Generic Name
Docetaxel
Brand Names
Docivyx, Beizray
FDA approval date: October 21, 2010
Classification: Microtubule Inhibitor
Form: Injection, Kit
What is Docivyx (Docetaxel)?
Docetaxel is a microtubule inhibitor indicated for: Breast Cancer : single agent for locally advanced or metastatic BC after chemotherapy failure; and with doxorubicin and cyclophosphamide as adjuvant treatment of operable node-positive BC.
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Brand Information
DOCIVYX (docetaxel)
1DOSAGE AND ADMINISTRATION
For all indications, toxicities may warrant dosage adjustments
1.1Breast Cancer
- For locally advanced or metastatic breast cancer after failure of prior chemotherapy, the recommended dose of DOCIVYX is 60 mg/m
- For the adjuvant treatment of operable node-positive breast cancer, the recommended DOCIVYX dose is 75 mg/m
1.2Non-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
- For chemotherapy-naive patients, DOCIVYX was evaluated in combination with cisplatin. The recommended dose of DOCIVYX is 75 mg/m
1.3Prostate Cancer
- For metastatic CRPC, the recommended dose of DOCIVYX is 75 mg/m
1.4Gastric Adenocarcinoma
- For gastric adenocarcinoma, the recommended dose of DOCIVYX is 75 mg/m
1.5Head 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
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
1.6Premedication 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
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
1.7Dosage Adjustments during Treatment
Breast Cancer
Patients who are dosed initially at 100 mg/m
Combination Therapy with DOCIVYX Injection in the Adjuvant Treatment of Breast Cancer
DOCIVYX in combination with doxorubicin and cyclophosphamide should be administered when the neutrophil count is ≥1,500 cells/mm
Non-small Cell Lung Cancer
Monotherapy with DOCIVYX for NSCLC treatment after failure of prior platinum-based chemotherapy
Patients who are dosed initially at 75 mg/m
Combination therapy with DOCIVYX for chemotherapy-naive NSCLC
For patients who are dosed initially at DOCIVYX 75 mg/m
Prostate Cancer
Combination therapy with DOCIVYX for metastatic CRPC
DOCIVYX should be administered when the neutrophil count is ≥1,500 cells/mm
Gastric or Head and Neck Cancer
DOCIVYX in combination with cisplatin and fluorouracil in gastric cancer or head and neck cancer
Patients treated with DOCIVYX in combination with cisplatin and fluorouracil must receive antiemetics and appropriate hydration according to current institutional guidelines. In both studies, G- CSF was recommended during the second and/or subsequent cycles in case of febrile neutropenia, or documented infection with neutropenia, or neutropenia lasting more than 7 days. If an episode of febrile neutropenia, prolonged neutropenia or neutropenic infection occurs despite G-CSF use, the DOCIVYX dose should be reduced from 75 mg/m
Recommended dose modifications for toxicities in patients treated with DOCIVYX in combination with cisplatin and fluorouracil are shown in Table 1.
Liver dysfunction: In case of AST/ALT >2.5 to ≤5 × ULN and AP ≤2.5 × ULN, or AST/ALT >1.5 to ≤5 × ULN and AP >2.5 to ≤5 × ULN, DOCIVYX should be reduced by 20%.
In case of AST/ALT >5 × ULN and/or AP >5 × ULN DOCIVYX should be stopped.
The dose modifications for cisplatin and fluorouracil in the gastric cancer study are provided below.
Cisplatin dose modifications and delays
Peripheral neuropathy: A neurological examination should be performed before entry into the study, and then at least every 2 cycles and at the end of treatment. In the case of neurological signs or symptoms, more frequent examinations should be performed and the following dose modifications can be made according to NCI-CTCAE grade:
- Grade 2: Reduce cisplatin dose by 20%.
- Grade 3: Discontinue treatment.
Ototoxicity: In the case of grade 3 toxicity, discontinue treatment.
Nephrotoxicity: In the event of a rise in serum creatinine ≥grade 2 (>1.5 × normal value) despite adequate rehydration, CrCl should be determined before each subsequent cycle and the following dose reductions should be considered (see Table 2).
For other cisplatin dosage adjustments, also refer to the manufacturers' prescribing information.
Fluorouracil dose modifications and treatment delays
For diarrhea and stomatitis, see Table 1.
In the event of grade 2 or greater plantar-palmar toxicity, fluorouracil should be stopped until recovery. The fluorouracil dosage should be reduced by 20%.
For other greater than grade 3 toxicities, except alopecia and anemia, chemotherapy should be delayed (for a maximum of 2 weeks from the planned date of infusion) until resolution to grade ≤1 and then recommenced, if medically appropriate.
For other fluorouracil dosage adjustments, also refer to the manufacturers' prescribing information.
Combination Therapy with Strong CYP3A4 Inhibitors
Avoid using concomitant strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin and voriconazole). There are no clinical data with a dose adjustment in patients receiving strong CYP3A4 inhibitors. Based on extrapolation from a pharmacokinetic study with ketoconazole in 7 patients, consider a 50% docetaxel dose reduction if patients require coadministration of a strong CYP3A4 inhibitor
1.8Administration Precautions
DOCIVYX is a hazardous anticancer drug and, as with other potentially toxic compounds, caution should be exercised when handling and preparing DOCIVYX solutions. The use of gloves is recommended
If DOCIVYX Injection solution, or final infusion solution should come into contact with the skin, immediately and thoroughly wash with soap and water. If DOCIVYX Injection solution, or final infusion solution should come into contact with mucosa, immediately and thoroughly wash with water.
Contact of the DOCIVYX with plasticized polyvinyl chloride (PVC) equipment or devices used to prepare solutions for infusion is not recommended. In order to minimize patient exposure to the plasticizer DEHP (di-2- ethylhexyl phthalate), which may be leached from PVC infusion bags or sets, the DOCIVYX final infusion solution should be administered through polyethylene-lined administration sets.
DOCIVYX Injection requires NO prior dilution with a diluent and is ready to add to the infusion solution.
Please follow the preparation instructions provided below.
1.9Preparation and Administration
DOCIVYX Injection (10 mg/mL) requires NO prior dilution with a diluent and is ready to add to the infusion solution. Use only a 21-gauge needle to withdraw DOCIVYX from the vial because larger bore needles (e.g., 18 and 19 gauge) may result in stopper coring and rubber particulates.
- DOCIVYX vials should be stored between 2°C and 25°C (36°F and 77°F). If the vials are stored under refrigeration, allow the appropriate number of vials of DOCIVYX vials to stand at room temperature for approximately 5 minutes before use.
- Using
- If a dose greater than 200 mg of DOCIVYX is required, use a larger volume of the infusion vehicle so that a concentration of 0.74 mg/mL DOCIVYX is not exceeded.
- Thoroughly mix the infusion by gentle manual rotation.
- As with all parenteral products, DOCIVYX should be inspected visually for particulate matter or discoloration prior to administration whenever the solution and container permit. If the DOCIVYX final infusion solution is not clear or appears to have precipitation, it should be discarded.
- DOCIVYX final infusion solution is supersaturated, therefore may crystallize over time. If crystals appear, the solution must no longer be used and shall be discarded.
The DOCIVYX final infusion solution should be administered intravenously as a 1-hour infusion under ambient room temperature (below 25°C) and lighting conditions.
1.10Stability
DOCIVYX final infusion solution, if stored between 2°C and 25°C (36°F and 77°F), is stable for 6 hours. DOCIVYX final infusion solution (in either 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP) should be used within 6 hours (including the 1-hour intravenous administration).
In addition, physical and chemical in-use stability of the infusion solution prepared as recommended has been demonstrated in non-PVC bags up to 48 hours when stored between 2°C and 8°C (36°F and 46°F).
2DOSAGE FORMS AND STRENGTHS
DOCIVYX (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.
3CONTRAINDICATIONS
DOCIVYX is contraindicated in patients with:
- neutrophil counts of <1500 cells/mm3
- a history of severe hypersensitivity reactions to docetaxel. Severe reactions, including anaphylaxis, have occurred
4ADVERSE REACTIONS
The most serious adverse reactions from DOCIVYX are:
- Toxic Deaths
- Hepatic Impairment
- Hematologic Effects
- Enterocolitis and Neutropenic Colitis
- Hypersensitivity Reactions
- Fluid Retention
- Second Primary Malignancies
- Cutaneous Reactions
- Neurologic Reactions
- Eye Disorders
- Asthenia
- Alcohol Content
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.
4.1Clinical Trials Experience
Breast Cancer
Monotherapy with DOCIVYX for locally advanced or metastatic breast cancer after failure of prior chemotherapy
DOCIVYX 100 mg/m
Hematologic reactions
Reversible marrow suppression was the major dose-limiting toxicity of DOCIVYX
Febrile neutropenia (<500 cells/mm
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
Hypersensitivity reactions
Severe hypersensitivity reactions have been reported
Fluid retention
Fluid retention can occur with the use of DOCIVYX
Cutaneous reactions
Severe skin toxicity is discussed elsewhere in the label
Severe nail disorders were characterized by hypo or hyperpigmentation, and occasionally by onycholysis (in 0.8% of patients with solid tumors) and pain.
Neurologic reactions
Neurologic reactions are discussed elsewhere in the label
Gastrointestinal reactions
Nausea, vomiting, and diarrhea were generally mild to moderate. Severe reactions occurred in 3%–5% of patients with solid tumors and to a similar extent among metastatic breast cancer patients. The incidence of severe reactions was 1% or less for the 92 breast cancer patients premedicated with 3-day corticosteroids.
Severe stomatitis occurred in 5.5% of patients with solid tumors, in 7.4% of patients with metastatic breast cancer, and in 1.1% of the 92 breast cancer patients premedicated with 3-day corticosteroids.
Cardiovascular reactions
Hypotension occurred in 2.8% of patients with solid tumors; 1.2% required treatment. Clinically meaningful events such as heart failure, sinus tachycardia, atrial flutter, dysrhythmia, unstable angina, pulmonary edema, and hypertension have occurred. Seven of 86 (8.1%) of metastatic breast cancer patients receiving DOCIVYX 100 mg/m
Infusion site reactions
Infusion site reactions were generally mild and consisted of hyperpigmentation, inflammation, redness or dryness of the skin, phlebitis, extravasation, or swelling of the vein.
Hepatic reactions
In patients with normal LFTs at baseline, bilirubin values greater than the ULN occurred in 8.9% of patients. Increases in AST or ALT >1.5 times the ULN, or alkaline phosphatase >2.5 times ULN, were observed in 18.9% and 7.3% of patients, respectively. While on DOCIVYX, increases in AST and/or ALT >1.5 times ULN concomitant with alkaline phosphatase >2.5 times ULN occurred in 4.3% of patients with normal LFTs at baseline. Whether these changes were related to the drug or underlying disease has not been established.
Hematologic and other toxicity: Relation to dose and baseline liver chemistry abnormalities
Hematologic and other toxicity is increased at higher doses and in patients with elevated baseline liver function tests (LFTs). In the following tables, adverse drug reactions are compared for three populations: 730 patients with normal LFTs given DOCIVYX at 100 mg/m
In the three-arm monotherapy trial, TAX313, which compared DOCIVYX 60 mg/m
The following adverse reactions were associated with increasing docetaxel doses: fluid retention (26%, 38%, and 46% at 60 mg/m
Combination therapy with DOCIVYX in the adjuvant treatment of breast cancer
The following table presents treatment-emergent adverse reactions observed in 744 patients, who were treated with DOCIVYX 75 mg/m
Of the 744 patients treated with TAC, 36.3% experienced severe treatment-emergent adverse reactions compared to 26.6% of the 736 patients treated with FAC. Dose reductions due to hematologic toxicity occurred in 1% of cycles in the TAC arm versus 0.1% of cycles in the FAC arm. Six percent of patients treated with TAC discontinued treatment due to adverse reactions, compared to 1.1% treated with FAC; fever in the absence of infection and allergy being the most common reasons for withdrawal among TAC-treated patients. Two patients died in each arm within 30 days of their last study treatment; 1 death per arm was attributed to study drugs.
Fever and infection
During the treatment period, fever in the absence of infection was seen in 46.5% of TAC-treated patients and in 17.1% of FAC-treated patients. Grade 3/4 fever in the absence of infection was seen in 1.3% and 0% of TAC and FAC-treated patients, respectively. Infection was seen in 39.4% of TAC- treated patients compared to 36.3% of FAC-treated patients. Grade 3/4 infection was seen in 3.9% and 2.2% of TAC-treated and FAC-treated patients, respectively. There were no septic deaths in either treatment arm during the treatment period.
Gastrointestinal reactions
In addition to gastrointestinal reactions reflected in the table above, 7 patients in the TAC arm were reported to have colitis/enteritis/large intestine perforation versus one patient in the FAC arm. Five of the 7 TAC-treated patients required treatment discontinuation; no deaths due to these events occurred during the treatment period.
Cardiovascular reactions
More cardiovascular reactions were reported in the TAC arm versus the FAC arm during the treatment period: arrhythmias, all grades (6.2% vs 4.9%), and hypotension, all grades (1.9% vs 0.8%). Twenty-six (26) patients (3.5%) in the TAC arm and 17 patients (2.3%) in the FAC arm developed CHF during the study period. All except one patient in each arm were diagnosed with CHF during the follow-up period. Two (2) patients in TAC arm and 4 patients in FAC arm died due to CHF. The risk of CHF was higher in the TAC arm in the first year, and then was similar in both treatment arms.
Adverse reactions during the follow-up period (median follow-up time of 8 years)
In study TAX316, the most common adverse reactions that started during the treatment period and persisted into the follow-up period in TAC and FAC patients are described below (median follow-up time of 8 years).
Nervous system disorders
In study TAX316, peripheral sensory neuropathy started during the treatment period and persisted into the follow-up period in 84 patients (11.3%) in TAC arm and 15 patients (2%) in FAC arm. At the end of the follow-up period (median follow-up time of 8 years), peripheral sensory neuropathy was observed to be ongoing in 10 patients (1.3%) in TAC arm, and in 2 patients (0.3%) in FAC arm.
Skin and subcutaneous tissue disorders
In study TAX316, alopecia persisting into the follow-up period after the end of chemotherapy was reported in 687 of 744 TAC patients (92.3%) and 645 of 736 FAC patients (87.6%). At the end of the follow-up period (actual median follow-up time of 8 years), alopecia was observed to be ongoing in 29 TAC patients (3.9%) and 16 FAC patients (2.2%).
Reproductive system and breast disorders
In study TAX316, amenorrhea that started during the treatment period and persisted into the follow-up period after the end of chemotherapy was reported in 202 of 744 TAC patients (27.2%) and 125 of 736 FAC patients (17.0%). Amenorrhea was observed to be ongoing at the end of the follow-up period (median follow-up time of 8 years) in 121 of 744 TAC patients (16.3%) and 86 FAC patients (11.7%).
General disorders and administration site conditions
In study TAX316, peripheral edema that started during the treatment period and persisted into the follow-up period after the end of chemotherapy was observed in 119 of 744 TAC patients (16.0%) and 23 of 736 FAC patients (3.1%). At the end of the follow-up period (actual median follow-up time of 8 years), peripheral edema was ongoing in 19 TAC patients (2.6%) and 4 FAC patients (0.5%).
In study TAX316, lymphedema that started during the treatment period and persisted into the follow-up period after the end of chemotherapy was reported in 11 of 744 TAC patients (1.5%) and 1 of 736 FAC patients (0.1%). At the end of the follow-up period (actual median follow-up time of 8 years), lymphedema was observed to be ongoing in 6 TAC patients (0.8%) and 1 FAC patient (0.1%).
In study TAX316, asthenia that started during the treatment period and persisted into the follow-up period after the end of chemotherapy was reported in 236 of 744 TAC patients (31.7%) and 180 of 736 FAC patients (24.5%). At the end of the follow-up period (actual median follow-up time of 8 years), asthenia was observed to be ongoing in 29 TAC patients (3.9%) and 16 FAC patients (2.2%).
Acute myeloid leukemia (AML)/Myelodysplastic syndrome (MDS)
AML occurred in the adjuvant breast cancer trial (TAX316). The cumulative risk of developing treatment-related AML at median follow-up time of 8 years in TAX316 was 0.4% for TAC-treated patients and 0.1% for FAC-treated patients. One TAC patient (0.1%) and 1 FAC patient (0.1%) died due to AML during the follow-up period (median follow-up time of 8 years). Myelodysplastic syndrome occurred in 2 of 744 (0.3%) patients who received TAC and in 1 of 736 (0.1%) patients who received FAC. AML occurs at a higher frequency when these agents are given in combination with radiation therapy.
Lung Cancer
Monotherapy with DOCIVYX for unresectable, locally advanced or metastatic NSCLC previously treated with platinum-based chemotherapy
DOCIVYX 75 mg/m
Combination therapy with DOCIVYX in chemotherapy-naïve advanced unresectable or metastatic NSCLC
Table 8 presents safety data from two arms of an open label, randomized controlled trial (TAX326) that enrolled patients with unresectable stage IIIB or IV non-small cell lung cancer and no history of prior chemotherapy. Adverse reactions were described using the NCI Common Toxicity Criteria except where otherwise noted.
Deaths within 30 days of last study treatment occurred in 31 patients (7.6%) in the docetaxel+cisplatin arm and 37 patients (9.3%) in the vinorelbine+cisplatin arm. Deaths within 30 days of last study treatment attributed to study drug occurred in 9 patients (2.2%) in the docetaxel+cisplatin arm and 8 patients (2.0%) in the vinorelbine+cisplatin arm.
The second comparison in the study, vinorelbine+cisplatin versus DOCIVYX+carboplatin (which did not demonstrate a superior survival associated with DOCIVYX
Prostate Cancer
Combination therapy with DOCIVYX in patients with CRPC
The following data are based on the experience of 332 patients, who were treated with DOCIVYX 75 mg/m
Gastric Cancer
Combination therapy with DOCIVYX in gastric adenocarcinoma
Data in the following table are based on the experience of 221 patients with advanced gastric adenocarcinoma and no history of prior chemotherapy for advanced disease who were treated with DOCIVYX 75 mg/m
Head and Neck Cancer
Combination therapy with DOCIVYX in head and neck cancer
Table 11 summarizes the safety data obtained from patients that received induction chemotherapy with DOCIVYX 75 mg/m
4.2Postmarketing Experience
The following adverse reactions have been identified from clinical trials and/or postmarketing surveillance. Because these reactions are reported from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Body as a whole: diffuse pain, chest pain, radiation recall phenomenon, injection site recall reaction (recurrence of skin reaction at a site of previous extravasation following administration of docetaxel at a different site) at the site of previous extravasation.
Cardiovascular: atrial fibrillation, deep vein thrombosis, ECG abnormalities, thrombophlebitis, pulmonary embolism, syncope, tachycardia, myocardial infarction. Ventricular arrhythmia, including ventricular tachycardia, in patients treated with docetaxel in combination regimens including doxorubicin, 5-fluorouracil and/or cyclophosphamide may be associated with fatal outcome.
Cutaneous: cutaneous lupus erythematosus, bullous eruptions such as erythema multiforme and severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome, toxic epidermal necrolysis and acute generalized exanthematous pustulosis, scleroderma-like changes (usually preceded by peripheral lymphedema), severe palmar-plantar erythrodysesthesia, and permanent alopecia.
Gastrointestinal: enterocolitis, including colitis, ischemic colitis, and neutropenic enterocolitis, which may be fatal. Abdominal pain, anorexia, constipation, duodenal ulcer, esophagitis, gastrointestinal hemorrhage, gastrointestinal perforation, intestinal obstruction, ileus, and dehydration as a consequence of gastrointestinal events.
Hearing: ototoxicity, hearing disorders and/or hearing loss, including during use with other ototoxic drugs.
Hematologic: bleeding episodes, disseminated intravascular coagulation (DIC), often in association with sepsis or multiorgan failure.
Hepatic: hepatitis, sometimes fatal, primarily in patients with pre-existing liver disorders.
Hypersensitivity: anaphylactic shock with fatal outcome in patients who received premedication. Severe hypersensitivity reactions with fatal outcome with docetaxel in patients who previously experienced hypersensitivity reactions to paclitaxel.
Metabolism and nutrition disorders: electrolyte imbalance, including hyponatremia, hypokalemia, hypomagnesemia, and hypocalcemia. Tumor lysis syndrome, sometimes fatal.
Neurologic: confusion, seizures or transient loss of consciousness, sometimes appearing during the infusion of the drug.
Ophthalmologic: conjunctivitis, lacrimation or lacrimation with or without conjunctivitis, cystoid macular edema (CME). Excessive tearing which may be attributable to lacrimal duct obstruction. Transient visual disturbances (flashes, flashing lights, scotomata), typically occurring during drug infusion and reversible upon discontinuation of the infusion, in association with hypersensitivity reactions.
Respiratory: dyspnea, acute pulmonary edema, acute respiratory distress syndrome/pneumonitis, interstitial lung disease, interstitial pneumonia, respiratory failure, and pulmonary fibrosis, which may be fatal. Radiation pneumonitis in patients receiving concomitant radiotherapy.
Renal: renal insufficiency and renal failure, the majority of cases were associated with concomitant nephrotoxic drugs.
Second primary malignancies: second primary malignancies, including AML, MDS, NHL, and renal cancer [see
Musculoskeletal disorder: myositis.
5DRUG INTERACTIONS
Docetaxel is a CYP3A4 substrate.
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
6OVERDOSAGE
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
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
7DESCRIPTION
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-
Docetaxel is a white to almost-white powder with an empirical formula of C
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
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.
8REFERENCES
- "OSHA Hazardous Drugs." http://www.osha.gov/SLTC/hazardousdrugs/index.html
9PATIENT COUNSELING 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
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
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
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
Second Primary Malignancies
Advise patients on the risk of second primary malignancies during treatment with DOCIVYX
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
Neurologic Reactions
Advise patients that neurosensory symptoms or peripheral neuropathy may occur. Instruct patients to immediately report neurologic reactions to their healthcare provider
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
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
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
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
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
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
Lactation
Advise women not to breastfeed during DOCIVYX treatment and for 1 week after the last dose
Infertility
Advise males of reproductive potential that DOCIVYX may impair fertility
Alcohol Content in DOCIVYX
Explain to patients the possible effects of the alcohol content in DOCIVYX, including possible effects on the central nervous system
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.
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
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
10PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
