PACLitaxel (Protein Bound)

Dosage Forms

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

Suspension Reconstituted, Intravenous:

Abraxane: 100 mg (1 ea)

Pharmacology

Mechanism of Action

Paclitaxel (protein bound) is an albumin-bound paclitaxel nanoparticle formulation; 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. May also distort mitotic spindles, resulting in the breakage of chromosomes. Paclitaxel may also suppress cell proliferation and modulate immune response.

Pharmacokinetics/Pharmacodynamics

Distribution

V_d: 1741 L (extensive extravascular distribution and/or tissue binding)

Metabolism

Hepatic primarily via CYP2C8 to 6-alpha-hydroxypaclitaxel; also to minor metabolites via CYP3A4

Excretion

Feces (~20%); urine (4% as unchanged drug, <1% as metabolites).

Clearance: 13 to 30 L/hour/m².

Half-Life Elimination

Terminal: 13 to 27 hours

Protein Binding

94%

Use in Specific Populations

Special Populations: Hepatic Function Impairment

Plasma paclitaxel exposure is increased in patients with hepatic impairment. Patients with moderate (bilirubin >1.5 to ≤3 × ULN and AST ≤10 × ULN) or severe (bilirubin >3 to ≤5 × ULN) hepatic impairment had ~20% increase in AUC compared with patients with normal hepatic function.

Use: Labeled Indications

Breast cancer, metastatic: Treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy; prior therapy should have included an anthracycline unless clinically contraindicated.

Non-small cell lung cancer, locally advanced or metastatic: First-line treatment of locally advanced or metastatic non-small cell lung cancer (in combination with carboplatin) in patients who are not candidates for curative surgery or radiation therapy.

Pancreatic adenocarcinoma, metastatic: First-line treatment of metastatic adenocarcinoma of the pancreas (in combination with gemcitabine).

Use: Off Label

Bladder cancer, metastatic, platinum-resistantb

Data from a small phase II multicenter study support the use of paclitaxel (protein bound) as second-line therapy in the treatment of platinum-resistant locally advanced or metastatic bladder cancer in patients with progression on or within 12 months of a platinum-based chemotherapy regimen Ko 2013.

Cervical cancer, advanced, recurrent or persistentb

Data from a small phase II study support the use of paclitaxel (protein bound) as second-line therapy in the treatment of recurrent or persistent advanced cervical cancer in patients who have received prior systemic therapy which did not include a taxane Alberts 2012.

Melanoma, metastaticb

Data from a phase II study support the use of paclitaxel (protein bound) as monotherapy in the treatment of patients with metastatic melanoma Hersh 2010.

Ovarian, fallopian tube, or primary peritoneal cancers (recurrent)b

Data from phase II studies support the use of paclitaxel (protein bound) in the treatment of recurrent or persistent ovarian, fallopian tube, or primary peritoneal cancers Coleman 2011, Teneriello 2009.

Contraindications

Baseline neutrophil count of <1,500/mm³; severe hypersensitivity reaction to paclitaxel (protein bound) or any component of the formulation

Dosage and Administration

Dosing: Adult

Note: When administered as part of a combination chemotherapy regimen, sequence of administration may vary by regimen; refer to specific protocol for sequence of administration. Premedication is not generally necessary prior to paclitaxel (protein bound), but may be needed in patients with prior mild to moderate hypersensitivity reactions.

Bladder cancer, metastatic, platinum-resistant (off-label use): IV: 260 mg/m² once every 3 weeks; continue until disease progression or unacceptable toxicity (Ko 2013).

Breast cancer, metastatic: IV: 260 mg/m² every 3 weeks (Gradishar 2005).

Off-label dosing/combinations: IV:

100 to 150 mg/m² on days 1, 8, and 15 of a 28-day cycle (Gradishar 2009) or

Breast cancer (triple-negative), locally advanced or metastatic: 100 mg/m² on days 1, 8, and 15 of a 28-day cycle (in combination with atezolizumab) until disease progression or unacceptable toxicity; paclitaxel (protein bound) or atezolizumab may be discontinued for toxicity independently of each other (Schmid 2018).

Cervical cancer, advanced, recurrent or persistent (off-label use): IV: 125 mg/m² on days 1, 8, and 15 of a 28-day cycle; continue until disease progression or unacceptable toxicity (Alberts 2012).

Melanoma, metastatic (off-label use): IV:

Previously treated patients: 100 mg/m² on days 1, 8, and 15 of a 28-day cycle; if tolerated, may increase dose by 25 mg/m² in cycle 2 and beyond (Hersh 2010).

Previously untreated patients: 150 mg/m² on days 1, 8, and 15 of a 28-day cycle (Hersh 2010).

Non-small cell lung cancer, locally advanced or metastatic: IV: 100 mg/m² on days 1, 8, and 15 of each 21-day cycle (in combination with carboplatin) (Socinski 2012).

Off-label combination: 100 mg/m² on days 1, 8, and 15 of each 21-day cycle (in combination with carboplatin and pembrolizumab) for 4 cycles, followed by pembrolizumab maintenance therapy (Paz-Ares 2018) or 100 mg/m² on days 1, 8, and 15 of each 21-day cycle (in combination with atezolizumab and carboplatin) for 4 to 6 cycles, followed by atezolizumab maintenance therapy (West 2019).

Ovarian, fallopian tube, or primary peritoneal cancer, recurrent (off-label use): IV: 260 mg/m² on day 1 of a 21-day cycle for 6 to 8 cycles (Teneriello 2009) or 100 mg/m² on days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity (Coleman 2011).

Pancreatic adenocarcinoma, metastatic: IV: 125 mg/m² on days 1, 8, and 15 of a 28-day cycle (in combination with gemcitabine) (Von Hoff 2013).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Adjustment for Toxicity

Breast cancer (metastatic; every-3-week regimen):

Severe neutropenia (<500 cells/mm³) ≥1 week: Reduce dose to 220 mg/m² for subsequent courses.

Recurrent severe neutropenia: Reduce dose to 180 mg/m² for subsequent courses.

Sensory neuropathy

Grade 1 or 2: Dosage adjustment generally not required.

Grade 3: Hold treatment until resolved to grade 1 or 2, then resume with reduced dose for all subsequent cycles.

Severe sensory neuropathy: Reduce dose to 220 mg/m² for subsequent courses.

Recurrent severe sensory neuropathy: Reduce dose to 180 mg/m² for subsequent courses.

Non-small cell lung cancer:

Neutropenia: ANC <1,500 cells/mm³: Withhold therapy until ANC is ≥1,500 cells/mm³ on day 1 or ≥500 cells/mm³ on days 8 or 15. Reduce dose upon therapy reinitiation if:

Neutropenic fever (ANC <500 cells/mm³ with fever >38°C) or delay of next cycle by >7 days due to ANC <1,500 cells/mm³or ANC <500 cells/mm³ for >7 days:

First occurrence: Permanently reduce dose to 75 mg/m².

Second occurrence: Permanently reduce dose to 50 mg/m²_.

Third occurrence: Discontinue therapy.

Thrombocytopenia: Platelet count <100,000 cells/mm³: Withhold therapy until platelet count is ≥100,000 cells/mm³ on day 1 or ≥50,000 cells/mm³ on days 8 or 15. Reduce dose upon therapy reinitiation if:

Platelet count <50,000 cells/mm³:

First occurrence: Permanently reduce dose to 75 mg/m².

Second occurrence: Discontinue therapy.

Sensory neuropathy: Withhold therapy for grade 3 or 4 peripheral neuropathy. Resume therapy at reduced doses when neuropathy resolves completely or improves to grade 1:

First occurrence: Permanently reduce dose to 75 mg/m².

Second occurrence: Permanently reduce dose to 50 mg/m².

Third occurrence: Discontinue therapy.

Pancreatic adenocarcinoma:

Note: Dose level reductions for toxicity (may also require WBC growth factors):

Full dose: 125 mg/m².

First dose reduction: 100 mg/m².

Second dose reduction: 75 mg/m².

If additional dose reduction is necessary: Discontinue.

Hematologic toxicity (neutropenia and/or thrombocytopenia):

Day 1: If ANC is <1,500 cells/mm³ or platelet count is <100,000 cells/mm³: Withhold therapy until ANC is ≥1,500 cells/mm³ and platelet count is ≥100,000 cells/mm³.

Day 8:

If ANC is 500 to <1,000 cells/mm³or platelet count is 50,000 to <75,000 cells/mm³: Reduce 1 dose level.

If ANC is <500 cells/mm³or platelet count is <50,000 cells/mm³: Withhold day 8 dose.

Day 15:

If day 8 doses were reduced or given without modification:

If ANC is 500 to <1,000 cells/mm³or platelet count is 50,000 to <75,000 cells/mm³: Reduce 1 dose level from day 8.

If ANC is <500 cells/mm³or platelet count is <50,000 cells/mm³: Withhold day 15 dose.

If day 8 doses were withheld:

If ANC is ≥1,000 cells/mm³or platelet count is ≥75,000 cells/mm³: Reduce 1 dose level from day 1.

If ANC is 500 to <1,000 cells/mm³or platelet count is 50,000 to <75,000 cells/mm³: Reduce 2 dose levels from day 1.

If ANC is <500 cells/mm³or platelet count is <50,000 cells/mm³: Withhold day 15 dose.

Neutropenic fever: Withhold therapy for grade 3 or 4 fever. Resume therapy at next lower dose level when fever resolves and ANC is ≥1,500 cells/mm³.

Peripheral neuropathy: Withhold therapy for grade 3 or 4 peripheral neuropathy. Resume therapy at next lower dose level when neuropathy improves to ≤ grade 1.

Dermatologic toxicity: For grade 2 or 3 toxicity, reduce dose to next lower dose level; if toxicity persists, discontinue.

Gastrointestinal toxicity: Withhold therapy for grade 3 mucositis or diarrhea. Resume therapy at next lower dose level when improves to ≤ grade 1.

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

Reconstitute vial with 20 mL NS to a concentration of 5 mg/mL. Add NS slowly (over a minimum of 1 minute), directing it along inside vial wall; allow vial to sit for 5 minutes, then gently swirl for 2 minutes; avoid foaming. If foaming or clumping occurs, allow solution to stand for at least 15 minutes until foaming subsides. Reconstituted solution will appear milky and homogenous without visible particulates; if particulates or settling are visible, gently invert vial to re-suspend. Discard reconstituted suspension if precipitates are observed. Draw calculated dose slowly into syringe, then place without further dilution into an empty sterile container. Note: Use of DEHP-free containers or administration sets is not necessary.

The use of syringes or IV bags containing silicone oil as a lubricant; may result in formation of proteinaceous strands. Note: The Canadian labeling recommends administering the infusion solution through a 15-micron filter if syringes/IV bags containing silicone oil are used and proteinaceous strands are observed; discard the solution if a filter is not available. Do not use a filter with a pore size <15 microns.

Administration

IV: Administer over 30 minutes (breast cancer and non-small cell lung cancer [NSCLC]) or over 30 to 40 minutes (pancreatic cancer); limiting the infusion rate to 30 minutes reduces the risk for infusion-related reaction. Monitor infusion site; avoid extravasation. When given on a weekly (off label) schedule, infusions were administered over ~30 minutes (Gradishar 2009; Hersh 2010; Rizvi 2008). When administered as part of a combination chemotherapy regimen, sequence of administration may vary by regimen; refer to specific protocol for sequence of administration. According to the manufacturer, paclitaxel (protein bound) should be given first, followed immediately by carboplatin (NSCLC) or gemcitabine (pancreatic cancer).

Storage

Store intact vials at 20°C to 25°C (68°F to 77°F) and protect from bright light. Freezing or refrigerating do not adversely affect the stability of intact vials. Protect reconstituted solution from light.

US labeling: Reconstituted solution in the vial as well as solution in infusion container for administration may be stored under refrigeration at 2°C to 8°C (36°F to 46°F) for up to 24 hours, although the manufacturer recommends immediate use. The total combined refrigerated storage time of both reconstituted solution in the vial and administration bag is 24 hours; solution may then be stored at room temperature (~25°C [77°F]) and ambient light for up to 4 hours.

Canadian labeling: Reconstituted solution in the vial may be stored under refrigeration at 2°C to 8°C (36°F to 46°F) for up to 8 hours, although the manufacturer recommends immediate use. Once transferred from vial to infusion bag for administration, use immediately or, if necessary, may store at 20°C to 25°C (68°F to 77°F) and ambient light for up to 8 hours.

Drug Interactions

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

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

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

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 (Protein Bound). Monitor therapy

CYP2C8 Inhibitors (Strong): May increase the serum concentration of PACLitaxel (Protein Bound). 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

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

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

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

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

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

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

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. 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

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

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

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

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 enhance the neutropenic effect of Immunosuppressants. 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 (Protein Bound) may enhance the neurotoxic effect of Vinorelbine. Monitor therapy

Adverse Reactions

Frequency may vary based on indication and/or concomitant therapy.

>10%:

Cardiovascular: ECG abnormality (60%; 35% in patients with a normal baseline), peripheral edema (10% to 46%)

Central nervous system: Peripheral sensory neuropathy (71%; grades 3/4: 10%; dose dependent; cumulative), fatigue (25% to 59%), peripheral neuropathy (48% to 54%; grade 3: 3% to 17%), headache (14%), depression (12%)

Dermatologic: Alopecia (50% to 90%), skin rash (10% to 30%)

Endocrine & metabolic: Dehydration (21%), increased gamma-glutamyl transferase (grades 3/4: 14%), hypokalemia (12%)

Gastrointestinal: Nausea (27% to 54%), diarrhea (15% to 44%), decreased appetite (17% to 36%), vomiting (12% to 36%), constipation (16%), dysgeusia (16%)

Genitourinary: Urinary tract infection (11%)

Hematologic & oncologic: Anemia (33% to 98%; grades 3/4: 1% to 28%), neutropenia (73% to 85%; grades 3/4: 34% to 47%), thrombocytopenia (2% to 74%; grades 3/4: ≤18%), bone marrow depression

Hepatic: Increased serum aspartate aminotransferase (39%), increased serum alkaline phosphatase (36%)

Infection: Infection (24%; including respiratory tract infection)

Neuromuscular & skeletal: Asthenia (16% to 47%), musculoskeletal pain (10% to 44%; myalgia/arthralgia), limb pain (11%)

Ophthalmic: Visual disturbance (13%; including blurred vision, keratitis)

Renal: Increased serum creatinine (11%)

Respiratory: Cough (7% to 17%), epistaxis (7% to 15%), dyspnea (1% to 12%)

Miscellaneous: Fever (41%)

1% to 10%:

Cardiovascular: Edema (10%), cardiac failure (<10%), hypertension (<10%), tachycardia (<10%), hypotension (≤5%), significant cardiovascular event (grades 3/4: 3%)

Gastrointestinal: Oral candidiasis (<10%), mucositis (7% to 10%)

Hematologic & oncologic: Hemorrhage (2%), febrile neutropenia (2%)

Hepatic: Increased serum bilirubin (7%)

Hypersensitivity: Hypersensitivity reaction (4%)

Infection: Sepsis (5%)

Ophthalmic: Cystoid macular edema (<10%)

Respiratory: Pneumonia (<10%), pneumonitis (4%)

Frequency not defined:

Cardiovascular: Ischemic heart disease, myocardial infarction, pulmonary thromboembolism, supraventricular tachycardia, thrombosis

<1%, postmarketing, and/or case reports: Anaphylaxis, atrioventricular block, autonomic neuropathy, bradycardia, cardiac arrhythmia, cerebrovascular accident, chest pain, cranial nerve palsy, decreased visual acuity, erythema, flushing, hepatic encephalopathy, hepatic necrosis, injection site reaction (mild), intestinal obstruction, intestinal perforation, ischemic colitis, left ventricular dysfunction, maculopapular rash, nail discoloration, neutropenic sepsis, optic nerve damage (rare), palmar-plantar erythrodysesthesia (in patients previously exposed to capecitabine), pancreatitis, pancytopenia, paralytic ileus, peripheral motor neuropathy, pneumothorax, pruritus, pulmonary embolism, radiation pneumonitis (with concurrent radiation therapy), radiation recall phenomenon, skin photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis, transient ischemic attacks, tumor lysis syndrome, vocal cord paralysis

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: [US Boxed Warning]: Bone marrow suppression, primarily neutropenia, may occur; monitor peripheral blood counts frequently. Baseline neutrophils should be ≥1,500/mm³ for administration on day 1 of each cycle; platelets should recover to >100,000/mm³ prior to day 1 of the next treatment cycle. Hematologic toxicity is dose-dependent and dose-limiting. For severe neutropenia, dose reductions may be recommended for subsequent cycles.
• Cardiovascular effects: 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]).
• Hypersensitivity: Severe (and sometimes fatal) hypersensitivity reactions (including anaphylaxis) have been reported; do not rechallenge after severe hypersensitivity reaction. Premedication is not generally necessary prior to paclitaxel (protein bound), although may be needed in patients with prior mild to moderate hypersensitivity reactions. Cross-sensitivity between paclitaxel (protein bound) and other taxanes has been reported and severe reactions, including anaphylaxis, may occur; closely monitor patients initiating therapy with a previous hypersensitivity to other taxanes. Use has not been studied in patients with a prior hypersensitivity reaction to conventional paclitaxel or to albumin.
• Neuropathy: Dose- and schedule-related sensory neuropathy is common; severe sensory neuropathy may occur. If ≥ grade 3 sensory neuropathy occurs, withhold therapy until resolution to grade 1 or 2 (breast cancer) or ≤ grade 1 (non-small cell lung cancer [NSCLC] and pancreatic cancer). Upon recovery, subsequent cycles should be dose reduced. Prior therapy with neurotoxic agents may influence the frequency and severity of neurologic toxicity.
• Ocular effects: Vision disturbances including decreased visual acuity associated with cystoid macular edema (CME) have been observed; resolution observed in most cases following therapy discontinuation. Consider prompt/complete ophthalmologic evaluation in patients with vision changes/decreased acuity.
• Pneumonitis: Pneumonitis (including fatal cases) was observed in clinical trials when used in combination with gemcitabine. Monitor for signs/symptoms of pneumonitis; interrupt therapy during diagnostic process. If pneumonitis is confirmed, permanently discontinue.
• Sepsis: Sepsis was observed in both neutropenic and non-neutropenic patients treated with paclitaxel (protein bound) in combination with gemcitabine for pancreatic cancer; biliary obstruction and/or the presence of a biliary stent may be risk factors for severe and/or fatal sepsis. Treat promptly with broad spectrum antibiotics if fever occurs (regardless of neutrophil count). May require therapy interruption and/or dosage reduction.

Disease-related concerns:

• Hepatic impairment: Exposure may be increased in patients with hepatic impairment; monitor closely; the risk of toxicities (particularly myelosuppression) is increased. Reduced initial dosages are recommended for breast cancer and NSCLC patients with moderate and severe hepatic impairment; use is not recommended in pancreatic patients with moderate or severe impairment (bilirubin >1.5 times ULN and AST ≤10 times ULN). Use is not recommended in patients with AST >10 times ULN or total bilirubin >5 times ULN.

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: Certain adverse events (myelosuppression, peripheral neuropathy, arthralgia, diarrhea, decreased appetite, dehydration, fatigue, and epistaxis) occurred more frequently in older adults ≥65 years compared to younger adults.

Dosage form specific issues:

• Albumin: Product contains albumin, which confers a remote risk of viral disease transmission and a theoretical risk of transmission of Creutzfeldt-Jakob disease.

Other warnings/precautions:

• Do not interchange: [US Boxed Warning]: Paclitaxel (protein-bound) is not interchangeable with other forms of paclitaxel, including Cremophor-based (polyoxyl 35/polyoxyethylated castor oil-based) or unbound paclitaxel.

Monitoring Parameters

CBC with differential (prior to day 1 of cycle for metastatic breast cancer and prior to days 1, 8, and 15 for non-small cell lung cancer and pancreatic cancer); monitor hepatic function; pregnancy test (prior to treatment initiation in females of reproductive potential). Monitor infusion site; monitor for neuropathy and for signs/symptoms of hypersensitivity, pneumonitis and sepsis

Pregnancy

Pregnancy Considerations

Based on the mechanism of action and on findings in animal reproduction studies, paclitaxel (protein bound) may cause fetal harm if administered during pregnancy.

An ex vivo human placenta perfusion model illustrated that paclitaxel (non-protein bound preparation) 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).

Females of reproductive potential should have a pregnancy test prior to treatment initiation and use effective contraception during therapy and for at least 6 months after the last paclitaxel (protein bound) dose. Males with female partners of reproductive potential should use effective contraception during therapy and for at least 3 months after the last paclitaxel (protein bound) dose.

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

• Muscle pain
• Joint pain
• Mouth irritation
• Mouth sores
• Hair loss
• Lack of appetite
• Change in taste
• Constipation

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

• Infection
• Fluid and electrolyte problems like mood changes, confusion, muscle pain or weakness, abnormal heartbeat, severe dizziness, passing out, fast heartbeat, increased thirst, seizures, loss of strength and energy, lack of appetite, unable to pass urine or change in amount of urine passed, dry mouth, dry eyes, or nausea or vomiting.
• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin.
• Shortness of breath
• Excessive weight gain
• Swelling of arms or legs
• Severe dizziness
• Passing out
• Chest pain
• Fast heartbeat
• Flushing
• Abnormal heartbeat
• Slow heartbeat
• Severe headache
• Severe nausea
• Vomiting
• Severe diarrhea
• Burning or numbness feeling
• Bruising
• Bleeding
• Nosebleed
• Severe loss of strength and energy
• Depression
• Vision changes
• Severe pulmonary disorder like lung or breathing problems like difficulty breathing, shortness of breath, or a cough that is new or worse.
• Severe injection site redness, burning, 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.