Paclitaxel Protein-bound
Paclitaxel Protein-bound Uses, Dosage, Side Effects, Food Interaction and all others data.
Paclitaxel Protein-bound promotes microtubule formation by enhancing the action of tubulin dimers, stabilising existing microtubules and preventing their disassembly, thereby disrupting normal cell division in the late G2 mitotic phase of the cell cycle. This results in the inhibition of cell replication.
Paclitaxel Protein-bound is a taxoid antineoplastic agent indicated as first-line and subsequent therapy for the treatment of advanced carcinoma of the ovary, and other various cancers including breast cancer. Paclitaxel Protein-bound is a novel antimicrotubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. In addition, paclitaxel induces abnormal arrays or "bundles" of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis.
| Trade Name | Paclitaxel Protein-bound |
| Availability | Prescription only |
| Generic | Paclitaxel |
| Paclitaxel Other Names | Paclitaxel, Taxol A |
| Related Drugs | Opdivo, methotrexate, tamoxifen, letrozole, Keytruda, Arimidex, carboplatin, pembrolizumab, doxorubicin, cisplatin |
| Weight | 100mg, |
| Type | Intravenous Powder For Injection, Intravenous |
| Formula | C47H51NO14 |
| Weight | Average: 853.9061 Monoisotopic: 853.330955345 |
| Protein binding | 89%-98% bound to plasma protein. The presence of cimetidine, ranitidine, dexamethasone, or diphenhydramine did not affect protein binding of paclitaxel. |
| Groups | Approved, Vet approved |
| Therapeutic Class | Cytotoxic Chemotherapy |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Paclitaxel Protein-bound Injection is used for first-line and subsequent therapy for the treatment of advanced carcinoma of the ovary. As first- line therapy, paclitaxel is used for combination with cisplatin.
Paclitaxel Protein-bound Injection is used for the adjuvant treatment of node-positive breast cancer administered sequentially to standard doxorubicin-containing combination chemotherapy. In the clinical trial, there was an overall favorable effect on disease-free and overall survival in the total population of patients with receptor-positive and receptor-negative tumors, but the benefit has been specifically demonstrated by available data (median follow-up 30 months) only in the patients with estrogen and progesterone receptor negative tumors.
Paclitaxel Protein-bound Injection is used for the treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy. Prior therapy should have included an anthracyclineunless clinically contraused. Paclitaxel Protein-bound Injection, in combination with cisplatin, is used for the first-line treatment of non-small cell lung cancer in patients who are not candidates for potentially curative surgery and/or radiation therapy. Paclitaxel Protein-bound Injection is used for the second-line treatment of AIDS-related Kaposi's sarcoma.
Paclitaxel Protein-bound is also used to associated treatment for these conditions: Advanced Cervical Cancer, Advanced Head and Neck Cancer, Advanced Ovarian Cancer, Advanced Soft Tissue Sarcoma, Esophageal Cancers, Fallopian Tube Cancer, Kaposi’s sarcoma, Locally Advanced Non-Small Cell Lung Cancer, Malignant Neoplasm of Stomach, Malignant Peritoneal Neoplasm, Metastatic Bladder Cancer, Metastatic Breast Cancer, Metastatic Melanoma, Metastatic Non-Small Cell Lung Cancer, Non-Small Cell Lung Carcinoma (NSCLC), Ovarian Cancer, Pancreatic Adenocarcinoma Metastatic, Advanced Bladder cancer, Advanced Thymoma, Metastatic Penile cancer, Refractory Small cell lung cancer, Refractory Testicular germ cell cancer
How Paclitaxel Protein-bound works
Paclitaxel Protein-bound 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.
Dosage
Paclitaxel Protein-bound dosage
Advanced non-small cell lung cancer: 135 mg/m2 over 24 hr or 175 mg/m2 over 3 hr, followed by cisplatin and repeated at 3 wk intervals.
Ovarian carcinoma: Primary treatment (in combination with cisplatin or carboplatin): 135 mg/m2 infused over 24 hr followed by cisplatin and repeated at 3 wk intervals. Secondary treatment (as a single agent): 135 or 175 mg/m2 infused over 3 hr once every 3 weeks.
Breast cancer: Adjuvant therapy; 2nd line monotherapy or 1st line treatment with trastuzumab: 175 mg/m2 infused over 3 hr once every 3 wk for 4 courses; when used with trastuzumab, the dose should be given the day after the 1st dose of trastuzumab or immediately after subsequent doses if well-tolerated. 1st line with doxorubicin: 220 mg/m2over 3 hr every 3 wk, the dose to be administered 24 hr after doxorubicin.
AIDS-related Kaposi's sarcoma: 135 mg/m2 over 3 hr every 3 weeks. Alternatively, 100 mg/m2 over 3 hr every 2 wk especially in patients with poor performance status.
Paclitaxel Protein-bound must be diluted before infusion. It can be diluted in 0.9% sodium chloride inj, 5% dextrose inj, 5% dextrose and 0.9% sodium chloride inj or 5% dextrose in lactated Ringer's inj to a concentration of 0.3-1.2 mg/ml.
Side Effects
Neutropenia, leukopenia, thrombocytopenia, anaemia, bleeding; hypersensitivity reactions (dyspnoea, flushing, chest pain, tachycardia, rash, hypotension, hypertension); bradycardia, abnormal ECG; neurotoxicity (mainly peripheral neuropathy), myalgia, arthralgia; nausea, vomiting, diarrhoea; severe mucositis, alopecia; rarely hepatic necrosis and encephalopathy, inj site reactions e.g. erythema, tenderness, skin discolouration, swelling; interstitial pneumonitis; infections (mainly UTIs and upper respiratory tract); mucosal inflammation, severe elevation in LFTs (aspartate aminotransferase and alkaline phosphatase).
Toxicity
Rat (ipr) LD50=32530 µg/kg. Symptoms of overdose include bone marrow suppression, peripheral neurotoxicity, and mucositis. Overdoses in pediatric patients may be associated with acute ethanol toxicity.
Precaution
Bone marrow suppression during therapy. Monitor cardiac function if conduction abnormalities result. Premedicaton (with corticosteroid, antihistamine and histamine H2-receptor antagonist) may be required to reduce risk of hypersensitivity reaction. Discontinue, if severe reactions e.g. hypotension, dyspnoea, angioedema or urticaria occur. Caution in patients with moderate hepatic impairment. Monitor for reactions of admin. Safety and efficacy in paediatric patients have not been established. Administer before platinum derivatives (cisplatin, carboplatin) if used in combination. Hazardous agent; use appropriate precautions for handling and disposal.
Interaction
Myelosuppression was more profound when given after cisplatin than with the alternate sequence (e.g., paclitaxel before cisplatin). CYP2C8 inducers e.g. carbamazepine, phenobarbital, phenytoin, rifampicin, rifapentine, and secobarbital may reduce levels or effects. CYP2C8 inhibitors e.g. gemfibrozil, ketoconazole, montelukast, and ritonavir may increase levels or effects. CYP3A4 inducers e.g. aminoglutethimide, carbamazepine, nafcillin, nevirapine, phenobarbital, phenytoin, and rifamycins may decrease the levels or effects. CYP3A4 inhibitors e.g. azole antifungals, clarithromycin, diclofenac, doxycycline, erythromycin, imatinib, isoniazid, nefazodone, nicardipine, propofol, protease inhibitors, quinidine, telithromycin, and verapamil may increase levels or effects. May increase anthracycline (eg doxorubicin, epirubicin) levels or toxicity; admin of anthracycline at least 24 hr prior to paclitaxel may reduce interaction. May decrease the absorption of cardiac glycosides (may only affect digoxin tablets); levels should be monitored.
Food Interaction
- Avoid echinacea. Co-administration may decrease the effectiveness of immunosuppressants, and echinacea may induce CYP3A4 increasing paclitaxel metabolism.
- Exercise caution with grapefruit products. Grapefruit inhibits CYP3A4 metabolism, which may increase the serum concentration of paclitaxel.
- Exercise caution with St. John's Wort. This herb induces the CYP3A4 metabolism of paclitaxel and may reduce its serum concentration.
[Moderate] MONITOR: Coadministration with inhibitors of CYP450 3A4, such as grapefruit juice, may increase the plasma concentrations of paclitaxel, which is a substrate of the isoenzyme.
Current data suggest that consumption of large quantities of grapefruit juice inhibit both intestinal and hepatic CYP450 3A4 due to certain compounds present in grapefruit.
Specific data for paclitaxel are lacking; however, in a case report of a 52-year-old woman with esophageal squamous cell carcinoma receiving a twice weekly chemotherapy regimen including intravenous docetaxel (40 mg In the absence of other CYP450 3A4 inhibitors, these effects were attributed to daily consumption of 250 mL of grapefruit juice, which the patient had been consuming for at least 3 months. Two weeks after the patient ceased the grapefruit juice, the docetaxel AUC was closer to the target value and the neutrophil count reduction was less than 35%. In addition, in a pharmacokinetic study consisting of 7 cancer patients, mean dose-normalized docetaxel AUC increased by 2.2-fold and clearance decreased by 49% when intravenous docetaxel was given at a reduced dosage of 10 mg Patients should be closely monitored for the development of paclitaxel toxicity, including diarrhea, mucositis, myelosuppression, and peripheral neuropathy and dose adjustment considered per local treatment protocols.
MANAGEMENT: Caution is recommended if paclitaxel is to be used in combination with grapefruit and grapefruit juice.
Paclitaxel Protein-bound Drug Interaction
Moderate: paclitaxel protein-bound, doxorubicin, aprepitant, pegfilgrastimMinor: ascorbic acidUnknown: aspirin, fluticasone / salmeterol, palonosetron, lorazepam, diphenhydramine, loratadine, ubiquinone, cyclophosphamide, apixaban, omega-3 polyunsaturated fatty acids, acetaminophen, albuterol, cyanocobalamin, cholecalciferol, ondansetron
Paclitaxel Protein-bound Disease Interaction
Major: infections, conduction disorders, hepatic dysfunction, myelosuppression, peripheral neuropathyModerate: anaphylaxis
Volume of Distribution
- 227 to 688 L/m^2 [apparent volume of distribution at steady-state, 24 hour infusion]
Elimination Route
When a 24 hour infusion of 135 mg/m^2 is given to ovarian cancer patients, the maximum plasma concentration (Cmax) is 195 ng/mL, while the AUC is 6300 ng•h/mL.
Half Life
When a 24 hour infusion of 135 mg/m^2 is given to ovarian cancer patients, the elimination half=life is 52.7 hours.
Clearance
- 21.7 L/h/m2 [Dose 135 mg/m2, infusion duration 24 h]
- 23.8 L/h/m2 [Dose 175 mg/m2, infusion duration 24 h]
- 7 L/h/m2 [Dose 135 mg/m2, infusion duration 3 h]
- 12.2 L/h/m2 [Dose 175 mg/m2, infusion duration 3 h]
Elimination Route
In 5 patients administered a 225 or 250 mg/m2 dose of radiolabeled paclitaxel as a 3-hour infusion, a mean of 71% of the radioactivity was excreted in the feces in 120 hours, and 14% was recovered in the urine.
Pregnancy & Breastfeeding use
Category D: There is positive evidence of human fetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).
Contraindication
History of hypersensitivity (especially macrogol glycerol ricinolate). Patients with baseline neutropenia of <1500 cells/mm3 (<1000 cells/mm3 for kaposi's sarcoma). Pregnancy and lactation. In kaposi's sarcoma, contraindicated in patients with concurrent, serious, uncontrolled infections.
Special Warning
Hepatic Impairment:
Advanced non-small cell lung cancer: Do not use in severe impairment, increased risk of hepatotoxicity. For detailed dosing recommendation, consult local protocol.
Ovarian carcinoma: Do not use in severe impairment, increased risk of hepatotoxicity. For detailed dosing recommendations, consult local protocol.
Breast cancer: Do not use in severe impairment, increased risk of hepatotoxicity. For detailed dosing recommendation, consult local protocol.
AIDS-related Kaposi's sarcoma: Do not use in severe impairment, increased risk of hepatotoxicity. For detailed dosing recommendation, consult local protocol.
Acute Overdose
Complications: bone marrow suppression, peripheral neurotoxicity and mucositis. There is no known antidote. Treatment is symptom specific and supportive.
Innovators Monograph
You find simplified version here Paclitaxel Protein-bound
Paclitaxel Protein-bound contains Paclitaxel see full prescribing information from innovator Paclitaxel Protein-bound Monograph, Paclitaxel Protein-bound MSDS, Paclitaxel Protein-bound FDA label
FAQ
What is Paclitaxel Protein-bound used for?
Paclitaxel Protein-bound is used for many different types of cancer.Paclitaxel Protein-bound is a chemotherapy drug.
How safe is Paclitaxel Protein-bound?
barnd is safe and effective in the treatment of advanced AIDS-related Kaposi's sarcoma.Lower dose of 80 mg/m2 was very well tolerated.
How does Paclitaxel Protein-bound work?
Paclitaxel Protein-bound works by stopping cancer cells from separating into two new cells. This blocks the growth of the cancer.
What are the common side effects of Paclitaxel Protein-bound?
Thw common side effects of Paclitaxel Protein-bound are Bleeding, blistering, burning, coldness, discoloration of the skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site,cracked lips.
Is Paclitaxel Protein-bound safe during pregnancy?
Paclitaxel Protein-bound can cause fetal harm when administered to a pregnant woman.If Paclitaxel Protein-bound is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus.
Is Paclitaxel Protein-bound safe during breastfeeding?
The manufacturer recommends that breastfeeding be discontinued during Paclitaxel Protein-bound therapy and for 2 weeks after the last dose. Paclitaxel Protein-bound may adversely affect the normal microbiome and chemical makeup of breastmilk.
Can I drink alcohol with Paclitaxel Protein-bound?
Paclitaxel Protein-bound contains alcohol and may cause a drunken feeling when the medicine is injected into your vein. Avoid drinking alcohol on the day of your Paclitaxel Protein-bound injection.
Can I drive after taking Paclitaxel Protein-bound?
There is no reason why you cannot continue driving between courses of Paclitaxel Protein-bound but you should remember that this medicine contains some alcohol and it may be unwise to drive or use machines immediately after a course of treatment.
When should I take Paclitaxel Protein-bound?
Paclitaxel Protein-bound is given after surgery to reduce the risk of breast cancer coming back in the future. It usually starts within a few weeks of your operation. If you are going to have radiotherapy you will usually complete your course of Paclitaxel Protein-bound first.
How do I know if Paclitaxel Protein-bound is working?
The best way to tell if chemotherapy is working for your cancer is through follow-up testing with your doctor. Throughout your treatment, an oncologist will conduct regular visits, and blood and imaging tests to detect cancer cells and whether they've grown or shrunk.
How long does Paclitaxel Protein-bound stay in my system?
Paclitaxel Protein-bound stays in the body within 2 -3 days of treatment but there are short-term and long-term side effects that patients may experience. Not all patients will experience all side effects but many will experience at least a few.
Who should not take Paclitaxel Protein-bound?
Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; feeling like you might pass out; swelling of your face, lips, tongue, or throat.
What happens if I overdose of Paclitaxel Protein-bound?
Since Paclitaxel Protein-bound is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.
What happens if I miss a dose of Paclitaxel Protein-bound?
Call your doctor for instructions if you miss an appointment for your Paclitaxel Protein-bound injection.
What happens if Paclitaxel Protein-bound is stopped?
If you decide to stop Paclitaxel Protein-bound, be sure you're still getting relief from symptoms such as pain, constipation, and nausea. This is called palliative care, and it's meant to improve your quality of life.
How long can I take Paclitaxel Protein-bound?
Paclitaxel Protein-bound is usually given as 4 treatments over 12 weeks 1 treatment every 3 weeks.
How long does it take for Paclitaxel Protein-bound to leave my body?
Paclitaxel Protein-bound generally takes about 48 to 72 hours for your body to break down and/or get rid of most chemo drugs.
Does Paclitaxel Protein-bound affect fertility?
The effect of some other chemotherapy drugs, such as Paclitaxel Protein-bound, on fertility has not been as widely studied, but evidence suggests they'll also affect fertility.
