and can't [80:<30 mL/minute) or end-stage renal disease; 1 use with caution in these patients. 1 Common Adverse Effects Myelosuppression 1 2 (neutropenia, 1 2 leukopenia, 1 2 anemia, 1 2 thrombocytopenia 1 2 ), diarrhea, 1 2 fatigue, 1 2 nausea, 1 2 vomiting, 1 2 constipation, 1 2 asthenia, 1 2 abdominal pain, 1 2 anorexia, 1 back pain, 1 2 hematuria, 1 2 peripheral neuropathy, 1 2 pyrexia, 1 2 dyspnea, 1 2 cough, 1 dysgeusia, 1 arthralgia, 1 2 alopecia. 1 Interactions for Cabazitaxel No formal drug interaction studies to date. 1 Metabolized principally by CYP3A4/5 and to a lesser extent by CYP2C8. 1 4 Cabazitaxel does not induce CYP isoenzymes in vitro. 1 In vitro data indicate low potential for inhibition of CYP isoenzymes 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4/5. 1 Substrate of P-glycoprotein (P-gp), but not a substrate of multidrug resistance proteins MRP1 and MRP2 or breast cancer resistance protein (BCRP). 1 Cabazitaxel 25 mg/m 2 is unlikely to inhibit MRP1, MRP2, P-gp, or BCRP in vivo. 1 Does not inhibit MRP1 or MRP2 in vitro; inhibition of P-gp transport and BCRP observed in vitro, but at concentrations at least 38 times those achieved clinically. 1 Drugs Affecting Hepatic Microsomal Enzymes Potent CYP3A inhibitors: Potential pharmacokinetic interaction (increased plasma cabazitaxel concentrations). 1 4 Avoid concomitant use. 1 Moderate CYP3A inhibitors: Use concomitantly with caution. 1 Potent CYP3A inducers: Potential pharmacokinetic interaction (decreased plasma cabazitaxel concentrations). 1 4 Avoid concomitant use. 1 Drugs Metabolized by Hepatic Microsomal Enzymes Unlikely to inhibit metabolism of drugs that are substrates of CYP isoenzymes 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, or 3A4/5. 1 Specific Drugs Drug Interaction Comments Anticonvulsants (carbamazepine, phenobarbital, phenytoin) Probable decrease in plasma cabazitaxel concentrations 1 Avoid concomitant use 1 Antifungals (itraconazole, ketoconazole, voriconazole) Probable increase in plasma cabazitaxel concentrations 1 Avoid concomitant use 1 Antimycobacterials (rifabutin, rifampin, rifapentine) Probable decrease in plasma cabazitaxel concentrations 1 4 Avoid concomitant use 1 HIV protease inhibitors (e.g., atazanavir, indinavir, nelfinavir, ritonavir, saquinavir) Probable increase in plasma cabazitaxel concentrations 1 4 Avoid concomitant use 1 Macrolides (clarithromycin, telithromycin) Probable increase in plasma cabazitaxel concentrations 1 4 Avoid concomitant use 1 Nefazodone Probable increase in plasma cabazitaxel concentrations 1 Avoid concomitant use 1 Prednisone, prednisolone No effect on cabazitaxel pharmacokinetics at prednisone or prednisolone dosage of 10 mg daily 1 St. John's wort ( Hypericum perforatum ) Probable decrease in plasma cabazitaxel concentrations 1 Avoid concomitant use 1 Cabazitaxel Pharmacokinetics Distribution Extent Not known whether cabazitaxel is distributed into human milk. 1 (See Lactation under Cautions.) Crosses placenta and distributes into milk in rats. 1 Plasma Protein Binding 89 92% (mainly albumin and lipoproteins). 1 Elimination Metabolism Extensively (>95%) metabolized in the liver, mainly by CYP3A4/5 and to a lesser extent by CYP2C8. 1 Elimination Route Eliminated in feces (76%) as metabolites and in urine (3.7%) as unchanged drug or metabolites; about 20 metabolites have been identified in urine or feces. 1 Half-life Terminal half-life: 95 hours. 1 Special Populations Hepatic impairment is expected to result in increased serum cabazitaxel concentrations. 1 (See Hepatic Impairment under Cautions.) Mild to moderate renal impairment (Cl cr 30 to> <80 mL/minute) does not substantially alter cabazitaxel pharmacokinetics. 1 Not studied in severe renal impairment (Cl cr> <30 mL/minute) or end-stage renal disease. 1 Stability Storage Parenteral Injection Concentrate 25°C (may be exposed to 15 30°C); do not refrigerate. 1 Diluted cabazitaxel solutions are supersaturated and may crystallize over time. 1 Use initial diluted solution (10 mg/mL) within 30 minutes of preparation. 1 Use final diluted solution (0.1 0.26 mg/mL) within 8 hours (including 1 hour for administration) if stored at room temperature or within 24 hours (including 1 hour for administration) if stored under refrigeration. 1 Compatibility For information on systemic interactions resulting from concomitant use, see Interactions. Parenteral Solution Compatibility Compatible Dextrose 5% in water 1 Sodium chloride 0.9% 1 Actions A semisynthetic taxoid derived from the major natural taxoid (10-deacetyl baccatin III) extracted from the needles of various species of yew trees ( Taxus species). 1 4 9 10 13 The 7,10-dimethoxy analog of docetaxel. 5 Like other taxanes (e.g., docetaxel, paclitaxel), cabazitaxel binds to β-tubulin subunits on microtubules and stabilizes and suppresses microtubule activity, thereby resulting in mitotic arrest and cell death. 1 3 4 9 10 11 12 13 Active against some cell lines and tumors that are resistant to various chemotherapeutic agents, including other taxanes (i.e., docetaxel, paclitaxel). 1 2 3 9 10 11 13 Advice to Patients Risk of hypersensitivity reactions. 1 Importance of informing clinician immediately if manifestations of severe hypersensitivity (e.g., rash, itching, dizziness or faintness, difficulty breathing, chest or throat tightness, facial swelling) occur. 1 Importance of informing clinician of any history of hypersensitivity to cabazitaxel or other agents containing polysorbate 80. 1 Risk of infection, including severe or potentially fatal infection. 1 Importance of patients monitoring their temperature frequently and immediately notifying clinician if fever or other manifestations of infection (e.g., cough, burning on urination, myalgia) occur. 1 Risk of dehydration. 1 Importance of informing clinician if substantial vomiting or diarrhea occurs. 1 Risk of renal failure. 1 Importance of informing clinician if decreased urine output occurs or if edema develops. 1 Importance of routine monitoring of blood cell counts. 1 Importance of taking the oral prednisone component of the cabazitaxel/prednisone regimen for prostate cancer as directed. 1 Importance of informing clinician if not adherent to oral prednisone regimen. 1 Importance of informing geriatric patients that certain adverse effects may be more frequent or severe in older patients. 1 (See Geriatric Use under Cautions.) Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. 1 Apprise patient of potential hazard to the fetus if used during pregnancy; women of childbearing potential should avoid becoming pregnant. 1 Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses. 1 Importance of informing patients of other important precautionary information. 1 (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. Cabazitaxel Routes Dosage Forms Strengths Brand Names Manufacturer Parenteral Injection concentrate, for IV infusion only 40 mg/mL (60 mg) Jevtana (with water for injection containing alcohol 13% w/w diluent) Sanofi-Aventis AHFS DI Essentials. Copyright 2017, Selected Revisions September 12, 2011. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814. References 1. Sanofi-Aventis. Jevtana (cabazitaxel) injection prescribing information. Bridgewater, NJ; 2010 Jun. 2. de Bono JS, Oudard S, Ozguroglu M et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet . 2010; 376:1147-54. [PubMed 20888992] 3. Pal SK, Twardowski P, Sartor O. Critical appraisal of cabazitaxel in the management of advanced prostate cancer. Clin Interv Aging . 2010; 5:395-402. [PubMed 21152241] 4. . New treatments for metastatic prostate cancer. Med Lett Drugs Ther . 2010; 52:69-70. 5. Sanofi-Aventis. Bridgewater, NJ: Personal Communication. 6. Froehner M, Wirth MP. Cabazitaxel for castration-resistant prostate cancer. Lancet . 2011; 377:121-2; author reply 122-3. [PubMed 21215875] 7. Pearson SD, Trissel LA. Leaching of diethylhexyl phthalate from polyvinyl chloride containers by selected drugs and formulation components. Am J Hosp Pharm . 1993; 50:1405-9. [PubMed 8362871] 8. Kullak-Ublick GA, Becker MB. Regulation of drug and bile salt transporters in liver and intestine. Drug Metab Rev . 2003; 35:305-17. [PubMed 14705863] 9. Kurata T, Shimada Y, Tamura T et al. Phase I and pharmacokinetic study of a new taxoid, RPR 109881A, given as a 1-hour intravenous infusion in patients with advanced solid tumors. J Clin Oncol . 2000; 18:3164-71. [PubMed 10963645] 10. Mita AC, Denis LJ, Rowinsky EK et al. Phase I and pharmacokinetic study of XRP6258 (RPR 116258A), a novel taxane, administered as a 1-hour infusion every 3 weeks in patients with advanced solid tumors. Clin Cancer Res . 2009; 15:723-30. [PubMed 19147780] 11. Pivot X, Koralewski P, Hidalgo JL et al. A multicenter phase II study of XRP6258 administered as a 1-h i.v. infusion every 3 weeks in taxane-resistant metastatic breast cancer patients. Ann Oncol . 2008; 19:1547-52. [PubMed 18436520] 12. Cisternino S, Bourasset F, Archimbaud Y et al. Nonlinear accumulation in the brain of the new taxoid TXD258 following saturation of P-glycoprotein at the blood-brain barrier in mice and rats. Br J Pharmacol . 2003; 138:1367-75. [PubMed 12711638] 13. Bouchet BP, Galmarini CM. Cabazitaxel, a new taxane with favorable properties. Drugs Today (Barc) . 2010; 46:735-42. [PubMed 21076710] 14. Sanofi-Aventis. Taxotere (docetaxel) injection concentrate prescribing information. Bridgewater, NJ; 2010 May. Next Interactions Print this page Add to My Med List More about cabazitaxel Side Effects During Pregnancy Dosage Information Drug Interactions Support Group En Español 0 Reviews Add your own review/rating Drug class: mitotic inhibitors Consumer resources Cabazitaxel Cabazitaxel Intravenous (Advanced Reading) Professional resources Cabazitaxel (Wolters Kluwer) Other brands: Jevtana Related treatment guides Prostate Cancer> ]} FEATURED: CAR-T Cell Therapy Overview Mechanism of Action KTE-C19 Studies KTE-C19 Cancer Targets Adverse Events Manufacturing Drug Status Rx Availability Prescription only D Pregnancy Category Positive evidence of risk N/A CSA Schedule Not a controlled drug Approval History Drug history at FDA Drug Class Mitotic inhibitors Related Drugs Prostate Cancer estradiol , Premarin , Estrace , bicalutamide , Casodex , Eligard , Xtandi , Zytiga , leuprolide , Taxotere , Lupron Depot , conjugated estrogens , docetaxel , Firmagon , Trelstar , enzalutamide , Zoladex , abiraterone , degarelix , Menest , flutamide , flax , Delestrogen , More... Cabazitaxel Rating No Reviews - Be the first! No Reviews - Be the first! Not Rated - Be the first!} } chronic
and in fact Cabazitaxel classic
EmoticonEmoticon