Paclitaxel – Interactions and Overdose

Background

Paclitaxel is a chemotherapeutic agent marketed under the brand name Taxol among others. Used as a treatment for various cancers, paclitaxel is a mitotic inhibitor that was first isolated in 1971 from the bark of the Pacific yew tree which contains endophytic fungi that synthesize paclitaxel. It is available as an intravenous solution for injection and the newer formulation contains albumin-bound paclitaxel marketed under the brand name Abraxane.

Properties and Characteristics of Paclitaxel

Drug class	Chemotherapeutic agent
Brand Names	Abraxane, Taxol
Synonyms	liposomal encapsulated paclitaxel, NAB-PACLITAXEL COMPONENT PACLITAXEL, Nanoparticulate paclitaxel, Paclitaxel, paclitaxel protein-bound particles, Paclitaxel protein-bound particles for injection suspension, Taxol A
Molecular Formula	C₄₇H₅₁NO₁₄
Molecular Weight	853.9 g/mol
IUPAC Name	[(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-diacetyloxy-15-[(2R,3S)-3-benzamido-2-hydroxy-3-phenylpropanoyl]oxy-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
Structural formula of main components
Pure active ingredient	Paclitaxel
Appearance	White to off-white crystalline powder
Melting point	216-217 °C
Solubility	Insoluble in water
Excretion	Excreted in the feces
Storage	Store the vials in original cartons between 20° to 25°C (68° to 77°F)
Available Forms	Injection, powder, for suspension, Solution
Prescription	Doctor prescription is required

Paclitaxel uses

Paclitaxel is a chemotherapy medication that is used to treat various types of cancer. It works by interfering with the growth and division of cancer cells, ultimately slowing down or stopping their growth. Here are some of the common uses of Paclitaxel:

Breast Cancer: Paclitaxel is used in the treatment of both early-stage and advanced-stage breast cancer. It may be used alone or in combination with other chemotherapy drugs or targeted therapies.
Ovarian Cancer: Paclitaxel is often used in combination with other chemotherapy drugs to treat ovarian cancer. It may be used after surgery or in advanced cases to help shrink tumors.
Non-Small Cell Lung Cancer (NSCLC): Paclitaxel may be used in combination with other chemotherapy agents for the treatment of non-small cell lung cancer, a common type of lung cancer.
Small Cell Lung Cancer (SCLC): In some cases, Paclitaxel is used to treat small cell lung cancer, either alone or in combination with other chemotherapy drugs.
Pancreatic Cancer: Paclitaxel is sometimes used as part of chemotherapy regimens for pancreatic cancer, often in combination with other drugs like gemcitabine.
Kaposi’s Sarcoma: Paclitaxel has been used to treat Kaposi’s sarcoma, a type of cancer that is often associated with HIV infection.
Cervical Cancer: It may be used in the treatment of advanced or recurrent cervical cancer in combination with other chemotherapy agents.
Head and Neck Cancer: Paclitaxel can be part of the treatment for certain head and neck cancers when combined with other chemotherapy drugs.
Esophageal Cancer: In some cases, Paclitaxel is used to treat esophageal cancer, often in combination with other drugs.
Bladder Cancer: Paclitaxel may be used to treat bladder cancer, especially in cases where other treatments have not been effective.
Stomach (Gastric) Cancer: Paclitaxel may be included in chemotherapy regimens for stomach cancer, often in combination with other drugs.

What side effects may I notice from receiving this medication?

Side effects that you should report to your doctor or health care professional as soon as possible:

Allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue
Breathing problems
Changes in vision
Fast, irregular heartbeat
High or low blood pressure
Mouth sores
Pain, tingling, numbness in the hands or feet
Signs of decreased platelets or bleeding – bruising, pinpoint red spots on the skin, black, tarry stools, blood in the urine
Signs of decreased red blood cells – unusually weak or tired, feeling faint or lightheaded, falls
Signs of infection – fever or chills, cough, sore throat, pain or difficulty passing urine
Signs and symptoms of liver injury like dark yellow or brown urine; general ill feeling or flu-like symptoms; light-colored stools; loss of appetite; nausea; right upper belly pain; unusually weak or tired; yellowing of the eyes or skin
Swelling of the ankles, feet, hands
Unusually slow heartbeat

Side effects that usually do not require medical attention (report to your doctor or health care professional if they continue or are bothersome):

Diarrhea
Hair loss
Loss of appetite
Muscle or joint pain
Nausea, vomiting
Pain, redness, or irritation at site where injected
Tiredness

This list may not describe all possible side effects. Call your doctor for medical advice about side effects.

Mechanism of action

Paclitaxel interferes with the normal function of microtubule growth. Whereas drugs like colchicine cause the depolymerization of microtubules in vivo, paclitaxel arrests their function by having the opposite effect; it hyper-stabilizes their structure. This destroys the cell’s ability to use its cytoskeleton in a flexible manner. Specifically, paclitaxel binds to the β subunit of tubulin. Tubulin is the “building block” of mictotubules, and the binding of paclitaxel locks these building blocks in place. The resulting microtubule/paclitaxel complex does not have the ability to disassemble. This adversely affects cell function because the shortening and lengthening of microtubules (termed dynamic instability) is necessary for their function as a transportation highway for the cell. Chromosomes, for example, rely upon this property of microtubules during mitosis. Further research has indicated that paclitaxel induces programmed cell death (apoptosis) in cancer cells by binding to an apoptosis stopping protein called Bcl-2 (B-cell leukemia 2) and thus arresting its function.

Drug Interactions with Paclitaxel

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are receiving this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

Measles Virus Vaccine, Live
Mumps Virus Vaccine, Live
Rotavirus Vaccine, Live
Rubella Virus Vaccine, Live
Varicella Virus Vaccine, Live
Zoster Vaccine, Live

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

Abametapir
Bacillus of Calmette and Guerin Vaccine, Live
Crizotinib
Dabrafenib
Ethinyl Estradiol
Fedratinib
Idarubicin
Ketoconazole
Leflunomide
Mavacamten
Netupitant
Omaveloxolone
Pazopanib
Selpercatinib
Taurursodiol
Valspodar
Yellow Fever Vaccine

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

Dalfopristin
Lapatinib
Quinupristin

Other Interactions

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Dosages of Paclitaxel

The dosage of Paclitaxel can vary depending on the specific type of cancer being treated, the patient’s overall health, and other factors. Paclitaxel is typically administered intravenously by a healthcare professional in a clinical setting such as a hospital or infusion center. The dosage is usually calculated based on the patient’s body surface area (BSA) or, in some cases, it may be calculated by body weight. Here are some typical dosage ranges for adult cancer patients:

For Breast Cancer

The typical dosage is in the range of 175 to 225 mg/m².
It is often given every 3 weeks in combination with other chemotherapy drugs.

For Ovarian Cancer

The dosage is typically in the range of 135 to 175 mg/m².
It is often given every 3 weeks in combination with other chemotherapy drugs.

For Lung Cancer (Non-Small Cell Lung Cancer – NSCLC):

The dosage can vary but is generally in the range of 135 to 175 mg/m².
It is often given every 3 weeks in combination with other chemotherapy drugs.

For Pancreatic Cancer:

The dosage may range from 80 to 125 mg/m².
It is often given weekly in combination with other chemotherapy agents.

For Cervical Cancer:

The typical dosage is in the range of 135 to 175 mg/m².
It is often given every 3 weeks in combination with other chemotherapy drugs.

For Kaposi’s Sarcoma:

The dosage can vary but is typically in the range of 100 to 135 mg/m².
It may be given every 2 or 3 weeks.

For Head and Neck Cancer:

The dosage can vary but is generally in the range of 135 to 175 mg/m².
It is often given every 3 weeks in combination with other chemotherapy drugs.

These are general guidelines, and the specific dosage and treatment schedule will be determined by your oncologist based on your individual condition and needs. It’s important to follow your healthcare provider’s instructions regarding the dosage and administration of Paclitaxel and to receive the drug only under the supervision of a qualified medical team, as Paclitaxel can have side effects that need to be managed and monitored during treatment.

In case of emergency/overdose

In case of overdose, call the poison control helpline. If the victim has collapsed, had a seizure, has trouble breathing, or can’t be awakened, immediately call emergency services.

Symptoms of overdose may include:

Pale skin
Shortness of breath
Excessive tiredness
Sore throat, fever, chills, and other signs of infection
Unusual bruising or bleeding
Numbness, burning, or tingling of the hands and feet
Sores in the mouth

What are warnings and precautions for paclitaxel?

Warnings

Paclitaxel should be administered under the supervision of an experienced cancer chemotherapy physician in a facility equipped to diagnose and manage complications.
Paclitaxel is contraindicated in patients with solid tumor who have baseline neutrophil counts less than 1500 cells/m³ and in patients with AIDS-related Kaposi sarcoma who have baseline neutrophil counts less than 1000 cells/m³; perform frequent peripheral blood counts to monitor for the occurrence of bone marrow suppression, primarily neutropenia, which may result in infection.
Fatal anaphylaxis and severe hypersensitivity reactions characterized by shortness of breath (dyspnea) and low blood pressure (hypotension) requiring treatment, skin swelling (angioedema), and generalized hives (urticarial) have occurred in patients despite premedication.
Pretreat all patients with corticosteroids, diphenhydramine, and H2 antagonists.
Do not re-challenge patients who experience severe hypersensitivity reactions to the drug.
This medication contains paclitaxel. Do not take Taxol if you are allergic to paclitaxel or any ingredients contained in this drug.
Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Pregnancy and Lactation

Use paclitaxel during pregnancy only in life-threatening emergencies when no safer drug is available. There is positive evidence of human fetal risk.
It is not known if paclitaxel is excreted in breast milk; do not nurse.

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