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: Premedication with dexamethasone (20 mg orally at 12 and 6 hours prior to the dose [reduce dexamethasone dose to 10 mg orally with advanced HIV disease]), diphenhydramine (50 mg IV 30 to 60 minutes prior to the dose), and cimetidine or famotidine (IV 30 to 60 minutes prior to the dose) is recommended.
Anal cancer, advanced (off-label use): IV: 80 mg/m2 on days 1, 8, and 15 every 4 weeks (in combination with carboplatin) for 6 cycles or until disease progression or unacceptable toxicity (Rao 2020) or 175 mg/m2 once every 3 weeks (in combination with carboplatin) (Kim 2014).
B ladder cancer, advanced or metastatic (off-label use):
Paclitaxel/gemcitabine regimens: IV: 150 mg/m2 every 2 weeks (in combination with gemcitabine) (Sternberg 2001) or 200 mg/m2 over 1 hour every 3 weeks (in combination with gemcitabine) for 6 cycles (Meluch 2001) or 175 mg/m2 over 3 hours once every 3 weeks (in combination with gemcitabine) for a maximum of 6 cycles (Albers 2011).
Paclitaxel/gemcitabine/cisplatin (PGC) regimen: IV: 80 mg/m2 on days 1 and 8 every 3 weeks (in combination with gemcitabine and cisplatin; refer to protocol for administration sequence details) for up to 6 cycles or until disease progression or unacceptable toxicity (Bellmunt 2012).
Single-agent paclitaxel: IV: 80 mg/m2 over 1 hour once weekly until disease progression or unacceptable toxicity (Vaughn 2002).
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 (Mitin 2013).
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]) (Citron 2003).
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) (Romond 2005) 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) (Dang 2008).
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) (Swain 2017).
TH ( HER-2 positive): IV: 80 mg/m2 once weekly for 12 weeks (in combination with trastuzumab) (Tolaney 2015).
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 (Dang 2015) 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 (Miller 2007) or 175 mg/m2 over 3 hours on day 1 every 3 weeks (in combination with gemcitabine) until disease progression or unacceptable toxicity (Albain 2008).
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 (Tewari 2014; Tewari 2017) or 175 mg/m2 every 3 weeks (in combination with bevacizumab and topotecan) until disease progression or unacceptable toxicity (Tewari 2014; Tewari 2017) or 135 mg/m2 over 24 hours every 3 weeks (in combination with cisplatin) for 6 cycles (Monk 2009; Moore 2004) or 135 mg/m2 over 3 hours every 3 weeks on day 1 (in combination with carboplatin) until disease progression or unacceptable toxicity (Kitagawa 2015) 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 (Colombo 2021).
Endometrial cancer, advanced or recurrent (off-label use): IV: 175 mg/m2 (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 (Miller 2020) 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 (Pectasides 2008) 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 (Secord 2007) 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 (Fader 2018) 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 (Homesley 2008) or 175 mg/m2 over 3 hours on day 1 every 3 weeks for 10 cycles (Lissoni 1996).
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 (Petrasch 1998) 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 (El-Rayes 2004) 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 (Ilson 2007).
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 (van Hagen 2012; van Meerten 2006).
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 (Wilke 2014) 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 (Gadgeel 2003) or 80 mg/m2 on days 1, 8, and 15 every 28 days (as a single agent) until disease progression or unacceptable toxicity (Hironaka 2013).
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 (Gibson 2005) 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) (Grau 2009).
Kaposi sarcoma, AIDS related: 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.
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 (Flaherty 2013) or 100 mg/m2 on days 1, 8, and 15 every 4 weeks (in combination with carboplatin) until disease progression or unacceptable toxicity (Rao 2006).
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 for 4 cycles (in combination with pembrolizumab and carboplatin) followed by pembrolizumab maintenance therapy (Paz-Ares 2018) 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 (Socinski 2018) or 200 mg/m2 on day 1 every 3 weeks for 6 cycles (in combination with carboplatin and bevacizumab) followed by bevacizumab maintenance therapy (Sandler 2006) 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 (Ohe 2007).
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 (Armstrong 2006). 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 (Pignata 2014) 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) (Burger 2011) or 80 mg/m2 over 1 hour on days 1, 8, and 15 every 3 weeks (in combination with carboplatin) for 6 cycles (Clamp 2019).
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 (SGO/ASCO [Wright 2016]).
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 (Kehoe 2015; Vergot 2010) 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 (Fagotti 2016) 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 (Clamp 2019) 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 (Clamp 2019).
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 (Pagliaro 2010).
Small cell lung cancer, relapsed/refractory (off-label use): IV: 175 mg/m2 over 3 hours every 3 weeks (as a single agent) for up to 5 cycles (Smit 1998) or 80 mg/m2 over 1 hour weekly for 6 weeks of an 8-week treatment cycle (as a single agent) until disease progression or unacceptable toxicity (Yamamoto 2006).
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 (Penel 2008) or 135 to 175 mg/m2 over 3 hours every 3 weeks (as a single agent) (Schlemmer 2008) or 75 to 100 mg/m2 once weekly (as a single agent) (Schlemmer 2008).
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 (Bokemeyer 2008) 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 (Kondagunta 2005) 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 (Einhorn 2007).
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 (Lemma 2011).
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) (ATA [Smallridge 2012]).
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) (ATA [Smallridge 2012]).
Unknown primary adenocarcinoma (off-label use): IV: 200 mg/m2 over 3 hours every 3 weeks (in combination with carboplatin) for 6 to 8 cycles (Briasoulis 2000) or 200 mg/m2 over 1 hour every 3 weeks (in combination with carboplatin and etoposide) for 4 to 8 cycles (Greco 2000).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling. However, dosage adjustment is likely not necessary (Krens 2019). The following have been recommended:
Hemodialysis: Paclitaxel may be used in patients with cancer on hemodialysis (no dosage adjustment is necessary), and because paclitaxel is not dialyzable, it may be used either before or after hemodialysis (Janus 2010; Krens 2019).
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
Refer to adult dosing.
American Society of Clinical Oncology Guidelines for appropriate chemotherapy dosing in adults with cancer with a BMI ≥30 kg/m2 : Utilize patient's actual body weight (full weight) for calculation of BSA- or weight-based dosing, particularly when the intent of therapy is curative; 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 with subsequent cycles, if cause of toxicity (eg, hepatic or renal impairment) is clearly established and fully resolved (ASCO [Griggs 2021]).
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
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Concentrate, Intravenous:
Generic: 100 mg/16.67 mL (16.7 mL); 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); 30 mg/5 mL (5 mL); 300 mg/50 mL (50 mL)
Yes
Paclitaxel injection contains polyoxyl 35/olyoxyethylated castor oil (Cremophor EL)
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, 16.7 mL, 50 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 with dexamethasone (20 mg orally or IV at 12 and 6 hours before the dose; reduce to 10 mg with advanced HIV disease), diphenhydramine (50 mg IV 30 to 60 minutes prior to the dose), and cimetidine 300 mg or famotidine 20 mg (IV 30 to 60 minutes prior to the dose) is recommended.
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 (ESMO/EONS [Perez Fidalgo 2012]; Polovich 2009). Clinical experience suggests hyaluronidase may be used in the management of paclitaxel extravasations (ESMO/EONS [Perez Fidalgo 2012]; Stanford 2003); 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 (Ener 2004; ESMO/EONS [Perez Fidalgo 2012]).
Intraperitoneal (off-label route): Solution was prepared in warmed saline and infused as rapidly as possible through an implantable intraperitoneal catheter (Armstrong 2006).
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); 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.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Flushing (28%), ECG abnormality (14% to 23%), edema (21%), hypotension (4% to 12%)
Dermatologic: Alopecia (87%), skin rash (12%)
Gastrointestinal: Nausea and vomiting (52%), diarrhea (38%), stomatitis (17% to 31%; grade 3/4: ≤3%)
Hematologic & oncologic: Neutropenia (78% to 98%; grade 4: 14% to 75%; median nadir: 11 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%), hemorrhage (14%)
Hepatic: Increased serum alkaline phosphatase (22%), increased serum aspartate aminotransferase (19%)
Hypersensitivity: Hypersensitivity reaction (31% to 45%)
Infection: Infection (15% to 30%)
Local: Injection site reaction (13%)
Nervous system: Peripheral neuropathy (42% to 70%; grades 3/4: ≤7%)
Neuromuscular & skeletal: Arthralgia (≤60%), myalgia (≤60%), asthenia (17%)
Miscellaneous: Fever (12%)
1% to 10%:
Cardiovascular: Bradycardia (3%), tachycardia (2%), hypertension (1%), cardiac arrhythmia (≤1%), syncope (≤1%), venous thrombosis (≤1%)
Dermatologic: Changes in nails (2%)
Hematologic & oncologic: Febrile neutropenia (2%)
Hepatic: Increased serum bilirubin (7%)
Hypersensitivity: Anaphylaxis (≤4%), severe hypersensitivity reaction (≤4%)
Respiratory: Dyspnea (2%)
Frequency not defined:
Dermatologic: Skin discoloration at injection site
Gastrointestinal: Abdominal pain, peritonitis
Hypersensitivity: Angioedema
Infection: Sepsis
Local: Erythema at injection site, swelling at injection site, tenderness at injection site
Respiratory: Pneumonia
<1%, postmarketing, and/or case reports: Acute myocardial infarction, anorexia, ascites, ataxia, atrial fibrillation, atrioventricular block, back pain, bigeminy, cardiac conduction disorder, cardiac failure, cellulitis, chills, confusion, conjunctivitis, constipation, dehydration, desquamation, dizziness, encephalopathy, esophagitis, exacerbation of scleroderma, fibrosis at injection site, headache, hearing loss, hepatic encephalopathy, hepatic necrosis, increased lacrimation, increased serum creatinine, induration at injection site, intestinal obstruction, intestinal perforation, interstitial pneumonitis, ischemic colitis, local skin exfoliation, maculopapular rash, malaise, neutropenic enterocolitis, optic nerve damage, ototoxicity, pancreatitis, paralytic ileus, phlebitis, photopsia, pruritus, pulmonary embolism, pulmonary fibrosis, radiation recall phenomenon, radiation pneumonitis, respiratory failure, seizure, shock, skin edema (diffuse), skin necrosis, skin sclerosis, Stevens-Johnson syndrome, subacute cutaneous lupus erythematosus (Sibaud 2016), supraventricular tachycardia, thickening of skin, tinnitus, tonic clonic epilepsy, toxic epidermal necrolysis, ventricular tachycardia (asymptomatic), vertigo, visual disturbance (scintillating scotomata)
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:
• Bone marrow suppression: Paclitaxel should not be administered in patients with solid tumors who have baseline neutrophil counts of <1,500/mm3 or in patients with AIDS-related Kaposi sarcoma if the baseline neutrophil count is <1,000/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. Bone marrow suppression (usually neutropenia) is dose dependent and is the dose-limiting toxicity; neutrophil nadir is usually at a median of 11 days. Subsequent cycles should not be administered until neutrophils are >1,500/mm3 (for solid tumors) and 1,000/mm3 (for Kaposi sarcoma); platelets should recover to 100,000/mm3. Reduce future doses by 20% for severe neutropenia (<500/mm3 for 7 days or more) and consider the use of supportive therapy, including growth factor treatment.
• 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 continuous cardiac monitoring during subsequent infusions for these patients. 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.
• Hypersensitivity: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. Minor hypersensitivity reactions (flushing, skin reactions, dyspnea, hypotension, or tachycardia) do not require interruption of treatment.
• Peripheral neuropathy: Peripheral neuropathy may commonly occur; patients with preexisting neuropathies from prior 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 in patients with total bilirubin >2 times ULN); dose reductions are recommended.
Special populations:
• Elderly: 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.
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
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
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
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
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
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: In the US, after receipt of the single dose COVID-19 adenovirus vector vaccine (Janssen), administer an additional 2nd dose using an mRNA COVID-19 vaccine, at least 28 days after the primary vaccine dose, in patients taking immunosuppressive therapies. 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: Consider administration of a 3rd dose of COVID-19 vaccine, at least 28 days after completion of the primary 2-dose series, in patients 5 years of age and older taking immunosuppressive therapies. 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
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
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
Echinacea: May diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider avoiding echinacea in patients receiving therapeutic immunosuppressants, such cytotoxic chemotherapy. If combined, monitor for reduced efficacy of cytotoxic chemotherapy. Risk D: Consider therapy modification
Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy
Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
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
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
Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy
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-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. 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
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
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 post-exposure rabies vaccination is required during immunosuppressant therapy, administer a 5th dose of vaccine and check for rabies antibodies. Risk D: Consider therapy modification
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
Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of 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 Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
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
Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Vaccines (Inactivated). 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 neurotoxic effect of Vinorelbine. 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
Females of reproductive potential 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.
Concentrate (PACLitaxel Intravenous)
30 mg/5 mL (per mL): $2.23 - $5.64
100 mg/16.7 mL (per mL): $2.03 - $3.10
100MG/16.67ML (per mL): $4.46
150 mg/25 mL (per mL): $3.17
300 mg/50 mL (per mL): $0.99 - $3.10
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