paclitaxel

Paclitaxel is a chemotherapy drug used to treat various types of cancers including ovarian cancer, breast cancer, non-small cell lung cancer and AIDS-related Kaposi sarcoma.

Paclitaxel is an anticancer drug that belongs to a class of medications known as antimicrotubular antineoplastics. Paclitaxel may be used as a first-line, second-line, or adjuvant treatment, often in combination with cisplatin, another chemotherapy drug used to treat cancer.

Paclitaxel is a natural alkaloid known as taxane derived from English yew (Taxus baccata), an evergreen tree. Paclitaxel stops cancer cell growth by preventing cell division (mitosis) in cancer cells. Paclitaxel stabilizes the structure of microtubules within cells, preventing them from normal dynamic reorganization that is required for cell division. This arrests the cell cycle midway, inhibits cell replication, and induces programmed cell death (apoptosis).

Paclitaxel is approved by the FDA for the treatment of following cancers:

• First-line (with cisplatin) and subsequent therapy for the treatment of advanced ovarian cancer
• Adjuvant treatment for node-positive breast cancer administered sequentially to standard doxorubicin-containing combination chemotherapy
• Treatment of metastatic breast cancer after combination chemotherapy has failed or cancer has relapsed after 6 months of adjuvant chemotherapy
• First-line treatment (with cisplatin) of non-small cell lung cancer in patients who are not candidates for potentially curative surgery and/or radiation therapy

Second-line treatment of acquired immunodeficiency syndrome (AIDS)-related Kaposi’s sarcoma

• Paclitaxel is used off-label to treat advanced, refractory, recurrent, or metastatic stages of cancers that include:
• Pancreatic cancer
• Anal cancer
• Penile cancer
• Bladder cancer
• Upper gastrointestinal cancer
• Cervical cancer
• Endometrial cancer
• Head and neck cancer
• Small cell lung cancer
• Melanoma
• Testicular germ cell tumor
• High-risk gestational trophoblastic neoplasia
• Thymoma/thymic carcinoma
• Thyroid cancer (anaplastic)
• Unknown primary adenocarcinoma

Orphan designations include:

• Esophageal cancer
• Adenocarcinoma of the stomach or lower esophagus
• Brain cancer
• Hormone-refractory prostate cancer
• Angiosarcoma

• Do not administer paclitaxel to patients with hypersensitivity to any of the components in the formulation.
• Do not administer paclitaxel to patients with:
  • Solid tumors who have baseline neutrophil counts of less than 1500 cells/mm3
  • AIDS-related Kaposi’s sarcoma with baseline neutrophil counts of less than 1000 cells/mm3
• Frequent blood cell counts should be performed on patients on paclitaxel therapy to monitor for occurrence of bone marrow suppression and low neutrophil counts (neutropenia) which can result in infection.
• Paclitaxel should be administered under the supervision of an experienced cancer chemotherapy physician in a facility equipped to diagnose and manage complications.
• All patients should be pretreated with corticosteroids, diphenhydramine, and H2 antagonists and monitored for hypersensitivity reactions. Despite premedication, fatal reaction have occurred, including anaphylaxis with hypotension and breathing difficulty. Patients who have severe reactions should not be rechallenged with the drug.
• Some patients have developed severe heart conduction abnormalities that required pacemaker placement. Cardiac conduction should be monitored during paclitaxel infusion and appropriate therapy instituted, if necessary.
• Risk of cardiac dysfunction increases if administered in conjunction with trastuzumab or anthracyclines. 
• Plasticized polyvinyl chloride (PVC) equipment or devices should be avoided for preparing paclitaxel solutions, to prevent plasticizer leaching into the solution. Use storing and administering equipment as recommended by the manufacturer.

Common side effects of paclitaxel include:

• Blood disorders, including:
  • Low count of neutrophil immune cells (neutropenia)
  • Low count of leukocyte immune cells (leukopenia)
  • Low red blood cell count (anemia)
  • Low platelet count (thrombocytopenia)
  • Low count of all types of blood cells (pancytopenia)
• Bleeding
• Infections
• Injection site reaction
• Leakage of drug out of the vein (extravasation)
• Skin rash
• Hair loss (alopecia)
• Hypersensitivity reactions
• Severe allergic reaction (anaphylaxis)
• Severe skin reactions such as:
  • Stevens-Johnson syndrome
  • Toxic epidermal necrolysis
• Nausea
• Vomiting
• Diarrhea
• Sore mouth (stomatitis)
• Mucous membrane inflammation (mucositis)
• Muscle pain (myalgia)
• Joint pain (arthralgia)
• Weakness (asthenia)
• Peripheral nerve disease (neuropathy)
• ECG abnormality
• Cardiac conduction abnormalities
• Slow heart rate (bradycardia)
• Low blood pressure (hypotension)
• Congestive heart failure
• Left ventricular dysfunction
• Swelling (edema)
• Flushing
• Dehydration
• High temperature (pyrexia)
• Grand mal seizure
• Kidney damage

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Injectable Solution

• 6 mg/mL

Adult:

Ovarian Cancer

• Premedicate to prevent hypersensitivity reactions (e.g., dexamethasone, diphenhydramine, H2 blockers)
• Previously untreated: 175 mg/m2 intravenously (IV) over 3 hours every 3 weeks (follow with cisplatin), OR
• 135 mg/m2 IV over 24 hours every 3 weeks (follow with cisplatin)
• Previously treated: Various regimens exist: 135-175 mg/m² IV over 3 hours every 3 weeks

Breast Cancer

• Node positive (adjuvant chemotherapy): 175 mg/m² intravenously (IV) over 3 hours every 3 weeks 4 times (with doxorubicin-containing regimen)
• Metastatic Disease (failure of initial chemotherapy or relapse within 6 months following adjuvant chemotherapy): 175 mg/m² IV over 3 hours every 3 weeks

Non-small Cell Lung Cancer

• 135 mg/m2 intravenously (IV) over 24 hours every 3 weeks (follow with cisplatin)

AIDS-related Kaposi's Sarcoma (2nd-line Treatment)

• 135 mg/m2 intravenously (IV) over 3 hours every 3 weeks; OR
• 100 mg/m2 IV over 3 hours every 2 weeks

Pancreatic Cancer (Off-label)

• Investigational: 125 mg/m2 intravenously (IV) with gemcitabine

Dosage Modifications

• If baseline PMN is less than 1500/m³, do not re-treat until PMN greater than 1500/m³ and platelet count greater than 100,000/m³
• If severe neutropenia occurs (PMN less than 500/m³ for 7 days), reduce subsequent doses by 20%
• Renal impairment: No dosage adjustment is required

Hepatic Impairment

With solid carcinomas and not Kaposi sarcoma

24-hour infusion

• AST/ALT less than 2 times upper limit of normal (ULN) and bilirubin up to 1.5 mg/dL: 135 mg/m² over 24 hours
• AST/ALT 2 to 10 times ULN and bilirubin up to 1.5 mg/dL: 100 mg/m² over 24 hours
• AST/ALT less than 10 times ULN and bilirubin 1.6-7.5 mg/dL: 50 mg/m² over 24 hours
• AST/ALT 10 times ULN or greater OR bilirubin greater than 7.5 mg/dL: Do not administer

3-hour infusion

• AST/ALT less than 10 times upper limit of normal (ULN) and bilirubin less than 1.25 times ULN: 175 mg/m² over 3 hours
• AST/ALT less than 10 times ULN and bilirubin 1.26-2 times ULN: 135 mg/m² over 3 hours
• AST/ALT less than 10 times ULN and bilirubin 2.01-5 times ULN: 90 mg/m² over 3 hours
• AST/ALT 10 times ULN or greater OR bilirubin greater than 5 times ULN: Do not administer

Pediatric:

• Safety and efficacy not established

• Paclitaxel overdose may cause symptoms that include bone marrow suppression, peripheral neurotoxicity, and mucous membrane inflammation (mucositis).
• There are reports of central nervous system toxicity from clinical trials in pediatric patients. The toxicity may be associated with the ethanol component of paclitaxel.
• There is no known antidote for paclitaxel overdose. Overdose may be treated with symptomatic and supportive care.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Paclitaxel has no known severe interactions with other drugs.
• Serious interactions of paclitaxel include:
  • abametapir
  • adenovirus types 4 and 7 live, oral
  • apalutamide
  • deferiprone
  • eluxadoline
  • erdafitinib
  • fexinidazole
  • idarubicin
  • idelalisib
  • influenza virus vaccine quadrivalent, adjuvanted
  • influenza virus vaccine trivalent, adjuvanted
  • ivosidenib
  • lasmiditan
  • lopinavir
  • mifepristone
  • nefazodone
  • pacritinib
  • palifermin
  • quinidine
  • ropeginterferon alfa 2b
  • selinexor
  • sotorasib
  • tepotinib
  • tucatinib
  • voxelotor
• Paclitaxel has moderate interactions with at least 124 different drugs.
• Paclitaxel has mild interactions with at least 63 different drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• Paclitaxel can cause fetal harm, do not use in pregnant women.
• Women of reproductive potential must practice effective contraception while on paclitaxel therapy.
• It is not known if paclitaxel is present in breast milk, however, many drugs are, and paclitaxel has potential for serious adverse reactions in the breastfed infant. Nursing mothers should discontinue breastfeeding while receiving paclitaxel.

• Paclitaxel can have serious side effects. If you have severe stomach pain or severe diarrhea, inform your healthcare provider immediately.
• Severe allergic reaction (anaphylaxis) is a medical emergency and can lead to death if not treated promptly. Contact your healthcare provider right away if you have symptoms of anaphylaxis which may include:
  • Rash or hives
  • Sudden swelling of face, lips, tongue or throat
  • Trouble swallowing
  • Breathing difficulty