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Paclitaxel

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Aug.05.2021

Paclitaxel

Indications/Dosage

Labeled

  • breast cancer
  • Kaposi's sarcoma
  • non-small cell lung cancer (NSCLC)
  • ovarian cancer

Off-Label

  • bladder cancer
  • endometrial cancer
  • esophageal cancer
  • head and neck cancer
  • penile cancer
  • peripheral blood stem cell (PBSC) mobilization
  • small cell lung cancer (SCLC)
  • thymic carcinoma
  • thymoma
† Off-label indication

For the treatment of breast cancer

for the neoadjuvant treatment of HER2-positive breast cancer in combination with trastuzumab, after completion of 4 cycles of 5-fluorouracil (5-FU) and cyclophosphamide (FEC-75)†

Intravenous dosage

Adults

80 mg/m2 IV once weekly in combination with trastuzumab (4 mg/kg IV over 90 minutes on week 1, then 2 mg/kg IV over 30 minutes once weekly), every 21 days for 4 cycles (12 weeks). Administer after completion of 4 cycles of cyclophosphamide 500 mg/m2 IV, epirubicin (75 mg/m2 IV), and 5-FU (500 mg/m2 IV) on day 1, every 21 days for 4 cycles (FEC-75).[63560] [63561] Epirubicin dose adjustments for subsequent cycles are recommended by the manufacturer based on nadir platelet counts, ANC, or grade 3 to 4 toxicity.[41751] Surgery should be performed after completion of paclitaxel plus trastuzumab therapy, followed by trastuzumab 6 mg/kg IV every 3 weeks for a total of 52 weeks from the first preoperative dose. In a randomized, phase 3 clinical trial, neoadjuvant treatment with FEC-75 followed by paclitaxel plus trastuzumab (sequential therapy) resulted in similar rates of pathologic complete response (pCR), disease-free survival (DFS), and overall survival (OS) compared with paclitaxel plus trastuzumab followed by FEC-75 plus trastuzumab (concurrent therapy). Sequential therapy was better tolerated and had a lower incidence of cardiac adverse reactions.[63560] [63561]

for the neoadjuvant treatment of high-risk, early-stage hormone receptor (HR)-negative, HER2-negative (triple-negative) breast cancer, in combination with carboplatin and pembrolizumab, followed by pembrolizumab/cyclophosphamide/doxorubicin†

Intravenous dosage

Adults

80 mg/m2 IV once weekly for 12 weeks in combination with carboplatin (AUC 5 IV on day 1 every 3 weeks for 4 cycles) and pembrolizumab (200 mg IV every 3 weeks OR 400 mg IV every 6 weeks); administer pembrolizumab prior to chemotherapy when given on the same day. Alternatively, carboplatin may be dosed once weekly at an AUC of 1.5 IV for 12 weeks. To prevent hypersensitivity reactions, all patients should be premedicated with dexamethasone 20 mg PO approximately 12 and 6 hours before paclitaxel, diphenhydramine (or equivalent) 50 mg IV 30 to 60 minutes before paclitaxel, and an IV H2-blocker 30 to 60 minutes before paclitaxel. After completion of 12 weeks of paclitaxel/carboplatin/pembrolizumab, continue neoadjuvant therapy with 4 cycles of doxorubicin (60 mg/m2 IV every 3 weeks) plus cyclophosphamide (600 mg/m2 IV every 3 weeks) and pembrolizumab (200 mg IV every 3 weeks OR 400 mg IV every 6 weeks), followed by surgery; administer pembrolizumab prior to chemotherapy when given on the same day. After surgery, administer pembrolizumab 200 mg IV every 3 weeks for up to 9 doses OR 400 mg IV every 6 weeks for up to 5 doses or until disease progression or unacceptable toxicity. Do not administer adjuvant pembrolizumab monotherapy to patients with disease progression or unacceptable toxicity related to neoadjuvant treatment with pembrolizumab plus chemotherapy. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Patients with high-risk (tumor size more than 1 cm but up to and including 2 cm in diameter with nodal involvement; or tumor size more than 2 cm in diameter regardless of nodal involvement), early stage triple-negative breast cancer were randomized to neoadjuvant treatment with pembrolizumab or placebo in combination with carboplatin and paclitaxel, followed by anthracycline and cyclophosphamide in a phase 3 clinical trial (KEYNOTE-522); after definitive surgery, patients received adjuvant pembrolizumab or placebo. Treatment with pembrolizumab plus chemotherapy significantly improved the rate of pathologic complete response (pCR) (63% vs. 55.6%) compared with placebo plus chemotherapy. The median event-free survival (EFS) was not reached in either arm, although EFS at 18 months was 91.3% in patients who received pembrolizumab compared with 85.3% in those who received placebo (HR 0.63; 95% CI, 0.43 to 0.93); overall survival results are immature.[66036] [57889]

for the neoadjuvant treatment of high-risk, early-stage hormone receptor (HR)-negative, HER2-negative (triple-negative) breast cancer, in combination with carboplatin and pembrolizumab, followed by pembrolizumab/cyclophosphamide/epirubicin†

Intravenous dosage

Adults

80 mg/m2 IV once weekly for 12 weeks in combination with carboplatin (AUC 5 IV on day 1 every 3 weeks for 4 cycles) and pembrolizumab (200 mg IV every 3 weeks OR 400 mg IV every 6 weeks); administer pembrolizumab prior to chemotherapy when given on the same day. Alternatively, carboplatin may be dosed once weekly at an AUC of 1.5 IV for 12 weeks. To prevent hypersensitivity reactions, all patients should be premedicated with dexamethasone 20 mg PO approximately 12 and 6 hours before paclitaxel, diphenhydramine (or equivalent) 50 mg IV 30 to 60 minutes before paclitaxel, and an IV H2-blocker 30 to 60 minutes before paclitaxel. After completion of 12 weeks of paclitaxel/carboplatin/pembrolizumab, continue neoadjuvant therapy with 4 cycles of epirubicin (90 mg/m2 IV every 3 weeks) plus cyclophosphamide (600 mg/m2 IV every 3 weeks) and pembrolizumab (200 mg IV every 3 weeks OR 400 mg IV every 6 weeks), followed by surgery; administer pembrolizumab prior to chemotherapy when given on the same day. After surgery, administer pembrolizumab 200 mg IV every 3 weeks for up to 9 doses OR 400 mg IV every 6 weeks for up to 5 doses or until disease progression or unacceptable toxicity. Do not administer adjuvant pembrolizumab monotherapy to patients with disease progression or unacceptable toxicity related to neoadjuvant treatment with pembrolizumab plus chemotherapy. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Patients with high-risk (tumor size more than 1 cm but up to and including 2 cm in diameter with nodal involvement; or tumor size more than 2 cm in diameter regardless of nodal involvement), early stage triple-negative breast cancer were randomized to neoadjuvant treatment with pembrolizumab or placebo in combination with carboplatin and paclitaxel, followed by anthracycline and cyclophosphamide in a phase 3 clinical trial (KEYNOTE-522); after definitive surgery, patients received adjuvant pembrolizumab or placebo. Treatment with pembrolizumab plus chemotherapy significantly improved the rate of pathologic complete response (pCR) (63% vs. 55.6%) compared with placebo plus chemotherapy. The median event-free survival (EFS) was not reached in either arm, although EFS at 18 months was 91.3% in patients who received pembrolizumab compared with 85.3% in those who received placebo (HR 0.63; 95% CI, 0.43 to 0.93); overall survival results are immature.[66036]

for adjuvant treatment of node-positive breast cancer administered sequentially to standard doxorubicin-containing combination chemotherapy

Intravenous dosage

Adults

175 mg/m2 IV over 3 hours every 3 weeks for 4 courses following completion of standard doxorubicin-based combination chemotherapy. In a study completed by the Cancer and Leukemia Group B (CALGB) Cooperative Research Group, the addition of sequential paclitaxel following standard combination chemotherapy with doxorubicin and cyclophosphamide reduced mortality by 26% and reduced the risk of recurrent breast cancer by 22% as compared to the combination alone.[29200] Alternately, paclitaxel 80 mg/m2 IV over 1 hour weekly for 12 weeks† significantly improved overall survival compared to every 3 week dosing in a phase 3 trial.[40586] Additionally, doxorubicin-based chemotherapy and sequential paclitaxel 175 mg/m2 IV have been administered every 14 days (dose-dense) for 4 courses.[47481] In patients with HER2-positive breast cancer, trastuzumab should be given in combination with paclitaxel.[28061]

for first line treatment of metastatic breast cancer that overexpresses the HER2 protein in combination with trastuzumab

Intravenous dosage

Adults

175 mg/m2 IV over 3 hours every 3 weeks in combination with trastuzumab (4 mg/kg IV then 2 mg/kg IV weekly).

for the front-line treatment of HER2-overexpressing metastatic breast cancer in combination with carboplatin and trastuzumab†

Intravenous dosage

Adults

175 mg/m2 IV in combination with carboplatin (AUC 6 IV) beginning in week 1 and repeated every 3 weeks for 6 cycles; alternatively, paclitaxel 80 mg/m2 IV and carboplatin (AUC 2 IV) may be administered weekly for 3 weeks with a 1 week rest to complete six 4-week cycles. Give either regimen with trastuzumab (4 mg/kg IV infused over 90 minutes in week 1, then 2 mg/kg IV infused over 30 minutes weekly starting in week 2); continue trastuzumab until disease progression or unacceptable toxicity. A phase 3 trial of 196 patients with previously untreated HER2-overexpressing metastatic breast cancer examined trastuzumab and paclitaxel with or without carboplatin. The primary end point, overall response rate, was significantly increased with the addition of carboplatin (52% vs. 36%). Progression-free survival was also superior in the carboplatin arm (10.7 months vs. 7.1 months). Grade 4 neutropenia (36% vs. 12%) and grade 3 thrombocytopenia (9% vs. 1%) occurred more frequently in the carboplatin arm.[34295] A comparison of 2 parallel phase 2 studies revealed an increase in overall response rate, median time to disease progression, and overall survival with weekly administration of carboplatin/paclitaxel versus every-3-week administration.[34296]

for the treatment of locally recurrent unresectable or metastatic, PD-L1 positive (CPS 10 or more), triple negative breast cancer (TNBC), in combination with pembrolizumab†

Intravenous dosage

Adults

90 mg/m2 on days 1, 8, and 15, every 28 days in combination with pembrolizumab (200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks until disease progression or up to 24 months in patients without progression); the number of cycles of paclitaxel was not specified.[66122] [66123] [57889] Administer pembrolizumab prior to chemotherapy when given on the same day. To prevent hypersensitivity reactions, all patients should be premedicated with dexamethasone 20 mg PO approximately 12 and 6 hours before paclitaxel, diphenhydramine 50 mg IV (or equivalent) 30 to 60 minutes before paclitaxel, and an IV H2-blocker 30 to 60 minutes before paclitaxel. In a multicenter, double-blind clinical trial (KEYNOTE-355), patients with locally recurrent unresectable or metastatic TNBC who had not been previously treated with chemotherapy in the metastatic setting were randomized to treatment with either pembrolizumab or placebo in combination with paclitaxel, nab-paclitaxel, or gemcitabine plus carboplatin regardless of tumor PD-L1 expression. The addition of pembrolizumab to chemotherapy significantly improved the median progression-free survival (9.7 months vs. 5.6 months) compared with placebo plus chemotherapy in the subgroup of patients with a CPS of 10 or more. The objective response rate was 53% compared with 40%, respectively (complete response, 17% vs. 13%) for a median duration of 19.3 months in the pembrolizumab arm and 7.3 months in the placebo arm.[57889] [66123]

for the first line treatment of metastatic breast cancer in combination with carboplatin†

Intravenous dosage

Adults

175 mg/m2 IV over 3 hours on day 1 in combination with carboplatin AUC 6 IV on day 1, every 3 weeks for 6 cycles has been studied.[50012] [50011]

for patients who have not previously received chemotherapy for metastatic HER2-negative breast cancer, in combination with bevacizumab†

Intravenous dosage

Adults

90 mg/m2 IV on days 1, 8, and 15 plus bevacizumab (10 mg/kg IV on days 1 and 15) given every 28 days has been studied. Treatment was continued until disease progression or unacceptable toxicity. Bevacizumab monotherapy could be continued at the discretion of the clinician, if unacceptable toxicity to paclitaxel developed while on combination treatment. In a phase III clinical trial of 722 patients with previously untreated metastatic breast cancer, paclitaxel was administered with or without bevacizumab. The primary end point, progression-free survival, was significantly improved in the bevacizumab/paclitaxel arm (11.8 months vs. 5.9 months), as was objective response rate (36.9% vs. 21.2%). However, overall survival was not significantly different between the treatment arms (26.7 months vs. 25.2 months). Grade 3 and 4 hypertension (14.8% vs. 0%), proteinuria (3.5% vs. 0%), neuropathy (23.6% vs. 17.6%), infection (9.3% vs. 2.9%), headaches (2.2% vs. 0%), fatigue (8.5% vs. 4.9%), and cerebrovascular ischemia (1.9% vs. 0%) all occurred significantly more frequently in the combination arm. Median duration of paclitaxel treatment in the combination arm was 7.1 months vs. 5.1 months in the paclitaxel alone arm. Of patients in the combination arm, 21.3% continued bevacizumab monotherapy for a median of 3.7 months after discontinuation of paclitaxel.[33131]

for metastatic breast cancer after the failure of combination chemotherapy or relapse within 6 months of adjuvant chemotherapy

Intravenous dosage

Adults

175 mg/m2 IV over 3 hours every 3 weeks.[29200] Doses of 135 mg/m2 to 175 mg/m2 IV over 3 hours, up to 250 mg/m2 IV over 24 hours, or 120 mg/m2 to 140 mg/m2 continuous IV for 96 hours (20 mg/m2 per day to 35 mg/m2 per day for 5 days continuous IV infusion) once every 3 weeks and 80 mg/m2 to 100 mg/m2 IV over 1 hour weekly have been studied in patients with metastatic disease.

NOTE: Paclitaxel has been designated an orphan drug by the FDA for this indication.

Intravenous dosage

Adults

135 mg/m2 IV infused over 3 hours once every 3 weeks or 100 mg/m2 IV over 3 hours every 2 weeks (dose intensity 45—50 mg/m2/week). In trials evaluating these schedules, the every 3-week regimen was more toxic than the other. In addition, all patients with low performance status were treated with the every 2-week schedule. Initiate or repeat paclitaxel treatment only if the absolute neutrophil count (ANC) is 1000/mm3 or higher. Reduce subsequent courses of paclitaxel by 20% for patients who experience severe neutropenia (ANC less than 500/mm3) for a week or longer; hematopoietic growth factor support may be required. Doses of 175 mg/m2 IV over 3 hours once every 3 weeks have been used. In a study of patients with treatment-resistant AIDS-related Kaposi's sarcoma, paclitaxel 100 mg/m2 IV over 3 hours every 2 weeks lead to a 59% overall response rate. As these patients had received extensive prior chemotherapy, G-CSF was required in 55% of paclitaxel cycles.[25765]

For the treatment of non-small cell lung cancer (NSCLC)

for first-line treatment of NSCLC, in combination with cisplatin, in patients who are not candidates for potentially curative surgery and/or radiation therapy

Intravenous dosage

Adults

135 mg/m2 IV over 24 hours on day 1, followed by cisplatin 75 mg/m2 IV, every 3 weeks. To prevent hypersensitivity reactions, all patients should be premedicated with dexamethasone 20 mg PO approximately 12 and 6 hours before paclitaxel, diphenhydramine 50 mg IV (or equivalent) 30 to 60 minutes before paclitaxel, and an IV H2-blocker 30 to 60 minutes before paclitaxel.[29200]

for the treatment of advanced or metastatic NSCLC in combination with carboplatin†

Intravenous dosage

Adults

200 mg/m2 IV on day 1 in combination with carboplatin (AUC 6 IV) on day 1 given every 21 days produced an overall survival of 12.3 months in a phase 3 comparison of 4 chemotherapy doublets in advanced NSCLC.[34305] In another similar 4-arm phase 3 comparison, paclitaxel 225 mg/m2 IV on day 1 in combination with carboplatin (AUC 6 IV) on day 1 given every 21 days, produced an overall survival of 7.8 months, which was similar to the reference regimen of cisplatin and paclitaxel.[41098]

for the treatment of advanced or metastatic NSCLC in combination with gemcitabine†

Intravenous dosage

Adults

Paclitaxel 200 mg/m2 IV on day 1 in combination with gemcitabine 1000 mg/m2 IV on days 1 and 8, every 3 weeks has been given.[27129] Alternately, paclitaxel 175 mg/m2 IV on day 1 in combination with gemcitabine 1250 mg/m2 IV on days 1 and 8, every 3 weeks has also been given.[49473]

for the first-line treatment of metastatic squamous NSCLC, in combination with carboplatin and pembrolizumab†

Intravenous dosage

Adults

200 mg/m2 IV on day 1 and carboplatin (AUC 6 IV on day 1) repeated every 3 weeks for 4 cycles in combination with pembrolizumab (200 mg IV every 3 weeks OR 400 mg IV every 6 weeks until disease progression or up to a maximum of 24 months). Administer pembrolizumab prior to chemotherapy when given on the same day. In a multicenter, randomized, double-blind clinical trial (KEYNOTE-407), treatment with pembrolizumab plus carboplatin and either paclitaxel or nab-paclitaxel (n = 278) significantly improved median overall survival (17.1 months vs. 11.6 months) and progression-free survival (6.4 months vs. 4.8 months) compared with placebo plus carboplatin and paclitaxel/nab-paclitaxel (n = 281) in patients with metastatic squamous NSCLC. The overall response rate was also significantly improved in the pembrolizumab arm (58% vs. 35%), for a median duration of 7.2 months and 4.9 months, respectively.[57889] [66530]

for the first-line treatment of unresectable, locally advanced, recurrent, or metastatic NSCLC in combination with carboplatin and bevacizumab†:

Intravenous dosage

Adults

200 mg/m2 IV over 3 hours on day 1, preceded by bevacizumab (15 mg/kg IV over 90 minutes), and followed by carboplatin (AUC 6 IV), every 3 weeks for 6 cycles of chemotherapy. The sequence of administration should be bevacizumab followed by paclitaxel, and then carboplatin. After completion of chemotherapy, continue bevacizumab (15 mg/kg IV), on day 1 of each 21-day cycle until disease progression or unacceptable toxicity. To prevent hypersensitivity reactions, all patients should be premedicated with dexamethasone 20 mg PO approximately 12 and 6 hours before paclitaxel, diphenhydramine (or equivalent) 50 mg IV 30 to 60 minutes before paclitaxel, and an IV H2-blocker 30 to 60 minutes before paclitaxel. If the first bevacizumab infusion is well tolerated, the second infusion may be given over 60 minutes; if the 60-minute infusion is well tolerated, subsequent infusions may be given over 30 minutes. In a randomized, open-label clinical trial (n = 878), median overall survival was significantly longer in chemotherapy-naive patients with locally advanced, metastatic, or recurrent nonsquamous NSCLC treated with bevacizumab/paclitaxel/carboplatin (BCP) compared with paclitaxel/carboplatin (CP) alone (12.3 months vs. 10.3 months); investigator-assessed progression-free survival (PFS) was also longer in the bevacizumab arm. In an exploratory analysis, the impact of bevacizumab was not significant in women, patients age 65 years and older, or in patients with weight loss of 5% or more at study entry.[60402]

for the first-line treatment of metastatic nonsquamous NSCLC without EGFR or ALK mutations, in combination with bevacizumab, atezolizumab, and carboplatin†

Intravenous dosage

Adults

200 mg/m2 IV on day 1, or 175 mg/m2 IV in Asian patients, every 3 weeks for a maximum of 4 to 6 cycles. To prevent hypersensitivity reactions, all patients should be premedicated with dexamethasone 20 mg PO approximately 12 and 6 hours before paclitaxel, diphenhydramine (or equivalent) 50 mg IV 30 to 60 minutes before paclitaxel, and an IV H2-blocker 30 to 60 minutes before paclitaxel. Administer in combination with atezolizumab (840 mg IV every 2 weeks; OR 1,200 mg IV every 3 weeks; OR 1,680 mg IV every 4 weeks until disease progression or unacceptable toxicity), bevacizumab (15 mg/kg IV until disease progression or unacceptable toxicity), and carboplatin (AUC 6 IV every 3 weeks for a maximum of 4 to 6 cycles). Administer atezolizumab prior to bevacizumab and chemotherapy when given on the same day. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In a multicenter, randomized, open-label, phase 3 clinical trial (IMpower150), treatment with atezolizumab plus bevacizumab/paclitaxel/carboplatin (ABCP) significantly improved overall survival in patients with metastatic nonsquamous NSCLC compared with BCP without atezolizumab (19.2 months vs. 14.7 months); overall survival with atezolizumab/paclitaxel/carboplatin was not significantly different from BCP. Progression-free survival was also significantly improved in the ABCP arm compared with BCP (8.5 months vs. 7 months). The objective response rate was 55% (complete response [CR], 4%) versus 42% (CR, 1%), respectively, for a median duration of 10.8 months and 6.5 months, respectively.[60793] [63819]

For the treatment of ovarian cancer

for first line treatment of ovarian cancer in combination with cisplatin

Intravenous dosage

Adults

135 mg/m2 IV over 24 hours or 175 mg/m2 IV over 3 hours once every 3 weeks, followed by cisplatin (75 mg/m2 IV). This combination improves duration of progression-free survival and overall survival of these women as compared to the combination of cyclophosphamide and cisplatin.[25761] The 3-hour paclitaxel infusion is associated with less myelosuppression but increased neurotoxicity versus the 24-hour infusion. The combination of paclitaxel (175 mg/m2 IV over 3 hours) and carboplatin (AUC 5—6) is better tolerated than the paclitaxel-cisplatin combination and also appears to yield a survival advantage.[25769]

for refractory or metastatic ovarian cancer

Intravenous dosage

Adults

135 mg/m2 or 175 mg/m2 IV over 3 hours once every 3 weeks. The optimal regimen has not yet been determined.[29200] Alternately, paclitaxel 80 mg/m2 IV over 1 hour weekly for an initial 12 weeks, followed by 4-week courses of 3 weekly doses with 1 week off, has been given until disease progression or unacceptable toxicity†. In 48 patients with platinum and paclitaxel-resistant ovarian cancer, the objective response rate was 20.9%.[40949]

for the first line treatment of ovarian cancer in combination with carboplatin†

Intravenous dosage

Adults

175 to 185 mg/m2 IV over 3 hours on day 1 in combination with carboplatin (AUC 5—7.5 IV on day 1), every 3 weeks for 6 cycles. In clinical trials, carboplatin/paclitaxel has been shown to be less toxic and produce similar efficacy to cisplatin/paclitaxel as first line treatment of patients with advanced ovarian cancer.[13626][40931][40932] Additionally, paclitaxel 80 mg/m2 IV on days 1, 8, and 15 in combination with carboplatin (AUC 6 IV on day 1), every 3 weeks for 6 cycles has been given. This dose-dense combination was compared to conventional carboplatin/paclitaxel in 631 patients with advanced ovarian cancer. Progression-free survival, the primary end point, was significantly higher in the dose-dense arm (28 months vs. 17.2 months, p = 0.0015).[40935]

for the first line treatment of optimally debulked, stage III ovarian cancer as an intraperitoneal and intravenous infusion in combination with intraperitoneal cisplatin†

Intravenous dosage and Intraperitoneal dosage†

Adults

Paclitaxel 135 mg/m2 intravenously over 24 hours on day 1 followed by cisplatin 100 mg/m2 intraperitoneally on day 2 and paclitaxel 60 mg/m2 intraperitoneally on day 8. Administer every 3 weeks for 6 cycles. Extended overall survival and progression-free survival in a phase III trial compared to cisplatin IV/paclitaxel IV.[32309]

For the first line treatment of advanced transitional-cell bladder cancer†, in combination with carboplatin

Intravenous dosage

Adults

225 mg/m2 IV over 3 hours on day 1 followed by carboplatin (AUC of 6) IV over 30 minutes on day 1 repeated every 21 days (CP regimen) for 6 cycles was compared with methotrexate 30 mg/m2 on days 1, 15, and 22, vinblastine 3 mg/m2 IV on days 2, 15, and 22, doxorubicin 30 mg/m2 on day 2, and cisplatin 70 mg/m2 on day 2 (MVAC regimen) in a randomized, phase III trial. In this study, the median overall survival (OS) times were 13.8 and 15.4 months with CP and MVAC, respectively (p = 0.75) in 85 patients (median follow-up of 32.5 months). This study was halted because of slow patient accrual and was therefore underpowered to detect a difference in the primary end point of OS. The progression-free survival time was 5.2 months in the CP arm and 8.7 months in the MVAC arm (p = 0.24). Grade 3 or higher toxicity reported less often with CP compared with MVAC included neutropenia (29% vs. 67%), anemia (5% vs. 38%), thrombocytopenia (10% vs. 21%), fatigue (10% vs. 24%), and dyspnea (2% vs. 14% ); grade 3 sensory neuropathy occurred more often with CP (15% vs. 2%). Additionally, worst degree toxicity of grade 4 or higher occurred in fewer patients in the CP arm (15% vs. 33%) and there was 1 treatment-related death in each study arm.[47217]

For the treatment of unresectable or metastatic squamous cell esophageal cancer†, in combination with cisplatin

Intravenous dosage

Adults

175 mg/m2 IV over greater than 2 hours followed by cisplatin 75 mg/m2 IV over 1 hour (with 2—3 L of a electrolyte hydration solution over 8 hours daily for 3 days) on day 1 repeated every 21 days (mean of 3 cycles)[48168] and paclitaxel 90 mg/m2 IV over 3 hours plus cisplatin 50 mg/m2 IV over 3 hours (with 1 L of prehydration and 3 L of post hydration) repeated every 2 weeks for up to 8 cycles (median of 5 cycles; range, 2—8 cycles)[48169] have been evaluated in patients with unresectable or metastatic squamous cell carcinoma of the esophagus in nonrandomized clinical trials. All patients received premedications with a 5-HT3 antagonist prior to chemotherapy and dexamethasone and antihistamines 30 minutes prior to paclitaxel.

For the treatment of advanced squamous cell head and neck cancer†, in combination with carboplatin and radiotherapy

Intravenous dosage

Adults

40—45 mg/m2 IV weekly in combination with carboplatin (100 mg/m2 IV weekly). Chemotherapy was administered weekly prior to radiation therapy. In a clinical trial, 62 patients were administered carboplatin/paclitaxel concomitantly with radiation therapy. An overall survival of 33 months was achieved. A complete response (CR) occurred in 75% of patients; among patients with a CR, an overall survival of 49 months was achieved. At a follow-up of 30 months, a local control rate of 63% was observed.[43182]

For peripheral blood stem cell (PBSC) mobilization† in hematologic malignancies

Intravenous dosage

Adults

200 mg/m2 IV has been given in combination with etoposide, cyclophosphamide, and dexamethasone, followed by filgrastim for peripheral blood stem cell mobilization (d-TEC regimen).[49692] Alternately, paclitaxel 250 mg/m2 IV has been given on day 1, followed by filgrastim starting on day 2 and continued through the completion of leukapheresis.[49693]

For the treatment of advanced or recurrent endometrial cancer in combination with doxorubicin and cisplatin†

Intravenous dosage

Adults

160 mg/m2 IV on day 2, in combination with doxorubicin (45 mg/m2) immediately followed by cisplatin (50 mg/m2) on day 1; give every 21 days. In clinical trials treatment was continued for up to 7 cycles or until disease progression, and filgrastim (5 mcg/kg) was administered on days 3—12. A phase III trial showed an increase in response rate, progression-free survival, and overall survival in patients receiving paclitaxel, doxorubicin, and cisplatin (TAP) vs. cisplatin and doxorubicin alone. Thrombocytopenia and neuropathy were higher in the TAP arm.[33938]

For the first line treatment of unresectable, advanced thymoma†, in combination with carboplatin

Intravenous dosage

Adults

225 mg/m2 IV over 3 hours followed by carboplatin AUC of 6 IV over 30 minutes on day 1 repeated every 21 days for up to 6 cycles resulted in an objective response rate (ORR) of 42.9% (complete response rate, 14.3%; median duration of response, 16.9 months) in 21 patients with invasive, recurrent, or metastatic thymoma in a multicenter, phase II study. This ORR was less than the prespecified ORR of 60% that would warrant further study of this regimen. At a median follow-up of 59.4 months, the median progression-free survival time was 16.7 months and the median overall survival time was not reached. Serious toxicity reported in this study included grade 4 neutropenia and grade 3 sensory neuropathy.[47361]

For the first line treatment of unresectable, advanced thymic carcinoma†, in combination with carboplatin

Intravenous dosage

Adults

225 mg/m2 IV over 3 hours followed by carboplatin AUC of 6 IV over 30 minutes on day 1 administered every 21 days for up to 6 cycles resulted in an objective response rate (ORR) of 21.7% (all partial responses; median duration of response, 4.5 months) in 23 patients with invasive, recurrent, or metastatic thymic carcinoma in a multicenter, phase II study. This ORR was less than the prespecified ORR of 45% that would warrant further study of this regimen. At a median follow-up of 63.8 months, the median progression-free survival and overall survival times were 5 and 20 months, respectively. Serious toxicity reported in this study included grade 4 neutropenia and grade 3 sensory neuropathy.[47361]

For the treatment of small cell lung cancer (SCLC)†

for the treatment of relapsed SCLC as a single agent†

Intravenous dosage

Adults

Paclitaxel can be given weekly or every 3 weeks as a single agent. Paclitaxel 175 mg/m2 IV on day 1, repeated every 3 weeks up to a maximum of 5 cycles has been given to patients with SCLC relapsed within 3 months of chemotherapy.[47066] Alternately, paclitaxel 80 mg/m2 IV once weekly for 6 weeks on and 2 weeks off has been given to patients refractory to chemotherapy or relapsed within 4 weeks of chemotherapy.[47067]

for chemotherapy-naive, extensive-stage SCLC in combination with topotecan†

Intravenous dosage

Adults

Paclitaxel 135 mg/m2 IV as a 24-hour infusion on day 5 following topotecan (given as 1 mg/m2 IV days 1—5) every 28 days was evaluated in a phase II trial for the treatment of chemotherapy-naive extensive stage SCLC. Initially, topotecan dosing was 1.25 mg/m2 IV on days 1—5; however, because of excessive hematologic toxicity in the first 3 patients, the dose was reduced as above. Patients received an average of 4 cycles of chemotherapy. The overall response rate was 69%, overall median survival was 54 weeks with a 1-year survival rate of 50%. Despite the use of prophylactic G-CSF, the incidence of grade 4 neutropenia was 31%, which may have been increased because of 24-hour administration of paclitaxel. Overall, response rates and tolerability of this regimen were comparable to platinum/etoposide.[28678]

for the treatment of relapsed SCLC in combination with carboplatin†

Intravenous dosage

Adults

175 mg/m2 IV on day 1 in combination with carboplatin AUC 7 IV on day 1, every 3 weeks for 5 cycles.[25767]

For the neoadjuvant treatment of locally advanced or metastatic penile cancer† in combination with cisplatin and ifosfamide

Intravenous dosage

Adults

175 mg/m2 IV over 3 hours on day 1 in combination with cisplatin 25 mg/m2/day IV over 2 hours on days 1—3 and ifosfamide 1200 mg/m2/day IV over 2 hours on days 1—3, repeated every 3—4 weeks.[51058]

Therapeutic Drug Monitoring

Maximum Dosage Limits

  • Adults

    135—175 mg/m2 IV over 3 hours or up to 250 mg/m2 IV over 24 hours every 3 weeks. Weekly paclitaxel at doses of 80—100 mg/m2 IV over 1 hour are under investigation. Studies of weekly doses have given paclitaxel for 3 consecutive weeks with 1 week off, 6 weeks consecutively with 2 weeks off, or weekly for >12 weeks continuously. Higher doses may be given as part of preparative regimens for bone marrow transplantation. For intraperitoneal administration, the maximum tolerated dose was 175 mg/m2 IP every 3—4 weeks. When given IP weekly, significant Grade 2 toxicities were seen at 75 mg/m2; the recommended dose for weekly IP administration is 60—65 mg/m2 IP.

Patients with Hepatic Impairment Dosing

NOTE: Recommended dose reductions are for the first course of therapy; subsequent dose reductions should be based on individual tolerance.[29200]

Dose reduction for 135 mg/m2 24-hour intravenous infusion:

AST/ALT 2 to 10 x ULN and total bilirubin 1.5 mg/dL or less: 100 mg/m2.

AST/ALT less than 10 x ULN and total bilirubin 1.6 to 7.5 mg/dL: 50 mg/m2.

AST/ALT 10 x ULN or higher or total bilirubin higher 7.5 mg/dL: Not recommended.[29200]

 

Dose reduction for 175 mg/m2 3-hour intravenous infusion:

AST/ALT less than 10 x ULN and total bilirubin 1.26 to 2 x ULN: 135 mg/m2.

AST/ALT less than 10 x ULN and total bilirubin 2.01 to 5 x ULN: 90 mg/m2.

AST/ALT 10 x ULN or higher or total bilirubin higher than 5 x ULN: Not recommended.[29200]

 

Dose adjustments of paclitaxel are required in patients with hepatic dysfunction, although exact guidelines are not available for other dosage regimens. In general, dosage reductions of at least 50% are recommended in patients with moderate or severe hyperbilirubinemia or substantially increased serum transferase levels. The results of a study of patients with elevated serum bilirubin and/or liver enzymes indicate that the dose of paclitaxel should not exceed 50 to 75 mg/m2 IV over 24 hours or 75 to 100 mg/m2 IV over 3 hours. In addition, patients with AST greater than 2 times the upper limit of normal should not be treated with doses higher than 50 mg/m2 IV over 24 hours.[25764]

Patients with Renal Impairment Dosing

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

† Off-label indication
Revision Date: 08/05/2021, 04:07:13 PM

References

13626 - Neijt JP, Engelholm SA, Tuxen MK, et al. Exploratory phase III study of paclitaxel and cisplatin versus paclitaxel and carboplatin in advanced ovarian cancer. J Clin Oncol 2000;18:3084-9225761 - McGuire WP, Hoskins WJ, Brady MF, et al. Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and IV ovarian cancer. N Engl J Med 1996;334:1-6.25764 - Venook AP, Egorin MJ, Rosner GL, et al. Phase I and pharmacokinetic trial of paclitaxel in patients with hepatic dysfunction: Cancer and Leukemia Group B 9264. J Clin Oncol 1998;16:1811-1819.25765 - Gill PS, Tulpule A, Espina BM, et al. Paclitaxel is safe and effective in the treatment of advanced AIDS-related Kaposi's sarcoma. J Clin Oncol 1999;17:1876-1883.25767 - Groen HJ, Fokkema E, Biesma B, et al. Paclitaxel and carboplatin in the treatment of small-cell lung cancer resistant to cyclophosphamide, doxorubicin, and etoposide: a non-cross-resistant schedule. J Clin Oncol 1999;17:927-932.25769 - Neijt JP, Bois A. Paclitaxel/carboplatin for the initial treatment of advanced ovarian cancer. Semin Oncol 1999;26(1 Suppl 2):78-83.27129 - Kosmidis P, Mylonakis N, Nicolaides C, et al. Paclitaxel plus carboplatin versus gemcitabine plus paclitaxel in advanced non-small cell lung cancer: a phase III randomized trial. J Clin Oncol 2002;20:3578-3585.28061 - Herceptin (trastuzumab) package insert. South San Francisco, CA: Genentech Inc.; 2021 Feb.28678 - Ramalingam S, Belani CP, Day R, et al. Phase II study of topotecan and paclitaxel for patients with previously untreated extensive stage small-cell lung cancer. Ann Oncology 2004;15:247-51.29200 - Taxol (paclitaxel) package insert. Princeton, NJ: Bristol-Meyers Squibb; 2011 Apr.32309 - Armstrong DK, Bundy B, Wenzel L, et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med 2006;354:34-43.33131 - Miller K, Wang M, Gralow J, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 2007;357:2666-7633938 - Fleming GF, Brunetto VL, Cella D, et al. Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: A Gynecologic Oncology Group Study. J Clin Oncol 2004;22:2159-2166.34295 - Robert N, Leyland-Jones B, Asmar L, et al. Randomized phase III study of trastuzumab, paclitaxel and carboplatin compared with trastuzumab and paclitaxel in women with HER-2-overexpressing metastatic breast cancer. J Clin Oncol 2006;24:2786-92.34296 - Perez E, Suman VJ, Rowland KM, et al. Two concurrent phase II trials of paclitaxel/carboplatin/trastuzumab (weekly or every 3-week schedule) as first-line therapy in women with HER2-overexpressing metastatic breast cancer: NCCTG study 983252. Clin Breast Cancer 2005;6:425-32.34305 - Ohe Y, Ohashi Y, Kubota K, et al. Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced non-small cell lung cancer: four-arm cooperative study in Japan. Ann Oncol 2007;18:317-323.40586 - Sparano JA, Wang M, Martino S, et al. Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med. 2008;358:1663-167140931 - Ozols RF, Bundy BN, Greer BE, et al. Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group Study. J Clin Oncol 2003;21:3194-3200.40932 - du Bois A, Luck HJ, Meier W, et al. A randomized clinical trial of cisplatin/paclitaxel versus carboplatin/paclitaxel as first-line treatment of ovarian cancer. J Natl Cancer Inst 2003;95:1320-1330.40935 - Katsumata N, Yasuda M, Takahashi F, et al. Dose-dense paclitaxel once a week in combination with carboplatin every 3 weeks for advanced ovarian cancer: a phase 3, open-label, randomised controlled trial. Lancet 2009;374:1331-1338.40949 - Markman M, Blessing J, Rubin SC, et al. Phase II trial of weekly paclitaxel (80 mg/m2) in platinum and paclitaxel-resistant ovarian and primary peritoneal cancers: a Gynecologic Oncology Group study. Gynecol Oncol 2006;101:436-440.41098 - Schiller JH, Harrington D, Belani CP, et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002;346:92-841751 - Ellence (epirubicin hydrochloride) package insert. New York, NY: Pfizer Inc; 2019 July.43182 - Suntharalingam M, Haas ML, Conley BA, et al. The use of carboplatin and paclitaxel with daily radiotherapy in patients with locally advanced squamous cell carcinomas of the head and neck. Int J Radiation Oncology Biol Phys 2000;47:49-56.47066 - Smit EF, Fokkema E, Biesma B, et al. A phase II study of paclitaxel in heavily pretreated patients with small-cell lung cancer. Br J Cancer 1998;77:347-351.47067 - Yamamoto N, Tsurutani J, Yoshimura N, et al. Phase II study of weekly paclitaxel for relapsed and refractory small cell lung cancer. Anticancer Res 2006;26:777-782.47217 - Dreicer R, Manola J, Roth BJ, et al. Phase III trial of methotrexate, vinblastine, doxorubicin, and cisplatin versus carboplatin and paclitaxel in patients with advanced carcinoma of the urothelium. Cancer 2004;100(8):1639-1645.47361 - Lemma GL, Lee JW, Aisner SC, et al. Phase II study of carboplatin and paclitaxel in advanced thymoma and thymic carcinoma. J Clin Oncol 2011;29(15):2060-2065.47481 - Dang C, et al. The safety of dose-dense doxorubicin and cyclophosphamide followed by paclitaxel with trastuzumab in HER-2/neu overexpressed/amplified breast cancer. J Clin Oncol 2008;26:1216-122248168 - Zhang X, Shen L, Li J, et al. A phase II trial of paclitaxel and cisplatin in patients with advanced squamous-cell carcinoma of the esophagus. Am J Clin Oncol 2008;31(1):29-33.48169 - Cho SH, Chung IJ, Song SY, et al. Bi-weekly chemotherapy of paclitaxel and cisplatin in patients with metastatic or recurrent esophageal cancer. J Korean Med Sci 2005;20(4):618-623.49473 - Smit EF, van Meerbeeck J, Lianes P, et al. Three-arm randomized study of two cisplatin-based regimens and paclitaxel plus gemcitabine in advanced non-small-cell lung cancer: a phase III trial of the European Organization for Research and Treatment of Cancer Lung Cancer Group – EORTC 08975. J Clin Oncol 2003;21:3909-3917.49692 - Bilgrami S, Bona RD, Edwards RL, et al. Dexamethasone, paclitaxel, etoposide, cyclophosphamide (d-TEC) and G-CSF for stem cell mobilisation in multiple myeloma. Bone Marrow Transplantation 2001;28:137-143.49693 - McKibbin T, Burzynski J, Greene R, et al. Paclitaxel and filgrastim for hematopoietic progenitor cell mobilization in patients with hematologic malignancies after failure of a prior mobilization regimen. Leukemia Lymphoma 2007;48:2360-2366.50011 - Fountzilas G, Dafni U, Dimopoulos MA, et al. A randomized phase III study comparing three anthracycline-free taxane-based regimens, as first line chemotherapy, in metastatic breast cancer. Breast Cancer Res Treat 2009;115:87-99.50012 - Fountzilas G, Kalofonos HP, Dafni U, et al. Paclitaxel and epirubicin versus paclitaxel and carboplatin as first-line chemotherapy in patients with advanced breast cancer: a phase III study conducted by the Hellenic Cooperative Oncology Group. Ann Oncol 2004;15:1517-1526.51058 - Pagliaro LC, Williams DL, Daliani D, et al. Neoadjuvant paclitaxel, ifosfamide, and cisplatin chemotherapy for metastatic penile cancer: a phase II study. J Clin Oncol 2010;28:3851-3857.57889 - Keytruda (pembrolizumab) injection package insert. Whitehouse Station, NJ: Merck Sharp and Dohme Corp.; 2023 April.60402 - Avastin (bevacizumab) IV package insert. South San Francisco, CA: Genentech, Inc.; 2022 Sept.60793 - Tecentriq (atezolizumab) injection package insert. South San Francisco, CA: Genentech, Inc.; 2022 Jan.63560 - Buzdar AU, Suman VJ, Meric-Bernstam F, et al. Fluorouracil, epirubicin, and cyclophosphamide (FEC-75) followed by paclitaxel plus trastuzumab versus paclitaxel plus trastuzumab followed by FEC-75 plus trastuzumab as neoadjuvant treatment for patients with HER2-positive breast cancer (Z1041): a randomized, controlled, phase 3 trial. Lancet Oncol. 2013;14:1317-1325.63561 - Buzdar AU, Suman VJ, Meric-Bernstam F, et al. Disease-free and overall survival among patients with operable HER2-positive breast cancer treated with sequential vs concurrent chemotherapy: The ACOSOG Z1041 (Alliance) randomized clinical trial. JAMA Oncology. 2018 Sep 6. doi: 10.1001/jamaoncol.2018.3691. [Epub ahead of print]63819 - Socinski MA, Jotte RM, Cappuzzo F, et al. Atezolizumab for first-line treatment of metastatic non-squamous NSCLC. NEJM. 2018;378(24):2288-2301.66036 - Schmid P, Cortes J, Pusztai L, et al. Pembrolizumab for Early Triple-Negative Breast Cancer. NEJM. 2020;382(9):810-821.66122 - Cortes Castan J, Guo Z, Karantza V, et al. KEYNOTE-355: Randomized, double-blind, phase III study of pembrolizumab (pembro) + chemotherapy (chemo) vs placebo (pbo) + chemo for previously untreated, locally recurrent, inoperable or metastatic triple-negative breast cancer (mTNBC). Annals of Oncology. 2017;28(10):x25.66123 - Cortes J, Cescon DW, Rugo HS, et al. KEYNOTE-355: Randomized, double-blind, phase III study of pembrolizumab + chemotherapy versus placebo + chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer. Journal of Clinical Oncology. 2020;38(15_suppl):1000.66530 - Paz-Ares L, Vicente D, Tafreshi A, et al. A Randomized, Placebo-Controlled Trial of Pembrolizumab Plus Chemotherapy in Patients With Metastatic Squamous NSCLC: Protocol-Specified Final Analysis of KEYNOTE-407. Journal of Thoracic Oncology. 2020;15(10):1657-1669.

How Supplied

Paclitaxel Solution for injection

Onxol 6mg/ml Solution for Injection (00172-3756) (Teva Pharmaceuticals USA) (off market)

Paclitaxel Solution for injection

Onxol 6mg/ml Solution for Injection (00172-3754) (Teva Pharmaceuticals USA) (off market)

Paclitaxel Solution for injection

Onxol 6mg/ml Solution for Injection (00172-3753) (Teva Pharmaceuticals USA) (off market)

Paclitaxel Solution for injection

Paclitaxel 100mg/16.7ml Solution for Injection (10518-0102) (Fresenius Kabi AG) (off market)

Paclitaxel Solution for injection

Paclitaxel 100mg/16.7ml Solution for Injection (10518-0102) (Fresenius Kabi AG) (off market)

Paclitaxel Solution for injection

Paclitaxel 100mg/16.7ml Solution for Injection (63323-0763) (Fresenius Kabi USA, LLC ) null

Paclitaxel Solution for injection

Paclitaxel 100mg/16.7ml Solution for Injection (63323-0763) (Fresenius Kabi USA, LLC ) null

Paclitaxel Solution for injection

Paclitaxel 100mg/16.7ml Solution for Injection (67457-0449) (Mylan Institutional LLC ) null

Paclitaxel Solution for injection

Paclitaxel 100mg/16.7ml Solution for Injection (51079-0962) (Mylan Institutional LLC ) (off market)

Paclitaxel Solution for injection

Paclitaxel 100mg/16.7ml Solution for Injection (00069-0076) (Mylan Institutional LLC ) (off market)

Paclitaxel Solution for injection

Paclitaxel 100mg/16.7ml Solution for Injection (00069-0076) (Pfizer Injectables) (off market)

Paclitaxel Solution for injection

Paclitaxel 100mg/16.7ml Solution for Injection (25021-0213) (Sagent Pharmaceuticals) null

Paclitaxel Solution for injection

Paclitaxel 100mg/16.7ml Solution for Injection (66758-0043) (Sandoz Inc. a Novartis Company) null

Paclitaxel Solution for injection

Paclitaxel 100mg/16.7ml Solution for Injection (00703-4766) (Teva Pharmaceuticals USA) (off market)

Paclitaxel Solution for injection

Paclitaxel 100mg/16.7ml Solution for Injection (00555-1984) (Teva Pharmaceuticals USA) (off market)

Paclitaxel Solution for injection

Paclitaxel 100mg/16.7ml Solution for Injection (45963-0613) (Teva/Actavis US) (off market)

Paclitaxel Solution for injection

Paclitaxel 100mg/16.7mL Solution for Injection (62332-0621) (Alembic Pharmaceuticals, Inc.) nullPaclitaxel 100mg/16.7mL Solution for Injection package photo

Paclitaxel Solution for injection

Paclitaxel 100mg/16.7mL Solution for Injection (47781-0594) (Alvogen, Inc.) (off market)

Paclitaxel Solution for injection

Paclitaxel 100mg/16.7mL Solution for Injection (70860-0200) (Athenex Pharmaceutical Division LLC) null

Paclitaxel Solution for injection

Paclitaxel 100mg/16.7mL Solution for Injection (51991-0937) (Breckenridge Inc) null

Paclitaxel Solution for injection

Paclitaxel 100mg/16.7mL Solution for Injection (72205-0062) (Novadoz Pharmaceuticals LLC) null

Paclitaxel Solution for injection

Paclitaxel 100mg/16.7mL Solution for Injection (00703-3216) (Teva Pharmaceuticals USA) null

Paclitaxel Solution for injection

Paclitaxel 100mg/16.7mL Solution for Injection (44567-0505) (WG Critical Care, LLC, a PharmaSphere Company) null

Paclitaxel Solution for injection

Paclitaxel 100mg/16.7mL Solution for Injection (PREMIER ProRx) (00703-4766) (Teva Pharmaceuticals USA) (off market)Paclitaxel 100mg/16.7mL Solution for Injection (PREMIER ProRx) package photo

Paclitaxel Solution for injection

Paclitaxel 100mg/16.7mL Solution for Injection (PREMIER ProRx) (00703-3216) (Teva Pharmaceuticals USA) null

Paclitaxel Solution for injection

Paclitaxel 100mg/16.7mL Solution for Injection (PREMIER ProRx) (45963-0613) (Teva/Actavis US) (off market)

Paclitaxel Solution for injection

Paclitaxel 150mg/25ml Solution for Injection (00703-4767) (Teva Pharmaceuticals USA) (off market)

Paclitaxel Solution for injection

Paclitaxel 150mg/25mL Solution for Injection (00703-3217) (Teva Pharmaceuticals USA) null

Paclitaxel Solution for injection

Paclitaxel 300mg/50ml Solution for Injection (10518-0102) (Fresenius Kabi AG) (off market)

Paclitaxel Solution for injection

Paclitaxel 300mg/50ml Solution for Injection (10518-0102) (Fresenius Kabi AG) (off market)

Paclitaxel Solution for injection

Paclitaxel 300mg/50ml Solution for Injection (63323-0763) (Fresenius Kabi USA, LLC ) null

Paclitaxel Solution for injection

Paclitaxel 300mg/50ml Solution for Injection (67457-0434) (Mylan Institutional LLC ) null

Paclitaxel Solution for injection

Paclitaxel 300mg/50ml Solution for Injection (51079-0963) (Mylan Institutional LLC ) (off market)Paclitaxel 300mg/50ml Solution for Injection package photo

Paclitaxel Solution for injection

Paclitaxel 300mg/50ml Solution for Injection (00069-0078) (Mylan Institutional LLC ) (off market)

Paclitaxel Solution for injection

Paclitaxel 300mg/50ml Solution for Injection (00069-0078) (Pfizer Injectables) (off market)

Paclitaxel Solution for injection

Paclitaxel 300mg/50ml Solution for Injection (25021-0213) (Sagent Pharmaceuticals) null

Paclitaxel Solution for injection

Paclitaxel 300mg/50ml Solution for Injection (66758-0043) (Sandoz Inc. a Novartis Company) null

Paclitaxel Solution for injection

Paclitaxel 300mg/50ml Solution for Injection (00703-4768) (Teva Pharmaceuticals USA) (off market)

Paclitaxel Solution for injection

Paclitaxel 300mg/50ml Solution for Injection (00555-1985) (Teva Pharmaceuticals USA) (off market)

Paclitaxel Solution for injection

Paclitaxel 300mg/50ml Solution for Injection (45963-0613) (Teva/Actavis US) (off market)

Paclitaxel Solution for injection

Paclitaxel 300mg/50mL Solution for Injection (62332-0622) (Alembic Pharmaceuticals, Inc.) nullPaclitaxel 300mg/50mL Solution for Injection package photo

Paclitaxel Solution for injection

Paclitaxel 300mg/50mL Solution for Injection (47781-0595) (Alvogen, Inc.) (off market)

Paclitaxel Solution for injection

Paclitaxel 300mg/50mL Solution for Injection (70860-0200) (Athenex Pharmaceutical Division LLC) null

Paclitaxel Solution for injection

Paclitaxel 300mg/50mL Solution for Injection (68001-0516) (BluePoint Laboratories) null

Paclitaxel Solution for injection

Paclitaxel 300mg/50mL Solution for Injection (51991-0938) (Breckenridge Inc) null

Paclitaxel Solution for injection

Paclitaxel 300mg/50mL Solution for Injection (63323-0763) (Fresenius Kabi USA, LLC ) null

Paclitaxel Solution for injection

Paclitaxel 300mg/50mL Solution for Injection (16714-0137) (NorthStar Rx LLC) null

Paclitaxel Solution for injection

Paclitaxel 300mg/50mL Solution for Injection (72205-0063) (Novadoz Pharmaceuticals LLC) null

Paclitaxel Solution for injection

Paclitaxel 300mg/50mL Solution for Injection (00703-3218) (Teva Pharmaceuticals USA) null

Paclitaxel Solution for injection

Paclitaxel 300mg/50mL Solution for Injection (44567-0506) (WG Critical Care, LLC, a PharmaSphere Company) null

Paclitaxel Solution for injection

Paclitaxel 300mg/50mL Solution for Injection (NOVAPLUS) (70860-0215) (Athenex Pharmaceutical Division LLC) null

Paclitaxel Solution for injection

Paclitaxel 300mg/50mL Solution for Injection (PREMIER ProRx) (00703-3218) (Teva Pharmaceuticals USA) null

Paclitaxel Solution for injection

Paclitaxel 300mg/50mL Solution for Injection (PREMIER ProRx) (00703-4768) (Teva Pharmaceuticals USA) (off market)

Paclitaxel Solution for injection

Paclitaxel 300mg/50mL Solution for Injection (PREMIER ProRx) (45963-0613) (Teva/Actavis US) (off market)

Paclitaxel Solution for injection

Paclitaxel 30mg/5ml Solution for Injection (10518-0102) (Fresenius Kabi AG) (off market)

Paclitaxel Solution for injection

Paclitaxel 30mg/5ml Solution for Injection (10518-0102) (Fresenius Kabi AG) (off market)

Paclitaxel Solution for injection

Paclitaxel 30mg/5ml Solution for Injection (63323-0763) (Fresenius Kabi USA, LLC ) null

Paclitaxel Solution for injection

Paclitaxel 30mg/5ml Solution for Injection (67457-0471) (Mylan Institutional LLC ) null

Paclitaxel Solution for injection

Paclitaxel 30mg/5ml Solution for Injection (00069-0079) (Mylan Institutional LLC ) (off market)

Paclitaxel Solution for injection

Paclitaxel 30mg/5ml Solution for Injection (51079-0961) (Mylan Institutional LLC ) (off market)

Paclitaxel Solution for injection

Paclitaxel 30mg/5ml Solution for Injection (00069-0079) (Pfizer Injectables) (off market)

Paclitaxel Solution for injection

Paclitaxel 30mg/5ml Solution for Injection (25021-0213) (Sagent Pharmaceuticals) null

Paclitaxel Solution for injection

Paclitaxel 30mg/5ml Solution for Injection (66758-0043) (Sandoz Inc. a Novartis Company) null

Paclitaxel Solution for injection

Paclitaxel 30mg/5ml Solution for Injection (45963-0613) (Teva/Actavis US) (off market)

Paclitaxel Solution for injection

Paclitaxel 30mg/5mL Solution for Injection (62332-0620) (Alembic Pharmaceuticals, Inc.) nullPaclitaxel 30mg/5mL Solution for Injection package photo

Paclitaxel Solution for injection

Paclitaxel 30mg/5mL Solution for Injection (47781-0593) (Alvogen, Inc.) (off market)

Paclitaxel Solution for injection

Paclitaxel 30mg/5mL Solution for Injection (70860-0200) (Athenex Pharmaceutical Division LLC) null

Paclitaxel Solution for injection

Paclitaxel 30mg/5mL Solution for Injection (51991-0936) (Breckenridge Inc) null

Paclitaxel Solution for injection

Paclitaxel 30mg/5mL Solution for Injection (63323-0763) (Fresenius Kabi USA, LLC ) null

Paclitaxel Solution for injection

Paclitaxel 30mg/5mL Solution for Injection (72205-0061) (Novadoz Pharmaceuticals LLC) null

Paclitaxel Solution for injection

Paclitaxel 30mg/5mL Solution for Injection (00703-3213) (Teva Pharmaceuticals USA) null

Paclitaxel Solution for injection

Paclitaxel 30mg/5mL Solution for Injection (PREMIER ProRx) (00703-3213) (Teva Pharmaceuticals USA) null

Paclitaxel Solution for injection

Paclitaxel 30mg/5mL Solution for Injection (PREMIER ProRx) (45963-0613) (Teva/Actavis US) (off market)

Paclitaxel Solution for injection

Paclitaxel 6mg/ml Solution for Injection (55390-0114) (Bedford Laboratories, a Hikma Company) (off market)Paclitaxel 6mg/ml Solution for Injection package photo

Paclitaxel Solution for injection

Paclitaxel 6mg/ml Solution for Injection (00074-4335) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Paclitaxel Solution for injection

Paclitaxel 6mg/ml Solution for Injection (61703-0342) (Hospira Worldwide, Inc., a Pfizer Company) null

Paclitaxel Solution for injection

Paclitaxel 6mg/ml Solution for Injection (00703-4764) (Teva Pharmaceuticals USA) (off market)

Paclitaxel Solution for injection

Paclitaxel 6mg/ml Solution for Injection (Amerinet) (55390-0314) (Bedford Laboratories, a Hikma Company) (off market)

Paclitaxel Solution for injection

Paclitaxel 6mg/ml Solution for Injection (NOVAPLUS) (55390-0304) (Bedford Laboratories, a Hikma Company) (off market)

Paclitaxel Solution for injection

Paclitaxel 6mg/ml Solution for Injection (OTN) (55390-0514) (Bedford Laboratories, a Hikma Company) (off market)

Paclitaxel Solution for injection

Paclitaxel 6mg/ml Solution for Injection (PREMIER ProRx) (00703-4764) (Teva Pharmaceuticals USA) (off market)

Paclitaxel Solution for injection

Taxol 100mg/16.7ml Solution for Injection (00015-3476) (Bristol Myers Squibb Oncology Products) (off market)Taxol 100mg/16.7ml Solution for Injection package photo

Paclitaxel Solution for injection

Taxol 300mg/50ml Solution for Injection (00015-3479) (Bristol Myers Squibb Oncology Products) (off market)Taxol 300mg/50ml Solution for Injection package photo

Paclitaxel Solution for injection

Taxol 30mg/5ml Solution for Injection (00015-3475) (Bristol Myers Squibb Oncology Products) (off market)Taxol 30mg/5ml Solution for Injection package photo

Description/Classification

Description

NOTE: Abraxane (paclitaxel bound to albumin), a specialized formulation of paclitaxel, is discussed in a separate monograph.

 

Paclitaxel is a semisynthetic antineoplastic agent. It is a diterpenoid taxane derivative from the bark of the Pacific yew tree, Taxus brevifolia. Paclitaxel was first discovered in 1971 as a result of the National Cancer Institute (NCI) screening program for natural cytotoxic products. Procurement and stability issues hindered the availability of paclitaxel for clinical use. Paclitaxel injection is very insoluble in water and requires formulation with Cremophor EL and ethanol. In 1991, an agreement between Bristol-Myers Squibb and the NCI led to the development alternative sources of paclitaxel. Paclitaxel has subsequently been isolated from other members of the Taxus genus and is produced by Taxomyces andreannae, a fungal endophyte isolated from the inner bark of the Pacific yew. The production of a semisynthetic form of paclitaxel using the precursor 10-deacetyl-baccatin III, which is found in the needles of the European yew, Taxus baccata, has allowed large supplies to be produced. Due to its unique mechanism of action, paclitaxel has been studied as a single agent and in combination with other chemotherapy agents in the treatment of many solid tumors including ovarian, breast, lung and head and neck cancers. The combination of paclitaxel and a platinum analog is considered the chemotherapy regimen of choice for women with stage III and IV ovarian cancer. Paclitaxel is part of first-line and adjuvant therapy for non-small cell lung cancer. The determination of the optimal dose and scheduling of paclitaxel continues to be investigated. Newer regimens include weekly and biweekly administration as well as shorter infusion times. The sequence of administration of paclitaxel in combination with other chemotherapy agents plays a critical role in toxicity and efficacy of the combination. Several new formulations of paclitaxel are in clinical trials and include a topical paclitaxel gel for psoriasis, a liposome-encapsulated intravenous product, an oral capsule, and a water-soluble, intravenous formulation (Paclical). The FDA provided orphan drug designation for Paclical for the treatment of ovarian cancer; orphan drug designation provides the manufacturer, Oasmia Pharmaceutical, with 7-year market exclusivity on the indication when the pharmaceutical is approved. The FDA first approved paclitaxel in 1992 for the treatment of ovarian cancer. Since this time, Taxol has received approval for a variety of indications including the second-line treatment of Kaposi's sarcoma, treatment of metastatic or relapsed breast cancer after failure of combination chemotherapy, adjuvant treatment of node-positive breast cancer following standard doxorubicin-based combination chemotherapy, and treatment of non-small lung carcinoma in combination with cisplatin.

Classifications

  • Antineoplastic and Immunomodulating Agents
    • Antineoplastics
      • Antineoplastic Plant Alkaloids and Other Natural Agents
        • Taxanes
Revision Date: 05/04/2009, 07:50:31 PM

References

Administration Information

General Administration Information

For storage information, see the specific product information within the How Supplied section.

Hazardous Drugs Classification

  • NIOSH 2016 List: Group 1 [63664]
  • NIOSH (Draft) 2020 List: Table 1
  • Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
  • Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.[63664]

Emetic Risk

  • Low
  • Administer routine antiemetic prophylaxis prior to treatment.[67389]

Extravasation Risk

  • Vesicant
  • Administer drug through a central venous line.[67387][55200]

Route-Specific Administration

Injectable Administration

  • Administer as an intravenous infusion. In clinical studies, paclitaxel has been administered intraperitoneally.
  • Prior to administration, patients should have documented neutrophil counts greater than 1,500 cells/mm3 and platelet counts greater than 100,000 cells/mm3. Patients with AIDS-related Kaposi's sarcoma should have neutrophil counts greater than 1,000 cells/mm3.
  • To prevent hypersensitivity reactions, all patients should be premedicated with dexamethasone 20 mg PO approximately 12 and 6 hours before paclitaxel, diphendydramine (or its equivalent) 50 mg IV 30 to 60 minutes prior to paclitaxel, and cimetidine 300 mg IV or famotidine 20 mg IV 30 to 60 minutes before paclitaxel. In patients with advanced HIV disease, reduce the dose of dexamethasone to 10 mg PO.
  • Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

 

Dilution:

  • Withdraw the appropriate dose of paclitaxel from the vial and dilute to a concentration of 0.3 to 1.2 mg/ml with either 0.9% Sodium Chloride Injection, 5% Dextrose Injection, 5% Dextrose and 0.9% Sodium Chloride Injection, or 5% Dextrose and Lactated Ringer's solution.
  • The Chemo Dispensing Pin device or similar devices with spikes should not be used in vials of Taxol since they can cause the stopper to collapse resulting in loss of sterility of the solution.
  • It is recommended that the infusion be prepared in glass or polypropylene bottles or polypropylene or polyolefin plastic bags and administered through polyethylene-lined administration sets. Do not use PVC administration sets or containers.
  • Diluted solutions are stable at room temperature for up to 27 hours.

Intravenous Administration

  • Use of an in-line filter of not greater than 0.22 micron pore size is required during administration.
  • Infuse IV according to the prescriber's directions as infusion times may vary according to indication. Paclitaxel has been administered as a 3-hour or a 24-hour IV infusion.[29200] Paclitaxel doses up to 100 mg/m2 IV weekly have been given as a 1-hour IV infusion.[42143]

Other Injectable Administration

Intraperitoneal infusion:

  • Paclitaxel is not approved by the FDA for intraperitoneal administration.
  • Dilute into 1 to 2 liters of 0.9% Sodium Chloride Injection, depending upon patient tolerability.
  • Warm to 37 degrees C and infuse as rapidly as tolerated into the peritoneal cavity
  • Patients should change positions at 15 minute intervals for 2 hours to ensure adequate intraabdominal distribution.

Clinical Pharmaceutics Information

From Trissel's 2‚Ñ¢ Clinical Pharmaceutics Database

Paclitaxel (solvent/surfactant)

pH Range
pH 4.4 to 5.6 (0.6 to 1.2 mg/mL in common infusion solutions)
ReferencesMcEvoy GK (ed). AHFS Drug Information (current edition). Bethesda, MD: American Society of Health-System Pharmacists.
Osmolality/Osmolarity
Paclitaxel 0.6 mg/mL diluted in dextrose 5% and in sodium chloride 0.9% is reported to have osmolalities of 436 mOsm/kg and 461 mOsm/kg, respectively.
ReferencesCobb HH. Stability of fludarabine phosphate, pentostatin, and amsacrine in commonly used infusion solutions and after filtration, and osmolality of various constituted chemotherapeutic agents. Ph.D. Dissertation. 1995;
Stability
Paclitaxel injection should be stored at controlled room temperature, but refrigeration or freezing does not adversely affect the drug's stability. However, exposure to cold temperatures may result in the formation of a precipitate. Warming the injection to room temperature should redissolve the precipitate without adversely affecting the injection. If the precipitate fails to redissolve, the injection should be discarded. Infusion Solutions: The manufacturer indicates that paclitaxel concentrated injection diluted for intravenous infusion to a concentration between 0.3 and 1.2 mg/mL is physically and chemically stable for 27 hours at room temperature near 25 degree C exposed to normal room light in the infusion solutions noted below. Dextrose 5% Dextrose 5% in Ringer's injection Dextrose 5% in sodium chloride 0.9% Sodium chloride 0.9% After dilution, the admixture may appear slightly hazy due to the surfactant content in the paclitaxel formulation. The haziness is normal and varies in intensity depending on the drug (and therefore surfactant) concentration. Natella et al. evaluated the stability of paclitaxel 0.3 and 0.75 mg/mL (diluent unspecified) using two analytical methods. HPLC analysis found 10% degradation in the 0.3-mg/mL solution in 7 days at room temperature and in 40 days refrigerated. At 0.75 mg/mL, 10% loss was found in 21 days at room temperature. Less than 10% loss occurred in 56 days (the longest time point determined) under refrigeration. Natella et al. also attempted to use infrared/ultraviolet spectrometry as an analytical tool, but the technique was unable to quantify paclitaxel degradation. Precipitation Potential: Although paclitaxel is stable in aqueous media, the drug has minimal solubility and is subject to precipitation after dilution in an infusion solution. The ethanol and Cremophor EL surfactant are present in the formulation to aid in dispersing the drug in infusion solutions, but precipitation may still occur on an irregular and unpredictable time frame, even within and below the manufacturer's recommended concentration range of 0.3 to 1.2 mg/mL. Cronquist and Daniels noted that the mechanism creating the erratic precipitation is uncertain. Factors that may influence the physical stability of paclitaxel in aqueous solutions include paclitaxel concentration, type of solution container, infusion solution, storage temperature, formulation pH, solution agitation, and possibly other factors. Exact and reliable prediction of long-term physical stability periods does not appear to be possible. Because of the irregularity and uncertainty of when or whether precipitation might occur, attention and vigilant observation are needed during paclitaxel administration. In addition, the use of an inline 0.22-micron filter is recommended by the manufacturer for the administration of paclitaxel infusions because of the potential for precipitation to occur. Beijnen et al. and Strong and Morris noted that the precipitation time frame of insoluble drugs such as paclitaxel in aqueous media may be shortened by factors over which there is little control such as the presence or formation of crystallization nuclei and agitation of the solution during storage, transportation, and administration as well as contact with incompatible drugs and device materials. However, Sautou-Miranda et al. noted that the precipitation potential increased as storage time increased; this is a factor that can and should be controlled. Limitation of the beyond-use period is essential to reduce the likelihood of precipitation occurrence. Pfeifer and Hale reported that precipitate formation was often observed in infusion tubing downstream from the infusion pump, which may be related to the agitation and compression created by the pumping mechanism. Donyai and Sewell reported the physical and chemical stability of paclitaxel 0.3 mg/mL and 1.2 mg/mL in sodium chloride 0.9% and in dextrose 5% in polyolefin (Viaflo, Baxter), polyethylene (Ecoflac, B. Braun) and glass containers at room temperature near 25 degree C and under refrigeration at 5 degree C. Precipitation was found to be the stability limiting factor in all cases; paclitaxel concentrations remained acceptable until precipitation appeared. Most of the solution stored at room temperature, the solution developed precipitation after 3 days. In dextrose 5% in glass containers, precipitation appeared in 7 to 8 days. Under refrigeration, precipitation appeared after the more variable time periods noted below. Although this is useful information, exact and reliable prediction of long-term physical stability periods does not appear to be possible. Paclitaxel 0.3 mg/mL in dextrose 5%: Viaflo- 13 days Ecoflac- 18 days Glass- 20 days Paclitaxel 1.2 mg/mL in dextrose 5%: Viaflo- 10 days Ecoflac- 12 days Glass- 10 days Paclitaxel 0.3 mg/mL in sodium chloride 0.9%: Viaflo- 13 days Ecoflac- 16 days Glass- 13 days Paclitaxel 1.2 mg/mL in sodium chloride 0.9%: Viaflo- 9 days Ecoflac- 12 days Glass- 8 days Kattige reported that generic paclitaxel (Mayne Pharma) with citric acid in the formulation at concentrations of 0.3, 0.75, and 1.2 mg/mL in dextrose 5% and in sodium chloride 0.9% in polyolefin containers exhibited variable times to precipitation. The variability was largely concentration dependent although other factors may also have played a role. Stability-indicating HPLC analysis found no decomposition of the paclitaxel making precipitation the limiting solution stability factor. At 0.3 mg/mL, no precipitation was observed over 6 to 8 days at room temperature and through 28 days refrigerated. At 0.75 mg/mL, no precipitation was observed over 4 to 6 days at room temperature and through 20 days refrigerated. Paclitaxel 1.2 mg/mL exhibited the shortest time to precipitation; no precipitate appeared over 4 days at room temperature and through 12 days refrigerated. However, all of the samples developed paclitaxel precipitation after these observation periods. Phospholipid Emulsion: Jain t al. evaluated the short-term physical stability of a new phospholipid emulsion formulation of paclitaxel in dextrose 5% and sodium chloride 0.9%. At paclitaxel concentrations of 0.2, 04, and 0.6 mg/mL, paclitaxel did not precipitate over the 3-hour observation period. However, at 0.8 and 1 mg/mL, paclitaxel precipitation occurred in 2 to 2.5 hours.
ReferencesAnon. Manufacturer's information and labeling. (Package insert).
ReferencesBeijnen JH, Beijnen-Bandhoe AU, Dubbelman AC, et al. Chemical and physical stability of etoposide and teniposide in commonly used infusion fluids. J Parenter Sci Tech. 1991; 45
ReferencesCronquist SE, Daniels M. Precipitation of of paclitaxel during infusion by pump. Am J Hosp Pharm. 1993; 50
ReferencesDonyai P, Sewell GJ. Physical and chemical stability of paclitaxel infusions in different container types. J Oncol Pharm Pract. 2006; 12
ReferencesJain J, Fernades C, Patravale V. Formulation development of parenteral phospholipid-based microemulsion of etoposide. AAPS PharmSciTech. 2010; 11
ReferencesKattige A. Long-term physical and chemical stability of a generic paclitaxel infusion under simulated storage and clinical-use conditions. Eur J Hosp Pharm Sci. 2006; 12
ReferencesNatella PA, Lemaitre F, Farinotti R, et al. State of the art of stability studies in oncology: example of paclitaxel. Int J Clin Pharm. 2012; 34
ReferencesPfeifer RW, Hale KN. Precipitation of paclitaxel during infusion by pump. Am J Hosp Pharm. 1993; 50
ReferencesSautou-Miranda V, Brigas F, Vanheerswynghels S, et al. Compatibility of paclitaxel in 5% glucose solution with ECOFLAC low-density polyethylene containers - stability under different storage conditions. Int J Pharm. 1999; 178
ReferencesSewell G. Long-term stability of a generic paclitaxel infusion. Physical stability was the key influence in establishing a shelf-life for paclitaxel infusion prepared from generic product. Eur J Hosp Pharm Sci. 2006; 12
ReferencesStrong DK, Morris LA. Precipitation of teniposide during infusion. Am J Hosp Pharm. 1990; 47
ReferencesTrissel LA, Bready BB. Turbidimetric assessment of the compatibility of taxol with selected other drugs during simulated Y-site injection. Am J Hosp Pharm. 1992; 49
pH Effects
Paclitaxel exhibits maximum stability in aqueous solution at about pH 4 to 5.
ReferencesTian JH, Stella VJ. Degradation of paclitaxel and related compounds in aqueous solutions III: degradation under acidic pH conditions and overall kinetics. J Pharm Sci. 2010; 99
Light Exposure
Paclitaxel injection should be protected from exposure to light during long-term storage.
ReferencesAnon. Manufacturer's information and labeling. (Package insert).
Freezing
Freezing paclitaxel injection does not adversely affect its stability. However, exposure to cold temperatures may result in the formation of a precipitate. Warming the injection to room temperature should redissolve the precipitate without adversely affecting the injection. If the precipitate fails to redissolve, the injection should be discarded.
ReferencesAnon. Manufacturer's information and labeling. (Package insert).
Filtration
The use of an inline 0.22-micron filter is recommended by the manufacturer for the administration of paclitaxel infusions because of the potential for precipitation to occur. No binding of paclitaxel to filter materials has been reported. The manufacturer indicates the use of filter sets such as the Ivex-2 that incorporates a small DEHP-plasticized PVC tubing segment is acceptable because the amount of leached DEHP is very small. Pall reported that paclitaxel 0.3 mg/mL underwent no loss due to filtration through a Supor membrane filter. Also see Precipitation Potential in the Stability Section.
ReferencesAnon. Manufacturer's information and labeling. (Package insert).
ReferencesAnon. Pall Medical Supor-membrane IV filter device drug-adsorption data. Data on file. 2004; 8
ReferencesWaugh WN, Trissel LA, Stella VI. Stability, compatibility, and plasticizer extraction of taxol (NSC-125973) injection diluted in infusion solutions and stored in various containers. Am J Hosp Pharm. 1991; 48
ReferencesXu QA, Trissel LA, Gilbert DL. Paclitaxel compatibility with the IV Express filter unit. Int J Pharmaceut Compound. 1998; 2
Sorption Leaching
Sorption: Paclitaxel has not been found to undergo sorption to polyvinyl chloride (PVC), ethylene vinyl acetate (EVA), low-density polyethylene, and glass containers or to various types of administration equipment including PVC and polyolefin sets and a polyurethane central catheter. Leaching: The manufacturer recommends that paclitaxel injection not contact PVC containers and equipment such as administration sets because of plasticizer leaching. For this reason, glass and polyolefin containers such as those made from polyethylene and polypropylene are generally used for paclitaxel dilution and administration. The Cremophor EL surfactant in the paclitaxel formulation leaches large amounts of diethylhexyl phthalate (DEHP) plasticizer from PVC containers and administration sets. The amount of leached DEHP increases with drug (and, therefore, surfactant) concentration, contact time, length and bore of administration set tubing, ambient temperature, and the amount of DEHP plasticizer present in the PVC. The manufacturers of paclitaxel and a number of authors of published articles recommend the use of non-PVC containers and equipment to avoid this problem such as glass, polypropylene, polyethylene and other polyolefin containers and non-PVC administration sets. Some administration sets may be promoted as being made of non-PVC components. Examples might include some nitroglycerin sets. But they may still have highly DEHP-plasticized PVC pumping segments with much higher DEHP concentrations than is used in the tubing. Care must be taken in selecting the proper set if leaching of large amounts of DEHP is to be avoided. Jobet-Hermelin et al. proposed a maximum DEHP acceptability limit of 5 mcg/mL from PVC containers and administration equipment based on metabolic and toxicologic evaluations. Tickner et al. have reviewed the health concerns associated with leached DEHP in patients. Several research studies have evaluated the extent of DEHP leaching from PVC containers and numerous administration and extension sets. Mazzo et al. reported that paclitaxel 0.3 and 1.2 mg/mL in dextrose 5% and in sodium chloride 0.9% leached substantial amounts of DEHP from PVC bags. The 0.3-mg/mL concentration leached about 21 to 30 mcg/mL of DEHP while the 1.2-mg/mL concentration leached 73 to 108 mcg/mL of DEHP. The drug also leached substantial amounts of DEHP from PVC administration set tubing. The 0.3- and 1.2-mg/mL concentrations leached about 18 mcg/mL and 114 mcg/mL, respectively. Allwood and Martin also found DEHP leaching from PVC containers and sets. As much as 30 mg of DEHP was leached from Baxter Flo-Gard Low Absorption reduced-PVC sets. Trissel et al. evaluated several dozen non-PVC administration and extension sets for compatibility with standard dilutions of paclitaxel for infusion. Most of the infusion sets and all of the extension sets (which were small) leached no DEHP or leached less than the amount in the FDA-approved Ivex-2 filter set. However, Trissel et al. reported that several administration sets with non-PVC tubing had highly plasticized PVC pumping segments that resulted in unacceptable amounts of leached DEHP. These included the Baxter vented nitroglycerin set (2C7552S), Baxter vented basic solution set (1C8355S), McGaw Horizon pump vented nitroglycerin set (V7450), and the McGaw Intelligent pump vented nitroglycerin set (V7150). Xu and Trissel reported that using either of two reduced-DEHP sets (models 11993-48 and L-12060) for the Abbott Acclaim pumps was acceptable for low concentration and short-term (3-hour) delivery of paclitaxel. However paclitaxel 1.2 mg/mL delivered slowly over 4 days resulted in unacceptable amounts of leached DEHP in the range of 30 to 150 mcg/mL. Xu et al. also reported that paclitaxel 0.3 and 1.2 mg/mL in dextrose 5% delivered through a PVC administration set plasticized with tris(2-ethylhexyl)trimellitate (TOTM) did not leach substantial amounts of plasticizer. Trevis et al. also reported that polysorbate 80 (a surfactant similar to the surfactant in the paclitaxel formulation) in concentrations from 0.05 to 2 mcg/mL at temperatures of 4, 25, and 37 degree C did not leach substantial amounts of tris(2-ethylhexyl)trimellitate (also known as TOTM and TETM) plasticizer from PVC plastic tubing plasticized with TOTM. Xu et al. also reported that a small amount of an unknown material leached from Baxter ethylene vinyl acetate (EVA) containers. Zhang et al. reported that an Arrow-Howes polyurethane central catheter was acceptable for the administration of paclitaxel 0.3 and 1.2 mg/mL in dextrose 5%, even during slow administration over 24 hours. HPLC analysis found no loss of paclitaxel due to sorption and no leached materials from the catheter. Theou et al. reported that under conditions simulating clinical infusion of paclitaxel, a reduction in leached DEHP of up to 96% could be achieved by the use of infusion bags and tubing that is free of DEHP plasticizer and the elimination of PVC precision flow regulators. Trissel et al. and Aloumanis et al. evaluated the potential for leaching of plasticizer and other plastic components from VISIV (Hospira) polyolefin bags. Paclitaxel vehicle equivalent to paclitaxel 1.2 mg/mL in dextrose 5% was tested for 24 hours at room temperature near 23 degree C. HPLC analysis found no leached plastic components within the 24-hour study period.
ReferencesAnon. Manufacturer's information and labeling. (Package insert).
ReferencesAllwood MC, Martin H. The extraction of diethylhexylphthalate (DEHP) from polyvinyl chloride components of intravenous infusion containers and administration sets by paclitaxel injection. Int J Pharm. 1996; 127
ReferencesAloumanis V, Ben M, Kupiec TC, et al. Drug compatibility with a new generation of VISIV polyolefin infusion containers. Int J Pharmaceut Compound. 2009; 13
ReferencesKattige A. Long-term physical and chemical stability of a generic paclitaxel infusion under simulated storage and clinical-use conditions. Eur J Hosp Pharm Sci. 2006; 12
ReferencesJobet-Hermelin I, Mallvais ML, Jacquot C, et al. Proposition d'une concentration limite acceptable du plastifiant librere par le poly(chlorure de vinyle) dans les solutions injectables aqueuses.[Proposal of an acceptability limit concentration of released plasticizer from polyvinyl chloride in infusion]. J Pharm Clin. 1996; 15
ReferencesMazzo DJ, Nguyen-Huu JJ, Pagniez S, et al. Compatibility of docetaxel and paclitaxel in intravenous solutions with polyvinyl chloride infusion materials. Am J Health-Syst Pharm. 1997; 54
ReferencesPearson SD, Trissel LA. Leaching of diethylhexyl phthalate from polyvinyl chloride containers by selected drugs and formulation components. Am J Hosp Pharm. 1993; 50
ReferencesSautou-Miranda V, Brigas F, Vanheerswynghels S, et al. Compatibility of paclitaxel in 5% glucose solution with ECOFLAC low-density polyethylene containers - stability under different storage conditions. Int J Pharm. 1999; 178
ReferencesTheou N, Harvard L, Maestroni ML, et al. Leaching of di(2-ethylhexyl)phthalate from polyvinyl chloride medical devices: recommendations for taxanes infusion. Eur J Hosp Pharm Sci. 2005; 11
ReferencesTickner JA, Schettler T, Guidotti T, et al. Health risks posed by use of di-2-ethylhexyl phthalate (DEHP) in PVC medical devices: a critical review. Am J Indust Med. 2001; 39
ReferencesTrissel LA, Xu QA, Kwan J, et al. Compatibility of paclitaxel injection vehicle with intravenous administration and extension sets. Am J Hosp Pharm. 1994; 51
ReferencesTrissel LA, Xu QA, Baker M. Drug compatibility with new polyolefin infusion solution containers. Am J Health-Syst Pharm. 2006; 63
ReferencesWaugh WN, Trissel LA, Stella VI. Stability, compatibility, and plasticizer extraction of taxol (NSC-125973) injection diluted in infusion solutions and stored in various containers. Am J Hosp Pharm. 1991; 48
ReferencesXu QA, Trissel LA, Davis MR. Compatibility of paclitaxel in 5% glucose and 0.9% sodium chloride injection in EVA minibags. Austral J Hosp Pharm. 1998; 28
ReferencesXu QA, Trissel LA. Compatibility of paclitaxel injection diluent with two reduced-phthalate aministration sets for the Acclaim pump. Int J Pharmaceut Compound. 1998; 2
ReferencesXu QA, Trissel LA, Gilbert DL. Paclitaxel compatibility with the IV Express filter unit. Int J Pharmaceut Compound. 1998; 2
ReferencesXu QA, Trissel LA, Gilbert DL. Paclitaxel compatibility with a TOTM-plasticized PVC administration set. Hosp Pharm. 1997; 32
ReferencesZhang Y, Trissel LA, Xu QA. Paclitaxel compatibility with a triple-lumen polyurethane central catheter. Hosp Pharm. 1998; 33
Other Information
Paclitaxel is cited by NIOSH as a drug that should be handled as hazardous. Microbial Growth Potential: Kramer reported that paclitaxel 0.7 mg/mL in sodium chloride 0.9% did not result in the loss of viability of 3 of 4 microbial species. Admixtures should be refrigerated whenever possible, and the potential for inadvertent contamination and microbial growth should be incorporated into decisions regarding beyond use periods. Lipiodol: Lee et al. reported on the physical and chemical stability of paclitaxel in a chemoembolization admixture with Lipiodol (Laboratories Guerbet), an oily contrast medium. Paclitaxel from Samyang Genex 2 to 10mg was added to 1 mL of the Lipiodol. Also, 1% tricaprylin and 1% ethanol was investigated for solubility enhancement at a 10-mg/mL concentration. The drug-oil mixture was flushed with argon and sonicated to speed up drug solubilization. Paclitaxel solubility in Lipiodol was found to be approximately 7.9 mg/g of Lipiodol or 10 mg/mL at room temperature. The solution was a uniform yellowish oily liquid after preparation. Within 2 weeks, turbidity had formed in the 10-mg/mL concentration from the precipitation of paclitaxel as needle-like crystalline aggregates that could be seen under polarized light. However, if the argon flush was omitted before sonication, the turbidity appeared more rapidly in just a few days. Paclitaxel 7 to 9 mg/mL remained clear for one month. At 5 to 6 mg/mL it remained clear for at least 9 months. Addition of 1% (v/v) ethanol or tricaprylin to the 10-mg/mL concentration kept the paclitaxel in solution for 4 months. No chemical instability of the paclitaxel occurred in 60 days at ambient room temperature by HPLC and X-ray diffraction analysis of the paclitaxel content of this latter formulation. Similar results were found with the 5-mg/ml concentration. Lipid Nanoemulsion: Kadam et al. reported on a demonstration project of the lipid stability of Clinoleic 20% and Intralipid 20% after incorporation of paclitaxel into the lipid phase. Paclitaxel concentrations of 1, 3, and 6 mg/mL were prepared by adding the drug into the respective lipid emulsions in glass flasks and vortex mixing for 5 minutes. This was followed by bath sonication for two hours at 4 degree C. Samples were stored at room temperature and 4 degree C for two weeks. The incorporation of paclitaxel did not affect lipid droplet size of either lipid emulsion with the Clinoleic formulation exhibiting smaller droplets. pH in both emulsions markedly decreased during room temperature storage possibly due to fatty acid hydrolysis. Under refrigeration, the pH of the Intralipid-based emulsion declined while the Clinoleic-based emulsion did not. In addition, the zeta potential of the Clinoleic formulation was greater. The authors concluded the Clinoleic exhibited greater droplet stability. It should be noted that no evaluation for the stability of paclitaxel was performed. No evaluation of the potential for drug microprecipitation was performed. Distribution of the drug in the lipid and aqueous phases was not evaluated. Finally, no sterilization was performed in this laboratory evaluation. The demonstration project was simply to evaluate the effects on lipid droplet stability and should NOT be considered adequate for clinical use. Quality Control: Lelievre et al. described an approach to quality control and accuracy assessment for 22 cancer chemotherapy drugs, including paclitaxel, which is designed to reduce the risk of erroneously prepared doses reaching patients. The technique utilized an ultraviolet (UV)-visible and infrared (IR) scanning analysis (Multispec, Microdom) of the finished dosage forms to verify the right molecule, concentration, and solution. Of 3149 doses of the 22 drugs tested, 7.82% varied by more than 10% from the intended concentration.
ReferencesAnon. Preventing occupational exposure to antineoplastic and other hazardous drugs in health care settings. NIOSH Publication No. 2004-165. 2004; 165
ReferencesKadam AN, Najlah M, Wan KW, et al. Stability of parenteral nanoemulsions loaded with paclitaxel: the influence of lipid phase composition, drug concentration and storage temperature. Pharm Dev Technol. 2014; 19
ReferencesKramer I. Viability of microorganisms in novel antineoplastic and antiviral drug solutions. J Oncol Pharm Pract. 1998; 4
ReferencesLee IH, Park YT, Roh K, et al. Stable paclitaxel formulations in oily contrast medium. J Control Release. 2005; 102
ReferencesLelievre B, Devys C, Daouphars M, et al. Qualitative and quantitative analysis of chemotherapy preparations. Eur J Hosp Pharm Pract. 2010; 16
Stability Max
Maximum reported stability periods: NOTE: Subject to erratic precipitation. Precipitation may occur before the maximum times noted below. See Stability. In D5W- 8 days at room temperature and up to 28 days refrigerated at low concentration. In NS- 8 days at room temperature and up to 28 days refrigerated at low concentration.
ReferencesDonyai P, Sewell GJ. Physical and chemical stability of paclitaxel infusions in different container types. J Oncol Pharm Pract. 2006; 12
ReferencesKattige A. Long-term physical and chemical stability of a generic paclitaxel infusion under simulated storage and clinical-use conditions. Eur J Hosp Pharm Sci. 2006; 12
ReferencesPourroy B, Botta C, Solas C, et al. Seventy-two-hour stability of Taxol in 5% dextrose or 0.9% sodium chloride in Viaflo, Freeflex, Ecoflac and Macoflex N non-PVC bags. J Clin Pharm Ther. 2005; 30
ReferencesXu Q, Trissel LA, Martinez JF. Stability of paclitaxel in 5% dextrose injection or 0.9% sodium chloride injection at 4, 22, or 32 degree C. Am J Hosp Pharm. 1994; 51
    Revision Date: 03/23/2022, 11:42:59 AMCopyright 2004-2023 by Lawrence A. Trissel. All Rights Reserved.

    References

    29200 - Taxol (paclitaxel) package insert. Princeton, NJ: Bristol-Meyers Squibb; 2011 Apr.42143 - Seidman AD, Hudis CA, Albanel J, et al. Dose-dense therapy with weekly 1-hour paclitaxel infusions in the treatment of metastatic breast cancer. J Clin Oncol 1998;16:3353-3361.55200 - Schulmeister L. Extravasation management: clinical update. Semin Oncol Nurs 2011;27(1):82-90.63664 - CDC National Institute for Occupational Safety and Health (NIOSH). NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2016. DHHS (NIOSH) Publication Number 2016-161, September 2016. Available on the World Wide Web at https://www.cdc.gov/niosh/docs/2016-161/pdfs/2016-161.pdf?id=10.26616/NIOSHPUB201616167387 - Perez Fidalgo, JA, Garcia Fabregat L, Cervantes A, et al. Management of chemotherapy extravasation: ESMO-EONS Clinical Practice Guidelines. Ann Oncol. 2012 Oct;23 Suppl; vii167-73.67389 - Hesketh PJ, Kris MG, Basch E, et al. Antiemetics: ASCO Guideline Update. J Clin Oncol. 2020 Aug 20;38(24):2782-2797.

    Adverse Reactions

    Mild

    • abdominal pain
    • alopecia
    • anorexia
    • arthralgia
    • asthenia
    • back pain
    • chills
    • diaphoresis
    • diarrhea
    • dizziness
    • fever
    • flushing
    • headache
    • infection
    • injection site reaction
    • lacrimation
    • maculopapular rash
    • malaise
    • myalgia
    • nail discoloration
    • nausea
    • paresthesias
    • pruritus
    • rash
    • syncope
    • tinnitus
    • vertigo
    • vomiting

    Moderate

    • anemia
    • ascites
    • ataxia
    • bleeding
    • bone marrow suppression
    • candidiasis
    • chest pain (unspecified)
    • confusion
    • conjunctivitis
    • constipation
    • dyspnea
    • edema
    • elevated hepatic enzymes
    • encephalopathy
    • erythema
    • esophagitis
    • hyperbilirubinemia
    • hyperesthesia
    • hypertension
    • hypotension
    • leukopenia
    • neutropenia
    • peripheral neuropathy
    • phlebitis
    • photopsia
    • pneumonitis
    • radiation recall reaction
    • scotomata
    • sinus tachycardia
    • stomatitis
    • supraventricular tachycardia (SVT)
    • thrombocytopenia

    Severe

    • anaphylactic shock
    • anemia
    • angioedema
    • arthralgia
    • atrial fibrillation
    • AV block
    • bradycardia
    • exfoliative dermatitis
    • hearing loss
    • hepatic encephalopathy
    • hepatic necrosis
    • ileus
    • leukoencephalopathy
    • leukopenia
    • myalgia
    • myocardial infarction
    • neutropenia
    • peripheral neuropathy
    • pleural effusion
    • pulmonary embolism
    • pulmonary fibrosis
    • renal failure (unspecified)
    • seizures
    • serious hypersensitivity reactions or anaphylaxis
    • Stevens-Johnson syndrome
    • thrombocytopenia
    • thromboembolism
    • tissue necrosis
    • toxic epidermal necrolysis
    • typhlitis
    • ventricular tachycardia

    Bone marrow suppression is the dose-limiting toxicity of paclitaxel. Results of pooled studies of single agent paclitaxel (given as 135 to 300mg/m2 over 3 or 24 hours) in the treatment of ovarian or breast cancer (n=812) demonstrate the following hematologic-related adverse reactions: neutropenia 90% (< 2000/mm3) and 52% (< 500/mm3); leukopenia 90% (< 4000/mm3) and 17% (< 1000/mm3); thrombocytopenia 20% (< 100,000/mm3) and 7% (< 50,000/mm3); and anemia 78% (< 11 g/dl) and 16% (< 8 g/dl). Bleeding was reported in 14% of patients. Red cell transfusions were necessary in 25% of patients and platelet transfusions occurred in 2% of patients. Neutrophil nadirs generally occur at a median of 11 days after paclitaxel treatment. When paclitaxel was given as part of combination therapy for Kaposi's sarcoma, ovarian, breast, or lung cancer during clinical trials, the incidence of hematologic toxicity was similar to single paclitaxel. In adjuvant breast cancer paclitaxel trials, the incidence of severe thrombocytopenia and platelet transfusions increased with higher doses of doxorubicin. Generally, the next cycle of paclitaxel should not be given until the baseline neutrophil count is > 1500 cells/mm3 and the platelet count is > 100,000 cells/mm3. If severe neutropenia (< 500 cells/mm3 for >7 days) occurs during therapy, the addition of colony-stimulating factors or a 20% reduction in paclitaxel dose is recommended for subsequent cycles. The incidence and severity of paclitaxel-induced myelosuppression are more significantly influenced by the duration of infusion versus the dose given.[29200] When given as a weekly infusion, myelosuppression is mild and does not appear to be cumulative even with prolonged therapy. Moderate leukopenia (WBC < 2000/mm3) was noted when paclitaxel was given intraperitoneally at doses >= 175mg/m2.[25770] In a phase III trial where paclitaxel IV was given in combination with intraperitoneal (IP) cisplatin and paclitaxel, leukopenia (WBC < 1000/mm3) and a platelet count < 25,000/mm3 occurred more frequently in those receiving the IP therapy, compared to those in the IV arm of the trial (76% vs. 64% and 12% vs. 4%, respectively). Other hematologic events occurred at a similar incidence in the 2 groups.[32309] Intraperitoneal paclitaxel given weekly at doses of 75 mg/m2 were associated with Grade 2 leukopenia.[32303]

    Fever (12% all treatment courses) was reported in paclitaxel clinical trials with or without infection. Febrile neutropenia was noted in 2—55% of patients. Other general adverse events reported include asthenia (17% of paclitaxel plus cisplatin patients), malaise, and anorexia. Edema was reported in 21% of all patients (17% without baseline edema) with only 1% of patients reporting severe edema. This was most commonly focal and disease-related.[29200]

    Serious hypersensitivity reactions or anaphylaxis characterized by dyspnea requiring treatment, a drop in blood pressure requiring treatment, angioedema, and generalized urticaria has occurred in 2 to 4% of patients in paclitaxel clinical trials. Other severe reactions include chest pain (unspecified) and tachycardia. Fatal reactions have occurred despite premedication. Results of pooled studies of single agent paclitaxel (given as 135 to 300mg/m2 over 3 or 24 hours) in the treatment of ovarian or breast cancer (n=812) demonstrated an overall incidence of hypersensitivity reactions in 41% of patients and 20% of all courses. There is no apparent dose or schedule effect for hypersensitivity reactions; 3-hour infusions are not associated with increased hypersensitivity reactions as compared to 24-hour infusions. Minor hypersensitivity reactions include mild flushing (28%), skin rash (unspecified) (12%), low blood pressure (4%), dyspnea (2%), tachycardia (2%), and high blood pressure (1%). Cases of chills, anaphylactic shock, back pain, abdominal pain, pain in the extremities, and diaphoresis in association of hypersensitivity reactions have also been noted. Mild reactions do not require interruption of therapy. However, severe reactions require immediate discontinuation of paclitaxel therapy and aggressive symptomatic management. Although this reaction may occur with any course of therapy, it usually happens with the first or second; no severe reactions have been reported after the third course. The reaction usually occurs within the first hour of the treatment course. Manufacturer recommended prophylaxis against hypersensitivity includes dexamethasone 20 mg 6 hours and 12 hours prior to paclitaxel administration followed by cimetidine 300 mg and diphenhydramine (or an equivalent) 50 mg 60 minutes prior to paclitaxel administration.[29200] Patients who have experienced a severe hypersensitivity reaction should not be retreated with the drug.[29200]

    Extravasation of paclitaxel is associated with an acute and delayed injection site reaction.[25525] Injection site reactions are more frequently observed during 24-hour infusions opposed to 3-hour infusions. Injection site reactions occurred in 13% of patients (n=812) in studies of single agent paclitaxel (given as 135—300 mg/m2 over 3 or 24 hours) in the treatment of ovarian or breast cancer. Reactions were usually mild and included erythema, tenderness, skin discoloration, or swelling at the injection site. More severe reactions include phlebitis, cellulitis, induration, skin exfoliation, fibrosis, and tissue necrosis.[29200] It appears that both the paclitaxel and the Cremophor EL (polyoxyethylated castor oil) vehicle may both contribute to the skin reactions.[46236] The onset of the reaction may be during a prolonged infusion while other times it may be delayed by 7—10 days. There are also reports of 'recall' reactions at the site of previous extravasation with subsequent paclitaxel administration. Currently there are no consistent guidelines for the management of paclitaxel extravasation.[29200] Local injection of hyaluronidase (150 units in 3 ml) may be beneficial in treating severe paclitaxel extravasation. Conflicting data exist regarding topical heating and cooling.[46236]

    Myalgia and arthralgia occur in 60% of paclitaxel patients; severe reactions were reported in 8% of patients. Symptoms are usually transient and usually occur 2—3 days following paclitaxel administration and then resolve within a few days. It is important to distinguish arthralgia and myalgias from treatment-related neuropathies. The intensity and frequency of arthralgias and myalgias tend to increase with increasing dose of paclitaxel, especially doses >= 190 mg/m2. They do not seem to be related to the duration of the infusion.[29200] In a study comparing 250 mg/m2 IV over 3 or 24 hours, the incidence of grade 3 arthralgia/myalgia was 19% for both treatment arms.[25774] Myalgia is common in the shoulder and paraspinal muscles. Arthralgias are common in the large joints of the arms and legs. Acetaminophen is not effective treatment even for mild symptoms. Non-steroidal anti-inflammatory agents such as ibuprofen may be used for the treatment of paclitaxel associated arthralgias and myalgias. For moderate or severe symptoms, corticosteroids or opiate agonists may be appropriate for short-term management. Anticonvulsants and tricyclic antidepressants have also been used for severe symptoms. Prophylactic administration of dexamethasone in patients who are predisposed to arthralgia and myalgia beginning on day 3 following paclitaxel infusion has been effective. The regimen of dexamethasone is 4 mg PO twice daily for 3 days, followed by 4 mg PO daily for 3 days.

    Transient skin reactions have been reported, secondary to paclitaxel hypersensitivity reactions; however, no other significant skin reactions have been significantly associated with paclitaxel administration. Maculopapular rash, pruritus, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported after  administration. In post-marketing surveillance, diffuse edema, thickening, and sclerosing of the skin have been reported. Exacerbation of the signs and symptoms of scleroderma has also been noted. Nail changes including pigmentation changes or nail discoloration, has been reported in 2% of patients during paclitaxel therapy.[29200]

    Hypotension during the first 3 hours of infusion occurred in 12% of patients and 3% of courses. Hypotension may also be associated with a hypersensitivity reaction (4%) in some patients and may require therapy. Bradycardia occurred in 3% of patients and 1% of all courses. These effects were usually asymptomatic. Neither dose or infusion schedule effect the incidence of hypotension or bradycardia. Prior anthracycline therapy also does not affect the incidence of hypotension or bradycardia. Close monitoring of vital signs during paclitaxel infusion is recommended. Severe cardiac conduction abnormalities occurred in about 1% of patients. Severe cardiovascular events occur rarely and may include syncope, rhythm abnormalities, hypertension, and venous thromboembolism. Cardiac arrhythmias included asymptomatic ventricular tachycardia, bigeminy, and complete AV block requiring a pacemaker. Cases of myocardial infarction have been reported. Congestive heart failure has been reported with paclitaxel primarily in patients who have received prior anthracycline therapy. Abnormalities in the ECG were reported in 23% of 812 patients in studies of single agent paclitaxel (given as 135—300mg/m2 over 3 or 24 hours) in the treatment of ovarian or breast cancer. In patients with a normal baseline ECG (n=559) in the pooled studies, abnormal ECGs were observed in 14% of patients. The most frequent ECG abnormalities reported were non-specific repolarization abnormalities, sinus bradycardia, sinus tachycardia, and premature beats. Among patients with normal ECGs at baseline, prior to anthracycline therapy did not influence the incidence of ECG changes. Atrial fibrillation and supraventricular tachycardia (SVT) have also been reported. When paclitaxel is used in combination with doxorubicin for the treatment of metastatic breast cancer, monitoring of cardiac function is recommended. In patients with non-small cell lung cancer treated with paclitaxel in combination with cisplatin, significant cardiovascular events occurred in 12—13% of patients. The apparent increase in cardiovascular events could be due to the increased cardiovascular risk factors in patients with lung cancer. Patients with cardiac disease should be carefully monitored while taking paclitaxel. Continuous cardiac monitoring is recommended for patients with serious cardiac conduction abnormalities.[29200]

    Peripheral neuropathy has been observed in as many as 60% (3% severe) of all patients treated with single-agent paclitaxel and in 52% (2% severe) of the patients without pre-existing neuropathy. The frequency and severity of neurologic reactions were dose-dependent in patients receiving single agent paclitaxel. The incidence of peripheral neuropathy increases with increasing cumulative paclitaxel doses. Paresthesias commonly occurred in the the form of hyperesthesia. Neurologic symptoms are observed in 27% of patients after the first course and 34—51% from courses 2—10. Some studies have shown an increase in the incidence of neurotoxicity with 3-hour infusions and may be due to increased AUC levels of paclitaxel, high paclitaxel peak serum concentrations, or both. Weekly therapy has been associated with mild to moderate neuropathies in the majority of patients. Severe reactions have been noted with weekly paclitaxel doses > 100 mg/m2. Symptoms usually begin 1—3 days after treatment and resolve within 3—6 months after the drug is discontinued. Development of severe symptoms requires a paclitaxel dose reduction of 20%. Sensory neuropathies occur most commonly but motor neuropathies may develop as well. Patients may lose vibratory, temperature, and pin-prick sensation. Loss of deep tendon reflexes, fine motor skills, and unsteady gait can also occur. These effects usually follow a stocking-and-glove pattern. Pre-existing neuropathy is not a contraindication for paclitaxel; although, these patients may be at increased risk to develop paclitaxel-induced neurotoxicity. Neuropathy has been the cause of discontinuation of paclitaxel in 1% of patients treated with paclitaxel alone. When paclitaxel is given in combination with cisplatin, sensory-motor neuropathy is common and can be dose-limiting. Patients who receive increased doses of paclitaxel with cisplatin had more pronounced neurotoxicity. Paclitaxel 175 mg/m2 over 3-hours plus cisplatin 75 mg/m2 results in an increased incidence and severity of neurologic reactions as compared to cyclophosphamide and cisplatin, 87% (21% severe) versus 52% (2% severe), respectively. Also, patients with pre-existing neuropathy had exacerbations of the neuropathies at lower doses of paclitaxel when given in combination with cisplatin.[29200] Intraperitoneal paclitaxel was associated with an increased incidence of severe or life-threatening neurologic events as compared to IV therapy (19% vs. 9%) in a phase III trial.[32309]

    In pooled studies of single agent paclitaxel (given as 135—300 mg/m2 over 3 or 24 hours) in the treatment of ovarian or breast cancer (n=812), common gastrointestinal adverse effects included nausea and vomiting (52%), diarrhea (38%), and stomatitis/mucositis (31%); these effects are usually mild to moderate in severity. Mucositis occurs more frequently with 24-hour paclitaxel infusions versus 3-hour infusions. Reports have also included intestinal/GI obstruction, intestinal/GI perforation, pancreatitis, ischemic colitis, dehydration, esophagitis, constipation, and ascites. Typhlitis (neutropenic enterocolitis) has been reported with paclitaxel administered as single agent and in combination with other chemotherapy agents.[29200] When given intraperitoneally, the dose limiting toxicity is the development of severe abdominal pain, which occurs at doses > 175 mg/m2.[25770] Intraperitoneal paclitaxel given weekly at doses of 75 mg/m2 were associated with Grade 2 abdominal pain, nausea, and vomiting.[32303]

    Alopecia is one of the most common adverse reactions to paclitaxel. Hair loss is usually complete and occurs over the entire body. It has been reported to occur in 87% of patients [29200], but probably occurs in 100%. Most patients will lose all scalp hair after the first treatment. Other body hair, including eyebrows, will be lost with subsequent treatments.

    Paclitaxel has been associated with a radiation recall reaction.[29200] In patients who have received previous radiation, paclitaxel may cause erythema, exfoliative dermatitis, pain, and burning similar to that experienced with the prior radiation therapy. Radiation pneumonitis has been reported in patients receiving concurrent paclitaxel and radiation therapy.[29200] Paclitaxel acts as a radiation sensitizer and may increase the incidence of radiation pneumonitis. Bilateral pneumonitis has been reported. In one series, patients developed interstitial infiltrates either during or within 6 hours of the administration of paclitaxel 200 mg/m2 IV over 3 hours. Symptoms reported included nonproductive cough, dyspnea, and oxygen desaturation. The symptoms responded to parenteral corticosteroids.[25775] Interstitial pneumonia, pulmonary fibrosis, and pulmonary embolism have also been reported during paclitaxel therapy. Rare cases of interstitial pneumonitis, lung fibrosis, and pulmonary embolism have been reported during safety surveillance for paclitaxel. Pleural effusion and respiratory failure have also been reported.[29200]

    Elevated hepatic enzymes have been reported in patients following paclitaxel treatment. In pooled studies of single agent paclitaxel (given as 135—300 mg/m2 over 3 or 24 hours) in the treatment of ovarian or breast cancer to patients with normal baseline hepatic function, reported increases were as follows: elevated bilirubin/hyperbilirubinemia (7%), elevated alkaline phosphatase (22%), and elevated AST (19%). There was no relationship to dose or schedule and prolonged exposure was not associated with cumulative hepatotoxicity. Compared to patients with solid tumors, patients with Kaposi's sarcoma have a higher incidence of elevated hepatic enzymes. Currently, there is no evidence to suggest that elevation in liver enzymes or hepatic dysfunction alters the effect of paclitaxel. If significant hepatic dysfunction occurs, dosages of paclitaxel may need to be reduced (see Dosage). There have been reports of hepatic necrosis and hepatic encephalopathy leading to death .[29200]

    In Kaposi's sarcoma patients treated with paclitaxel, 18—34% of patients had increased serum creatinine and 5 patients had Grade 3 or 4 renal toxicity. One patient with suspected HIV nephropathy of grade 4 severity had to discontinue therapy. The other 4 patients had renal insufficiency with reversible increases in serum creatinine. Patients with gynecological cancers treated with paclitaxel in combination with cisplatin may have an increased risk of renal failure (unspecified) than patients treated with cisplatin alone. Compared to patients with solid tumors, patients with Kaposi's sarcoma have a higher incidence of renal toxicity.[29200]

    Infection was reported in 30% of patients in studies of single agent paclitaxel (given as 135—300 mg/m2 over 3 or 24 hours) in the treatment of ovarian or breast cancer. Infection was associated with fatalities in 1% of patients and included sepsis, pneumonia, and peritonitis. Urinary tract infections and upper respiratory tract infection were the most common infectious episodes. In immunocompromised patients with advanced HIV-disease and Kaposi's sarcoma, 61% (range 54—76% in studies) reported at least one opportunistic infection. These infections included cytomegalovirus (27—45%), herpes simplex (11—38%), Pneumocystis carinii (14—21%), M. avium intracellulare (4—24%), esophageal candidiasis (7—9%), cryptosporidiosis (7%), cryptococcal meningitis (2—3%), and leukoencephalopathy (2%).[29200]

    Other than peripheral neuropathy serious neurologic reactions following paclitaxel administration are rare (< 1%) and have included grand mal seizures, syncope, ataxia, and neuroencephalopathy (encephalopathy). Rarely, autonomic neuropathy resulting in paralytic ileus has been reported. Convulsions, dizziness, headache, and confusion have also been reported. In pediatric patients, CNS toxicity has been associated with paclitaxel doses of 350—420 mg/m2 IV over 3 hours. This toxicity is probably due to the high ethanol content of the vehicle given over a short period of time and the concurrent administration of antihistamines. However, the potential effects of paclitaxel on the CNS status of children cannot be ruled out. Paclitaxel also contains dehydrated alcohol USP (396 mg/ml); therefore, consideration should be given to possible CNS effects associated with alcohol.[29200]

    Optic nerve and/or visual disturbances (scintillating scotomata) have been reported with the use of paclitaxel, especially in patients receiving higher than recommended doses. These effects have generally been reversible; however, some cases suggest the possibility of persistent optic nerve damage. Post-marketing reports have also included ototoxicity, specifically hearing loss and tinnitus. Other adverse events that have been reported include conjunctivitis, increased lacrimation, photopsia, visual floaters, and vertigo.[29200]

    Revision Date: 02/28/2018, 02:24:21 PM

    References

    25525 - Herrington JD, Figuerroa JA. Severe necrosis due to paclitaxel extravasation. Pharmacotherapy 1997;17:163-5.25770 - Markman M, Rowinsky E, Hakes T, et al. Phase I trial of intraperitoneal taxol: a Gynecologic Oncology Group study. J Clin Oncol 1992;10:1485-1491.25774 - Mamounas E. Effect of Taxol duration of infusion in advanced breast cancer (ABC): Results from NSABP B-26 trial comparing 3 to 24-hr infusion of high-dose Taxol. Proc Am Soc Clin Oncol 1998;17:389a.25775 - Khan A, McNally D, Tutschka PL, et al. Paclitaxel-induced acute bilateral pneumonitis. Ann Pharmacother 1997;31:1471-1474.29200 - Taxol (paclitaxel) package insert. Princeton, NJ: Bristol-Meyers Squibb; 2011 Apr.32303 - Francis P, Rowinsky E, Schneider J et al. Phase I feasibility study of weekly paclitaxel: a Gynecologic Oncology Group pilot study. J Clin Oncol 1995;13:2961-7.32309 - Armstrong DK, Bundy B, Wenzel L, et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med 2006;354:34-43.46236 - Stanford BL, Hardwicke F. A review of clinical experience with paclitaxel extravasations. Support Care Cancer 2003;11:270-77.

    Contraindications/Precautions

    Absolute contraindications are italicized.

    • neutropenia
    • polyoxyethylated castor oil hypersensitivity
    • accidental exposure
    • alcoholism
    • angina
    • AV block
    • bone marrow suppression
    • bradycardia
    • breast-feeding
    • cardiac arrhythmias
    • cardiac disease
    • children
    • dental disease
    • dental work
    • driving or operating machinery
    • extravasation
    • geriatric
    • heart failure
    • hepatic disease
    • herpes infection
    • infection
    • intramuscular administration
    • intramuscular injections
    • Kaposi's sarcoma
    • myocardial infarction
    • ocular exposure
    • peripheral neuropathy
    • pregnancy
    • radiation therapy
    • requires a specialized care setting
    • requires an experienced clinician
    • serious hypersensitivity reactions or anaphylaxis
    • subcutaneous administration
    • taxane hypersensitivity
    • thrombocytopenia
    • vaccination
    • varicella
    • viral infection

    Paclitaxel is contraindicated in patients who have a history of severe paclitaxel hypersensitivity; those patients with a history of other taxane hypersensitivity should be given paclitaxel with caution. A risk of serious hypersensitivity reactions or anaphylaxis has been reported in patients receiving paclitaxel. Patients with known polyoxyethylated castor oil hypersensitivity should not receive the Taxol formulation or should receive it cautiously and with premedication. Polyoxyethylated compound (Cremophor EL) is believed to be responsible for anaphylactoid reactions. Severe hypersensitivity reactions (e.g., acute bronchospasm and/or hypotension) have occurred despite antihistamine (H1- and H2-blockers) and corticosteroid premedication. Hypersensitivity reactions may occur within minutes of beginning an infusion. Severe may reactions necessitate the immediate discontinuation of the infusion. Patients should be monitored closely.

    Paclitaxel is associated with dose-related bone marrow suppression. It should not be given to patients with severe thrombocytopenia or neutropenia, with solid tumors who have baseline neutrophil counts of less than 1,500 cells/mm3, with AIDS-related Kaposi's sarcoma, or with baseline neutrophil count is less than 1000 cells/mm3; these patients may have more frequent and severe hematologic toxicities, infections (including opportunistic infections), and febrile neutropenia compared to patients with solid tumors. In all patients, blood counts should be monitored frequently during treatment. Generally, the next cycle should not be given until neutrophils reach 1500/mm3 and higher (1000/mm3 for Kaposi's sarcoma patients) and platelets recover to 100,000/mm3 or higher. In patients with a neutrophil count of less than 500 cells/mm3 for longer than 1 week, consider adding colony-stimulating factor support or reducing subsequent paclitaxel doses by 20%. Due to these severe adverse reactions, paclitaxel requires an experienced clinician knowledgeable in the use of cancer chemotherapeutic agents. Administration requires a specialized care setting such as a hospital or treatment facility so that facilities are readily available for appropriate management of complications. Use cautiously in patients who have myelosuppression due to previous therapy such as other chemotherapy or radiotherapy; these patients may be more susceptible to the myelosuppressive effects of paclitaxel. Patients with active infection should be treated prior to receiving paclitaxel. Patients with a history of varicella zoster, other herpes infection (e.g., herpes simplex), or other viral infection are at risk for reactivation of the infection when treated with chemotherapy.[29200]

    Severe conduction abnormalities have been documented in during paclitaxel therapy and in some cases requiring pacemaker placement. If patients develop significant cardiac conduction abnormalities during paclitaxel infusion, appropriate therapy should be administered and continuous cardiac monitoring should be performed during subsequent therapy with paclitaxel. Patients with cardiac disease including angina, cardiac arrhythmias including AV block, history of congestive heart failure, or myocardial infarction within the past 6 months should be carefully monitored during paclitaxel therapy due to the potential for serious cardiac complications. In addition, patients receiving paclitaxel in combination with doxorubicin for metastatic breast cancer should be considered for cardiac monitoring. In a review of gynecologic cancer patients with major risk factors who received paclitaxel, no evidence of additive adverse effects was noted. As many of the reports of severe cardiac events were seen in early trials of paclitaxel as a result of hypersensitivity reactions, appropriate premedication appears to have decreased the incidence of these effects. It should be noted that patients with severe conduction abnormalities were not included in this review.[25773] Because bradycardia is a common adverse reaction, patients receiving drugs known to cause bradycardia, such as beta-blockers, calcium-channel blockers, and digoxin, also should be monitored carefully.[29200]

    Preexisting peripheral neuropathy is not a contraindication for paclitaxel; although, these patients may be at increased risk to develop paclitaxel-induced neurotoxicity. Exacerbation of pre-existing neuropathies may occur at relatively low paclitaxel doses. Patients who have been exposed to agents that may cause neurotoxicity, such as cisplatin, may also be at increased risk for paclitaxel-induced neurotoxicity. Patients with severe neurotoxic symptoms should have their paclitaxel doses reduced by 20%.

    Geriatric patients are at increased risk for adverse reactions to paclitaxel therapy. In most studies, severe myelosuppression was more frequent in elderly patients; in some studies, severe neuropathy was more common in the elderly. In two clinical studies of non-small cell lung cancer (NSCLC), the elderly patients treated with paclitaxel had a higher incidence of cardiovascular events.

    Paclitaxel should be used cautiously in patients with known hepatic disease. Because paclitaxel is extensively metabolized through cytochrome P-450 system, excessive toxicity may occur in patients with hyperbilirubinemia and elevated liver enzymes. Limited data suggest myelotoxicity may be increased in patients with serum bilirubin > 2 times ULN. Patients with hepatic disease may require dose reductions (see Dosage).[29200]

    Paclitaxel is classified as FDA pregnancy risk category D and has been shown to produce toxic effects, including death, in fetal animal studies. There are no data concerning the effects in pregnant women. Therefore, paclitaxel should be avoided during pregnancy, and females of childbearing potential should be instructed to avoid becoming pregnant during paclitaxel therapy. If a women becomes pregnant while receiving this drug, she should be counseled of the potential harm to the fetus and the possibility of loss of pregnancy.[29200]

    It is unknown whether paclitaxel is excreted into human breast milk; paclitaxel was excreted into the breast milk of lactating rats at concentrations higher than those seen in plasma. Because of the potential for serious adverse reactions in nursing infants, patients should be instructed to discontinue breast-feeding during paclitaxel therapy.[29200]

    Patients who have received prior radiation therapy are at risk for radiation recall reactions when receiving paclitaxel. These patients should be monitored closely. In addition, paclitaxel may increase the efficacy and/or the adverse reactions of radiation therapy.

    Intramuscular injections should be avoided in patients with platelet counts < 50,000/mm3 who are receiving paclitaxel. IM injections can cause bleeding, bruising, or hematomas in patients with paclitaxel-induced thrombocytopenia.

    Myelosuppressive effects of paclitaxel can increase the risk of infection or bleeding; therefore, dental work should be delayed until blood counts have returned to normal. Patients, especially those with dental disease, should be instructed in proper oral hygiene, including caution in use of regular toothbrushes, dental floss, and toothpicks.

    The Taxol formulation of paclitaxel contains a high concentration of ethanol (49.7% (v/v)). Consideration should be given to the CNS effects and other effects of alcohol. Special consideration may be prudent in individuals with alcoholism or a history of substance abuse. Patients should be cautioned regarding driving or operating machinery following infusion of Taxol as the high alcohol content infused over a short period of time may theoretically cause impairment in some persons.

    The safe and effective use of paclitaxel in children has not been established. There have been reports of central nervous system toxicity, rarely associated with death, in a pediatric clinical trial in which Taxol was infused at doses ranging from 350—420 mg/m2 IV over 3 hours. The toxicity is thought to be due to the high concentration of alcohol in the Taxol vehicle and the short infusion time. However, the effect of antihistamine premedication and the high dose of paclitaxel used in this study, over twice the adult recommended dose, cannot be discounted as possible attributing factors.

    Paclitaxel is considered a vesicant. Extravasation of paclitaxel infusions should be avoided as tissue necrosis has been reported following paclitaxel extravasation.[25525] Patients should be closely monitored during IV infusions for signs and symptoms of extravasation such as pain, swelling and poor blood return. In some cases the onset of the extravasation reaction either occurred during a prolonged infusion or was delayed by 7 to 10 days. Patients who have previously experienced a paclitaxel extravasation may have a 'recall' reaction at the previous extravasation site during subsequent paclitaxel infusions. It is recommended that prolonged paclitaxel infusions not be given through peripheral lines due to the potential for severe reactions if extravasated. Intramuscular administration and subcutaneous administration of paclitaxel should be avoided.

    Use care to avoid accidental exposure to paclitaxel during preparation, handling and administration. The use of protective gowns, gloves and goggles is recommended. Avoid ocular exposure of paclitaxel solutions. If exposure occurs, the eye should be rinsed immediately and thoroughly; seek medical attention.

    Vaccination during chemotherapy with paclitaxel or radiation therapy should be avoided because the antibody response is suboptimal. When chemotherapy is being planned, vaccination should precede the initiation of chemotherapy by >= 2 weeks. The administration of live vaccines to immunocompromised patients should be avoided. Those undergoing chemotherapy should not be exposed to others who have recently received the oral poliovirus vaccine (OPV). Measles-mumps-rubella (MMR) vaccination is not contraindicated for the close contacts, including health care professionals, of immunocompromised patients. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination. When exposed to a vaccine-preventable disease such as measles, severely immunocompromised children should be considered susceptible regardless of their vaccination history.

    Revision Date: 02/28/2018, 02:20:48 PM

    References

    25525 - Herrington JD, Figuerroa JA. Severe necrosis due to paclitaxel extravasation. Pharmacotherapy 1997;17:163-5.25773 - Markman M, Kennedy A, Webster K, et al. Paclitaxel administration to gynecologic cancer patients with major cardiac risk factors. J Clin Oncol 1998;16:3483-3485.29200 - Taxol (paclitaxel) package insert. Princeton, NJ: Bristol-Meyers Squibb; 2011 Apr.

    Mechanism of Action

    Mechanism of Action: Paclitaxel is an antimicrotubule chemotherapy agent. Although both bind to tubulin, the mechanism of action of paclitaxel differs from the vinca alkaloids. Paclitaxel promotes the assembly of microtubules and stabilizes their formation by inhibiting depolymerization. These microtubules are extremely stable and non-functional. In addition to functioning as components of the spindle apparatus within the cell, normal microtubules also maintain cell shape, assist in cellular motility, attachment, and intracellular transport, and modulate interactions with growth factors. The primary effect of paclitaxel is to inhibit the cell cycle during mitosis. Paclitaxel also inhibits the transition from G0 to S phase by disrupting tubulin in the cell membrane and/or direct inhibition of the disassembly of the cytoskeleton interrupting intracellular transport and communications.

    Microtubules are in equilibrium with tubulin heterodimers, the building blocks of microtubules, which consist of alpha- and beta-subunits. Paclitaxel reversibly binds to the N-terminal 31 amino acids of the beta-tubulin subunit of the microtubule rather than the tubulin subunits. The binding site of paclitaxel is different from the binding site of colchicine, epipodophyllotoxins, and vinblastine. Paclitaxel shifts the equilibrium towards microtubule assembly. Cells treated with paclitaxel show distinctive morphologic effects. Multiple bundles of microtubules are noted in paclitaxel treated cells. These bundles form during all phases of the cell cycle. Abnormal spindle asters are formed during mitosis. Paclitaxel also induces the expression of tumor necrosis factor-alpha and inhibits angiogenesis, although the exact roles of these actions in the cytotoxic effects of paclitaxel is not known. Paclitaxel acts as a radiation sensitizer due to its ability to stop the cell cycle during the premitotic G2 and mitotic phases, which are the most sensitive to the effects of radiation.

    Paclitaxel will induce varying intracellular effects depending upon the intracellular concentration and cell type. In vitro studies have shown a minimum concentration for cytotoxic effects. As the taxane concentration increases, the dose-response decreases. Prolonged exposure to taxanes is critical to cytotoxicity and is more important than increasing the drug concentration.

    Resistance to paclitaxel may develop via two different mechanisms. Alterations in the alpha- and beta-tubulin subunits can decrease the rate of polymerization into microtubules. When this occurs, administration of taxanes may actually normalize the rate of microtubule assembly. The second mechanism is through multidrug resistance (MDR), which results in decreased intracellular drug accumulation and retention. This mechanism of resistance primarily affects naturally occurring chemotherapy agents. MDR is due to overexpression of the mdr-1 gene, which encodes for a membrane P-glycoprotein (P-gp) that acts as a drug efflux pump. The degree of resistance is proportional to the amount of P-gp. There is not complete cross-resistance between the taxanes and anthracyclines; the exact role of MDR in paclitaxel resistance has not been determined.

    Revision Date: 02/07/2009, 02:52:24 AM

    References

    Pharmacokinetics

    Paclitaxel is given by IV administration; an oral formulation is undergoing clinical evaluation. Paclitaxel undergoes nonlinear pharmacokinetics due to saturable distribution and/or metabolism. Nonlinear pharmacokinetics are especially evident when administered over shorter periods (i.e., 3 hours) versus initial studies of 24-hour or longer infusions. Clinical implications of the nonlinear pharmacokinetics include disproportionate increases in AUC, peak plasma concentrations, and toxicity with dose increases, while dose reductions may lead to decreased cytotoxicity. Tissue sites are saturated at relatively low concentrations (those achieved with < 175 mg/m2 over 3 hours) and metabolism is saturated at higher doses (>= 175 mg/m2 over 3 hours). Peak tissue concentrations do not change significantly doses are increased from 135 to 250 mg/m2 administered as 3- or 24-hour infusions. The rate and extent of tissue saturation are greater with shorter infusion schedules.[25762] Neutropenia and, to a lesser extent, neurotoxicity have been associated with exposure of cells above a critical plasma concentration (> 0.05 micromolar/L) or increased duration of exposure and do not correlate to dosage.

     

    Paclitaxel is extensively protein bound (95—98%) to tissue proteins, especially tubulin. It is widely distributed throughout the body except for the brain and testes. Following a 3-hour infusion the alpha-half-life is 16 minutes, beta-half life is 140 minutes, and final elimination half-life is about 19 hours.[25763] Paclitaxel is metabolized primarily via cytochrome P-450 (CYP) isoenzymes 2C8 to 6-alpha-hydroxypaclitaxel, and to a lesser extent by 3A4 to minor metabolites 3'-p-hydroxypaclitaxel and 6-alpha,3'-para-dihydroxypaclitaxel. Alterations of metabolism may occur when drugs affecting the CYP system are given concurrently. In addition, sequence-dependent drug interactions have been documented with paclitaxel and other chemotherapy agents. Elimination is due to hepatic metabolism, biliary and fecal excretion, and tissue binding. Approximately 70—80% of the dose is eliminated in the feces within 1 week. Only 1—8% of paclitaxel is eliminated unchanged in the urine.

     

    Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, CYP2C8, P-gp

    Paclitaxel is a substrate of the cytochrome P450 (CYP) isoenzymes 2C8 and 3A4, and of the multidrug resistance protein, P-glycoprotein (P-gp).[28498][49806][58751]

    Route-Specific Pharmacokinetics

    Oral Route

    Paclitaxel has poor oral availability due to its high affinity for P-glycoprotein, a multi-drug transport enzyme present in high levels in the GI tract. In clinical studies, oral paclitaxel has been given in combination with cyclosporine to improve the bioavailability, as cyclosporine blocks the activity of P-glycoprotein (see Drug Interactions).

    Other Route(s)

    Intraperitoneal route

    When given intraperitoneally (IP), exposure to the peritoneal cavity exceeds plasma exposure by about 1000-times. Paclitaxel is slowly cleared from the peritoneal cavity resulting in significant concentrations persisted within the peritoneal cavity for > 24—48 hours after a single IP administration.[25770] The prolonged terminal half-life when given IP is thought to be due to Cremophor El diluent used in the Taxol product. In one small trial, the terminal half life of IP paclitaxel was 28.7 +/- 8.72 hours versus a terminal IV half-life of 17 +/- 11.3 hours.[32312] The systemic bioavailability of IP paclitaxel in this study was 31.4 +/- 5.18%. Elimination from ascites fluid is also extremely slow with detectable levels still present after 18 days and an apparent disappearance half-life in ascites fluid of about 140 hours.[32312]

    Special Populations

    Hepatic Impairment

    Appropriate dose adjustments in patients with hepatic dysfunction have not been determined and patient specific evaluation is required. In a small study examining the safety of paclitaxel in patients with elevated bilirubin concentrations and liver enzymes, doses needed to be reduced. Patients who received paclitaxel over 3 hours had serum concentrations > 0.05 micromolar/L for longer than expected, when compared to historical controls. Patients with increased serum AST levels but normal bilirubin levels experienced more toxicity and did not tolerate single doses > 50 mg/m2 given over 24 hours.[25764] It has been recommended to reduce paclitaxel doses by at least 50% in patients with moderate or severe hyperbilirubinemia or substantially increased serum AST levels.

    Renal Impairment

    Dosage adjustments in patients with renal impairment are not required.

    Revision Date: 01/29/2015, 03:00:56 PM

    References

    25762 - Rowinsky EK. The taxanes: dosing and scheduling considerations. Oncology 1997;11(3 Suppl 2):7-19.25763 - Eisenhauer EA, Vermorken JB. The taxoids, comparative clinical pharmacology and therapeutic potential. Drugs 1998;55:5-30.25764 - Venook AP, Egorin MJ, Rosner GL, et al. Phase I and pharmacokinetic trial of paclitaxel in patients with hepatic dysfunction: Cancer and Leukemia Group B 9264. J Clin Oncol 1998;16:1811-1819.25770 - Markman M, Rowinsky E, Hakes T, et al. Phase I trial of intraperitoneal taxol: a Gynecologic Oncology Group study. J Clin Oncol 1992;10:1485-1491.28498 - Lum BL, Gosland MP, Kaubish S, et al. Molecular targets in oncology; implications of the multidrug resistance gene. Pharmacotherapy 1993;13:88-109.32312 - Gelderblom H, Verweij J, van Zomeren DM, et al. Influence of Cremophor EL on the bioavailability of intraperitoneal paclitaxel. Clin Cancer Res 2002;8:1237-41.49806 - Taxol (paclitaxel) prescribing information. Bristol Myers Squibb: Princeton, NJ; 2011 Apr.58751 - Paclitaxel prescribing information. Hospira, Inc: Lake Forest, IL; 2012 Feb.

    Pregnancy/Breast-feeding

    pregnancy

    Paclitaxel is classified as FDA pregnancy risk category D and has been shown to produce toxic effects, including death, in fetal animal studies. There are no data concerning the effects in pregnant women. Therefore, paclitaxel should be avoided during pregnancy, and females of childbearing potential should be instructed to avoid becoming pregnant during paclitaxel therapy. If a women becomes pregnant while receiving this drug, she should be counseled of the potential harm to the fetus and the possibility of loss of pregnancy.[29200]

    breast-feeding

    It is unknown whether paclitaxel is excreted into human breast milk; paclitaxel was excreted into the breast milk of lactating rats at concentrations higher than those seen in plasma. Because of the potential for serious adverse reactions in nursing infants, patients should be instructed to discontinue breast-feeding during paclitaxel therapy.[29200]

    Revision Date: 03/09/2012, 10:24:17 AM

    References

    29200 - Taxol (paclitaxel) package insert. Princeton, NJ: Bristol-Meyers Squibb; 2011 Apr.

    Interactions

    Level 1 (Severe)

    • Live Vaccines

    Level 2 (Major)

    • Acetaminophen; Ibuprofen
    • Amlodipine; Celecoxib
    • Bismuth Subcitrate Potassium; Metronidazole; Tetracycline
    • Bismuth Subsalicylate; Metronidazole; Tetracycline
    • Bupivacaine; Meloxicam
    • Celecoxib
    • Celecoxib; Tramadol
    • Chlorpheniramine; Ibuprofen; Pseudoephedrine
    • Cyclosporine
    • Diclofenac
    • Diclofenac; Misoprostol
    • Diflunisal
    • Diphenhydramine; Ibuprofen
    • Diphenhydramine; Naproxen
    • Disulfiram
    • Etodolac
    • Fenoprofen
    • Filgrastim, G-CSF
    • Flurbiprofen
    • Gemfibrozil
    • grapefruit juice
    • Hydrocodone; Ibuprofen
    • Ibuprofen
    • Ibuprofen; Famotidine
    • Ibuprofen; Oxycodone
    • Ibuprofen; Pseudoephedrine
    • Idelalisib
    • Indomethacin
    • Ketoprofen
    • Ketorolac
    • Lansoprazole; Naproxen
    • Lumacaftor; Ivacaftor
    • Meclofenamate Sodium
    • Mefenamic Acid
    • Meloxicam
    • Metronidazole
    • Mitotane
    • Nabumetone
    • Naproxen
    • Naproxen; Esomeprazole
    • Naproxen; Pseudoephedrine
    • Nonsteroidal antiinflammatory drugs
    • Oxaprozin
    • Penicillamine
    • Piroxicam
    • Sulindac
    • Sumatriptan; Naproxen
    • Tbo-Filgrastim
    • Tolmetin
    • Valdecoxib
    • Vemurafenib

    Level 3 (Moderate)

    • Adagrasib
    • Apalutamide
    • Aprepitant, Fosaprepitant
    • Asciminib
    • Atazanavir
    • Atazanavir; Cobicistat
    • Belzutifan
    • Berotralstat
    • Brigatinib
    • Carbamazepine
    • Cenobamate
    • Ceritinib
    • Cholera Vaccine
    • Clopidogrel
    • Cobicistat
    • Conivaptan
    • Crizotinib
    • Cyclophosphamide
    • Daclatasvir
    • Darunavir; Cobicistat
    • Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide
    • Deferasirox
    • Doxorubicin
    • Doxorubicin Liposomal
    • Dronedarone
    • Duvelisib
    • Efavirenz
    • Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate
    • Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate
    • Elbasvir; Grazoprevir
    • Elexacaftor; tezacaftor; ivacaftor
    • Eltrombopag
    • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide
    • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate
    • Emapalumab
    • Enzalutamide
    • Epirubicin
    • Erlotinib
    • Etravirine
    • Fedratinib
    • Fosamprenavir
    • Gadobenate Dimeglumine
    • Glecaprevir; Pibrentasvir
    • Isavuconazonium
    • Ketoconazole
    • Lapatinib
    • Lefamulin
    • Leflunomide
    • Lenacapavir
    • Letermovir
    • Levoketoconazole
    • Lonafarnib
    • Lorlatinib
    • Mavacamten
    • Mitapivat
    • Mobocertinib
    • Netupitant, Fosnetupitant; Palonosetron
    • Nevirapine
    • Odevixibat
    • Olutasidenib
    • Omaveloxolone
    • Oritavancin
    • Palifermin
    • Pazopanib
    • Pexidartinib
    • Pirtobrutinib
    • Posaconazole
    • Ribociclib
    • Ribociclib; Letrozole
    • Rifapentine
    • Rolapitant
    • SARS-CoV-2 (COVID-19) vaccines
    • Simeprevir
    • Sodium Phenylbutyrate; Taurursodiol
    • Sofosbuvir; Velpatasvir; Voxilaprevir
    • Sotorasib
    • Spironolactone
    • Spironolactone; Hydrochlorothiazide, HCTZ
    • Stiripentol
    • Telotristat Ethyl
    • Teriflunomide
    • Thalidomide
    • Tuberculin Purified Protein Derivative, PPD
    • Tucatinib
    • Voriconazole
    • Voxelotor
    • Zafirlukast

    Level 4 (Minor)

    • Amoxicillin; Clarithromycin; Omeprazole
    • Barbiturates
    • Bortezomib
    • Bosentan
    • Cabozantinib
    • Carboplatin
    • Clarithromycin
    • Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir
    • Delavirdine
    • Diltiazem
    • Erythromycin
    • Fenofibrate
    • Fenofibric Acid
    • Fluconazole
    • Fluoxetine
    • Fluvoxamine
    • Hydantoins
    • Imatinib
    • Indinavir
    • Isoniazid, INH; Pyrazinamide, PZA; Rifampin
    • Isoniazid, INH; Rifampin
    • Itraconazole
    • Lansoprazole; Amoxicillin; Clarithromycin
    • Ledipasvir; Sofosbuvir
    • Lopinavir; Ritonavir
    • Nefazodone
    • Nelfinavir
    • Nicardipine
    • Nirmatrelvir; Ritonavir
    • Olanzapine; Fluoxetine
    • Ombitasvir; Paritaprevir; Ritonavir
    • Omeprazole; Amoxicillin; Rifabutin
    • Rifabutin
    • Rifampin
    • Ritonavir
    • Rufinamide
    • Saquinavir
    • Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole
    • Trametinib
    • Trandolapril; Verapamil
    • Trimethoprim
    • Verapamil
    • Vonoprazan; Amoxicillin; Clarithromycin
    • Zonisamide
    Acetaminophen; Ibuprofen: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5938] Adagrasib: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of paclitaxel with adagrasib is necessary due to the risk of increased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A substrate and adagrasib is a strong CYP3A inhibitor. In vitro, coadministration with both strong and moderate CYP3A inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A inhibitors. [29200] [68325] Amlodipine; Celecoxib: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5938] Amoxicillin; Clarithromycin; Omeprazole: (Minor) Paclitaxel is partially metabolized by CYP3A4. The systemic clearance of paclitaxel may be decreased if coadministered with clarithromycin, an inhibitor of CYP3A4. [4718] [5938] Apalutamide: (Moderate) Monitor for decreased efficacy of paclitaxel if coadministration with apalutamide is necessary. Paclitaxel is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. [28498] [49806] [62874] Aprepitant, Fosaprepitant: (Moderate) Aprepitant, fosaprepitant is indicated for the prophylaxis of chemotherapy-induced nausea/vomiting and is often used in combination with paclitaxel. However, use caution and monitor for a possible increase in non-emetogenic paclitaxel-related adverse effects for several days after administration of a multi-day aprepitant regimen. Paclitaxel is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer. The AUC of another CYP3A4 substrate, midazolam, was significantly increased when coadministered with oral aprepitant; theoretically, this could also occur with paclitaxel. However, oral aprepitant was commonly administered with paclitaxel in clinical trials without dose adjustments for potential drug interactions; the aprepitant manufacturer does not recommend a paclitaxel dose adjustment. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. [28498] [30676] [40027] [49806] Asciminib: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of asciminib is necessary due to the risk of increased plasma concentrations of paclitaxel. Paclitaxel is a CYP2C8 substrate and asciminib is a weak CYP2C8 inhibitor. In vitro, the metabolism of paclitaxel to 6-alpha-hydroxypaclitaxel was inhibited by another inhibitor of CYP2C8. [29200] [67087] Atazanavir: (Moderate) Due to atazanavir-induced inhibition of CYP3A4 isoenzymes, atazanavir may inhibit the metabolism and thus, increase the serum concentrations of drugs that are largely metabolized via CYP3A4 including paclitaxel. If atazanavir and paclitaxel must be coadministered, the dosage of paclitaxel may need to be downwardly adjusted and conversely, upward dosage adjustment of paclitaxel may be required when atazanavir is discontinued. [4718] Atazanavir; Cobicistat: (Moderate) Due to atazanavir-induced inhibition of CYP3A4 isoenzymes, atazanavir may inhibit the metabolism and thus, increase the serum concentrations of drugs that are largely metabolized via CYP3A4 including paclitaxel. If atazanavir and paclitaxel must be coadministered, the dosage of paclitaxel may need to be downwardly adjusted and conversely, upward dosage adjustment of paclitaxel may be required when atazanavir is discontinued. [4718] (Moderate) Plasma concentrations of paclitaxel may be elevated when administered concurrently with cobicistat. Cobicistat is a strong inhibitor of CYP3A4 and P-glycoprotein (P-gp) inhibitor, while paclitaxel is a CYP3A4 and P-gp substrate. Some experts state that pharmacokinetic interactions between paclitaxel and some CYP3A4 inhibitors do not appear to be clinically significant. However, combining the drugs in clinical practice may require close monitoring to ensure proper therapeutic responses. [29211] [46390] [49806] [51664] [58000] Barbiturates: (Minor) Paclitaxel is metabolized by hepatic cytochrome P450 isoenzymes 2C8 and 3A4. Potential interactions may occur in vivo with any agent that induces CYP2C8 or CYP3A4 isoenzymes including barbiturates. [5938] Belzutifan: (Moderate) Monitor for decreased efficacy of paclitaxel if coadministration with belzutifan is necessary due to the risk of decreased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A substrate and belzutifan is a weak CYP3A inducer. [29200] [66785] Berotralstat: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of paclitaxel with berotralstat is necessary due to the risk of increased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A4 substrate and berotralstat is a moderate CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors. [29200] [66159] Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Major) Medications with significant alcohol content should not be ingested during therapy with metronidazole and should be avoided for 3 days after therapy is discontinued. Some formulations of paclitaxel contain a high level of ethanol. Administration to patients receiving or who have recently received metronidazole may result in disulfiram-like reactions. A disulfiram reaction would not be expected to occur with non-ethanol containing formulations. [28581] [29200] [48545] Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Medications with significant alcohol content should not be ingested during therapy with metronidazole and should be avoided for 3 days after therapy is discontinued. Some formulations of paclitaxel contain a high level of ethanol. Administration to patients receiving or who have recently received metronidazole may result in disulfiram-like reactions. A disulfiram reaction would not be expected to occur with non-ethanol containing formulations. [28581] [29200] [48545] Bortezomib: (Minor) Monitor patients for the development of peripheral neuropathy when receiving bortezomib in combination with other drugs that can cause peripheral neuropathy like paclitaxel; the risk of peripheral neuropathy may be additive. [9774] Bosentan: (Minor) Co-administration of bosentan with other drugs which are metabolized by hepatic enzymes has not been studied. Bosentan is an inducer of cytochrome P450 enzymes, specifically the CYP2C9 and CYP3A4 isoenzymes, and may decrease concentrations of drugs metabolized by these enzymes including paclitaxel. [4718] [5938] Brigatinib: (Moderate) Monitor for decreased efficacy of paclitaxel if coadministration with brigatinib is necessary due to the risk of decreased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A4 substrate and brigatinib is a weak CYP3A4 inducer. [29200] [61909] Bupivacaine; Meloxicam: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5938] Cabozantinib: (Minor) Monitor for an increase in paclitaxel-related adverse reactions if coadministration with cabozantinib is necessary; a dose adjustment of paclitaxel may be necessary. Paclitaxel is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown. [28498] [52506] [60738] Carbamazepine: (Moderate) Paclitaxel is metabolized by hepatic cytochrome P450 isoenzymes 2C8 and 3A4. Potential interactions may occur in vivo with any agent that induces CYP2C8 or CYP3A4 isoenzymes including carbamazepine. Clinicians should be alert to changes in the clinical effects of paclitaxel. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted when carbamazepine is used with paclitaxel. [4718] [5938] Carboplatin: (Minor) In vitro studies have shown an increase in cytotoxicity with either the simultaneous or sequential administration of paclitaxel and carboplatin. It appears that paclitaxel followed by carboplatin is more cytotoxic. The pharmacokinetics of either agent is not affected by this sequence of administration. [2563] [5949] Celecoxib: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5938] Celecoxib; Tramadol: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5938] Cenobamate: (Moderate) Monitor for decreased efficacy of paclitaxel if coadministration with cenobamate is necessary due to the risk of decreased paclitaxel concentrations of paclitaxel. Paclitaxel is a CYP3A4 substrate and cenobamate is a moderate CYP3A4 inducer. [28498] [49806] [64768] Ceritinib: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration with ceritinib is necessary. Ceritinib is a strong CYP3A4 inhibitor and paclitaxel is metabolized by CYP3A4. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors. [28498] [49806] [57094] Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5938] Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine. [60871] Clarithromycin: (Minor) Paclitaxel is partially metabolized by CYP3A4. The systemic clearance of paclitaxel may be decreased if coadministered with clarithromycin, an inhibitor of CYP3A4. [4718] [5938] Clopidogrel: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of paclitaxel with clopidogrel is necessary due to the risk of increased plasma concentrations of paclitaxel. Paclitaxel is a CYP2C8 substrate and clopidogrel is a moderate CYP2C8 inhibitor. In vitro, the metabolism of paclitaxel to 6-alpha-hydroxypaclitaxel was inhibited by another inhibitor of CYP2C8. [28435] [29200] Cobicistat: (Moderate) Plasma concentrations of paclitaxel may be elevated when administered concurrently with cobicistat. Cobicistat is a strong inhibitor of CYP3A4 and P-glycoprotein (P-gp) inhibitor, while paclitaxel is a CYP3A4 and P-gp substrate. Some experts state that pharmacokinetic interactions between paclitaxel and some CYP3A4 inhibitors do not appear to be clinically significant. However, combining the drugs in clinical practice may require close monitoring to ensure proper therapeutic responses. [29211] [46390] [49806] [51664] [58000] Conivaptan: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of paclitaxel with conivaptan is necessary due to the risk of increased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A substrate and conivaptan is a moderate CYP3A inhibitor. In vitro, coadministration with moderate CYP3A inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A inhibitors. [29200] [31764] Crizotinib: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration with crizotinib is necessary. Paclitaxel is a CYP3A4 substrate and crizotinib is a moderate CYP3A inhibitor. [45458] [49806] Cyclophosphamide: (Moderate) Closely monitor complete blood counts if coadministration of cyclophosphamide with paclitaxel is necessary. Increased hematologic toxicity has been reported when cyclophosphamide was administered after paclitaxel infusion. [65780] [65781] [65782] Cyclosporine: (Major) In vitro, the metabolism of paclitaxel is inhibited by cyclosporine, but cyclosporine concentrations used exceeded those found in vivo following normal therapeutic doses used in transplantation. Additionally, cyclosporine blocks the multidrug resistance (MDR) P-glycoprotein, which is a mechanism of resistance to naturally occurring (non-synthetic) chemotherapy agents. These agents could enhance paclitaxel's activity and toxicity. Paclitaxel has poor oral availability due to its high affinity for P-glycoprotein present in high levels in the GI tract. In clinical studies, oral paclitaxel has been given in combination with cyclosporine to improve the bioavailability of paclitaxel, due to cyclosporine-induced blockade of P-glycoprotein located in the in GI tract. The bioavailability of oral paclitaxel was 8-fold higher when given in combination with cyclosporine than after oral paclitaxel alone. Therapeutic concentrations were achieved within 7.4 hours, comparable to an equivalent IV dose. [28001] [28155] [28498] [46115] [49806] [58209] Daclatasvir: (Moderate) Systemic exposure of paclitaxel, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of paclitaxel; monitor patients for potential adverse effects. [28498] [49806] [60001] Darunavir; Cobicistat: (Moderate) Plasma concentrations of paclitaxel may be elevated when administered concurrently with cobicistat. Cobicistat is a strong inhibitor of CYP3A4 and P-glycoprotein (P-gp) inhibitor, while paclitaxel is a CYP3A4 and P-gp substrate. Some experts state that pharmacokinetic interactions between paclitaxel and some CYP3A4 inhibitors do not appear to be clinically significant. However, combining the drugs in clinical practice may require close monitoring to ensure proper therapeutic responses. [29211] [46390] [49806] [51664] [58000] Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Plasma concentrations of paclitaxel may be elevated when administered concurrently with cobicistat. Cobicistat is a strong inhibitor of CYP3A4 and P-glycoprotein (P-gp) inhibitor, while paclitaxel is a CYP3A4 and P-gp substrate. Some experts state that pharmacokinetic interactions between paclitaxel and some CYP3A4 inhibitors do not appear to be clinically significant. However, combining the drugs in clinical practice may require close monitoring to ensure proper therapeutic responses. [29211] [46390] [49806] [51664] [58000] Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Minor) Concurrent administration of paclitaxel (or nanoparticle albumin-bound paclitaxel) with dasabuvir; ombitasvir; paritaprevir; ritonavir may result in increased paclitaxel plasma concentrations and risk for toxicity. Caution and close monitoring are advised if these drugs are administered together. Paclitaxel is metabolized by the hepatic isoenzymes CYP2C8 and CYP3A4; ritonavir is a potent CYP3A4 inhibitor. In addition, paclitaxel is a substrate of the drug transporter P-glycoprotein (P-gp), and ritonavir also inhibits P-gp. Paritaprevir also inhibits P-gp. [28498] [49806] [58664] (Minor) Due to ritonavir's potential inhibitory effects on various hepatic isoenzymes, numerous drug interactions may occur with ritonavir. Close monitoring of serum drug concentrations and/or therapeutic and adverse effects is required when paclitaxel (a CYP2C8 and CYP3A4 substrate) is coadministered with ritonavir (a CYP3A4 inhibitor). In addition, paclitaxel is a substrate of the drug transporter P-glycoprotein (P-gp), and ritonavir also inhibits P-gp. [28001] [28341] [28380] [28498] [49806] [56579] [58664] Deferasirox: (Moderate) Deferasirox inhibits CYP2C8. Paclitaxel is a substrate for CYP2C8. The concomitant administration of deferasirox and the CYP2C8 substrate repaglinide (single dose of 0.5 mg) resulted in an increase in repaglinide Cmax by 62% and an increase in AUC 2.3-fold. Although specific drug interaction studies of deferasirox and paclitaxel are not available, a similar interaction may occur. The dose of paclitaxel may need to be decreased if coadministered with deferasirox. [31807] Delavirdine: (Minor) Delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as paclitaxel, should be expected with concurrent use of delavirdine. [4718] Diclofenac: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5938] Diclofenac; Misoprostol: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5938] Diflunisal: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5938] Diltiazem: (Minor) Additive bradycardia may occur in patients receiving paclitaxel and other drugs known to cause bradycardia, such as certain calcium-channel blockers, such as diltiazem. These patients should be monitored carefully. Paclitaxel is metabolized by hepatic cytochrome P450 (CYP) isoenzymes 2C8 and 3A4. Paclitaxel metabolism may be inhibited by diltiazem, a moderate CYP3A4 inhibitor. Combining the drugs in clinical practice may require close monitoring to ensure proper therapeutic responses; monitor patients for symptoms and signs of toxicity, such as myelosuppression and peripheral neuropathy. [49806] [58751] Diphenhydramine; Ibuprofen: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5938] Diphenhydramine; Naproxen: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5938] Disulfiram: (Major) Some formulations of paclitaxel injection contain a high level of ethanol. Administration to patients receiving or who have recently received disulfiram may result in disulfiram-like reactions. A disulfiram reaction would not be expected to occur with non-ethanol containing formulations. [29200] [48545] Doxorubicin Liposomal: (Moderate) Use paclitaxel and doxorubicin together with caution. Administer doxorubicin prior to paclitaxel; the AUC values of doxorubicin and its metabolites may increase if paclitaxel is given first. Paclitaxel and doxorubicin are both CYP3A4 substrates. [58751] [61628] Doxorubicin: (Moderate) Use paclitaxel and doxorubicin together with caution. Administer doxorubicin prior to paclitaxel; the AUC values of doxorubicin and its metabolites may increase if paclitaxel is given first. Paclitaxel and doxorubicin are both CYP3A4 substrates. [58751] [61628] Dronedarone: (Moderate) Dronedarone is metabolized by and is an inhibitor of CYP3A; dronedarone also inhibits P-gp. Paclitaxel is a substrate for CYP3A4 and P-gp. The concomitant administration of dronedarone with CYP3A4 and P-gp substrates may result in increased exposure of the substrate and should, therefore, be undertaken with caution. [36101] Duvelisib: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration with duvelisib is necessary. Coadministration may increase the exposure of paclitaxel. Paclitaxel is a CYP3A4 substrate and duvelisib is a moderate CYP3A4 inhibitor. [49806] [63571] Efavirenz: (Moderate) Efavirenz induces CYP3A4 and may decrease serum concentrations of drugs metabolized by this enzyme, such as paclitaxel. [28442] [4718] Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Efavirenz induces CYP3A4 and may decrease serum concentrations of drugs metabolized by this enzyme, such as paclitaxel. [28442] [4718] Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Efavirenz induces CYP3A4 and may decrease serum concentrations of drugs metabolized by this enzyme, such as paclitaxel. [28442] [4718] Elbasvir; Grazoprevir: (Moderate) Administering paclitaxel with elbasvir; grazoprevir may result in elevated paclitaxel plasma concentrations. Paclitaxel is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events. [28498] [49806] [60523] Elexacaftor; tezacaftor; ivacaftor: (Moderate) Monitor for paclitaxel-related adverse reactions during coadministration of elexacaftor; tezacaftor; ivacaftor as concurrent use may increase exposure of paclitaxel. Paclitaxel is a substrate for the transporters OATP1B1 and OATP1B3; elexacaftor; tezacaftor; ivacaftor may inhibit uptake of OATP1B1 and OATP1B3. [56579] [64697] Eltrombopag: (Moderate) Monitor patients for paclitaxel adverse reactions if coadministered with eltrombopag. Eltrombopag is an inhibitor of the transporter OATP1B1. Drugs that are substrates for this transporter, such as paclitaxel, may exhibit an increase in systemic exposure if coadministered with eltrombopag. [40392] [56579] Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Plasma concentrations of paclitaxel may be elevated when administered concurrently with cobicistat. Cobicistat is a strong inhibitor of CYP3A4 and P-glycoprotein (P-gp) inhibitor, while paclitaxel is a CYP3A4 and P-gp substrate. Some experts state that pharmacokinetic interactions between paclitaxel and some CYP3A4 inhibitors do not appear to be clinically significant. However, combining the drugs in clinical practice may require close monitoring to ensure proper therapeutic responses. [29211] [46390] [49806] [51664] [58000] Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Plasma concentrations of paclitaxel may be elevated when administered concurrently with cobicistat. Cobicistat is a strong inhibitor of CYP3A4 and P-glycoprotein (P-gp) inhibitor, while paclitaxel is a CYP3A4 and P-gp substrate. Some experts state that pharmacokinetic interactions between paclitaxel and some CYP3A4 inhibitors do not appear to be clinically significant. However, combining the drugs in clinical practice may require close monitoring to ensure proper therapeutic responses. [29211] [46390] [49806] [51664] [58000] Emapalumab: (Moderate) Monitor for decreased efficacy of paclitaxel and adjust the dose as needed during coadministration with emapalumab. Paclitaxel is a CYP2C8 substrate with a narrow therapeutic range. Emapalumab may normalize CYP450 activity, which may decrease the efficacy of drugs that are CYP450 substrates due to increased metabolism. [63767] Enzalutamide: (Moderate) Monitor for decreased efficacy of paclitaxel if coadministration with enzalutamide is necessary. Paclitaxel is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer. [51727] [58751] Epirubicin: (Moderate) Monitor for an increase in epirubicin-related adverse reactions, including hematologic and gastrointestinal toxicities, if coadministration with paclitaxel is necessary. Coadministration of paclitaxel immediately before or after epirubicin increased the mean AUC of epirubicin by 5% to 109%; the mean AUC of epirubicinol and 7-deoxy-aglycone (inactive metabolites) increased by 120% and 70%, respectively, when paclitaxel was administered immediately after epirubicin. Epirubicin had no effect on the exposure of paclitaxel. [41751] Erlotinib: (Moderate) The use of taxane-based chemotherapy with erlotinib appears to be one of the risk factors for gastrointestinal (GI) perforation with erlotinib. Monitor for symptoms of GI perforation (e.g., severe abdominal pain, fever, nausea, and vomiting) if coadministration of erlotinib with a taxane chemotherapy agent is necessary. [30555] Erythromycin: (Minor) Paclitaxel is metabolized by hepatic cytochrome P450 (CYP) isoenzymes 2C8 and 3A4. Erythromycin is a CYP3A4 inhibitor. In vitro, the metabolism of paclitaxel is inhibited by various agents (e.g., ketoconazole, verapamil, diazepam, quinidine, dexamethasone, tenopiside, etoposide, and vincristine) but concentrations used exceeded those found in vivo following normal therapeutic doses. Closely monitor patients for toxicity when administering paclitaxel with any of these agents. [49806] Etodolac: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5938] Etravirine: (Moderate) Etravirine is a CYP3A4 inducer/substrate and a P-glycoprotein (PGP) inhibitor and paclitaxel is a CYP3A4 and PGP substrate. Caution is warranted if these drugs are coadministered. [33718] [5228] [5938] Fedratinib: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration with fedratinib is necessary. Coadministration may increase the exposure of paclitaxel. Paclitaxel is a CYP3A4 substrate and fedratinib is a moderate CYP3A4 inhibitor. [49806] [64568] Fenofibrate: (Minor) Paclitaxel is a substrate of CYP2C8, and fenofibrate is a CYP2C8 inhibitor. If coadministration is necessary, use caution and monitor for increased paclitaxel side effects, including myelosuppression and peripheral neuropathy. [49952] [58751] Fenofibric Acid: (Minor) Paclitaxel is a substrate of CYP2C8, and fenofibric acid is a weak CYP2C8 inhibitor. If coadministration is necessary, use caution and monitor for increased paclitaxel side effects, including myelosuppression and peripheral neuropathy. [49952] [58751] Fenoprofen: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5938] Filgrastim, G-CSF: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert their toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy. [4670] Fluconazole: (Minor) Paclitaxel is metabolized by hepatic cytochrome P450 isoenzymes 2C8 and 3A4. The metabolism of paclitaxel may be inhibited by drugs that inhibit these enzymes, including fluconazole. Closely monitor patients for toxicity when administering paclitaxel with fluconazole. [4718] [5938] Fluoxetine: (Minor) Paciltaxel is metabolized by cytochrome P450 3A enzymes. Drugs that inhibit the CYP3A enzymes, such as fluoxetine, can significantly reduce the metabolism of paclitaxel. [4718] [5235] Flurbiprofen: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5938] Fluvoxamine: (Minor) Paclitaxel is metabolized by hepatic cytochrome P450 isoenzymes 2C8 and 3A4. Inhibitors of these enzymes, such as fluvoxamine, may increase the serum concentration of paclitaxel. Closely monitor patients for toxicity when administering paclitaxel with fluvoxamine. [4718] [5938] Fosamprenavir: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of paclitaxel with fosamprenavir is necessary due to the risk of increased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. In vitro, coadministration with both strong and moderate CYP3A inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A inhibitors. [29012] [29200] Gadobenate Dimeglumine: (Moderate) Gadobenate dimeglumine is a substrate for the canalicular multi-specific organic anion transporter (MOAT). Use with other MOAT substrates, such as paclitaxel, may result in prolonged systemic exposure of the coadministered drug. Caution is advised if these drugs are used together. [58462] Gemfibrozil: (Major) Paclitaxel is a substrate of CYP2C8 and gemfibrozil is a potent CYP2C8 inhibitor. Paclitaxel concentrations are expected to increase with the co-use of gemfibrozil. Consider alternative therapy to gemfibrozil. If coadministration is necessary, use caution and monitor for increased paclitaxel side effects, including myelosuppression and peripheral neuropathy. [58751] Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with the coadministration of glecaprevir and paclitaxel as coadministration may increase serum concentrations of paclitaxel and increase the risk of adverse effects. Paclitaxel is a substrate of P-glycoprotein (P-gp); glecaprevir is a P-gp inhibitor. [28498] [49806] [62201] (Moderate) Caution is advised with the coadministration of pibrentasvir and paclitaxel as coadministration may increase serum concentrations of paclitaxel and increase the risk of adverse effects. Paclitaxel is a substrate of P-glycoprotein (P-gp); pibrentasvir is a P-gp inhibitor. [28498] [49806] [62201] Grapefruit juice: (Major) Advise patients to avoid grapefruit juice while taking paclitaxel due to the risk of increased paclitaxel exposure. Paclitaxel is a CYP3A4 substrate and grapefruit juice is a strong CYP3A4 inhibitor. [49806] [58104] [58751] Hydantoins: (Minor) Paclitaxel is metabolized by hepatic cytochrome P450 isoenzymes 2C8 and 3A4. Potential interactions may occur in vivo with any agent that induces CYP2C8 or CYP3A4 isoenzymes including hydantoins. This combination could potentially decrease chemotherapy efficacy. [4718] [5938] Hydrocodone; Ibuprofen: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5938] Ibuprofen: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5938] Ibuprofen; Famotidine: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5938] Ibuprofen; Oxycodone: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5938] Ibuprofen; Pseudoephedrine: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5938] Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with paclitaxel, a CYP3A substrate, as paclitaxel toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. [5228] [57675] [5938] Imatinib: (Minor) Imatinib is a potent inhibitor of cytochrome P450 3A4 and may increase concentrations of other drugs metabolized by this enzyme. Caution is recommended when administering imatinib with other CYP3A4 substrates including paclitaxel. [4966] Indinavir: (Minor) Indinavir inhibits cytochrome P450 3A4. Although specific interactions have not been studied, Indinavir may reduce the metabolism of CYP3A4 substrates, such as paclitaxel, and caution is warranted with coadministration. [4718] Indomethacin: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5938] Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with paclitaxel may result in increased serum concentrations of paclitaxel. Paclitaxel is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Caution and close monitoring are advised if these drugs are used together. [28498] [49806] [59042] Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Minor) Paclitaxel is metabolized by hepatic cytochrome P450 isoenzymes 2C8 and 3A4. Closely monitor patients for possibly decreased efficacy when administering paclitaxel with any agent that induces CYP2C8 or CYP3A4 isoenzymes, such as rifampin. [5938] Isoniazid, INH; Rifampin: (Minor) Paclitaxel is metabolized by hepatic cytochrome P450 isoenzymes 2C8 and 3A4. Closely monitor patients for possibly decreased efficacy when administering paclitaxel with any agent that induces CYP2C8 or CYP3A4 isoenzymes, such as rifampin. [5938] Itraconazole: (Minor) Due to itraconazole-induced inhibition of cytochrome P450 3A4, interactions are possible with agents that are substrates of this enzyme including paclitaxel. [4718] [5938] Ketoconazole: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of paclitaxel with ketoconazole is necessary due to the risk of increased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A4 substrate and ketoconazole is a strong CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors. [27982] [29200] [67231] Ketoprofen: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5938] Ketorolac: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5938] Lansoprazole; Amoxicillin; Clarithromycin: (Minor) Paclitaxel is partially metabolized by CYP3A4. The systemic clearance of paclitaxel may be decreased if coadministered with clarithromycin, an inhibitor of CYP3A4. [4718] [5938] Lansoprazole; Naproxen: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5938] Lapatinib: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration with lapatinib is necessary. Paclitaxel is a CYP3A4 and P-glycoprotein (P-gp) substrate. Lapatinib is a weak CYP3A4 inhibitor as well as a P-gp inhibitor. The 24-hour systemic exposure (AUC) of paclitaxel was increased by 23% in cancer patients receiving concomitant lapatinib; this increase in paclitaxel exposure may have been underestimated from the in vivo evaluation due to study design limitations. [28498] [33192] [49806] Ledipasvir; Sofosbuvir: (Minor) Caution and close monitoring of paclitaxel-associated adverse reactions is advised with concomitant administration of ledipasvir. Paclitaxel is a substrate of the drug transporter P-glycoprotein (P-gp); ledipasvir is a P-gp inhibitor. Taking these drugs together may increase paclitaxel plasma concentrations. [28498] [49806] [58167] Lefamulin: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration with oral lefamulin is necessary. Coadministration may increase the exposure of paclitaxel. Paclitaxel is a CYP3A4 substrate and oral lefamulin is a moderate CYP3A4 inhibitor; an interaction is not expected with intravenous lefamulin. [49806] [64576] Leflunomide: (Moderate) Closely monitor for for paclitaxel-induced side effects when these drugs are used together. In some patients, a dosage reduction of paclitaxel may be required. Following oral administration, leflunomide is metabolized to an active metabolite, teriflunomide, which is responsible for essentially all of leflunomide's in vivo activity. Paclitaxel is a substrate for CYP2C8. In vivo data suggest that teriflunomide is an inhibitor of CYP2C8, as Cmax and AUC increased 1.7- and 4.2-fold, respectively, following concurrent use of another CYP2C8 substrate. [49634] Lenacapavir: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of paclitaxel with lenacapavir is necessary due to the risk of increased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A substrate and lenacapavir is a moderate CYP3A inhibitor. In vitro, coadministration with both strong and moderate CYP3A inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A inhibitors. [29200] [68383] Letermovir: (Moderate) An increase in the plasma concentration of paclitaxel may occur if given with letermovir. In patients who are also receiving treatment with cyclosporine, the magnitude of this interaction may be amplified. Paclitaxel is a CYP3A4 substrate. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor. [49806] [62611] Levoketoconazole: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of paclitaxel with ketoconazole is necessary due to the risk of increased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A4 substrate and ketoconazole is a strong CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors. [27982] [29200] [67231] Live Vaccines: (Contraindicated) Do not administer live vaccines to paclitaxel recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving paclitaxel. At least 2 weeks before initiation of paclitaxel therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Paclitaxel recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased. [29200] [43236] Lonafarnib: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of paclitaxel with lonafarnib is necessary due to the risk of increased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A4 substrate and lonafarnib is a strong CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors. [29200] [66129] Lopinavir; Ritonavir: (Minor) Due to ritonavir's potential inhibitory effects on various hepatic isoenzymes, numerous drug interactions may occur with ritonavir. Close monitoring of serum drug concentrations and/or therapeutic and adverse effects is required when paclitaxel (a CYP2C8 and CYP3A4 substrate) is coadministered with ritonavir (a CYP3A4 inhibitor). In addition, paclitaxel is a substrate of the drug transporter P-glycoprotein (P-gp), and ritonavir also inhibits P-gp. [28001] [28341] [28380] [28498] [49806] [56579] [58664] Lorlatinib: (Moderate) Monitor for decreased efficacy of paclitaxel if coadministration with lorlatinib is necessary. Paclitaxel is a CYP3A4 substrate and lorlatinib is a moderate CYP3A4 inducer. [28498] [49806] [63732] Lumacaftor; Ivacaftor: (Major) Lumacaftor; ivacaftor may alter the therapeutic effects of paclitaxel; caution and close monitoring are advised if these drugs are used together. The paclitaxel dosage may need to be adjusted. Paclitaxel is metabolized by CYP3A4 (and CYP2C8) and is a substrate of the P-glycoprotein (P-gp) efflux transporter. Lumacaftor is a strong CYP3A inducer; in vitro data also suggest lumacaftor; ivacaftor may induce and/or inhibit P-gp. Although induction of paclitaxel through the CYP3A pathway may lead to decreased drug efficacy, the net effect of lumacaftor; ivacaftor on P-gp transport is not clear. Monitor the patient for chemotherapeutic efficacy and adverse effects. In a study designed to determine the maximum tolerated dose of paclitaxel, patients receiving concomitant enzyme-inducing anticonvulsants (e.g., phenytoin, carbamazepine, phenobarbital) tolerated significantly higher doses of paclitaxel as compared to those who were not. Although no prospectively validated dosage adjustment regimen is available, this study suggested a possible need to increase the dose of paclitaxel as much as 50% in patients receiving concurrent enzyme-inducing anticonvulsant therapy. Of note, patients receiving enzyme-inducing anticonvulsants experienced a dose-limiting toxicity of central neurotoxicity while those not receiving anticonvulsants experienced dose-limiting toxicities of myelosuppression, GI toxicity, and fatigue. [28498] [29231] [49806] [59891] Mavacamten: (Moderate) Monitor for decreased efficacy of paclitaxel if coadministration with mavacamten is necessary due to the risk of decreased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. [29200] [67543] Meclofenamate Sodium: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5938] Mefenamic Acid: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5938] Meloxicam: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5938] Metronidazole: (Major) Medications with significant alcohol content should not be ingested during therapy with metronidazole and should be avoided for 3 days after therapy is discontinued. Some formulations of paclitaxel contain a high level of ethanol. Administration to patients receiving or who have recently received metronidazole may result in disulfiram-like reactions. A disulfiram reaction would not be expected to occur with non-ethanol containing formulations. [28581] [29200] [48545] Mitapivat: (Moderate) Monitor for decreased efficacy of paclitaxel if coadministration with mitapivat is necessary due to the risk of decreased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A substrate and mitapivat is a weak CYP3A inducer. [29200] [67403] Mitotane: (Major) Concomitant use of mitotane with paclitaxel should be undertaken with caution as it could result in decreased plasma concentrations of paclitaxel, leading to reduced efficacy. Mitotane is a strong CYP3A4 inducer and paclitaxel is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of paclitaxel. [28498] [41934] [49806] Mobocertinib: (Moderate) Monitor for decreased efficacy of paclitaxel if coadministration with mobocertinib is necessary due to the risk of decreased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A substrate and mobocertinib is a weak CYP3A inducer. [29200] [66990] Nabumetone: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5938] Naproxen: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5938] Naproxen; Esomeprazole: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5938] Naproxen; Pseudoephedrine: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5938] Nefazodone: (Minor) Paclitaxel is metabolized by hepatic cytochrome P450 isoenzymes 2C8 and 3A4. Inhibitors of these enzymes, such as nefazodone, may cause increased serum concentration and side effects of paclitaxel. Closely monitor patients for toxicity when administering paclitaxel with any of these agents. [4718] [5938] Nelfinavir: (Minor) Nelfinavir may inhibit the metabolism of other substrates of cytochrome P450 3A4 such as paclitaxel. [4718] Netupitant, Fosnetupitant; Palonosetron: (Moderate) Netupitant is a moderate inhibitor of CYP3A4 and should be used with caution in patients receiving concomitant medications that are primarily metabolized through CYP3A4, such as paclitaxel. The plasma concentrations of CYP3A4 substrates can increase when co-administered with netupitant. The inhibitory effect on CYP3A4 can last for multiple days. If coadministration is necessary, use caution and monitor for chemotherapeutic related adverse reactions. [58171] Nevirapine: (Moderate) Monitor for decreased efficacy of paclitaxel if coadministration with nevirapine is necessary due to the risk of decreased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A substrate and nevirapine is a weak CYP3A inducer. [29200] [42456] Nicardipine: (Minor) Paclitaxel is a substrate of CYP2C8 and 3A4; in vitro, nicardipine is a moderate inhibitor of both CYP2C8 and 3A4. If coadministration is necessary, use caution and monitor for increased paclitaxel side effects, including myelosuppression and peripheral neuropathy. [50341] [56565] [58751] Nirmatrelvir; Ritonavir: (Minor) Due to ritonavir's potential inhibitory effects on various hepatic isoenzymes, numerous drug interactions may occur with ritonavir. Close monitoring of serum drug concentrations and/or therapeutic and adverse effects is required when paclitaxel (a CYP2C8 and CYP3A4 substrate) is coadministered with ritonavir (a CYP3A4 inhibitor). In addition, paclitaxel is a substrate of the drug transporter P-glycoprotein (P-gp), and ritonavir also inhibits P-gp. [28001] [28341] [28380] [28498] [49806] [56579] [58664] Nonsteroidal antiinflammatory drugs: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5938] Odevixibat: (Moderate) Monitor for decreased efficacy of paclitaxel if coadministration with odevixibat is necessary due to the risk of decreased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A substrate and odevixibat is a weak CYP3A inducer. [29200] [66816] Olanzapine; Fluoxetine: (Minor) Paciltaxel is metabolized by cytochrome P450 3A enzymes. Drugs that inhibit the CYP3A enzymes, such as fluoxetine, can significantly reduce the metabolism of paclitaxel. [4718] [5235] Olutasidenib: (Moderate) Monitor for decreased efficacy of paclitaxel if coadministration with olutasidenib is necessary due to the risk of decreased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A substrate and olutasidenib is a weak CYP3A inducer. [29200] [68242] Omaveloxolone: (Moderate) Monitor for decreased efficacy of paclitaxel if coadministration with omaveloxolone is necessary due to the risk of decreased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A and CYP2C8 substrate and omaveloxolone is a weak CYP3A and CYP2C8 inducer. [29200] [68644] Ombitasvir; Paritaprevir; Ritonavir: (Minor) Concurrent administration of paclitaxel (or nanoparticle albumin-bound paclitaxel) with dasabuvir; ombitasvir; paritaprevir; ritonavir may result in increased paclitaxel plasma concentrations and risk for toxicity. Caution and close monitoring are advised if these drugs are administered together. Paclitaxel is metabolized by the hepatic isoenzymes CYP2C8 and CYP3A4; ritonavir is a potent CYP3A4 inhibitor. In addition, paclitaxel is a substrate of the drug transporter P-glycoprotein (P-gp), and ritonavir also inhibits P-gp. Paritaprevir also inhibits P-gp. [28498] [49806] [58664] (Minor) Due to ritonavir's potential inhibitory effects on various hepatic isoenzymes, numerous drug interactions may occur with ritonavir. Close monitoring of serum drug concentrations and/or therapeutic and adverse effects is required when paclitaxel (a CYP2C8 and CYP3A4 substrate) is coadministered with ritonavir (a CYP3A4 inhibitor). In addition, paclitaxel is a substrate of the drug transporter P-glycoprotein (P-gp), and ritonavir also inhibits P-gp. [28001] [28341] [28380] [28498] [49806] [56579] [58664] Omeprazole; Amoxicillin; Rifabutin: (Minor) Paclitaxel is metabolized by hepatic cytochrome P450 isoenzymes 2C8 and 3A4. Potential interactions may occur in vivo with any agent that induces CYP2C8 or CYP3A4 isoenzymes including rifabutin. [5938] Oritavancin: (Moderate) Paclitaxel is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of paclitaxel may be reduced if these drugs are administered concurrently. [28498] [29200] [57741] Oxaprozin: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5938] Palifermin: (Moderate) Palifermin should not be administered within 24 hours before, during infusion of, or within 24 hours after administration of antineoplastic agents. [54912] Pazopanib: (Moderate) Coadministration of pazopanib (800 mg by mouth once daily) and paclitaxel (80 mg/m2 IV once weekly) resulted in a mean increase of 26% and 31% in paclitaxel AUC and Cmax, respectively. [37098] Penicillamine: (Major) Do not use penicillamine with antineoplastic agents due to the increased risk of developing severe hematologic and renal toxicity. [28834] Pexidartinib: (Moderate) Monitor for decreased efficacy of paclitaxel if coadministration with pexidartinib is necessary due to the risk of decreased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. [29200] [64535] Piroxicam: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5938] Pirtobrutinib: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of paclitaxel with pirtobrutinib is necessary due to the risk of increased plasma concentrations of paclitaxel. Paclitaxel is a CYP2C8 substrate and pirtobrutinib is a moderate CYP2C8 inhibitor. In vitro, the metabolism of paclitaxel to 6-alpha-hydroxypaclitaxel was inhibited by another inhibitor of CYP2C8. [29200] [68520] Posaconazole: (Moderate) Posaconazole and paclitaxel should be coadministered with caution due to an increased potential for adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of paclitaxel. Further, both paclitaxel and posaconazole are substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of the other drug. This complex interaction may cause alterations in the plasma concentrations of both posaconazole and paclitaxel, ultimately resulting in an increased risk of adverse events. [32723] [5228] [5938] Ribociclib: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration with ribociclib is necessary. Paclitaxel is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor. [49806] [61816] Ribociclib; Letrozole: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration with ribociclib is necessary. Paclitaxel is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor. [49806] [61816] Rifabutin: (Minor) Paclitaxel is metabolized by hepatic cytochrome P450 isoenzymes 2C8 and 3A4. Potential interactions may occur in vivo with any agent that induces CYP2C8 or CYP3A4 isoenzymes including rifabutin. [5938] Rifampin: (Minor) Paclitaxel is metabolized by hepatic cytochrome P450 isoenzymes 2C8 and 3A4. Closely monitor patients for possibly decreased efficacy when administering paclitaxel with any agent that induces CYP2C8 or CYP3A4 isoenzymes, such as rifampin. [5938] Rifapentine: (Moderate) Monitor for decreased efficacy of paclitaxel if coadministration with rifapentine is necessary due to the risk of decreased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. [29200] [65685] Ritonavir: (Minor) Due to ritonavir's potential inhibitory effects on various hepatic isoenzymes, numerous drug interactions may occur with ritonavir. Close monitoring of serum drug concentrations and/or therapeutic and adverse effects is required when paclitaxel (a CYP2C8 and CYP3A4 substrate) is coadministered with ritonavir (a CYP3A4 inhibitor). In addition, paclitaxel is a substrate of the drug transporter P-glycoprotein (P-gp), and ritonavir also inhibits P-gp. [28001] [28341] [28380] [28498] [49806] [56579] [58664] Rolapitant: (Moderate) Use caution if paclitaxel and rolapitant are used concurrently, and monitor for paclitaxel-related adverse effects. Paclitaxel is a P-glycoprotein (P-gp) substrate, where an increase in exposure may significantly increase adverse effects; rolapitant is a P-gp inhibitor. When rolapitant was administered with another P-gp substrate, digoxin, the day 1 Cmax and AUC were increased by 70% and 30%, respectively; the Cmax and AUC on day 8 were not studied. [28498] [49806] [60142] Rufinamide: (Minor) Rufinamide is not metabolized through hepatic CYP isozymes; however, it is a weak inducer of CYP3A4. In theory, decreased exposure of drugs that are extensively metabolized by CYP3A4, such as paclitaxel, may occur during concurrent use with rufinamide. [11449] Saquinavir: (Minor) Although saquinavir does not inhibit cytochrome-based metabolism to the same degree as ritonavir, saquinavir may cause elevated plasma concentrations of drugs which are substrates for CYP3A4 isoenzymes including paclitaxel. Patients should be monitored for toxicities associated with paclitaxel. [4718] SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine. [65107] [66080] Simeprevir: (Moderate) Simeprevir, a mild intestinal CYP3A4 inhibitor, may increase the side effects of paclitaxel, which is a CYP3A4 substrate. Monitor patients for adverse effects of paclitaxel, such as myelosuppression, myalgia/arthralgia, and peripheral neuropathy. [28498] [29200] [56471] Sodium Phenylbutyrate; Taurursodiol: (Moderate) Monitor for decreased efficacy and/or increased paclitaxel-related adverse reactions if coadministration with taurursodiol is necessary. Concomitant use may alter paclitaxel exposure. Paclitaxel is a CYP3A and CYP2C8 substrate and taurursodiol is a weak CYP3A inducer and CYP2C8 inhibitor. The net effect on paclitaxel exposure is unknown. [29200] [68007] Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Plasma concentrations of paclitaxel, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with voxilaprevir, a P-gp inhibitor. Monitor patients for increased side effects if these drugs are administered concurrently. [28498] [49806] [62131] Sotorasib: (Moderate) Monitor for decreased efficacy of paclitaxel if coadministration with sotorasib is necessary due to the risk of decreased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A4 substrate and sotorasib is a moderate CYP3A4 inducer. [29200] [66700] Spironolactone: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of paclitaxel with spironolactone is necessary due to the risk of increased plasma concentrations of paclitaxel. Paclitaxel is a CYP2C8 substrate and spironolactone is a CYP2C8 inhibitor. In vitro, the metabolism of paclitaxel to 6-alpha-hydroxypaclitaxel was inhibited by another inhibitor of CYP2C8. [29200] [62209] Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of paclitaxel with spironolactone is necessary due to the risk of increased plasma concentrations of paclitaxel. Paclitaxel is a CYP2C8 substrate and spironolactone is a CYP2C8 inhibitor. In vitro, the metabolism of paclitaxel to 6-alpha-hydroxypaclitaxel was inhibited by another inhibitor of CYP2C8. [29200] [62209] Stiripentol: (Moderate) Consider a dose reduction of paclitaxel when coadministered with stiripentol. Coadministration may increase plasma concentrations of paclitaxel resulting in an increased risk of adverse reactions. Paclitaxel is a substrate of CYP2C8; stiripentol may inhibit CYP2C8 at clinically relevant concentrations. [28498] [49806] [63456] Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Minor) Paclitaxel is a substrate of CYP2C8; in vitro, trimethoprim is a mild inhibitor of CYP2C8. If coadministration is necessary, use caution and monitor for increased paclitaxel side effects, including myelosuppression and peripheral neuropathy. This interaction may also be applicable to combination products containing trimethoprim, including sulfamethoxazole; trimethoprim (also known as SMX-TMP or cotrimoxazole). [43888] [55864] [57878] [58751] Sulindac: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5938] Sumatriptan; Naproxen: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5938] Tbo-Filgrastim: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert their toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy. [4670] Telotristat Ethyl: (Moderate) Monitor for decreased efficacy of paclitaxel if coadministration with telotristat is necessary due to the risk of decreased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A4 substrate and telotristat is a weak CYP3A4 inducer. [29200] [61795] Teriflunomide: (Moderate) Increased monitoring is recommended if teriflunomide is administered concurrently with CYP2C8 substrates, such as paclitaxel. In vivo studies demonstrated that teriflunomide is an inhibitor of CYP2C8. Coadministration may lead to increased exposure to CYP2C8 substrates; however, the clinical impact of this has not yet been determined. Monitor for increased adverse effects. [51794] Thalidomide: (Moderate) Thalidomide and other agents that cause peripheral neuropathy such as paclitaxel should be used cautiously due to the potential for additive effects. [49713] Tolmetin: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5938] Trametinib: (Minor) Paclitaxel is a substrate of CYP2C8; in vitro, trametinib is a mild inhibitor of CYP2C8. If coadministration is necessary, use caution and monitor for increased paclitaxel side effects, including myelosuppression and peripheral neuropathy. [54807] [58751] Trandolapril; Verapamil: (Minor) Additive bradycardia may occur in patients receiving paclitaxel and other drugs known to cause bradycardia, such as certain calcium-channel blockers. In vitro, the metabolism of paclitaxel via CYP3A4 was inhibited by verapamil, a moderate CYP3A4 inhibitor. However, the verapamil concentrations used exceeded those found in vivo following normal therapeutic doses. Verapamil also blocks the multidrug resistance (MDR) P-glycoprotein, which is a mechanism of resistance to naturally occurring (non-synthetic) chemotherapy agents. Verapamil could enhance paclitaxel's activity and toxicity through this mechanism as well. Small clinical trials have indicated that the coadministration of r-verapamil, an isomer of verapamil, and paclitaxel results in a significant decrease in paclitaxel clearance and an increase in paclitaxel toxicity. Some experts state that pharmacokinetic interactions between paclitaxel and verapamil do not appear to be clinically significant in vivo. However, combining the drugs in clinical practice may require close monitoring; monitor for paclitaxel induced side effects such as myelosuppression, infection, or peripheral neuropathy. [28498] [29211] [49806] [58751] Trimethoprim: (Minor) Paclitaxel is a substrate of CYP2C8; in vitro, trimethoprim is a mild inhibitor of CYP2C8. If coadministration is necessary, use caution and monitor for increased paclitaxel side effects, including myelosuppression and peripheral neuropathy. This interaction may also be applicable to combination products containing trimethoprim, including sulfamethoxazole; trimethoprim (also known as SMX-TMP or cotrimoxazole). [43888] [55864] [57878] [58751] Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy. [43298] [43299] Tucatinib: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration with tucatinib is necessary. Tucatinib is a strong CYP3A4 inhibitor and paclitaxel is metabolized by CYP3A4. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors. [49806] [65295] Valdecoxib: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5938] Vemurafenib: (Major) Avoid the concomitant use of vemurafenib and paclitaxel; increased paclitaxel exposure may occur. If co-administration is unavoidable, consider a paclitaxel dose reduction and monitor patients carefully for signs and symptoms of paclitaxel toxicity (e.g., neutropenia, peripheral neuropathy). Vemurafenib is a substrate and weak inducer of CYP3A4 and a substrate and inhibitor of P-glycoprotein (P-gp); paclitaxel is a CYP3A4 and P-gp substrate with a narrow therapeutic index. [28498] [45335] [58751] Verapamil: (Minor) Additive bradycardia may occur in patients receiving paclitaxel and other drugs known to cause bradycardia, such as certain calcium-channel blockers. In vitro, the metabolism of paclitaxel via CYP3A4 was inhibited by verapamil, a moderate CYP3A4 inhibitor. However, the verapamil concentrations used exceeded those found in vivo following normal therapeutic doses. Verapamil also blocks the multidrug resistance (MDR) P-glycoprotein, which is a mechanism of resistance to naturally occurring (non-synthetic) chemotherapy agents. Verapamil could enhance paclitaxel's activity and toxicity through this mechanism as well. Small clinical trials have indicated that the coadministration of r-verapamil, an isomer of verapamil, and paclitaxel results in a significant decrease in paclitaxel clearance and an increase in paclitaxel toxicity. Some experts state that pharmacokinetic interactions between paclitaxel and verapamil do not appear to be clinically significant in vivo. However, combining the drugs in clinical practice may require close monitoring; monitor for paclitaxel induced side effects such as myelosuppression, infection, or peripheral neuropathy. [28498] [29211] [49806] [58751] Vonoprazan; Amoxicillin; Clarithromycin: (Minor) Paclitaxel is partially metabolized by CYP3A4. The systemic clearance of paclitaxel may be decreased if coadministered with clarithromycin, an inhibitor of CYP3A4. [4718] [5938] Voriconazole: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration with voriconazole is necessary. Paclitaxel is a CYP3A4 substrate and voriconazole is a strong CYP3A4 inhibitor. [28158] [49806] Voxelotor: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of paclitaxel with voxelotor is necessary due to the risk of increased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A substrate and voxelotor is a moderate CYP3A inhibitor. In vitro, coadministration with both strong and moderate CYP3A inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A inhibitors. [29200] [64778] Zafirlukast: (Moderate) Published data indicate zafirlukast inhibits CYP2C8 rather potently. Until further data are available to confirm the absence of drug interactions, CYP2C8 metabolized drugs, such as paclitaxel, may require closer monitoring when used in conjunction with zafirlukast. [5938] [7806] Zonisamide: (Minor) Zonisamide is a weak inhibitor of P-glycoprotein (P-gp), and paclitaxel is a substrate of P-gp. There is theoretical potential for zonisamide to affect the pharmacokinetics of drugs that are P-gp substrates. Use caution when starting or stopping zonisamide or changing the zonisamide dosage in patients also receiving drugs which are P-gp substrates. [28498] [28843] [49806]
    Revision Date: 04/06/2023, 01:52:00 AM

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    Monitoring Parameters

    • CBC with differential
    • ECG
    • LFTs
    • serum bilirubin (total and direct)

    US Drug Names

    • Onxol
    • Taxol
    ;