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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(pac li TAKS el)
Generic Available (U.S.)
Yes
Index Terms
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of breast, nonsmall cell lung, and ovarian cancers; treatment of AIDS-related Kaposi's sarcoma (KS)
Use: Unlabeled/Investigational
Treatment of bladder, cervical, small cell lung, and head and neck cancers; treatment of (unknown primary) adenocarcinoma
Pregnancy Risk Factor
D
Pregnancy Considerations
Animal studies have demonstrated embryotoxicity, fetal toxicity, and maternal toxicity. There are no adequate and well-controlled studies in pregnant women. Women of childbearing potential should be advised to avoid becoming pregnant.
Lactation
Excretion in breast milk unknown/contraindicated
Breast-Feeding Considerations
Due to the potential for serious adverse reactions, breast-feeding is contraindicated.
Contraindications
Hypersensitivity to paclitaxel, Cremophor® EL (polyoxyethylated castor oil), or any component of the formulation
Warnings/Precautions
Boxed warnings:
• Bone marrow suppression: See “Concerns related to adverse effects” below.
• Experienced physician: See “Other warnings/precautions” below.
• Hypersensitivity reactions: See “Concerns related to adverse effects” below.
Special handling:
• Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects:
• Bone marrow suppression: [U.S. Boxed Warning]: Bone marrow suppression is the dose-limiting toxicity; do not administer if baseline absolute neutrophil count (ANC) is <1500 cells/mm3 (<1000 cells/mm3 for patients with AIDS-related KS); reduce future doses by 20% for severe neutropenia (<500 cells/mm3 for 7 days or more) and consider the use of supportive therapy, including growth factor treatment. When administered as sequential infusions, taxane derivatives (docetaxel, paclitaxel) should be administered before platinum derivatives (carboplatin, cisplatin) to limit myelosuppression.
• Cardiovascular effects: Infusion-related hypotension, bradycardia, and/or hypertension may occur; frequent monitoring of vital signs is recommended, especially during the first hour of the infusion. Rare but severe conduction abnormalities have been reported; conduct cardiac monitoring during subsequent infusions for these patients.
• Hypersensitivity reactions: [U.S. Boxed Warning]: Severe hypersensitivity reactions have been reported; premedication may minimize this effect. Stop infusion and do not rechallenge for severe hypersensitivity reactions (hypotension requiring treatment, dyspnea requiring bronchodilators, angioedema, urticaria). Minor hypersensitivity reactions (flushing, skin reactions, dyspnea, hypotension, or tachycardia) do not require interruption of treatment.
• Peripheral neuropathy: With use, peripheral neuropathy may occur; patients with pre-existing neuropathies from chemotherapy or coexisting conditions (eg, diabetes mellitus) may be at a higher risk; reduce dose by 20% for severe neuropathy.
Disease-related concerns:
• Hepatic impairment: Use with extreme caution in patients with hepatic dysfunction (myelotoxicity may be worsened); dose reductions are recommended.
Special populations:
• Elderly: Use with caution in the elderly; increased risk of toxicity (neutropenia, neuropathy).
• Pediatrics: Safety and efficacy have not been established in children.
Dosage form specific issues:
• Dehydrated alcohol: Formulations contain dehydrated alcohol; may cause adverse CNS effects.
Other warnings/precautions:
• Experienced physician: [U.S. Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician.
Adverse Reactions
Percentages reported with single-agent therapy. Note: Myelosuppression is dose related, schedule related, and infusion-rate dependent (increased incidences with higher doses, more frequent doses, and longer infusion times) and, in general, rapidly reversible upon discontinuation.
>10%:
Cardiovascular: Flushing (28%), ECG abnormal (14% to 23%), edema (21%), hypotension (4% to 12%)
Dermatologic: Alopecia (87%), rash (12%)
Gastrointestinal: Nausea/vomiting (52%), diarrhea (38%), mucositis (17% to 35%; grades 3/4: up to 3%), stomatitis (15%; most common at doses >390 mg/m2), abdominal pain (with intraperitoneal paclitaxel)
Hematologic: Neutropenia (78% to 98%; grade 4: 14% to 75%; onset 8-10 days, median nadir 11 days, recovery 15-21 days), leukopenia (90%; grade 4: 17%), anemia (47% to 90%; grades 3/4: 2% to 16%), thrombocytopenia (4% to 20%; grades 3/4: 1% to 7%), bleeding (14%)
Hepatic: Alkaline phosphatase increased (22%), AST increased (19%)
Local: Injection site reaction (erythema, tenderness, skin discoloration, swelling: 13%)
Neuromuscular & skeletal: Peripheral neuropathy (42% to 70%; grades 3/4: up to 7%), arthralgia/myalgia (60%), weakness (17%)
Renal: Creatinine increased (observed in KS patients only: 18% to 34%; severe: 5% to 7%)
Miscellaneous: Hypersensitivity reaction (31% to 45%; grades 3/4: up to 2%), infection (15% to 30%)
1% to 10%:
Cardiovascular: Bradycardia (3%), tachycardia (2%), hypertension (1%), rhythm abnormalities (1%), syncope (1%), venous thrombosis (1%)
Dermatologic: Nail changes (2%)
Hematologic: Febrile neutropenia (2%)
Hepatic: Bilirubin increased (7%)
Respiratory: Dyspnea (2%)
<1%, postmarketing, and/or case reports: Anaphylaxis, arrhythmia, ataxia, atrial fibrillation, AV block, back pain, cardiac conduction abnormalities, cellulitis, CHF, chills, conjunctivitis, dehydration, enterocolitis, extravasation recall, hepatic encephalopathy, hepatic necrosis, induration, intestinal obstruction, intestinal perforation, interstitial pneumonia, ischemic colitis, lacrimation increased, maculopapular rash, malaise, MI, myocardial ischemia, necrotic changes and ulceration following extravasation, neuroencephalopathy, neutropenic enterocolitis, neutropenic typhlitis, ototoxicity (tinnitus and hearing loss), pancreatitis, paralytic ileus, phlebitis, pneumonitis, pruritus, pulmonary embolism, pulmonary fibrosis, radiation recall, radiation pneumonitis, renal insufficiency, scleroderma exacerbation, seizure, skin edema (diffuse), skin exfoliation, skin fibrosis, skin necrosis, skin sclerosis, skin thickening, Stevens-Johnson syndrome, supraventricular tachycardia, toxic epidermal necrolysis, ventricular tachycardia (asymptomatic), visual disturbances (scintillating scotomata)
Metabolism/Transport Effects
Substrate of CYP2C8 (major), CYP3A4 (major), P-glycoprotein; Induces CYP3A4 (weak)
Drug Interactions
Antineoplastic Agents (Anthracycline): Taxane Derivatives may enhance the adverse/toxic effect of Antineoplastic Agents (Anthracycline). Taxane Derivatives may increase the serum concentration of Antineoplastic Agents (Anthracycline). Taxane Derivatives may also increase the formation of toxic anthracycline metabolites in heart tissue. Risk D: Consider therapy modification
BCG: Immunosuppressants may diminish the therapeutic effect of BCG. Risk X: Avoid combination
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Management: Upon completion/discontinuation of conivaptan, allow at least 7 days before initiating therapy with drugs that are CYP3A4 substrates. Risk D: Consider therapy modification
CYP2C8 Inducers (Highly Effective): May increase the metabolism of CYP2C8 Substrates (High risk). Risk C: Monitor therapy
CYP2C8 Inhibitors (Moderate): May decrease the metabolism of CYP2C8 Substrates (High risk). Risk C: Monitor therapy
CYP2C8 Inhibitors (Strong): May decrease the metabolism of CYP2C8 Substrates (High risk). Risk D: Consider therapy modification
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Deferasirox: May increase the serum concentration of CYP2C8 Substrates (High risk). Risk C: Monitor therapy
Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Risk C: Monitor therapy
DOXOrubicin: Taxane Derivatives may decrease the metabolism of DOXOrubicin. Risk D: Consider therapy modification
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider therapy modification
Herbs (CYP3A4 Inducers): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Risk D: Consider therapy modification
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination
P-Glycoprotein Inducers: May decrease the serum concentration of P-Glycoprotein Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy
P-Glycoprotein Inhibitors: May increase the serum concentration of P-Glycoprotein Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy
Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination
Platinum Derivatives: May enhance the myelosuppressive effect of Taxane Derivatives. Administer Taxane derivative before Platinum derivative when given as sequential infusions to limit toxicity. Risk D: Consider therapy modification
Reverse Transcriptase Inhibitors (Non-Nucleoside): May decrease the metabolism of PACLitaxel. Risk C: Monitor therapy
Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Risk X: Avoid combination
Saxagliptin: CYP3A4 Inducers may decrease the serum concentration of Saxagliptin. Risk C: Monitor therapy
Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Risk C: Monitor therapy
SORAfenib: May enhance the adverse/toxic effect of PACLitaxel. Management: Concurrent sorafenib with carboplatin and paclitaxel in patients with squamous cell lung cancer is contraindicated. Use in other settings is not specifically contraindicated but should be approached with added caution. Risk X: Avoid combination
Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Trastuzumab: PACLitaxel may increase the serum concentration of Trastuzumab. Trastuzumab may decrease the serum concentration of PACLitaxel. Risk C: Monitor therapy
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Risk C: Monitor therapy
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Vaccinial infections may develop. Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Risk X: Avoid combination
Vinorelbine: PACLitaxel may enhance the neurotoxic effect of Vinorelbine. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Herb/Nutraceutical: Avoid black cohosh, dong quai in estrogen-dependent tumors. Avoid valerian, St John's wort (may decrease paclitaxel levels), kava kava, gotu kola (may increase CNS depression).
Storage
Store intact vials at room temperature of 20°C to 25°C (68°F to 77°F). Protect from light. Solutions in D5W and NS are stable for up to 3 days at room temperature (25°C).
Paclitaxel should be dispensed in either glass or non-PVC containers (eg, Excel™/PAB™). Use nonpolyvinyl (non-PVC) tubing (eg, polyethylene) to minimize leaching. Formulated in a vehicle known as Cremophor® EL (polyoxyethylated castor oil). Cremophor® EL has been found to leach the plasticizer DEHP from polyvinyl chloride infusion bags or administration sets. Contact of the undiluted concentrate with plasticized polyvinyl chloride (PVC) equipment or devices is not recommended.
Reconstitution
Dilute in 250-1000 mL D5W, D5LR, D5NS, or NS to a concentration of 0.3-1.2 mg/mL. Chemotherapy dispensing devices (eg, Chemo Dispensing Pin™) should not be used to withdraw paclitaxel from the vial.
Compatibility
Stable in D5W, D5LR, D5NS, NS.
Y-site administration: Compatible: Acyclovir, amikacin, aminophylline, ampicillin/sulbactam, bleomycin, butorphanol, calcium chloride, carboplatin, cefepime, cefotetan, ceftazidime, ceftriaxone, cimetidine, cisplatin, cladribine, cyclophosphamide, cytarabine, dacarbazine, dexamethasone sodium phosphate, diphenhydramine, doxorubicin, droperidol, etoposide, etoposide phosphate, famotidine, floxuridine, fluconazole, fluorouracil, furosemide, ganciclovir, gatifloxacin, gemcitabine, gentamicin, granisetron, haloperidol, heparin, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, hydromorphone, ifosfamide, linezolid, lorazepam, magnesium sulfate, mannitol, meperidine, mesna, methotrexate, metoclopramide, morphine, nalbuphine, ondansetron, ondansetron with ranitidine, pentostatin, potassium chloride, prochlorperazine edisylate, propofol, ranitidine, sodium bicarbonate, thiotepa, topotecan, vancomycin, vinblastine, vincristine, zidovudine. Incompatible: Amphotericin B, amphotericin B cholesteryl sulfate complex, chlorpromazine, doxorubicin liposome, hydroxyzine, methylprednisolone sodium succinate, mitoxantrone.
Compatibility when admixed: Compatible: Carboplatin, doxorubicin. Variable (consult detailed reference): Cisplatin.
Mechanism of Action
Paclitaxel promotes microtubule assembly by enhancing the action of tubulin dimers, stabilizing existing microtubules, and inhibiting their disassembly, interfering with the late G2 mitotic phase, and inhibiting cell replication. In addition, the drug can distort mitotic spindles, resulting in the breakage of chromosomes. Paclitaxel may also suppress cell proliferation and modulate immune response.
Pharmacodynamics/Kinetics
Distribution:
Vd: Widely distributed into body fluids and tissues; affected by dose and duration of infusion
Vdss:
1- to 6-hour infusion: 67.1 L/m2
24-hour infusion: 227-688 L/m2
Protein binding: 89% to 98%
Metabolism: Hepatic via CYP2C8 and 3A4; forms metabolites (primarily 6α-hydroxypaclitaxel)
Half-life elimination:
1- to 6-hour infusion: Mean (beta): 6.4 hours
3-hour infusion: Mean (terminal): 13.1-20.2 hours
24-hour infusion: Mean (terminal): 15.7-52.7 hours
Excretion: Feces (~70%, 5% as unchanged drug); urine (14%)
Clearance: Mean: Total body: After 1- and 6-hour infusions: 5.8-16.3 L/hour/m2; After 24-hour infusions: 14.2-17.2 L/hour/m2
Dosage
Premedication with dexamethasone (20 mg orally or I.V. at 12 and 6 hours or 14 and 7 hours before the dose; reduce dexamethasone dose to 10 mg orally with advanced HIV disease), diphenhydramine (50 mg I.V. 30-60 minutes prior to the dose), and cimetidine, famotidine, or ranitidine (I.V. 30-60 minutes prior to the dose) is recommended.
Adults: I.V.: Refer to individual protocols
Ovarian carcinoma: 135-175 mg/m2 over 3 hours every 3 weeks or
135 mg/m2 over 24 hours every 3 weeks or
50-80 mg/m2 over 1-3 hours weekly or
1.4-4 mg/m2/day continuous infusion for 14 days every 4 weeks
Metastatic breast cancer: 175-250 mg/m2 over 3 hours every 3 weeks or
50-80 mg/m2 weekly or
1.4-4 mg/m2/day continuous infusion for 14 days every 4 weeks
Nonsmall cell lung carcinoma: 135 mg/m2 over 24 hours every 3 weeks
AIDS-related Kaposi's sarcoma: 135 mg/m2 over 3 hours every 3 weeks or
100 mg/m2 over 3 hours every 2 weeks
Intraperitoneal (unlabeled route): Ovarian carcinoma: 60 mg/m2 on day 8 of a 21-day treatment cycle for 6 cycles, in combination with I.V. paclitaxel and intraperitoneal cisplatin. Note: Administration of intraperitoneal paclitaxel should include the standard paclitaxel premedication regimen.
Dosage modification for toxicity (solid tumors, including ovary, breast, and lung carcinoma): Courses of paclitaxel should not be repeated until the neutrophil count is ≥1500 cells/mm3 and the platelet count is ≥100,000 cells/mm3; reduce dosage by 20% for patients experiencing severe peripheral neuropathy or severe neutropenia (neutrophil <500 cells/mm3 for a week or longer)
Dosage modification for immunosuppression in advanced HIV disease: Paclitaxel should not be given to patients with HIV if the baseline or subsequent neutrophil count is <1000 cells/mm3. Additional modifications include: Reduce dosage of dexamethasone in premedication to 10 mg orally; reduce dosage by 20% in patients experiencing severe peripheral neuropathy or severe neutropenia (neutrophil <500 cells/mm3 for a week or longer); initiate concurrent hematopoietic growth factor (G-CSF) as clinically indicated
Dosage adjustment in renal impairment: There are no FDA-approved labeling guidelines for dosage adjustment in patients with renal impairment. Aronoff (2007) recommends no dosage adjustment necessary for adults with Clcr <50 mL/minute.
Dosage adjustment in hepatic impairment: Note: The FDA-approved labeling recommendations are based upon the patient's first course of therapy where the usual dose would be 135 mg/m2 dose over 24 hours or the 175 mg/m2 dose over 3 hours in patients with normal hepatic function. Dosage in subsequent courses should be based upon individual tolerance. Adjustments for other regimens are not available.
24-hour infusion:
Transaminases <2 times upper limit of normal (ULN) and bilirubin level ≤1.5 mg/dL: 135 mg/m2
Transaminases 2-<10 times ULN and bilirubin level ≤1.5 mg/dL: 100 mg/m2
Transaminases <10 times ULN and bilirubin level 1.6-7.5 mg/dL: 50 mg/m2
Transaminases ≥10 times ULN or bilirubin level >7.5 mg/dL: Avoid use
3-hour infusion:
Transaminases <10 times ULN and bilirubin level ≤1.25 times ULN: 175 mg/m2
Transaminases <10 times ULN and bilirubin level 1.26-2 times ULN: 135 mg/m2
Transaminases <10 times ULN and bilirubin level 2.01-5 times ULN: 90 mg/m2
Transaminases ≥10 times ULN or bilirubin level >5 times ULN: Avoid use
Dosage: Combination Regimens
Bladder cancer:
Paclitaxel-Carboplatin (Bladder Cancer)
Paclitaxel-Carboplatin-Gemcitabine
Paclitaxel-Gemcitabine
Breast cancer:
AC/Paclitaxel (Sequential)
AC-Paclitaxel-Trastuzumab
Gemcitabine-Paclitaxel (Breast Cancer)
ICE-T
Paclitaxel-Bevacizumab
Paclitaxel-Vinorelbine
Trastuzumab-Paclitaxel
Trastuzumab-Paclitaxel-Carboplatin
Trastuzumab-Paclitaxel (Weekly)
Cervical cancer:
Carboplatin-Paclitaxel (Cervical Cancer)
Cisplatin-Paclitaxel (Cervical Cancer)
Esophageal cancer:
Paclitaxel-Carboplatin (Esophageal Cancer)
Paclitaxel-Cisplatin (Esophageal Cancer)
Paclitaxel-Cisplatin-Fluorouracil (Esophageal Cancer)
Paclitaxel-Fluorouracil (Esophageal Cancer)
Head and neck cancer:
Cisplatin-Paclitaxel (Head and Neck Cancer)
Paclitaxel-Cetuximab
Lung cancer (nonsmall cell):
Carbo-Tax (NSCLC)
CaT (NSCLC)
Paclitaxel-Carboplatin-Bevacizumab
PC (NSCLC)
Ovarian cancer:
Carboplatin-Paclitaxel (Ovarian Cancer)
Cisplatin-Paclitaxel (Intraperitoneal Regimen)
Cisplatin-Paclitaxel (Ovarian Cancer)
Gemcitabine-Paclitaxel (Ovarian Cancer)
Prostate cancer:
Estramustine-Paclitaxel
Paclitaxel + Estramustine + Carboplatin
Paclitaxel + Estramustine + Etoposide
Sarcoma, soft tissue: ICE-T
Testicular cancer: Paclitaxel-Ifosfamide-Cisplatin
Unknown primary, adenocarcinoma:
Carboplatin-Paclitaxel (Unknown Primary)
Paclitaxel-Carboplatin-Etoposide (Unknown Primary)
Paclitaxel-Carboplatin-Gemcitabine (Unknown Primary)
Unknown primary, squamous cell: Paclitaxel-Cisplatin-Fluorouracil (Unknown Primary)
Administration: I.V.
Infuse over 1-96 hours. When administered as sequential infusions, taxane derivatives should be administered before platinum derivatives (cisplatin, carboplatin) to limit myelosuppression and to enhance efficacy.
Premedication with dexamethasone (20 mg orally or I.V. at 12 and 6 hours or 14 and 7 hours before the dose; reduce to 10 mg with advanced HIV disease), diphenhydramine (50 mg I.V. 30-60 minutes prior to the dose), and cimetidine 300 mg, famotidine 20 mg, or ranitidine 50 mg (I.V. 30-60 minutes prior to the dose) is recommended.
Administer I.V. infusion over 1-24 hours; infuse through a 0.22 micron in-line filter and nonsorbing administration set.
Administration: Other
Intraperitoneal: 1- to 2-hour infusion
Administration: I.V. Detail
pH: 4.4-5.6
Monitoring Parameters
CBC with differential; monitor for hypersensitivity reactions, vital signs (frequently during the first hour of infusion), continuous cardiac monitoring (patients with conduction abnormalities)
Reference Range
Mean maximum serum concentrations: 435-802 ng/mL following 24-hour infusions of 200-275 mg/m2 and were approximately 10% to 30% of those following 6-hour infusions of equivalent doses
Patient Education
This drug is only administered by intravenous infusion; you will be monitored closely during and following infusions. Immediately report burning, pain, or swelling at infusion site; unusual chest pain or tightness, rapid heartbeat, or palpitations; difficulty breathing; difficulty swallowing; or nausea or vomiting during infusion. You will be more susceptible to infection. It is important that you maintain adequate nutrition and fluid intake unless instructed to restrict fluid intake. May cause nausea, vomiting, sore mouth, loss of hair (will grow back after therapy), or diarrhea (if persistent, consult prescriber). Report chest pain, palpitations, or swelling of extremities; difficult breathing; pain or decreased sensation in extremities; unusual signs of weakness, fatigue, or lethargy; or persistent gastrointestinal disturbances.
Geriatric Considerations
Elderly patients may have a higher incidence of severe neuropathy, severe myelosuppression, or cardiovascular events as compared to younger patients.
Additional Information
Sensory neuropathy is almost universal at doses >250 mg/m2; motor neuropathy is uncommon at doses <250 mg/m2. Myopathic effects are common with doses >200 mg/m2, generally occur within 2-3 days of treatment, and resolve over 5-6 days. Intraperitoneal administration of paclitaxel is associated with a higher incidence of chemotherapy related toxicity.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Severe, potentially dose-limiting mucositis and stomatitis.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
None reported
Mental Health: Effects on Psychiatric Treatment
May cause neutropenia; use caution with clozapine and carbamazepine
Nursing: Physical Assessment/Monitoring
Paclitaxel (protein bound) is not interchangeable with paclitaxel (conventional). Assess patient carefully for cautious use indications and contraindications. Infusion site must be monitored closely to avoid extravasation. Monitor for hypersensitivity reaction, cardiovascular abnormalities, sensory neuropathy, myelosuppression, and GI irritation prior to, during, and between each infusion.
Oncology: Emetic Potential
Low (10% to 30%)
Oncology: Vesicant
May be an irritant
Oncology: Bone Marrow Comments
Glutamine may decrease mucositis
Oncology: Bone Marrow - High Dose
I.V.: 250-775 mg/m2; generally combined with other high-dose chemotherapy; maximum dose as single agent: 825 mg/m2
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution: 6 mg/mL (5 mL, 16.7 mL, 20 mL, 25 mL, 50 mL)
References
Armstrong DK, Bundy B, Wenzel L, et al, “Intraperitoneal Cisplatin and Paclitaxel in Ovarian Cancer,” N Engl J Med, 2006, 354(1):34-43.
Aronoff GR, Bennett WM, Berns JS, et al, Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children, 5th ed. Philadelphia, PA: American College of Physicians; 2007, p 101.
Baker AF and Dorr RT, “Drug Interactions With the Taxanes: Clinical Implications,” Cancer Treat Rev, 2001, 27(4):221-33.
Floyd JD, Nguyen DT, Lobins RL, et al, “Cardiotoxicity of Cancer Therapy,” J Clin Oncol, 2005, 23(30):7685-96.
Hesketh PJ, Kris MG, Grunberg SM, et al, “Proposal for Classifying the Acute Emetogenicity of Cancer Chemotherapy,” J Clin Oncol, 1997, 15(1):103-9.
Holmes FA, “Paclitaxel Combination Therapy in the Treatment of Metastatic Breast Cancer: A Review,” Semin Oncol, 1996, 23(5 Suppl 11):46-56.
Longnecker SM, Donehower RC, Cates AE, et al, “High-Performance Liquid Chromatographic Assay for Taxol in Human Plasma and Urine and Pharmacokinetics in a Phase I Trial,” Cancer Treat Rep, 1987, 71(1):53-9.
Mekhail TM and Markman M, “Paclitaxel in Cancer Therapy,” Expert Opin Pharmacother, 2002, 3(6):755-66.
Miller K, Wang M, Gralow J, et al, “Paclitaxel Plus Bevacizumab Versus Paclitaxel Alone for Metastatic Breast Cancer,” N Engl J Med, 2007, 357(26):2666-76.
Morgan C, Tillett T, Braybrooke J, et al, “Management of Uncommon Chemotherapy-Induced Emergencies,” Lancet Oncol, 2011 [epub ahead of print].
Rowinsky EK and Donehower RC, “Paclitaxel (Taxol),” N Engl J Med, 1995, 332(15):1004-14.
Rowinsky EK, “The Taxanes: Dosing and Scheduling Considerations,” Oncology, 1997, 11(3 Suppl 2):7-19.
Seetalarom K, Kudelka AP, Verschraegen CF, et al, “Taxanes in Ovarian Cancer Treatment,” Curr Opin Obstet Gynecol, 1997, 9(1):14-20.
Sonnichsen DS and Relling MV, “Clinical Pharmacokinetics of Paclitaxel,” Clin Pharmacokinet, 1994, 27(4):256-69.
Spencer CM and Faulds D, “Paclitaxel. A Review of Its Pharmacodynamic and Pharmacokinetic Properties and Therapeutic Potential in the Treatment of Cancer,” Drugs, 1994, 48(5):794-847.
International Brand Names
Lexi-Comp.com
Last full review/revision May 2011
Content last modified May 2011
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