Version May 2024
Paclitaxel should be administered 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.
Anaphylaxis and severe hypersensitivity reactions characterized by dyspnea and hypotension requiring treatment, angioedema, and generalized urticaria have occurred in 2% to 4% of patients receiving paclitaxel in clinical trials. Fatal reactions have occurred in patients despite premedication. All patients should be pretreated with corticosteroids, diphenhydramine, and histamine H2 antagonists. Patients who experience severe hypersensitivity reactions to paclitaxel should not be rechallenged with the drug.
Paclitaxel therapy should not be given to patients with solid tumors who have baseline neutrophil counts of less than 1,500 cells/mm3 or to patients with AIDS-related Kaposi sarcoma if the baseline neutrophil count is less than 1,000 cells/mm3. In order to monitor the occurrence of bone marrow suppression, primarily neutropenia, which may be severe and result in infection, it is recommended that frequent peripheral blood cell counts be performed on all patients receiving paclitaxel.
Note: The manufacturers recommend premedication with dexamethasone (20 mg orally at 12 and 6 hours prior to paclitaxel [reduce dexamethasone dose to 10 mg orally with advanced HIV disease]), diphenhydramine (50 mg IV 30 to 60 minutes prior to paclitaxel), and cimetidine or famotidine (IV 30 to 60 minutes prior to paclitaxel). Alternative premedication regimens have also been described. Refer to citations for further information.
Data from several reports support the use of a single 10 or 20 mg IV dexamethasone dose (in combination with diphenhydramine and an H2 antagonist) to prevent hypersensitivity reactions (HSR) in patients receiving paclitaxel (Ref).
Data from a prospective single-arm study and a retrospective analysis suggest dexamethasone may be omitted from future cycles of paclitaxel chemotherapy if no HSR occurred during the initial cycles; in the studies, patients received standard dexamethasone, diphenhydramine, and an H2 antagonist premedication prior to the first 2 paclitaxel doses, and if no HSR occurred during the first 2 infusions, dexamethasone was omitted from the premedication regimen for the remaining cycles (Ref). In another retrospective study, patients received the standard premedication regimen prior to the first 2 paclitaxel infusions; if no HSR occurred, all premedications were discontinued for future paclitaxel doses (Ref).
AIDS-related Kaposi sarcoma: IV: 135 mg/m2 over 3 hours every 3 weeks or 100 mg/m2 over 3 hours every 2 weeks (due to dose-related toxicity, the 100 mg/m2 dose should be used for patients with a lower performance status). Note: Reduce the dexamethasone premedication dose to 10 mg.
B ladder cancer, advanced or metastatic (off-label use):
Paclitaxel/gemcitabine regimens: IV: 150 mg/m2 every 2 weeks (in combination with gemcitabine) (Ref) or 200 mg/m2 over 1 hour every 3 weeks (in combination with gemcitabine) for 6 cycles (Ref) or 175 mg/m2 over 3 hours once every 3 weeks (in combination with gemcitabine) for a maximum of 6 cycles (Ref).
Paclitaxel/cisplatin/gemcitabine (PCG) regimen: IV: 80 mg/m2 on days 1 and 8 every 3 weeks (in combination with cisplatin and gemcitabine; refer to protocol for administration sequence details) for up to 6 cycles or until disease progression or unacceptable toxicity (Ref).
Single-agent paclitaxel: IV: 80 mg/m2 over 1 hour once weekly until disease progression or unacceptable toxicity (Ref).
Chemoradiation (muscle invasive bladder cancer):
Induction: IV: 50 mg/m2 on days 1, 8, and 15 (in combination with cisplatin and radiation), followed by consolidation chemoradiation (in patients who achieved a complete response) of 50 mg/m2 on days 1 and 8 (in combination with cisplatin and radiation).
Adjuvant chemotherapy (following chemoradiation and surgery): IV: 50 mg/m2 on days 1 and 8 (in combination with gemcitabine and cisplatin) every 3 weeks for 4 cycles. Refer to protocol for further details (Ref).
Breast cancer, adjuvant treatment: IV: 175 mg/m2 over 3 hours every 3 weeks for 4 cycles (administer sequentially following an anthracycline-containing regimen).
Off-label dosing/combinations:
AC-T (dose dense): IV: 175 mg/m2 every 2 weeks for 4 cycles (with growth factor support; following 4 cycles of dose-dense doxorubicin and cyclophosphamide [AC]) (Ref).
AC -TH (HER-2 positive): IV: 80 mg/m2 once weekly for 12 weeks or 175 mg/m2 every 3 weeks for 4 cycles (in combination with trastuzumab, following 4 cycles of AC) (Ref) or 175 mg/m2 every 2 weeks for 4 cycles (with growth factor support; in combination with trastuzumab, following 4 cycles of dose-dense AC) (Ref).
AC-THP (neoadjuvant therapy; HER-2 positive): IV: 80 mg/m2 once weekly for 12 weeks (in combination with pertuzumab and trastuzumab; following 4 cycles of dose-dense AC) (Ref).
TH ( HER-2 positive): IV: 80 mg/m2 once weekly for 12 weeks (in combination with trastuzumab) (Ref).
Keynote-522 regimen (early triple-negative breast cancer; neoadjuvant therapy): IV: 80 mg/m2 once weekly (in combination with carboplatin and pembrolizumab [first neoadjuvant therapy]) for 12 weeks, followed by second neoadjuvant therapy of pembrolizumab plus chemotherapy, followed by adjuvant pembrolizumab (Ref).
Breast cancer, metastatic or relapsed: IV: 175 mg/m2 over 3 hours every 3 weeks.
Off-label dosing/combinations: IV: 80 mg/m2 once weekly (in combination with trastuzumab and pertuzumab); if progression-free after 6 months, paclitaxel may be discontinued and trastuzumab and pertuzumab continued until disease progression or unacceptable toxicity (Ref) or 90 mg/m2 on days 1, 8, and 15 of a 28-day cycle (in combination with bevacizumab) until disease progression or unacceptable toxicity (Ref) or 175 mg/m2 over 3 hours on day 1 every 3 weeks (in combination with gemcitabine) until disease progression or unacceptable toxicity (Ref).
Cervical cancer, advanced (off-label use): IV: 135 or 175 mg/m2 every 3 weeks (in combination with bevacizumab and cisplatin) until disease progression or unacceptable toxicity (Ref) or 175 mg/m2 every 3 weeks (in combination with bevacizumab and topotecan) until disease progression or unacceptable toxicity (Ref) or 135 mg/m2 over 24 hours every 3 weeks (in combination with cisplatin) for 6 cycles (Ref) or 135 mg/m2 over 3 hours every 3 weeks on day 1 (in combination with carboplatin) until disease progression or unacceptable toxicity (Ref) or 175 mg/m2 on day 1 every 3 weeks (in combination with pembrolizumab and either cisplatin or carboplatin, ± bevacizumab) for 6 cycles; patients could continue chemotherapy beyond 6 cycles if experiencing clinical benefit without unacceptable toxicity; refer to protocol for further information (Ref).
Endometrial cancer, advanced or recurrent (off-label use): IV: 175 mg/m2 over 3 hours (135 mg/m2 in patients with a history of pelvic/spine irradiation) on day 1 every 3 weeks (in combination with carboplatin) for up to 7 cycles (Ref) or 175 mg/m2 over 3 hours on day 1 every 3 weeks (in combination with carboplatin and dostarlimab) for 6 cycles, followed by dostarlimab monotherapy until disease progression, unacceptable toxicity, or for up to 3 years (Ref) or 175 mg/m2 over 3 hours on day 1 every 3 weeks (in combination with carboplatin) for 6 to 9 cycles or until disease progression or unacceptable toxicity (Ref) or 80 mg/m2 over 1 hour on days 1, 8, and 15 every 28 days (in combination with carboplatin) until disease progression or unacceptable toxicity (Ref) or (for HER2-positive uterine serous cancer) 175 mg/m2 over 3 hours on day 1 every 3 weeks (in combination with carboplatin and trastuzumab) for ~6 cycles, followed by trastuzumab maintenance therapy (Ref) or 80 mg/m2 over 1 hour on days 1, 8, 15, and 22 every 28 days for at least 2 cycles and until disease progression or unacceptable toxicity (Ref) or 175 mg/m2 over 3 hours on day 1 every 3 weeks for 10 cycles (Ref).
Esophageal cancer, metastatic or unresectable locally advanced (off-label use): IV: 90 mg/m2 over 3 hours on day 1 every 14 days (in combination with cisplatin) until disease progression or unacceptable toxicity (Ref) or 200 mg/m2 (cycle 1; escalated to 225 mg/m2 in cycle 2 if acceptable ANC and platelets) over 3 hours on day 1 every 3 weeks (in combination with carboplatin) until best response (Ref) or 80 mg/m2 over 1 hour on days 1, 8, 15, and 22 every 28 days (as a single agent) until disease progression or unacceptable toxicity (Ref).
Esophageal/esophagogastric cancer, preoperative chemoradiation (off-label use): IV: 50 mg/m2 over 1 hour on days 1, 8, 15, 22, and 29 (in combination with carboplatin and radiation therapy) followed by surgery within 4 to 6 weeks (Ref).
Gastric cancer, metastatic or unresectable locally advanced (off-label use): IV: 80 mg/m2 on days 1, 8, and 15 every 28 days (in combination with ramucirumab) until disease progression or unacceptable toxicity (Ref) or 200 mg/m2 (cycle 1; escalated to 225 mg/m2 in cycle 2 if acceptable ANC and platelets) over 3 hours on day 1 every 3 weeks (in combination with carboplatin); evaluate for response every 2 cycles (Ref) or 80 mg/m2 on days 1, 8, and 15 every 28 days (as a single agent) until disease progression or unacceptable toxicity (Ref).
Gestational trophoblastic neoplasia, high-risk, refractory (off-label use): TP/TE regimen: IV: 135 mg/m2 over 3 hours on days 1 and 15 of a 28-day cycle (in combination with cisplatin and etoposide; TP [paclitaxel and cisplatin] alternates every 2 weeks with TE [paclitaxel and etoposide]); continue until hCG level is normal for at least 8 weeks, or until treatment resistance (plateaued or rising hCG) or unacceptable toxicity (Ref).
Head and neck cancers, advanced (off-label use): IV: 175 mg/m2 over 3 hours every 3 weeks (in combination with cisplatin) for at least 6 cycles (Ref) or 80 mg/m2 over 1 hour once weekly for 6 consecutive weeks, or until disease progression or unacceptable toxicity (if disease response or stabilization occurred) (Ref).
Melanoma, advanced or metastatic (alternative therapy) (off-label use): IV: 225 mg/m2 over 3 hours on day 1 every 3 weeks (in combination with carboplatin) for 4 cycles followed by (if dose not previously reduced) 175 mg/m2 over 3 hours on day 1 every 3 weeks (in combination with carboplatin) for up to 6 additional cycles (Ref) or 100 mg/m2 on days 1, 8, and 15 every 4 weeks (in combination with carboplatin) until disease progression or unacceptable toxicity (Ref).
Non–small cell lung cancer: IV: 135 mg/m2 over 24 hours every 3 weeks (in combination with cisplatin) or
Off-label dosing/combinations: IV: 200 mg/m2 on day 1 every 3 weeks (in combination with carboplatin and cemiplimab) for 4 cycles followed by cemiplimab until disease progression or unacceptable toxicity, or for up to 108 weeks; refer to protocol for further information (Ref) or 175 or 200 mg/m2 on day 1 every 3 weeks (in combination with carboplatin and nivolumab; neoadjuvant therapy) for up to 3 cycles; refer to protocol for further information, including histology details (Ref) or 200 mg/m2 on day 1 every 3 weeks (in combination with carboplatin, nivolumab, and ipilimumab; squamous histology) for 2 cycles; nivolumab/ipilimumab therapy continued until disease progression, unacceptable toxicity, or for up to 2 years in patients without disease progression (Ref) or 200 mg/m2 on day 1 every 3 weeks for 4 cycles (in combination with pembrolizumab and carboplatin) followed by pembrolizumab maintenance therapy (Ref) or 200 mg/m2 (175 mg/m2 for Asian patients) on day 1 every 3 weeks for 4 to 6 cycles (in combination with atezolizumab, bevacizumab [non-squamous non-small cell lung cancer], and carboplatin) followed by atezolizumab/bevacizumab maintenance therapy (Ref) or 200 mg/m2 on day 1 every 3 weeks for 6 cycles (in combination with carboplatin and bevacizumab) followed by bevacizumab maintenance therapy (Ref) or 200 mg/m2 over 3 hours on day 1 every 3 weeks (in combination with carboplatin) for at least 3 cycles and until disease progression or unacceptable toxicity (Ref).
Ovarian cancer, advanced:
Previously treated: IV: 135 or 175 mg/m2 over 3 hours every 3 weeks.
Previously untreated: IV: 175 mg/m2 over 3 hours every 3 weeks (in combination with cisplatin) or 135 mg/m2 over 24 hours administered every 3 weeks (in combination with cisplatin).
Previously untreated (off-label route): Intraperitoneal: 60 mg/m2 on day 8 of a 21-day treatment cycle for 6 cycles, in combination with IV paclitaxel (135 mg/m2 over 24 hours on day 1) and intraperitoneal cisplatin (Ref). Note: Administration of intraperitoneal paclitaxel should include the standard paclitaxel premedication regimen.
Previously untreated (off-label combinations): IV: 175 mg/m2 over 3 hours every 3 weeks (in combination with carboplatin) for 6 cycles, or 60 mg/m2 over 1 hour weekly (in combination with carboplatin) for 18 weeks (Ref) or 175 mg/m2 on day 1 every 3 weeks (in combination with bevacizumab [delayed until cycle 2] and carboplatin) for up to 6 cycles, followed by bevacizumab monotherapy for a total of up to 22 cycles or until disease progression (whichever occurs earlier) (Ref) or 80 mg/m2 over 1 hour on days 1, 8, and 15 every 3 weeks (in combination with carboplatin) for 6 cycles (Ref).
Neoadjuvant therapy (off-label combination/schedule): Note: According to guidelines from the Society of Gynecologic Oncology and American Society of Clinical Oncology for neoadjuvant chemotherapy in newly diagnosed advanced ovarian cancer, neoadjuvant therapy should be utilized only in properly selected patients. Selection criteria include patients with newly diagnosed suspected stage IIIC or IV ovarian cancer who have a high perioperative risk profile and/or a low likelihood of achieving cytoreduction to <1 cm of residual disease (Ref).
IV: 175 mg/m2 over 3 hours on day 1 every 3 weeks (in combination with carboplatin) for 3 neoadjuvant cycles, followed by debulking surgery, followed by 3 additional chemotherapy cycles (Ref) or 175 mg/m2 on day 1 every 3 weeks (in combination with carboplatin) for 3 to 4 neoadjuvant cycles, followed by debulking surgery, followed by 2 to 3 additional chemotherapy cycles, for a total of 6 cycles (Ref) or 175 mg/m2 over 3 hours on day 1 every 3 weeks (in combination with carboplatin) for a total of 6 cycles, with debulking surgery occurring after cycles 3 to 6 (Ref) or 80 mg/m2 over 1 hour on days 1, 8, and 15 every 3 weeks (in combination with carboplatin) for a total of 6 cycles, with debulking surgery occurring after cycles 3 to 6 (Ref).
Penile cancer, metastatic (off-label use): IV: 175 mg/m2 over 3 hours every 3 to 4 weeks (in combination with ifosfamide and cisplatin) for 4 cycles (Ref).
Soft tissue sarcoma, angiosarcoma, advanced/unresectable (off-label use): IV: 80 mg/m2 over 1 hour on days 1, 8, and 15 of a 4-week treatment cycle (as a single agent) for up to 6 cycles (Ref) or 135 to 175 mg/m2 over 3 hours every 3 weeks (as a single agent) (Ref) or 75 to 100 mg/m2 once weekly (as a single agent) (Ref).
Testicular germ cell tumors, relapsed/refractory (off-label use): IV: 80 mg/m2 over 1 hour on days 1 and 8 of a 3-week treatment cycle (in combination with gemcitabine and oxaliplatin) for 2 cycles beyond best response and up to a maximum of 8 cycles (Ref) or 250 mg/m2 over 24 hours on day 1 of a 3-week treatment cycle (in combination with ifosfamide, mesna, cisplatin, and filgrastim) for 4 cycles (Ref) or 100 mg/m2 over 1 hour on days 1, 8, and 15 of a 4-week treatment cycle (in combination with gemcitabine) for up to 6 cycles (Ref).
Thymoma/thymic carcinoma, advanced (off-label use): IV: 225 mg/m2 over 3 hours every 3 weeks (in combination with carboplatin) for up to 6 cycles (Ref).
Thyroid cancer, anaplastic (off-label use; based on limited data ):
Adjuvant or radiosensitizing therapy: IV: 30 to 60 mg/m2 once weekly as a single agent or 50 mg/m2 once weekly (in combination with carboplatin) (Ref).
Advanced or metastatic disease: IV: 60 to 90 mg/m2 once weekly as a single agent or 135 to 200 mg/m2 once every 3 to 4 weeks as a single agent or 60 to 100 mg/m2 once weekly (in combination with carboplatin) or 135 to 175 mg/m2 once every 3 to 4 weeks (in combination with carboplatin) (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Kenar D. Jhaveri, MD; Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: IV: No dosage adjustment likely to be necessary for any degree of kidney impairment (Ref).
Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2): Note: Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Young patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Ref).
IV: No dosage adjustment necessary (Ref).
Hemodialysis, intermittent (thrice weekly): Not significantly dialyzable (Ref): IV: No dosage adjustment or supplemental dose necessary (Ref).
Peritoneal dialysis: IV: No dosage adjustment necessary (Ref).
CRRT: IV: No dosage adjustment necessary (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): IV: No dosage adjustment necessary (Ref).
Note: The manufacturer's labeled dosage adjustment recommendations are based upon the patient's first course of therapy where the usual dose (in patients with normal hepatic function) would be 135 mg/m2 dose over 24 hours or the 175 mg/m2 dose over 3 hours. 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 to <10 times ULN and bilirubin level ≤1.5 mg/dL: 100 mg/m2
Transaminases <10 times ULN and bilirubin level 1.6 to 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 to 2 times ULN: 135 mg/m2
Transaminases <10 times ULN and bilirubin level 2.01 to 5 times ULN: 90 mg/m2
Transaminases ≥10 times ULN or bilirubin level >5 times ULN: Avoid use
American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2: Utilize patient's actual body weight for calculation of BSA- or weight-based dosing; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m2; if a dose reduction is utilized due to toxicity, may consider resumption of full, weight-based dosing (or previously tolerated dose level) with subsequent cycles only if dose escalations are allowed in the prescribing information, if contributing underlying factors (eg, hepatic or kidney impairment) are sufficiently resolved, AND if performance status has markedly improved or is considered adequate (Ref).
Refer to protocol and/or study reference for specific dosage adjustment details.
Dosage modification for toxicity (solid tumors, including ovary, breast, and lung carcinoma): Adjustment recommendations are based on the labeled doses (135 mg/m2 dose over 3 hours or 24 hours every 3 weeks or 175 mg/m2 dose over 3 hours every 3 weeks): Courses of paclitaxel should not be repeated until the neutrophil count is ≥1,500/mm3 and the platelet count is ≥100,000/mm3; reduce dosage by 20% for patients experiencing severe peripheral neuropathy or severe neutropenia (neutrophil <500/mm3 for a week or longer).
Dosage modification for immunosuppression in AIDS-related Kaposi sarcoma: Adjustment recommendations are based on the labeled doses (135 mg/m2 over 3 hours every 3 weeks or 100 mg/m2 over 3 hours every 2 weeks): Paclitaxel should not be given to patients with HIV if the baseline or subsequent neutrophil count is <1,000/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/mm3 for a week or longer); initiate concurrent hematopoietic growth factor (G-CSF) as clinically indicated.
Refer to adult dosing.
Neutropenia is the main dose-limiting hematologic toxicity of paclitaxel. Severe, grade 4 neutropenia and febrile neutropenia have been reported. Less frequently, paclitaxel may cause thrombocytopenia, and anemia but severe cases are rare. Neutrophil nadir is generally rapidly reversible (Ref).
Onset: Intermediate; neutrophil nadir typically occurs at a median of 11 days.
Risk factors:
• Higher doses
• Longer duration of infusion (Ref)
• Extent of prior cytotoxic chemotherapy (Ref)
Immediate, severe hypersensitivity reactions characterized by dyspnea and hypotension requiring treatment, angioedema, and generalized urticaria have occurred with paclitaxel. All grade hypersensitivity reactions occur in ~10% of premedicated patients. Fatal hypersensitivity reactions have been reported (Ref). Delayed hypersensitivity reactions are less common and include maculopapular rash, Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), and acute generalized exanthematous pustulosis (AGEP) (Ref).
Mechanism:
• Immediate hypersensitivity reactions: Non–dose-related, not schedule dependent. While patients may have direct immunologic response to paclitaxel itself, the hypersensitivity reactions are more often associated with the solubilizing agent, polyoxyl 35 castor oil (Cremophor EL, Kolliphor EL) (Ref). These reactions are likely due to complement activation or direct release of mast cell mediators such as histamine and tryptase, although may be IgE or IgG-mediated responses directed against the taxane moiety or Kolliphor EL (Ref).
• Delayed hypersensitivity reactions are T-cell mediated (Ref).
Onset:
• Immediate hypersensitivity reactions: Rapid; often occur within the first 30 minutes of infusion and rarely after the third course of paclitaxel (Ref).
• Delayed hypersensitivity reactions: Varied; may occur 48 hours to 1 week after paclitaxel (Ref). Delayed reactions may predispose patients to severe or fatal immediate hypersensitivity reactions with subsequent doses (Ref).
Risk factors:
• History of hypersensitivity to other drugs formulated in polyoxyl 35 castor oil (Cremophor EL, Kolliphor EL)
• History of hypersensitivity to other formulations of paclitaxel (such as nab-paclitaxel (Ref)
• Younger age (Ref)
• Obesity (BMI >25) (Ref)
Peripheral neuropathy, primarily a distal sensory neuropathy, may occur with paclitaxel. Neuropathy presents as a mixture of paresthesias and dysesthesias, including burning, numbness, tingling, and shooting pains, typically in a stocking-glove distribution (Ref). While severe symptoms are unusual, peripheral neuropathy often leads to subsequent dose reductions in many patients. Most mild to moderate cases resolve several months after discontinuation but may be longer in patients with diabetes. Severe neuropathy may be irreversible in some patients (Ref).
Mechanism: Dose and cumulative dose-related; Taxanes may either be directly toxic to nerve cells and/or aggregation of microtubules in neuronal cells may lead to neuropathies (Ref). The tips of the longest nerves are affected first, contributing to its distribution (Ref).
Onset: Delayed; onset is dose and cumulative dose-dependent (Ref).
Risk factors:
• Dose and cumulative dose
• Older patients (Ref)
• Patients with diabetes (with or without preexisting neuropathy) (Ref)
• Concurrent or sequential treatment with other neuropathy inducing chemotherapies (eg, platinums, vinca, proteosome inhibitors) (Ref)
• Obesity and low physical activity (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: ECG abnormality (14% to 23%), edema (21%; severe edema: 1%), hypotension (12%)
Dermatologic: Alopecia (87%)
Gastrointestinal: Diarrhea (38%), nausea and vomiting (52%), stomatitis (17% to 31%; grade 3/4: ≤3%)
Hematologic & oncologic: Anemia (47% to 90%; grades 3/4: 2% to 16%), hemorrhage (14%), leukopenia (90%; grade 4: 17%), neutropenia (78% to 98%; grade 4: 14% to 75%), thrombocytopenia (4% to 20%; grades 3/4: 1% to 7%)
Hepatic: Increased serum alkaline phosphatase (22%), increased serum aspartate aminotransferase (19%)
Hypersensitivity: Hypersensitivity reaction (31% to 45%; severe hypersensitivity reaction: ≤4%)
Infection: Infection (15% to 30%)
Local: Injection-site reaction (13%)
Nervous system: Asthenia (17%), peripheral neuropathy (42% to 70%; grades 3/4: ≤7%)
Neuromuscular & skeletal: Arthralgia (≤60%), myalgia (≤60%)
Miscellaneous: Fever (12%)
1% to 10%:
Cardiovascular: Bradycardia (3%), cardiac arrhythmia (≤1%; including bigeminy, complete atrioventricular block, ventricular tachycardia [asymptomatic]), hypertension (≤1%), syncope (≤1%), venous thrombosis (≤1%)
Dermatologic: Changes in nails (2%)
Hematologic & oncologic: Febrile neutropenia (2%)
Hepatic: Increased serum bilirubin (7%)
Hypersensitivity: Anaphylaxis (≤4%), angioedema (≤4%)
<1%: Nervous system: Ataxia, encephalopathy, tonic-clonic seizure
Frequency not defined:
Gastrointestinal: Peritonitis
Infection: Sepsis
Local: Erythema at injection site, skin discoloration at injection site, swelling at injection site, tenderness at injection site
Respiratory: Pneumonia
Postmarketing:
Cardiovascular: Acute myocardial infarction (Lodha 2021), atrial fibrillation (Arbuck 1993), pulmonary embolism, supraventricular tachycardia (Arbuck 1993)
Dermatologic: Acute generalized exanthematous pustulosis (Medeiros 2022), maculopapular rash (Picard 2015), pruritus, skin edema (diffuse), skin sclerosis, Stevens-Johnson syndrome (Hiraki 2004), thickening of skin, toxic epidermal necrolysis (Picard 2015)
Endocrine & metabolic: Dehydration
Gastrointestinal: Anorexia, constipation, esophagitis, intestinal obstruction, intestinal perforation, ischemic colitis, neutropenic enterocolitis, pancreatitis
Hepatic: Ascites, hepatic encephalopathy, hepatic necrosis
Local: Cellulitis at injection site, fibrosis at injection site, induration at injection site, injection-site phlebitis, local skin exfoliation (injection site), tissue necrosis at injection site
Nervous system: Autonomic neuropathy, confusion, dizziness, headache, malaise, seizure, vertigo
Neuromuscular & skeletal: Exacerbation of scleroderma, subacute cutaneous lupus erythematosus (Sibaud 2016)
Ophthalmic: Conjunctivitis, increased lacrimation, optic nerve damage, photopsia, visual disturbance (including scintillating scotomata and visual floaters)
Otic: Hearing loss, tinnitus
Renal: Increased serum creatinine
Respiratory: Interstitial pneumonitis, pleural effusion, pulmonary fibrosis, respiratory failure
Miscellaneous: Radiation recall phenomenon
Hypersensitivity to paclitaxel, polyoxyl 35/polyoxyethylated castor oil (Cremophor EL), or any component of the formulation; treatment of solid tumors in patients with baseline neutrophil counts <1,500/mm3; treatment of Kaposi sarcoma in patients with baseline neutrophil counts <1,000/mm3.
Concerns related to adverse effects:
• Cardiovascular effects: Infusion-related hypotension, bradycardia, and/or hypertension may occur. Rare but severe conduction abnormalities have been reported. In a scientific statement from the American Heart Association, conventional paclitaxel has been determined to be an agent that may either cause direct myocardial toxicity or exacerbate underlying myocardial dysfunction (magnitude: moderate) (AHA [Page 2016])
• Extravasation: Paclitaxel is an irritant with vesicant-like properties; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation. Injection-site reactions are generally mild (skin discoloration, tenderness, erythema, or swelling) and occur more commonly with an extended infusion duration (eg, 24 hours); injection-site reactions may be delayed (7 to 10 days). More severe reactions (phlebitis, cellulitis, skin exfoliation, necrosis, fibrosis, and induration) have also been reported. Recall skin reactions may occur despite administering through a different IV site.
Disease-related concerns:
• Hepatic impairment: Use with extreme caution in patients with hepatic dysfunction (myelotoxicity may be worsened in patients with total bilirubin >2 times ULN); dose reductions are recommended.
Special populations:
• Older adult: Use with caution in elderly patients due to increased risk of toxicity (severe neutropenia, neuropathy, and cardiovascular events).
Other warnings/precautions:
• Excipients: Conventional paclitaxel formulations contain polyoxyl 35/polyoxyethylated castor oil (Cremophor EL), which is associated with hypersensitivity reactions. Formulations also contain dehydrated alcohol which may cause adverse CNS effects.
• Intraperitoneal administration: Intraperitoneal administration of paclitaxel is associated with a higher incidence of chemotherapy- related toxicity (Armstrong 2006).
CNS toxicity has been reported in pediatric patients receiving high doses of paclitaxel (350 to 420 mg/m2 as a 3-hour infusion) possibly due to the ethanol contained in the formulation.
Paclitaxel injection contains polyoxyl 35/olyoxyethylated castor oil (Cremophor EL)
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Concentrate, Intravenous:
Generic: 100 mg/16.7 mL (16.7 mL); 30 mg/5 mL (5 mL); 150 mg/25 mL (25 mL); 300 mg/50 mL (50 mL)
Concentrate, Intravenous [preservative free]:
Generic: 100 mg/16.7 mL (16.7 mL [DSC]); 30 mg/5 mL (5 mL [DSC]); 300 mg/50 mL (50 mL [DSC])
Yes
Concentrate (PACLitaxel Intravenous)
30 mg/5 mL (per mL): $1.92 - $5.64
100 mg/16.7 mL (per mL): $1.22 - $4.46
150 mg/25 mL (per mL): $3.17
300 mg/50 mL (per mL): $0.91 - $3.56
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Concentrate, Intravenous:
Generic: 6 mg/mL (5 mL, 16.7 mL, 25 mL, 50 mL, 100 mL); 30 mg/5 mL (5 mL)
IV: Infuse over 3 or 24 hours (depending on indication/protocol); some off-label protocols use a 1-hour infusion. Infuse through a 0.22-micron in-line filter and polyethylene-lined (non-PVC) administration set. When administered as a part of a combination chemotherapy regimen, sequence of administration may vary by regimen; refer to specific protocol for sequence recommendation.
Premedication is recommended to prevent hypersensitivity reactions. Refer to "Dosing: Adult" for premedication regimen details.
Irritant with vesicant-like properties; avoid extravasation. Ensure proper needle or catheter position prior to administration.
Extravasation management: If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); remove needle/cannula; initiate antidote (hyaluronidase) if appropriate; remove needle/cannula; elevate extremity. Information conflicts regarding the use of warm or cold compresses (Ref). Clinical experience suggests hyaluronidase may be used in the management of paclitaxel extravasations (Ref); data is limited.
If using hyaluronidase: If needle/cannula still in place: Administer 1 to 6 mL (150 units/mL) into existing IV line; usual dose is 1 mL for each 1 mL of extravasated drug; if needle/cannula has been removed, inject subcutaneously in a clockwise manner around area of extravasation; may repeat several times over the next 3 to 4 hours (Ref).
Intraperitoneal (off-label route): Solution was prepared in warmed saline and infused as rapidly as possible through an implantable intraperitoneal catheter (Ref).
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Breast cancer: Adjuvant treatment of node-positive breast cancer (as sequential therapy following anthracycline-containing combination chemotherapy); treatment of metastatic breast cancer after failure of combination chemotherapy (for metastatic disease) or relapse within 6 months of adjuvant chemotherapy (prior therapy should have included an anthracycline unless contraindicated).
Kaposi sarcoma (AIDS-related): Second-line treatment of AIDS-related Kaposi sarcoma.
Non-small cell lung cancer: First-line treatment of non-small cell lung cancer (in combination with cisplatin) in patients who are not candidates for potentially curative surgery and/or radiation therapy.
Ovarian cancer: Subsequent therapy for treatment of advanced ovarian cancer; first-line therapy of ovarian cancer (in combination with cisplatin).
Anal cancer (advanced); Bladder cancer, advanced or metastatic; Cervical cancer, advanced; Endometrial cancer, advanced or recurrent; Esophageal cancer (metastatic or unresectable locally advanced); Esophageal/esophagogastric cancer, preoperative chemoradiation; Gastric cancer (metastatic or unresectable locally advanced); Gestational trophoblastic neoplasia, high-risk, refractory; Head and neck cancers, advanced; Melanoma (advanced or metastatic); Penile cancer, metastatic; Small cell lung cancer, relapsed/refractory; Soft tissue sarcoma (angiosarcoma), advanced/unresectable; Testicular germ cell tumors, relapsed/refractory; Thymoma/thymic carcinoma, advanced; Thyroid cancer (anaplastic); Unknown primary adenocarcinoma
PACLitaxel may be confused with cabazitaxel, DOCEtaxel, PARoxetine, Paxil
PACLitaxel (conventional) may be confused with PACLitaxel (protein-bound)
Taxol may be confused with Abraxane, Paxil, Taxotere
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
Substrate of CYP2C8 (major), CYP3A4 (major), OATP1B1/1B3 (SLCO1B1/1B3), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification
Amisulpride (Oral): May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Anthracyclines: Taxane Derivatives may enhance the adverse/toxic effect of Anthracyclines. Taxane Derivatives may increase the serum concentration of Anthracyclines. Taxane Derivatives may also increase the formation of toxic anthracycline metabolites in heart tissue. Management: Consider separating doxorubicin and paclitaxel administration by as much time as possible, using liposomal doxorubicin or epirubicin instead of doxorubicin, or using docetaxel instead of paclitaxel. Monitor closely for cardiovascular and other toxicities. Risk D: Consider therapy modification
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy
Antithymocyte Globulin (Equine): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of cytotoxic chemotherapy is reduced. Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy
Arginine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Atazanavir: May increase the serum concentration of PACLitaxel (Conventional). Management: Use of paclitaxel or other narrow therapeutic index CYP2C8 substrates with atazanavir without concurrent ritonavir is not recommended. If paclitaxel is used with ritonavir-boosted atazanavir, monitor for increased paclitaxel exposure. Risk X: Avoid combination
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Bexarotene (Systemic): PACLitaxel (Conventional) may increase the serum concentration of Bexarotene (Systemic). Bexarotene (Systemic) may decrease the serum concentration of PACLitaxel (Conventional). Risk C: Monitor therapy
Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination
Chikungunya Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing cytotoxic chemotherapy several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy
CYP2C8 Inhibitors (Moderate): May increase the serum concentration of PACLitaxel (Conventional). Risk C: Monitor therapy
CYP2C8 Inhibitors (Strong): May increase the serum concentration of PACLitaxel (Conventional). Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of PACLitaxel (Conventional). Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of PACLitaxel (Conventional). Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of PACLitaxel (Conventional). Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of PACLitaxel (Conventional). Risk C: Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and cytotoxic chemotherapy. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification
Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
DOXOrubicin (Conventional): PACLitaxel (Conventional) may increase the serum concentration of DOXOrubicin (Conventional). Management: Administer doxorubicin prior to paclitaxel if these agents are used in combination. Monitor cardiac function if combined. Risk D: Consider therapy modification
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy
Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating chemotherapy if possible. If vaccination occurs less than 2 weeks prior to or during chemotherapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as cytotoxic chemotherapy. Risk D: Consider therapy modification
Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification
Levodopa-Foslevodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Foslevodopa. Risk C: Monitor therapy
Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Lumacaftor and Ivacaftor: May decrease the serum concentration of CYP2C8 Substrates (High Risk with Inhibitors or Inducers). Lumacaftor and Ivacaftor may increase the serum concentration of CYP2C8 Substrates (High Risk with Inhibitors or Inducers). Risk C: Monitor therapy
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Nadofaragene Firadenovec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy
Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification
Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy
Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D: Consider therapy modification
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). 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. Management: Administer paclitaxel before cisplatin, when given as sequential infusions, to limit toxicity. Problems associated with other taxane/platinum combinations are possible, although unsubstantiated. Administering the taxane before platinum is likely warranted Risk D: Consider therapy modification
Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification
Ritlecitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Silodosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants, such as cytotoxic chemotherapy, prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
SORAfenib: May enhance the adverse/toxic effect of PACLitaxel (Conventional). 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
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Ublituximab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy
Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of chemotherapy when possible. Patients vaccinated less than 14 days before initiating or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Vinorelbine: PACLitaxel (Conventional) may enhance the adverse/toxic effect of Vinorelbine. Specifically hematologic toxicity may be increased. PACLitaxel (Conventional) may enhance the neurotoxic effect of Vinorelbine. Risk C: Monitor therapy
Warfarin: PACLitaxel (Conventional) may enhance the anticoagulant effect of Warfarin. Risk C: Monitor therapy
Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Patients should be advised to avoid becoming pregnant.
Paclitaxel crosses the placenta (Berveiller 2012; Berveiller 2019). In one case, paclitaxel was detected in cord blood 7 days after the last maternal dose. Paclitaxel was not detected in cord blood when delivery occurred 21 days after the last maternal dose in a second case (Berveiller 2019).
Due to pregnancy-induced physiologic changes, some pharmacokinetic properties of paclitaxel may be altered during pregnancy (Van Calsteren 2010; van Hasselt 2014).
Use of paclitaxel may be appropriate for the treatment of breast cancer and some gynecologic cancers during pregnancy (Amant 2019; Korenaga 2020; Loibl 2015; Shachar 2017). The European Society for Medical Oncology has published guidelines for diagnosis, treatment, and follow-up of cancer during pregnancy; the guidelines recommend referral to a facility with expertise in cancer during pregnancy and encourage a multidisciplinary team (obstetrician, neonatologist, oncology team). In general, if chemotherapy is indicated, it should be avoided in the first trimester and there should be a 3-week time period between the last chemotherapy dose and anticipated delivery, and chemotherapy should not be administered beyond week 33 of gestation. Close monitoring is recommended (ESMO [Peccatori 2013]).
A long-term observational research study is collecting information about the diagnosis and treatment of cancer during pregnancy. For additional information about the pregnancy and cancer registry or to become a participant, contact Cooper Health (1-877-635-4499).
Paclitaxel is present in breast milk.
Information is available from a mother (3 months' postpartum) treated with paclitaxel 30 mg/m2 (56.1 mg) and carboplatin once weekly for papillary thyroid cancer. Milk samples were obtained 4 to 316 hours after the infusion given at the sixth and final week of therapy. The average paclitaxel milk concentration over the testing interval was 0.78 mg/L. Although maternal serum concentrations were not noted in the report, the relative infant dose (RID) to a breastfeeding infant was calculated to be ~17% of the maternal dose. Paclitaxel continued to be detected in breast milk when sampled at 172 hours after the dose and was below the limit of detection (0.08 mg/L) when sampled at 316 hours after the infusion (Griffin 2012). In a second case report, breast milk was sampled over 15 days following the ninth weekly dose of paclitaxel 80 mg/m2 for the treatment of breast cancer, first diagnosed during pregnancy. Peak breast milk concentrations (0.1114 mg/L) occurred 2.75 hours after the maternal dose and were below the limit of quantification (<0.0025 mg/L) at 71.25 hours. Authors of this study calculated the RID of paclitaxel 72 hours after the maternal dose to be <1%, based on actual maternal weight (Jackson 2019).
Due to the potential for serious adverse reactions in a breastfeeding infant, breastfeeding is not recommended by the manufacturer. Avoidance of breastfeeding for 6 to 10 days after the last paclitaxel dose, based on the serum half-life, has been suggested (ABM [Johnson 2020]).
CBC with differential and platelet count (frequently), liver and kidney function. Monitor for hypersensitivity reactions, vital signs (frequently during the first hour of infusion), continuous cardiac monitoring (patients with conduction abnormalities). Monitor for signs/symptoms of peripheral neuropathy. Monitor infusion site during infusion.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
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.
Vdss: 24-hour infusion: 227 to 688 L/m2; biphasic with initial rapid distribution to the peripheral compartment; later phase is a slow efflux of paclitaxel from the peripheral compartment; widely distributed into body fluids and tissues; affected by dose and duration of infusion
Protein binding: 89% to 98%
Metabolism: Hepatic via CYP2C8 and 3A4; forms metabolites (primarily 6α-hydroxypaclitaxel)
Half-life elimination:
Children: 4.6 to 17 hours (varies with dose and infusion duration)
Adults:
3-hour infusion: Mean (terminal): ~13 to 20 hours
24-hour infusion: Mean (terminal): ~16 to 53 hours
Excretion: Feces (~71%; ~5% as unchanged drug); urine (~14%)
Hepatic function impairment: Plasma paclitaxel exposure is increased.
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