- Injection, lyophilized powder for suspension (albumin bound) 100 mg
- Injection, solution, concentrate 6 mg/mL
Paclitaxel is a novel antimicrotubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability inhibits the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. In addition, paclitaxel induces abnormal arrays or bundles of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis, further disrupting cell function.
C max is 18,741 ng/mL.Paclitaxel injection solution
Following 3- and 24-h infusions, C max is 195 to 3,650 ng/mL and AUC is 6,300 to 15,007 ng•h/mL.
89% to 98% protein bound. Extensive extravascular distribution and/or tissue binding.Abraxane
Vd is 632 L/m 2 .Paclitaxel injection solution
Vd is 227 to 688 L/m 2 at steady state with 24-h infusion.
Paclitaxel is metabolized primarily to 6-alpha-hydroxypaclitaxel by isoenzymes CYP2C8 and to 2 minor metabolites, 3′-p-hydroxypaclitaxel and 6-alpha,3′-p-dihyroxypaclitaxel by CYP3A4.
Excreted in the urine (4%) and in the feces (20%). Terminal half-life is approximately 27 h and total body Cl is 15 L/h/m 2 .Paclitaxel injection solution
Excreted in the urine (14%) and in the feces (71%). Following 3- and 24-h infusions, the half-life is 13.1 to 52.7 h and total body Cl is 12.2 to 23.8 L/h/m 2 .
Special PopulationsRenal Function Impairment
The effect of renal dysfunction on the disposition of paclitaxel has not been investigated.Hepatic Function Impairment
Plasma paclitaxel exposure is increased.
Indications and UsageAbraxane
For the treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 mo of adjuvant chemotherapy.Paclitaxel injection solution
As first-line and subsequent therapy for the treatment of advanced carcinoma of the ovary; adjuvant treatment of node-positive breast cancer administered sequentially to standard doxorubicin-containing combination chemotherapy; treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 mo of adjuvant chemotherapy; in combination with cisplatin, for the first-line treatment of non–small cell lung cancer (NSCLC) in patients who are not candidates for potentially curative surgery and/or radiation therapy; for the second-line treatment of AIDS-related Kaposi sarcoma.
Paclitaxel injection solution has been used for squamous cell head and neck cancer, small cell lung cancer, bladder cancer, esophageal cancer, testicular cancer, endometrial cancer, prostate cancer, gastric cancer, germ cell tumors, and refractory leukemia and recurrent Wilms tumor in children. Abraxane has been used for NSCLC, metastatic melanoma, and squamous cell cancer of the tongue, head and neck, or anal canal.
Hypersensitivity reactions to paclitaxel or other drugs formulated in Cremophor EL (polyoxyethylated castor oil) (paclitaxel injection solution only); patients with solid tumors who have baseline neutrophil count of fewer than 1,500 cells/mm 3 or in patients with AIDS-related Kaposi sarcoma with baseline neutrophil counts of less than 1,000 cells/mm 3 .
Dosage and AdministrationAbraxane
Adults Breast cancer
IV 260 mg/m 2 over 30 min every 3 wk. For patients experiencing severe neutropenia (neutrophil count less than 500 cells/mm 3 for 1 wk or longer) or severe sensory neuropathy, reduce dose to 220 mg/m 2 for subsequent courses. For recurrence of severe neutropenia or severe sensory neuropathy, reduce dose to 180 mg/m 2 . For grade 3 sensory neuropathy, hold treatment until resolution to grade 1 or 2, and reduce the dose for all subsequent courses of treatment.Paclitaxel injection solution
Reduce dose by 20% for all subsequent courses in patients with severe neuropathy or severe neutropenia (neutrophil count less than 500 cells/mm 3 for longer than 7 days).AIDS-related Kaposi sarcoma
IV 135 mg/m 2 over 3 h once every 3 wk or 100 mg/m 2 over 3 h once every 2 wk (dose intensity 45 to 50 mg/m 2 /wk). Initiate with concomitant granulocyte colony-stimulating factor as clinically indicated.Breast cancer
IV 175 mg/m 2 over 3 h every 3 wk. When used as adjuvant treatment, administer for 4 courses sequentially to doxorubicin-containing combination chemotherapy.Non–small cell lung cancer
IV 135 mg mg/m 2 over 24 h followed by cisplatin 75 mg/m 2 . Repeat every 3 wk.Ovarian cancer
IV For previously treated patients, 135 mg/m 2 or 175 mg/m 2 administered over 3 h every 3 wk. For untreated patients, 175 mg/m 2 over 3 h or 135 mg/m 2 over 24 h every 3 wk; follow each paclitaxel dose with cisplatin 75 mg/m 2 .Pretreatment Regimen
To reduce incidence of hypersensitivity reactions to paclitaxel injection solution, premedicate with oral dexamethasone 20 mg 12 and 6 h before paclitaxel administration (dexamethasone 10 mg in AIDS patients), diphenhydramine (or its equivalent) 50 mg IV 30 to 60 min before paclitaxel administration, and an IV H 2 blocker (cimetidine 300 mg, ranitidine 50 mg, or famotidine 20 mg) 30 to 60 min before paclitaxel administration. Premedication is not required prior to Abraxane .Hepatic Function Impairment
IV Dosage recommendations are for the first course of therapy. The need for further dose adjustments in subsequent courses should be based on individual tolerance. For serum bilirubin 1.26 to 2 × the ULN and AST more than 10 × the ULN, reduce dose to 200 mg/m 2 . For serum bilirubin 2.01 to 5 × the ULN and AST more than 10 × the ULN, reduce dose to 130 mg/m 2 ; a dose increase to 200 mg/m 2 in subsequent courses should be considered based on individual tolerance. For serum bilirubin more than 5 × the ULN or AST more than 10 × the ULN, do not administer.Paclitaxel injection solution
IV For 135 mg/m 2 over 24 h regimen only, reduce dose of first course of therapy as follows: transaminase levels 2 to less than 10 × the ULN and bilirubin 1.5 mg/dL or less, give 100 mg/m 2 ; transaminase levels less than 10 × the ULN and bilirubin 1.6 to 7.5 mg/dL, give 50 mg/m 2 ; transaminase levels more than 10 × the ULN or bilirubin more than 7.5 mg/dL, not recommended. For 175 mg/m 2 over 3 h regimen only, reduce dose of first course of therapy as follows: transaminase levels less than 10 × the ULN and bilirubin 1.26 to 2 × the ULN, give 135 mg/m 2 ; transaminase levels less than 10 × the ULN and bilirubin 2.01 to 5 × the ULN, give 90 mg/m 2 ; transaminase levels 10 × the ULN or more or bilirubin more than 5 × the ULN, not recommended. Dose reduction for subsequent courses is based on individual tolerance.
- Abraxane cannot be substituted for or with other paclitaxel formulations.
- Paclitaxel is considered a cytotoxic agent. Follow safe handling procedures when preparing, administering, or dispensing paclitaxel.
- Use gloves when handling paclitaxel. If paclitaxel solution contacts the skin, wash the skin immediately and thoroughly with soap and water. Adverse reactions after topical exposure included burning, redness, and tingling. If paclitaxel contacts mucous membranes, thoroughly flush the membranes with water. Upon inhalation, burning eyes, chest pain, dyspnea, nausea, and sore throat have been reported.
- If signs or symptoms of extravasation occur, stop the infusion immediately.
- For IV infusion over 30 min.
- Reconstitute with sodium chloride 0.9% injection only. Slowly add, over a minimum of 1 min, 20 mL of sodium chloride 0.9% injection by directing solution flow onto the inside wall of the vial. Do not inject the sodium chloride directly onto the lyophilized cake because this will result in foaming. Allow the vial to sit for a minimum of 5 min then gently swirl and/or invert the vial slowly for at least 2 min until complete dissolution of the cake/powder occurs. If foaming or clumping occurs, let the solution stand for at least 15 min until foam subsides. Each milliliter of reconstituted suspension provides paclitaxel 5 mg/mL.
- The reconstituted suspension should be milky and homogeneous without visible particles. If particles or settling are visible, gently invert the vial until complete resuspension has occurred. Discard the reconstituted suspension if precipitates are observed.
- Transfer prescribed amount of reconstituted suspension from the vial into an empty, sterile IV bag (plasticized PVC containers, PVC or non-PVC type IV bag).
- Do not administer through an in-line filter.
- Paclitaxel injection solution
- For IV infusion over 3 or 24 h.
- Ensure patient is premedicated with a corticosteroid, diphenhydramine, and H 2 antagonist to prevent severe hypersensitivity reactions.
- Paclitaxel must be diluted prior to infusion. Dilute prescribed dose in sodium chloride 0.9% injection, dextrose 5% injection, dextrose 5% and sodium chloride 0.9% injection, or dextrose 5% in Ringer's injection to provide final concentration of paclitaxel 0.3 to 1.2 mg/mL.
- Do not administer if particulate matter, cloudiness, or discoloration is noted. A slight haziness may be noted.
- Avoid contact of undiluted paclitaxel solution with PVC equipment or devices. Store diluted paclitaxel solutions in bottles (eg, glass, polypropylene) or plastic bags (eg, polypropylene, polyolefin), and administer through polyethylene-lined administration sets.
- Administer through an in-line filter with a microporous membrane no greater than 0.22 microns.
- Do not use the Chemo Dispensing Pin device or similar devices with spikes with vials of paclitaxel because they can cause the stopper to collapse, resulting in the loss of sterile integrity of the paclitaxel solution.
Store unopened vials between 68° and 77°F in the original package. Refrigeration or freezing do not adversely affect the stability of paclitaxel. Use reconstituted suspension immediately. If not used immediately, vials can be replaced in original carton to protect suspension from bright light and stored in the refrigerator (between 36° and 46°F) for a max of 8 h. The reconstituted suspension in infusion bag is stable at ambient temperatures and lighting conditions for up to 8 h.Paclitaxel injection solution
Store unopened vials between 68° and 77°F in the original package. Protect from light. Refrigeration or freezing do not adversely affect the stability of paclitaxel. Upon refrigeration, components in the vial may precipitate but will redissolve upon reaching room temperature with little or no agitation. Use diluted solution for infusion immediately. If not used immediately, the diluted solution is stable at ambient temperature (approximately 77°F) and lighting conditions for up to 27 h. Multiple-dose vials may be stored up to 28 days after initial needle puncture.
Paclitaxel injection solution contains dehydrated alcohol; consider possible CNS and other effects of alcohol.Cisplatin
Paclitaxel Cl may decrease when given after cisplatin, resulting in increased hematologic toxicity. Observe patients for signs of paclitaxel toxicity. Adjust the paclitaxel dose as needed.CYP-450 2C8 (eg, rifampin) and 3A4 inducers (eg, carbamazepine, phenobarbital, rifampin)
May induce the metabolism of paclitaxel, decreasing the pharmacologic effects. Closely monitor the response to paclitaxel when starting or stopping CYP2C8 and CYP3A4 inducers. Adjust paclitaxel treatment as needed.CYP-450 2C8 (eg, gemfibrozil) and 3A4 inhibitors (eg, ketoconazole)
May decrease the metabolism of paclitaxel, increasing paclitaxel plasma concentrations and pharmacologic effects as well as risk of adverse reactions. If coadministration cannot be avoided, a paclitaxel dose reduction may be needed.Doxorubicin
Paclitaxel may increase plasma concentrations of doxorubicin and its active metabolite, doxorubicinol. Observe patients for signs of toxicity and adjust the dose as needed.Palifermin
Coadministration of palifermin and paclitaxel within the same 24-h time period may increase the severity and duration of oral mucositis. Do not administer palifermin within 24 h before, during, or 24 h after administration of paclitaxel.Vaccines, live
The risk of live vaccine–induced adverse reactions may be increased by coadministration of paclitaxel. Defer coadministration of live vaccines.
The following adverse reactions data are based on patients who received single-agent paclitaxel injection solution or Abraxane .
Abnormal ECG (60%); hypotension (17%); bradycardia (3%); atrial fibrillation; cardiac ischemia/infarction; MI; stroke; supraventricular tachycardia; thrombosis/embolism; transient ischemic attack.
Peripheral neuropathy (79% [severe symptoms 10%]); sensory neuropathy (71% [severe symptoms 10%]); asthenia (47% [severe symptoms 8%]); confusional state; convulsions; dizziness; headache; malaise; vertigo; cranial nerve palsies (postmarketing).
Alopecia (90%); nail changes (2%); skin abnormalities related to radiation recall; maculopapular rash; pruritus; Stevens-Johnson syndrome; TEN; erythema, generalized or maculopapular rash, photosensitivity reactions, thickening and sclerosing of the skin (postmarketing).
Visual disturbances (13% [severe 1%]); conjunctivitis; increased lacrimation; photopsia; visual floaters; ototoxicity, vocal cord paresis (postmarketing).
Diarrhea (90% [severe symptoms 1%]); nausea, vomiting (70%); mucositis (45% [severe symptoms 3%]); anorexia; ascites; constipation; esophagitis; intestinal obstruction and/or perforation; ischemic colitis; neutropenic enterocolitis (typhilitis); pancreatitis.
Neutropenia (100%); anemia, leukopenia (90%); febrile neutropenia (55%); thrombocytopenia (52%); red cell transfusions (25%); bleeding (14%); platelet transfusion (2%); pancytopenia.
Elevated AST (39%); elevated alkaline phosphatase (36%); elevated GGT (14%); elevated bilirubin (7%); hepatic necrosis; hepatic encephalopathy.
Hypersensitivity (45% [severe 2%]).
Injection-site reaction (13%).
Arthralgia, myalgia (93% [severe symptoms 16%]).
Elevated creatinine (34% [severe 7%]); renal toxicity.
Dyspnea (12%); cough (7%); interstitial pneumonia; lung fibrosis; pleural effusion; pulmonary embolism; respiratory failure.
Infections (30%); edema (21% [severe symptoms 1%]); fever (12%); autonomic neuropathy resulting in paralytic ileus; dehydration.
Administer under the supervision of a health care provider experienced in the use of cancer chemotherapeutic agents. Appropriate management of complications is possible only when adequate diagnostic and treatment facilities are readily available.Neutropenia
Do not give to patients with solid tumors who have baseline neutrophil counts of less than 1,500 cells/mm 3 and do not give to patients with AIDS-related Kaposi sarcoma if the baseline neutrophil count is less than 1,000 cells/mm 3 . In order to monitor the occurrence of bone marrow suppression, primarily neutropenia, which may be severe and result in infection, perform frequent peripheral blood cell counts on all patients receiving paclitaxel.Abraxane
An albumin form of paclitaxel may substantially affect a drug's functional properties relative to those of the drug in solution. Do not substitute for or with other paclitaxel formulations.Paclitaxel injection solution
Anaphylaxis and severe hypersensitivity reactions characterized by dyspnea and hypotension requiring treatment, angioedema, and generalized urticaria have occurred. Fatal reactions have occurred in patients despite premedication. Pretreat all patients with corticosteroids, diphenhydramine, and H 2 antagonists. Do not rechallenge patients who experience severe hypersensitivity reactions to paclitaxel with the drug.
Frequently monitor CBC, differential, and platelet counts. Closely monitor the infusion site for possible infiltration during administration. Monitor vital signs frequently, especially during the first hour. Monitor patients with hepatic impairment closely.
Category D . Can cause fetal harm.
Undetermined. Avoid breast-feeding.
Safety and efficacy not established.
Severe myelosuppression, neuropathy, and CV events may occur more frequently.
Exercise caution when administering to patients with moderate to severe hepatic impairment; dosage adjustments are required.
Adverse events, such as fatigue, lethargy, and malaise, may affect the ability to drive and use machines.
Because Abraxane contains human albumin, it carries an extremely remote risk for transmission of viral diseases or Creutzfeldt-Jakob disease.
Severe conduction abnormalities have been documented in fewer than 1% of patients during paclitaxel injection solution therapy, sometimes requiring a pacemaker. Hypotension, hypertension, and bradycardia also have been observed.
Peripheral and sensory neuropathy occurs frequently.
Injection-site reactions, including reactions secondary to extravasation, are usually mild and consisted of erythema, tenderness, skin discoloration, or swelling at the injection site. Recurrence of skin reactions at a site of previous extravasation following administration of paclitaxel at a different site (recall) has been reported rarely. Rare reports of more severe events, such as phlebitis, cellulitis, induration, skin exfoliation, necrosis, and fibrosis, have also been received.
Use in men
Advise men to avoid fathering a child while receiving paclitaxel treatment.
Bone marrow suppression, mucositis, peripheral neurotoxicity.
- Inform patients that allergic reactions, causing death in rare cases, may occur. Certain premedications administered prior to paclitaxel injection solution can prevent or reduce the chance of a serious allergic reaction.
- Inform patients that complete hair loss, or alopecia, almost always occurs. This usually involves loss of the eyebrows, eyelashes, and pubic hair as well as scalp hair.
- Inform patients that joint and muscle pain may occur a few days after paclitaxel treatment. These symptoms usually disappear in a few days. Instruct patients that although pain medicine may not be necessary, they should tell their health care provider if they are uncomfortable.
- Inform patients that paclitaxel sometimes causes irritation at the site where it enters the vein. Reactions may include discomfort, redness, swelling, inflammation (of the surrounding skin or of the vein itself), and ulceration (open sores). These reactions are usually caused by the IV fluid leaking into the surrounding area. Instruct patients that if they notice anything unusual at the site of the injection (needle), either during or after treatment, they should tell their health care provider right away.
- Inform patients that paclitaxel treatment may cause anemia. Patients can feel tired, tire easily, appear pale, and become short of breath. Instruct patients to contact their health care provider if they experience any of these symptoms following paclitaxel treatment.
- Inform patients that some patients develop redness or sores in the mouth or on the lips. These symptoms might occur a few days after the paclitaxel treatment and usually decrease or disappear within 1 wk. Instruct patients to talk with their health care provider about proper mouth care and other ways to prevent or reduce the chance of developing mucositis.
- Advise patients that numbness, tingling, or burning in the hands or feet (neuropathy) occurs often and usually gets better or goes away within several months of completing treatment.
- Inform patients that paclitaxel may cause asthenia, fatigue, weakness, lethargy, and malaise.
- Inform patients that nausea, vomiting, or diarrhea may follow paclitaxel use.
- Advise women to avoid becoming pregnant and to avoid breast-feeding while being treated with paclitaxel.
- Advise men to avoid fathering a child during treatment with paclitaxel.
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