PACLitaxel (Conventional)

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)

Pharmacology

Mechanism of Action

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.

Pharmacokinetics/Pharmacodynamics

Distribution

V_dss: 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%

Use in Specific Populations

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: Off Label

Bladder cancer, advanced or metastaticb

Data from 2 small phase II studies support the use of paclitaxel (in combination with gemcitabine) in the treatment of advanced or metastatic bladder cancer Meluch 2001, Sternberg 2001.

Cervical cancer, advanceda

Data from a large randomized study supports the use of paclitaxel (in combination with bevacizumab and either cisplatin or topotecan) in the treatment of advanced cervical cancer Tewari 2014.

Data from two phase III studies support the use of paclitaxel (in combination with cisplatin) in the treatment of advanced cervical cancer Monk 2009, Moore 2004.

Esophageal/gastric cancer, preoperative chemoradiationa

Data from a randomized phase III study supports the use of paclitaxel (in combination with carboplatin and radiation therapy) in the preoperative management of esophageal and gastric cancers van Hagen 2012.

Head and neck cancers, advanceda

Data from a randomized phase III study supports the use of paclitaxel (in combination with cisplatin) in the management of advanced head and neck cancer Gibson 2005.

Ovarian cancer, intraperitoneal (off-label route)a

Data from a large randomized phase III study supports the use of intraperitoneal paclitaxel in the treatment of newly diagnosed advanced ovarian cancer Armstrong 2006.

Penile cancer, metastaticb

Data from a small phase II study supports the use of neoadjuvant chemotherapy (paclitaxel, ifosfamide, and cisplatin) in patients with penile cancer who have bulky regional lymph node metastases Pagliaro 2010.

Small cell lung cancer, relapsed/refractoryb

Data from two small phase II studies support the use of paclitaxel (as a single agent) in the treatment of relapsed or refractory small cell lung cancer Smit 1998, Yamamoto 2006.

Soft tissue sarcoma (angiosarcoma), advanced/unresectableb

Data from a small phase II study and a retrospective study support the use of paclitaxel (as a single agent) in the treatment of advanced or unresectable angiosarcoma Penel 2008, Schlemmer 2008.

Testicular germ cell tumors, relapsed/refractoryb

Data from a small phase II study supports the use of paclitaxel (in combination with gemcitabine and oxaliplatin) in the treatment of relapsed or refractory testicular germ cell tumors Bokemeyer 2008. Data from another small phase II study supports the use of paclitaxel (in combination with ifosfamide and cisplatin) in the treatment of relapsed or refractory testicular germ cell tumors Kondagunta 2005. Data from a phase II study supports the use of paclitaxel (in combination with gemcitabine) as salvage treatment for progressive testicular germ cell tumors following high dose chemotherapy with transplant Einhorn 2007.

Thymoma/thymic carcinoma, advancedb

Data from a small phase II study supports the use of paclitaxel (in combination with carboplatin) in the treatment of advanced thymoma/thymic carcinoma Lemma 2011.

Unknown primary adenocarcinomab

Data from a small phase II study supports the use of paclitaxel (in combination with carboplatin) in the treatment of unknown primary adenocarcinoma Briasoulis 2000. Data from another small phase II study supports the use of paclitaxel (in combination with carboplatin and etoposide) for the treatment of unknown primary adenocarcinoma Greco 2000.

Additional Off-Label Uses

Endometrial carcinoma; Esophageal cancer (metastatic/unresectable); Gastric cancer (metastatic/unresectable); Melanoma; Thyroid cancer (anaplastic).

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.

Dosage and Administration

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

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.

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

Off-label dosing/combinations: IV: 200 mg/m² on day 1 every 3 weeks for 4 cycles (in combination with pembrolizumab and carboplatin) followed by pembrolizumab maintenance therapy (Paz-Ares 2018) or 200 mg/m² (175 mg/m² for Asian patients) on day 1 every 3 weeks for 4 to 6 cycles (in combination with atezolizumab, bevacizumab, and carboplatin) followed by atezolizumab/bevacizumab maintenance therapy (Socinski 2018)

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) or 175 mg/m² on day 1 every 3 weeks (in combination with bevacizumab [delayed until cycle 2] and carboplatin) for up to 6 cycles, followed by bevacizumab monotherapy for a total of up to 22 cycles or until disease progression (whichever occurs earlier) (Burger 2011)

Neoadjuvant therapy (off-label combination/schedule): Note: According to guidelines from the Society of Gynecologic Oncology and American Society of Clinical Oncology for neoadjuvant chemotherapy in newly diagnosed advanced ovarian cancer, neoadjuvant therapy should be utilized only in properly selected patients. Selection criteria include patients with newly diagnosed suspected stage IIIC or IV ovarian cancer who have a high perioperative risk profile and/or a low likelihood of achieving cytoreduction to <1 cm of residual disease (SGO/ASCO [Wright 2016]).

IV: 175 mg/m² over 3 hours on day 1 every 3 weeks (in combination with carboplatin) for 3 neoadjuvant cycles, followed by debulking surgery, followed by 3 additional chemotherapy cycles (Kehoe 2015; Vergot 2010) or 175 mg/m² on day 1 every 3 weeks (in combination with carboplatin) for 3 to 4 neoadjuvant cycles, followed by debulking surgery, followed by 2 to 3 additional chemotherapy cycles, for a total of 6 cycles (Fagotti 2016).

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: Adjustment for Toxicity

Dosage modification for toxicity (solid tumors, including ovary, breast, and lung carcinoma): Adjustment recommendations are based on the labeled doses (135 mg/m² dose over 3 hours or 24 hours every 3 weeks or 175 mg/m² dose over 3 hours every 3 weeks): Courses of paclitaxel should not be repeated until the neutrophil count is ≥1,500/mm³ and the platelet count is ≥100,000/mm³; reduce dosage by 20% for patients experiencing severe peripheral neuropathy or severe neutropenia (neutrophil <500/mm³ for a week or longer)

Dosage modification for immunosuppression in AIDS-related Kaposi sarcoma: Adjustment recommendations are based on the labeled doses (135 mg/m² over 3 hours every 3 weeks or 100 mg/m² over 3 hours every 2 weeks): Paclitaxel should not be given to patients with HIV if the baseline or subsequent neutrophil count is <1,000/mm³. Additional modifications include: Reduce dosage of dexamethasone in premedication to 10 mg orally; reduce dosage by 20% in patients experiencing severe peripheral neuropathy or severe neutropenia (neutrophil <500/mm³ for a week or longer); initiate concurrent hematopoietic growth factor (G-CSF) as clinically indicated

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

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) if appropriate; remove needle/cannula; elevate extremity. Information conflicts regarding the use of warm or cold compresses (Perez Fidalgo 2012; Polovich 2009). Clinical experience suggests hyaluronidase may be used in the management of paclitaxel extravasations (Stanford 2003; Perez Fidalgo 2012); data is limited.

If using hyaluronidase: If needle/cannula still in place: Administer 1 to 6 mL (150 units/mL) into existing IV line; usual dose is 1 mL for each 1 mL of extravasated drug; if needle/cannula has been removed, inject subcutaneously in a clockwise manner around area of extravasation; may repeat several times over the next 3 to 4 hours (Ener 2004; Perez Fidalgo 2012).

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

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

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

Anthracyclines: Taxane Derivatives may enhance the adverse/toxic effect of Anthracyclines. Taxane Derivatives may increase the serum concentration of Anthracyclines. Taxane Derivatives may also increase the formation of toxic anthracycline metabolites in heart tissue. 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 (High risk with Inhibitors). 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

Baricitinib: Immunosuppressants may enhance the immunosuppressive effect of Baricitinib. Management: Use of baricitinib in combination with potent immunosuppressants such as azathioprine or cyclosporine is not recommended. Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted. Consider therapy modification

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

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

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 (High risk with Inducers). Monitor therapy

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

Bromperidol: Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents. Avoid combination

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Monitor therapy

Cladribine: May enhance the immunosuppressive effect of Immunosuppressants. Avoid combination

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Avoid combination

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). 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 (High risk with Inhibitors). Avoid combination

CYP2C8 Inhibitors (Moderate): May increase the serum concentration of PACLitaxel (Conventional). Monitor therapy

CYP2C8 Inhibitors (Strong): May increase the serum concentration of PACLitaxel (Conventional). Monitor therapy

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

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). 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 (High risk with Inhibitors). Monitor therapy

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

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). 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

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Consider therapy modification

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

Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

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

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). 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

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

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

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 (High risk with Inhibitors). Monitor therapy

Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

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

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Lasmiditan: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Avoid combination

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

Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Consider therapy modification

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

Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Consider therapy modification

Lorlatinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. Consider therapy modification

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

Mesalamine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). 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 (High risk with Inducers). 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

Naftopidil: 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 (High risk with Inhibitors). Monitor therapy

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

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

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. 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

Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Consider therapy modification

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

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

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

Pidotimod: Immunosuppressants may diminish the therapeutic effect of Pidotimod. 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

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

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

Quinagolide: 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

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Siponimod: Immunosuppressants may enhance the immunosuppressive effect of Siponimod. Monitor therapy

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy. Consider therapy modification

Smallpox and Monkeypox Vaccine (Live): Immunosuppressants may diminish the therapeutic effect of Smallpox and Monkeypox Vaccine (Live). 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

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). 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

Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). 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. Consider therapy modification

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

Upadacitinib: Immunosuppressants may enhance the immunosuppressive effect of Upadacitinib. Avoid combination

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. Exceptions: Smallpox and Monkeypox Vaccine (Live). Avoid combination

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

Adverse Reactions

>10%:

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

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

Gastrointestinal: Nausea and vomiting (52%), diarrhea (38%), stomatitis (17% to 31%; grade 3/4: ≤3%)

Hematologic & oncologic: Neutropenia (78% to 98%; grade 4: 14% to 75%; median nadir: 11 days), leukopenia (90%; grade 4: 17%), anemia (47% to 90%; grades 3/4: 2% to 16%), thrombocytopenia (4% to 20%; grades 3/4: 1% to 7%), hemorrhage (14%)

Hepatic: Increased serum alkaline phosphatase (22%), increased serum aspartate aminotransferase (19%)

Hypersensitivity: Hypersensitivity reaction (31% to 45%)

Infection: Infection (15% to 30%)

Local: Injection site reaction (13%)

Nervous system: Peripheral neuropathy (42% to 70%; grades 3/4: ≤7%)

Neuromuscular & skeletal: Arthralgia (≤60%), myalgia (≤60%), asthenia (17%)

Miscellaneous: Fever (12%)

1% to 10%:

Cardiovascular: Bradycardia (3%), tachycardia (2%), hypertension (1%), cardiac arrhythmia (≤1%), syncope (≤1%), venous thrombosis (≤1%)

Dermatologic: Changes in nails (2%)

Hematologic & oncologic: Febrile neutropenia (2%)

Hepatic: Increased serum bilirubin (7%)

Hypersensitivity: Anaphylaxis (≤4%), severe hypersensitivity reaction (≤4%)

Respiratory: Dyspnea (2%)

Frequency not defined:

Dermatologic: Skin discoloration at injection site

Gastrointestinal: Abdominal pain, peritonitis

Hypersensitivity: Angioedema

Infection: Sepsis

Local: Erythema at injection site, swelling at injection site, tenderness at injection site

Respiratory: Pneumonia

<1%, postmarketing, and/or case reports: Acute myocardial infarction, anorexia, ascites, ataxia, atrial fibrillation, atrioventricular block, back pain, bigeminy, cardiac conduction disorder, cardiac failure, cellulitis, chills, confusion, conjunctivitis, constipation, dehydration, desquamation, dizziness, encephalopathy, esophagitis, exacerbation of scleroderma, fibrosis at injection site, headache, hearing loss, hepatic encephalopathy, hepatic necrosis, increased lacrimation, increased serum creatinine, induration at injection site, intestinal obstruction, intestinal perforation, interstitial pneumonitis, ischemic colitis, local skin exfoliation, maculopapular rash, malaise, neutropenic enterocolitis, optic nerve damage, ototoxicity, pancreatitis, paralytic ileus, phlebitis, photopsia, pruritus, pulmonary embolism, pulmonary fibrosis, radiation recall phenomenon, radiation pneumonitis, respiratory failure, seizure, shock, skin edema (diffuse), skin necrosis, skin sclerosis, Stevens-Johnson syndrome, subacute cutaneous lupus erythematosus (Sibaud 2016), supraventricular tachycardia, thickening of skin, tinnitus, tonic clonic epilepsy, toxic epidermal necrolysis, ventricular tachycardia (asymptomatic), vertigo, visual disturbance (scintillating scotomata)

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. In a scientific statement from the American Heart Association, conventional paclitaxel has been determined to be an agent that may either cause direct myocardial toxicity or exacerbate underlying myocardial dysfunction (magnitude: moderate) (AHA [Page 2016])
• Extravasation: Paclitaxel is an irritant with vesicant-like properties; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation. Injection-site reactions are generally mild (skin discoloration, tenderness, erythema, or swelling) and occur more commonly with an extended infusion duration (eg, 24 hours); injection-site reactions may be delayed (7 to 10 days). More severe reactions (phlebitis, cellulitis, skin exfoliation, necrosis, fibrosis, and induration) have also been reported. Recall skin reactions may occur despite administering through a different IV site.
• Hypersensitivity 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).

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

Pregnancy Risk Factor

D

Pregnancy Considerations

Adverse events have been observed in animal reproduction. 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 females (van Hasselt 2014). Females of reproductive 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

What is this drug used for?

• It is used to treat cancer.

Frequently reported side effects of this drug

• Mouth sores
• Hair loss
• Nausea
• Vomiting
• Diarrhea
• Muscle pain
• Joint pain

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Infection
• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin.
• Bleeding like vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding
• Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain
• Shortness of breath
• Edema
• Severe dizziness
• Passing out
• Chest pain
• Fast heartbeat
• Flushing
• Abnormal heartbeat
• Slow heartbeat
• Severe headache
• Severe abdominal pain
• Burning or numbness feeling
• Severe loss of strength and energy
• Vision changes
• Severe injection site redness, burning, edema, pain or irritation
• Signs of a significant reaction like 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. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.