Skip to Content
May is Hepatitis Awareness Month. Read more...

PACLitaxel

Pronunciation

Pronunciation

(pac li TAKS el con VEN sha nal)

Index Terms

  • Conventional Paclitaxel
  • Onxyl
  • Taxol

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Concentrate, Intravenous:

Generic: 100 mg/16.7 mL (16.7 mL); 30 mg/5 mL (5 mL); 150 mg/25 mL (25 mL); 300 mg/50 mL (50 mL)

Concentrate, Intravenous [preservative free]:

Generic: 100 mg/16.7 mL (16.7 mL); 30 mg/5 mL (5 mL); 300 mg/50 mL (50 mL)

Pharmacologic Category

  • Antineoplastic Agent, Antimicrotubular
  • Antineoplastic Agent, Taxane Derivative

Pharmacology

Paclitaxel promotes microtubule assembly by enhancing the action of tubulin dimers, stabilizing existing microtubules, and inhibiting their disassembly, interfering with the late G2 mitotic phase, and inhibiting cell replication. In addition, the drug can distort mitotic spindles, resulting in the breakage of chromosomes. Paclitaxel may also suppress cell proliferation and modulate immune response.

Distribution

Vdss: 24-hour infusion: 227 to 688 L/m2; biphasic with initial rapid distribution to the peripheral compartment; later phase is a slow efflux of paclitaxel from the peripheral compartment; widely distributed into body fluids and tissues; affected by dose and duration of infusion

Metabolism

Hepatic via CYP2C8 and 3A4; forms metabolites (primarily 6α-hydroxypaclitaxel)

Excretion

Feces (~71%; ~5% as unchanged drug); urine (~14%)

Half-Life Elimination

Children: 4.6 to 17 hours (varies with dose and infusion duration)

Adults:

3-hour infusion: Mean (terminal): ~13 to 20 hours

24-hour infusion: Mean (terminal): ~16 to 53 hours

Protein Binding

89% to 98%

Special Populations: Hepatic Function Impairment

Plasma paclitaxel exposure is increased.

Use: Labeled Indications

Breast cancer: Adjuvant treatment of node-positive breast cancer; treatment of metastatic breast cancer after failure of combination chemotherapy or relapse within 6 months of adjuvant chemotherapy (prior therapy should have included an anthracycline)

Kaposi sarcoma (AIDS-related): Second-line treatment of AIDS-related Kaposi sarcoma

Non-small cell lung cancer: First-line treatment of non-small cell lung cancer (in combination with cisplatin) in patients who are not candidates for potentially curative surgery and/or radiation therapy

Ovarian cancer: Subsequent therapy for treatment of advanced ovarian cancer; first-line therapy of ovarian cancer (in combination with cisplatin)

Use: Unlabeled

Treatment of bladder, cervical, small cell lung, and head and neck cancers; treatment of (unknown primary) adenocarcinoma

Contraindications

Hypersensitivity to paclitaxel, polyoxyl 35/polyoxyethylated castor oil (Cremophor EL), or any component of the formulation; treatment of solid tumors in patients with baseline neutrophil counts <1,500/mm3; treatment of Kaposi sarcoma in patients with baseline neutrophil counts <1,000/mm3.

Dosing: Adult

Note: Premedication with dexamethasone (20 mg orally at 12 and 6 hours prior to the dose [reduce dexamethasone dose to 10 mg orally with advanced HIV disease]), diphenhydramine (50 mg IV 30 to 60 minutes prior to the dose), and cimetidine, famotidine, or ranitidine (IV 30 to 60 minutes prior to the dose) is recommended.

Breast cancer, adjuvant treatment: IV: 175 mg/m2 over 3 hours every 3 weeks for 4 cycles (administer sequentially following an anthracycline-containing regimen)

Breast cancer, metastatic or relapsed: IV: 175 mg/m2 over 3 hours every 3 weeks

Non-small cell lung cancer: IV: 135 mg/m2 over 24 hours every 3 weeks (in combination with cisplatin)

Ovarian cancer, advanced:

Previously treated: IV: 135 or 175 mg/m2 over 3 hours every 3 weeks

Previously untreated: IV: 175 mg/m2 over 3 hours every 3 weeks (in combination with cisplatin) or 135 mg/m2 over 24 hours administered every 3 weeks (in combination with cisplatin)

Intraperitoneal (off-label route): 60 mg/m2 on day 8 of a 21-day treatment cycle for 6 cycles, in combination with IV paclitaxel (135 mg/m2 over 24 hours on day 1) and intraperitoneal cisplatin (Armstrong, 2006). Note: Administration of intraperitoneal paclitaxel should include the standard paclitaxel premedication regimen.

Previously untreated (off-label combination): IV: 175 mg/m2 over 3 hours every 3 weeks (in combination with carboplatin) for 6 cycles, or 60 mg/m2 over 1 hour weekly (in combination with carboplatin) for 18 weeks (Pignata, 2014)

Kaposi sarcoma, AIDS related: IV: 135 mg/m2 over 3 hours every 3 weeks or 100 mg/m2 over 3 hours every 2 weeks (due to dose-related toxicity, the 100 mg/m2 dose should be used for patients with a lower performance status). Note: Reduce the dexamethasone premedication dose to 10 mg.

Bladder cancer, advanced or metastatic (off-label use): IV: 150 mg/m2 every 2 weeks (in combination with gemcitabine) (Sternberg, 2001) or 200 mg/m2 over 1 hour every 3 weeks (in combination with gemcitabine) for 6 cycles (Meluch, 2001)

Cervical cancer, advanced (off-label use): IV: 135 or 175 mg/m2 every 3 weeks (in combination with bevacizumab and cisplatin) until disease progression or unacceptable toxicity (Tewari, 2014) or 175 mg/m2 every 3 weeks (in combination with bevacizumab and topotecan) until disease progression or unacceptable toxicity (Tewari, 2014) or 135 mg/m2 over 24 hours every 3 weeks (in combination with cisplatin) for 6 cycles (Monk, 2009; Moore, 2004).

Esophageal/gastric cancer, preoperative chemoradiation (off-label use): IV: 50 mg/m2 on days 1, 8, 15, 22, and 29 (in combination with carboplatin and radiation therapy) followed by surgery within 4 to 6 weeks (van Hagen, 2012)

Head and neck cancers, advanced (off-label use): IV: 175 mg/m2 over 3 hours every 3 weeks (in combination with cisplatin) for at least 6 cycles (Gibson, 2005)

Penile cancer, metastatic (off-label use): IV: 175 mg/m2 over 3 hours every 3 to 4 weeks (in combination with ifosfamide and cisplatin) for 4 cycles (Pagliaro, 2010)

Small cell lung cancer, relapsed/refractory (off-label use): IV: 175 mg/m2 over 3 hours every 3 weeks (as a single agent) for up to 5 cycles (Smit, 1998) or 80 mg/m2 over 1 hour weekly for 6 weeks of an 8-week treatment cycle (as a single agent) until disease progression or unacceptable toxicity (Yamamoto, 2006)

Soft tissue sarcoma (angiosarcoma), advanced/unresectable (off-label use): IV: 80 mg/m2 over 1 hour on days 1, 8, and 15 of a 4-week treatment cycle (as a single agent) for up to 6 cycles (Penel, 2008) or 135 to 175 mg/m2 over 3 hours every 3 weeks (as a single agent) (Schlemmer, 2008) or 75 to 100 mg/m2 once weekly (as a single agent) (Schlemmer, 2008)

Testicular germ cell tumors, relapsed/refractory (off-label use): IV: 80 mg/m2 over 1 hour on days 1 and 8 of a 3-week treatment cycle (in combination with gemcitabine and oxaliplatin) for 2 cycles beyond best response and up to a maximum of 8 cycles (Bokemeyer, 2008) or 250 mg/m2 over 24 hours on day 1 of a 3-week treatment cycle (in combination with ifosfamide, mesna, cisplatin, and filgrastim) for 4 cycles (Kondagunta, 2005) or 100 mg/m2 over 1 hour on days 1, 8, and 15 of a 4-week treatment cycle (in combination with gemcitabine) for up to 6 cycles (Einhorn, 2007)

Thymoma/thymic carcinoma, advanced (off-label use): IV: 225 mg/m2 over 3 hours every 3 weeks (in combination with carboplatin) for up to 6 cycles (Lemma, 2011)

Unknown primary adenocarcinoma (off-label use): IV: 200 mg/m2 over 3 hours every 3 weeks (in combination with carboplatin) for 6 to 8 cycles (Briasoulis, 2000) or 200 mg/m2 over 1 hour every 3 weeks (in combination with carboplatin and etoposide) for 4 to 8 cycles (Greco, 2000)

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer’s labeling. Aronoff (2007) recommends no dosage adjustment necessary for adults with CrCl <50 mL/minute.

Dosing: Hepatic Impairment

Note: The manufacturer's labeling recommendations are based upon the patient's first course of therapy where the usual dose would be 135 mg/m2 dose over 24 hours or the 175 mg/m2 dose over 3 hours in patients with normal hepatic function. Dosage in subsequent courses should be based upon individual tolerance. Adjustments for other regimens are not available.

24-hour infusion:

Transaminases <2 times upper limit of normal (ULN) and bilirubin level ≤1.5 mg/dL: 135 mg/m2

Transaminases 2 to <10 times ULN and bilirubin level ≤1.5 mg/dL: 100 mg/m2

Transaminases <10 times ULN and bilirubin level 1.6 to 7.5 mg/dL: 50 mg/m2

Transaminases ≥10 times ULN or bilirubin level >7.5 mg/dL: Avoid use

3-hour infusion:

Transaminases <10 times ULN and bilirubin level ≤1.25 times ULN: 175 mg/m2

Transaminases <10 times ULN and bilirubin level 1.26 to 2 times ULN: 135 mg/m2

Transaminases <10 times ULN and bilirubin level 2.01 to 5 times ULN: 90 mg/m2

Transaminases ≥10 times ULN or bilirubin level >5 times ULN: Avoid use

Dosing: Adjustment for Toxicity

Dosage modification for toxicity (solid tumors, including ovary, breast, and lung carcinoma): Courses of paclitaxel should not be repeated until the neutrophil count is ≥1,500/mm3 and the platelet count is ≥100,000/mm3; reduce dosage by 20% for patients experiencing severe peripheral neuropathy or severe neutropenia (neutrophil <500/mm3 for a week or longer)

Dosage modification for immunosuppression in advanced HIV disease: Paclitaxel should not be given to patients with HIV if the baseline or subsequent neutrophil count is <1000 cells/mm3. Additional modifications include: Reduce dosage of dexamethasone in premedication to 10 mg orally; reduce dosage by 20% in patients experiencing severe peripheral neuropathy or severe neutropenia (neutrophil <500/mm3 for a week or longer); initiate concurrent hematopoietic growth factor (G-CSF) as clinically indicated

Dosing: Obesity

ASCO Guidelines for appropriate chemotherapy dosing in obese adults with cancer: Utilize patient’s actual body weight (full weight) for calculation of body surface area- or weight-based dosing, particularly when the intent of therapy is curative; manage regimen-related toxicities in the same manner as for nonobese patients; if a dose reduction is utilized due to toxicity, consider resumption of full weight-based dosing with subsequent cycles, especially if cause of toxicity (eg, hepatic or renal impairment) is resolved (Griggs, 2012).

Reconstitution

Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]). Dilute for infusion in 250 to 1,000 mL D5W, D5LR, D5NS, or NS to a concentration of 0.3 to 1.2 mg/mL, use a non-PVC container (glass or polyethylene). Chemotherapy dispensing devices (eg, Chemo Dispensing Pin) should not be used to withdraw paclitaxel from the vial; closed system transfer devices may not be compatible with undiluted paclitaxel.

Administration

IV: Infuse over 3 or 24 hours (depending on indication/protocol); some off-label protocols use a 1-hour infusion. Infuse through a 0.22-micron in-line filter and polyethylene-lined (non-PVC) administration set. When administered as a part of a combination chemotherapy regimen, sequence of administration may vary by regimen; refer to specific protocol for sequence recommendation.

Premedication with dexamethasone (20 mg orally or IV at 12 and 6 hours before the dose; reduce to 10 mg with advanced HIV disease), diphenhydramine (50 mg IV 30 to 60 minutes prior to the dose), and cimetidine 300 mg, famotidine 20 mg, or ranitidine 50 mg (IV 30 to 60 minutes prior to the dose) is recommended.

Irritant with vesicant-like properties; avoid extravasation. Ensure proper needle or catheter position prior to administration.

Extravasation management: If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); remove needle/cannula; initiate antidote (hyaluronidase); remove needle/cannula; elevate extremity. Information conflicts regarding the use of warm or cold compresses (Perez Fidalgo, 2012; Polovich, 2009).

Hyaluronidase: If needle/cannula still in place: Administer 1 to 6 mL (150 units/mL) into existing IV line; usual dose is 1 mL for each 1 mL of extravasated drug; if needle/cannula has been removed, inject subcutaneously in a clockwise manner around area of extravasation; may repeat several times over the next 3 to 4 hours (Ener, 2004).

Intraperitoneal (off-label route): Solution was prepared in warmed saline and infused as rapidly as possible through an implantable intraperitoneal catheter (Armstrong, 2006).

Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]).

Compatibility

Stable in D5W, NS.

Y-site administration: Incompatible with amphotericin B, amphotericin B cholesteryl sulfate complex, chlorpromazine, doxorubicin liposome, hydroxyzine, methylprednisolone sodium succinate, mitoxantrone.

Storage

Store intact vials at room temperature of 20°C to 25°C (68°F to 77°F). Protect from light. Solutions diluted for infusion in D5W and NS are stable for up to 27 hours at ambient temperature (~25°C).

Paclitaxel should be dispensed in either glass or non-PVC containers (eg, Excel/PAB). Use nonpolyvinyl (non-PVC) tubing (eg, polyethylene) to minimize leaching. Formulated in a vehicle known as polyoxyl 35/polyoxyethylated castor oil (Cremophor EL), which has been found to leach the plasticizer DEHP from polyvinyl chloride infusion bags or administration sets. Contact of the undiluted concentrate with plasticized polyvinyl chloride (PVC) equipment or devices is not recommended.

Drug Interactions

Abiraterone Acetate: May increase the serum concentration of CYP2C8 Substrates. Monitor therapy

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification

Antineoplastic Agents (Anthracycline, Systemic): Taxane Derivatives may enhance the adverse/toxic effect of Antineoplastic Agents (Anthracycline, Systemic). Taxane Derivatives may increase the serum concentration of Antineoplastic Agents (Anthracycline, Systemic). Taxane Derivatives may also increase the formation of toxic anthracycline metabolites in heart tissue. Consider therapy modification

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy

Aprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Atazanavir: May increase the serum concentration of PACLitaxel (Conventional). Management: Use of paclitaxel or other narrow therapeutic index CYP2C8 substrates with atazanavir without concurrent ritonavir is not recommended. If paclitaxel is used with ritonavir-boosted atazanavir, no significant interaction is expected. Avoid combination

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Bexarotene (Systemic): PACLitaxel (Conventional) may increase the serum concentration of Bexarotene (Systemic). Bexarotene (Systemic) may decrease the serum concentration of PACLitaxel (Conventional). Monitor therapy

Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

CYP2C8 Inducers (Strong): May increase the metabolism of CYP2C8 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

CYP2C8 Inhibitors (Moderate): May decrease the metabolism of CYP2C8 Substrates. Monitor therapy

CYP2C8 Inhibitors (Strong): May decrease the metabolism of CYP2C8 Substrates. Consider therapy modification

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Monitor therapy

CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP2C8 Substrates. Management: Seek alternatives to the CYP2C8 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Deferasirox: May increase the serum concentration of CYP2C8 Substrates. Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Avoid combination

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination

DOXOrubicin (Conventional): Taxane Derivatives may decrease the metabolism of DOXOrubicin (Conventional). Management: Consider using docetaxel instead of paclitaxel as a way to avoid this potential interaction, and monitor closely for toxic effects of doxorubicin. Administer doxorubicin prior to paclitaxel when used concomitantly. Consider therapy modification

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates. Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification

Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Monitor therapy

Luliconazole: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Mifepristone: May increase the serum concentration of CYP2C8 Substrates. Management: Use CYP2C8 substrates at the lowest recommended dose, and monitor closely for adverse effects (including myopathy), during and in the 2 weeks following mifepristone treatment. Consider therapy modification

Mifepristone: May increase the serum concentration of CYP3A4 Substrates. Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification

Mitotane: May decrease the serum concentration of CYP3A4 Substrates. Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Netupitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification

Osimertinib: May increase the serum concentration of CYP3A4 Substrates. Osimertinib may decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Platinum Derivatives: May enhance the myelosuppressive effect of Taxane Derivatives. Administer Taxane derivative before Platinum derivative when given as sequential infusions to limit toxicity. Consider therapy modification

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Ranolazine: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy

SORAfenib: May enhance the adverse/toxic effect of PACLitaxel (Conventional). Management: Concurrent sorafenib with carboplatin and paclitaxel in patients with squamous cell lung cancer is contraindicated. Use in other settings is not specifically contraindicated but should be approached with added caution. Avoid combination

St John's Wort: May decrease the serum concentration of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Avoid combination

Trastuzumab: May decrease the serum concentration of PACLitaxel (Conventional). PACLitaxel (Conventional) may increase the serum concentration of Trastuzumab. Monitor therapy

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Avoid combination

Vinorelbine: PACLitaxel (Conventional) may enhance the neurotoxic effect of Vinorelbine. Monitor therapy

Adverse Reactions

Percentages reported with single-agent therapy. Note: Myelosuppression is dose related, schedule related, and infusion-rate dependent (increased incidences with higher doses, more frequent doses, and longer infusion times) and, in general, rapidly reversible upon discontinuation.

>10%:

Cardiovascular: Flushing (28%), ECG abnormal (14% to 23%), edema (21%), hypotension (4% to 12%)

Dermatologic: Alopecia (87%), rash (12%)

Gastrointestinal: Nausea/vomiting (52%), diarrhea (38%), mucositis (17% to 35%; grades 3/4: up to 3%), stomatitis (15%; most common at doses >390 mg/m2), abdominal pain (with intraperitoneal paclitaxel)

Hematologic: Neutropenia (78% to 98%; grade 4: 14% to 75%; onset 8-10 days, median nadir 11 days, recovery 15-21 days), leukopenia (90%; grade 4: 17%), anemia (47% to 90%; grades 3/4: 2% to 16%), thrombocytopenia (4% to 20%; grades 3/4: 1% to 7%), bleeding (14%)

Hepatic: Alkaline phosphatase increased (22%), AST increased (19%)

Local: Injection site reaction (erythema, tenderness, skin discoloration, swelling: 13%)

Neuromuscular & skeletal: Peripheral neuropathy (42% to 70%; grades 3/4: up to 7%), arthralgia/myalgia (60%), weakness (17%)

Renal: Creatinine increased (observed in KS patients only: 18% to 34%; severe: 5% to 7%)

Miscellaneous: Hypersensitivity reaction (31% to 45%; grades 3/4: up to 2%), infection (15% to 30%)

1% to 10%:

Cardiovascular: Bradycardia (3%), tachycardia (2%), hypertension (1%), rhythm abnormalities (1%), syncope (1%), venous thrombosis (1%)

Dermatologic: Nail changes (2%)

Hematologic: Febrile neutropenia (2%)

Hepatic: Bilirubin increased (7%)

Respiratory: Dyspnea (2%)

<1% (Limited to important or life-threatening): Anaphylaxis, arrhythmia, ataxia, atrial fibrillation, AV block, back pain, cardiac conduction abnormalities, cellulitis, CHF, chills, conjunctivitis, dehydration, enterocolitis, extravasation recall, hepatic encephalopathy, hepatic necrosis, induration, intestinal obstruction, intestinal perforation, interstitial pneumonia, ischemic colitis, lacrimation increased, maculopapular rash, malaise, MI, myocardial ischemia, necrotic changes and ulceration following extravasation, neuroencephalopathy, neutropenic enterocolitis, neutropenic typhlitis, ototoxicity (tinnitus and hearing loss), pancreatitis, paralytic ileus, phlebitis, pneumonitis, pruritus, pulmonary embolism, pulmonary fibrosis, radiation recall, radiation pneumonitis, renal insufficiency, seizure, skin exfoliation, skin fibrosis, skin necrosis, Stevens-Johnson syndrome, supraventricular tachycardia, toxic epidermal necrolysis, ventricular tachycardia (asymptomatic), visual disturbances (scintillating scotomata)

ALERT: U.S. Boxed Warning

Experienced physician:

Administer under the supervision of a health care provider experienced in the use of cancer chemotherapeutic agents. Appropriate management of complications is possible only when adequate diagnostic and treatment facilities are readily available.

Hypersensitivity reactions:

Anaphylaxis and severe hypersensitivity reactions characterized by dyspnea and hypotension requiring treatment, angioedema, and generalized urticaria have occurred in 2% to 4% of patients in clinical trials. Fatal reactions have occurred in patients despite premedication. Pretreat all patients with corticosteroids, diphenhydramine, and histamine H2 antagonists. Do not rechallenge patients who experience severe hypersensitivity reactions to paclitaxel.

Bone marrow suppression:

Do not give to patients with solid tumors who have baseline neutrophil counts of less than 1,500 cells/mm3 or to patients with AIDS-related Kaposi sarcoma if the baseline neutrophil count is less than 1,000 cells/mm3. To monitor the occurrence of bone marrow suppression, primarily neutropenia, which may be severe and result in infection, perform frequent peripheral blood cell counts on all patients.

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: [US Boxed Warning]: Bone marrow suppression (primarily neutropenia; may be severe or result in infection) may occur. Monitor blood counts frequently. Do not administer if baseline neutrophil count is <1,500/mm3 (for solid tumors) or <1,000/mm3 (for patients with AIDS-related Kaposi sarcoma). Bone marrow suppression (usually neutropenia) is dose-dependent and is the dose-limiting toxicity; neutrophil nadir is usually at a median of 11 days. Subsequent cycles should not be administered until neutrophils are >1,500/mm3 (for solid tumors) and 1,000/mm3 (for Kaposi sarcoma); platelets should recover to 100,000/mm3. Reduce future doses by 20% for severe neutropenia (<500/mm3 for 7 days or more) and consider the use of supportive therapy, including growth factor treatment.

• Cardiovascular effects: Infusion-related hypotension, bradycardia, and/or hypertension may occur; frequent monitoring of vital signs is recommended, especially during the first hour of the infusion. Rare but severe conduction abnormalities have been reported; conduct continuous cardiac monitoring during subsequent infusions for these patients.

• Extravasation: Paclitaxel is an irritant with vesicant-like properties; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation. Injection-site reactions are generally mild (skin discoloration, tenderness, erythema, or swelling) and occur more commonly with an extended infusion duration (eg, 24 hours); injection-site reactions may be delayed (7 to 10 days). More severe reactions (phlebitis, cellulitis, skin exfoliation, necrosis, fibrosis, and induration) have also been reported. Recall skin reactions may occur despite administering through a different IV site.

• Hypersensitivity reactions: [US Boxed Warning]: Anaphylaxis and severe hypersensitivity reactions (dyspnea requiring bronchodilators, hypotension requiring treatment, angioedema, and/or generalized urticaria) have occurred in 2% to 4% of patients in clinical studies. Premedicate with corticosteroids, diphenhydramine, and H2 antagonists prior to infusion. Some reactions have been fatal despite premedication. If severe hypersensitivity occurs, stop infusion and do not rechallenge. Minor hypersensitivity reactions (flushing, skin reactions, dyspnea, hypotension, or tachycardia) do not require interruption of treatment.

• Peripheral neuropathy: Peripheral neuropathy may commonly occur; patients with preexisting neuropathies from prior chemotherapy or coexisting conditions (eg, diabetes mellitus) may be at a higher risk; reduce dose by 20% for severe neuropathy.

Disease-related concerns:

• Hepatic impairment: Use with extreme caution in patients with hepatic dysfunction (myelotoxicity may be worsened in patients with total bilirubin >2 times ULN); dose reductions are recommended.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Use with caution in the elderly; increased risk of toxicity (severe neutropenia, neuropathy, and cardiovascular events).

Special handling:

• Hazardous agent: Use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]).

Other warnings/precautions:

• Excipients: Conventional paclitaxel formulations contain polyoxyl 35/polyoxyethylated castor oil (Cremophor EL), which is associated with hypersensitivity reactions. Formulations also contain dehydrated alcohol which may cause adverse CNS effects.

• Experienced physician: [US Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician. Administer in a facility sufficient to appropriately diagnose and manage complications.

• Intraperitoneal administration: Intraperitoneal administration of paclitaxel is associated with a higher incidence of chemotherapy- related toxicity (Armstrong, 2006).

Monitoring Parameters

CBC with differential and platelet count, liver and kidney function; monitor for hypersensitivity reactions, vital signs (frequently during the first hour of infusion), continuous cardiac monitoring (patients with conduction abnormalities); monitor infusion site during infusion.

Pregnancy Risk Factor

D

Pregnancy Considerations

Adverse events (embryotoxicity, fetal toxicity, and maternal toxicity) have been observed in animal reproduction studies at doses less than the recommended human dose. An ex vivo human placenta perfusion model illustrated that paclitaxel crossed the placenta at term. Placental transfer was low and affected by the presence of albumin; higher albumin concentrations resulted in lower paclitaxel placental transfer (Berveiller, 2012). Some pharmacokinetic properties of paclitaxel may be altered in pregnant women (van Hasselt, 2014). Women of childbearing potential should be advised to avoid becoming pregnant. A pregnancy registry is available for all cancers diagnosed during pregnancy at Cooper Health (877-635-4499).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience mouth sores or hair loss. Have patient report immediately to prescriber signs of infection, signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), shortness of breath, excessive weight gain, swelling of arms or legs, severe dizziness, passing out, angina, tachycardia, flushing, arrhythmia, bradycardia, severe headache, severe abdominal pain, severe nausea, vomiting, severe diarrhea, bruising, bleeding, severe muscle pain, severe joint pain, burning or numbness feeling, loss of strength and energy, vision changes, or severe injection site pain or irritation (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

Hide