among patients dosed at 60 mg/m 2 , mortality related to treatment occurred in 0.6% (3/481) of patients with normal liver function, 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 the deaths. Non-small Cell Lung Cancer DOCIVYX administered at a dose of 100 mg/m 2 in patients with locally advanced or metastatic non-small cell lung cancer who had 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/m 2 dose in the randomized trials. Among patients who experienced treatment-related mortality at the 75 mg/m 2 dose level, 3 of 5 patients had an ECOG PS of 2 at study entry [see Dosage and Administration (2.2) , Clinical Studies (14) ] . 5.2 Hepatic Impairment Patients with elevations of bilirubin or abnormalities of transaminase concurrent with alkaline phosphatase are at increased risk for the development of severe neutropenia, febrile neutropenia, infections, severe thrombocytopenia, severe stomatitis, severe skin toxicity, and toxic death. Avoid DOCIVYX in patients with bilirubin > upper limit of normal (ULN), or to patients with AST and/or ALT >1.5 × ULN concomitant with alkaline phosphatase >2.5 × ULN [see Warnings and Precautions (5.1) ] . For patients with isolated elevations of transaminase >1.5 × ULN, consider DOCIVYX dose modifications [see Dosage and Administration (2.7) ] . Measure bilirubin, AST or ALT, and alkaline phosphatase prior to each cycle of DOCIVYX therapy. 5.3 Hematologic Effects Perform frequent peripheral blood cell counts on all patients receiving DOCIVYX. Do not retreat patients with subsequent cycles of DOCIVYX until neutrophils recover to a level >1500 cells/mm 3 [see Contraindications (4) ] . Avoid retreating patients until platelets recover to a level >100,000 cells/mm 3 . A 25% reduction in the dose of DOCIVYX is recommended during subsequent cycles following severe neutropenia (<500 cells/mm 3 ) lasting 7 days or more, febrile neutropenia, or a grade 4 infection in a DOCIVYX cycle [see Dosage and Administration (2.7) ] . Neutropenia (<2000 neutrophils/mm 3 ) occurs in virtually all patients given 60 mg/m 2 to 100 mg/m 2 of DOCIVYX and grade 4 neutropenia (<500 cells/mm 3 ) occurs in 85% of patients given 100 mg/m 2 and 75% of patients given 60 mg/m 2 . Frequent monitoring of blood counts is, therefore, essential so that dose can be adjusted. DOCIVYX should not be administered to patients with neutrophils <1500 cells/mm 3 . Febrile neutropenia occurred in about 12% of patients given 100 mg/m 2 but was very uncommon in patients given 60 mg/m 2 . Hematologic responses, febrile reactions and infections, and rates of septic death for different regimens are dose related [see Adverse Reactions (6.1), Clinical Studies (14) ] . Three breast cancer patients with severe liver impairment (bilirubin >1.7 times ULN) developed fatal gastrointestinal bleeding associated with severe drug-induced thrombocytopenia. In gastric cancer patients treated with docetaxel in combination with cisplatin and fluorouracil (TCF), febrile neutropenia and/or neutropenic infection occurred in 12% of patients receiving G-CSF compared to 28% who did not. Patients receiving TCF should be closely monitored during the first and subsequent cycles for febrile neutropenia and neutropenic infection [see Dosage and Administration (2.7), Adverse Reactions (6) ] . 5.4 Enterocolitis and Neutropenic Colitis Enterocolitis and neutropenic colitis (typhlitis) have occurred in patients treated with DOCIVYX alone and in combination with other chemotherapeutic agents, despite the coadministration of G-CSF. Caution is recommended for patients with neutropenia, particularly at risk for developing gastrointestinal complications. Enterocolitis and neutropenic enterocolitis may develop at any time, and could lead to death as early as the first day of symptom onset. Monitor patients closely from onset of any symptoms of gastrointestinal toxicity.
Side effects
The most serious adverse reactions from DOCIVYX are: Toxic Deaths [see Boxed Warning , Warnings and Precautions (5.1) ] Hepatic Impairment [see Boxed Warning , Warnings and Precautions (5.2) ] Hematologic Effects [see Boxed Warning , Warnings and Precautions (5.3) ] Enterocolitis and Neutropenic Colitis [see Warnings and Precautions (5.4) ] Hypersensitivity Reactions [see Boxed Warning , Warnings and Precautions (5.5) ] Fluid Retention [see Boxed Warning , Warnings and Precautions (5.6) ] Second Primary Malignancies [see Warnings and Precautions (5.7) ] Cutaneous Reactions [see Warnings and Precautions (5.8) ] Neurologic Reactions [see Warnings and Precautions (5.9) ] Eye Disorders [see Warnings and Precautions (5.10)] Asthenia [see Warnings and Precautions (5.11) ] Alcohol Content [see Warnings and Precautions (5.13) ] The most common adverse reactions across all DOCIVYX indications are infections, neutropenia, anemia, febrile neutropenia, hypersensitivity, thrombocytopenia, neuropathy, dysgeusia, dyspnea, constipation, anorexia, nail disorders, fluid retention, asthenia, pain, nausea, diarrhea, vomiting, mucositis, alopecia, skin reactions, and myalgia. Incidence varies depending on the indication. Adverse reactions are described according to indication. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Responding patients may not experience an improvement in performance status on therapy and may experience worsening. The relationship between changes in performance status, response to therapy, and treatment-related side effects has not been established. Most common adverse reactions across all DOCIVYX indications are infections, neutropenia, anemia, febrile neutropenia, hypersensitivity, thrombocytopenia, neuropathy, dysgeusia, dyspnea, constipation, anorexia, nail disorders, fluid retention, asthenia, pain, nausea, diarrhea, vomiting, mucositis, alopecia, skin reactions, and myalgia. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Avyxa Pharma,LLC at 1-888-520-0954 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience Breast Cancer Monotherapy with DOCIVYX for locally advanced or metastatic breast cancer after failure of prior chemotherapy DOCIVYX 100 mg/m 2 : Adverse drug reactions occurring in at least 5% of patients are compared for three populations who received DOCIVYX administered at 100 mg/m 2 as a 1-hour infusion every 3 weeks: 2045 patients with various tumor types and normal baseline liver function tests; the subset of 965 patients with locally advanced or metastatic breast cancer, both previously treated and untreated with chemotherapy, who had normal baseline liver function tests; and an additional 61 patients with various tumor types who had abnormal liver function tests at baseline. These reactions were described using COSTART terms and were considered possibly or probably related to DOCIVYX. At least 95% of these patients did not receive hematopoietic support. The safety profile is generally similar in patients receiving DOCIVYX for the treatment of breast cancer and in patients with other tumor types. (See Table 3.) Table 3: Summary of Adverse Reactions in Patients Receiving DOCIVYX at 100 mg/m 2 * Normal Baseline LFTs: Transaminases ≤1.5 times ULN or alkaline phosphatase ≤2.5 times ULN or isolated elevations of transaminases or alkaline phosphatase up to 5 times ULN † Elevated Baseline LFTs: AST and/or ALT >1.5 times ULN concurrent with alkaline phosphatase >2.5 times ULN ‡ Febrile Neutropenia: ANC grade 4 with fever >38°C with intravenous antibiotics and/or hospitalization Adverse Reaction All Tumor Types Normal LFTs* n=2045 % All Tumor Types Elevated LFTs † n=61 % Breast Cancer Normal LFTs * n=965 % Hematologic Neutropenia <2000 cells/mm3 96 96 99 <500 cells/mm3 75 88 86 Leukopenia <4000 cells/mm3 96 98 99 <1000 cells/mm3 32 47 44 Thrombocytopenia <100,000 cells/mm3 8 25 9 Anemia <11 g/dL 90 92 94 <8 g/dL 9 31 8 Febrile Neutropenia‡ 11 26 12 Septic Death 2 5 1 Non-Septic Death 1 7 1 Infections Any Severe 22 6 33 16 22 6 Fever in Absence of Infection Any Severe 31 2 41 8 35 2 Hypersensitivity Reactions Regardless of Premedication Any 21 20 18 Severe 4 10 3 With 3-day Premedication n=92 n=3 n=92 Any 15 33 15 Severe 2 0 2 Fluid Retention Regardless of Premedication Any 47 39 60 Severe 7 8 9 With 3-day Premedication n=92 n=3 n=92 Any 64 67 64 Severe 7 33 7 Neurosensory Any Severe 49 4 34 0 58 6 Cutaneous Any Severe 48 5 54 10 47 5 Nail Changes Any Severe 31 3 23 5 41 4 Gastrointestinal Nausea Vomiting Diarrhea Severe 39 22 39 5 38 23 33 5 42 23 43 6 Stomatitis Any Severe 42 6 49 13 52 7 Alopecia 76 62 74 Asthenia Any Severe 62 13 53 25 66 15 Myalgia Any Severe 19 2 16 2 21 2 Arthralgia 9 7 8 Infusion Site Reactions 4 3 4 Hematologic reactions Reversible marrow suppression was the major dose-limiting toxicity of DOCIVYX [see Warnings and Precautions (5.3) ]. The median time to nadir was 7 days, while the median duration of severe neutropenia (<500 cells/mm 3 ) was 7 days. Among 2045 patients with solid tumors and normal baseline LFTs, severe neutropenia occurred in 75.4% and lasted for more than 7 days in 2.9% of cycles. Febrile neutropenia (<500 cells/mm 3 with fever >38°C with intravenous antibiotics and/or hospitalization) occurred in 11% of patients with solid tumors, in 12.3% of patients with metastatic breast cancer, and in 9.8% of 92 breast cancer patients premedicated with 3-day corticosteroids. Severe infectious episodes occurred in 6.1% of patients with solid tumors, in 6.4% of patients with metastatic breast cancer, and in 5.4% of 92 breast cancer patients premedicated with 3-day corticosteroids. Thrombocytopenia (<100,000 cells/mm 3 ) associated with fatal gastrointestinal hemorrhage has been reported.
Drug interactions
Docetaxel is a CYP3A4 substrate. In vitro studies have shown that the metabolism of docetaxel may be modified by the concomitant administration of compounds that induce, inhibit, or are metabolized by cytochrome P450 3A4. In vivo studies showed that the exposure of docetaxel increased 2.2-fold when it was coadministered with ketoconazole, a potent inhibitor of CYP3A4. Protease inhibitors, particularly ritonavir, may increase the exposure of docetaxel. Concomitant use of DOCIVYX and drugs that inhibit CYP3A4 may increase exposure to docetaxel and should be avoided. In patients receiving treatment with DOCIVYX, close monitoring for toxicity and a DOCIVYX dose reduction could be considered if systemic administration of a potent CYP3A4 inhibitor cannot be avoided [see Dosage and Administration (2.7), Clinical Pharmacology (12.3) ]. Cytochrome P450 3A4 inducers, inhibitors, or substrates: May alter docetaxel metabolism. ( 7 )
Use in specific populations
Lactation: Advise women not to breastfeed. ( 8.2 ) Females and Males of Reproductive Potential: Verify pregnancy status of females prior to initiation of DOCIVYX. ( 8.3 ) 8.1 Pregnancy Risk Summary Based on findings in animal reproduction studies and its mechanism of action, DOCIVYX can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . Available data from case reports in the literature and pharmacovigilance with docetaxel use in pregnant women are not sufficient to inform the drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. DOCIVYX contains alcohol which can interfere with neurobehavioral development [see Clinical Considerations] . In animal reproductive studies, administration of docetaxel to pregnant rats and rabbits during the period of organogenesis caused an increased incidence of embryo-fetal toxicities, including intrauterine mortality, at doses as low as 0.02 and 0.003 times the recommended human dose based on body surface area, respectively [ see Data ]. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, miscarriage, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations DOCIVYX contains alcohol [see Warnings and Precautions (5.13) ] . Published studies have demonstrated that alcohol is associated with fetal harm including central nervous system abnormalities, behavioral disorders, and impaired intellectual development. Data Animal data Intravenous administration of ≥0.3 and 0.03 mg/kg/day docetaxel to pregnant rats and rabbits, respectively, during the period of organogenesis caused an increased incidence of intrauterine mortality, resorptions, reduced fetal weights, and fetal ossification delays. Maternal toxicity was also observed at these doses, which were approximately 0.02 and 0.003 times the daily maximum recommended human dose based on body surface area, respectively. 8.2 Lactation Risk Summary There is no information regarding the presence of docetaxel in human milk, or on its effects on milk production or the breastfed child. No lactation studies in animals have been conducted. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with DOCIVYX and for 1 week after the last dose. 8.3 Females and Males of Reproductive Potential Based on findings in animals, DOCIVYX can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1) ] . Pregnancy Testing Verify pregnancy status in females of reproductive potential prior to initiating DOCIVYX. Contraception Females Based on genetic toxicity findings, advise females of reproductive potential to use effective contraception during treatment and for 2 months after the last dose of DOCIVYX. Males Based on genetic toxicity findings, advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 4 months after the last dose of DOCIVYX. Infertility Based on findings in animal studies, DOCIVYX may impair fertility in males of reproductive potential [see Nonclinical Toxicology (13.1) ] . 8.4 Pediatric Use The alcohol content of DOCIVYX should be taken into account when given to pediatric patients [see Warnings and Precautions (5.13) ] . The efficacy of DOCIVYX in pediatric patients as monotherapy or in combination has not been established. The overall safety profile of DOCIVYX in pediatric patients receiving monotherapy or TCF was consistent with the known safety profile in adults. DOCIVYX has been studied in a total of 289 pediatric patients: 239 in 2 trials with monotherapy and 50 in combination treatment with cisplatin and 5-fluorouracil (TCF). DOCIVYX Monotherapy DOCIVYX monotherapy was evaluated in a dose-finding phase 1 trial in 61 pediatric patients (median age 12.5 years, range 1–22 years) with a variety of refractory solid tumors. The recommended dose was 125 mg/m 2 as a 1-hour intravenous infusion every 21 days. The primary dose limiting toxicity was neutropenia. The recommended dose for DOCIVYX monotherapy was evaluated in a phase 2 single-arm trial in 178 pediatric patients (median age 12 years, range 1–26 years) with a variety of recurrent/refractory solid tumors. Efficacy was not established with tumor response rates ranging from one complete response (CR) (0.6%) in a patient with undifferentiated sarcoma to four partial responses (2.2%) seen in one patient each with Ewing Sarcoma, neuroblastoma, osteosarcoma, and squamous cell carcinoma. DOCIVYX in Combination DOCIVYX was studied in combination with cisplatin and 5-fluorouracil (TCF) versus cisplatin and 5- fluorouracil (CF) for the induction treatment of nasopharyngeal carcinoma (NPC) in pediatric patients prior to chemoradiation consolidation. Seventy-five patients (median age 16 years, range 9 to 21 years) were randomized (2:1) to DOCIVYX (75 mg/m 2 ) in combination with cisplatin (75 mg/m2) and 5- fluorouracil (750 mg/m 2 ) (TCF) or to cisplatin (80 mg/m 2 ) and 5-fluorouracil (1000 mg/m 2 /day) (CF). The primary endpoint was the CR rate following induction treatment of NPC. One patient out of 50 in the TCF group (2%) had a complete response while none of the 25 patients in the CF group had a complete response. Pharmacokinetics Pharmacokinetic parameters for docetaxel were determined in 2 pediatric solid tumor trials. Following docetaxel administration at 55 mg/m 2 to 235 mg/m 2 in a 1-hour intravenous infusion every 3 weeks in 25 patients aged 1 to 20 years (median 11 years), docetaxel clearance was 17.3±10.9 L/h/m 2 .
Pregnancy
8.1 Pregnancy Risk Summary Based on findings in animal reproduction studies and its mechanism of action, DOCIVYX can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . Available data from case reports in the literature and pharmacovigilance with docetaxel use in pregnant women are not sufficient to inform the drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. DOCIVYX contains alcohol which can interfere with neurobehavioral development [see Clinical Considerations] . In animal reproductive studies, administration of docetaxel to pregnant rats and rabbits during the period of organogenesis caused an increased incidence of embryo-fetal toxicities, including intrauterine mortality, at doses as low as 0.02 and 0.003 times the recommended human dose based on body surface area, respectively [ see Data ]. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, miscarriage, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations DOCIVYX contains alcohol [see Warnings and Precautions (5.13) ] . Published studies have demonstrated that alcohol is associated with fetal harm including central nervous system abnormalities, behavioral disorders, and impaired intellectual development. Data Animal data Intravenous administration of ≥0.3 and 0.03 mg/kg/day docetaxel to pregnant rats and rabbits, respectively, during the period of organogenesis caused an increased incidence of intrauterine mortality, resorptions, reduced fetal weights, and fetal ossification delays. Maternal toxicity was also observed at these doses, which were approximately 0.02 and 0.003 times the daily maximum recommended human dose based on body surface area, respectively.
Pediatric use
8.4 Pediatric Use The alcohol content of DOCIVYX should be taken into account when given to pediatric patients [see Warnings and Precautions (5.13) ] . The efficacy of DOCIVYX in pediatric patients as monotherapy or in combination has not been established. The overall safety profile of DOCIVYX in pediatric patients receiving monotherapy or TCF was consistent with the known safety profile in adults. DOCIVYX has been studied in a total of 289 pediatric patients: 239 in 2 trials with monotherapy and 50 in combination treatment with cisplatin and 5-fluorouracil (TCF). DOCIVYX Monotherapy DOCIVYX monotherapy was evaluated in a dose-finding phase 1 trial in 61 pediatric patients (median age 12.5 years, range 1–22 years) with a variety of refractory solid tumors. The recommended dose was 125 mg/m 2 as a 1-hour intravenous infusion every 21 days. The primary dose limiting toxicity was neutropenia. The recommended dose for DOCIVYX monotherapy was evaluated in a phase 2 single-arm trial in 178 pediatric patients (median age 12 years, range 1–26 years) with a variety of recurrent/refractory solid tumors. Efficacy was not established with tumor response rates ranging from one complete response (CR) (0.6%) in a patient with undifferentiated sarcoma to four partial responses (2.2%) seen in one patient each with Ewing Sarcoma, neuroblastoma, osteosarcoma, and squamous cell carcinoma. DOCIVYX in Combination DOCIVYX was studied in combination with cisplatin and 5-fluorouracil (TCF) versus cisplatin and 5- fluorouracil (CF) for the induction treatment of nasopharyngeal carcinoma (NPC) in pediatric patients prior to chemoradiation consolidation. Seventy-five patients (median age 16 years, range 9 to 21 years) were randomized (2:1) to DOCIVYX (75 mg/m 2 ) in combination with cisplatin (75 mg/m2) and 5- fluorouracil (750 mg/m 2 ) (TCF) or to cisplatin (80 mg/m 2 ) and 5-fluorouracil (1000 mg/m 2 /day) (CF). The primary endpoint was the CR rate following induction treatment of NPC. One patient out of 50 in the TCF group (2%) had a complete response while none of the 25 patients in the CF group had a complete response. Pharmacokinetics Pharmacokinetic parameters for docetaxel were determined in 2 pediatric solid tumor trials. Following docetaxel administration at 55 mg/m 2 to 235 mg/m 2 in a 1-hour intravenous infusion every 3 weeks in 25 patients aged 1 to 20 years (median 11 years), docetaxel clearance was 17.3±10.9 L/h/m 2 . Docetaxel was administered in combination with cisplatin and 5-fluorouracil (TCF), at dose levels of 75 mg/m 2 in a 1-hour intravenous infusion day 1 in 28 patients aged 10 to 21 years (median 16 years, 17 patients were older than 16). Docetaxel clearance was 17.9±8.75 L/h/m 2 , corresponding to an AUC of 4.20±2.57 μg·h/mL. In summary, the body surface area adjusted clearance of docetaxel monotherapy and TCF combination in children were comparable to those in adults [see Clinical Pharmacology (12.3) ] .
Geriatric use
8.5 Geriatric Use In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy in elderly patients. Non-small Cell Lung Cancer In a study conducted in chemotherapy-naive patients with NSCLC (TAX326), 148 patients (36%) in the DOCIVYX+cisplatin group were 65 years of age or greater. There were 128 patients (32%) in the vinorelbine+cisplatin group 65 years of age or greater. In the DOCIVYX+cisplatin group, patients less than 65 years of age had a median survival of 10.3 months (95% CI: 9.1 months, 11.8 months) and patients 65 years or older had a median survival of 12.1 months (95% CI: 9.3 months, 14 months). In patients 65 years of age or greater treated with DOCIVYX+cisplatin, diarrhea (55%), peripheral edema (39%) and stomatitis (28%) were observed more frequently than in the vinorelbine+cisplatin group (diarrhea 24%, peripheral edema 20%, stomatitis 20%). Patients treated with DOCIVYX+cisplatin who were 65 years of age or greater were more likely to experience diarrhea (55%), infections (42%), peripheral edema (39%) and stomatitis (28%) compared to patients less than the age of 65 administered the same treatment (43%, 31%, 31% and 21%, respectively). When DOCIVYX was combined with carboplatin for the treatment of chemotherapy-naive, advanced non-small cell lung carcinoma, patients 65 years of age or greater (28%) experienced higher frequency of infection compared to similar patients treated with DOCIVYX+cisplatin, and a higher frequency of diarrhea, infection and peripheral edema than elderly patients treated with vinorelbine+cisplatin. Prostate Cancer Of the 333 patients treated with DOCIVYX every three weeks plus prednisone in the CRPC study (TAX327), 209 patients were 65 years of age or greater and 68 patients were older than 75 years. In patients treated with DOCIVYX every three weeks, the following treatment-emergent adverse reactions occurred at rates ≥10% higher in patients 65 years of age or greater compared to younger patients: anemia (71% vs 59%), infection (37% vs 24%), nail changes (34% vs 23%), anorexia (21% vs 10%), weight loss (15% vs 5%), respectively. Breast Cancer In the adjuvant breast cancer trial (TAX316), DOCIVYX in combination with doxorubicin and cyclophosphamide was administered to 744 patients of whom 48 (6%) were 65 years of age or greater. The number of elderly patients who received this regimen was not sufficient to determine whether there were differences in safety and efficacy between elderly and younger patients. Gastric Cancer Among the 221 patients treated with DOCIVYX in combination with cisplatin and fluorouracil in the gastric cancer study, 54 were 65 years of age or older and 2 patients were older than 75 years. In this study, the number of patients who were 65 years of age or older was insufficient to determine whether they respond differently from younger patients. However, the incidence of serious adverse reactions was higher in the elderly patients compared to younger patients. The incidence of the following adverse reactions (all grades, regardless of relationship): lethargy, stomatitis, diarrhea, dizziness, edema, febrile neutropenia/neutropenic infection occurred at rates ≥10% higher in patients who were 65 years of age or older compared to younger patients. Elderly patients treated with TCF should be closely monitored. Head and Neck Cancer Among the 174 and 251 patients who received the induction treatment with DOCIVYX in combination with cisplatin and fluorouracil (TPF) for SCCHN in the TAX323 and TAX324 studies, 18 (10%) and 32 (13%) of the patients were 65 years of age or older, respectively. These clinical studies of DOCIVYX in combination with cisplatin and fluorouracil in patients with SCCHN did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. Other reported clinical experience with this treatment regimen has not identified differences in responses between elderly and younger patients.
Overdosage
There is no known antidote for DOCIVYX overdosage. In case of overdosage, the patient should be kept in a specialized unit where vital functions can be closely monitored. Anticipated complications of overdosage include: bone marrow suppression, peripheral neurotoxicity, and mucositis. Patients should receive therapeutic G-CSF as soon as possible after discovery of overdose. Other appropriate symptomatic measures should be taken, as needed. In two reports of overdose, one patient received 150 mg/m 2 and the other received 200 mg/m 2 as 1-hour infusions. Both patients experienced severe neutropenia, mild asthenia, cutaneous reactions, and mild paresthesia, and recovered without incident. In mice, lethality was observed following single intravenous doses that were ≥154 mg/kg (about 4.5 times the human dose of 100 mg/m 2 on a mg/m 2 basis); neurotoxicity associated with paralysis, non- extension of hind limbs, and myelin degeneration was observed in mice at 48 mg/kg (about 1.5 times the human dose of 100 mg/m 2 basis). In male and female rats, lethality was observed at a dose of 20 mg/kg (comparable to the human dose of 100 mg/m 2 on a mg/m 2 basis) and was associated with abnormal mitosis and necrosis of multiple organs.
Description
Docetaxel is an antineoplastic agent belonging to the taxoid family. It is prepared by semisynthesis beginning with a precursor extracted from the renewable needle biomass of yew plants. The chemical name for docetaxel is (2R,3S)-N-carboxy-3-phenylisoserine, N- tert -butyl ester, 13-ester with 5β-20- epoxy-1,2α,4,7β,10β,13α-hexahydroxytax-11-en-9-one 4-acetate 2-benzoate, trihydrate. Docetaxel has the following structural formula: Docetaxel is a white to almost-white powder with an empirical formula of C 43 H 53 NO 14 ·3H 2 O, and a molecular weight of 861.9. It is highly lipophilic and practically insoluble in water. DOCIVYX (docetaxel) Injection is a sterile, non-pyrogenic, pale-yellow to brownish-yellow solution at 10 mg/mL concentration. Each mL contains 10 mg docetaxel (anhydrous), 0.38 grams of sulfoxybutyl ether cyclodextrin (SBECD), 0.16 grams of polyethylene glycol 300, 40 mg of polyvinylpyrrolidone k 12 , and 0.22 grams of dehydrated alcohol in water for injection, with citric acid for pH adjustment. DOCIVYX is available in single-dose vials containing 20 mg (2 mL), 80 mg (8 mL) or 160 mg (16 mL) docetaxel (anhydrous). DOCIVYX requires NO prior dilution with a diluent and is ready to add to the infusion solution. Docetaxel-Structure
Mechanism of action
12.1 Mechanism of Action Docetaxel is an antineoplastic agent that acts by disrupting the microtubular network in cells that is essential for mitotic and interphase cellular functions. Docetaxel binds to free tubulin and promotes the assembly of tubulin into stable microtubules while simultaneously inhibiting their disassembly. This leads to the production of microtubule bundles without normal function and to the stabilization of microtubules, which results in the inhibition of mitosis in cells. Docetaxel's binding to microtubules does not alter the number of protofilaments in the bound microtubules, a feature which differs from most spindle poisons currently in clinical use.
How supplied
16.1 How Supplied DOCIVYX ® Injection is supplied in a single-dose vial as a sterile, pyrogen-free, non-aqueous, pale-yellow to brownish-yellow solution. Discard unused portion. DOCIVYX ® (docetaxel) Injection, 10 mg/mL, is available as carton of one single-dose vial in the following strengths: 20 mg/2 mL (NDC: 83831-101-02) 80 mg/8 mL (NDC: 83831-102-08) 160 mg/16 mL (NDC: 83831-103-16) 16.2 Storage Store between 2°C and 25°C (36°F and 77°F). Retain in the original package to protect from light. Freezing does not adversely affect the product. 16.3 Handling and Disposal DOCIVYX is a hazardous drug. Follow applicable special handling and disposal procedures. 16.1 How Supplied DOCIVYX ® Injection is supplied in a single-dose vial as a sterile, pyrogen-free, non-aqueous, pale-yellow to brownish-yellow solution. Discard unused portion. DOCIVYX ® (docetaxel) Injection, 10 mg/mL, is available as carton of one single-dose vial in the following strengths: 20 mg/2 mL (NDC: 83831-101-02) 80 mg/8 mL (NDC: 83831-102-08) 160 mg/16 mL (NDC: 83831-103-16)
Patient information
Advise the patient to read the FDA-approved patient labeling (Patient Information). Bone Marrow Suppression Advise patients that periodic assessment of their blood count will be performed to detect neutropenia, thrombocytopenia, and/ or anemia [see Contraindications (4) , Warnings and Precautions (5.3) ] . Instruct patients to monitor their temperature frequently and immediately report any occurrence of fever. Enterocolitis and Neutropenic Colitis Advise patients of the symptoms of colitis, such as abdominal pain or tenderness, and/or diarrhea, with or without fever, and instruct patients to promptly contact their healthcare provider if they experience these symptoms [see Dosage and Administration (2.7) and Warnings and Precautions (5.4) ] . Hypersensitivity Reactions Ask patients whether they have previously received paclitaxel therapy, and if they have experienced a hypersensitivity reaction to paclitaxel. Instruct patients to immediately report to their healthcare provider signs of a hypersensitivity reaction [see Contraindications (4), Warnings and Precautions (5.5) ] . Fluid Retention Advise patients to report signs of fluid retention such as peripheral edema in the lower extremities, weight gain, and dyspnea immediately to their healthcare provider [see Warnings and Precautions (5.6) ] . Second Primary Malignancies Advise patients on the risk of second primary malignancies during treatment with DOCIVYX [see Warnings and Precautions (5.7) ] . Cutaneous Reactions Advise patients that localized erythema of the extremities and severe skin toxicities may occur. Instruct patients to immediately report severe cutaneous reactions to their healthcare provider [see Dosage and Administration (2.7) and Warnings and Precautions (5.8) ] . Neurologic Reactions Advise patients that neurosensory symptoms or peripheral neuropathy may occur. Instruct patients to immediately report neurologic reactions to their healthcare provider [see Dosage and Administration (2.7) and Warnings and Precautions (5.9) ] . Eye Disorders Advise patients that vision disturbances and excessive tearing are associated with DOCIVYX administration. Instruct patients to immediately report any vision changes to their healthcare provider [see Warnings and Precautions (5.10) ] . Gastrointestinal Reactions Explain to patients that nausea, vomiting, diarrhea, and constipation are associated with DOCIVYX administration. Instruct patients to report any severe events to their healthcare provider [see Adverse Reactions (6) ] . Cardiac Disorders Advise patients to report any irregular and/or rapid heartbeat, severe shortness of breath, dizziness, and/or fainting immediately to their healthcare provider [see Adverse Reactions (6) ] . Other Common Adverse Reactions Advise patients that other common adverse reactions associated with DOCIVYX may include alopecia (cases of permanent hair loss have been reported), asthenia, anorexia, dysgeusia, mucositis, myalgia, nail disorders, or pain. Instruct patients to report these reactions to their healthcare provider if serious events occur [see Adverse Reactions (6) ] . Importance of Corticosteroids Explain the significance of oral corticosteroids such as dexamethasone administration to the patient to help facilitate compliance. Instruct patients to report to their healthcare provider if they were not compliant with the oral corticosteroid regimen [see Dosage and Administration (2.6) ] . Embryo-Fetal Toxicity DOCIVYX can cause fetal harm. Advise patients to inform their healthcare provider of a known or suspected pregnancy. Advise patients to avoid becoming pregnant while receiving this drug. Advise female patients of reproductive potential to use effective contraception during treatment and for 2 months after the last dose of DOCIVYX. Advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 4 months after the last dose of DOCIVYX [see Warnings and Precautions (5.12) , and Use in Specific Populations (8.1, 8.3) ] . Lactation Advise women not to breastfeed during DOCIVYX treatment and for 1 week after the last dose [see Use in Specific Populations (8.2) ] . Infertility Advise males of reproductive potential that DOCIVYX may impair fertility [see Nonclinical Toxicology (13.1) ] . Alcohol Content in DOCIVYX Explain to patients the possible effects of the alcohol content in DOCIVYX, including possible effects on the central nervous system [see Warnings and Precautions (5.13) ] . Tumor Lysis Syndrome Advise patients of the potential risk of tumor lysis syndrome and to immediately report any signs or symptoms associated with this event (nausea, vomiting, confusion, shortness of breath, seizure, irregular heartbeat, dark or cloudy urine, reduced amount of urine, unusual tiredness, muscle cramps) to their healthcare provider. Advise patients of the importance of keeping scheduled appointment for blood work or other laboratory tests and of drinking adequate fluids to avoid dehydration. [see Warnings and Precautions (5.14) ] . Ability to Drive or Operate Machines Explain to patients that DOCIVYX may impair their ability to drive or operate machines due to its side effects [see Adverse Reactions (6) ] or due to the alcohol content of DOCIVYX [see Warnings and Precautions (5.13) ] . Advise them not to drive or use machines if they experience these side effects during treatment. Drug Interactions Inform patients about the risk of drug interactions and the importance of providing a list of prescription and non-prescription drugs to their healthcare provider [see Drug Interactions (7) ] . Avyxa Pharma, LLC New Jersey 07054, USA Made in China Rx Only Image
Label text from the FDA structured product label by Avyxa Pharma, LLC (revised Jul 15, 2025). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Docetaxel in 3 products
Docivyx NDC products (3)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 83831-101 | Docetaxel 20 mg/2mL Injection, Solution | Avyxa Pharma, LLC | NDA |
| 83831-102 | Docetaxel 80 mg/8mL Injection, Solution | Avyxa Pharma, LLC | NDA |
| 83831-103 | Docetaxel 160 mg/16mL Injection, Solution | Avyxa Pharma, LLC | NDA |
Frequently asked questions
What is Docivyx used for?
1 INDICATIONS AND USAGE DOCIVYX is a microtubule inhibitor indicated for: Breast Cancer (BC) : single agent for locally advanced or metastatic BC after chemotherapy failure; and with doxorubicin and cyclophosphamide as adjuvant treatment of operable node-positive BC ( 1.1 ) Non-small Cell Lung Cancer (NSCLC): single agent for locally advanced or metastatic NSCLC after platinum therapy failure;…
What are the side effects of Docivyx?
The most serious adverse reactions from DOCIVYX are: Toxic Deaths [see Boxed Warning , Warnings and Precautions (5.1) ] Hepatic Impairment [see Boxed Warning , Warnings and Precautions (5.2) ] Hematologic Effects [see Boxed Warning , Warnings and Precautions (5.3) ] Enterocolitis and Neutropenic Colitis [see Warnings and Precautions (5.4) ] Hypersensitivity Reactions [see Boxed Warning , Warnings… See the full label for the complete list.
Who makes Docivyx?
Docivyx is listed by 1 labeler in the FDA NDC directory, including Avyxa Pharma, LLC.