paclitaxel

PAK-li-tax-el

Therapeutic Classification: antineoplastics

Pharmacologic Classification: taxoids

High Alert

Paclitaxel

Advanced ovarian cancer (in combination with cisplatin).
Non-small cell lung cancer (NSCLC) when potentially curative surgery and/or radiation therapy is not an option.
Metastatic breast cancer unresponsive to other therapy.
Node-positive breast cancer when administered sequentially to standard combination chemotherapy that includes doxorubicin.
Treatment of AIDS-related Kaposi sarcoma.

Paclitaxel (albumin-bound)

Metastatic breast cancer after treatment failure or relapse where therapy included an anthracycline.
Locally advanced or metastatic NSCLC when potentially curative surgery or radiation therapy is not an option (in combination with carboplatin).
Metastatic pancreatic adenocarcinoma (in combination with gemcitabine).

Interferes with the normal cellular microtubule function that is required for interphase and mitosis.

Therapeutic effects:

Death of rapidly replicating cells, particularly malignant ones.

Absorption: IV administration results in complete bioavailability.

Distribution: Widely distributed to tissues.

Protein Binding: 89–98%.

Metabolism/Excretion: Highly metabolized by the liver primarily by the CYP2C8 and CYP3A4 isoenzymes; <10% excreted unchanged in urine.

Half-Life: Paclitaxel: 13–52 hr; Paclitaxel protein-bound particles (albumin-bound): 27 hr.

(effect on WBCs)

ROUTE	ONSET	PEAK	DURATION
IV	unknown	11 days	3 wk

Contraindicated in:

Hypersensitivity to paclitaxel, other taxanes, or castor oil (paclitaxel);
Severe hypersensitivity to paclitaxel protein-bound particles (paclitaxel protein-bound particles);
AST >10 times upper limit of normal (ULN) or total bilirubin >5 times ULN (paclitaxel protein-bound particles);
Moderate or severe hepatic impairment (pancreatic adenocarcinoma only for paclitaxel protein-bound particles);
Known alcohol intolerance;
Neutrophil count ≤1500 cells/mm³ (for patients with ovarian, lung, breast, or pancreatic cancer) or ≤1000 cells/mm³ (for patients with AIDS-related Kaposi sarcoma);
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Moderate or severe hepatic impairment (↓ dose);
Active infection;
↓bone marrow reserve;
Rep: Women of reproductive potential and men with female partners of reproductive potential;
Pedi: Safety and effectiveness not established in children;
Geri: Older adults may have ↑ risk of adverse reactions.

CV: ECG changes, edema, hypotension, bradycardia

Derm: alopecia, STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS (TEN)

GI: ↑liver enzymes, diarrhea, mucositis, nausea, vomiting, pancreatitis

GU: renal failure

Hemat: anemia, neutropenia, thrombocytopenia

Local: injection site reactions

MS: arthralgia, myalgia

Neuro: peripheral neuropathy, dizziness, headache, seizures

Resp: cough, dyspnea, interstitial pneumonia, PULMONARY EMBOLISM, PULMONARY FIBROSIS

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS), SEPSIS

Drug-drug:

CYP3A4 inhibitors, including atazanavir, clarithromycin, itraconazole, ketoconazole, nefazodone, nelfinavir, and ritonavir, may ↑ levels and risk of toxicity; concurrent use should be undertaken with caution.
CYP3A4 inducers, including carbamazepine, rifampin, and phenytoin, may ↓ levels and effectiveness; concurrent use should be undertaken with caution.
Gemfibrozil may ↑ levels and risk of toxicity; concurrent use should be undertaken with caution.
↑risk of myelosuppression with other antineoplastics or radiation therapy.
Myelosuppression ↑ when given after cisplatin.
May ↑ levels and risk of toxicity of doxorubicin.
May ↓ antibody response to and ↑ risk of adverse reactions from live-virus vaccines.

Paclitaxel

Ovarian Cancer
IV (Adults ): Previously untreated patients: 175 mg/m² over 3 hr every 3 wk or 135 mg/m² over 24 hr every 3 wk, followed by cisplatin; Previously treated patients: 135 mg/m² or 175 mg/m² over 3 hr every 3 wk.

Hepatic Impairment

IV (Adults 24-hr infusion): Transaminase levels <2 times ULN and bilirubin levels ≤1.5 mg/dL: 135 mg/m² over 24 hr. Transaminase levels 2–<10 times ULN and bilirubin levels ≤1.5 mg/dL: 100 mg/m² over 24 hr. Transaminase levels <10 times ULN and bilirubin levels 1.6–7.5 mg/dL: 50 mg/m² over 24 hr. Transaminase levels ≥10 times ULN or bilirubin levels >7.5 mg/dL: Avoid use.

Hepatic Impairment

IV (Adults 3-hr infusion): Transaminase levels <10 times ULN and bilirubin levels ≤1.25 times ULN: 175 mg/m² over 3 hr. Transaminase levels <10 times ULN and bilirubin levels 1.26–2 times ULN: 135 mg/m² over 3 hr. Transaminase levels <10 times ULN and bilirubin levels 2.01–5 times ULN: 90 mg/m² over 3 hr. Transaminase levels ≥10 times ULN or bilirubin levels >5 times ULN: Avoid use.
Breast Cancer
IV (Adults ): Adjuvant treatment of node-positive breast cancer: 175 mg/m² over 3 hr every 3 wk for 4 courses administered sequentially to doxorubicin-containing combination chemotherapy; Failure of initial therapy for metastatic disease or relapse within 6 mo of adjuvant therapy: 175 mg/m² over 3 hr every 3 wk.

Hepatic Impairment

IV (Adults 3-hr infusion): Transaminase levels <10 times ULN and bilirubin levels ≤1.25 times ULN: 175 mg/m² over 3 hr. Transaminase levels <10 times ULN and bilirubin levels 1.26–2 times ULN: 135 mg/m² over 3 hr. Transaminase levels <10 times ULN and bilirubin levels 2.01–5 times ULN: 90 mg/m² over 3 hr. Transaminase levels ≥10 times ULN or bilirubin levels >5 times ULN: Avoid use.
Non-Small Cell Lung Cancer
IV (Adults ): 135 mg/m² over 24 hr every 3 wk, followed by cisplatin.

Hepatic Impairment

IV (Adults 24-hr infusion): Transaminase levels <2 times ULN and bilirubin levels ≤1.5 mg/dL: 135 mg/m² over 24 hr. Transaminase levels 2–<10 times ULN and bilirubin levels ≤1.5 mg/dL: 100 mg/m² over 24 hr. Transaminase levels <10 times ULN and bilirubin levels 1.6–7.5 mg/dL: 50 mg/m² over 24 hr. Transaminase levels ≥10 times ULN or bilirubin levels >7.5 mg/dL: Avoid use.
AIDS-Related Kaposi Sarcoma
IV (Adults ): 135 mg/m² over 3 hr every 3 wk or 100 mg/m² over 3 hr every 2 wk (dose ↓/adjustment may be necessary in patients with advanced HIV infection).

Hepatic Impairment

IV (Adults 3-hr infusion): Transaminase levels <10 times ULN and bilirubin levels ≤1.25 times ULN: 175 mg/m² over 3 hr. Transaminase levels <10 times ULN and bilirubin levels 1.26–2 times ULN: 135 mg/m² over 3 hr. Transaminase levels <10 times ULN and bilirubin levels 2.01–5 times ULN: 90 mg/m² over 3 hr. Transaminase levels ≥10 times ULN or bilirubin levels >5 times ULN: Avoid use.

Paclitaxel Protein-Bound Particles (Albumin-Bound)

Breast Cancer
IV (Adults ): 260 mg/m² over 30 min every 3 wk.

Hepatic Impairment

IV (Adults ): AST levels <10 times ULN and bilirubin levels 1.51–3 times ULN: 200 mg/m² over 30 min every 3 wk; may ↑ to 260 mg/m² for the 3rd course based on individual tolerance; AST levels <10 times ULN and bilirubin levels 3.01–5 times ULN: 200 mg/m² over 30 min every 3 wk; may ↑ to 260 mg/m² for the 3rd course based on individual tolerance; AST levels >10 times ULN or bilirubin levels >5 times ULN: Avoid use.
Non-Small Cell Lung Cancer
IV (Adults ): 100 mg/m² over 30 min on Days 1, 8, and 15 of each 21-day cycle.

Hepatic Impairment

IV (Adults ): AST levels <10 times ULN and bilirubin levels 1.51–3 times ULN): 80 mg/m² over 30 min on Days 1, 8, and 15 of each 21-day cycle; may ↑ to 100 mg/m² for the 3rd course based on individual tolerance; AST levels <10 times ULN and bilirubin levels 3.01–5 times ULN: 80 mg/m² over 30 min on Days 1, 8, and 15 of each 21-day cycle; may ↑ to 100 mg/m² for the 3rd course based on individual tolerance; AST levels >10 times ULN or bilirubin levels >5 times ULN): Avoid use.
Pancreatic Adenocarcinoma
IV (Adults ): 125 mg/m² over 30–40 min on Days 1, 8, and 15 of each 28-day cycle.

Hepatic Impairment

IV (Adults ): Moderate or severe hepatic impairment: Avoid use.

Paclitaxel

(Generic available)

Solution for injection: 6 mg/mL

Paclitaxel Protein-Bound Particles (Albumin-Bound)

Lyophilized powder for injection: 100 mg/vial

Monitor vital signs frequently, especially during 1st hr of the infusion.
Monitor cardiovascular status especially during 1st 3 hr of infusion. Hypotension and bradycardia are common but usually do not require treatment. Continuous ECG monitoring is recommended only for patients with serious underlying conduction abnormalities or those concurrently taking doxorubicin.
Monitor for bone marrow suppression. Assess for bleeding (bleeding gums; bruising; petechiae; guaiac stools, urine, or emesis) and avoid IM injections and taking rectal temperatures if platelet count is low. Apply pressure to venipuncture sites for 10 min. Assess for signs of infection during neutropenia. Anemia may occur. Monitor for dyspnea and orthostatic hypotension. Granulocyte-colony stimulating factor (G-CSF) may be used if necessary.
Monitor intake and output, appetite, and nutritional intake. Paclitaxel causes nausea and vomiting in 50% of patients. Prophylactic antiemetics may be used. Adjust diet as tolerated to help maintain fluid and electrolyte balance and nutritional status.
Assess for arthralgia and myalgia, which usually begin 2–3 days after therapy and resolve within 5 days. Pain is usually relieved by nonopioid analgesics but may be severe enough to require treatment with opioid analgesics.
Assess for rash periodically during therapy. May cause SJS and TEN. If rash severe or if accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis, and/or eosinophilia, discontinue paclitaxel.
Paclitaxel: Monitor for hypersensitivity reactions continuously during the 1st 30 min and frequently thereafter. These occur frequently (19%), usually during the 1st 10 min of paclitaxel infusion, after the 1st or 2nd dose. Most common manifestations are dyspnea, flushing, tachycardia, rash, hypotension, and chest pain. If these occur, stop infusion and notify health care provider. Treatment may include bronchodilators, epinephrine, antihistamines, and corticosteroids. Keep these agents and resuscitative equipment close by in the event of an anaphylactic reaction. Other manifestations of hypersensitivity reactions include flushing and rash. Patients experiencing hypersensitivity reactions should not be rechallenged with paclitaxel.
Assess for development of peripheral neuropathy. If severe symptoms occur, subsequent dose should be ↓ by 20%.
Paclitaxel Protein-Bound (Albumin-Bound): Do not rechallenge patients who experience a severe hypersensitivity reaction.
Sensory neuropathy is dose- and schedule-dependent. If Grade ≥3 sensory neuropathy, hold paclitaxel protein-bound (albumin-bound) until resolution to Grade <2 for metastatic breast cancer or until resolution to Grade ≤1 for NSCLC and pancreatic cancer followed by a dose ↓ for all subsequent courses of therapy.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.
Paclitaxel: Monitor CBC and differential before and periodically during therapy. The nadir of leukopenia occurs in 11 days, with recovery by days 15–21. If neutrophil counts <500/mm³ for ≥1 wk,↓ dose by 20% for subsequent courses.
- Paclitaxel Protein-Bound Particles (Albumin-Bound)Monitor CBC and differential frequently, including before starting therapy and prior to dosing on Day 1 (for breast cancer), 8, and 15 (for NSCLC and pancreatic cancer). For Breast Cancer: If severe neutropenia (ANC <500 cells/mm³ for ≥7 days),↓ dose to 220 mg/m². If recurrence of severe neutropenia,↓ dose to 180 mg/m². For NSCLC: If neutropenic fever (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,↓ dose on 1st occurrence to 75 mg/m² and on 2nd occurrence, ↓ dose to 50 mg/m². For 3rd occurrence, discontinue therapy. If severe neutropenia (ANC <500 cells/mm³ for ≥7 days),↓ dose in subsequent courses. If platelet count <50,000/mm³, for 1st occurrence, ↓ dose to 75 mg/m². Discontinue therapy at 2nd occurrence. For Pancreatic Cancer: On Day 1, if ANC <1500 cells/mm³ OR platelet count <100,000 cells/mm³, hold next dose until recovery. On Day 8, if ANC 500–<1000 cells/mm³ OR platelet count 50,000–<75,000 cells/mm³,↓ dose one level; on Day 8, if ANC <500 cells/mm³ OR <50,000 cells/mm³, hold dose. On Day 15, if Day 8 doses were ↓ or given without modification and ANC 500–<1000 cells/mm³ OR platelet count 50,000–<75,000 cells/mm³,↓ dose one level from Day 8. On Day 15, if Day 8 doses were ↓ or given without modification and ANC <500 cells/mm³ OR platelet count <50,000 cells/mm³, hold doses. On Day 15, if Day 8 doses were held and ANC ≥1000 cells/mm³ OR platelet count ≥75,000 cells/mm³,↓ dose one level from Day 1. On Day 15, if Day 8 doses were held and ANC 500–<1000 cells/mm³ OR platelet count 50,000–<75,000 cells/mm³,↓ dose two levels from Day 1. On Day 15, if Day 8 doses were held and ANC <500 cells/mm³ OR platelet count <50,000 cells/mm³, hold doses.
- Monitor AST, ALT, LDH, and bilirubin before and periodically during therapy.

Do not confuse paclitaxel with docetaxel or paclitaxel protein-bound particles.
Paclitaxel should be administered under the supervision of a physician experienced in the use of cancer chemotherapeutic agents.

Consider premedication in patients who have had prior hypersensitivity reactions to paclitaxel protein-bound (albumin-bound).
Dose Reduction for Pancreatic Cancer: Full dose: 125 mm/m². 1st dose ↓: 100 mm/m². 2nd dose ↓: 75 mm/m². If additional dose ↓ required, discontinue therapy.

Paclitaxel

IV Administration:

Pretreatment is recommended for all patients and should include dexamethasone 20 mg PO (10 mg for patients with advanced HIV disease) 12 hr and 6 hr before paclitaxel, diphenhydramine 50 mg IV 30–60 min before paclitaxel, and famotidine 20 mg IV 30–60 min before paclitaxel.
Paclitaxel is a vesicant. If extravasation occurs, immediately stop infusion. Leave needle/cannula in place temporarily but do not flush the line. Gently aspirate extravasated solution; then remove needle/cannula. Elevate patient's extremity and apply dry cold compresses for 20 min 4 times day for 1–2 days. Initiate hyaluronidase antidote for refractory cases in addition to supportive management. For hyaluronidase, inject 1–6 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 SUBQ in a clockwise manner around area of extravasation; may repeat several times over the next 3–4 hr.
Y-Site Compatibility:
- acyclovir
- alemtuzumab
- allopurinol
- amikacin
- aminophylline
- ampicillin
- ampicillin/sulbactam
- anidulafungin
- argatroban
- atracurium
- azithromycin
- aztreonam
- bivalirudin
- bleomycin
- bumetanide
- buprenorphine
- busulfan
- butorphanol
- calcium chloride
- calcium gluconate
- carboplatin
- carmustine
- caspofungin
- cefazolin
- cefepime
- cefotaxime
- cefotetan
- cefoxitin
- ceftazidime
- ceftriaxone
- cefuroxime
- chloramphenicol
- ciprofloxacin
- cisatracurium
- cisplatin
- cladribine
- clindamycin
- cyclophosphamide
- cyclosporine
- cytarabine
- dacarbazine
- dactinomycin
- dantrolene
- daptomycin
- daunorubicin
- dexamethasone
- dexmedetomidine
- dexrazoxane
- diltiazem
- diphenhydramine
- dobutamine
- dopamine
- doxorubicin hydrochloride
- doxycycline
- droperidol
- enalaprilat
- ephedrine
- epinephrine
- epirubicin
- ertapenem
- erythromycin
- esmolol
- etoposide
- etoposide phosphate
- famotidine
- fentanyl
- floxuridine
- fluconazole
- fludarabine
- fluorouracil
- foscarnet
- fosphenytoin
- furosemide
- ganciclovir
- gemcitabine
- gentamicin
- glycopyrrolate
- granisetron
- haloperidol
- heparin
- hydralazine
- hydrocortisone
- hydromorphone
- ifosfamide
- imipenem/cilastatin
- insulin regular
- irinotecan
- isoproterenol
- ketorolac
- leucovorin
- levofloxacin
- lidocaine
- linezolid
- lorazepam
- magnesium sulfate
- mannitol
- meperidine
- meropenem
- mesna
- methadone
- methotrexate
- metoclopramide
- metoprolol
- metronidazole
- midazolam
- milrinone
- minocycline
- mitomycin
- morphine
- moxifloxacin
- nafcillin
- nalbuphine
- naloxone
- nicardipine
- nitroglycerin
- nitroprusside
- norepinephrine
- octreotide
- ondansetron
- oxaliplatin
- palonosetron
- pamidronate
- pantoprazole
- pemetrexed
- pentamidine
- pentobarbital
- pentostatin
- phenobarbital
- phentolamine
- phenylephrine
- piperacillin/tazobactam
- potassium acetate
- potassium chloride
- potassium phosphates
- procainamide
- prochlorperazine
- promethazine
- propofol
- remifentanil
- rituximab
- sodium acetate
- sodium bicarbonate
- sodium phosphates
- succinylcholine
- sufentanil
- tacrolimus
- theophylline
- thiotepa
- tigecycline
- tirofiban
- tobramycin
- topotecan
- trastuzumab
- trimethoprim/sulfamethoxazole
- vancomycin
- vasopressin
- vecuronium
- verapamil
- vinblastine
- vincristine
- vinorelbine
- voriconazole
- zidovudine
- zoledronic acid
Y-Site Incompatibility:
- amiodarone
- amphotericin B deoxycholate
- amphotericin B liposomal
- chlorpromazine
- diazepam
- digoxin
- doxorubicin liposomal
- gemtuzumab ozogamicin
- idarubicin
- indomethacin
- labetalol
- methylprednisolone
- mitoxantrone
- phenytoin
- propranolol

Paclitaxel Protein-Bound Particles (Albumin-Bound)

IV Administration:

Paclitaxel protein bound particles is an irritant. If extravasation occurs, immediately stop infusion. Leave needle/cannula in place temporarily but do not flush the line. Gently aspirate extravasated solution; then remove needle/cannula. Elevate patient's extremity and apply dry cold compresses for 20 min 4 times day for 1–2 days.
Intermittent Infusion: Reconstitution: Reconstitute by slowly adding 20 mL to each vial over 1 min. Direct solution to inside wall of vial to prevent foaming. Allow vial to sit for >5 min to ensure proper wetting of cake/powder. Gently swirl or invert vial for 2 min until powder is completely dissolved; avoid foaming. If foaming or clumping occurs, allow vial to stand for 15 min until foaming dissolves. Suspension should be milky and homogenous without visible particles. If particles or settling are visible, gently invert vial to resuspend. Concentration: 5 mg/mL. Inject appropriate amount of reconstituted suspension into empty sterile PVC IV bag. Do not use an in-line filter during administration. Do not administer suspension that is discolored or contains particulate matter. Should be administered immediately but is stable for 8 hr if refrigerated. Discard unused portion.
Rate: Administer over 30 min.
Y-Site Compatibility:
- carboplatin
- dexamethasone
- gemcitabine
- granisetron
- palonosetron

Explain purpose and side effects of medication. Advise patient to read Patient Information before starting therapy.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care provider before taking other medications.
Advise patient to notify health care provider immediately of rash, difficulty breathing, or symptoms of hypersensitivity reaction occurs.
Instruct patient to notify health care provider promptly if fever; chills; cough; hoarseness; sore throat; signs of infection; lower back or side pain; painful or difficult urination; bleeding gums; bruising; petechiae; blood in stools, urine, or emesis; dyspnea; or orthostatic hypotension occurs. Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush and electric razor and to avoid falls. Caution patient not to drink alcoholic beverages or to take medication containing aspirin or NSAIDs; may precipitate gastric bleeding.
May cause dizziness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
Instruct patient to notify health care provider if abdominal pain, yellow skin, weakness, paresthesia, gait disturbances, or joint or muscle aches occur.
Instruct patient to inspect oral mucosa for redness and ulceration. If mouth sores occur, advise patient to use sponge brush and rinse mouth with water after eating and drinking. Stomatitis usually resolves in 5–7 days.
Discuss with patient the possibility of hair loss. Complete hair loss usually occurs after 14–21 days and is reversible after discontinuation of therapy. Explore coping strategies.
Instruct patient not to receive any vaccinations without advice of health care provider.
Rep: Advise women of reproductive potential to use a nonhormonal method of contraception during therapy and for ≥6 mo after last dose of therapy and to avoid breastfeeding during therapy and for 2 wk after last dose. Advise men with female partners of reproductive potential to use effective contraception during therapy and for ≥3 mo after last dose. May impair fertility in women and men.

Death of rapidly replicating cells, particularly malignant ones.

PACLitaxel: ~~Taxol,~~

PACLitaxel protein-bound particles (albumin-bound): Abraxane

section name header

Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Route/Dosage ⬆ ⬇

Availability ⬆ ⬇

Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Evaluation/Desired Outcomes ⬆ ⬇

US Brand Names ⬆