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Paclitaxel

Class: Antineoplastic Agents
- Antimitotic Agents
- Antimicrotubule Agents
VA Class: AN900
Chemical Name: [2aR-[2aα,4β,4aβ,6β,9α(αR*,βS*),11α,1-2α,12aα,12bα]]-β-(Benzoylamino)-α-hydroxybenzenepropanoic acid 6, 12b-bis(acetyloxy)-12-(benzoyloxy)-2a,3,4,4a,5,6,9,10,11,12,12a-,12b-dodecahydro-4, 11-dihydroxy-4a,8,13,13-tetramethyl-5-oxo-7,11-methano-1H-cyclodeca[3,4]benz [1,2-b]oxet -9-yl ester
Molecular Formula: C47H51NO14
CAS Number: 33069-62-4
Brands: Abraxane, Onxol, formerly available as Taxol

Medically reviewed by Drugs.com on Jul 19, 2021. Written by ASHP.

Warning

  • Conventional paclitaxel: Anaphylaxis and severe hypersensitivity reactions (dyspnea and hypotension requiring treatment, angioedema, and/or generalized urticaria) reported. Fatal reactions reported despite premedication. Administer premedication (corticosteroids, diphenhydramine, histamine H2-receptor antagonists) to all patients. Do not administer paclitaxel to patients with a history of severe hypersensitivity reactions to the drug.

  • Paclitaxel should not be administered to patients with solid tumors with baseline ANC <1500/mm3 or to patients with AIDS-related Kaposi’s sarcoma with baseline ANC <1000/mm3. Monitor blood cell counts frequently.

  • Albumin-bound paclitaxel differs from conventional paclitaxel; do not substitute albumin-bound paclitaxel for conventional paclitaxel or vice versa.

  • Administer only under the supervision of qualified clinicians experienced in the use of cytotoxic therapy. Adequate diagnostic and treatment facilities should be readily available to manage complications.

Introduction

Antineoplastic agent; natural or semisynthetic diterpene from the bark of the Western (Pacific) yew (Taxus brevifolia) or needles and twigs of Taxus baccata.

Uses for Paclitaxel

Ovarian Cancer

Conventional paclitaxel: Treatment of advanced carcinoma of the ovary. Used as first-line therapy with carboplatin or cisplatin; this regimen is considered the treatment of choice for primary therapy of advanced ovarian cancer. Used alone or in combination therapy as second-line (salvage) therapy or subsequent therapy in patients with advanced ovarian epithelial cancer.

Combined therapy with IV paclitaxel, intraperitoneal cisplatin, and intraperitoneal paclitaxel: Use is recommended (accepted) for the initial adjuvant treatment of optimally debulked stage III epithelial ovarian cancer in patients with good performance status (Gynecologic Oncology Group [GOG] performance status of 0–2).

Breast Cancer

Conventional paclitaxel: Adjuvant therapy in patients with evidence of axillary node tumor involvement; administered sequentially to standard doxorubicin-containing combination therapy.

Conventional paclitaxel: Treatment of breast cancer in patients who have metastatic disease refractory to combination chemotherapy or who have experienced relapse within 6 months of adjuvant chemotherapy; prior therapy should have included an anthracycline antineoplastic agent (e.g., doxorubicin) unless clinically contraindicated.

Conventional paclitaxel: Treatment of breast cancer in combination with trastuzumab for tumors that overexpress the HER2 protein.

Albumin-bound paclitaxel: Used alone for the treatment of breast cancer in patients who have metastatic disease refractory to conventional combination chemotherapy or who have experienced relapse within 6 months of adjuvant therapy; prior therapy should have included an anthracycline antineoplastic agent (e.g., doxorubicin) unless clinically contraindicated.

Non-small Cell Lung Cancer (NSCLC)

Conventional paclitaxel: First-line treatment of advanced NSCLC in combination with carboplatin or cisplatin in patients for whom potentially curative surgery and/or radiation therapy are not possible.

Albumin-bound paclitaxel: First-line treatment of advanced NSCLC in combination with carboplatin in patients for whom potentially curative surgery or radiation therapy is not possible.

Conventional paclitaxel: Adjuvant therapy in selected patients with completely resected NSCLC; used in conjunction with a platinum agent (e.g., carboplatin).

Small Cell Lung Cancer

Conventional paclitaxel: Active in the treatment of small cell lung carcinoma.

AIDS-related Kaposi’s Sarcoma

Conventional paclitaxel: Second-line therapy for the palliative treatment of advanced or refractory AIDS-related Kaposi’s sarcoma (designated an orphan drug by FDA for this use).

Pancreatic Cancer

Albumin-bound paclitaxel: First-line therapy of metastatic adenocarcinoma of the pancreas in combination with gemcitabine.

Esophageal Cancer

Conventional paclitaxel: Has been used for the treatment of esophageal cancer .

Bladder Cancer

Conventional paclitaxel: Active in the treatment of transitional cell bladder cancer.

Head and Neck Cancer

Conventional paclitaxel: Active in the treatment of advanced (metastatic or locally recurrent) squamous cell carcinoma of the head and neck.

Cervical Cancer

Conventional paclitaxel: Active in the treatment of cervical cancer.

Endometrial Cancer

Conventional paclitaxel: Has been used for the treatment of endometrial cancer.

Paclitaxel Dosage and Administration

General

  • Consult specialized references for procedures for proper handling and disposal of antineoplastic drugs.

  • Conventional paclitaxel: Premedicate all patients before paclitaxel administration, including intraperitoneal administration, to prevent severe hypersensitivity reactions. Oral dexamethasone 20 mg (10 mg for HIV-infected patients) administered approximately 12 and 6 hours before paclitaxel as well as IV diphenhydramine hydrochloride (or similar antihistamine) 50 mg and either IV cimetidine hydrochloride (300 mg of cimetidine) or ranitidine hydrochloride (50 mg of ranitidine) administered 30–60 minutes before paclitaxel can be given.

  • Albumin-bound paclitaxel: Premedication generally not required, but may be necessary in patients who experienced a hypersensitivity reaction during a previous course.

Administration

Administer conventional and albumin-bound paclitaxel by IV infusion. Conventional paclitaxel also administered intraperitoneally.

Handle cautiously (by trained nonpregnant personnel); use protective equipment (e.g., gloves) and wash hands after removal of the gloves.

Immediately treat accidental contact with skin by thoroughly washing with soap and water; immediately treat accidental contact with mucous membranes by thoroughly washing with water. Dyspnea, chest pain, ocular burning, sore throat, and nausea reported upon inhalation.

IV Administration

Conventional Paclitaxel

For solution and drug compatibility information, see Compatibility under Stability.

Administer by IV infusion.

Contact of undiluted paclitaxel for injection concentrate with plasticized polyvinyl chloride (PVC) equipment or devices used to prepare solutions for infusion is not recommended. Diethylhexyl phthalate (DEHP) can be leached from PVC containers.

Diluted paclitaxel solutions preferably should be stored in glass or polypropylene containers or in plastic (polypropylene or polyolefin) bags and administered through polyethylene-lined administration sets.

A hydrophilic, microporous inline filter with a pore size ≤0.22 µm is necessary during administration. Use of filter devices such as IVEX-2 filters, which incorporate short inlet and outlet PVC-coated tubing, has not resulted in significant leaching of DEHP.

Do not use a Chemo Dispensing Pen or similar device; these devices may cause the stopper to collapse and contaminate the solution (resulting in loss of sterility).

Dilution of Conventional Paclitaxel

The concentrate for injection must be diluted prior to administration.

Dilute in 0.9% sodium chloride injection, 5% dextrose injection, 5% dextrose and 0.9% sodium chloride injection, or 5% dextrose in Ringer’s injection to a final paclitaxel concentration of 0.3–1.2 mg/mL.

Rate of Administration of Conventional Paclitaxel

Infuse appropriate dose IV over 3 or 24 hours, depending on the treatment regimen.

Albumin-bound Paclitaxel

Administer by IV infusion; do not use inline filters.

Reconstitution of Albumin-bound Paclitaxel

Add 20 mL of 0.9% sodium chloride injection to a vial containing 100 mg of paclitaxel lyophilized powder; slowly inject the diluent onto the inside wall of the vial. Allow the vial to sit for ≥5 minutes (to ensure wetting of cake/powder); then, gently swirl and/or invert vial for ≥2 minutes. Handle in such a manner to avoid foaming. Resulting preparation contains 5 mg/mL.

Withdraw appropriate dose from vial and transfer to an empty sterile PVC IV bag. DEHP-free containers and administration sets not needed.

Rate of Administration of Albumin-bound Paclitaxel

Infuse appropriate dose IV over 30 minutes. Limiting infusion duration to 30 minutes reduces risk of infusion-related reactions.

Intraperitoneal Instillation

In patients with advanced epithelial ovarian cancer (GOG-172 study), dose was diluted in 1 L of 0.9% sodium chloride solution that was warmed to 37°C and infused through a surgically implanted peritoneal catheter, followed by intraperitoneal infusion of 1 L of warmed saline solution. Following peritoneal infusion, patient was asked to roll into a different position every 15 minutes for the next 2 hours to disperse the drug throughout the peritoneal cavity.

Consult specialized sources for guidance on how to administer intraperitoneal therapy. Further study needed to optimize techniques for intraperitoneal therapy to minimize risk of complications (e.g., infection, catheter obstruction, catheter retraction, bowel perforation, pain, leakage, port access problems).

Dosage

Consult manufacturer's labeling and published protocols for formulation-specific regimens and specific dosages, methods of administration, and administration sequence of other antineoplastic agents used in combination regimens.

Adults

Ovarian Cancer
IV (Conventional Paclitaxel)

Previously untreated patients: 175 mg/m2 given over 3 hours followed by cisplatin 75 mg/m2 in repeated 3-week cycles. Alternatively, 135 mg/m2 given over 24 hours followed by cisplatin 75 mg/m2 in repeated 3-week cycles.

Previously treated patients: 135 mg/m2 or 175 mg/m2 given over 3 hours in repeated 3-week cycles.

Reduce dose by 20% for subsequent cycles in patients who experience severe neutropenia (ANC <500/mm3 for >7 days) or severe peripheral neuropathy.

IV and Intraperitoneal (Conventional Paclitaxel)†

Previously untreated patients with optimally debulked disease: IV paclitaxel 135 mg/m2 by 24-hour infusion on day 1, followed by intraperitoneal cisplatin 100 mg/m2 on day 2 and intraperitoneal paclitaxel 60 mg/m2 on day 8, has been administered every 21 days for up to 6 cycles.

Modified regimens (e.g., with shorter IV infusion times that may permit outpatient administration) are being investigated.

Breast Cancer
IV (Conventional Paclitaxel)

Adjuvant therapy: 175 mg/m2 given over 3 hours in repeated 3-week cycles for 4 cycles administered sequentially to doxorubicin-containing chemotherapy.

Treatment after failure of initial therapy for metastatic disease or relapse within 6 months of adjuvant therapy: 175 mg/m2 given over 3 hours in repeated 3-week cycles.

Reduce dose by 20% for subsequent cycles in patients who experience severe neutropenia (ANC <500/mm3 for >7 days) or severe peripheral neuropathy.

IV (Albumin-bound Paclitaxel)

Treatment after failure of initial therapy for metastatic disease or relapse within 6 months of adjuvant therapy: 260 mg/m2 every 3 weeks.

Reduce dose to 220 mg/m2 for subsequent cycles in patients who experience severe neutropenia (ANC <500/mm3 for >7 days) or severe sensory neuropathy. Reduce dose to 180 mg/m2 if severe neutropenia or severe sensory neuropathy recurs. For grade 3 sensory neuropathy, withhold therapy until resolution to grade 1 or 2; when therapy is resumed, reduce dose.

Non-small Cell Lung Cancer (NSCLC)
IV (Conventional Paclitaxel)

135 mg/m2 given over 24 hours followed by cisplatin 75 mg/m2 in repeated 3-week cycles. Alternatively, 175 mg/m2 given over 3 hours followed by cisplatin 80 mg/m2 in repeated 3-week cycles has been used.

Reduce dose by 20% for subsequent cycles in patients who experience severe neutropenia (ANC <500/mm3 for >7 days) or severe peripheral neuropathy.

IV (Albumin-bound Paclitaxel)

100 mg/m2 given over 30 minutes on days 1, 8, and 15, followed by carboplatin (target AUC 6 mg/mL per minute) on day 1 of each 21-day cycle.

Table 1. Dosage Modification for Toxicity in Patients Receiving Albumin-bound Paclitaxel and Carboplatin for NSCLC354

Toxicity

Episode

Albumin-bound Paclitaxel and Carboplatin Dosage Modification

Febrile neutropenia (ANC <500/mm3 with fever >38°C)

or

delay of next cycle by >7 days for ANC <1500/mm3

or

ANC <500/mm3 for >7 days

First

Withhold both drugs until ANC ≥1500/mm3 and platelets ≥100,000/mm3 on day 1 or ANC ≥500/mm3 and platelets ≥50,000/mm3 on day 8 or 15 of the cycle; upon resumption, permanently reduce albumin-bound paclitaxel dose to 75 mg/m2 and carboplatin target AUC to 4.5 mg/mL per minute

Second

Withhold both drugs until ANC ≥1500/mm3 and platelets ≥100,000/mm3 on day 1 or ANC ≥500/mm3 and platelets ≥50,000/mm3 on day 8 or 15 of the cycle; upon resumption, permanently reduce albumin-bound paclitaxel dose to 50 mg/m2 and carboplatin target AUC to 3 mg/mL per minute

Third

Discontinue both drugs

Thrombocytopenia (platelet count <50,000/mm3)

First

Withhold both drugs until ANC ≥1500/mm3 and platelets ≥100,000/mm3 on day 1 or ANC ≥500/mm3 and platelets ≥50,000/mm3 on day 8 or 15 of the cycle; upon resumption, permanently reduce albumin-bound paclitaxel dose to 75 mg/m2 and carboplatin target AUC to 4.5 mg/mL per minute

Second

Discontinue both drugs

Severe (grade 3 or 4) peripheral neuropathy

First

Withhold both drugs until neuropathy is grade 1 or less; upon resumption, permanently reduce albumin-bound paclitaxel dose to 75 mg/m2 and carboplatin target AUC to 4.5 mg/mL per minute

Second

Withhold both drugs until neuropathy is grade 1 or less; upon resumption, permanently reduce albumin-bound paclitaxel dose to 50 mg/m2 and carboplatin target AUC to 3 mg/mL per minute

Third

Discontinue both drugs

AIDS-related Kaposi’s Sarcoma
IV (Conventional Paclitaxel)

135 mg/m2 given over 3 hours in repeated 3-week cycles. Alternatively, 100 mg/m2 over 3 hours in repeated 2-weeks cycles. The regimen given every 3 weeks is more toxic than the regimen given every 2 weeks; patients with poor performance status have been treated with paclitaxel 100 mg/m2.

Reduce dose by 20% for subsequent cycles in patients who experience severe neutropenia (ANC <500/mm3 for >7 days); initiate granulocyte colony stimulating factor (G-CSF) as indicated.

Pancreatic Cancer
IV (Albumin-bound Paclitaxel)

125 mg/m2 given over 30–40 minutes followed by gemcitabine 1 g/m2 IV over 30–40 minutes on days 1, 8, and 15 of each 28-day cycle.

When dosage modification is necessary, reduce dose of albumin-bound paclitaxel in decrements of 25 mg/m2 (i.e., 1 dose level) and gemcitabine in decrements of 200 mg/m2 (i.e., 1 dose level); however, if a dose of albumin-bound paclitaxel 75 mg/m2 or a dose of gemcitabine 600 mg/m2 requires further reduction, discontinue both drugs.

Table 2. Dosage Modification for Hematologic Toxicity in Patients Receiving Albumin-bound Paclitaxel and Gemcitabine for Pancreatic Cancer354

Cycle Day and Cell Counts (cells/mm3)

Albumin-bound Paclitaxel and Gemcitabine Dosage Modification

Day 1:

ANC <1500 or platelet count <100,000

Delay start of cycle until recovery

Day 8:

ANC 500 to <1000 or platelet count 50,000 to <75,000

Reduce dose of both drugs by 1 dose level

ANC <500 or platelet count <50,000

Withhold day 8 dose of both drugs

Day 15 (when day 8 doses were reduced or given without modification):

ANC 500 to <1000 or platelet count 50,000 to <75,000

Reduce dose of both drugs by 1 dose level from day 8

ANC <500 or platelet count <50,000

Withhold day 15 dose of both drugs

Day 15 (when day 8 doses were withheld):

ANC ≥1000 or platelet count ≥75,000

Reduce dose of both drugs by 1 dose level from day 1

ANC 500 to <1000 or platelet count 50,000 to <75,000

Reduce dose of both drugs by 2 dose levels from day 1

ANC <500 or platelet count <50,000

Withhold day 15 dose of both drugs

Table 3. Dosage Modification for Other Toxicities in Patients Receiving Albumin-bound Paclitaxel and Gemcitabine for Pancreatic Cancer354

Toxicity

Albumin-bound Paclitaxel and Gemcitabine Dosage Modification

Febrile neutropenia (grade 3 or 4)

Withhold both drugs until fever resolves and ANC is ≥1500/mm3; upon resumption, reduce dose of both drugs by 1 dose level

Severe (grade 3 or 4) peripheral neuropathy

Withhold albumin-bound paclitaxel until neuropathy is grade 1 or less; upon resumption, reduce albumin-bound paclitaxel dose by 1 dose level. No gemcitabine dose reduction required

Dermatologic toxicity (grade 2 or 3)

Reduce dose of both drugs by 1 dose level. Discontinue both drugs if toxicity persists

GI toxicity (grade 3 mucositis or diarrhea)

Withhold both drugs until GI toxicity is grade 1 or less; upon resumption, reduce dose of both drugs by 1 dose level

Special Populations

Hepatic Impairment

Increased risk of toxicity, particularly grade 3 or 4 myelosuppression. Adjust dosage as follows and closely monitor patients.

Ovarian Cancer
IV (Conventional Paclitaxel)

See Table 4 for recommended initial doses; base further dose reductions in subsequent courses on individual tolerance. Differences in criteria for bilirubin concentrations between the 3- and 24- hour infusions are due to differences in clinical trial design.

Table 4. Recommended Initial Doses of Conventional Paclitaxel for Ovarian Cancer in Patients with Hepatic Impairment1362

Transaminase Concentration

Bilirubin Concentration

Recommended Initial Dose (for 3- or 24-Hour Infusion)

<2 times ULN

and

≤1.5 mg/dL

135 mg/m2 over 24 hours

2 to <10 times ULN

and

≤1.5 mg/dL

100 mg/m2 over 24 hours

<10 times ULN

and

1.6–7.5 mg/dL

50 mg/m2 over 24 hours

≥10 times ULN

or

>7.5 mg/dL

Not recommended

<10 times ULN

and

≤1.25 times ULN

175 mg/m2 over 3 hours

<10 times ULN

and

1.26–2 times ULN

135 mg/m2 over 3 hours

<10 times ULN

and

2.01–5 times ULN

90 mg/m2 over 3 hours

≥10 times ULN

or

>5 times ULN

Not recommended

Breast Cancer
IV (Conventional Paclitaxel)

See Table 5 for recommended initial doses; base further dose reductions in subsequent courses on individual tolerance.

Table 5. Recommended Initial Doses of Conventional Paclitaxel for Breast Cancer in Patients with Hepatic Impairment1362

Transaminase Concentration

Bilirubin Concentration

Recommended Initial Dose (for 3-Hour Infusion)

<10 times ULN

and

≤1.25 times ULN

175 mg/m2

<10 times ULN

and

1.26–2 times ULN

135 mg/m2

<10 times ULN

and

2.01–5 times ULN

90 mg/m2

≥10 times ULN

or

>5 times ULN

Not recommended

IV (Albumin-bound Paclitaxel)

See Table 6 for recommended initial doses; base further dose reductions in subsequent courses on individual tolerance.

Table 6. Recommended Initial Doses of Albumin-bound Paclitaxel for Breast Cancer in Patients with Hepatic Impairment354

AST Concentration

Bilirubin Concentration

Recommended Initial Dose (for 30-Minute Infusion)

<10 times ULN

and

≤1.25 times ULN

260 mg/m2

<10 times ULN

and

1.26–2 times ULN

200 mg/m2

<10 times ULN

and

2.01–5 times ULN

130 mg/m2; may increase to 200 mg/m2 in subsequent courses based on tolerance

>10 times ULN

or

>5 times ULN

Not recommended

Non-small Cell Lung Cancer (NSCLC)
IV (Conventional Paclitaxel)

See Table 7 for recommended initial doses; base further dose reductions in subsequent courses on individual tolerance.

Table 7. Recommended Initial Doses of Conventional Paclitaxel for NSCLC in Patients with Hepatic Impairment1362

Transaminase Concentration

Bilirubin Concentration

Recommended Initial Dose (for 24-Hour Infusion)

<2 times ULN

and

≤1.5 times ULN

135 mg/m2

2 to <10 times ULN

and

≤1.5 times ULN

100 mg/m2

<10 times ULN

and

1.6–7.5 times ULN

50 mg/m2

≥10 times ULN

or

>7.5 times ULN

Not recommended

IV (Albumin-bound Paclitaxel)

Patients with serum bilirubin concentrations exceeding the ULN were excluded from clinical studies of albumin-bound paclitaxel for NSCLC.

See Table 8 for recommended initial doses; base further dose reductions in subsequent courses on individual tolerance.

Table 8. Recommended Initial Doses of Albumin-bound Paclitaxel for NSCLC in Patients with Hepatic Impairment354

AST Concentration

Bilirubin Concentration

Recommended Initial Dose (for 30-Minute Infusion)

<10 times ULN

and

≤1.25 times ULN

100 mg/m2

<10 times ULN

and

1.26–2 times ULN

75 mg/m2

<10 times ULN

and

2.01–5 times ULN

50 mg/m2

>10 times ULN

or

>5 times ULN

Not recommended

AIDS-related Kaposi’s Sarcoma
IV (Conventional Paclitaxel)

Data not available to make dosage recommendations.

Pancreatic Cancer
IV (Albumin-bound Paclitaxel)

Patients with serum bilirubin concentrations exceeding the ULN were excluded from clinical studies in pancreatic cancer.

If AST <10 times ULN and bilirubin ≤1.25 times ULN, give usual initial dose of 125 mg/m2 over 30–40 minutes. Base further dose reductions in subsequent courses on individual tolerance.

Not recommended if AST >10 times ULN, bilirubin >5 times ULN, or AST <10 times ULN and bilirubin 1.26–5 times ULN.

Renal Impairment

Conventional paclitaxel: Reduction of dosage does not appear to be necessary.

Cautions for Paclitaxel

Contraindications

    Conventional Paclitaxel
  • Known hypersensitivity to paclitaxel, polyoxyl 35 castor oil (Cremophor EL, polyethoxylated castor oil), or any other ingredient in the formulation.

  • Baseline ANC <1500/mm3 in patients with solid tumors.

  • Baseline ANC <1000/mm3 in patients with AIDS-related Kaposi’s sarcoma.

    Albumin-bound Paclitaxel
  • Baseline ANC <1500/mm3.

  • Severe hypersensitivity reaction during a previous course.

Warnings/Precautions

Warnings

Adequate Patient Evaluation and Monitoring

Administer only under the supervision of qualified clinicians experienced in the use of cytotoxic therapy.

Patients must have recovered from acute toxicities (e.g., ANC >1500/mm3 [>1000/mm3 for patients with Kaposi’s sarcoma], platelets >100,000/mm3) of previous cytotoxic therapy before each cycle.

Prior to and during therapy with conventional paclitaxel, assess blood cell counts, serum bilirubin, and AST and/or ALT.

During therapy with albumin-bound paclitaxel, assess blood cell counts frequently, including before each dose.

Hematologic Effects

Dose-dependent and dose-limiting bone marrow suppression (mainly neutropenia). Thrombocytopenia occurs less commonly than neutropenia.

Conventional paclitaxel: Neutrophil nadir at day 10–12, return to baseline by day 15–21. Platelet nadir at day 8–9.

Cardiovascular Effects

Severe conduction abnormalities documented with conventional paclitaxel; pacemaker placement needed in some patients. Institute appropriate therapy if clinically important conduction abnormalities occur; perform continuous cardiac monitoring during subsequent cycles.

Hypotension, bradycardia, and hypertension reported during infusion of conventional paclitaxel; interruption of therapy not needed for mild symptoms. Interruption or discontinuance may be needed because of initial or recurrent hypertension.

Monitor vital signs frequently during conventional paclitaxel administration, especially during the first hour of the infusion. Continuous cardiac monitoring not required except in patients with serious conduction abnormalities.

Hypotension or bradycardia reported during infusion of albumin-bound paclitaxel: specific therapy or interruption of paclitaxel not needed. ECG abnormalities reported.

Fetal/Neonatal Morbidity and Mortality

Embryotoxic and fetotoxic. (See Pregnancy under Cautions.)

Therapy with albumin-bound paclitaxel not advised in men wishing to father a child.

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylaxis and severe reactions, characterized by dyspnea and hypotension requiring treatment, angioedema, and generalized urticaria, reported during infusion of conventional paclitaxel. Fatal reactions reported in patients who received premedication.

Anaphylaxis and severe reactions, including fatal cases, also reported during infusion of albumin-bound paclitaxel.

Premedicate patients with corticosteroids, diphenhydramine, and histamine H2-receptor antagonists to reduce the severity of hypersensitivity reactions during infusion of conventional paclitaxel. (See General under Dosage and Administration.)

Interruption of therapy with conventional paclitaxel generally is not needed for mild reactions (e.g., flushing, localized skin reactions, hypotension, tachycardia). Discontinue immediately and treat if severe reaction occurs (hypotension requiring treatment, dyspnea requiring bronchodilators, angioedema, generalized urticaria).

Do not administer conventional or albumin-bound paclitaxel to any patient who experienced a severe hypersensitivity reaction during a previous course. Not known whether patients who exhibit hypersensitivity to conventional paclitaxel can subsequently tolerate albumin-bound paclitaxel.

Sulfite Sensitivity

Some formulations of conventional paclitaxel contain sulfites, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.

Major Toxicities

Nervous System Effects

Neuropathy (sensory, peripheral) occurs frequently with conventional or albumin-bound paclitaxel; severe symptoms are unusual. Neuropathy is dose and schedule dependent. Reduce dose for severe symptoms.

Infectious Complications

Infectious episodes (e.g., sepsis, pneumonia, peritonitis, urinary and respiratory tract infections) reported with conventional paclitaxel; fatal infections reported rarely.

Opportunistic infection reported frequently in patients with AIDS-related Kaposi's sarcoma receiving conventional paclitaxel. Febrile neutropenia reported more frequently with conventional paclitaxel 135 mg/m2 compared with 100 mg/m2.

Infectious episodes (e.g., oral candidiasis, respiratory and urinary tract infections, pneumonia) reported with albumin-bound paclitaxel.

Sepsis (irrespective of ANC) reported in patients with pancreatic cancer receiving albumin-bound paclitaxel and gemcitabine; risk factors for severe or fatal sepsis include biliary obstruction or presence of biliary stent. Initiate broad-spectrum anti-infectives if fever develops (regardless of ANC).

Injection Site Reaction

Injection site reactions to conventional paclitaxel, including reactions secondary to extravasation, are mild and characterized by erythema, tenderness, skin discoloration, or swelling at the injection site. Reactions more frequent with the 24-hour infusion than the 3-hour infusion. Recurrence of skin reactions at a previous site of extravasation (i.e., “recall” reactions) following administration at a different injection site reported rarely.

Severe events (phlebitis, cellulitis, induration, skin exfoliation, necrosis, fibrosis) reported rarely with conventional paclitaxel.

Injection site reaction to conventional paclitaxel usually occurs during prolonged infusion; delayed onset of reaction, 3–13 days after infusion, also reported.

Specific treatment for extravasation reactions to conventional paclitaxel unknown. Monitor the infusion site for possible infiltration during administration.

Mild injection site reactions to albumin-bound paclitaxel reported infrequently. Monitor the infusion site for possible infiltration during administration.

Respiratory Effects

Pneumonitis, sometimes fatal, reported infrequently with albumin-bound paclitaxel and gemcitabine. Monitor for pneumonitis. If signs and symptoms develop, interrupt therapy during evaluation; permanently discontinue therapy in patients diagnosed with pneumonitis.

Interstitial pneumonia, lung fibrosis, radiation pneumonitis, pneumothorax, and pulmonary embolism also reported with conventional or albumin-bound paclitaxel.

General Precautions

Prescribing and Dispensing Precautions

Ensure accuracy of prescription; similarity of spelling of Taxol (paclitaxel) and Taxotere (docetaxel) may result in errors.

Risk of Transmissible Agents in Plasma-derived Preparations

Albumin-bound paclitaxel: Potential vehicle for transmission of viruses or other infectious agents. Despite screening for certain viruses, remote risk for transmission of viral infections. Theoretical risk for transmission of Creutzfeldt-Jacob disease.

Specific Populations

Pregnancy

Category D.

Lactation

Distributed into milk in rats; not known whether distributed into human milk. Discontinue nursing or the drug because of the potential risk to nursing infant.

Pediatric Use

Safety and efficacy not established.

CNS toxicity, rarely fatal, reported in pediatric patients receiving high doses of conventional paclitaxel (350–420 mg/m2) by 3-hour IV infusion. Paclitaxel injection contains dehydrated alcohol; toxicity may have resulted from administration of large amounts of alcohol over a short period of time. The use of concomitant antihistamine may intensify the toxic effect of the alcohol. The possibility of a direct toxic effect of paclitaxel itself cannot be ruled out.

Geriatric Use

Conventional paclitaxel: No substantial differences in efficacy relative to younger adults. Severe myelosuppression and severe neuropathy reported more frequently in geriatric individuals than in younger adults. Increased incidence of cardiovascular events noted in geriatric patients receiving conventional paclitaxel for NSCLC.

Albumin-bound paclitaxel for metastatic breast cancer: No difference in toxicity relative to younger adults observed in clinical studies.

Albumin-bound paclitaxel and carboplatin for NSCLC: No overall differences in efficacy relative to younger adults, but toxicity (myelosuppression, peripheral neuropathy, arthralgia) more common in patients ≥65 years of age.

Albumin-bound paclitaxel and gemcitabine for pancreatic cancer: No overall differences in efficacy relative to younger adults, but toxicity (diarrhea, decreased appetite, dehydration, epistaxis) more common in patients ≥65 years of age.

Hepatic Impairment

Conventional paclitaxel: Myelotoxicity may be exacerbated in patients with total bilirubin >2 times ULN. Use with extreme caution in these patients; dosage adjustment recommended. (See Hepatic Impairment under Dosage and Administration.)

Albumin-bound paclitaxel: Toxicity may be exacerbated. Use with caution; adjust dosage in patients with moderate or severe impairment. Patients with baseline serum bilirubin exceeding the ULN were excluded from clinical trials for NSCLC and pancreatic cancer. (See Hepatic Impairment under Dosage and Administration.)

Renal Impairment

Albumin-bound paclitaxel: Not systematically evaluated in patients with renal impairment.

Common Adverse Effects

Conventional paclitaxel: Alopecia, myelosuppression (neutropenia, leukopenia, anemia, thrombocytopenia), neuropathy (peripheral, sensory), myalgia/arthralgia, nausea and vomiting, diarrhea, mucositis, infection, hypersensitivity reaction, abnormal ECG, elevated alkaline phosphatase concentrations, elevated Scr.

Albumin-bound paclitaxel: Alopecia, myelosuppression (neutropenia, thrombocytopenia, anemia), neuropathy (peripheral, sensory), myalgia/arthralgia, nausea, diarrhea, mucositis, fatigue/asthenia, infection, peripheral edema, abnormal ECG, elevated AST and alkaline phosphatase concentrations, elevated Scr, pyrexia, decreased appetite, rash, dehydration.

Interactions for Paclitaxel

Metabolized by CYP2C8 and CYP3A4.

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interactions possible with drugs that are inhibitors, inducers, or substrates of CYP2C8 or CYP3A4 with possible alteration in metabolism of paclitaxel and/or other drug. Use concomitantly with caution.

Specific Drugs

Drug

Interaction

Comments

Anticonvulsants (phenobarbital, phenytoin)

Decreased paclitaxel concentrations

Carboplatin

Administration of conventional paclitaxel followed by carboplatin associated with less severe thrombocytopenia compared with carboplatin alone; no pharmacokinetic interaction

Administration of albumin-bound paclitaxel followed by carboplatin associated with no clinically important changes in paclitaxel exposure; carboplatin AUC 23% higher than targeted value, but half-life and clearance consistent with carboplatin alone

Cisplatin

Sequence-dependent interaction; increased severity of myelosuppression when conventional paclitaxel administered following cisplatin compared with the alternative sequence

Paclitaxel clearance reduced by 25–33% when conventional paclitaxel administered following cisplatin

CNS depressants

Potentiation of CNS depression due to alcohol in the conventional paclitaxel formulation

Use concomitantly with caution

Cyclophosphamide

Sequence-dependent interaction; increased severity of neutropenia and thrombocytopenia when conventional paclitaxel (24-hour infusion) administered before cyclophosphamide

Cyclosporine

Paclitaxel metabolism inhibited in vitro at concentrations greater than usual therapeutic concentrations

Dexamethasone

Paclitaxel metabolism inhibited in vitro at concentrations greater than usual therapeutic concentrations

Did not displace paclitaxel from plasma proteins in vitro

Diazepam

Paclitaxel metabolism inhibited in vitro at concentrations greater than usual therapeutic concentrations

Diphenhydramine

Did not displace paclitaxel from plasma proteins in vitro

Doxorubicin

Conventional paclitaxel: Increased plasma concentrations of doxorubicin and its active metabolite

In vitro synergistic cytotoxic effects

17α-Ethinyl estradiol

Paclitaxel metabolism inhibited in vitro

Etoposide

Paclitaxel metabolism inhibited in vitro at concentrations greater than usual therapeutic concentrations

Histamine H2-receptor antagonists

Cimetidine, famotidine: Pharmacokinetic interaction unlikely

Cimetidine, ranitidine: Did not displace paclitaxel from plasma proteins in vitro

HIV protease inhibitors

Possible interaction

Ketoconazole

Paclitaxel metabolism inhibited in vitro at concentrations greater than usual therapeutic concentrations

Quinidine

Paclitaxel metabolism inhibited in vitro at concentrations greater than usual therapeutic concentrations

Teniposide

Paclitaxel metabolism inhibited in vitro at concentrations greater than usual therapeutic concentrations

Testosterone

Paclitaxel metabolism inhibited in vitro

Verapamil

Paclitaxel metabolism inhibited in vitro at concentrations greater than usual therapeutic concentrations

Vincristine

Paclitaxel metabolism inhibited in vitro at concentrations greater than usual therapeutic concentrations

Paclitaxel Pharmacokinetics

Absorption

Conventional paclitaxel: Exhibits nonlinear pharmacokinetic behavior when administered over short periods (i.e., 3 hours).

Albumin-bound paclitaxel: Increase in AUC proportional to increase in dose for doses of 80–375 mg/m2. Duration of infusion does not affect pharmacokinetics.

Special Populations

Conventional paclitaxel: Plasma paclitaxel exposure increased with abnormal serum bilirubin concentrations ≤2 times ULN.

Albumin-bound paclitaxel: Plasma paclitaxel exposure following 260- or 200-mg/m2 dose in patients with mild or moderate hepatic impairment, respectively, was similar to exposure observed in patients with normal hepatic function.

Distribution

Extent

Widely distributed.

Conventional paclitaxel is detected in ascitic fluid; does not penetrate the CNS.

Not known whether paclitaxel is distributed into human milk.

Following administration of albumin-bound paclitaxel, concentration of drug in tumor cells is increased compared with concentration achieved following an equivalent dose of conventional paclitaxel.

Plasma Protein Binding

88–98%.

Elimination

Metabolism

Metabolized by CYP2C8 and, to a lesser extent, by CYP3A4.

Elimination Route

Excreted principally in feces as metabolites and unchanged drug.

Minimal urinary excretion.

Half-life

Conventional paclitaxel: Average elimination half-life: 5.8 hours for 6- to 24-hour infusions, 2.33 hours for 3-hour infusions.

Albumin-bound paclitaxel: 27 hours.

Stability

Storage

Parenteral

For Injection Concentrate (Conventional Paclitaxel)

20–25°C in the original package to protect from light.

No adverse effect on drug from freezing or refrigeration. Drug or vehicle that precipitates during refrigeration or freezing will redissolve at room temperature without potency loss.

Solutions for infusion are stable at ambient temperature (approximately 25°C) and lighting conditions for up to 27 hours.

Suspension for Injection (Albumin-bound Paclitaxel)

20–25°C in the original package to protect from bright light.

Use reconstituted suspension immediately; alternatively, store vial in the original package for up to 8 hours at 2–8°C. No adverse effect on drug from freezing or refrigeration.

Discard reconstituted suspension if precipitation occurs.

Reconstituted suspension for infusion is stable in the IV infusion bag at ambient temperature (approximately 25°C) and lighting conditions for up to 4 hours.

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility (Conventional Paclitaxel)HID

Compatible

Sodium chloride 0.9%

Variable

Dextrose 5% in water; white precipitate noted occasionally distal to pump chamber

Drug Compatibility (Conventional Paclitaxel)
Admixture CompatibilityHID

Compatible

Carboplatin

Doxorubicin HCl

Variable

Cisplatin

Y-site CompatibilityHID

Compatible

Acyclovir sodium

Amikacin sulfate

Aminophylline

Ampicillin sodium–sulbactam sodium

Anidulafungin

Bleomycin sulfate

Butorphanol tartrate

Calcium chloride

Carboplatin

Cefotetan disodium

Ceftazidime

Ceftriaxone sodium

Cisplatin

Cladribine

Cyclophosphamide

Cytarabine

Dacarbazine

Dexamethasone sodium phosphate

Diphenhydramine HCl

Doripenem

Doxorubicin HCl

Droperidol

Etoposide

Etoposide phosphate

Famotidine

Floxuridine

Fluconazole

Fluorouracil

Furosemide

Ganciclovir sodium

Gemcitabine HCl

Gentamicin sulfate

Granisetron HCl

Haloperidol lactate

Heparin sodium

Hydrocortisone sodium succinate

Hydromorphone HCl

Ifosfamide

Linezolid

Lorazepam

Magnesium sulfate

Mannitol

Meperidine HCl

Mesna

Methotrexate sodium

Metoclopramide HCl

Morphine sulfate

Nalbuphine HCl

Ondansetron HCl

Ondansetron HCl with ranitidine HCl

Oxaliplatin

Palonosetron HCl

Pemetrexed disodium

Pentostatin

Potassium chloride

Prochlorperazine edisylate

Propofol

Ranitidine HCl

Sodium bicarbonate

Thiotepa

Topotecan HCl

Vancomycin HCl

Vinblastine sulfate

Vincristine sulfate

Zidovudine

Incompatible

Amphotericin B

Amphotericin B cholesteryl sulfate complex

Chlorpromazine HCl

Doxorubicin HCl liposome injection

Hydroxyzine HCl

Methylprednisolone sodium succinate

Mitoxantrone HCl

Actions

  • A natural or semisynthetic diterpene extracted from the bark of the Western (Pacific) yew (Taxus brevifolia) or produced from the needles and twigs of a more prevalent yew (Taxus baccata). Structurally and pharmacologically similar to docetaxel.

  • Disrupts the microtubular network in cells that is essential for mitotic and interphase cellular function.

Advice to Patients

  • Importance of recognizing and reporting adverse effects including myelosuppressive effects and infectious complications.

  • Importance of reporting adverse effects including persistent vomiting, diarrhea, or signs of dehydration.

  • Advise patient about sensory neuropathy. Importance of reporting numbness, tingling, pain, or weakness involving the extremities.

  • Importance of reading the patient information leaflet.

  • Advise patient about probable alopecia, fatigue/asthenia, and myalgia/arthralgia.

  • Advise patient about risk of severe or fatal hypersensitivity reaction.

  • Advise patient about risk of pneumonitis. Importance of reporting sudden onset of dry persistent cough or shortness of breath.

  • Potential for alcohol in conventional paclitaxel to impair mental alertness or physical coordination; avoid driving or operating machinery until effects on individual known.

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed; necessity for clinicians to advise women to avoid pregnancy during therapy. Importance of advising men to avoid fathering a child during therapy. (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

  • Importance of patients informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

PACLitaxel

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, concentrate, for IV infusion

6 mg/mL*

Onxol

Teva

Paclitaxel Injection

PACLitaxel (albumin-bound)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injectable suspension, for IV infusion

100 mg (of paclitaxel)

Abraxane

Celgene

AHFS DI Essentials™. © Copyright 2021, Selected Revisions July 27, 2015. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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