.png?width=200&height=94&name=PDR_stacked_purple%20(002).png)
Onxol
Classes
Taxanes
Administration
Hazardous Drugs Classification
NIOSH 2016 List: Group 1
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.
Emetic Risk
Low
Administer routine antiemetic prophylaxis prior to treatment.
Extravasation Risk
Vesicant
Administer drug through a central venous line.
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.
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. Paclitaxel doses up to 100 mg/m2 IV weekly have been given as a 1-hour IV infusion.
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.
Adverse Reactions
neutropenia / Delayed / 52.0-52.0
leukopenia / Delayed / 17.0-17.0
anemia / Delayed / 16.0-16.0
arthralgia / Delayed / 8.0-8.0
myalgia / Early / 8.0-8.0
thrombocytopenia / Delayed / 7.0-7.0
angioedema / Rapid / 2.0-4.0
bradycardia / Rapid / 3.0-3.0
peripheral neuropathy / Delayed / 3.0-3.0
leukoencephalopathy / Delayed / 2.0-2.0
thromboembolism / Delayed / 1.0-1.0
AV block / Early / 1.0-1.0
ventricular tachycardia / Early / 1.0-1.0
seizures / Delayed / 0-1.0
serious hypersensitivity reactions or anaphylaxis / Rapid / Incidence not known
anaphylactic shock / Rapid / Incidence not known
tissue necrosis / Early / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
myocardial infarction / Delayed / Incidence not known
atrial fibrillation / Early / Incidence not known
typhlitis / Delayed / Incidence not known
pulmonary fibrosis / Delayed / Incidence not known
pleural effusion / Delayed / Incidence not known
exfoliative dermatitis / Delayed / Incidence not known
pulmonary embolism / Delayed / Incidence not known
hepatic necrosis / Delayed / Incidence not known
hepatic encephalopathy / Delayed / Incidence not known
renal failure (unspecified) / Delayed / Incidence not known
ileus / Delayed / Incidence not known
hearing loss / Delayed / Incidence not known
stomatitis / Delayed / 31.0-31.0
elevated hepatic enzymes / Delayed / 19.0-22.0
edema / Delayed / 21.0-21.0
bleeding / Early / 14.0-14.0
sinus tachycardia / Rapid / 14.0-14.0
hypotension / Rapid / 4.0-12.0
candidiasis / Delayed / 7.0-9.0
hyperbilirubinemia / Delayed / 7.0-7.0
dyspnea / Early / 2.0-4.0
hypertension / Early / 1.0-1.0
encephalopathy / Delayed / 0-1.0
ataxia / Delayed / 0-1.0
bone marrow suppression / Delayed / Incidence not known
chest pain (unspecified) / Early / Incidence not known
erythema / Early / Incidence not known
phlebitis / Rapid / Incidence not known
supraventricular tachycardia (SVT) / Early / Incidence not known
hyperesthesia / Delayed / Incidence not known
esophagitis / Delayed / Incidence not known
ascites / Delayed / Incidence not known
constipation / Delayed / Incidence not known
pneumonitis / Delayed / Incidence not known
radiation recall reaction / Delayed / Incidence not known
confusion / Early / Incidence not known
scotomata / Delayed / Incidence not known
conjunctivitis / Delayed / Incidence not known
photopsia / Delayed / Incidence not known
alopecia / Delayed / 87.0-87.0
infection / Delayed / 30.0-61.0
vomiting / Early / 52.0-52.0
nausea / Early / 52.0-52.0
diarrhea / Early / 38.0-38.0
flushing / Rapid / 28.0-28.0
asthenia / Delayed / 17.0-17.0
injection site reaction / Rapid / 13.0-13.0
fever / Early / 12.0-12.0
rash / Early / 12.0-12.0
nail discoloration / Delayed / 2.0-2.0
syncope / Early / 1.0-1.0
paresthesias / Delayed / 60.0
malaise / Early / Incidence not known
anorexia / Delayed / Incidence not known
chills / Rapid / Incidence not known
back pain / Delayed / Incidence not known
diaphoresis / Early / Incidence not known
abdominal pain / Early / Incidence not known
maculopapular rash / Early / Incidence not known
pruritus / Rapid / Incidence not known
dizziness / Early / Incidence not known
headache / Early / Incidence not known
lacrimation / Early / Incidence not known
tinnitus / Delayed / Incidence not known
vertigo / Early / Incidence not known
Boxed Warning
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.
Common Brand Names
Onxol, Taxol
Dea Class
Rx
Description
Semisynthetic, diterpenoid taxane derivative from the bark of the Pacific yew tree; sequence of administration in combination with other agents is important in toxicity and efficacy; effective in numerous disease including breast, lung, ovarian, and bladder cancers, Kaposi's sarcoma alone or as part of combination regimens.
Dosage And Indications
175 mg/m2 IV over 3 hours every 3 weeks. 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.
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. 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. Additionally, doxorubicin-based chemotherapy and sequential paclitaxel 175 mg/m2 IV have been administered every 14 days (dose-dense) for 4 courses. In patients with HER2-positive breast cancer, trastuzumab should be given in combination with paclitaxel.
175 mg/m2 IV over 3 hours every 3 weeks in combination with trastuzumab (4 mg/kg IV then 2 mg/kg IV weekly).
NOTE: In February 2008, the FDA granted accelerated approval to bevacizumab for the treatment of previously untreated metastatic HER2-negative breast cancer in combination with paclitaxel. In December 2010, the FDA's Center for Drug Evaluation and Research (CDER), the agency which granted the accelerated approval, recommended removal of the breast cancer indication for bevacizumab. This recommendation came after reviewing the results of 4 clinical studies of bevacizumab in combination with various chemotherapy agents (e.g., an anthracycline, docetaxel, capecitabine, or paclitaxel) in women with breast cancer and determining that the data indicate that bevacizumab does not prolong overall survival in breast cancer patients or provide a sufficient benefit in slowing disease progression to outweigh the significant risk to patients. Genentech, the manufacturer of Avastin (bevacizumab), disagreed with this assessment and was granted a public hearing on CDER's withdrawal proposal, which took place in June 2011. A final decision to remove the breast cancer indication from the bevacizumab label was rendered by the FDA Commissioner in November 2011.
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.
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. 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.
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). Epirubicin dose adjustments for subsequent cycles are recommended by the manufacturer based on nadir platelet counts, ANC, or grade 3 to 4 toxicity. 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.
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.
NOTE: Pembrolizumab is FDA-approved in combination with sequential paclitaxel/carboplatin followed by cyclophosphamide/doxorubicin for this indication.
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.
NOTE: Pembrolizumab is FDA-approved in combination with sequential paclitaxel/carboplatin followed by cyclophosphamide/epirubicin for this indication.
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.
NOTE: Select patients for treatment based on the presence of positive PD-L1 expression. Information on FDA-approved tests for the detection of PD-L1 expression in TNBC is available at http://www.fda.gov/CompanionDiagnostics.
NOTE: Pembrolizumab is FDA-approved in combination with carboplatin and gemcitabine for this indication. 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. 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.
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.
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.
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. 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.
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. 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.
NOTE: Pembrolizumab is FDA-approved in combination with carboplatin and paclitaxel for this indication.
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.
NOTE: Bevacizumab is FDA-approved in combination with carboplatin and paclitaxel for this indication.
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.
NOTE: Atezolizumab is FDA-approved in combination with bevacizumab, paclitaxel, and carboplatin for this indication.
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.
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. 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.
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. 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).
135 mg/m2 or 175 mg/m2 IV over 3 hours once every 3 weeks. The optimal regimen has not yet been determined. 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%.
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.
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.
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) 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) 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.
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.
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). 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.
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 to 12. A phase 3 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.
NOTE: Dostarlimab is FDA approved in combination with carboplatin and paclitaxel for this indication.
NOTE: Select patients for treatment based on the presence of dMMR in the tumor specimen. Information on FDA-approved tests for the detection of dMMR status is available at www.fda.gov/companiondiagnostics. Intravenous dosage Adults
175 mg/m2 on day 1 in combination with dostarlimab (500 mg IV on day 1) and carboplatin (AUC 5 on day 1) repeated every 3 weeks for 6 doses; administer dostarlimab prior to chemotherapy on day 1 of each cycle. Starting 3 weeks after the sixth dose, give single-agent dostarlimab 1,000 mg IV every 6 weeks until disease progression or for up to 3 years. At a median follow-up time of approximately 25 months, the 24-month investigator-assessed progression-free survival rates were significantly higher the dostarlimab plus carboplatin and paclitaxel arm compared with the placebo plus carboplatin and paclitaxel arm in patients with primary advanced or recurrent endometrial cancer in the overall study population (n = 494; 36.1% vs. 18.1%; hazard ratio (HR) = 0.64; 95% CI, 0.51 to 0.8) and in a subpopulation of 118 patients with dMMR/MSI-H tumors (61.4% vs. 15.7%; HR = 0.28; 95% CI, 0.16 to 0.5) in a randomized, double-blind, phase 3 (RUBY) trial. At the time of this interim analysis, the 24-month overall survival rates were also significantly improved in patients who received dostarlimab compared with placebo in the overall (71.3% vs. 56%; HR = 0.64; 95% CI, 0.46 to 0.87) and dMMR/MSI-H subgroup (83.3% vs. 58.7%; HR = 0.3; 95% CI, 0.13 to 0.7) populations. In the overall population, 54.7% of patients had endometrioid carcinoma-type endometrial cancer, 47.8% of patients had recurrent disease, and 82.6% had not received external pelvic radiation.
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.
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.
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.
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. 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.
175 mg/m2 IV on day 1 in combination with carboplatin AUC 7 IV on day 1, every 3 weeks for 5 cycles.
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.
†Indicates off-label use
Dosing Considerations
Dosage adjustments for hematologic and non-hematologic toxicities:
If neutrophil count less than 500/mm3 for longer than 7 days or neutropenic fever: Consider adding colony-stimulating factor support with next cycle or dose reducing paclitaxel by 20%.
Severe peripheral neuropathy: Reduce paclitaxel dose by 20%.
NOTE: Recommended dose reductions are for the first course of therapy; subsequent dose reductions should be based on individual tolerance.
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.
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.
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.
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
Drug Interactions
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.
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.
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.
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.
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.
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.
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.
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.
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. (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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Clarithromycin: (Minor) Paclitaxel is partially metabolized by CYP3A4. The systemic clearance of paclitaxel may be decreased if coadministered with clarithromycin, an inhibitor of CYP3A4.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Dexamethasone: (Moderate) Monitor for decreased efficacy of paclitaxel if coadministration with dexamethasone is necessary due to the risk of decreased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A substrate and dexamethasone is a weak CYP3A inducer.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Efavirenz: (Moderate) Efavirenz induces CYP3A4 and may decrease serum concentrations of drugs metabolized by this enzyme, such as paclitaxel.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Efavirenz induces CYP3A4 and may decrease serum concentrations of drugs metabolized by this enzyme, such as paclitaxel.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Efavirenz induces CYP3A4 and may decrease serum concentrations of drugs metabolized by this enzyme, such as paclitaxel.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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. (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.
Glycerol Phenylbutyrate: (Moderate) Monitor for decreased efficacy of paclitaxel if coadministration with glycerol phenylbutyrate is necessary due to the risk of decreased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A substrate and glycerol phenylbutyrate is a weak CYP3A inducer.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Itraconazole: (Minor) Due to itraconazole-induced inhibition of cytochrome P450 3A4, interactions are possible with agents that are substrates of this enzyme including paclitaxel.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Nelfinavir: (Minor) Nelfinavir may inhibit the metabolism of other substrates of cytochrome P450 3A4 such as paclitaxel.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Ritlecitinib: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of paclitaxel with ritlecitinib is necessary due to the risk of increased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A substrate and ritlecitinib 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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
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.
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.
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.
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.
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.
Thalidomide: (Moderate) Thalidomide and other agents that cause peripheral neuropathy such as paclitaxel should be used cautiously due to the potential for additive effects.
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.
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.
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.
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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
How Supplied
Onxol/Paclitaxel/Taxol Intravenous Inj Sol: 1mL, 6mg
Maximum Dosage
The suggested maximum tolerated dose (MTD) for paclitaxel is dependent on performance status, other chemotherapy agents or radiation given in combination, and disease state. The optimal dose or infusion duration of paclitaxel has not been determined. Therefore, dosing may vary from protocol to protocol. If questions arise, clinicians should consult the appropriate references to verify the dose.
Adults135—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.
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.
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. 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. 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).
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. 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. 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.
Pregnancy And Lactation
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.
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.