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PACLitaxel (Conventional)

Medically reviewed by Drugs.com. Last updated on Jul 21, 2020.

Pronunciation

(pac li TAKS el con VEN sha nal)

Index Terms

  • Conventional Paclitaxel
  • Onxol
  • Taxol

Dosage Forms

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

Concentrate, Intravenous:

Generic: 100 mg/16.67 mL (16.7 mL); 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)

Off Label Uses

Anal cancer (advanced)

Data from a multicenter, international, randomized phase 2 study support the use of conventional paclitaxel (in combination with carboplatin) for the treatment of advanced anal cancer in patients who had not received prior therapy for advanced disease [Rao 2020]. Data from a small, retrospective study also support the use of paclitaxel (in combination with carboplatin) for the treatment of advanced anal cancer [Kim 2014].

Bladder cancer, advanced or metastatic

Data from 2 small phase 2 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, advanced

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

Data from 2 phase 3 studies support the use of paclitaxel (in combination with cisplatin) in the treatment of advanced cervical cancer [Monk 2009], [Moore 2004].

Endometrial cancer (advanced or recurrent)

Data from several studies support the use of paclitaxel (in combination with carboplatin) in the treatment of advanced/metastatic or recurrent endometrial cancer [Miller 2012], [Pectasides 2008], [Secord 2007]. Data from a small, randomized, controlled, phase 2 study support the use of paclitaxel (in combination with carboplatin and trastuzumab) for the treatment of advanced (stage III or IV) or recurrent, HER2-positive endometrial (uterine serous) cancer [Fader 2018].

Esophageal cancer (metastatic or unresectable locally advanced)

Data from a small study support the use of paclitaxel (in combination with cisplatin) in the treatment of locally advanced, recurrent, or metastatic esophageal cancer [Petrasch 1998]. Data from a phase 2 study support the use of paclitaxel (in combination with carboplatin) in the treatment of advanced esophageal cancer [El-Rayes 2004]. Data from another study support the use of paclitaxel as a single agent for the treatment of advanced esophageal cancer in patients unable to tolerate combination chemotherapy regimens [Ilson 2007].

Esophageal/esophagogastric cancer, preoperative chemoradiation

Data from a randomized, phase 3 study support the use of paclitaxel (in combination with carboplatin and radiation therapy) in the preoperative management of esophageal and esophagogastric junction cancers [van Hagen 2012]. Data from a phase 2 study also support the use of paclitaxel (in combination with carboplatin and radiation therapy) in the treatment of esophageal cancer [van Meerten 2006].

Gastric cancer (metastatic or unresectable locally advanced)

Data from a large, randomized, phase 3 study support the use of paclitaxel (in combination with ramucirumab) in the treatment of metastatic or unresectable locally advanced gastric or gastroesophageal junction cancer [Wilke 2014]. Data from a small phase 2 study also support the use of paclitaxel (in combination with carboplatin) in patients with locally advanced unresectable or metastatic gastric cancer [Gadgeel 2003]. Data from a phase 3 study support the use of single-agent paclitaxel as second-line treatment of metastatic or recurrent gastric cancer [Hironaka 2013].

Head and neck cancers, advanced

Data from a randomized, phase 3 study support the use of paclitaxel (in combination with cisplatin) in the management of advanced head and neck cancer [Gibson 2005].

Melanoma (advanced or metastatic)

Data from a large phase 3 study support the use of paclitaxel (in combination with carboplatin) for treatment of metastatic melanoma if cytotoxic chemotherapy is indicated [Flaherty 2013]. Data from a retrospective review suggest that paclitaxel (in combination with carboplatin) may be beneficial as a second-line regimen for the treatment of advanced or metastatic melanoma [Rao 2006].

Ovarian cancer, intraperitoneal (off-label route)

Data from a large, randomized, phase 3 study support the use of intraperitoneal paclitaxel in the treatment of newly diagnosed advanced ovarian cancer [Armstrong 2006].

Penile cancer, metastatic

Data from a small, phase 2 study support 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/refractory

Data from 2 small, phase 2 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/unresectable

Data from a small, phase 2 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/refractory

Data from a small, phase 2 study support 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 2 study support 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 2 study support 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, advanced

Data from a small, phase 2 study support the use of paclitaxel (in combination with carboplatin) in the treatment of advanced thymoma/thymic carcinoma [Lemma 2011].

Thyroid cancer (anaplastic)

Based on the American Thyroid Association anaplastic thyroid cancer guidelines, paclitaxel (either as a single agent or in combination with carboplatin) may be effective in the treatment of anaplastic thyroid cancer (either as adjuvant therapy, a radiosensitizing agent, or in the management of advanced or metastatic disease).

Unknown primary adenocarcinoma

Data from a small, phase 2 study support the use of paclitaxel (in combination with carboplatin) in the treatment of unknown primary adenocarcinoma [Briasoulis 2000]. Data from another small, phase 2 study support the use of paclitaxel (in combination with carboplatin and etoposide) for the treatment of unknown primary adenocarcinoma [Greco 2000].

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 or famotidine (IV 30 to 60 minutes prior to the dose) is recommended.

Anal cancer, advanced (off-label use): IV: 80 mg/m2 on days 1, 8, and 15 every 4 weeks (in combination with carboplatin) for 6 cycles or until disease progression or unacceptable toxicity (Rao 2020) or 175 mg/m2 once every 3 weeks (in combination with carboplatin) (Kim 2014).

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).

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.

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).

Endometrial cancer, advanced or recurrent (off-label use): IV: 175 mg/m2 (135 mg/m2 in patients with a history of pelvic/spine irradiation) on day 1 every 3 weeks (in combination with carboplatin) for 7 cycles (Miller 2012) or 175 mg/m2 over 3 hours on day 1 every 3 weeks (in combination with carboplatin) for 6 to 9 cycles or until disease progression or unacceptable toxicity (Pectasides 2008) or 80 mg/m2 over 1 hour on days 1, 8, and 15 every 28 days (in combination with carboplatin) until disease progression or unacceptable toxicity (Secord 2007) or (for HER2-positive uterine serous cancer) 175 mg/m2 over 3 hours on day 1 every 3 weeks (in combination with carboplatin and trastuzumab) for ~6 cycles, followed by trastuzumab maintenance therapy (Fader 2018).

Esophageal cancer, metastatic or unresectable locally advanced (off-label use): IV: 90 mg/m2 over 3 hours on day 1 every 14 days (in combination with cisplatin) until disease progression or unacceptable toxicity (Petrasch 1998) or 200 mg/m2 (cycle 1; escalated to 225 mg/m2 in cycle 2 if acceptable ANC and platelets) over 3 hours on day 1 every 3 weeks (in combination with carboplatin) until best response (El-Rayes 2004) or 80 mg/m2 over 1 hour on days 1, 8, 15, and 22 every 28 days (as a single agent) until disease progression or unacceptable toxicity (Ilson 2007).

Esophageal/esophagogastric cancer, preoperative chemoradiation (off-label use): IV: 50 mg/m2 over 1 hour 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; van Meerten 2006).

Gastric cancer, metastatic or unresectable locally advanced (off-label use): IV: 80 mg/m2 on days 1, 8, and 15 every 28 days (in combination with ramucirumab) until disease progression or unacceptable toxicity (Wilke 2014) or 200 mg/m2 (cycle 1; escalated to 225 mg/m2 in cycle 2 if acceptable ANC and platelets) over 3 hours on day 1 every 3 weeks (in combination with carboplatin); evaluate for response every 2 cycles (Gadgeel 2003) or 80 mg/m2 on days 1, 8, and 15 every 28 days (as a single agent) until disease progression or unacceptable toxicity (Hironaka 2013).

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).

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.

Melanoma, advanced or metastatic (alternative therapy) (off-label use): IV: 225 mg/m2 over 3 hours on day 1 every 3 weeks (in combination with carboplatin) for 4 cycles followed by (if dose not previously reduced) 175 mg/m2 over 3 hours on day 1 every 3 weeks (in combination with carboplatin) for up to 6 additional cycles (Flaherty 2013) or 100 mg/m2 on days 1, 8, and 15 every 4 weeks (in combination with carboplatin) until disease progression or unacceptable toxicity (Rao 2006).

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 [non-squamous non-small cell lung cancer], 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).

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).

Thyroid cancer, anaplastic (off-label use; based on limited data): IV:

Adjuvant or radiosensitizing therapy: 30 to 60 mg/m2 once weekly as a single agent or 50 mg/m2 once weekly (in combination with carboplatin) (ATA [Smallridge 2012]).

Advanced or metastatic disease: 60 to 90 mg/m2 once weekly as a single agent or 135 to 200 mg/m2 once every 3 to 4 weeks as a single agent or 60 to 100 mg/m2 once weekly (in combination with carboplatin) or 135 to 175 mg/m2 once every 3 to 4 weeks (in combination with carboplatin) (ATA [Smallridge 2012]).

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).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

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

American Society of Clinical Oncology 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 (ASCO [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 or famotidine 20 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 (ESMO/EONS [Perez Fidalgo 2012]; Polovich 2009). Clinical experience suggests hyaluronidase may be used in the management of paclitaxel extravasations (ESMO/EONS [Perez Fidalgo 2012]; Stanford 2003); 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; ESMO/EONS [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

5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

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

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 used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Consider therapy modification

Amisulpride (Oral): May enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

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. Management: Consider separating doxorubicin and paclitaxel administration by as much time as possible, using liposomal doxorubicin or epirubicin instead of doxorubicin, or using docetaxel instead of paclitaxel. Monitor closely for cardiovascular and other toxicities. 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

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). Management: Consider avoiding this combination. Some combinations are specifically contraindicated by manufacturers; others may have recommended dose adjustments. If combined, monitor for increased substrate effects. Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to concomitant therapy when possible. If concomitant therapy cannot be avoided, monitor for reduced clinical effects of the CYP3A4 substrate. 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. Management: Consider avoiding Echinacea in patients receiving therapeutic immunosuppressants. If coadministered, monitor for reduced efficacy of the immunosuppressant during concomitant use. 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

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

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

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

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

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering 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. Management: Avoid use of immunosuppressants (including systemic corticosteroids) prior to initiation of nivolumab. Use of immunosuppressants after administration of nivolumab (eg, for immune-related toxicity) is unlikely to affect nivolumab efficacy. 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

Ozanimod: Immunosuppressants may enhance the immunosuppressive effect of Ozanimod. 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

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. Management: Administer paclitaxel before cisplatin, when given as sequential infusions, to limit toxicity. Problems associated with other taxane/platinum combinations are possible, although unsubstantiated. Administering the taxane before platinum is likely warranted 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

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Management: Consider avoiding concomitant use of roflumilast and immunosuppressants as recommended by the Canadian product monograph. Inhaled or short-term corticosteroids are unlikely to be problematic. 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

Talimogene Laherparepvec: Immunosuppressants may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk for disseminated herpetic infection may be increased. 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

Upadacitinib: Immunosuppressants may enhance the immunosuppressive effect of Upadacitinib. Management: Concomitant use of upadacitinib with potent immunosuppressants is not recommended. Avoid combination

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated less than 2 weeks before starting or 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

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>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)

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. 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.

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.

Reproductive Considerations

Females of reproductive potential should be advised to avoid becoming pregnant.

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).

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.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Hair loss

• Feeling tired or weak

• Diarrhea, upset stomach, or throwing up

• Mouth sores

• Muscle or joint pain

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Nerve problems (numbness, tingling, or burning feeling in your hands or feet) that are very bad, cause problems with daily living, or do not go away

• Infection like fever, chills, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or wound that will not heal

• Bleeding like throwing up or coughing up blood; vomit that looks like coffee grounds; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a cause or that get bigger; or bleeding you cannot stop

• High or low blood pressure like very bad headache or dizziness, passing out, or change in eyesight

• Kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain

• Shortness of breath

• Swelling

• Flushing

• Chest pain or pressure

• Fast, slow, or abnormal heartbeat

• Change in eyesight

• Redness, burning, pain, swelling, blisters, skin sores, or leaking of fluid where the drug is going into the body

• Liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, 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 limited summary of general information about the medicine’s uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.